FN Thomson Reuters Web of Science™ VR 1.0 PT B AU Wise, SP AF Wise, SP BE Bloedel, JR Ebner, TJ Wise, SP TI Evolution of neuronal activity during conditional motor learning SO ACQUISITION OF MOTOR BEHAVIOR IN VERTEBRATES LA English DT Proceedings Paper CT Satellite Seminar on the Acquisition of Motor Behavior in Vertebrates, at the 5th Annual Neural Control of Movement Meeting CY APR 23-25, 1995 CL KEY WEST, FL C1 NIMH,NEUROPHYSIOL LAB,POOLESVILLE,MD. NR 0 TC 17 Z9 17 U1 0 U2 0 PU M I T PRESS PI CAMBRIDGE PA 55 HAYWARD ST, CAMBRIDGE, MA 02142 BN 0-262-02404-7 PY 1996 BP 261 EP 286 PG 26 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA BG52E UT WOS:A1996BG52E00012 ER PT B AU Hallett, M PascualLeone, A Topka, H AF Hallett, M PascualLeone, A Topka, H BE Bloedel, JR Ebner, TJ Wise, SP TI Adaptation and skill learning: Evidence for different neural substrates SO ACQUISITION OF MOTOR BEHAVIOR IN VERTEBRATES LA English DT Proceedings Paper CT Satellite Seminar on the Acquisition of Motor Behavior in Vertebrates, at the 5th Annual Neural Control of Movement Meeting CY APR 23-25, 1995 CL KEY WEST, FL C1 NINCDS,MED NEUROL BRANCH,BETHESDA,MD 20892. NR 0 TC 18 Z9 18 U1 0 U2 0 PU M I T PRESS PI CAMBRIDGE PA 55 HAYWARD ST, CAMBRIDGE, MA 02142 BN 0-262-02404-7 PY 1996 BP 289 EP 301 PG 13 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA BG52E UT WOS:A1996BG52E00013 ER PT J AU Hampel, H Berger, C MullerSpahn, F AF Hampel, H Berger, C MullerSpahn, F TI Modified oral anticoagulant potency in an amitriptyline-treated patient? SO ACTA HAEMATOLOGICA LA English DT Article DE amitriptyline; anticoagulation, oral; antidepressant, tricyclic; drug-drug interaction; phenprocoumon ID DRUG AB We report the case of a 74-year-old female patient who received the antidepressant amitriptyline because of a major depression. Incidence of acute lower extremity venous thrombosis required an additional oral anticoagulant therapy with phenprocoumon. During the simultaneous adjustment of both substances, the Quick value displayed great fluctuations which only disappeared after discontinuation of the amitriptyline medication. This finding is discussed as an aspect of a possible drug-drug interaction between amitriptyline and phenprocoumon. C1 UNIV MUNICH,DEPT PSYCHIAT,D-8000 MUNICH,GERMANY. UNIV BASEL,DEPT PSYCHIAT,BASEL,SWITZERLAND. RP Hampel, H (reprint author), NIA,NEUROSCI LAB,NIH,BLDG 10,ROOM 6C414,BETHESDA,MD 20892, USA. NR 13 TC 1 Z9 1 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0001-5792 J9 ACTA HAEMATOL-BASEL JI Acta Haematol. PY 1996 VL 96 IS 3 BP 178 EP 180 PG 3 WC Hematology SC Hematology GA VK537 UT WOS:A1996VK53700011 PM 8876616 ER PT J AU Linnekin, D Weiler, SR Mou, S DeBerry, CS Keller, JR Ruscetti, FW Ferris, DK Longo, DL AF Linnekin, D Weiler, SR Mou, S DeBerry, CS Keller, JR Ruscetti, FW Ferris, DK Longo, DL TI JAK2 is constitutively associated with c-kit and is phosphorylated in response to stem cell factor SO ACTA HAEMATOLOGICA LA English DT Article; Proceedings Paper CT 9th Symposium of Molecular Biology of Hematopoiesis CY JUN 23-27, 1995 CL GENOA, ITALY SP Menarini Int Fdn, Italy, Ist Cantonale Patol, Locarno, Switzerland, Amgen Roche SpA, Chugai Rhone Poulenc, Ortho Biotech, CellPro Inc, Europe NV SA, Schering Plough SpA, Schering Plough Int, Wellcome Italia SpA, Glaxo Grp Res Ltd, Baxter Healthcare Corp, Miltenyi Biotec, Blackwell Sci, Le Petit, Marion Merrell Dow, Impress, Stem Cell, SyStemix, Ortho Biotech Inc, Beckman, Sandoz, Immunokontact, Vestar, Liposome, Stockton, Pasteur Merieux, OPA, Intercept, Plenum DE cytokine; growth factor; JAK2; phosphorylation; signal transduction; stem cell factor ID COLONY-STIMULATING FACTOR; TYROSINE PHOSPHORYLATION; GROWTH-FACTOR; SIGNAL-TRANSDUCTION; KINASE; RECEPTOR; PROTEIN; INTERLEUKIN-3; ACTIVATION; PATHWAYS AB Stem cell factor (SCF) interacts with the receptor tyrosine kinase c-Kit and has potent effects on hematopoiesis, We have examined the role of JAK2 in the SCF signal transduction pathway. JAK2 and c-Kit were constitutively associated, and treatment with SCF resulted in rapid and transient tyrosine phosphorylation of JAK2, Incubation of cells with JAK2 antisense oligonucleotides resulted in significant decreases in SCF-induced proliferation, These data suggest that JAK2 plays a role in SCF-induced proliferation. C1 NCI,FREDERICK CANC RES & DEV CTR,SAIC FREDERICK,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. RP Linnekin, D (reprint author), NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21702, USA. NR 30 TC 17 Z9 17 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0001-5792 J9 ACTA HAEMATOL-BASEL JI Acta Haematol. PY 1996 VL 95 IS 3-4 BP 224 EP 228 PG 5 WC Hematology SC Hematology GA UM164 UT WOS:A1996UM16400013 PM 8677747 ER PT J AU Suzuki, K Hemmi, A Katoh, R Kawaoi, A AF Suzuki, K Hemmi, A Katoh, R Kawaoi, A TI Differential image analysis of proliferating cell nuclear antigen (PCNA) expression level during experimental thyroid carcinogenesis SO ACTA HISTOCHEMICA ET CYTOCHEMICA LA English DT Article DE proliferating cell nuclear antigen (PCNA); image analysis; thyroid gland; carcinogenesis ID DNA POLYMERASE-DELTA; PARAFFIN-EMBEDDED SECTIONS; CYCLIN-DEPENDENT KINASES; FLOW CYTOMETRIC ANALYSIS; S-PHASE CELLS; AUXILIARY PROTEIN; MONOCLONAL-ANTIBODIES; HUMAN-TISSUES; REPLICATION; RAT AB Immunostaining of proliferating cell nuclear antigen (PCNA), which can be applied to routinely processed tissue sections, has extended the applications of cell kinetic studies. PCNA immunostaining intensity of cells varies among individual nuclei in tissue sections. To determine the changes in PCNA expression level during carcinogenesis, we employed an image analyzer to evaluate PCNA staining intensity in diisopropanolnitrosamine (DIPN)-induced neoplastic lesions of rat thyroid glands. In the normal thyroid gland, only small numbers of cells showed weak PCNA expression. The percentage of PCNA-positive cells increased during carcinogenesis, i.e. hyperplasia, adenoma, and then carcinoma. Analysis of PCNA staining intensity histograms revealed that the population of cells with stronger intensity increased during carcinogenesis, i.e. from adenoma to carcinoma. However, the percentage of cells with weak PCNA staining increased in hyperplasia, and did not change in intensity during further carcinogenic sequelae. These differences in PCNA expression level recognized by immunostaining intensity may reflect different cell kinetics between the process of hyperplasia and that of differentiation from adenoma to carcinoma. C1 NIDDKD, NIH, BIOCHEM & METAB LAB, CELL REGULAT SECT, BETHESDA, MD 20892 USA. RP Suzuki, K (reprint author), YAMANASHI MED UNIV, DEPT PATHOL, 1110 SHIMOKATO, YAMANASHI 40938, JAPAN. NR 37 TC 1 Z9 1 U1 0 U2 0 PU JAPAN SOC HISTOCHEMISTRY & CYTOCHEMISTRY PI KYOTO PA C/O NAKANISHI PRINTING CO LTD, SHIMODACHIURI-OGAWA, KAMIGYO-KU, KYOTO, 602-8048, JAPAN SN 0044-5991 EI 1347-5800 J9 ACTA HISTOCHEM CYTOC JI Acta Histochem. Cytochem. PY 1996 VL 29 IS 2 BP 99 EP 105 PG 7 WC Cell Biology SC Cell Biology GA VP965 UT WOS:A1996VP96500003 ER PT J AU Figg, WD Dawson, N Middleman, MN Brawley, O Lush, RM Senderowicz, A Steinberg, SH Tompkins, A Reed, E Sartor, O AF Figg, WD Dawson, N Middleman, MN Brawley, O Lush, RM Senderowicz, A Steinberg, SH Tompkins, A Reed, E Sartor, O TI Flutamide withdrawal and concomitant initiation of aminoglutethimide in patients with hormone refractory prostate cancer SO ACTA ONCOLOGICA LA English DT Article ID ANDROGEN-RECEPTOR GENE; MUTATION; ANTIGEN; CELLS RP Figg, WD (reprint author), NCI,NIH,DIV CANC TREATMENT,CLIN ONCOL PROGRAM,CLIN PHARMACOL BRANCH,BLDG 10,ROOM 5A01,BETHESDA,MD 20892, USA. RI Figg Sr, William/M-2411-2016 NR 17 TC 6 Z9 7 U1 0 U2 0 PU SCANDINAVIAN UNIVERSITY PRESS PI OSLO PA PO BOX 2959 TOYEN, JOURNAL DIVISION CUSTOMER SERVICE, N-0608 OSLO, NORWAY SN 0284-186X J9 ACTA ONCOL JI Acta Oncol. PY 1996 VL 35 IS 6 BP 763 EP 765 PG 3 WC Oncology SC Oncology GA VR932 UT WOS:A1996VR93200022 PM 8938230 ER PT J AU Panyutin, IG Neumann, RD AF Panyutin, IG Neumann, RD TI Sequence-specific DNA breaks produced by triplex-directed decay of iodine-125 SO ACTA ONCOLOGICA LA English DT Article; Proceedings Paper CT 3rd International Symposium on Biophysical Aspects of Auger Processes CY AUG 24-25, 1995 CL UNIV LUND, LUND, SWEDEN HO UNIV LUND ID OLIGONUCLEOTIDES; I-125 AB Tripler forming oligonucleotides (TFO) labeled with Auger emitters could be ideal vehicles to deliver radioactive-decay energy to specific DNA sequences, causing DNA breaks and, subsequently, inactivation of these sequences. To demonstrate this approach we labeled with I-125 (two I-125 per molecule on average) a purine-rich 38-mer which forms a stable tripler with a polypurine polypyrimidine stretch in the human HPRT gene. Decay of I-125 in the bound TFO was shown to cause sequence-specific double strand breaks (DSB) in the target HPRT sequence cloned into plasmid DNA. No sequence-specific breaks were observed if (125)-labeled TFO were not bound to the plasmid DNA, After 60 days of decay accumulation (one I-125 half-life) approximately a quarter of all plasmid molecules contained sequence-specific DSB, corresponding to 0.3 site-specific DSB per decay. Sequencing gel analysis shows that the DNA breaks are distributed within a few bases of the maxima at those bases opposite to the positions of I-125 in the TFO. RP Panyutin, IG (reprint author), NIH,CTR CLIN,DEPT NUCL MED,BLDG 10,RM 1C401,BETHESDA,MD 20892, USA. NR 10 TC 46 Z9 49 U1 1 U2 1 PU SCANDINAVIAN UNIVERSITY PRESS PI OSLO PA PO BOX 2959 TOYEN, JOURNAL DIVISION CUSTOMER SERVICE, N-0608 OSLO, NORWAY SN 0284-186X J9 ACTA ONCOL JI Acta Oncol. PY 1996 VL 35 IS 7 BP 817 EP 823 DI 10.3109/02841869609104032 PG 7 WC Oncology SC Oncology GA WA054 UT WOS:A1996WA05400007 PM 9004758 ER PT J AU Perkins, KA Benowitz, N Henningfield, J Newhouse, P Pomerleau, O Swan, G AF Perkins, KA Benowitz, N Henningfield, J Newhouse, P Pomerleau, O Swan, G TI Society for research on nicotine and tobacco SO ADDICTION LA English DT Editorial Material ID SMOKING CESSATION; TOLERANCE; HALOPERIDOL AB The proceedings of the inaugural scientific meeting of the Society for Research on Nicotine and Tobacco (SRNT) are summarized. The primary objective of the meeting was to foster the exchange of information on the effects of nicotine and tobacco use, as well as factors which influence their use, drawing from biological, behavioral and social sciences. Much of this research can be viewed as a tale of ''two'' drugs-nicotine as a Key to an important public health problem, and nicotine as a classical tool of physiological and pharmacological research. A historical overview of research on ''both'' drugs is provided first. Public policy alternatives for reducing the prevalence of tobacco use have been derived in part from basic and clinical research results and are briefly outlined. Evidence for genetic determinants on nicotine use and effects is presented using data from twin studies and from molecular genetic research with humans and animals. Consistent with this research, there is evidence of individual differences in pharmacokinetics and effects of nicotine, which could account for differences in smoking behavior and nicotine dependence. Finally, recent developments in the therapeutic uses of nicotine and novel nicotinic agonists with schizophrenia, Alzheimer's disease, Parkinson's disease, Tourette's syndrome and ulcerative colitis are presented. Overall, the research presented at the meeting demonstrated the vast diversity of areas of study involving nicotine and tobacco, as well as the rich opportunities for cross-communication among researchers from different disciplines. C1 UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA 94110. NIDA,ADDICT RES CTR,CLIN PHARMACOL BRANCH,BALTIMORE,MD 21224. UNIV VERMONT,CLIN NEUROSCI RES UNIT,BURLINGTON,VT 05401. UNIV MICHIGAN,ANN ARBOR,MI 48108. SRI INT,HLTH SCI & POLICY PROGRAM,MENLO PK,CA 94025. RP Perkins, KA (reprint author), UNIV PITTSBURGH,SCH MED,WESTERN PSYCHIAT INST & CLIN,3811 OHARA ST,PITTSBURGH,PA 15213, USA. RI Perkins, Kenneth/E-4085-2010; Newhouse, Paul/J-4597-2014 NR 31 TC 11 Z9 11 U1 0 U2 1 PU CARFAX PUBL CO PI ABINGDON PA PO BOX 25, ABINGDON, OXFORDSHIRE, ENGLAND OX14 3UE SN 0965-2140 J9 ADDICTION JI Addiction PD JAN PY 1996 VL 91 IS 1 BP 129 EP 137 DI 10.1111/j.1360-0443.1996.tb03168.x PG 9 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA TQ693 UT WOS:A1996TQ69300019 PM 8822021 ER PT J AU Heishman, SJ Henningfield, JE AF Heishman, SJ Henningfield, JE TI Nicotine substitution during tobacco abstinence SO ADDICTION LA English DT Meeting Abstract C1 NIDA,ADDICT RES CTR,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CARFAX PUBL CO PI ABINGDON PA PO BOX 25, ABINGDON, OXFORDSHIRE, ENGLAND OX14 3UE SN 0965-2140 J9 ADDICTION JI Addiction PD JAN PY 1996 VL 91 IS 1 BP 140 EP 140 PG 1 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA TQ693 UT WOS:A1996TQ69300028 ER PT J AU Schuh, LM Henningfield, JE Pickworth, WB Rothman, R Ohuoha, D Keenan, RM AF Schuh, LM Henningfield, JE Pickworth, WB Rothman, R Ohuoha, D Keenan, RM TI Pharmacodynamic effects of cotinine SO ADDICTION LA English DT Meeting Abstract C1 NIDA,ADDICT RES CTR,BALTIMORE,MD 21224. NR 0 TC 1 Z9 1 U1 1 U2 1 PU CARFAX PUBL CO PI ABINGDON PA PO BOX 25, ABINGDON, OXFORDSHIRE, ENGLAND OX14 3UE SN 0965-2140 J9 ADDICTION JI Addiction PD JAN PY 1996 VL 91 IS 1 BP 143 EP 143 PG 1 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA TQ693 UT WOS:A1996TQ69300043 ER PT J AU Schindler, CW AF Schindler, CW TI Cocaine and cardiovascular toxicity SO ADDICTION BIOLOGY LA English DT Review ID CORONARY-ARTERY VASOCONSTRICTION; INDUCED VENTRICULAR-FIBRILLATION; CENTRAL-NERVOUS-SYSTEM; CONSCIOUS SQUIRREL-MONKEYS; PRIMARY CULTURE SYSTEM; HEART-RATE DYNAMICS; INTRAVENOUS COCAINE; ANESTHETIZED DOGS; CHEST PAIN; MALIGNANT ARRHYTHMIAS AB Over the past 10 years a great deal has been learned about the cardiovascular effects of cocaine. In particular, the acute effects of cocaine have been studied extensively. Upon acute administration cocaine increases blood pressure and heart rate, primarily through an action on the sympathetic nervous system. Cocaine also suppresses the baroreflex response and vagal tone, further contributing to its effects on heart rate. Ar the same time cocaine is increasing the work-load on the heart it induces coronary artery vasoconstriction, potentially leading to cardiac ischemia. At higher doses cocaine can depress ventricular function and slow electrical conduction in the heart. Both these effects appear to be mediated by cocaine's local anesthetic action. The effects of cocaine mediated by the sympathetic nervous system are greatly reduced in anesthetized animals. Further, when cocaine is administered repeatedly over a short period of time, acute tolerance can develop to the sympathomimetic effects of cocaine. In contrast, the effects of cocaine mediated by its local anesthetic action do not appear blunted by anesthesia or susceptible to acute tolerance. With chronic administration, higher doses appear to induce tolerance while lower doses may induce sensitization to cocaine's sympathomimetic effects. Cocaine also induces a variety of pathological changes in the heart, including myocardial contraction band necrosis and ventricular hypertrophy. These effects of cocaine on the heart can all contribute to potentially lethal cardiovascular events. In addition to the effects of cocaine alone, the metabolites of cocaine may also contribute to cocaine's cardiovascular toxicity, and both licit and illicit drugs used in combination with cocaine might potentially alter its cardiovascular effects. RP Schindler, CW (reprint author), NIDA,ADDICT RES CTR,DIV INTRAMURAL RES,PRECLIN PHARMACOL LAB,NIH,POB 5180,BALTIMORE,MD 21224, USA. NR 136 TC 29 Z9 29 U1 3 U2 4 PU CARFAX PUBL CO PI ABINGDON PA PO BOX 25, ABINGDON, OXFORDSHIRE, ENGLAND OX14 3UE SN 1355-6215 J9 ADDICT BIOL JI Addict. Biol. PD JAN PY 1996 VL 1 IS 1 BP 31 EP 47 DI 10.1080/1355621961000124676 PG 17 WC Biochemistry & Molecular Biology; Substance Abuse SC Biochemistry & Molecular Biology; Substance Abuse GA VF951 UT WOS:A1996VF95100004 PM 12893485 ER PT J AU Lerman, C Audrain, J Orleans, CT Boyd, R Gold, K Main, D Caporaso, N AF Lerman, C Audrain, J Orleans, CT Boyd, R Gold, K Main, D Caporaso, N TI Investigation of mechanisms linking depressed mood to nicotine dependence SO ADDICTIVE BEHAVIORS LA English DT Article ID SMOKING CESSATION; MAJOR DEPRESSION; TOLERANCE QUESTIONNAIRE; CIGARETTE-SMOKING; CLONIDINE; EXERCISE; SUPPORT; WOMEN AB The present study examined the cognitive-behavioral linkages between depressed mood and level of nicotine dependence in smokers seeking smoking cessation treatment. Prior to treatment, 202 subjects completed validated self-report measures of smoking history, depressive symptomatology, ''self medication'' processes, ''learned helplessness'' processes, and nicotine dependence. Results revealed that 48% of the study population scored in the ''depressed'' range on the Center for Epidemiologic Studies (CES-D) depression scale. Further, these smokers reported significantly higher levels of nicotine dependence than other nondepressed smokers. Depressed and nondepressed smokers did not differ with respect to several cognitions related to learned helplessness theory. However, depressed smokers were more likely to report ''self medication'' processes (i.e., negative affect reduction smoking and stimulation smoking). In addition, multivariable regression and path analyses suggested that negative affect reduction smoking and stimulation smoking are sequential mediators of the depression-nicotine dependence relationship. These results underscore the need to screen for depressive symptomatology among smokers seeking treatment, and to develop cessation treatments that are tailored to the needs of depressed smokers. C1 FOX CHASE CANC CTR, PHILADELPHIA, PA 19111 USA. JOHNSON & JOHNSON CONSUMER PROD INC, BEHAV TECHNOL, SKILLMAN, NJ USA. NCI, GENET EPIDEMIOL BRANCH, BETHESDA, MD USA. RP Lerman, C (reprint author), GEORGETOWN UNIV, MED CTR, VINCENT T LOMBARDI CANC RES CTR, 2233 WISCONSIN AVE NW, SUITE 535, WASHINGTON, DC 20007 USA. FU NCI NIH HHS [R01 CA63562] NR 45 TC 162 Z9 165 U1 1 U2 12 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4603 EI 1873-6327 J9 ADDICT BEHAV JI Addict. Behav. PD JAN-FEB PY 1996 VL 21 IS 1 BP 9 EP 19 DI 10.1016/0306-4603(95)00032-1 PG 11 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA TZ047 UT WOS:A1996TZ04700002 PM 8729703 ER PT J AU Chiorini, JA Wiener, SM Yang, L Smith, RH Safer, B Kilcoin, NP Liu, Y Urcelay, E Kotin, RM AF Chiorini, JA Wiener, SM Yang, L Smith, RH Safer, B Kilcoin, NP Liu, Y Urcelay, E Kotin, RM TI The roles of AAV rep proteins in gene expression and targeted integration SO ADENO-ASSOCIATED VIRUS (AAV) VECTORS IN GENE THERAPY SE CURRENT TOPICS IN MICROBIOLOGY AND IMMUNOLOGY LA English DT Review ID ADENO-ASSOCIATED VIRUS; INHIBITS CELLULAR-TRANSFORMATION; DOMINANT-NEGATIVE MUTANT; ADENOASSOCIATED VIRUS; WILD-TYPE; TERMINAL REPEATS; DNA; SITE; REPLICATION; IDENTIFICATION RP Chiorini, JA (reprint author), NHLBI,MOL HEMATOL BRANCH,NIH,MSC 1654,10 CTR DR,BETHESDA,MD 20892, USA. RI kotin, robert/B-8954-2008 NR 43 TC 27 Z9 27 U1 2 U2 2 PU SPRINGER-VERLAG BERLIN PI BERLIN 33 PA HEIDELBERGER PLATZ 3, W-1000 BERLIN 33, GERMANY SN 0070-217X J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 1996 VL 218 BP 25 EP 33 PG 9 WC Immunology; Microbiology SC Immunology; Microbiology GA BJ66L UT WOS:A1996BJ66L00002 PM 8794243 ER PT B AU Catt, KJ Hunyady, L Ji, H Tian, Y Baukal, AJ Clark, AJL Balla, T AF Catt, KJ Hunyady, L Ji, H Tian, Y Baukal, AJ Clark, AJL Balla, T BE Vinson, GP Anderson, DC TI Structure-function properties and signaling pathways of the angiotensin AT(1) receptor SO ADRENAL GLANDS, VASCULAR SYSTEM AND HYPERTENSION LA English DT Proceedings Paper CT International Workshop on Adrenal Glands, Vascular System and Hypertension CY APR 20-22, 1995 CL HONG KONG, HONG KONG SP Hong Kong Soc Study Endocrinol Metab & Reprod, Armed Far East Ltd, Merck Sharp & Dohme Asia Ltd, Sandoz Pharm Ltd, Hong Kong Div, Searle Pharm, Parke Davis, Zeneca China Ltd RP Catt, KJ (reprint author), NICHHD,ENDOCRINOL & REPROD RES BRANCH,NIH,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOCIETY ENDOCRINOLOGY PI BRISTOL PA 17/18 THE COURTYARD, WOODLANDS ALMONDSBURY, BRISTOL, ENGLAND BS12 4NQ BN 1-898099-07-3 PY 1996 BP 3 EP 21 PG 19 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA BH23S UT WOS:A1996BH23S00001 ER PT B AU Arai, K Chrousos, GP AF Arai, K Chrousos, GP BE Vinson, GP Anderson, DC TI Glucocorticoid and mineralocorticoid resistance: Clinical and molecular aspects SO ADRENAL GLANDS, VASCULAR SYSTEM AND HYPERTENSION LA English DT Proceedings Paper CT International Workshop on Adrenal Glands, Vascular System and Hypertension CY APR 20-22, 1995 CL HONG KONG, HONG KONG SP Hong Kong Soc Study Endocrinol Metab & Reprod, Armed Far East Ltd, Merck Sharp & Dohme Asia Ltd, Sandoz Pharm Ltd, Hong Kong Div, Searle Pharm, Parke Davis, Zeneca China Ltd RP Arai, K (reprint author), NICHHD,DEV ENDOCRINOL BRANCH,NIH,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOCIETY ENDOCRINOLOGY PI BRISTOL PA 17/18 THE COURTYARD, WOODLANDS ALMONDSBURY, BRISTOL, ENGLAND BS12 4NQ BN 1-898099-07-3 PY 1996 BP 211 EP 226 PG 16 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA BH23S UT WOS:A1996BH23S00016 ER PT B AU Cutler, RG AF Cutler, RG BE Klatz, RM TI The molecular and evolutionary aspects of human aging and longevity SO ADVANCES IN ANTI-AGING MEDICINE, VOL 1 SE ADVANCES IN ANTI-AGING MEDICINE LA English DT Proceedings Paper CT 1994 Conference on Anti-Aging Medicine CY 1994 CL LAS VEGAS, NV SP Amer Acad Anti Aging Med C1 NIA,GERONTOL RES CTR,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 BN 0-913113-71-9 J9 ADV ANTI AGING MED PY 1996 VL 1 BP 71 EP 99 PG 29 WC Geriatrics & Gerontology; Pharmacology & Pharmacy SC Geriatrics & Gerontology; Pharmacology & Pharmacy GA BE51Q UT WOS:A1996BE51Q00009 ER PT S AU Horowits, R Luo, G Zhang, JQ Herrera, AH AF Horowits, R Luo, G Zhang, JQ Herrera, AH BE Ebashi, S TI Nebulin and nebulin-related proteins in striated muscle SO ADVANCES IN BIOPHYSICS, VOL. 33, 1996: MUSCLE ELASTIC PROTEINS SE ADVANCES IN BIOPHYSICS LA English DT Review CT 1st International Symposium on Muscle Elastic Proteins CY OCT 26-28, 1995 CL CHIBA UNIV, KEYAKI KAIKAN, CHIBA, JAPAN SP Japan Soc Promot Sci, Goho Life Sci Int fund, Naito Fdn, Uehara Mem Fdn, Chiba Convent Bur, Chiba Univ HO CHIBA UNIV, KEYAKI KAIKAN ID SKELETAL-MUSCLE; INVIVO PHOSPHORYLATION; MONOCLONAL-ANTIBODIES; SARCOMERE MATRIX; ACTIN-FILAMENTS; THIN-FILAMENTS; LIM DOMAIN; Z-LINE; TITIN; CONNECTIN RP Horowits, R (reprint author), NIAMSD, NIH, BETHESDA, MD 20892 USA. NR 32 TC 6 Z9 6 U1 1 U2 1 PU JAPAN SCIENTIFIC SOC PRESS PI TOKYO PA 2-10 HONGO, 6-CHOME, BUNKYO-KU, TOKYO, 113, JAPAN SN 0065-227X J9 ADV BIOPHYS JI Adv.Biophys. PY 1996 VL 33 BP 143 EP 150 PG 8 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA BG91J UT WOS:A1996BG91J00012 PM 8922109 ER PT J AU Werner, H LeRoith, D AF Werner, H LeRoith, D TI The role of the insulin-like growth factor system in human cancer SO ADVANCES IN CANCER RESEARCH, VOL 68 SE ADVANCES IN CANCER RESEARCH LA English DT Review ID HUMAN-BREAST-CANCER; FACTOR-I RECEPTOR; MESSENGER-RIBONUCLEIC-ACID; WILMS-TUMOR LOCUS; MANNOSE 6-PHOSPHATE RECEPTOR; BECKWITH-WIEDEMANN SYNDROME; BINDING-PROTEIN IGFBP; NONISLET CELL TUMORS; ZINC FINGER PROTEIN; HUMAN LUNG-TUMORS RP Werner, H (reprint author), NIDDKD,NIH,DIABET BRANCH,BETHESDA,MD 20892, USA. NR 272 TC 226 Z9 232 U1 0 U2 4 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0065-230X J9 ADV CANCER RES JI Adv.Cancer Res. PY 1996 VL 68 BP 183 EP 223 DI 10.1016/S0065-230X(08)60354-1 PG 41 WC Oncology SC Oncology GA BF47Q UT WOS:A1996BF47Q00005 PM 8712068 ER PT J AU Kallioniemi, OP Visakorpi, T AF Kallioniemi, OP Visakorpi, T TI Genetic basis and clonal evolution of human prostate cancer SO ADVANCES IN CANCER RESEARCH, VOL 68 SE ADVANCES IN CANCER RESEARCH LA English DT Review ID GROWTH-FACTOR RECEPTOR; TUMOR-SUPPRESSOR GENE; CELL-LINES; E-CADHERIN; INSITU HYBRIDIZATION; CYTOGENETIC ANALYSIS; ONCOGENE MUTATIONS; COLORECTAL-CANCER; MYC PROTOONCOGENE; FREQUENT LOSS C1 TAMPERE UNIV, CANC GENET LAB, INST MED TECHNOL, SF-33101 TAMPERE, FINLAND. TAMPERE UNIV HOSP, FIN-33101 TAMPERE, FINLAND. RP Kallioniemi, OP (reprint author), NIH, NATL CTR HUMAN GENOME RES, BETHESDA, MD 20892 USA. RI Kallioniemi, Olli/H-5111-2011; Kallioniemi, Olli/H-4738-2012 OI Kallioniemi, Olli/0000-0002-3231-0332; Kallioniemi, Olli/0000-0002-3231-0332 NR 148 TC 59 Z9 59 U1 2 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0065-230X J9 ADV CANCER RES JI Adv.Cancer Res. PY 1996 VL 68 BP 225 EP 255 DI 10.1016/S0065-230X(08)60355-3 PG 31 WC Oncology SC Oncology GA BF47Q UT WOS:A1996BF47Q00006 PM 8712069 ER PT J AU Varmus, H AF Varmus, H TI The pastorian: A legacy of Louis Pasteur SO ADVANCES IN CANCER RESEARCH, VOL 69 SE ADVANCES IN CANCER RESEARCH LA English DT Item About an Individual RP Varmus, H (reprint author), NIH,BLDG 10,BETHESDA,MD 20878, USA. NR 0 TC 2 Z9 2 U1 1 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0065-230X J9 ADV CANCER RES JI Adv.Cancer Res. PY 1996 VL 69 BP 1 EP 16 DI 10.1016/S0065-230X(08)60858-1 PG 16 WC Oncology SC Oncology GA BG20R UT WOS:A1996BG20R00001 PM 8791677 ER PT J AU Chidambaram, A Dean, M AF Chidambaram, A Dean, M TI Genetics of the nevoid basal cell carcinoma syndrome SO ADVANCES IN CANCER RESEARCH, VOL 70 SE ADVANCES IN CANCER RESEARCH LA English DT Review ID GORLIN SYNDROME; SOMATIC MOSAICISM; PROTEUS SYNDROME; CHROMOSOME-9; LOCALIZATION; FAMILIES; MOUSE C1 NCI,FREDERICK CANC RES & DEV CTR,CANC RES & DEV CTR,FREDERICK,MD 21702. RP Chidambaram, A (reprint author), NCI,FREDERICK CANC RES & DEV CTR,INTRAMURAL RES SUPPORT PROGRAM,SAIC FREDERICK,FREDERICK,MD 21702, USA. RI Dean, Michael/G-8172-2012 OI Dean, Michael/0000-0003-2234-0631 NR 49 TC 12 Z9 12 U1 0 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0065-230X J9 ADV CANCER RES JI Adv.Cancer Res. PY 1996 VL 70 BP 49 EP 61 DI 10.1016/S0065-230X(08)60871-4 PG 13 WC Oncology SC Oncology GA BG71E UT WOS:A1996BG71E00003 PM 8902053 ER PT J AU Rosenberg, SA Kawakami, Y Robbins, PF Wang, RF AF Rosenberg, SA Kawakami, Y Robbins, PF Wang, RF TI Identification of the genes encoding cancer antigens: Implications for cancer immunotherapy SO ADVANCES IN CANCER RESEARCH, VOL 70 SE ADVANCES IN CANCER RESEARCH LA English DT Review ID TUMOR-INFILTRATING LYMPHOCYTES; CYTOLYTIC T-LYMPHOCYTES; HUMAN-MELANOMA ANTIGENS; E-CADHERIN EXPRESSION; CLASS-I MOLECULES; METASTATIC MELANOMA; MESSENGER-RNA; MONOCLONAL-ANTIBODY; AUTOLOGOUS TUMOR; DIFFERENTIATION ANTIGEN RP Rosenberg, SA (reprint author), NCI,SURG BRANCH,DEPT CLIN SCI,BLDG 10,BETHESDA,MD 20892, USA. RI Kawakami, Yutaka /E-7429-2013 OI Kawakami, Yutaka /0000-0003-4836-2855 NR 123 TC 76 Z9 78 U1 1 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0065-230X J9 ADV CANCER RES JI Adv.Cancer Res. PY 1996 VL 70 BP 145 EP 177 DI 10.1016/S0065-230X(08)60874-X PG 33 WC Oncology SC Oncology GA BG71E UT WOS:A1996BG71E00006 PM 8902056 ER PT S AU Chu, E Allegra, CJ AF Chu, E Allegra, CJ BE Weber, G TI The role of thymidylate synthase in cellular regulation SO ADVANCES IN ENZYME REGULATION, VOL 36 SE ADVANCES IN ENZYME REGULATION LA English DT Article; Proceedings Paper CT 36th Symposium on Regulation of Enzyme Activity and Synthesis in Normal and Neoplastic Tissues CY OCT 02-03, 1995 CL INDIANAPOLIS, IN ID COLON-CANCER-CELLS; TRANSFER-RNA SYNTHETASE; TUMOR-SUPPRESSOR GENE; KINASE MESSENGER-RNA; DIHYDROFOLATE-REDUCTASE; ESCHERICHIA-COLI; THYMIDINE KINASE; BINDING-SITE; MOUSE FIBROBLASTS; BREAST-CANCER RP Chu, E (reprint author), NCI,USN,MED ONCOL BRANCH,BETHESDA,MD 20889, USA. NR 69 TC 45 Z9 45 U1 0 U2 1 PU PERGAMON PRESS LTD PI OXFORD PA THE BOULEVARD LANGFORD LANE KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0065-2571 BN 0-08-042894-0 J9 ADV ENZYME REGUL PY 1996 VL 36 BP 143 EP 163 DI 10.1016/0065-2571(95)00004-6 PG 21 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BG03K UT WOS:A1996BG03K00009 PM 8869745 ER PT J AU Hathcock, KS Hodes, RJ AF Hathcock, KS Hodes, RJ TI Role of the CD28-B7 costimulatory pathways in T cell-dependent B cell responses SO ADVANCES IN IMMUNOLOGY, VOL 62 SE ADVANCES IN IMMUNOLOGY LA English DT Review ID ANTIGEN-PRESENTING CELLS; ACTIVATED LYMPHOCYTES-T; CTLA-4 COUNTER-RECEPTOR; PRIMARY IMMUNE-RESPONSE; GERMINAL-CENTERS; MONOCLONAL-ANTIBODY; DENDRITIC CELLS; IN-VITRO; FUNCTIONAL EXPRESSION; PHOSPHATIDYLINOSITOL 3-KINASE C1 NIA,NIH,BETHESDA,MD 20892. RP Hathcock, KS (reprint author), NCI,EXPT IMMUNOL BRANCH,BLDG 10,BETHESDA,MD 20892, USA. NR 141 TC 30 Z9 31 U1 1 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0065-2776 J9 ADV IMMUNOL JI Adv.Immunol. PY 1996 VL 62 BP 131 EP 166 DI 10.1016/S0065-2776(08)60429-0 PG 36 WC Immunology SC Immunology GA BG02G UT WOS:A1996BG02G00004 PM 8781268 ER PT J AU Fleisher, TA AF Fleisher, TA TI Evaluation of the potentially immunodeficient patient SO ADVANCES IN INTERNAL MEDICINE, VOL 41 SE ADVANCES IN INTERNAL MEDICINE LA English DT Review ID NATURAL-KILLER-CELLS; T-CELLS; CYTOKINE PROFILES; VIRUS INFECTION; DISEASE; COMPLEMENT; HYPERSENSITIVITY; IMMUNOGLOBULIN; IMMUNOLOGY; DEFICIENCY RP Fleisher, TA (reprint author), NIH,WARREN G MAGNUSON CLIN CTR,DEPT CLIN PATHOL,SERV IMMUNOL,BETHESDA,MD 20892, USA. NR 81 TC 6 Z9 6 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146 SN 0065-2822 J9 ADV INTERNAL MED JI Adv.Intern.Med. PY 1996 VL 41 BP 1 EP 30 PG 30 WC Medicine, General & Internal SC General & Internal Medicine GA BF11R UT WOS:A1996BF11R00001 PM 8903585 ER PT S AU Walworth, CM Tavel, JA Kovacs, JA AF Walworth, CM Tavel, JA Kovacs, JA BE Schrier, RW TI Treatment and prevention of opportunistic infections in patients with human immunodeficiency virus infection SO ADVANCES IN INTERNAL MEDICINE, VOL 41 SE ADVANCES IN INTERNAL MEDICINE LA English DT Review ID PNEUMOCYSTIS-CARINII PNEUMONIA; IMMUNE-DEFICIENCY-SYNDROME; AVIUM COMPLEX INFECTION; HIV-POSITIVE PATIENTS; MUCOCUTANEOUS HERPES-SIMPLEX; CENTRAL-NERVOUS-SYSTEM; ACUTE TOXOPLASMA ENCEPHALITIS; LIPOSOMAL AMPHOTERICIN-B; ISOSPORA-BELLI INFECTION; PLACEBO-CONTROLLED TRIAL C1 NIH, DEPT CRIT CARE MED, CTR CLIN, BETHESDA, MD 20892 USA. RP Walworth, CM (reprint author), NIAID, NIH, IMMUNOREGULAT LAB, 9000 ROCKVILLE PIKE, BETHESDA, MD 20892 USA. NR 222 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146 USA SN 0065-2822 BN 0-8151-8314-3 J9 ADV INTERNAL MED JI Adv.Intern.Med. PY 1996 VL 41 BP 31 EP 84 PG 54 WC Medicine, General & Internal SC General & Internal Medicine GA BF11R UT WOS:A1996BF11R00002 PM 8903586 ER PT J AU Dickler, HB Gelfand, EW AF Dickler, HB Gelfand, EW TI Current perspectives on the use of intravenous immunoglobulin SO ADVANCES IN INTERNAL MEDICINE, VOL 41 SE ADVANCES IN INTERNAL MEDICINE LA English DT Review ID BONE-MARROW TRANSPLANTATION; IDIOPATHIC THROMBOCYTOPENIC PURPURA; CHRONIC LYMPHOCYTIC-LEUKEMIA; IMMUNE GLOBULIN THERAPY; INFLAMMATORY DEMYELINATING POLYNEUROPATHY; AUTOIMMUNE HEMOLYTIC-ANEMIA; PLACEBO-CONTROLLED TRIAL; CHRONIC FATIGUE SYNDROME; HIGH-RISK INFANTS; GAMMA-GLOBULIN C1 NATL JEWISH CTR IMMUNOL & RESP DIS,DEPT PEDIAT,DIV BASIC SCI,DENVER,CO. RP Dickler, HB (reprint author), NIAID,NIH,DIV ALLERGY IMMUNOL & TRANSPLANTAT,CLIN IMMUNOL BRANCH,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 151 TC 16 Z9 17 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146 SN 0065-2822 J9 ADV INTERNAL MED JI Adv.Intern.Med. PY 1996 VL 41 BP 641 EP 680 PG 40 WC Medicine, General & Internal SC General & Internal Medicine GA BF11R UT WOS:A1996BF11R00017 PM 8903601 ER PT B AU Gandjbakhche, AH Bonner, RF Gannot, I Knutson, J Navai, R Nossal, R Weiss, GH AF Gandjbakhche, AH Bonner, RF Gannot, I Knutson, J Navai, R Nossal, R Weiss, GH BE Alfano, RR Katzir, A TI Fluorescent photon migration theory for turbid biological media SO ADVANCES IN LASER AND LIGHT SPECTROSCOPY TO DIAGNOSE CANCER AND OTHER DISEASES III: OPTICAL BIOPSY, PROCEEDINGS SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT 3rd Conference on Advances in Laser and Light Spectroscopy to Diagnose Cancer and Other Diseases - Optical Biopsy CY JAN 29-30, 1996 CL SAN JOSE, CA SP Soc Photo Opt Instrumentat Engineers, CUNY, New York State Ctr Adv Technol Ultrafast Photon Mat & Appl, Medisci Technol Corp AB Fluorescence imaging in situ may provide highly specific identification of cell types and altered metabolic activity near the surface of tissue. Most approaches to developing the necessary analytical framework for quantitative 3-D use are based on numerical solutions of some form of transport equation. These are highly computer-intensive and can only be carried out for specified parameters. We apply a random walk model for photon migration which enables us to find an exact expression for the frequency-dependent fluorescent signal emitted from the site of a single fluorophore. Our general expression allows for broad variation of the degree of absorptivity, and is potentially important in providing a basis for the development of fluorescence image reconstruction algorithms. RP Gandjbakhche, AH (reprint author), NIH,BETHESDA,MD 20892, USA. RI Bonner, Robert/C-6783-2015 NR 0 TC 3 Z9 3 U1 0 U2 0 PU SPIE - INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA PO BOX 10, BELLINGHAM, WA 98227-0010 BN 0-8194-2053-0 J9 P SOC PHOTO-OPT INS PY 1996 VL 2679 BP 8 EP 15 DI 10.1117/12.237577 PG 8 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BH60V UT WOS:A1996BH60V00002 ER PT S AU Softky, WR AF Softky, WR BE Touretzky, DS Mozer, MC Hasselmo, ME TI Unsupervised pixel-prediction SO ADVANCES IN NEURAL INFORMATION PROCESSING SYSTEMS 8: PROCEEDINGS OF THE 1995 CONFERENCE SE ADVANCES IN NEURAL INFORMATION PROCESSING SYSTEMS LA English DT Proceedings Paper CT 9th Annual Conference on Neural Information Processing Systems (NIPS) CY NOV 27-30, 1995 CL DENVER, CO C1 NIDDK,MATH RES BRANCH,NIH,BETHESDA,MD 20814. NR 0 TC 5 Z9 5 U1 0 U2 0 PU M I T PRESS PI CAMBRIDGE PA 55 HAYWARD ST, CAMBRIDGE, MA 02142 SN 1049-5258 BN 0-262-20107-0 J9 ADV NEUR IN PY 1996 VL 8 BP 809 EP 815 PG 3 WC Computer Science, Information Systems; Neurosciences SC Computer Science; Neurosciences & Neurology GA BG45M UT WOS:A1996BG45M00114 ER PT B AU Optican, LM McClurkin, JW AF Optican, LM McClurkin, JW BE Gath, I Inbar, GF TI Temporal encoding of visual features by cortical neurons SO ADVANCES IN PROCESSING AND PATTERN ANALYSIS OF BIOLOGICAL SIGNALS LA English DT Proceedings Paper CT Bat-Sheva De Rotschild Seminar on Advances in Processing and Pattern Analysis of Biological Signals CY MAR 19-25, 1995 CL TECHNION, ISRAEL INST TECHNOL, HAIFA, ISRAEL SP Bat Sheva De Rotschild Fdn, Technion, Israel Inst Technol, Israel Acad Sci & Humanities, Minist Sci & Arts, Israel HO TECHNION, ISRAEL INST TECHNOL C1 NEI,SENSORIMOTOR RES LAB,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PLENUM PRESS DIV PLENUM PUBLISHING CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 BN 0-306-45215-4 PY 1996 BP 195 EP 204 PG 10 WC Engineering, Biomedical SC Engineering GA BF97T UT WOS:A1996BF97T00014 ER PT B AU Hampshire, V Bacher, J Dennis, M Wolff, A Yarko, M AF Hampshire, V Bacher, J Dennis, M Wolff, A Yarko, M BE Tumbleson, ME Schook, LB TI Early characterization of Panepinto micro/miniature swine for use as transgenic animal models SO ADVANCES IN SWINE IN BIOMEDICAL RESEARCH, VOLS 1 AND 2 LA English DT Proceedings Paper CT International Symposium on Swine in Biomedical Research CY OCT 22-25, 1995 CL UNIV MARYLAND, COLLEGE PK, MD HO UNIV MARYLAND AB The science of producing transgenic animals is advancing rapidly with the resulting manipulated offspring being utilized for biomedical modeling, possible xenotransplantation to humans and agricultural livestock production. The pig is one species under investigation which could have application in any of the aforementioned categories. We will highlight general facts regarding transgenic livestock, aspects of microinjection and our current work performed on developing the Panepinto micro size pig as an animal model for research requiring genetic manipulation. Specifically, a pilot study was undertaken with a hybrid cross of Yucatan micropigs and Vietnamese potbellied pigs as models for potential transgenic work using superovulatory techniques, follicular harvest and reimplantation. The advantage of using a small, easily managed animal needed to be balanced against the low reproductive efficiency of these pigs as compared to domestic breeds. The pilot study and subsequent followup work demonstrate our early experiences with the model and the direction in which this investigation should proceed. RP Hampshire, V (reprint author), NIH,CARNIVORE UNGULATE UNIT,NATL CTR RES RESOURCES,VET RESOURCES PROGRAM,BLDG 28,ROOM 104,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU PLENUM PRESS DIV PLENUM PUBLISHING CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 BN 0-306-45495-5 PY 1996 BP 671 EP 679 PG 9 WC Medicine, Research & Experimental; Veterinary Sciences; Zoology SC Research & Experimental Medicine; Veterinary Sciences; Zoology GA BH12G UT WOS:A1996BH12G00059 ER PT J AU Detels, R Mann, D Carrington, M Hennessey, K Wu, Z Hirji, KF Wiley, D Visscher, BR Giorgi, JV AF Detels, R Mann, D Carrington, M Hennessey, K Wu, Z Hirji, KF Wiley, D Visscher, BR Giorgi, JV TI Resistance to HIV infection may be genetically mediated SO AIDS LA English DT Letter ID SERONEGATIVE HOMOSEXUAL MEN; MULTICENTER AIDS COHORT; VIRUS-REPLICATION; TYPE-1; DNA C1 UNIV CALIF LOS ANGELES,DEPT MED & BIOMATH,LOS ANGELES,CA 90024. NCI,PRI DYNCORP,FREDERICK,MD 21701. RP Detels, R (reprint author), UNIV CALIF LOS ANGELES,DEPT EPIDEMIOL,MULTICTR AIDS COHORT STUDY,LOS ANGELES CTR,LOS ANGELES,CA 90024, USA. NR 19 TC 13 Z9 13 U1 1 U2 2 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0269-9370 J9 AIDS JI Aids PD JAN PY 1996 VL 10 IS 1 BP 102 EP 104 DI 10.1097/00002030-199601000-00016 PG 3 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA TP241 UT WOS:A1996TP24100016 PM 8924238 ER PT J AU DSouza, MP Mathieson, BJ AF DSouza, MP Mathieson, BJ TI Early phases of HIV type 1 infection SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Editorial Material ID NATURAL-KILLER CELLS; TOXIC LYMPHOCYTES-T; SIMPLEX VIRUS TYPE-1; CHORIOMENINGITIS VIRUS; ADOPTIVE TRANSFER; INVIVO; PLASMA; MICE; INTERFERON AB A workshop entitled ''Early Phases of HIV-1 Infection'' was held to review current research on the immunological and virological aspects of early phases of HIV infection in humans and in animal models, to identify studies for future research, and to foster collaborations among investigators in the biomedical community, In infections of adults, the appearance of cytotoxic T lymphocyte activity, when present, coincides with a decrease in viral load as measured by plasma viremia, In neonatal infections, however, an initial decrease in viral load has been observed months before cytotoxic T lymphocytes are detected, Immunological data, from a limited number of patients, indicated that CD8(+) cytotoxic T lymphocytes detected early after HIV-1 infection may recognize epitopes in any of several HIV-1 proteins: Env, Gag, Pol, Tat, and Nef, With regard to the humoral antibody response, anti-Env binding antibodies appear before neutralizing antibodies and do not predict the appearance of neutralizing activity, The time at which neutralizing antibody appears is variable and unpredictable, Preliminary data indicate that early viral peak load does not predict disease progression in many cases, and the phenotype or virulence of the virus appears to be a critical variable, However, the quantity of HIV-I RNA in plasma is a strong CD4(+) T cell-independent predictor of outcome following HIV-1 seroconversion in homosexual men, Early, high virus load with sustained viremia is often accompanied, in both adults and infants, by the inability to mount an effective immune response, resulting in rapid disease progression. C1 NIH,OFF AIDS RES,BETHESDA,MD 20892. RP DSouza, MP (reprint author), NIAID,DIV AIDS,PATHOGENESIS & BASIC RES BRANCH,6003 EXECUT BLVD,SOLAR BLDG,ROOM 2B35,BETHESDA,MD 20892, USA. NR 41 TC 26 Z9 26 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD JAN 1 PY 1996 VL 12 IS 1 BP 1 EP 9 DI 10.1089/aid.1996.12.1 PG 9 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA TP430 UT WOS:A1996TP43000001 PM 8825612 ER PT J AU Mo, HM Markowitz, M Majer, P Burt, SK Gulnik, SV Suvorov, LI Erickson, JW Ho, DD AF Mo, HM Markowitz, M Majer, P Burt, SK Gulnik, SV Suvorov, LI Erickson, JW Ho, DD TI Design, synthesis, and resistance patterns of MP-134 and MP-167, two novel inhibitors of HIV type 1 protease SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID VIRAL INFECTIVITY; IMMUNODEFICIENCY; CELLS; PROTEINASE; PARTICLES AB Inhibitors of HIV-1 protease represent a new class of antiretroviral compounds, Here, we report the design and synthesis of two novel C2 symmetry-based inhibitors, MP-134 and MP-167, specifically targeted against HIV-1 variants with reduced sensitivity to another related protease inhibitor, A-77003. In addition, we describe the in vitro selection of viral variants with reduced sensitivity to these two protease inhibitors. An isoleucine-to-valine substitution at residue 84 (I84V) of the HIV-1 protease confers resistance to MP-134, whereas a glycine-to-valine substitution at residue 48 (G48V) confers resistance to MP-167, Testing other protease inhibitors against these variants has revealed specific overlapping patterns of resistance among these agents, These findings have important implications in the design of combination regimens using multiple protease inhibitors and underscore the need to develop non-cross-resistant compounds to be used toward this goal. C1 NYU,SCH MED,AARON DIAMOND AIDS RES CTR,NEW YORK,NY 10016. NCI,FREDERICK CANC RES & DEV CTR,SAIC FREDERICK,STRUCT BIOCHEM PROGRAM,FREDERICK,MD 21702. FU NIAID NIH HHS [AI 27665, AI 132427, AI 125541] NR 30 TC 4 Z9 4 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD JAN 1 PY 1996 VL 12 IS 1 BP 55 EP 61 DI 10.1089/aid.1996.12.55 PG 7 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA TP430 UT WOS:A1996TP43000008 PM 8825619 ER PT J AU Marcelletti, JF Lusso, P Katz, DH AF Marcelletti, JF Lusso, P Katz, DH TI n-Docosanol inhibits in vitro replication of HIV and other retroviruses SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID VIRUSES C1 NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. RP Marcelletti, JF (reprint author), LIDAK PHARMACEUT,11077 N TORREY PINES RD,LA JOLLA,CA 92037, USA. NR 9 TC 6 Z9 6 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD JAN 1 PY 1996 VL 12 IS 1 BP 71 EP 74 DI 10.1089/aid.1996.12.71 PG 4 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA TP430 UT WOS:A1996TP43000010 PM 8825621 ER PT J AU Allen, JP AF Allen, JP TI Subtypes of alcoholics based on psychometric measures SO ALCOHOL HEALTH & RESEARCH WORLD LA English DT Article DE AOD dependence; disorder classification; psychological assessment; personality test; motivation; treatment; comorbidity; patient monitoring ID PERSONALITY-CHARACTERISTICS; MOTIVATIONAL SUBTYPES; CLUSTER-ANALYSIS; TYPOLOGY; PROFILES; ABUSERS; SAMPLE AB One approach to subtyping alcoholics is the use of psychometric tests that quantify a person's personality characteristics, psychological characteristics, and intelligence, For example, researchers have used the personality Research Form, which measures basic personality traits, to establish alcoholism typologies, Other psychometric measures that have been employed in the classification of alcoholics, such as the Minnesota Multiphasic Personality inventory and the Millon Clinical Multiaxial Inventory, measure the presence of cc-occurring psychiatric disorders in the patients. Still other subtypes are based on tests assessing the patient's motivation for treatment, Although clinicians hope to use psychometric typologies to improve treatment planning and monitoring for their patients, several questions remain to be answered by additional research before the instruments and the typologies based on them achieve broad applicability. RP Allen, JP (reprint author), NIAAA,TREATMENT RES BRANCH,BETHESDA,MD, USA. NR 34 TC 3 Z9 3 U1 1 U2 3 PU NATL INST ALCOHOL ABUSE ALCOHOLISM PI ROCKVILLE PA 6000 EXECUTIVE BLVD, ROCKVILLE, MD 20892-7003 SN 0090-838X J9 ALCOHOL HEALTH RES W JI Alcohol Health Res. World PY 1996 VL 20 IS 1 BP 24 EP 29 PG 6 WC Substance Abuse SC Substance Abuse GA VK876 UT WOS:A1996VK87600006 ER PT J AU Grant, BF Pickering, RP AF Grant, BF Pickering, RP TI Comorbidity between DSM-IV alcohol and drug use disorders - Results from the National Longitudinal Alcohol Epidemiologic Survey SO ALCOHOL HEALTH & RESEARCH WORLD LA English DT Article DE comorbidity; AODD (alcohol and other drug use disorders); survey; epidemiology; United States; longitudinal study; diagnostic criteria ID ABUSE; POPULATION AB Research has not yet determined the answers to many questions regarding the comorbidity of alcohol and drug use disorders. Past studies often have not distinguished abuse from dependence and use and have not made diagnoses according to psychiatric classifications, This study relies on data from the 1992 National Longitudinal Alcohol Epidemiologic Survey which attempts to address these concerns. The study demonstrates a pervasive co-occurrence of alcohol and drug use disorders in the general population. Further, the comorbidity of alcohol and drug dependence is found to be significantly greater than the comorbidity of alcohol and drug abuse. RP Grant, BF (reprint author), NIAAA, DIV BIOMETRY & EPIDEMIOL, BIOMETRY BRANCH, BETHESDA, MD USA. NR 16 TC 17 Z9 17 U1 0 U2 1 PU NATL INST ALCOHOL ABUSE ALCOHOLISM PI ROCKVILLE PA 6000 EXECUTIVE BLVD, ROCKVILLE, MD 20892-7003 USA SN 0090-838X J9 ALCOHOL HEALTH RES W JI Alcohol Health Res. World PY 1996 VL 20 IS 1 BP 67 EP 72 PG 6 WC Substance Abuse SC Substance Abuse GA VK876 UT WOS:A1996VK87600012 ER PT J AU Deitz, DK Williams, GD Dufour, MC AF Deitz, DK Williams, GD Dufour, MC TI Alcohol consumption and dietary practices in the US population - 1987 and 1992 SO ALCOHOL HEALTH & RESEARCH WORLD LA English DT Article DE AOD consumption; nutrition; diet; health related behavior; state of health; survey; AOD use pattern; comparative study; fats; carbohydrates; Vitamins; salts; mineral nutrients ID ABSTINENCE; MODERATE; OBESITY; FATS AB Research indicates that the link between alcohol and poor nutrition is highly complex, Alcohol consumption is known to disrupt nutritional status via several mechanisms, One mechanism by which alcohol may affect nutrition is by inducing changes in dietary practices. Findings are presented based oil 2 years of data from a national survey of health-related activities, The relationship between alcohol consumption and dietary practices-such as types of food consumed whether vitamins were taken, belief that diet influences health, and frequency of eating out-is examined. The results show that associations exist between alcohol and diet after controlling for demographic and health variables, These findings have important implications for understanding the interaction between alcohol intake and nutritional status and the effect of this interaction on overall health. C1 NIAAA,BETHESDA,MD. RP Deitz, DK (reprint author), CSR INC,NIAAA,WASHINGTON,DC, USA. NR 24 TC 6 Z9 6 U1 0 U2 0 PU NATL INST ALCOHOL ABUSE ALCOHOLISM PI ROCKVILLE PA 6000 EXECUTIVE BLVD, ROCKVILLE, MD 20892-7003 SN 0090-838X J9 ALCOHOL HEALTH RES W JI Alcohol Health Res. World PY 1996 VL 20 IS 2 BP 128 EP 140 PG 13 WC Substance Abuse SC Substance Abuse GA XW451 UT WOS:A1996XW45100010 ER PT J AU Dufour, MC AF Dufour, MC TI Risks and benefits of alcohol use over the life span SO ALCOHOL HEALTH & RESEARCH WORLD LA English DT Article DE moderate AOD use; amount of AOD use; therapeutic drug effect; risk assessment; heart disorder; AODR (alcohol and other drug related) disorder; AODR mortality; age; traffic accident; impaired health; AOD associated consequences ID CONSUMPTION; MORTALITY AB Especially at low and moderate drinking levels, alcohol consumption can be associated with benefits (e.g. protection against coronary heart disease) as well as risks (e.g. increased risk of accidents). These benefits and risks may change across a person's life span. To determine the likely net outcome of alcohol consumption, one must weigh the probable risks and benefits for each drinker. These assessments are based on the individual drinker's consumption levels, his or her personal characteristics (e.g. age or preexisting risk factors for coronary heart disease), and subjective values as well as on social considerations. The validity of such assessments also depends on the accuracy with which alcohol consumption and ali:alcohol-related consequences can be measured. RP Dufour, MC (reprint author), NIAAA,BETHESDA,MD, USA. NR 14 TC 15 Z9 16 U1 0 U2 2 PU NATL INST ALCOHOL ABUSE ALCOHOLISM PI ROCKVILLE PA 6000 EXECUTIVE BLVD, ROCKVILLE, MD 20892-7003 SN 0090-838X J9 ALCOHOL HEALTH RES W JI Alcohol Health Res. World PY 1996 VL 20 IS 3 BP 145 EP 151 PG 7 WC Substance Abuse SC Substance Abuse GA WC834 UT WOS:A1996WC83400001 ER PT J AU Gordis, E AF Gordis, E TI Alcohol research and social policy - An overview SO ALCOHOL HEALTH & RESEARCH WORLD LA English DT Article DE public policy on AOD; AOD consumption; research; minimum drinking age laws; warning label; alcoholic beverage; moderate AOD use; therapeutic drug effect; United States; federal government; government agency AB Science can facilitate the task of choosing among complex social policies, although if rarely serves as the only basis for policy development. Science's role in policy formation can be decisive when public support already exists, as with the passage of the Federal Uniform Drinking Age Act. Science can assess a policy after it has been implemented as in the scientific evaluation of the health warning labels on alcoholic beverage containers. In addition, science can investigate the short- and long-term benefits and risks of areas where the development of policies is likely. An example is the current scientific examination of the tradeoffs involved in moderate alcohol consumption. RP Gordis, E (reprint author), NIAAA,BETHESDA,MD, USA. NR 11 TC 2 Z9 3 U1 0 U2 0 PU NATL INST ALCOHOL ABUSE ALCOHOLISM PI ROCKVILLE PA 6000 EXECUTIVE BLVD, ROCKVILLE, MD 20892-7003 SN 0090-838X J9 ALCOHOL HEALTH RES W JI Alcohol Health Res. World PY 1996 VL 20 IS 4 BP 208 EP 212 PG 5 WC Substance Abuse SC Substance Abuse GA WN686 UT WOS:A1996WN68600001 ER PT J AU Chaska, B Kiley, JP Millman, RP Phillips, BA Rogus, SD Strohl, KP Strollo, PJ Suratt, PM Walsh, JK Weiss, JW White, D Zepf, B AF Chaska, B Kiley, JP Millman, RP Phillips, BA Rogus, SD Strohl, KP Strollo, PJ Suratt, PM Walsh, JK Weiss, JW White, D Zepf, B TI Sleep apnea: Is your patient at risk? (Reprinted) SO AMERICAN FAMILY PHYSICIAN LA English DT Reprint ID NASAL CPAP; CHILDREN; SURGERY; THERAPY; ADULTS; OXYGEN AB Obstructive sleep apnea is a breathing disorder characterized by repeated collapse of the upper airway during sleep, with cessation of breathing. Four percent of middle-aged men and 2 percent of middle-aged women meet minimal criteria for the sleep apnea syndrome. Risk factors include loud, chronic snoring, obesity (especially nuchal), hypertension, excessive daytime sleepiness, and an increased tendency for automobile and work-related accidents. Cardiovascular comorbidity and complications include systemic hypertension, arrhythmias and possibly myocardial ischemia and myocardial infarction in patients with coronary artery disease. Diagnosis is confirmed by a sleep study; currently, polysomnography is the optimum test. Treatment options range from behavioral therapy alone for mild cases to a combination of behavioral approaches and continuous positive airway pressure and/or surgery for moderate and severe cases. Continuous positive airway pressure is the most effective noninvasive treatment. Primary care physicians play a key role in the identification, management and follow-up of patients with sleep apnea. C1 NHLBI,OFF PREVENT EDUC & CONTROL,BETHESDA,MD 20892. NR 38 TC 16 Z9 16 U1 0 U2 1 PU AMER ACAD FAMILY PHYSICIANS PI KANSAS CITY PA 8880 WARD PARKWAY, KANSAS CITY, MO 64114-2797 SN 0002-838X J9 AM FAM PHYSICIAN JI Am. Fam. Physician PD JAN PY 1996 VL 53 IS 1 BP 247 EP 253 PG 7 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA TQ021 UT WOS:A1996TQ02100026 ER PT J AU Mail, PD AF Mail, PD TI Alcohol abuse in urban Indian adolescents and women: A longitudinal study for assessment and risk evaluation - Comment SO AMERICAN INDIAN AND ALASKA NATIVE MENTAL HEALTH RESEARCH LA English DT Article ID POLICY RP Mail, PD (reprint author), NIAAA,NIH,WILCO BLDG,SUITE 505,ROCKVILLE,MD 20892, USA. NR 32 TC 0 Z9 0 U1 0 U2 0 PU UNIVERSITY PRESS COLORADO PI NIWOT PA PO BOX 849, NIWOT, CO 80544 SN 0893-5394 J9 AM INDIAN ALASKA NAT JI Am. Indian Alsk. Nativ. Ment. Health Res. PY 1996 VL 7 IS 1 BP 48 EP 53 PG 6 WC Psychology, Clinical SC Psychology GA TW047 UT WOS:A1996TW04700003 ER PT J AU Tarone, RE Chu, KC AF Tarone, RE Chu, KC TI Evaluation of birth cohort patterns in population disease rates SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE breast neoplasms; cohort effect; models, statistical; mortality; Poisson distribution; women ID BREAST-CANCER; AGE-PERIOD; TRENDS; MORTALITY; RISK AB Interpretation of trends in disease rates using conventional age-period-cohort analyses is made difficult by the lack of a unique set of parameters specifying any given model. Because of difficulties inherent in age-period-cohort models, neither the magnitude nor the direction of a linear trend in birth cohort effects or calendar period effects can be determined unambiguously. This leads to considerable uncertainty in making inferences regarding disease etiology based on birth cohort or calendar period trends. In this paper, the authors demonstrate that changes in the direction or magnitude of long term trends can be identified unequivocally in age-period-cohort analyses, and they provide parametric methods for evaluating such changes in trend within the usual Poisson regression framework. Such changes can have important implications for disease etiology. This is demonstrated in applications of the proposed methods to the investigation of birth cohort trends in female breast cancer mortality rates obtained from the National Center for Health Statistics for the United States (1970-1989) and from the World Health Organization for Japan (1955-1979). C1 NCI,DIV CANC PREVENT & CONTROL,EARLY DETECT BRANCH,BETHESDA,MD 20892. RP Tarone, RE (reprint author), NCI,DIV CANC ETIOL,BIOSTAT BRANCH,EXECUT PLAZA N,ROOM 403,BETHESDA,MD 20892, USA. NR 22 TC 79 Z9 82 U1 0 U2 2 PU AMER J EPIDEMIOLOGY PI BALTIMORE PA 624 N BROADWAY RM 225, BALTIMORE, MD 21205 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JAN 1 PY 1996 VL 143 IS 1 BP 85 EP 91 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA TN424 UT WOS:A1996TN42400010 PM 8533751 ER PT J AU Milton, RC AF Milton, RC TI Diet and nuclear lens opacities SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Letter RP Milton, RC (reprint author), NEI,DIV BIOMETRY & EPIDEMIOL,BETHESDA,MD 20892, USA. NR 4 TC 1 Z9 1 U1 0 U2 1 PU AMER J EPIDEMIOLOGY PI BALTIMORE PA 624 N BROADWAY RM 225, BALTIMORE, MD 21205 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JAN 1 PY 1996 VL 143 IS 1 BP 101 EP 101 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA TN424 UT WOS:A1996TN42400012 PM 8533741 ER PT J AU Edmundson, E Parcel, GS Perry, CL Feldman, HA Smyth, M Johnson, CC Layman, A Bachman, K Perkins, T Smith, K Stone, E AF Edmundson, E Parcel, GS Perry, CL Feldman, HA Smyth, M Johnson, CC Layman, A Bachman, K Perkins, T Smith, K Stone, E TI The effects of the child and adolescent trial for cardiovascular health intervention on psychosocial determinants of cardiovascular disease risk behavior among third-grade students SO AMERICAN JOURNAL OF HEALTH PROMOTION LA English DT Article DE cardiovascular disease; children; prevention; social cognitive theory ID PHYSICAL-ACTIVITY; PROMOTION; DIET AB Purpose. The Child and Adolescent Trial for Cardiovascular Health is a multi-site study of a school-based intervention designed to reduce or prevent the development of risk factors for cardiovascular disease. The goal was to change (or prevent) related risk behaviors and the psychosocial variables that theoretically influence those behaviors. Design. A nested design was used in which schools served as the primary unit of analysis. Twenty-four schools participated at each of four sites (Austin, San Diego, Minneapolis, and New Orleans). Each site had 10 control and 14 intervention schools. Setting and Subject. Ninety-six schools (with more than 6000 students) in the four sites were randomized to three treatment conditions: control, school-based interventions, and school-plus-family interventions. The sample included approximately equal numbers of males and females and was 67.5% white, 13.9% African-American, 13.9% Hispanic, and 4.7% other. Measures. The psychosocial determinants measured included improvements in dietary knowledge, intentions, self-efficacy, usual behavior, perceived social reinforcement for healthy food choices, and perceived reinforcement and self-efficacy for physical activity. Results. The findings indicated significant improvements in all the psychosocial determinants measured (p < .0001). The results revealed a greater impact in the school-plus-family intervention schools for two determinants, usual dietary behavior and intentions to eat heart-healthy foods. Conclusions. These findings support theory-based interventions for changing selected psychosocial determinants of cardiovascular disease risk behavior among children. C1 UNIV TEXAS,HLTH SCI CTR,HOUSTON,TX 77030. UNIV MINNESOTA,MINNEAPOLIS,MN 55455. NEW ENGLAND RES INST INC,WATERTOWN,MA. TULANE UNIV,SCH PUBL HLTH & TROP MED,NEW ORLEANS,LA 70112. UNIV CALIF SAN DIEGO,SAN DIEGO,CA 92103. NHLBI,BETHESDA,MD 20892. RP Edmundson, E (reprint author), UNIV TEXAS,DEPT KINESIOL,BLE 222,AUSTIN,TX 78712, USA. NR 23 TC 39 Z9 39 U1 0 U2 3 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0890-1171 J9 AM J HEALTH PROMOT JI Am. J. Health Promot. PD JAN-FEB PY 1996 VL 10 IS 3 BP 217 EP 225 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA TP443 UT WOS:A1996TP44300012 PM 10163302 ER PT J AU Pearson, JD Blackman, MR Harman, SM AF Pearson, JD Blackman, MR Harman, SM TI Longitudinal age-specific reference values for serum androgen and sex hormone binding globulin levels in healthy men. SO AMERICAN JOURNAL OF HUMAN BIOLOGY LA English DT Meeting Abstract C1 NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 1042-0533 J9 AM J HUM BIOL JI Am. J. Hum. Biol. PY 1996 VL 8 IS 1 BP 152 EP 152 PG 2 WC Anthropology; Biology SC Anthropology; Life Sciences & Biomedicine - Other Topics GA TV926 UT WOS:A1996TV92600063 ER PT J AU Henrich, WL Agodoa, LE Barrett, B Bennett, WM Blantz, RC Buckalew, VM DAgati, VD DeBroe, ME Duggin, GG Eknoyan, G Elseviers, MM Gomez, RA Matzke, GR Porter, GA Sabatini, S Stoff, JS Striker, GE Winchester, JF AF Henrich, WL Agodoa, LE Barrett, B Bennett, WM Blantz, RC Buckalew, VM DAgati, VD DeBroe, ME Duggin, GG Eknoyan, G Elseviers, MM Gomez, RA Matzke, GR Porter, GA Sabatini, S Stoff, JS Striker, GE Winchester, JF TI Analgesics and the kidney: Summary and recommendations to the scientific advisory board of the National Kidney Foundation from an Ad Hoc committee of the National Kidney Foundation SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Editorial Material C1 NIH,BETHESDA,MD 20892. MEM UNIV NEWFOUNDLAND,DIV NEPHROL,ST JOHNS,NF,CANADA. OREGON HLTH SCI UNIV,DEPT MED,DIV NEPHROL,PORTLAND,OR 97201. UNIV CALIF SAN DIEGO,SCH MED,DIV NEPHROL HYPERTENS,SAN DIEGO,CA 92103. WAKE FOREST UNIV,BOWMAN GRAY SCH MED,DIV NEPHROL,WINSTON SALEM,NC. COLUMBIA UNIV,COLL PHYS & SURG,RENAL PATHOL LAB,NEW YORK,NY 10027. UNIV ANTWERP HOSP,DEPT NEPHROL HYPERTENS,ANTWERP,BELGIUM. ROYAL PRINCE ALFRED HOSP,SYDNEY,NSW,AUSTRALIA. UNIV VIRGINIA,HLTH SCI CTR,CHILD HLTH RES CTR,DIV PEDIAT NEPHROL,CHARLOTTESVILLE,VA 22903. UNIV PITTSBURGH,SCH PHARM,DEPT PHARM & THERAPEUT,PITTSBURGH,PA 15260. TEXAS TECH UNIV,HLTH SCI CTR,SCH MED,DEPT PHYSIOL,LUBBOCK,TX 79430. UNIV MASSACHUSETTS,MED CTR,RENAL MED DIV,WORCESTER,MA. GEORGETOWN UNIV,MED CTR,DIV NEPHROL,WASHINGTON,DC 20057. BAYLOR COLL MED,DEPT MED,NEPHROL SECT,HOUSTON,TX 77030. RP Henrich, WL (reprint author), MED COLL OHIO,DEPT MED,POB 10008,TOLEDO,OH 43699, USA. NR 1 TC 97 Z9 102 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD JAN PY 1996 VL 27 IS 1 BP 162 EP 165 DI 10.1016/S0272-6386(96)90046-3 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA TN799 UT WOS:A1996TN79900022 PM 8546133 ER PT J AU Thomas, DL Gruninger, SE Siew, C Joy, ED Quinn, TC AF Thomas, DL Gruninger, SE Siew, C Joy, ED Quinn, TC TI Occupational risk of hepatitis C infections among general dentists and oral surgeons in North America SO AMERICAN JOURNAL OF MEDICINE LA English DT Article ID VIRUS-INFECTION; DRUG-USERS; B VIRUS; VACCINATION; PERSONNEL; ANTIBODY AB PURPOSE: To assess the occupational risk of hepatitis C virus (HCV) infection among dental personnel. METHODS: Three hundred forty-three oral surgeons and 305 general dentists were recruited at national meetings of the American Dental Association and matched by gender, age, years of practice, and location of practice. Each participant completed a detailed questionnaire designed to measure occupational risk of blood-borne infections and supplied a sample of blood. Antibodies to HCV (anti-HCV) were assessed by second-generation enzyme immunoassay and recombinant immunoblot assay. As a marker of occupational exposure to blood-borne viruses, hepatitis B virus (HBV) surface antigen and antibodies to HBV surface and core antigens were measured by enzyme immunoassay. RESULTS: Anti-HCV was found in 2.0% of oral surgeons and 0.7% of general dentists (odds ratio [OR] = 3.2, P = 0.133). Anti-HCV was more prevalent (P < 0.01) in dental personnel who were older, had more years of practice, and had serologic markers of HBV infection. Serologic markers of HBV infection were found in 7.8% of general dentists and 21.2% of oral surgeons (OR 3.1, P < 0.001). CONCLUSIONS: These data confirm high rates of HBV infection among dental personnel, but suggest that the risk of HCV infection is considerably lower. C1 AMER DENT ASSOC HLTH FDN,CHICAGO,IL. MED COLL GEORGIA,DEPT ORAL SURG,AUGUSTA,GA 30912. NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. RP Thomas, DL (reprint author), JOHNS HOPKINS UNIV,SCH MED,DIV INFECT DIS,1155 ROSS BLDG,720 RUTLAND AVE,BALTIMORE,MD 21205, USA. NR 17 TC 79 Z9 82 U1 0 U2 1 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9343 J9 AM J MED JI Am. J. Med. PD JAN PY 1996 VL 100 IS 1 BP 41 EP 45 DI 10.1016/S0002-9343(96)90009-1 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA TT033 UT WOS:A1996TT03300009 PM 8579085 ER PT J AU Agodoa, LY Jones, CA Held, PJ AF Agodoa, LY Jones, CA Held, PJ TI End-stage renal disease in the USA: Data from the United States renal data system SO AMERICAN JOURNAL OF NEPHROLOGY LA English DT Article DE ESRD; USRDS; incidence; mortality; dialysis dose; Kt/V AB Treated end-stage renal disease continues to increase at an alarming rate in the US. There has been an exponential growth in the incidence rate between 1982 and 1991 at the rate of 8.76% per year. Approximately 218,042 patients received treatment for ESRD in 1991, of which 49,909 were new patients. Although the increase in the incidence rate is seen for all the major disease categories responsible for ESRD, diabetes mellitus, probably type 2, and hypertension are responsible for the bulk of the increase. African Americans and Native Americans have shown the most dramatic increase; diabetes being the major reason for both races, but for African Americans, hypertension is the leading cause of ESRD. A bulk of the increase in the ESRD patient population has been in the older age (greater than 65 years of age) group. The mortality rate for the ESRD patient population, and, specifically, for the dialysis population remains relatively high, with 1-year survival probabilities of approximately 78%. Some of the contributing factors cited for the high death rate, especially in the dialysis patient population include inadequate dialysis dose, low flux of the dialysis membranes, shortened dialysis times, an increase in the age of the ESRD population, and bioincompatible dialysis membranes. The effect of the widely practiced dialyzer reuse on dialysis patient morbidity and mortality remains unclear. C1 NIDDKD,END STAGE RENAL DIS PROGRAM,BETHESDA,MD 20892. NIDDKD,DIV KIDNEY UROL & HEMATOL DIS,PROGRAM EPIDEMIOL,BETHESDA,MD 20892. UNIV MICHIGAN,US RENAL DATA SYST COORDINATING CTR,ANN ARBOR,MI 48109. NR 15 TC 35 Z9 35 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0250-8095 J9 AM J NEPHROL JI Am. J. Nephrol. PD JAN-FEB PY 1996 VL 16 IS 1 BP 7 EP 16 DI 10.1159/000168965 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA TL221 UT WOS:A1996TL22100002 PM 8719761 ER PT J AU Li, ZH Li, L Zielke, R Cheng, L Xiao, RP Crow, MT StetlerStevenson, G Froehlich, J Lakatta, EG AF Li, ZH Li, L Zielke, R Cheng, L Xiao, RP Crow, MT StetlerStevenson, G Froehlich, J Lakatta, EG TI Increased expression of 72-kd type IV collagenase (MMP-2) in human aortic atherosclerotic lesions SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID MATRIX; LOCALIZATION; MEMBRANE; INVASION; PLAQUES; ENZYME AB MMP-2, a secreted 72-kd metalloproteinase that specifically degrades type IV collagen as well as denatured collagens, has been implicated in smooth muscle cell migration To evaluate the possible contribution of this enzyme to the formation and Progression of the atherosclerotic lesion, the expression of MMP-2 was studied in human aortic tissue. MMP-2 was visualized in frozen sections of the aortic wall by an immunofluorescent technique with a polyclonal antibody. Expression of MMP-2 in the aortic extracts was also studied by zymography and Western blotting Our results reveal that a greater amount of MMP-2 is present in fatty streaks and atherosclerotic plaques as compared with normal regions of the aorta. Immunoblotting analysis showed that MMP-2 was expressed in atherosclerotic plaques > fatty streak > normal aortic wall ia a ratio of approximately 4:2:1. Zymograms show that both forms (activated and latent) of MMP-2 increased in the atherosclerotic plaques The presence of macrophages, detected by an immunohistochemical technique in some areas of higher MMP-2 expression suggests that these cells are a possible source of MMP-2. We conclude that MMP-2 collagenase may have a role in the formation and progression of the atherosclerotic lesion and may be involved in clinical complications of atherosclerosis, such as fissure and rupture, leading thrombosis. C1 NIA,CARDIOVASC SCI LAB,BALTIMORE,MD 21224. UNIV MARYLAND,DEPT PEDIAT,BRAIN & TISSUE BANK,BALTIMORE,MD 21201. NCI,BETHESDA,MD 20892. RI Stetler-Stevenson, William/H-6956-2012 OI Stetler-Stevenson, William/0000-0002-5500-5808 NR 32 TC 176 Z9 199 U1 0 U2 3 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD JAN PY 1996 VL 148 IS 1 BP 121 EP 128 PG 8 WC Pathology SC Pathology GA TP291 UT WOS:A1996TP29100014 PM 8546199 ER PT J AU Kwon, ED Zablocki, K Peters, EM Jung, KY GarciaPerez, A Burg, MB AF Kwon, ED Zablocki, K Peters, EM Jung, KY GarciaPerez, A Burg, MB TI Betaine and inositol reduce MDCK cell glycerophosphocholine by stimulating its degradation SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE organic osmolytes; compatible osmolytes; glycerophosphocholine, choline phosphodiesterase; renal medulla; hypertonicity; urea ID ORGANIC OSMOLYTE GLYCEROPHOSPHORYLCHOLINE; COLLECTING DUCT CELLS; RENAL-CELLS; OSMOREGULATION; METABOLISM; KIDNEYS; UREA; GPC AB The amount of glycerophosphocholine (GPC) in renal medullary cells in vivo and in cultured renal [Madin-Darby canine kidney (MDCK)] cells varies with extracellular NaCl and urea. We previously showed that this is largely due to modulation of GPC degradation catalyzed by GPC:choline phosphodiesterase (GPC: PDE). GPC also varies inversely with the levels of other compatible osmolytes, the accumulation of which is induced by high tonicity. We tested whether GPC:PDE activity and GPC degradation are affected by accumulation of compatible osmolytes other than GPC. We find that MDCK cell GPC content decreases when the cells take up betaine and/or inositol from the medium. The effect is considerably greater for cells in isosmotic or high-NaCl medium than in high-urea medium. This difference is associated with suppression of betaine and inositol accumulation with high urea. We then measured GPC:PDE activity with a novel chemiluminescent assay. Addition of inositol and/or betaine to the medium greatly increases GPC:PDE activity in cells in isosmotic or high-NaCl media, but the increase is much less in high-urea medium. The increases in GPC:PDE activity, associated with the presence of betaine, are accompanied by commensurate increases in absolute rates of endogenous GPC degradation by cells in isosmotic or high-NaCl medium. We found previously that, in MDCK cells incubated for 2 days in high-NaCl medium, the rate of GPC synthesis from phosphatidylcholine is increased, correlated with an increase in phospholipase activity. However, in the present experiments, betaine accumulation has no effect on phospholipase activity under those conditions and, thus, presumably does not affect GPC synthesis. Collectively, these data support the conclusion that betaine and/or inositol reduces GPC by increasing GPC degradation catalyzed by GPC:PDE. This mechanism enables GPC to be reciprocally regulated relative to other compatible osmolytes, thus maintaining an appropriate total osmolyte content. RP Kwon, ED (reprint author), NHLBI, KIDNEY & ELECTROLYTE METAB LAB, BLDG 10, RM 6N307, BETHESDA, MD 20892 USA. NR 18 TC 5 Z9 5 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD JAN PY 1996 VL 270 IS 1 BP C200 EP C207 PG 8 WC Cell Biology; Physiology SC Cell Biology; Physiology GA TT104 UT WOS:A1996TT10400021 PM 8772445 ER PT J AU SheikhHamad, D Ferraris, JD Dragolovich, J Preuss, HG Burg, MB Garciaperez, A AF SheikhHamad, D Ferraris, JD Dragolovich, J Preuss, HG Burg, MB Garciaperez, A TI CD9 antigen mRNA is induced by hypertonicity in two renal epithelial cell lines SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE differential mRNA display polymerase chain reaction; osmoregulation; osmotic stress; cluster of differentiation ID DIPHTHERIA-TOXIN RECEPTOR; KIDNEY ALDOSE REDUCTASE; HIGH EXTRACELLULAR NACL; MOLECULAR-CLONING; MEDULLARY CELLS; INOSITOL COTRANSPORTER; DIFFERENTIAL DISPLAY; MESSENGER-RNA; MDCK CELLS; PROTEIN AB In diverse organisms, cells adapt to hyperosmotic stress by accumulating organic osmolytes. Mammalian renal medullary cells are routinely under osmotic stress. Two renal cell lines, Madin-Darby canine kidney (MDCK) and PAP-HT85, have been widely used to study mammalian osmotic regulation. In these epithelial cells, extracellular hypertonicity induces gene transcription of proteins directly involved in the metabolism and transport of organic osmolytes. This induction is relatively specific and not part of a generalized stress response. Little is known about the signal transduction pathway between cellular detection of extracellular osmolality and increased specific gene transcription. Here, using differential mRNA display polymerase chain reaction on MDCK cells in isotonic vs. hypertonic medium, we identify a cDNA product corresponding to CD9 antigen mRNA. CD9 antigen is a cell surface glycoprotein originally found in cells of the immune system. Although CD9 antigen has been structurally characterized, its function is unclear. We further demonstrate that CD9 antigen mRNA is present in MDCK and PAP-HT85 cells and that its mRNA abundance is induced by extracellular hypertonicity, but not by heat stress. Also, we show that accumulation of organic osmolytes markedly attenuates the CD9 mRNA induction, as only recently demonstrated with genes involved in the hyperosmotic stress response. This suggests a role for CD9 antigen in this response. C1 NHLBI, KIDNEY & ELECTROLYTE METAB LAB, BETHESDA, MD 20892 USA. NR 45 TC 20 Z9 20 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD JAN PY 1996 VL 270 IS 1 BP C253 EP C258 PG 6 WC Cell Biology; Physiology SC Cell Biology; Physiology GA TT104 UT WOS:A1996TT10400027 PM 8772451 ER PT J AU Eakes, AT Hymer, TK Rosenthal, MJ Moss, J Katz, MS AF Eakes, AT Hymer, TK Rosenthal, MJ Moss, J Katz, MS TI Alterations of adenylyl cyclase-linked G proteins in rat liver during aging SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE beta-adrenergic receptor; cholera toxin; pertussis toxin; adenosine 5'-diphosphate ribosylation factor ID BETA-ADRENERGIC-RECEPTOR; ADP-RIBOSYLATION; HEPATOCYTES; BINDING; GTP; IDENTIFICATION; GLYCOGENOLYSIS; SUBUNITS; ENZYME AB beta-Adrenergic stimulation of adenylyl cyclase in rat liver increases during aging. We examined whether this increase is related to alterations in the stimulatory and inhibitory G proteins (G(s) and G(i)) linked to adenylyl cyclase. Levels of immunoreactive alpha- and beta-subunits of G(s) and G(i) in liver plasma membranes from 6-, 12-, 18-, and 24-mo-old rats were unchanged with age, as was pertussis toxin-catalyzed [P-32]ADP ribosylation of G(i) alpha. Cholera toxin-catalyzed [P-32]ADP ribosylation of G(s) alpha and G(s) bioactivity, assessed as reconstitution of adenylyl cyclase activity in S49 cyc(-) cell membranes, increased two- to threefold between 6 and 12-18 mo, and declined by 24 mo. Recombinant ADP ribosylation factor (ARF) enhanced cholera toxin labeling of G(s) alpha at all ages, yet abolished the increase in toxin labeling at 12-18 mo. Auto-ADP ribosylation of the cholera toxin A(1) peptide also increased transiently with age. Alteration of G(s) alpha, as reflected by increased cholera toxin labeling and G(s) bioactivity, may be involved in the regulation of beta-adrenergic-responsive adenylyl cyclase in rat liver during aging. Moreover, changes in endogenous ARF levels could contribute to age differences in cholera toxin labeling of G(s) alpha. C1 UNIV TEXAS, GERIATR RES EDUC & CLIN CTR 182, AUDIE L MURPHY MEM VET HOSP,DEPT MED, HLTH SCI CTR, SAN ANTONIO, TX 78284 USA. UNIV CALIF LOS ANGELES, SCH MED, SAN FERNANDO VALLEY PROGRAM, SEPULVEDA, CA 91343 USA. VET AFFAIRS MED CTR, CTR GERIATR RES EDUC & CLIN, SEPULVEDA, CA 91343 USA. NHLBI, NIH, PULM CRIT CARE MED BRANCH, BETHESDA, MD 20892 USA. NR 32 TC 5 Z9 5 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD JAN PY 1996 VL 270 IS 1 BP E126 EP E132 PG 7 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA TT393 UT WOS:A1996TT39300019 PM 8772484 ER PT J AU Paulais, M Valdez, IH Fox, PC Evans, RL Turner, RJ AF Paulais, M Valdez, IH Fox, PC Evans, RL Turner, RJ TI Ion transport systems in human labial acinar cells SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE salivary gland; fluid secretion; chloride secretion; stimulus-secretion coupling; fluorescent dyes ID SALIVARY-GLANDS; INTRACELLULAR-PH; FLUID SECRETION; CL--HCO3 EXCHANGE; SJOGRENS SYNDROME; NA+/H+ EXCHANGE; NA-H; RAT; HCO3; INVOLVEMENT AB Human labial acini were assayed for the presence of ion transport systems associated with salivary fluid secretion using microfluorometric methods; Na+-K+-Cl- cotransport and Na+/H+ exchange activities (determined by their bumetanide and amiloride sensitivities, respectively) were found at levels similar to 50% of those seen in similarly assayed rat parotid acini, but little, if any, Cl-/HCO3- exchange activity was observed. Also, when human labial acini were stimulated with the muscarinic agonist carbachol, little evidence of the intracellular acidification associated with HCO3- secretion by other salivary glands was found. Na+/H+ exchange activity in human labial acini was downregulated (similar to 40%) by beta-adrenergic stimulation and upregulated (approximately threefold) by muscarinic stimulation. In contrast, beta-adrenergic stimulation produced only a marginally significant increase in Na+-K+-Cl- cotransport activity, and muscarinic stimulation was without effect. We conclude that basolateral Na+-K+-Cl- cotransport appears to be the dominant mechanism driving Cl- secretion and thereby fluid secretion in this tissue. C1 NIDR, CLIN INVEST & PATIENT CARE BRANCH, BETHESDA, MD 20892 USA. RI Paulais, Marc/E-5623-2017 NR 31 TC 11 Z9 11 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD JAN PY 1996 VL 270 IS 1 BP G213 EP G219 PG 7 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA TT394 UT WOS:A1996TT39400027 PM 8772520 ER PT J AU Jones, PP Spraul, M Matt, KS Seals, DR Skinner, JS Ravussin, E AF Jones, PP Spraul, M Matt, KS Seals, DR Skinner, JS Ravussin, E TI Gender does not influence sympathetic neural reactivity to stress in healthy humans SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE microneurography; muscle sympathetic nerve activity; cold presser; isometric exercise; mental stress ID CORONARY HEART-DISEASE; CARDIOVASCULAR REACTIVITY; PLASMA NOREPINEPHRINE; SEX-DIFFERENCES; NERVE ACTIVITY; FOLLOW-UP; RESPONSES; EXERCISE; MUSCLE; AGE AB Previous data support the idea of heightened sympathetically mediated cardiovascular reactivity in males. However, definitive conclusions cannot be made because of inconsistent reports, possibly stemming from imprecise measurement of sympathetic activity and/or failure to equate the stress stimuli between genders. The present study tested the hypothesis that males exhibit heightened sympathetic reactivity that is associated with heightened cardiovascular and plasma catecholamine responses. In 37 healthy adults (20 males, 17 females: age = 20-42 yr), direct recordings of skeletal muscle sympathetic nerve activity (MSNA), plasma catecholamines, heart rate, blood pressure, and perceived stress were measured before and during three laboratory stressors (isometric handgrip, cold presser, and mental arithmetic). MSNA, catecholamine, and cardiovascular reactivity (defined as change from rest) were not consistently different between genders. For the isometric handgrip, when expressed as absolute unit changes, males had larger MSNA responses (P < 0.01), which were partially explained by greater contraction force; they did not differ in terms of percent change from baseline or in perceived stress. The responses to the cold presser and mental arithmetic tasks were similar between genders. These findings indicate that stress-evoked vasoconstrictor neural excitation and the associated increases in blood pressure are not consistently influenced by gender. C1 UNIV COLORADO, DEPT MED CARDIOL, BOULDER, CO 80309 USA. NIDDKD, CLIN DIABET & NUTR SECT, NATL INST HLTH, PHOENIX, AZ 85016 USA. ARIZONA STATE UNIV, EXERCISE & SPORT RES INST, TEMPE, AZ 85287 USA. RP Jones, PP (reprint author), UNIV COLORADO, DEPT KINESIOL, CAMPUS BOX 354, BOULDER, CO 80309 USA. NR 38 TC 60 Z9 60 U1 1 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD JAN PY 1996 VL 270 IS 1 BP H350 EP H357 PG 8 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA TV391 UT WOS:A1996TV39100045 PM 8769771 ER PT J AU Layton, HE Knepper, MA Chou, CL AF Layton, HE Knepper, MA Chou, CL TI Permeability criteria for effective function of passive countercurrent multiplier SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL FLUID AND ELECTROLYTE PHYSIOLOGY LA English DT Article DE kidney; inner medulla; thin descending limb; thin ascending limb; urea permeability; isolated perfused tubule; chinchilla; urine concentrating mechanism; mathematical model ID MEDULLARY COLLECTING DUCT; RENAL CONCENTRATING MECHANISM; HYPERTONIC URINE FORMATION; DESCENDING VASA RECTA; THICK ASCENDING LIMB; CENTRAL CORE MODEL; UREA TRANSPORT; SODIUM-CHLORIDE; 3-DIMENSIONAL ANATOMY; ION CONDUCTANCE AB The urine concentrating effect of the mammalian renal inner medulla has been attributed to countercurrent multiplication of a transepithelial osmotic difference arising from passive absorption of NaCl from thin ascending limbs of long loops of Henle. This study assesses, both mathematically and experimentally, whether the permeability criteria for effective function of this passive hypothesis are consistent with transport properties measured in long loops of Henle of chinchilla. Mathematical simulations incorporating loop of Henle transepithelial permeabilities idealized for the passive hypothesis generated a steep inner medullary osmotic gradient, confirming the fundamental feasibility of the passive hypothesis. However, when permeabilities measured in chinchilla were used, no inner medullary gradient was generated. A key parameter in the apparent failure of the passive hypothesis is the long-loop descending limb (LDL) urea permeability, which must be small to prevent significant transepithelial urea flux into inner medullary LDL. Consequently, experiments in isolated perfused thin LDL were conducted to determine whether the urea permeability may be lower under conditions more nearly resembling those in the inner medulla. LDL segments were dissected from 30-70% of the distance along the inner medullary axis of the chinchilla kidney. The factors tested were NaCl concentration (125-400 mM in perfusate and bath), urea concentration (5-500 mM in perfusate and bath), calcium concentration (2-8 mM in perfusate and bath), and protamine concentration (300 mu g/ml in perfusate). None of these factors significantly altered the measured urea permeability, which exceeded 20 x 10(-5) cm/s for all conditions. Simulation results show that this moderately high urea permeability in LDL is an order of magnitude too high for effective operation of the passive countercurrent multiplier. C1 NHLBI, KIDNEY & ELECTROLYTE METAB LAB, BETHESDA, MD 20892 USA. RP Layton, HE (reprint author), DUKE UNIV, DEPT MATH, BOX 90320, DURHAM, NC 27708 USA. FU NIDDK NIH HHS [DK-42091] NR 52 TC 45 Z9 45 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0363-6127 J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Fluid Electrolyte Physiol. PD JAN PY 1996 VL 270 IS 1 BP F9 EP F20 PG 12 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA TT558 UT WOS:A1996TT55800002 PM 8769818 ER PT J AU Champoux, M Kriete, MF Higley, JD Suomi, SJ AF Champoux, M Kriete, MF Higley, JD Suomi, SJ TI CBC and serum chemistry differences between Indian-derived and Chinese-Indian hybrid rhesus monkey infants SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Article DE rhesus monkey; hemogram; serum chemistry; infant ID TRAITS AB Hematological and clinical biochemistry measures are commonly utilized as indicators of the health status of nonhuman primates, Among individuals in a population of a given species, there may be considerable variation in these parameters, Still wider variation may be found among different strains or subspecies of some orders. To date, few studies have addressed this phenomenon among strains of nonhuman primates of a given species, Blood samples for hematological and serum biochemical analyses were obtained from 29 Indian-derived and 13 Chinese-Indian hybrid nursery-reared rhesus macaque infants. Total protein, mean corpuscular hemoglobin concentration, mean corpuscular hemoglobin, erythrocyte count, hemoglobin, and hematocrit were all higher in the hybrid infants, These results indicate that the origin or strain of the animal should be considered when designing studies using rhesus macaques. (C) 1996 Wiley-Liss, Inc. C1 NICHHD,COMPARAT ETHOL LAB,POOLESVILLE,MD. NEI,VET RES & RESOURCES SECT,BETHESDA,MD 20892. NIAAA,DICBR,CLIN STUDIES LAB,PRIMATE UNIT,BETHESDA,MD 20892. NR 19 TC 17 Z9 17 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PY 1996 VL 39 IS 1 BP 79 EP 84 DI 10.1002/(SICI)1098-2345(1996)39:1<79::AID-AJP6>3.0.CO;2-P PG 6 WC Zoology SC Zoology GA UF262 UT WOS:A1996UF26200006 ER PT J AU Mentis, MJ Horwitz, B Grady, CL Alexander, GE VanMeter, JW Maisog, JM Pietrini, P Schapiro, MB Rapoport, SI AF Mentis, MJ Horwitz, B Grady, CL Alexander, GE VanMeter, JW Maisog, JM Pietrini, P Schapiro, MB Rapoport, SI TI Visual cortical dysfunction in Alzheimer's disease evaluated with a temporally graded ''stress test'' during PET SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID POSITRON EMISSION TOMOGRAPHY; CEREBRAL BLOOD-FLOW; GANGLION-CELL DEGENERATION; BALINTS SYNDROME; SPATIAL VISION; DEMENTIA; PATHWAYS; IMPAIRMENT; OBJECT; CORTEX AB Objective: Visual-processing abnormalities commonly contribute to typical Alzheimer's disease symptoms, bur their detailed pathophysiology remains unknown. To investigate why patients with Alzheimer's disease have greater difficulty performing visuoconstructive (magnocellular-dominated) tasks than face- or color-perception (parvocellular-dominated) tasks, the authors measured brain activation in response to a temporally graded visual stimulus (neural stress test) during positron emission tomography. Method: The stress test measured regional cerebral blood flow (CBF) in response to a patterned flash stimulus in the resting state (0 Hz in the dark) and at frequencies of 1, 2, 4, 7, and 14 Hz. Ten patients with Alzheimer's disease and 12 age- and sex-matched comparison subjects were studied. Results: The striate response at 7 Hz and 14 Hz (the degree of regional CBF increase from that at 0 Hz) was significantly less in the patients than in the comparison subjects, whereas the change in regional CBF at the lower frequencies did not differ between groups. In bilateral middle temporal association areas activated by motion and dominated by magnocellular input, regional CBF at 1 Hz (the frequency with maximal apparent motion) was significantly greater than at 0 Hz in the comparison subjects but not in the patients. Conclusions: The magnocellular visual system normally responds to high-frequency input and motion; the failure of response in the striate cortex at high but not low frequencies in the Alzheimer's patients suggests greater magnocellular than parvocellular dysfunction at these levels. Activation failure in the middle temporal areas in the patients supports magnocellular dysfunction. The finding that the Alzheimer's disease group had abnormal visual cortical function emphasizes the importance of clinical visuospatial evaluation of patients with Alzheimer's disease to fully understand symptom production and to plan interventions. RP Mentis, MJ (reprint author), NIA, NEUROSCI LAB, BLDG 10, ROOM 6C414, BETHESDA, MD 20892 USA. NR 79 TC 72 Z9 76 U1 2 U2 4 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD JAN PY 1996 VL 153 IS 1 BP 32 EP 40 PG 9 WC Psychiatry SC Psychiatry GA TN397 UT WOS:A1996TN39700008 PM 8540589 ER PT J AU Kulynych, JJ Vladar, K Jones, DW Weinberger, DR AF Kulynych, JJ Vladar, K Jones, DW Weinberger, DR TI Superior temporal gyrus volume in schizophrenia: A study using MRI morphometry assisted by surface rendering SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID MAGNETIC-RESONANCE; GRAY-MATTER; CEREBRAL ASYMMETRY; PLANUM-TEMPORALE; ABNORMALITIES; LOBE; BRAIN; REDUCTION; MORPHOLOGY; HUMANS AB Objective: Interpretation of the literature concerning superior temporal gyrus volume in patients with schizophrenia is complicated by methodological variation between studies and by the difficulty of identifying gyral boundaries in serial sections. Method: With the aid of three-dimensional cortical renderings, the authors developed a morphometric approach in which information from the cortical surface is incorporated into gyral boundary decisions. Using this technique, they assessed superior temporal gyrus volume in young right-handed male patients with schizophrenia and in right-handed male comparison subjects. They also compared their technique with existing slice-based morphometric methods by using previously reported subcortical landmarks to define the gyral boundaries. Results: There was no significant main effect of diagnosis and no significant diagnosis-by-hemisphere interaction. Significant leftward laterality was present only among comparison subjects. Leftward superior temporal gyrus laterality did not correlate with leftward laterality of the planum temporale. No significant reduction in superior temporal gyrus volume was revealed in the patients. No significant leftward laterality was detected with the slice-based technique, suggesting that a significant portion of superior temporal gyrus tissue is omitted with this approach. The lack of findings could not be explained by a general absence of morphometric abnormalities in this group of subjects because the patients had significantly larger lateral ventricles. Conclusions: Significant reduction in the superior temporal gyrus volume was not confirmed in this group of patients with schizophrenia, probably because of the small effect size of this finding. Methodological variation is an important factor in determining superior temporal gyrus volume on magnetic resonance imaging scans. C1 ST ELIZABETH HOSP,NIMH,CLIN BRAIN DISORDERS BRANCH,INTRAMURAL RES PROGRAM,NCSE,WASHINGTON,DC 20032. ST ELIZABETH HOSP,NIMH,CTR NEUROSCI,WASHINGTON,DC 20032. NR 44 TC 51 Z9 51 U1 2 U2 2 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD JAN PY 1996 VL 153 IS 1 BP 50 EP 56 PG 7 WC Psychiatry SC Psychiatry GA TN397 UT WOS:A1996TN39700010 PM 8540591 ER PT J AU Cohen, J Ghezzi, F Romero, R Ghidini, A Mazor, M Tolosa, JE Goncalves, LF Gomez, R AF Cohen, J Ghezzi, F Romero, R Ghidini, A Mazor, M Tolosa, JE Goncalves, LF Gomez, R TI GRO alpha in the fetomaternal and amniotic fluid compartments during pregnancy and parturition SO AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY LA English DT Article DE GRO alpha; chemokine; infection; preterm labor; cytokines ID INFLAMMATORY CYTOKINES; STIMULATORY ACTIVITY; MICROBIAL INVASION; PRETERM; CELLS; EXPRESSION; TERM; FIBROBLASTS; SECRETION; PROTEIN AB PROBLEM: GRO alpha/MGSA is a new member of the chemokine superfamily CXC(alpha) and is produced by a variety of cells including macrophages, fibroblasts, epithelial, and endothelial cells, and keratinocytes. This chemokine has chemoattractant activity and may participate in neutrophil recruitment and activation during the course of intrauterine infection. This study was conducted to investigate the effect of labor and microbial invasion of the amniotic cavity (MIAC) on amniotic fluid, fetal, and maternal plasma GRO alpha concentrations. METHOD: A cross-sectional study was designed using parameters that included gestational age, results of amniotic fluid (AF) cultures, and labor status at the time of amniocentesis. Fluid was retrieved by transabdominal amniocentesis. MIAC was defined as a positive amniotic fluid culture for bacteria. Umbilical cord blood was retrieved at the time of delivery. Amniotic fluid, maternal and fetal plasma GRO alpha concentrations were measured with a sen- Human Development, Bethesda, Maryland sitive and specific ELISA (Quantikine, R&D Systems, Minneapolis, MN). RESULTS: 1) GRO alpha was detectable in amniotic fluid, umbilical cord, and maternal plasma ROMERO samples; 2) GRO alpha concentrations in amniotic fluid increased with advancing gestational age; 3) Both term and preterm gestations with MIAC were associated with higher amniotic fluid GROa concentrations than those with sterile amniotic fluid, independent of the labor status (term, MIAC, labor: median 2.7 ng/ml, range 1.4-12.7 vs. term, no MIAC, labor: median 2.1 ng/ml, range 0.7-3.4, vs term, no MIAC, no labor: median 1.9 ng/ml, range 1.8-4.2; P <0.005; preterm: MIAC median 5 ng/ml, range 0.6-47.9 vs. no MIAC: median 2.3 ng/ml, range 0.5-10; P <0.008); 4) A strong correlation was found between umbilical cord plasma GRO alpha concentrations and neonatal neutrophil count, and between GRO alpha concentrations and white blood cell count in the amniotic fluid (r = 0.67, P < 0.0005 and r = 0.38, P < 0.001, respectively). CONCLUSION: GRO alpha is a physiologic constituent of amniotic fluid and cord blood. Amniotic fluid GRO alpha concentrations increase with gestational age. Intrauterine infection both preterm and at term is associated with an increase in GRO alpha concentrations of amniotic fluid, suggesting that GRO alpha may play an important role in recruitment of neutrophils into the amniotic cavity. (C) Munksgaard, Copenhagen C1 NICHHD,INTRAMURAL DIV,PERINATOL RES BRANCH,BETHESDA,MD 20892. WAYNE STATE UNIV,HUTZEL HOSP,DEPT OBSTET & GYNECOL,DETROIT,MI 48202. GEORGETOWN UNIV,MED CTR,DEPT OBSTET & GYNECOL,WASHINGTON,DC 20057. OI Ghezzi, Fabio/0000-0003-3949-5410 NR 19 TC 42 Z9 42 U1 0 U2 2 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 8755-8920 J9 AM J REPROD IMMUNOL JI Am. J. Reprod. Immunol. PD JAN PY 1996 VL 35 IS 1 BP 23 EP 29 PG 7 WC Immunology; Reproductive Biology SC Immunology; Reproductive Biology GA TQ195 UT WOS:A1996TQ19500005 PM 8789556 ER PT J AU Danel, C Erzurum, SC McElvaney, NG Crystal, RG AF Danel, C Erzurum, SC McElvaney, NG Crystal, RG TI Quantitative assessment of the epithelia and inflammatory cell populations in large airways of normals and individuals with cystic fibrosis SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article ID CONDUCTANCE REGULATOR GENE; POTENTIAL DIFFERENCE; RESPIRATORY-TRACT; EXPRESSION; INVIVO; LUNG AB Nasal and bronchial brushings and bronchial biopsies were evaluated from patients with cystic fibrosis (CF) and from normal subjects to quantify epithelial and inflammatory cell types. Epithelia in both groups were dominated by ciliated cells. The relative proportions of epithelial cells recovered by brushing and biopsy were similar, but with more basal cells from biopsies than from brushings. In nasal brushings, the numbers and percentages of epithelial subtypes were similar in both groups. In bronchial brushings, the number of recovered cells was 2.5-fold increased in the CF group compared with that in the normal group because of large numbers of neutrophils. The proportion of ciliated cells was lower in the CF group than in the normal group. Thus, even though the CF transmembrane conductance regulator mutations are expressed similarly in the nasal and bronchial epithelium in CF, the consequences are different, with little inflammation and no changes in the proportions of epithelial cells in the nasal epithelium, compared with marked neutrophil inflammation on the epithelial surface and significant changes in epithelial populations in the large airways. Airway brushing permits repetitive evaluation of the airway epithelium in CF, a useful methodology in the assessment of new therapies for this disorder. C1 CORNELL UNIV,MED CTR,NEW YORK HOSP,DIV PULM & CRIT CARE MED,NEW YORK,NY 10021. NHLBI,PULM BRANCH,BETHESDA,MD 20892. RI McElvaney, Noel/A-6809-2010 NR 35 TC 50 Z9 50 U1 0 U2 1 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD JAN PY 1996 VL 153 IS 1 BP 362 EP 368 PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA TP461 UT WOS:A1996TP46100053 PM 8542144 ER PT J AU Davenport, EA Nettesheim, P AF Davenport, EA Nettesheim, P TI Regulation of mucociliary differentiation of rat tracheal epithelial cells by type I collagen gel substratum SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article ID EXTRACELLULAR-MATRIX; GENE-EXPRESSION; RETINOIC ACID; CULTURE; GROWTH; INVITRO; MARKERS; INVIVO; SHAPE AB Adult rat tracheal epithelial cells plated at low density on type I collagen gel-coated permeable membranes in air-liquid interface cultures rapidly proliferate to reach high cell densities and display a pseudostratified mucociliary epithelium after 2 wk in culture. To determine the importance of exogenous extracellular matrix for RTE cell growth and differentiation, RTE cells were seeded on uncoated or type I collagen gel-coated membranes, Growth rate and plateau cell densities were similar under these two conditions; however, RTE cell attachment was twofold higher on type I collagen gel-coated membranes. Cell distribution during log growth was significantly different, with numerous small colonies observed on Giemsa-stained uncoated membranes and fewer, larger colonies observed on type I collagen gel-coated membranes. Under both conditions, the epithelial morphology was predominantly pseudostratified in plateau-phase cultures. Based on experiments measuring the percentage of secretory cells and the amount of mucous secretion, development of the secretory cell phenotype was delayed in the absence of exogenous matrix but reached similar levels of secretory differentiation by day 13 of culture. In contrast, the development of ciliated cells was markedly reduced on uncoated membranes, These data suggest that although plating cells on type I collagen gel enhances cell attachment and accelerates the onset of secretory differentiation, type I collagen gel seems to be more critical for ciliated cell differentiation than for secretory cell differentiation. C1 NIEHS,PULM PATHOBIOL LAB,AIRWAY CELL BIOL GRP,RES TRIANGLE PK,NC 27709. NR 31 TC 43 Z9 45 U1 0 U2 1 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 1044-1549 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD JAN PY 1996 VL 14 IS 1 BP 19 EP 26 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA TQ022 UT WOS:A1996TQ02200002 PM 8534482 ER PT J AU Gray, TE Guzman, K Davis, CW Abdullah, LH Nettesheim, P AF Gray, TE Guzman, K Davis, CW Abdullah, LH Nettesheim, P TI Mucociliary differentiation of serially passaged normal human tracheobronchial epithelial cells SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article ID HUMAN TRACHEAL EPITHELIUM; VITAMIN-A-DEFICIENCY; ORGAN-CULTURES; BIOCHEMICAL-CHARACTERIZATION; MONOCLONAL-ANTIBODIES; MUCOUS GLYCOPROTEINS; SQUAMOUS METAPLASIA; RETINOIC ACID; SECRETIONS; SUBSTRATUM AB The goal of our studies was to establish procedures for subculturing normal human tracheobronchial epithelial (NHTBE) cells without compromising their ability to differentiate into mucous and ciliated cells (i.e., differentiation competence) and to study the regulation of airway secretions by epidermal growth factor (EGF) and retinoic acid (RA). Primary NHTBE cells were obtained from a commercial source and subcultured repeatedly in serum-free medium on plastic tissue culture dishes. The subcultured cells were tested after every passage for differentiation competence in air-liquid interface (ALI) cultures. The apical secretions of cultured NHTBE cells were characterized by immunoblotting. Western blotting, or enzyme-linked immunosorbent assay using a variety of antibodies. They contained mucin-like materials as well as lysozyme, lactoferrin, and secretory leukocyte protease inhibitor (SLPI). We found that an EGF concentration of 25 ng/ml, which is commonly used in airway cell cultures, adversely affected growth, mucin production, and morphology of ALI cultures and that RA was essential for mucociliary differentiation. Without RA, the epithelium became squamous and mucin secretions decreased 300- to 900-fold. In contrast, secretion of lysozyme, lactoferrin, and SLPI was significantly increased in RA-depleted cultures. Cells of passage 2 (P-2) through P-4 remained competent to differentiate into mucous and ciliated cells when grown in ALI cultures. However, mucin secretion and ciliagenesis decreased in P-3 and P-4 cell cultures and P-3 but not P-4 cell cultures exhibited bioelectric properties characteristic of airway epithelium. We concluded that P-2 and P-3 NHTBE cell cultures retain many important features of normal airway epithelium. This enables one to conduct many studies of airway cell biology with a greatly expanded (6,000-fold) cell pool. C1 NIEHS,PULM PATHOBIOL LAB,RES TRIANGLE PK,NC 27709. UNIV N CAROLINA,DEPT PHYSIOL,CHAPEL HILL,NC. UNIV N CAROLINA,DEPT MED,CHAPEL HILL,NC. NR 37 TC 332 Z9 340 U1 1 U2 11 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 1044-1549 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD JAN PY 1996 VL 14 IS 1 BP 104 EP 112 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA TQ022 UT WOS:A1996TQ02200012 PM 8534481 ER PT J AU Jaffe, ES Chan, JKC Su, IJ Frizzera, G Mori, S Feller, AC Ho, FCS AF Jaffe, ES Chan, JKC Su, IJ Frizzera, G Mori, S Feller, AC Ho, FCS TI Report of the workshop on nasal and related extranodal angiocentric T natural killer cell lymphomas - Definitions, differential diagnosis, and epidemiology SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Editorial Material DE T-cell lymphoma; nasal lymphoma; lethal midline granuloma; angiocentric lymphoma; natural killer cells; Epstein-Barr virus ID EPSTEIN-BARR-VIRUS; LETHAL MIDLINE GRANULOMA; NON-HODGKINS-LYMPHOMAS; FETAL NK CELLS; T-CELL; IMMUNOPROLIFERATIVE LESIONS; MALIGNANT-LYMPHOMA; POLYMORPHIC RETICULOSIS; CLINICOPATHOLOGICAL ENTITY; MOLECULAR ANALYSIS AB A workshop jointly sponsored by the University of Hong Kong and the Society for Hematopathology explored the definition, differential diagnosis, and epidemiology of angiocentric lymphomas presenting in the nose and other extranodal sites. The participants concluded that nasal T/ natural killer (NK) cell lymphoma is a distinct clinicopathologic entity highly associated with Epstein-Barr virus (EBV). In situ hybridization for EBV can be very valuable in early diagnosis, especially if tissue is sparse. The cytologic spectrum is broad, ranging from small or medium-sized cells to large transformed cells. Histologic progression often occurs with time. Necrosis is nearly always present, and angioinvasion by tumor cells is seen in most cases. Nasal T/NK cell lymphoma has a characteristic immunophenotype: CD2-positive, CD56-positive, but usually negative for surface CD3. Cytoplasmic CD3 can be detected in paraffin sections. Clonal T-cell receptor gene rearrangement is not found. Tumors with an identical phenotype and genotype occur in other extranodal sites, most commonly in the skin, subcutis, and gastrointestinal tract, and should be referred to as nasal-type T/NK cell lymphomas. The differential diagnosis includes lymphomatoid granulomatosis, blastic or monomorphic NK cell lymphoma/leukemia, CD56-positive peripheral T-cell lymphoma, and enteropathy-associated T-cell lymphoma. C1 UNIV HONG KONG,QUEEN MARY HOSP,DEPT PATHOL,POKFULAM,HONG KONG. NCI,PATHOL LAB,BETHESDA,MD 20892. NATL TAIWAN UNIV HOSP,DEPT PATHOL,TAIPEI,TAIWAN. NYU,MED CTR,NEW YORK,NY 10016. UNIV TOKYO,TOKYO,JAPAN. UNIV LUBECK,W-2400 LUBECK,GERMANY. UNIV HONG KONG,DEPT PATHOL,HONG KONG,HONG KONG. RI Feller, Alfred/E-3853-2010; Su, Ih-Jen/B-2655-2010 NR 55 TC 541 Z9 589 U1 0 U2 33 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD JAN PY 1996 VL 20 IS 1 BP 103 EP 111 DI 10.1097/00000478-199601000-00012 PG 9 WC Pathology; Surgery SC Pathology; Surgery GA TQ557 UT WOS:A1996TQ55700012 PM 8540601 ER PT B AU Simon, R Freedman, LS AF Simon, R Freedman, LS GP AMER STAT ASSOC TI Bayesian design and analysis of 2 by 2 factorial clinical trials SO AMERICAN STATISTICAL ASSOCIATION - 1996 PROCEEDINGS OF THE SECTION ON BAYESIAN STATISTICAL SCIENCE LA English DT Proceedings Paper CT Symposium of the Section on Bayesian Statistical Science, at the Annual Meeting of the American-Statistical-Association CY AUG 04-08, 1996 CL CHICAGO, IL SP Amer Stat Assoc, Sect Bayesian Stat Sci DE Clinical trials; factorial design; Bayesian analysis RP Simon, R (reprint author), NCI,6130 EXECUT BLVD,ROOM 739,ROCKVILLE,MD 20852, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 1429 DUKE ST, ALEXANDRIA, VA 22314 BN 1-883276-36-5 PY 1996 BP 180 EP 185 PG 6 WC Statistics & Probability SC Mathematics GA BJ14W UT WOS:A1996BJ14W00035 ER PT B AU Drury, TF AF Drury, TF GP AMER STAT ASSOC TI An evaluation of nonresponse bias on NHANES III phase 1 oral health estimates SO AMERICAN STATISTICAL ASSOCIATION - 1996 PROCEEDINGS OF THE SOCIAL STATISTICS SECTION LA English DT Proceedings Paper CT Conference of the Social-Statistics-Section, at the Annual Meeting of the American-Statistical-Association CY AUG 04-08, 1996 CL CHICAGO, IL SP Amer Stat Assoc, Social Stat Sect DE nonresponse bias; NHANES III; oral health surveys RP Drury, TF (reprint author), NIDR,45 CTR DR,MSC 6401,ROOM 3AN,44A,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 1429 DUKE ST, ALEXANDRIA, VA 22314 BN 1-883276-48-9 PY 1996 BP 132 EP 135 PG 4 WC Social Sciences, Mathematical Methods; Statistics & Probability SC Mathematical Methods In Social Sciences; Mathematics GA BJ01F UT WOS:A1996BJ01F00026 ER PT J AU Rabinovitz, M AF Rabinovitz, M TI Uncharged tRNA-phosphofructokinase interaction in amino acid deficiency SO AMINO ACIDS LA English DT Article DE amino acid deficiency; uncharged tRNA; phosphofructokinase; fructose-1,6-diphosphate; G1 restriction point ID POLYPEPTIDE-CHAIN INITIATION; CULTURED MAMMALIAN-CELLS; PROTEIN-SYNTHESIS; TRANSFER-RNA; CYCLIC-AMP; GLYCOLYSIS; INVIVO; FIBROBLASTS; DEPRIVATION; ONCOGENES AB When the tRNA of mammalian cells is incompletely charged due to amino acid deficiency or by analogs which cannot be activated, many metabolic events become limited. This rapid demise of cell function appears to be due to the inhibition of phosphofructokinase (PFK) by uncharged tRNA (FEBS Lett 302: 113 (1992)). Charged tRNA has been shown to be ''sequestered within the protein synthetic machinery'', (Negrutskii, B. S. and Deutscher, M. P. (1992) Proc Natl Acad Sci USA 89: 3601) and would therefore be removed from an inhibitory role. Besides the direct demonstration that tRNA inhibits PFK in an assay regarded as indicative of its control mechanism, several reports in the literature support this model. These include 1) The rapid onset of inhibition of glycolysis and glucose uptake by intact cells upon amino acid deficiency and the similar lesion at the 43S ribosomal subunit on glucose or amino acid deprivation. 2) The recognition that unusually high concentrations of cAMP required to stimulate protein synthesis in energy depleted or gel filtered lysates correlates with its action on PFK as an analog of the positive effector, adenosine-5'-monophosphate. 3) The often repeated observation that the product of PFK activity, fructose-1,6-diphosphate, is a stimulant of protein synthesis (see Jackson, R. J., et al. (1983) Eur J Biochem 131: 289). This diphosphate has been shown to be the proximate effector binding to eIF-2B, the guanine nucleotide exchange factor (Singh, L. P. Arror, A. R. and Wahba, A. J. (1994), FASEB J. 8: 279) which by releasing GDP bound to the inactive GDP:eIF-2 complex, permits the factor to initiate a new peptide chain. The above information supports the view that the block at the G1 restriction point in the cell cycle of normal cells brought about by amino acid deprivation is a result of inhibition of protein synthesis through the phosphofructokinase-uncharged tRNA mechanism. This is consistent with observations in the literature that tumor and transformed cells, which are more resistant to this block (Pardee, A. B., Proc Natl Acad Sci USA 71: 1286-1291 (1974)) have a higher phosphofructokinase activity or higher levels of fructose-1,6-diphosphate. C1 NIH, BETHESDA, MD 20892 USA. NR 53 TC 7 Z9 7 U1 0 U2 0 PU SPRINGER WIEN PI WIEN PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 WIEN, AUSTRIA SN 0939-4451 J9 AMINO ACIDS JI Amino Acids PY 1996 VL 10 IS 2 BP 99 EP 108 DI 10.1007/BF00806583 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UE813 UT WOS:A1996UE81300001 PM 24178472 ER PT J AU Park, MH Joe, YA Kang, KR Lee, YB Wolff, EC AF Park, MH Joe, YA Kang, KR Lee, YB Wolff, EC TI The polyamine-derived amino acid hypusine: Its post-translational formation in eIF-5A and its role in cell proliferation SO AMINO ACIDS LA English DT Review DE amino acids; hypusine; deoxyhypusine; eIF-5A; polyamines; posttranslational modification ID EUKARYOTIC INITIATION FACTOR-4D; CONTAINING PROTEIN; BOVINE BRAIN; POSTTRANSLATIONAL FORMATION; SACCHAROMYCES-CEREVISIAE; DEOXYHYPUSINE; IDENTIFICATION; PURIFICATION; BIOSYNTHESIS; SPERMIDINE AB The unusual amino acid hypusine [N-epsilon-(4-amino-2-hydroxybutyl)lysine] is a unique component of one cellular protein, eukaryotic translation initiation factor 5A (eIF-5A, old terminology, eIF-4D). It is formed posttranslationally and exclusively in this protein in two consecutive enzymatic reactions, (i) modification of a single lysine residue of the eIF-5A precursor protein by the transfer of the 4-aminobutyl moiety of the polyamine spermidine to its epsilon-amino group to form the intermediate, deoxyhypusine [N-epsilon-(4-aminobutyl)lysine] and (ii) subsequent hydroxylation of this intermediate to form hypusine. The amino acid sequences surrounding the hypusine residue are strictly conserved in all eukaryotic species examined, suggesting the fundamental importance of this amino acid throughout evolution. Hypusine is required for the activity of eIF-5A in vitro. There is strong evidence that hypusine and eIF-5A are vital for eukaryotic cell proliferation. Inactivation of both of the eIF-5A genes is lethal in yeast and the hypusine modification appears to be a requirement for yeast survival (Schnier et al., 1991 [Mol Cell Biol 11: 3105-3114]; Wohl et al., 1993 [Mol Gen Genet 241: 305-311]). Furthermore, inhibitors of either of the hypusine biosynthetic enzymes, deoxyhypusine synthase or deoxyhypusine hydroxylase, exert strong anti-proliferative effects in mammalian cells, including many human cancer cell lines. These inhibitors hold potential as a new class of anticancer agents, targeting one specific eukaryotic cellular reaction, hypusine biosynthesis. RP Park, MH (reprint author), NIDR,CELLULAR DEV & ONCOL LAB,NIH,BLDG 30,RM 211,BETHESDA,MD 20892, USA. NR 51 TC 23 Z9 24 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0939-4451 J9 AMINO ACIDS JI Amino Acids PY 1996 VL 10 IS 2 BP 109 EP 121 DI 10.1007/BF00806584 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UE813 UT WOS:A1996UE81300002 PM 24178473 ER PT S AU Yanagihara, R Garruto, RM Gajdusek, DC AF Yanagihara, R Garruto, RM Gajdusek, DC BE Nakano, I Hirano, A TI Evidence for cohort effect in the disappearance of high-incidence amyotrophic lateral sclerosis SO AMYOTROPHIC LATERAL SCLEROSIS: PROGRESS AND PERSPECTIVES IN BASIC RESEARCH AND CLINICAL APPLICATION SE INTERNATIONAL CONGRESS SERIES LA English DT Proceedings Paper CT 11th Tokyo-Metropolitan-Institute-for-Neuroscience (TMIN) International Symposium on Amyotrophic Lateral Sclerosis - Progress and Perspectives in Basic Research and Clinical Application CY OCT 25-27, 1995 CL TOKYO, JAPAN SP Tokyo Metropolitan Inst Neurosci DE motor neuron disease; western Pacific; Guam; West New Guinea; epidemiology; aluminum C1 NINCDS,NIH,CENT NERVOUS SYST STUDIES LAB,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE PUBL B V PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0531-5131 BN 0-444-82286-0 J9 INT CONGR SER PY 1996 VL 1104 BP 142 EP 153 PG 12 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA BG35V UT WOS:A1996BG35V00023 ER PT J AU Simpson, JT Torok, DS Girard, JE Markey, SP AF Simpson, JT Torok, DS Girard, JE Markey, SP TI Analysis of amino acids in biological fluids by pentafluorobenzyl chloroformate derivatization and detection by electron capture negative ionization mass spectrometry SO ANALYTICAL BIOCHEMISTRY LA English DT Article ID GAS-CHROMATOGRAPHIC DETERMINATION AB Pentafluorobenzyl chloroformate (PFBCF) has been utilized as a derivatization reagent for amino acids (AAs) in biological fluids with subsequent detection by electron capture negative ionization mass spectrometry (ECNI/MS), AAs were derivatized in one step in aqueous solution, plasma, and whole blood at room temperature, To demonstrate quantitative analysis, phenylalanine concentrations were determined in human plasma AAs were derivatized in one step using PFBCF and a mixture of water, ethanol, and The N-pentafluorobenzvloxycarbonyl amino acid ethyl esters (f phi-AA-OEt) exhibited good GC properties and the ECNI mass spectra are dominated by the [M-181](-) ion, The f phi-AA-OEt derivatives can be easily detected at the femtomole level by selected ion monitoring, Phenethyl alcohol was also derivatized, using anhydrous conditions, and the resulting PFB carbonate's ECNI mass spectrum was dominated by the [M-181](-) ion, The ECNI molar response of the PFB carbonate derivative is two times that of the corresponding pentafluorobenzoate. (C) 1996 Academic Press, Inc. C1 NIMH,ANALYT BIOCHEM SECT,BETHESDA,MD 20892. AMERICAN UNIV,DEPT CHEM,WASHINGTON,DC 20016. NR 14 TC 19 Z9 19 U1 2 U2 4 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD JAN 1 PY 1996 VL 233 IS 1 BP 58 EP 66 DI 10.1006/abio.1996.0007 PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA TR136 UT WOS:A1996TR13600007 PM 8789147 ER PT J AU RealiForster, C Kolobow, T Giacomini, M Hayashi, T Horiba, K Ferrans, VJ AF RealiForster, C Kolobow, T Giacomini, M Hayashi, T Horiba, K Ferrans, VJ TI New ultrathin-walled endotracheal tube with a novel laryngeal seal design - Long-term evaluation in sheep SO ANESTHESIOLOGY LA English DT Article DE anesthetic techniques, tracheal intubation; aspiration, trachea, pathology; equipment, design, tracheal tube, larynx, pathology ID NOSOCOMIAL PNEUMONIA; INTUBATED PATIENTS; COMPLICATIONS; ASPIRATION; PRESSURE AB Background: A new endotracheal tube (ETT) was fabricated and tested in sheep, It had no tracheal cuff; airway seal was achieved at the level of the glottis through a no-pressure seal made of ''gills''; the laryngeal portion was oval-shaped; and the wall thickness was reduced to 0.2 mm. Methods: Sheep were tracheally intubated either with a standard tube or with the new tube, and their lungs were mechanically ventilated for 1 or 3 days. Air leak was recorded at different peak inspiratory pressures (PIPs). Liquid seepage into the trachea was assessed using an indicator dye. Tracheolaryngeal lesions were scored grossly and histologically. Results: There was no air leak up to 40 cmH(2)O of PIP, La either group, in short- and long-term studies. Methylene blue leaked across the cuff in two sheep with standard ETTs. No dye leaked across the gills with the new ETTs. In the new ETT group, the trachea appeared better preserved, grossly and histologically, than in the standard ETT group at both 1 and 3 days (P < 0.05). At day 1, the larynx and vocal cords appeared grossly less injured in the new ETT group (P < 0.05), whereas there was no difference at day 3. Histology did not show significant difference on vocal cords, epiglottis, and larynx between the two groups at any time. Conclusions: The novel, no-pressure seal design of the new ETT is highly effective in preventing air leak and aspiration. It causes no significant tracheal injury. C1 NHLBI,IR PB,PATHOL SECT,BETHESDA,MD 20892. RP RealiForster, C (reprint author), NHLBI,IR PB,SECT PULM & CARDIAC ASSIST DEVICES,PULM CRIT CARE MED BRANCH,BLDG 10,ROOM 5D17,BETHESDA,MD 20892, USA. NR 18 TC 34 Z9 34 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD JAN PY 1996 VL 84 IS 1 BP 162 EP 172 DI 10.1097/00000542-199601000-00019 PG 11 WC Anesthesiology SC Anesthesiology GA TQ552 UT WOS:A1996TQ55200021 PM 8572330 ER PT J AU Baumrind, S BenBassat, Y Bravo, LA Curry, S Korn, EL AF Baumrind, S BenBassat, Y Bravo, LA Curry, S Korn, EL TI Partitioning the components of maxillary tooth displacement by the comparison of data from three cephalometric superimpositions SO ANGLE ORTHODONTIST LA English DT Article DE cephalometrics; metallic implants; craniofacial growth; orthopedic and orthodontic tooth movement ID METALLIC IMPLANTS; QUANTITATION; CEPHALOGRAMS; GROWTH AB Using roentgenographic cephalograms from a sample of subjects with metallic implants, appropriately superimposed tracings were used to distinguish developmental and treatment-associated displacements of the maxillary central incisor and first molar associated with ''local'' changes within the periodontium from ''secondary'' changes which reflect sutural and appositional growth at more distant osseous loci. Tracings were superimposed on anterior cranial base (ACB), on the maxillary implants only (IMP_MAX), and according to the best fit of maxillary anatomic structures without reference to the implants (A_MAX). Using the IMP_MAX superimposition, one could measure total local displacement at any landmark taking into consideration the effects of all appositional and resorptive changes on the superior and anterior surfaces of the palate, whereas using the A_MAX superimposition one could measure local displacement without consideration of surface appositional and resorptive changes. If the second of these measurements were subtracted from the first, the result would be a direct measurement of the effects of surface appositional and resorptive changes as they are expressed at that particular landmark. This strategy has enabled us to quantify and report the amount of accommodation which occurs at the location of each dental landmark in association with the resorptive and appositional changes which occur through time on the superior and anterior surfaces of the hard palate. C1 UNIV MED & DENT NEW JERSEY,NEWARK,NJ 07103. HEBREW UNIV JERUSALEM,HADASSAH SCH DENT MED,DEPT ORTHODONT,IL-91010 JERUSALEM,ISRAEL. UNIV MURCIA,FAC MED,SCH STOMATOL,MURCIA,SPAIN. NCI,BIOMETR RES BRANCH,CLIN TRIALS SECT,BETHESDA,MD. RP Baumrind, S (reprint author), UNIV CALIF SAN FRANCISCO,SCH DENT,DEPT GROWTH & DEV,CRANOFACIAL RES & INSTRUMENTAT LAB,SAN FRANCISCO,CA 94143, USA. FU NIDCR NIH HHS [DE07332, DE08713] NR 44 TC 8 Z9 12 U1 1 U2 1 PU ANGLE ORTHODONTISTS RES EDUC FOUNDATION INC PI APPLETON PA 100 W LAWRENCE ST, SUITE 406, APPLETON, WI 54911 SN 0003-3219 J9 ANGLE ORTHOD JI Angle Orthod. PY 1996 VL 66 IS 2 BP 111 EP 124 PG 14 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA UD940 UT WOS:A1996UD94000010 PM 8712489 ER PT J AU Shi, XL Wang, PC Jiang, HG Mao, Y Ahmed, N Dalal, N AF Shi, XL Wang, PC Jiang, HG Mao, Y Ahmed, N Dalal, N TI Vanadium(IV) causes 2'-deoxyguanosine hydroxylation and deoxyribonucleic acid damage via free radical reactions SO ANNALS OF CLINICAL AND LABORATORY SCIENCE LA English DT Article ID LIPID-PEROXIDATION PRODUCTS; CHELATING-AGENTS; HUMAN-ERYTHROCYTES; HYDROGEN-PEROXIDE; VANADATE; DNA; IONS; MICE; ESR; COOXYGENATION AB Vanadium(IV) caused molecular oxygen dependent 2'-deoxyguanosine (dG) hydroxylation to form 8-hydroxyl-2'-deoxyguanosine (8-OHdG). During a 15-minute incubation of 1.0 mM dG and 1.0 mM VOSO4 (vanadium(IV)) in phosphate buffer solution (pH 7.4) at room temperature under ambient air, dG was converted to 8-OHdG with a yield of about 0.31 percent. Catalase and formate inhibited the 8-OHdG formation while superoxide dismutase enhanced it. Diethylenetriaminepentaacetic acid (DTPA) and deferoxamine blocked the 8-OHdG formation. Incubation of vanadium(IV) with dG in argon did not generate any significant amount of 8-OHdG, indicating the role of molecular oxygen in the mechanism of vanadium(IV)-induced dG hydroxylation. Vanadium(IV) also caused molecular oxygen dependent deoxyribonucleic acid (DNA) strand breaks in a pattern similar to that observed for dG hydroxylation. Reaction of vanadium(IV) with H2O2 generated OH radicals, which were inhibited by DTPA and deferoxamine. Incubation of vanadium(IV) with dG or with DNA in the presence of H2O2 resulted in an enhanced 8-OHdG formation and substantial DNA strand breaks. Reaction of vanadium(IV) with t-butyl hydroperoxide generated hydroperoxide-derived free radicals, which caused 8-OHdG formation from dG and DNA strand breaks. C1 HENAN MED UNIV,DEPT LAB TEST,ZHENGZHOU,PEOPLES R CHINA. NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC,FREDERICK,MD 21702. W VIRGINIA UNIV,DEPT CHEM,MORGANTOWN,WV 26506. RP Shi, XL (reprint author), NCI,LAB EXPTL PATHOL,BLDG 41,ROOM C301,BETHESDA,MD 20892, USA. RI Shi, Xianglin/B-8588-2012 NR 45 TC 39 Z9 39 U1 1 U2 2 PU INST CLINICAL SCIENCE INC PI PHILADELPHIA PA 1833 DELANCEY PLACE, PHILADELPHIA, PA 19103 SN 0091-7370 J9 ANN CLIN LAB SCI JI Ann. Clin. Lab. Sci. PD JAN-FEB PY 1996 VL 26 IS 1 BP 39 EP 49 PG 11 WC Medical Laboratory Technology SC Medical Laboratory Technology GA TR948 UT WOS:A1996TR94800005 PM 8834359 ER PT J AU Backlund, E Sorlie, PD Johnson, NJ AF Backlund, E Sorlie, PD Johnson, NJ TI The shape of the relationship between income and mortality in the United States - Evidence from the national longitudinal mortality study SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE income; mortality; poverty; socioeconomic factors; age factors; sex factors ID SOCIOECONOMIC-STATUS; SOCIAL-CLASS; DEATH-INDEX; HEALTH; DIFFERENTIALS; INEQUALITIES; DISEASE; DEBATE; TRENDS AB A follow-up study based on a large national sample was used to examine differences in the well-established inverse gradient between income and mortality at different income levels. The study showed the income-mortality gradient to be much smaller at high income levels than at low to moderate income levels in the working age (25 to 64 years) and elderly (over 65 years) populations for men and women both before and after adjustment for other socioeconomic variables. In addition, a much larger gradient existed for working age women at extreme poverty levels than for those women at low to moderate income levels. The income-mortality gradient was much smaller in the elderly than in the working age population. The study also examined the ability of several different mathematic functions of income to delineate the relationship between income and mortality. The study suggested that the health benefits associated with increased income diminish as income increases. C1 NHLBI,EPIDEMIOL & BIOMETRY PROGRAM,NIH,BETHESDA,MD 20892. RP Backlund, E (reprint author), US BUR CENSUS,VICTIMIZAT & EXPENDITURES BRANCH,FED BLDG 3,ROOM 3716,SUITLAND,MD 20233, USA. NR 33 TC 151 Z9 155 U1 0 U2 15 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 1047-2797 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD JAN PY 1996 VL 6 IS 1 BP 12 EP 20 DI 10.1016/1047-2797(95)00090-9 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA UC779 UT WOS:A1996UC77900003 PM 8680619 ER PT J AU Harris, MI AF Harris, MI TI Medical care for patients with diabetes - Epidemiologic aspects SO ANNALS OF INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT 5th Regenstrief Conference on Risks and Benefits of Intensive Management in Non-Insulin-dependent Diabetes Mellitus CY DEC 11-13, 1994 CL WASHINGTON, D.C. SP Regemstroef Omst, NIH, NIDDKD, Ctr Dis Control & Prevent, Div Diabetes Translat ID UNITED-STATES; BLOOD-GLUCOSE; COMPLICATIONS TRIAL; MELLITUS; ADULTS; INTERVENTIONS; RELIABILITY; INFORMATION; PHYSICIANS; BEHAVIORS AB Objective: To describe the epidemiologic characteristics of physician care and self-care for adults with diabetes in the U.S. population. Design and Subjects: Data are drawn from the 1989 National Health Interview Survey, in which a personal household interview was administered to a representative sample of U.S. adults aged 18 years or older. The response rate was 96% (n = 84 572). All subjects identified as having diabetes previously diagnosed by a physician were asked a series of questions about their diabetes. Response rate for this representative sample of U.S. diabetic patients was 95% (n = 2405). Measurements: Self-reported information was obtained about various aspects of diabetes care, including care by physicians and self-care practices of the diabetic persons. Sociodemographic and clinical factors that may influence diabetes care were also determined. Results: More than 90% of diabetic adults had one physician for the usual care of their diabetes, but 32% made fewer than four visits to this physician each year. Most physician visits by diabetic patients were not made to diabetes specialists, and the visit rate to other health care professionals such as ophthalmologists, podiatrists, and nutritionists was low. About half of insulin-treated diabetic subjects used multiple daily insulin injections; and 40% of patients with insulin-dependent diabetes mellitus, 26% of those with non-insulin-dependent diabetes mellitus (NIDDM) who were taking insulin, and 5% of those with NIDDM who were not taking insulin monitored their blood glucose level daily. Diabetes patient education classes had been attended by 35% of diabetic adults. Conclusions: These and other data indicate that medical care for diabetic patients and their self-care practices may not be optimal for prevention of diabetes complications. The Diabetes Control and Complications Trial showed that achieving and maintaining near-normal glycemia, with a concomitant 50% to 70% reduction in diabetes complications, may require close monitoring and ongoing support from a health care team, ample financial resources, and advanced patient knowledge and motivation. Providing this level of diabetes management to all diabetic persons may require major changes in the health care system and in patient self-care practices. RP Harris, MI (reprint author), NIDDKD, NATCHER BLDG, ROOM 5AN24, 45 CTR DR, MSC 6600, BETHESDA, MD 20892 USA. NR 39 TC 77 Z9 79 U1 0 U2 1 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD JAN 1 PY 1996 VL 124 IS 1 BP 117 EP 122 PN 2 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA TL944 UT WOS:A1996TL94400007 PM 8554202 ER PT J AU Savage, PJ AF Savage, PJ TI Cardiovascular complications of diabetes mellitus: What we know and what we need to know about their prevention SO ANNALS OF INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT 5th Regenstrief Conference on Risks and Benefits of Intensive Management in Non-Insulin-dependent Diabetes Mellitus CY DEC 11-13, 1994 CL WASHINGTON, DC SP Regemstroef Omst, NIH, NIDDKD, Ctr Dis Control & Prevent, Div Diabetes Translat ID CORONARY HEART-DISEASE; RISK-FACTORS; POPULATION; MORTALITY; FRAMINGHAM; PROGRAM; ONSET; MEN AB Cardiovascular disease is a major cause of morbidity and mortality in patients with non-insulin-dependent diabetes mellitus (NIDDM). With an increase in the number of older diabetic persons, an increase in U.S. minority populations with high rates of diabetes, and the proven success of new methods to reduce microvascular complications, the importance of diabetic macrovascular complications will increase. The relative effectiveness of different treatments to reduce the incidence of diabetic cardiovascular complications is poorly understood. In addition to relative efficacy, issues related to patient burden and the economic cost of different treatments must be considered. Some of the information needed to improve therapy will be available soon from ongoing clinical trials. Obtaining definitive answers to other questions, especially those related to the relative benefit of intensive glucose level control compared with control of other known cardiovascular disease risk factors, will require additional studies. Although several questions unique to diabetic patients remain unanswered, results of previous clinical trials done among largely nondiabetic participants can be used to develop interim recommendations for cardiovascular disease prevention. Until definitive guidelines for prevention are established, combining aggressive therapy for known cardiovascular disease risk factors with efforts to normalize the glucose level offers the best chance to reduce the higher risk for cardiovascular disease associated with NIDDM. RP Savage, PJ (reprint author), NHLBI,EPIDEMIOL & BIOMETRY PROGRAM,DECA,2 ROCKLEDGE CTR,RM 8154,6701 ROCKLEDGE DR,BETHESDA,MD 20892, USA. NR 30 TC 78 Z9 82 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD JAN 1 PY 1996 VL 124 IS 1 BP 123 EP 126 PN 2 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA TL944 UT WOS:A1996TL94400008 PM 8554203 ER PT J AU Miller, DH Albert, PS Barkhof, F Francis, G Frank, JA Hodgkinson, S Lublin, FD Paty, DW Reingold, SC Simon, J AF Miller, DH Albert, PS Barkhof, F Francis, G Frank, JA Hodgkinson, S Lublin, FD Paty, DW Reingold, SC Simon, J TI Guidelines for the use of magnetic resonance techniques in monitoring the treatment of multiple sclerosis SO ANNALS OF NEUROLOGY LA English DT Article ID ACUTE OPTIC NEURITIS; STATUS SCALE EDSS; DISEASE-ACTIVITY; FOLLOW-UP; IMAGING LESIONS; MRI; BRAIN; ABNORMALITIES; SPECTROSCOPY; IMAGES AB Because of the major difficulties in measuring clinical end points in multiple sclerosis (MS) treatment trials, there has been much enthusiasm for using magnetic resonance imaging (MRT) findings as an alternative outcome. To provide international consensus guidelines for the use of MRI in MS clinical trials, a task force of the US National MS Society was convened. The recommendations of the task force are presented in this review. Given the high sensitivity for detecting pathological activity in relapsing-remitting and secondary progressive MS, monthly T2-weighted and gadolinium-enhanced brain MRT is an excellent tool for short-term exploratory trials of new agents where it serves as the primary end point; in particular, failure to demonstrate a reduction in lesion activity avoids the time, cost, and risks of a larger clinical end point study. However, conventional MRI findings have a limited correlation with disability in established MS. The primary end point of a definitive trial should therefore be clinical, although serial MRI at 6- to 12-month intervals is a useful secondary end point in providing an index of pathological progression. In trials of patients presenting with clinically isolated syndromes suggestive of MS, MRT findings can be used in the entry criteria, and as a secondary outcome measure, but conversion to clinically definite MS should be the primary outcome. The pathological substrates of irreversible disability are demyelination and axonal loss. Putative magnetic resonance markers for these processes include decreased N-acetylaspartate on proton magnetic resonance spectroscopy, decreased magnetization transfer ratios, hypointensity on T1-weighted images, and loss of short T2 water fractions, some of which relate more closely to disability than conventional MRI findings. Further technical developments should lead to more accurate quantitation, greater pathological specificity, and stronger clinical correlations. C1 NIH,BETHESDA,MD 20892. FREE UNIV AMSTERDAM HOSP,AMSTERDAM,NETHERLANDS. MONTREAL NEUROL INST,MONTREAL,PQ,CANADA. LIVERPOOL HOSP,SYDNEY,NSW,AUSTRALIA. JEFFERSON MED COLL,PHILADELPHIA,PA. UNIV BRITISH COLUMBIA,VANCOUVER,BC V5Z 1M9,CANADA. NATL MUTIPLE SCLEROSIS SOC,NEW YORK,NY. UNIV COLORADO,HLTH SCI CTR,DENVER,CO. RP Miller, DH (reprint author), INST NEUROL,QUEEN SQ,LONDON WC1N 3BG,ENGLAND. OI Hodgkinson, Suzanne/0000-0002-9029-6663 NR 93 TC 393 Z9 397 U1 2 U2 11 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD JAN PY 1996 VL 39 IS 1 BP 6 EP 16 DI 10.1002/ana.410390104 PG 11 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA TT880 UT WOS:A1996TT88000003 PM 8572668 ER PT J AU Racke, MK Critchfield, JM Quigley, L Cannella, B Raine, CS McFarland, HF Lenardo, MJ AF Racke, MK Critchfield, JM Quigley, L Cannella, B Raine, CS McFarland, HF Lenardo, MJ TI Intravenous antigen administration as a therapy for autoimmune demyelinating disease SO ANNALS OF NEUROLOGY LA English DT Article ID MYELIN BASIC-PROTEIN; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; T-CELL CLONES; CENTRAL-NERVOUS-SYSTEM; MULTIPLE-SCLEROSIS; PROTEOLIPID PROTEIN; ADOPTIVE TRANSFER; LYMPHOCYTES-T; MICE; INTERLEUKIN-2 AB Experimental allergic encephalomyelitis is a prototypic autoimmune disease characterized by central nervous system inflammation and demyelination. Previously, we demonstrated that intravenous administration of high doses of myelin basic protein abrogated the clinical and pathological signs of experimental allergic encephalomyelitis by causing the deletion of encephalitogenic, CD4(+), myelin basic protein-specific T cells through antigen-induced programmed cell death. In the present study, we further characterized the ability of intravenous antigen administration to attenuate an immune response by myelin basic protein-reactive encephalitogenic T cells. We demonstrated that multiple injections of myelin basic protein are required to achieve a therapeutic response, and that this form of therapy is effective even after prolonged chronic disease. These studies showed that although interleukin-2-stimulated cell cycling is an important factor leading to T-cell death, the administration of exogenous interleukin-2 with antigen can result in the aggravation of clinical disease compared to administration of antigen alone. More importantly, administration of myelin basic protein alone without interleukin-2 was sufficient to reduce autoreactive T cells and clinical disease in experimental autoimmune encephalomyelitis. Our experiments support the rationale for antigen-specific therapy aimed at inducing the programmed death of autoreactive T cells in autoimmune diseases, potentially including the human demyelinating disease multiple sclerosis. C1 NINCDS,NIH,NEUROIMMUNOL BRANCH,BETHESDA,MD 20892. NIAID,NIH,IMMUNOL LAB,BETHESDA,MD 20892. ALBERT EINSTEIN COLL MED,DEPT PATHOL NEUROPATHOL,BRONX,NY 10467. FU NINDS NIH HHS [NS 11920, NS 08952, NS 07098] NR 48 TC 43 Z9 44 U1 0 U2 1 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD JAN PY 1996 VL 39 IS 1 BP 46 EP 56 DI 10.1002/ana.410390108 PG 11 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA TT880 UT WOS:A1996TT88000007 PM 8572666 ER PT J AU Tedeschi, G Bertolino, A Massaquoi, SG Campbell, G Patronas, NJ Bonavita, S Barnett, AS Alger, JR Hallett, M AF Tedeschi, G Bertolino, A Massaquoi, SG Campbell, G Patronas, NJ Bonavita, S Barnett, AS Alger, JR Hallett, M TI Proton magnetic resonance spectroscopic imaging in patients with cerebellar degeneration SO ANNALS OF NEUROLOGY LA English DT Article ID N-ACETYLASPARTATE; H-1-NMR SPECTROSCOPY; MULTIPLE-SCLEROSIS; RAT-BRAIN; INVIVO; ATAXIA; TUMORS; MRS AB Using proton magnetic resonance spectroscopic imaging, we studied the cerebellum of 9 patients with cerebellar degeneration and of 9 age-matched normal control subjects. This technique permits the simultaneous measurement of N-acetylaspartate, choline-containing compounds, creatine/phosphocreatine, and lactate signal intensities from four 15-mm slices divided into 0.84-ml single-volume elements. Because patients with cerebellar degeneration often show substantial atrophy on magnetic resonance imaging (MRI), we specifically chose to analyze the spectroscopic signals only from tissue that did not have an atrophic appearance on the MRI. The spectroscopic findings showed a significant reduction of N-acetylaspartate in all parts of the cerebellum, a significant correlation with MRI scores of cerebellar atrophy, and a significant correlation with clinical rating scores of cerebellar disturbance. Our method of analysis suggests the presence of a neuodegenerative process in cerebellar areas that do not appear to be atrophic on the MRI. Some limitations of proton magnetic resonance spectroscopic imaging in the present study were related to the partial field inhomogeneity characteristics of the posterior fossa, the anatomical location of the cerebellum, and the particularly severe cerebellar atrophy in some of the patients. C1 NINCDS,NEUROIMAGING BRANCH,BETHESDA,MD 20892. NINCDS,MED NEUROL BRANCH,BETHESDA,MD 20892. NINCDS,BIOMETRY & FIELD STUDIES BRANCH,BETHESDA,MD 20892. UNIV CALIF LOS ANGELES,DEPT RADIOL SCI,LOS ANGELES,CA 90024. RP Tedeschi, G (reprint author), NIH,BLDG 10,ROOM 1C451,BETHESDA,MD 20892, USA. RI Bertolino, Alessandro/O-6352-2016 OI Bertolino, Alessandro/0000-0002-1251-1380 NR 42 TC 28 Z9 28 U1 0 U2 0 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD JAN PY 1996 VL 39 IS 1 BP 71 EP 78 DI 10.1002/ana.410390111 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA TT880 UT WOS:A1996TT88000010 PM 8572670 ER PT J AU Longo, DL AF Longo, DL TI Chemotherapy alone in the treatment of patients with early stage Hodgkin's disease SO ANNALS OF ONCOLOGY LA English DT Article; Proceedings Paper CT 3rd International Symposium on Hodgkins Lymphoma CY SEP 18-23, 1995 CL COLOGNE, GERMANY SP Deut Krebshilfe, German Minist Res & Technol, Deut Forschungsgemeinsch, City Cologne, Nordrhein Westfalen, European Community DE chemotherapy; early stages; Hodgkin's disease ID RADIATION-THERAPY; RANDOMIZED TRIAL; RADIOTHERAPY; MOPP; LAPAROTOMY; ADJUVANT; RISK AB Studies employing chemotherapy in early stage Hodgkin's disease suggest that this approach is at least comparable to radiation therapy in treatment outcome. Since the long-term disease-free survival in early stages approaches 90%, it is unlikely to further improve these results substantially. Thus, the major goal is the reduction of toxicity. The future choice of therapy will be influenced by the long-term toxicity of these approaches which has to be monitored carefully. RP Longo, DL (reprint author), NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21702, USA. NR 19 TC 5 Z9 5 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 1996 VL 7 SU 4 BP 85 EP 89 PG 5 WC Oncology SC Oncology GA UZ462 UT WOS:A1996UZ46200016 PM 8836416 ER PT J AU Dukoff, R Horak, ID Hassan, R Rosenstein, DL AF Dukoff, R Horak, ID Hassan, R Rosenstein, DL TI Akathisia associated with prochlorperazine as an antiemetic: A case report SO ANNALS OF ONCOLOGY LA English DT Letter ID CHEMOTHERAPY C1 NCI,BETHESDA,MD 20892. RP Dukoff, R (reprint author), NIMH,BETHESDA,MD 20892, USA. NR 8 TC 1 Z9 1 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD JAN PY 1996 VL 7 IS 1 BP 103 EP 103 PG 1 WC Oncology SC Oncology GA TX517 UT WOS:A1996TX51700023 PM 9081380 ER PT J AU Davidson, BJ Ludlow, CL AF Davidson, BJ Ludlow, CL TI Long-term effects of botulinum toxin injections in spasmodic dysphonia SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article DE botulinum toxin; spasmodic dysphonia ID FOCAL LARYNGEAL DYSTONIA; SPASTIC DYSPHONIA; QUANTITATIVE-ANALYSIS; HEMIFACIAL SPASM; MUSCLE; BLEPHAROSPASM; EMG AB The purpose was to examine whether physiological changes can be found in laryngeal muscles following repeated treatment with botulinum toxin injections in spasmodic dysphonia. Seven patients whose treatment consisted of multiple unilateral thyroarytenoid injections were examined more than 6 months following their most recent botulinum toxin injection by fiberoptic laryngoscopy and electromyography. Comparisons were made between injected and contralateral noninjected muscles' motor unit characteristics, muscle activation patterns, and vocal fold movement characteristics. The results demonstrated that motor unit characteristics differed between injected and noninjected muscles and that these differences were greater in patients less than 12 months since last injection. Motor unit duration differences were reduced and motor unit amplitude and numbers of turns were increased in muscles sampled over 1 year after injection. These results suggest that while the physiologic effects of botulinum toxin are reversible, the reinnervation process continues past 12 months following injection. C1 GEORGETOWN UNIV,MED CTR,DEPT OTOLARYNGOL HEAD & NECK SURG,WASHINGTON,DC 20007. NIDOCD,VOICE & SPEECH SECT,BETHESDA,MD. OI Ludlow, Christy/0000-0002-2015-6171 NR 41 TC 33 Z9 33 U1 0 U2 0 PU ANNALS PUBL CO PI ST LOUIS PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 SN 0003-4894 J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD JAN PY 1996 VL 105 IS 1 BP 33 EP 42 PG 10 WC Otorhinolaryngology SC Otorhinolaryngology GA TQ035 UT WOS:A1996TQ03500006 PM 8546422 ER PT J AU Piscitelli, SC Minor, JR Saville, MW Davey, RT AF Piscitelli, SC Minor, JR Saville, MW Davey, RT TI Immune-based therapies for treatment of HIV infection SO ANNALS OF PHARMACOTHERAPY LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; TUMOR-NECROSIS-FACTOR; STIMULATORY FACTOR INTERLEUKIN-12; RECOMBINANT HUMAN INTERLEUKIN-2; ANTI-HIV-1 THERAPEUTIC AGENTS; PERIPHERAL-BLOOD LYMPHOCYTES; INTERFERON-ALPHA THERAPY; PLACEBO-CONTROLLED TRIAL; KAPOSIS-SARCOMA; NATURAL-KILLER AB OBJECTIVE: To review the in vitro, animal, and clinical data on immune-based therapies for treatment of HIV infection. DATA SOURCES: An extensive MEDLINE search was performed for interleukins, interferons, immunotoxins, tumor necrosis factor (TNF)-directed agents, vaccines, and gene therapy. STUDY SELECTION: In vitro experiments with immune-based agents in cell lines infected with HIV were included. In addition, all human studies and case reports that used these agents in patients infected with HIV were selected. Additional literature included abstracts from international meetings on HIV and AIDS. DATA EXTRACTION: Data regarding activity, efficacy, and toxicity a were extracted from in vitro and in vivo studies. When conflicting data were observed, both viewpoints were stated to give an unbiased analysis. Because HIV research involves multiple social, ethical, and scientific issues, perspectives on these problems were addressed, where appropriate. DATA SYNTHESIS: Current antiretroviral therapy is limited to short-term responses and has minimal effect on overall survival. Because the human immune response to HIV infection is effective at keeping the virus suppressed for a number of years, a focus of HIV research has been to examine immune-based therapies for treatment of HIV infection that attempt to augment, enhance, or boost the patient's immune system. Interleukins, interferons, immunotoxins, TNF-directed therapies, vaccines, and gene therapy have been studied in patients infected with HN. Properties shared among these therapeutic modalities include adverse effect profiles, response rates dependent on baseline immunocompetence, the potential to activate viral replication, the need for supportive care, and sensitive laboratory tests required for monitoring. CONCLUSIONS: Immune-based agents represent a new approach to the treatment of HIV infection. Whereas antiretrovirals only inhibit viral replication, these agents are designed to enhance the immune system of the patient. Future attempts to manage HIV infection may combine standard nucleoside analogs with immune-based therapies. C1 NIAID,LAB IMMUMOREGULAT,BETHESDA,MD 20892. RP Piscitelli, SC (reprint author), NIAID,WARREN G MAGNUSON CLIN CTR,DEPT PHARM,BLDG 10,ROOM 1N257,BETHESDA,MD 20892, USA. NR 145 TC 6 Z9 6 U1 0 U2 0 PU HARVEY WHITNEY BOOKS CO PI CINCINNATI PA PO BOX 42696, CINCINNATI, OH 45242 SN 1060-0280 J9 ANN PHARMACOTHER JI Ann. Pharmacother. PD JAN PY 1996 VL 30 IS 1 BP 62 EP 76 PG 15 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA TP440 UT WOS:A1996TP44000011 PM 8773168 ER PT J AU Billingsley, KG Fraker, DL Strassmann, G Loeser, C Fliot, HM Alexander, HR AF Billingsley, KG Fraker, DL Strassmann, G Loeser, C Fliot, HM Alexander, HR TI Macrophage-derived tumor necrosis factor and tumor-derived of leukemia inhibitory factor and interleukin-6: Possible cellular mechanisms of cancer cachexia SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article DE cachexia; cytokine; macrophage; tumor necrosis factor; leukemia inhibitory factor; interleukin-6 ID FACTOR-ALPHA; INVOLVEMENT; INTERFERON; RAT AB Background: The cellular basis for augmented cytokine production in the tumor-bearing host is not known. Recently leukemia inhibitory factor (LIF) and interleukin (IL)-6, produced by a variety of tumors, have been implicated as mediators of cachexia. Methods: Five murine tumor cell lines were tested for the production of these cytokines. 4JK tumor was further tested to determine if IL-1, tumor necrosis factor (TNF), or cocultivation with RAW 264 cells augmented IL-6 or LIF production. Results: 4JK from in vivo tumors produced significantly more IL-6 than did 4JK from culture, indicating that tumor production of IL-6 and LIF is potentially augmented by infiltrating macrophages. When 4JK was cocultured with RAW 264 cells, TNF, or IL-1 in vitro, a three- to 15-fold increase in tumor production of LIF and IL-6 was noted (p(2) less than or equal to 0.03). Conversely, in coculture experiments performed with a neutralizing TNF antibody, a 50% reduction in tumor production of LIF and IL-6 was noted (p(2) < 0.04). Resting RAW cells produced only minimal quantities of TNF; however, when RAW cells were exposed to tumor-conditioned supernatant from 4JK, their TNF production was markedly increased. Conclusions: In the tumor microenvironment, host macrophages may be activated and produce inflammatory cytokines such as TNF. Local TNF then appears to act on tumor cells to stimulate production of IL-6 and LIF. Enhanced tumor production of cytokine mediators may contribute to deleterious effects of neoplastic growth on the host. C1 NCI,SURG BRANCH,SURG METAB SECT,BETHESDA,MD 20892. OTSUKA AMER PHARMACEUT INC,MARYLAND RES LABS,ROCKVILLE,MD. NR 17 TC 17 Z9 18 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD JAN PY 1996 VL 3 IS 1 BP 29 EP 35 DI 10.1007/BF02409048 PG 7 WC Oncology; Surgery SC Oncology; Surgery GA TP425 UT WOS:A1996TP42500005 PM 8770299 ER PT J AU Bartels, CJ Rosenberg, SA Yang, JC AF Bartels, CJ Rosenberg, SA Yang, JC TI Adoptive cellular immunotherapy of cancer in mice using allogeneic T-cells SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article DE adoptive immunotherapy; T cell ID TUMOR-INFILTRATING LYMPHOCYTES; MELANOMA ANTIGENS; RECOGNITION AB Background: Adoptive cellular immunotherapy with autologous tumor-infiltrating lymphocytes (TILs) can induce tumor regression in patients with metastatic melanoma but requires both surgical tumor harvest and successful expansion of lymphocytes in vitro. In cases in which tumors are inaccessible or TILs fail to grow, the adoptive transfer of allogeneic TILs, haplotype matched for the restriction element for a common tumor antigen, represents a possible treatment alternative. Such TILs show in vitro cross-reactivity for allogeneic tumors but have not been evaluated for in vivo activity. Methods: An F-1 hybrid mouse (C57BL/6 X DBA-2 [B6D2 F-1]) was used to generate TILs (F-1 TILs) expressing both H-2(b) and H-2(d) class I major histocompatibility complex (MHC) determinants, which were used to treat established autologous lung metastases in C57BL/6 (B6) parental strain mice. Results: H-2(b) mice bearing the fully syngeneic MC-38 tumor were treated with F-1 TILs, and a 98-100% reduction in 4-day-old established lung metastasis was achieved. However, B6 mice bearing MC-38 tumors after preimmunization with H-2(d) splenocytes did not show a response to F-1 TILs. Preimmunization of B6 mice by intravenous injection of H-2(d) splenocytes at varying times before F-1 TIL administration showed a dramatic reduction in F-1 TIL efficacy when alloimmunization occurred as early as 2 days before therapy. Immunization against an unrelated haplotype (H-2(b)) sharing no MHC genes with the F-1 TILs resulted in a smaller reduction of F-1 TIL efficacy, possibly due to shared minor determinants. Conclusion: Allogeneic TILs sharing an MHC restriction element for a common tumor antigen can be used to successfully treat established metastases in the nonallosensitized host. C1 NCI,SURG BRANCH,BETHESDA,MD 20892. NR 16 TC 8 Z9 8 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD JAN PY 1996 VL 3 IS 1 BP 67 EP 73 DI 10.1007/BF02409054 PG 7 WC Oncology; Surgery SC Oncology; Surgery GA TP425 UT WOS:A1996TP42500011 PM 8770305 ER PT J AU Beutler, JA Lindner, ABA McCloud, TG AF Beutler, JA Lindner, ABA McCloud, TG TI Further studies on phorbol ester bioactivity in the Euphorbiaceae SO ANNALS OF THE MISSOURI BOTANICAL GARDEN LA English DT Article ID SYSTEMATICS AB Six hundred and thirty-four organic extracts, including 36 previously untested genera of the Euphorbiaceae, were examined in a phorbol dibutyrate receptor binding assay. Phorbol bioactivity was newly detected in the genera Anthostema, Blachia, Borneodendron, Dichostemma, Spirostachys, Tapoides, Trigonostemon and Wetria. C1 NCI,FREDERICK CANC RES & DEV CTR,CHEM SYNTHESIS & ANAL LAB,SAIC FREDERICL,FREDERICK,MD 21702. RP Beutler, JA (reprint author), NCI,FREDERICK CANC RES & DEV CTR,LAB DRUG DISCOVERY RES & DEV,DEV THERAPEUT PROG,FREDERICK,MD 21702, USA. RI Beutler, John/B-1141-2009 OI Beutler, John/0000-0002-4646-1924 NR 13 TC 6 Z9 7 U1 0 U2 1 PU MISSOURI BOTANICAL GARDEN PI ST LOUIS PA 2345 TOWER GROVE AVENUE, ST LOUIS, MO 63110 SN 0026-6493 J9 ANN MO BOT GARD JI Ann. Mo. Bot. Gard. PY 1996 VL 83 IS 4 BP 530 EP 533 DI 10.2307/2399992 PG 4 WC Plant Sciences SC Plant Sciences GA VX648 UT WOS:A1996VX64800009 ER PT J AU Hirsch, R LethbridgeCejku, M Scott, WW Reichle, R Plato, CC Tobin, J Hochberg, MC AF Hirsch, R LethbridgeCejku, M Scott, WW Reichle, R Plato, CC Tobin, J Hochberg, MC TI Association of hand and knee osteoarthritis: Evidence for a polyarticular disease subset SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Article ID OSTEO-ARTHRITIS; GENERAL-POPULATION; GRADING SCALES; JOINT; EPIDEMIOLOGY; RELIABILITY; PROGRESSION; PREVALENCE AB Objective-To examine the association between hand and knee osteoarthritis (OA) in a community based population. Methods-Radiographs of 695 participants aged greater than or equal to 40 years in the Baltimore Longitudinal Study of Aging were read for changes of OA, using Kellgren-Lawrence grade greater than or equal to 2 as the case definition. Results-Logistic regression analyses, adjusting for age, gender and body mass index, revealed a significant association between OA in the knee and the following joint groups: distal and proximal interphalangeal (DIP, PIP) and Hand2 (OA in two or more hand joint groups) for grade 2-4 and grade 3-4 disease, and the first carpometacarpal (CMC1) joint for grade 3-4 disease. Conclusion There is an association between OA in hand sites and the knee. The strength of the associations increases with increasing disease severity. For the PIP site, there is a trend toward increasing strength of association for increasing numbers of affected joints and bilateral disease. C1 UNIV MARYLAND,SCH MED,BALTIMORE,MD 21201. JOHNS HOPKINS UNIV,SCH MED,BALTIMORE,MD. NIA,GERONTOL RES CTR,BALTIMORE,MD. RP Hirsch, R (reprint author), NIAMSD,OFF PREVENT EPIDEMIOL & CLIN APPLICAT,NATCHER BLDG,ROOM 5AN-40,45 CTR DR,MSC 6500,BETHESDA,MD 20892, USA. NR 22 TC 64 Z9 64 U1 1 U2 1 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 0003-4967 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD JAN PY 1996 VL 55 IS 1 BP 25 EP 29 DI 10.1136/ard.55.1.25 PG 5 WC Rheumatology SC Rheumatology GA TM485 UT WOS:A1996TM48500005 PM 8572729 ER PT J AU Stadtman, TC AF Stadtman, TC TI Selenocysteine SO ANNUAL REVIEW OF BIOCHEMISTRY LA English DT Review DE selenophosphate; Se-dependent deiodinases; Se-Mo coordination; secys-thioredoxin reductase; selenocysteyl-tRNA(Sec); secys insertion elements; 21st amino acid ID CLOSTRIDIAL GLYCINE REDUCTASE; GLUTATHIONE-PEROXIDASE GENE; ESCHERICHIA-COLI; SELENOPROTEIN SYNTHESIS; MESSENGER-RNA; AMINO-ACID; UGA CODON; NUCLEOTIDE-SEQUENCE; SELENIUM METABOLISM; PROTEIN-COMPONENTS AB Selenocysteine is recognized as the 21st amino acid in ribosome-mediated protein synthesis and its specific incorporation is directed by the UGA codon. Unique tRNAs that have complementary UCA anticodons are aminoacylated with serine, the seryl-tRNA is converted to selenocysteyl-tRNA and the latter binds specifically to a special elongation factor and is delivered to the ribosome. Recognition elements within the mRNAs are essential for translation of UGA as selenocysteine. A reactive oxygen-labile compound, selenophosphate, is the selenium donor required for synthesis of selenocysteyl-tRNA. Selenophosphate synthetase, which forms selenophosphate from selenide and ATP, is found in various prokaryotes, eukaryotes, and archaebacteria. The distribution and properties of selenocysteine-containing enzymes and proteins that have been discovered to date are discussed. Artificial selenoenzymes such as selenosubtilisin have been produced by chemical modification. Genetic engineering techniques also have been used to replace cysteine residues in proteins with selenocysteine. The mechanistic roles of selenocysteine residues in the glutathione peroxidase family of enzymes, the 5' deiodinases, formate dehydrogenases, glycine reductase, and a few hydrogenases are discussed. In some cases a marked decrease in catalytic activity of an enzyme is observed when a selenocysteine residue is replaced with cysteine. This substitution caused complete loss of glycine reductase selenoprotein A activity. RP Stadtman, TC (reprint author), NHLBI,NIH,BETHESDA,MD 20892, USA. NR 85 TC 663 Z9 693 U1 13 U2 80 PU ANNUAL REVIEWS INC PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 SN 0066-4154 J9 ANNU REV BIOCHEM JI Annu. Rev. Biochem. PY 1996 VL 65 BP 83 EP 100 PG 18 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UV922 UT WOS:A1996UV92200004 PM 8811175 ER PT J AU Hurley, JH AF Hurley, JH TI The sugar kinase heat shock protein 70 actin super family: Implications of conserved structure for mechanism SO ANNUAL REVIEW OF BIOPHYSICS AND BIOMOLECULAR STRUCTURE LA English DT Review DE protein structure; conformational change; X-ray crystallography; enzyme regulation; enzyme mechanism ID YEAST HEXOKINASE-A; ESCHERICHIA-COLI; GLYCEROL KINASE; ATP HYDROLYSIS; COGNATE PROTEIN; COMPLEX; GLUCOSE; BINDING; DISSOCIATION; FILAMENT AB Sugar kinases, stress-70 proteins, and actin belong to a superfamily defined by a fold consisting of two domains with the topology beta beta beta alpha beta alpha beta alpha. These enzymes catalyze ATP phosphoryl transfer or hydrolysis coupled to a large conformational change in which the two domains close around the nucleotide. The beta 1-beta 2 turns of each domain form hydrogen bonds with ATP phosphates, and conserved Asp, Glu or Gin residues coordinate Mg2+ or Ca2+ through bound waters. The activity of superfamily members is regulated by various effecters, some of which act by promoting or inhibiting the conformational change. Nucleotide hydrolysis eliminates interdomain bridging interactions between the second beta 1-beta 2 turn and the ATP gamma-phosphate. This is proposed to destabilize the closed conformation and affect the orientation of the two domains, which might in turn regulate the activity of kinase oligomers, stress-70 protein-protein complexes, and actin filaments. RP Hurley, JH (reprint author), NIDDKD,MOLEC BIOL LAB,NIH,BETHESDA,MD 20892, USA. NR 75 TC 114 Z9 116 U1 1 U2 4 PU ANNUAL REVIEWS INC PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 SN 1056-8700 J9 ANNU REV BIOPH BIOM JI Annu. Rev. Biophys. Biomolec. Struct. PY 1996 VL 25 BP 137 EP & PG 27 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA UT116 UT WOS:A1996UT11600007 PM 8800467 ER PT J AU Wickner, RB AF Wickner, RB TI Prions and RNA viruses of Saccharomyces cerevisiae SO ANNUAL REVIEW OF GENETICS LA English DT Review DE [URE3]; [PSI]; double-stranded RNA virus; killer; SKI ID DOUBLE-STRANDED-RNA; POL FUSION PROTEIN; RIBOSOMAL FRAMESHIFTING EFFICIENCY; KILLER TOXIN GENE; L-A-VIRUS; MESSENGER-RNA; N-ACETYLTRANSFERASE; TRANSGENIC MICE; CAP STRUCTURE; COAT PROTEIN AB Saccharomyces cerevisiae is host to the dsRNA viruses L-A (including its killer toxin-encoding satellite, M) and L-BC, the 20S and 23S ssRNA replicons, and the putative prions, [URE3] and [PSI]. review the genetic and biochemical evidence indicating that [URE3] and [PSI] are prion forms of Ure2p and Sup35p, respectively. Each has an N-terminal domain involved in propagation or generation of the prion state and a C-terminal domain responsible for the protein's normal function, nitrogen regulation, or translation termination, respectively. The L-A dsRNA virus expression, replication, and RNA packaging are reviewed. L-A uses a -1 ribosomal frameshift to produce a Gag-Pol fusion protein. The host SKI2, SKI3, and SKI8 proteins block translation of nonpoly(A) mRNAs (such as viral mRNA). Mutants deficient in 60S ribosomal subunits replicate L-A poorly, but not if cells are also ski(-). Interaction of 60S subunits with the 3' polyA is suggested. SKI1/XRN1 is a 5' --> 3' exoribonuclease that degrades uncapped mRNAs. The viral Gag protein decapitates cellular mRNAs apparently to decoy this enzyme from working on viral mRNA. RP Wickner, RB (reprint author), NIDDKD,NID,NIH,BETHESDA,MD 20892, USA. NR 145 TC 57 Z9 58 U1 0 U2 1 PU ANNUAL REVIEWS INC PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 SN 0066-4197 J9 ANNU REV GENET JI Annu. Rev. Genet. PY 1996 VL 30 BP 109 EP 139 DI 10.1146/annurev.genet.30.1.109 PG 31 WC Genetics & Heredity SC Genetics & Heredity GA WA812 UT WOS:A1996WA81200006 PM 8982451 ER PT J AU Gottesman, S AF Gottesman, S TI Proteases and their targets in Escherichia coli SO ANNUAL REVIEW OF GENETICS LA English DT Review DE Clp; Lon; RpoS; heat shock; SOS ID ATP-DEPENDENT PROTEASE; HEAT-SHOCK RESPONSE; PHAGE LAMBDA-REPRESSOR; SITE-DIRECTED MUTAGENESIS; SIGNAL PEPTIDE PEPTIDASE; OUTER-MEMBRANE PROTEINS; N-END RULE; CLP PROTEASE; LON PROTEASE; GENE-PRODUCT AB Proteolysis in Escherichia coli serves to rid the cell of abnormal and misfolded proteins and to limit the time and amounts of availability of critical regulatory proteins. Most intracellular proteolysis is initiated by energy-dependent proteases, including Lon, ClpXP, and HflB; HflB is the only essential E. coli protease. The ATPase domains of these proteases mediate substrate recognition. Recognition elements in target are not well defined, but are probably not specific amino acid sequences. Naturally unstable protein substrates include the regulatory sigma factors for heat shock and stationary phase gene expression, sigma 32 and RpoS. Other cellular proteins serve as environmental sensors that modulate the availability of the unstable proteins to the proteases, resulting in rapid changes in sigma factor levels and therefore in gene transcription. Many of the specific proteases found in E. coli are well-conserved in both prokaryotes and eukaryotes, and serve critical functions in developmental systems. RP Gottesman, S (reprint author), NCI,MOL BIOL LAB,BLDG 37,ROOM 2E18,BETHESDA,MD 20892, USA. NR 262 TC 490 Z9 506 U1 6 U2 50 PU ANNUAL REVIEWS INC PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 SN 0066-4197 J9 ANNU REV GENET JI Annu. Rev. Genet. PY 1996 VL 30 BP 465 EP 506 DI 10.1146/annurev.genet.30.1.465 PG 42 WC Genetics & Heredity SC Genetics & Heredity GA WA812 UT WOS:A1996WA81200017 PM 8982462 ER PT J AU Ebnet, K Kaldjian, EP Anderson, AO Shaw, S AF Ebnet, K Kaldjian, EP Anderson, AO Shaw, S TI Orchestrated information transfer underlying leukocyte endothelial interactions SO ANNUAL REVIEW OF IMMUNOLOGY LA English DT Review DE leukocyte-endothelial adhesion; chemokines; information transfer; recruitment; reticular network ID MONOCYTE CHEMOTACTIC PROTEIN; PLATELET-ACTIVATING-FACTOR; RAT LYMPH-NODES; T-CELL ADHESION; VASCULAR ENDOTHELIUM; LYMPHOCYTES-T; MESSENGER-RNA; GROWTH-FACTOR; HUMAN SKIN; EXPRESSION AB The specificity and efficiency of leukocyte binding to endothelial cells (ECs) depends on coordinated information transfer from the underlying tissue to endothelium and from there to the leukocyte. We address three distinct information-transfer points in this system: 1. How does the leukocyte read information from the EC? This process is best accounted for by the paradigm of a multi-step adhesion cascade optimized for rapid information readout; it consists of primary adhesion (rolling/tethering), triggering, and strong adhesion. Recent studies with T cells, monocytes, and eosinophils confirm the generality of the paradigm. The concept of primary adhesion has been expanded to involve not only the selectins, but also certain integrins; furthermore, it depends on receptor concentration on leukocyte microvilli. 2. What information from the underlying tissue does the EC transform into signals for the leukocytes? And what rules govern that process ? We illustrate the principles with chemokines, believed to participate in the triggering step. The endothelium displays chemokines either (a) directly by ''posting'' them from other cells or (b) by integrating a variety of tissue and environmental signals and ''relaying'' that information by producing its own chemokines and surface adhesion molecules. The rules for this endothelial transduction include specificity coupled with redundancy, amplification, synergy, and coordinated induction of ensembles of molecules. Finally, 3. How does the relevant information reach the endothelium? Simple diffusion is sufficient to deliver signals from cells close to the vessel. However, longer range soluble mediator transport appears to be facilitated by fiber bundles, particularly those ensheathed by fibroblastic reticular cells in the lymph node. RP Ebnet, K (reprint author), NCI,EXPTL IMMUNOL BRANCH,NIH,BETHESDA,MD 20892, USA. RI Ebnet, Klaus/C-8314-2009 NR 133 TC 171 Z9 172 U1 0 U2 0 PU ANNUAL REVIEWS INC PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 SN 0732-0582 J9 ANNU REV IMMUNOL JI Annu. Rev. Immunol. PY 1996 VL 14 BP 155 EP 177 DI 10.1146/annurev.immunol.14.1.155 PG 23 WC Immunology SC Immunology GA UH429 UT WOS:A1996UH42900008 PM 8717511 ER PT J AU Jones, BD Falkow, S AF Jones, BD Falkow, S TI Salmonellosis: Host immune responses and bacterial virulence determinants SO ANNUAL REVIEW OF IMMUNOLOGY LA English DT Review DE typhoid fever; macrophage survival; M cells; bacterial invasion; Salmonella ID NECROSIS-FACTOR-ALPHA; CULTURED EPITHELIAL-CELLS; OUTER-MEMBRANE PROTEIN; GROWTH-FACTOR-RECEPTOR; TYPHOID-FEVER; TYPHIMURIUM VIRULENCE; YERSINIA-ENTEROCOLITICA; MOLECULAR CHARACTERIZATION; INTERFERON-GAMMA; MAMMALIAN-CELLS AB The lifestyle of bacterial pathogens requires them to establish infection in the face of host immunity. Upon entering a potential host, a variety of interactions are initiated, the outcome of which depends upon a myriad of attributes of each of the participants. In this review we discuss the interactions that occur between pathogenic Salmonella species and the host immune systems, but when appropriate to broaden perspective, we have provided a general overview of the interactions between bacterial pathogens and animal hosts. Pathogenic Salmonella species possess an array of invasion genes that produce proteins secreted by a specialized type III secretion apparatus, These proteins are used by the bacteria to penetrate the intestinal mucosa by invading and destroying specialized epithelial M cells of the Peyer's patches. This manuever deposits the bacteria directly within the confines of the reticuloendothelial system. The host responds to these actions with nonspecific phagocytic cells and an imflammatory response as well as by activating specific cellular and humoral immune responses. Salmonella responds to this show of force directly. It appears that the bacteria invade and establish a niche within the very cells that have been sent to destroy them. Efforts are underway to characterize the factors that allow these intracellular bacteria to customize intracellular vacuoles for their own purposes. It is the constant play between these interactions that determines the outcome of the host infection, and clearly they will also shape the evolution of new survival strategies for both the bacterium and the host. C1 NIH,ROCKY MT LABS,MICROSCOPY BRANCH,HAMILTON,MT 59840. STANFORD UNIV,SCH MED,DEPT MICROBIOL & IMMUNOL,STANFORD,CA 94305. RP Jones, BD (reprint author), UNIV IOWA,SCH MED,DEPT MICROBIOL,IOWA CITY,IA 52242, USA. FU NIAID NIH HHS [AI-26195, AI38268]; NIDDK NIH HHS [DK38707] NR 156 TC 276 Z9 280 U1 1 U2 14 PU ANNUAL REVIEWS INC PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 SN 0732-0582 J9 ANNU REV IMMUNOL JI Annu. Rev. Immunol. PY 1996 VL 14 BP 533 EP 561 DI 10.1146/annurev.immunol.14.1.533 PG 29 WC Immunology SC Immunology GA UH429 UT WOS:A1996UH42900022 PM 8717524 ER PT J AU Dunbar, CE AF Dunbar, CE TI Gene transfer to hematopoietic stem cells: Implications for gene therapy of human disease SO ANNUAL REVIEW OF MEDICINE LA English DT Review DE retrovirus; adeno-associated virus; gene expression; transplantation ID BONE-MARROW CELLS; HUMAN ADENOSINE-DEAMINASE; ADENOASSOCIATED VIRUS; PROGENITOR CELLS; TRANSDUCTION; EXPRESSION; INFECTION; VECTOR; INTEGRATION; INVITRO AB Transfer of new genetic material to hematopoietic stem cells and expression of the gene product in daughter cells of various lineages is an exciting approach to the treatment of congenital and acquired human diseases. This review summarizes the current status of retroviral and adeno-associated viral vectors for gene transfer to human hematopoietic cells, including extensive preclinical data as well as preliminary results from ongoing clinical trials. RP Dunbar, CE (reprint author), NHLBI,HEMATOL BRANCH,BETHESDA,MD 20892, USA. NR 43 TC 64 Z9 64 U1 0 U2 4 PU ANNUAL REVIEWS INC PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 SN 0066-4219 J9 ANNU REV MED JI Annu. Rev. Med. PY 1996 VL 47 BP 11 EP 20 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA UE597 UT WOS:A1996UE59700002 PM 8712765 ER PT J AU Leonard, WJ AF Leonard, WJ TI The molecular basis of X-linked severe combined immunodeficiency: Defective cytokine receptor signaling SO ANNUAL REVIEW OF MEDICINE LA English DT Review DE XSCID; IL-2 receptor; common gamma chain; gamma(c); immunodeficiency ID GAMMA-CHAIN; IL-2 RECEPTOR; FUNCTIONAL COMPONENT; INTERLEUKIN-2; GENE AB X-linked severe combined immunodeficiency (XSCID) is an inherited disease characterized by profoundly diminished cell-mediated and humoral immunity. XSCID was found to result from mutations in the interleukin-2 (IL-2) receptor gamma chain. Knowledge of the genetic defect has important implications for prenatal and postnatal diagnosis, carrier female identification, and the possibility of gene therapy. The fact that the phenotype and clinical manifestations in XSCID are more severe than the abnormalities found in humans or mice deficient in IL-2 led to the speculation and subsequent confirmation that the IL-2 receptor is not the only receptor to contain the gamma-chain. Instead, the gamma chain is also a component of the receptors for IL-4, IL-7, IL-9, and IL-15 and is now denoted as the common cytokine receptor gamma chain, gamma(c). The role of gamma(c) in signaling and lymphoid development and the implications of a shared receptor component are discussed. RP Leonard, WJ (reprint author), NHLBI,LAB MOLEC IMMUNOL,NIH,BETHESDA,MD 20892, USA. NR 52 TC 130 Z9 134 U1 1 U2 16 PU ANNUAL REVIEWS INC PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 SN 0066-4219 J9 ANNU REV MED JI Annu. Rev. Med. PY 1996 VL 47 BP 229 EP 239 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA UE597 UT WOS:A1996UE59700022 PM 8712778 ER PT J AU Ghosh, S Collins, FS AF Ghosh, S Collins, FS TI The geneticist's approach to complex disease SO ANNUAL REVIEW OF MEDICINE LA English DT Review DE complex disease; linkage analysis; phenotypes; genotypes; linkage disequilibrium ID DEPENDENT DIABETES-MELLITUS; FAMILIAL ALZHEIMERS-DISEASE; QUANTITATIVE TRAIT LOCI; AFFECTED RELATIVE PAIRS; PEDIGREE-MEMBER METHOD; LINKAGE ANALYSIS; COLORECTAL-CANCER; INSULIN GENE; ASSOCIATIONS; STRATEGIES AB Many studies are in progress worldwide to elucidate the genetics of complex diseases. Nevertheless, few articles are available that provide the scientific rationale and give guidelines for such ambitious endeavours. We describe the methodology and background necessary to study the genetics of complex disease and discuss how to analyze the data. We also provide a table of some ongoing studies. In particular, we wish to emphasize the analysis of intermediate, heritable, quantitative traits as a means of dissecting the genetic basis of a complex trait. RP Ghosh, S (reprint author), NIH,NATL CTR HUMAN GENOME RES,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 103 TC 46 Z9 48 U1 1 U2 1 PU ANNUAL REVIEWS INC PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 SN 0066-4219 J9 ANNU REV MED JI Annu. Rev. Med. PY 1996 VL 47 BP 333 EP 353 PG 21 WC Medicine, General & Internal SC General & Internal Medicine GA UE597 UT WOS:A1996UE59700029 PM 8712786 ER PT J AU Tsigos, C Chrousos, GP AF Tsigos, C Chrousos, GP TI Differential diagnosis and management of Cushing's syndrome SO ANNUAL REVIEW OF MEDICINE LA English DT Review DE hypercortisolism; pseudo-Cushing; glucocorticoids; corticotropin-releasing factor; adrenalectomy ID CORTICOTROPIN-RELEASING HORMONE; BRONCHIAL CARCINOID-TUMORS; DEXAMETHASONE SUPPRESSION TEST; ECTOPIC ACTH SYNDROME; STIMULATION TEST; FREE CORTISOL; DISEASE; HYPERCORTISOLISM; RESPONSES AB The diagnosis of endogenous Cushing's syndrome requires demonstration of an increased cortisol secretion rate, best achieved by urinary free cortisol excretion determinations. In borderline or confusing cases, loss of diurnal cortisol rhythmicity, a combined dexamethasone/corticotropin releasing hormone (CRH) test, or close monitoring of the patient for a few months will be helpful in ruling out pseudo-Cushing's. Primary adrenal Cushing's syndrome can be ruled out on the basis of a normal or elevated basal and/or CRH-stimulated plasma adrenocorticotropin (ACTH) and a negative adrenal computed tomography. ACTH-dependent Cushing's syndrome can then be differentiated on the basis of a CRH test and imaging procedures. A discrete pituitary lesion on magnetic resonance imaging and a standard CRH test with results consistent with such a lesion are sufficient to proceed to transsphenoidal surgery. If no discrete pituitary lesion is present, or if the CRH test is equivocal, bilateral simultaneous inferior petrosal sinus sampling with CRH administration is necessary to distinguish between a pituitary and an ectopic source. Surgery is the treatment of choice for all types of Cushing's syndrome. In the few cases in which transsphenoidal surgery fails or the disease recurs, repeat transsphenoidal surgery, or radiation therapy in association with mitotane treatment, is a reasonable alternative. Bilateral adrenalectomy effectively cures hypercortisolism if resection of the ACTH-secreting tumor is unsuccessful and radiation/medical therapy fails. C1 NICHHD, DEV ENDOCRINOL BRANCH, NIH, BETHESDA, MD 20892 USA. RP Tsigos, C (reprint author), UNIV ATHENS, SCH MED, DEPT EXPTL PHYSIOL, GR-11527 ATHENS, GREECE. NR 52 TC 42 Z9 47 U1 0 U2 0 PU ANNUAL REVIEWS INC PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 SN 0066-4219 J9 ANNU REV MED JI Annu. Rev. Med. PY 1996 VL 47 BP 443 EP 461 PG 19 WC Medicine, General & Internal SC General & Internal Medicine GA UE597 UT WOS:A1996UE59700037 PM 8712794 ER PT J AU Norquist, GS Regier, DA AF Norquist, GS Regier, DA TI The epidemiology of psychiatric disorders and the De Facto mental health care system SO ANNUAL REVIEW OF MEDICINE LA English DT Review DE epidemiology; mental health; psychiatry; service utilization ID CATCHMENT-AREA-PROGRAM; ADDICTIVE-DISORDERS; MEDICAL OUTCOMES; GENERAL-PRACTICE; UNITED-STATES; DEPRESSION; RECOGNITION; PREVALENCE; SERVICES AB Recent national epidemiologic studies have provided data on the number of people in the United States with mental and addictive disorders. Many of these people receive their care in the general medical care sector. This has important implications for diagnosis and treatment of mental and addictive disorders. RP Norquist, GS (reprint author), NIMH,DIV EPIDEMIOL & SERV RES,ROCKVILLE,MD 20857, USA. NR 29 TC 57 Z9 57 U1 1 U2 2 PU ANNUAL REVIEWS INC PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 SN 0066-4219 J9 ANNU REV MED JI Annu. Rev. Med. PY 1996 VL 47 BP 473 EP 479 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA UE597 UT WOS:A1996UE59700039 PM 8712797 ER PT J AU Rosenberg, SA AF Rosenberg, SA TI The immunotherapy of solid cancers based on cloning the genes encoding tumor-rejection antigens SO ANNUAL REVIEW OF MEDICINE LA English DT Review DE interleukin-2; gp100; MART-1; melanoma; lymphocytes ID HUMAN-MELANOMA ANTIGENS; INFILTRATING LYMPHOCYTES; RECOMBINANT INTERLEUKIN-2; RECOGNITION; RESPONSES; CELLS AB Cellular immune reactions play a major role in the host reaction to growing cancers. Tumor infiltrating lymphocytes (TIL) can be isolated from melanomas and can specifically recognize unique tumor antigens. The adoptive transfer of TIL plus interleukin-2 can mediate tumor regression in patients with metastatic melanoma. Tn capable of mediating tumor regression have been used to clone and sequence a variety of the genes that encode the tumor-regression antigens recognized by these TIL. This information has opened new opportunities for the development of cancer immunotherapies. These gene products can be used to generate lymphocytes, in vitro, with improved antitumor activity for use in adoptive transfer. Active immunization can be performed using either the immunodominant peptides present in these proteins or by incorporating the tumor antigen genes into recombinant viruses. Cancer vaccine trials using many of these approaches have recently begun. Attempts to apply a similar strategy to epithelial tumors such as breast and ovarian cancer are underway. RP Rosenberg, SA (reprint author), NCI,DEPT HLTH & HUMAN SERV,NIH,BETHESDA,MD 20892, USA. NR 38 TC 82 Z9 83 U1 0 U2 1 PU ANNUAL REVIEWS INC PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 SN 0066-4219 J9 ANNU REV MED JI Annu. Rev. Med. PY 1996 VL 47 BP 481 EP 491 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA UE597 UT WOS:A1996UE59700040 PM 8712798 ER PT J AU Whittaker, CJ Klier, CM Kolenbrander, PE AF Whittaker, CJ Klier, CM Kolenbrander, PE TI Mechanisms of adhesion by oral bacteria SO ANNUAL REVIEW OF MICROBIOLOGY LA English DT Review DE coaggregation; adherence; invasion; receptors ID ACTINOMYCES-VISCOSUS T14V; PORPHYROMONAS BACTEROIDES GINGIVALIS; NUCLEOTIDE-SEQUENCE ANALYSIS; STREPTOCOCCUS-SANGUIS G9B; CELL-WALL POLYSACCHARIDE; SURFACE PROTEIN ANTIGEN; GRAM-POSITIVE BACTERIA; AGGLUTININ-MEDIATED ADHERENCE; FUSOBACTERIUM-NUCLEATUM T18; FIMBRIA-ASSOCIATED ADHESIN AB Adherence to a surface is a key element for colonization of the human oral cavity by the more than 500 bacterial taxa recorded from oral samples. Three surfaces are available: teeth, epithelial mucosa, and the nascent surface created as each new bacterial cell binds to existing dental plaque. Oral bacteria exhibit specificity for their respective colonization sites. Such specificity is directed by adhesin-receptor cognate pairs on genetically distinct cells. Colonization is successful when adherent cells grow and metabolically participate in the oral bacterial community. The potential roles of adherence-relevant molecules are discussed in the context of the dynamic nature of the oral econiche. RP Whittaker, CJ (reprint author), NIDR, MICROBIAL ECOL LAB, NIH, BETHESDA, MD 20892 USA. NR 220 TC 233 Z9 239 U1 3 U2 27 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0066-4227 J9 ANNU REV MICROBIOL JI Annu. Rev. Microbiol. PY 1996 VL 50 BP 513 EP 552 DI 10.1146/annurev.micro.50.1.513 PG 40 WC Microbiology SC Microbiology GA VL560 UT WOS:A1996VL56000018 PM 8905090 ER PT J AU Pantaleo, G Fauci, AS AF Pantaleo, G Fauci, AS TI Immunopathogenesis of HIV infection SO ANNUAL REVIEW OF MICROBIOLOGY LA English DT Review DE primary infection; virologic events; immunologic events; mechanisms of virus escape ID HUMAN-IMMUNODEFICIENCY-VIRUS; HUMAN MONOCLONAL-ANTIBODIES; FOLLICULAR DENDRITIC CELLS; AIDS-RELATED COMPLEX; CD4 BINDING-SITE; T-HELPER CELLS; LYMPHOID ORGANS; SYNERGISTIC NEUTRALIZATION; GENETIC-VARIATION; TYPE-1 INFECTION AB The rate of progression of HIV disease may be substantially different among HIV- infected individuals. Following infection of the host with any virus, the delicate balance between virus replication and the immune response to the virus determines both the outcome of the infection, i.e. the persistence versus elimination of the virus, and the different rates of progression. During primary HIV infection, a burst of viremia occurs that disseminates virus to the lymphoid organs. A potent immune response ensues that substantially, but usually not completely, curtails virus replication. This inability of the immune system to completely eliminate the virus leads to establishment of chronic, persistent infection that over time leads to profound immunosuppression. The potential mechanisms of virus escape from an otherwise effective immune response have been investigated. Clonal deletion of HIV-specific cytotoxic T-cell clones and sequestration of virus-specific cytotoxic cells away from the major site of virus replication represent important mechanisms of virus escape from the immune response that favor persistence of HIV. Qualitative differences in the primary immune response to AIV (i.e. mobilization of a restricted versus broader T-cell receptor repertoire) are associated with different rates of disease progression. Therefore, the initial interaction between the virus and immune system of the host is critical for the subsequent clinical outcome. RP Pantaleo, G (reprint author), NIAID,IMMUNOREGULAT LAB,NIH,BLDG 10,BETHESDA,MD 20892, USA. RI Pantaleo, Giuseppe/K-6163-2016 NR 103 TC 182 Z9 188 U1 1 U2 7 PU ANNUAL REVIEWS INC PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 SN 0066-4227 J9 ANNU REV MICROBIOL JI Annu. Rev. Microbiol. PY 1996 VL 50 BP 825 EP 854 DI 10.1146/annurev.micro.50.1.825 PG 30 WC Microbiology SC Microbiology GA VL560 UT WOS:A1996VL56000028 PM 8905100 ER PT J AU Peoples, RW Li, CY Weight, FF AF Peoples, RW Li, CY Weight, FF TI Lipid vs protein theories of alcohol action in the nervous system SO ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY LA English DT Review DE alcohol; membrane; protein; central nervous system; neurotransmitter-gated ion channels ID NICOTINIC ACETYLCHOLINE-RECEPTOR; RAT HIPPOCAMPAL-NEURONS; ANESTHETIC TARGET SITES; ACTIVATED ION CURRENT; GENERAL-ANESTHESIA; ETHANOL POTENTIATION; HIGH-PRESSURE; STEREOSPECIFIC ACTIONS; VOLATILE ANESTHETICS; NEUROBLASTOMA-CELLS AB There has been a long-standing debate concerning whether alcohols produce their effects in the central nervous system (CNS) by acting on lipids or proteins. Lipid theories postulate that alcohols act via some perturbation of the membrane lipids of CNS neurons, whereas protein theories propose that alcohols act by interacting with a neuronal protein site. Although the primary site of action differs in the two theories, both theories postulate that the CNS effects of alcohols ultimately result from alterations in protein function. This review discusses lipid and protein theories of alcohol action and the evidence supporting these theories. In addition, the effects of alcohols on the function of neurotransmitter-gated ion channels are discussed, as several types of these receptor-ion channels have been found to be sensitive to the actions of alcohols, and recent studies on those actions have yielded new insights into the question of whether the primary action of alcohols involves lipids or proteins. RP Peoples, RW (reprint author), NIAID,MOLEC & CELLULAR NEUROBIOL LAB,NIH,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 111 TC 133 Z9 134 U1 1 U2 7 PU ANNUAL REVIEWS INC PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 SN 0362-1642 J9 ANNU REV PHARMACOL JI Annu. Rev. Pharmacol. Toxicol. PY 1996 VL 36 BP 185 EP 201 PG 17 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA UH635 UT WOS:A1996UH63500008 PM 8725387 ER PT J AU Erickson, JW Burt, SK AF Erickson, JW Burt, SK TI Structural mechanisms of HIV drug resistance SO ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY LA English DT Review DE AIDS; protease; reverse transcriptase; antiviral drug; human immunodeficiency virus (HIV); mutations ID HUMAN-IMMUNODEFICIENCY-VIRUS; REVERSE-TRANSCRIPTASE; NONNUCLEOSIDE INHIBITORS; ANGSTROM RESOLUTION; CRYSTAL-STRUCTURE; ANTIVIRAL DRUGS; PROTEASE; TYPE-1; SENSITIVITY; ALLOPHENYLNORSTATINE AB Antiviral therapy for AIDS has focused on the discovery and design of inhibitors for two main enzyme targets of the human immunodeficiency virus type 1 (HIV)-reverse transcriptase (RT) and protease (PR). Despite several classes of promising new anti-HIV agents, the clinical emergence of drug-resistant variants of HIV has severely limited the long-term effectiveness of these drugs. Genetic analysis of resistant virus has identified a number of critical mutations in the RT and PR genes. Structural analysis of inhibitor-enzyme complexes and mutational modeling studies are leading to a better understanding of how these drug-resistance mutations exert their effects at a structural level. These insights have implications for the design of new drugs and therapeutic strategies to combat drug resistance to AIDS. RP Erickson, JW (reprint author), NCI,FREDERICK CANC RES & DEV CTR,SAIC,FREDERICK BIOMED SUPERCOMP CTR,STRUCT BIOCHEM PROGRAM,FREDERICK,MD 21702, USA. NR 74 TC 133 Z9 134 U1 3 U2 10 PU ANNUAL REVIEWS INC PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 SN 0362-1642 J9 ANNU REV PHARMACOL JI Annu. Rev. Pharmacol. Toxicol. PY 1996 VL 36 BP 545 EP 571 PG 27 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA UH635 UT WOS:A1996UH63500022 PM 8725401 ER PT J AU Wolff, MS Collman, GW Barrett, JC Huff, J AF Wolff, MS Collman, GW Barrett, JC Huff, J TI Breast cancer and environmental risk factors: Epidemiological and experimental findings SO ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY LA English DT Review DE exposure; chemicals; animal models; timing; chemical carcinogenesis ID ACUTE POSTPARTUM MASTITIS; EXPERIMENTAL-ANIMALS; CIGARETTE-SMOKING; HUMAN CARCINOGENS; BOMB SURVIVORS; CHEMICALS; HYPOTHESIS; MORTALITY; WOMEN; 2,3,7,8-TETRACHLORODIBENZO-PARA-DIOXIN AB Breast cancer has long been associated with reproductive hormone exposures. Recently, greater attention has been focused on environmental exposures that may be responsible for some proportion of breast cancer incidence. Several etiologic aspects are discussed. A number of chemicals induce breast cancer in rodents-including solvents, pesticides, and polycyclic aromatic hydrocarbons-and these might serve as leads for studies in humans. In women, strong links have been established between breast cancer risk and ionizing radiation. Evidence for nonionizing radiation (electromagnetic field) exposures and breast cancer is suggestive, albeit limited. Occupational exposures have not been identified as breast cancer risks, but several associations need further study, including solvents and pesticides. Time of life when exposures take place is important, and this claim is strongly supported by data on cigarette smoking and radiation. Also, basic research has demonstrated that mammary tissue is more susceptible to carcinogenesis at certain periods of breast development. Likewise, prenatal, neonatal, and adolescent exposures deserve continuing attention. Research on etiology of breast cancer should measure environmental exposures and take into account the time of life at which these occur. Complex interactions between exogenous and endogenous carcinogenic agents need further focus, as modulated by varying genetically determined individual susceptibilities. C1 CUNY MT SINAI SCH MED,NEW YORK,NY 10029. RP Wolff, MS (reprint author), NIEHS,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 113 TC 97 Z9 101 U1 1 U2 5 PU ANNUAL REVIEWS INC PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 SN 0362-1642 J9 ANNU REV PHARMACOL JI Annu. Rev. Pharmacol. Toxicol. PY 1996 VL 36 BP 573 EP 596 PG 24 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA UH635 UT WOS:A1996UH63500023 PM 8725402 ER PT J AU Spiegel, AM AF Spiegel, AM TI Defects in G protein-coupled signal transduction in human disease SO ANNUAL REVIEW OF PHYSIOLOGY LA English DT Review DE receptor; mutations; hormone resistance; GTPase; endocrine hyperfunction ID CONSTITUTIVELY ACTIVATING MUTATION; NEPHROGENIC DIABETES-INSIPIDUS; DOMINANT RETINITIS-PIGMENTOSA; LUTEINIZING-HORMONE RECEPTOR; STIMULATE ADENYLYL CYCLASE; MCCUNE-ALBRIGHT SYNDROME; VASOPRESSIN RECEPTOR; PRECOCIOUS PUBERTY; PITUITARY-TUMORS; ALPHA-SUBUNIT AB G proteins couple receptors for many hormones and neurotransmitters to effecters that regulate second messenger metabolism. G protein-coupled receptors comprise a superfamily with the common structural feature of a single polypeptide with seven membrane-spanning domains. G proteins themselves are heterotrimers with an cl subunit that binds guanine nucleotides. In the basal state, G proteins tightly bind GDP; receptor activation allows exchange of bound GDP for GTP that activates the G protein and causes it to modulate effector activity. An intrinsic GTPase activity hydrolyzes bound GTP to GDP thereby deactivating the G protein. The effects (cholera, whooping cough) of bacterial toxins that target G proteins for covalent modification signal the potential importance of G protein dysfunction as a cause of human disease. Conceptually, G protein dysfunction could involve gain or loss of function. For Gs, examples of both types have already been defined. Mutations in G protein-coupled receptors have also been identified in several human diseases. Germline loss of function mutations in rhodopsin, cone opsins, the V2 vasopressin receptor, ACTH receptor, and calcium-sensing receptor are responsible for retinitis pigmentosa, color blindness, nephrogenic diabetes insipidus, familial ACTH resistance, and familial hypocalciuric hypercalcemia, respectively. Missense mutations that cause constitutive receptor activation have been identified in the TSH and LH receptors. RP Spiegel, AM (reprint author), NIDDKD,METAB DIS BRANCH,NATL INST HLTH,BETHESDA,MD 20892, USA. NR 90 TC 158 Z9 163 U1 1 U2 14 PU ANNUAL REVIEWS INC PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 SN 0066-4278 J9 ANNU REV PHYSIOL JI Annu. Rev. Physiol. PY 1996 VL 58 BP 143 EP 170 DI 10.1146/annurev.physiol.58.1.143 PG 28 WC Physiology SC Physiology GA UB984 UT WOS:A1996UB98400008 PM 8815789 ER PT J AU Guralnik, JM Fried, LP Salive, ME AF Guralnik, JM Fried, LP Salive, ME TI Disability as a public health outcome in the aging population SO ANNUAL REVIEW OF PUBLIC HEALTH LA English DT Article DE aging; disability; functional status; frailty; functional assessment ID TERM CARE SERVICES; OLDER PERSONS; MAINTAINING MOBILITY; PHYSICAL-DISABILITY; FUNCTIONAL STATUS; ELDERLY PATIENTS; PERFORMANCE-TEST; ALAMEDA COUNTY; SELF-REPORT; LATE-LIFE AB Improvements in life expectancy in the twentieth century have resulted from major declines in mortality at younger ages, but it is less well recognized that mortality declines at older ages have also played a substantial role in prolonging expectation of life. A person reaching age 65 in 1900 could expect to live an additional 11.9 years. Life expectancy at age 65 rose to 14.4 years by 1960 and then increased by about three years in the next three decades, reaching 17.5 years in 1992 (56, 70). As a greater proportion of the population survives to very old ages, the public health impact of the burden of disease and disability and related utilization of medical care and need for supportive and long-term care has become an important concern. In particular, the ability of the older person to function independently in the community is a critically important public health issue. A growing body of research in the last decade has addressed the measurement of disability, factors related to its onset, consequences of disability, and the potential for preventive interventions. This article summarizes the state of the art in these areas and discusses their public health relevance. C1 JOHNS HOPKINS MED INST, DEPT MED, BALTIMORE, MD 21205 USA. JOHNS HOPKINS MED INST, DEPT EPIDEMIOL, BALTIMORE, MD 21205 USA. RP Guralnik, JM (reprint author), NIA, EPIDEMIOL DEMOG & BIOMETRY PROGRAM, BETHESDA, MD 20892 USA. NR 96 TC 207 Z9 210 U1 10 U2 24 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0163-7525 EI 1545-2093 J9 ANNU REV PUBL HEALTH JI Annu. Rev. Public Health PY 1996 VL 17 BP 25 EP 46 DI 10.1146/annurev.pu.17.050196.000325 PG 22 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA UK766 UT WOS:A1996UK76600003 PM 8724214 ER PT J AU Plant, M Zimmerman, EM Goldstein, RA AF Plant, M Zimmerman, EM Goldstein, RA TI Health hazards to humans associated with domestic pets SO ANNUAL REVIEW OF PUBLIC HEALTH LA English DT Article DE asthma; hypersensitivity diseases; bites by animals; infectious diseases; immunocompromised patients ID PIGEON-BREEDERS LUNG; CAT-SCRATCH DISEASE; FEL-D-I; UNITED-STATES; ANIMAL BITES; DUST MITE; ASTHMA; ALLERGENS; EXPOSURE; IMMUNOTHERAPY AB Allergy to pets, particularly when manifested as asthma, is an important health hazard. The health impact of severe clinical disease associated with allergy to pets can be minimized by avoidance of pets. Many individuals with milder disease keep their pets and obtain medications for relief of their allergy symptoms. Bird fancier's disease can result in profound deterioration of pulmonary function, and requires avoidance of bird exposure. Animal bites are the commonest health hazard of domestic pets and result in tissue damage and infection risk. Bites are treated by cleaning the wound, and appropriate use of antibiotics and tetanus prophylaxis. Diverse infectious diseases are transmitted to humans by their pets; these diseases are particularly dangerous to immunocompromised individuals. The infectious diseases can be partly prevented by avoiding ill animals and by washing of hands following exposure to pets or pet-derived secretions. They can be treated by appropriate antibiotics and/or specific immune globulins and/or vaccines. RP Plant, M (reprint author), NIAID,DIV ALLERGY IMMUNOL & TRANSPLANTAT,NIH,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 84 TC 8 Z9 9 U1 2 U2 9 PU ANNUAL REVIEWS INC PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 SN 0163-7525 J9 ANNU REV PUBL HEALTH JI Annu. Rev. Public Health PY 1996 VL 17 BP 221 EP 245 PG 25 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA UK766 UT WOS:A1996UK76600014 PM 8724225 ER PT J AU Schooler, C AF Schooler, C TI Cultural and social-structural explanations of cross-national psychological differences SO ANNUAL REVIEW OF SOCIOLOGY LA English DT Article DE culture; social structure; attitudes; psychological functioning ID UNITED-STATES; OCCUPATIONAL CONDITIONS; CLASS BOUNDARIES; JAPAN; PERMEABILITY; BEHAVIOR; CANADA; NORWAY; SWEDEN AB This chapter examines cross-national differences in individual values, attitudes, and behaviors. The central question raised is how social-structural and cultural factors account for the differences found. After discussing a series of theoretical issues raised by this question, the chapter reviews the findings of four quantitative sociological research programs on modern cross-national differences. The program on individual modernity led by Alex Inkeles established that social-structural conditions associated with industrialization are linked to an increase in individuals' being open to new experience, rejecting traditional authority, and taking a rational, ambitious, orderly apl,roach to both work and human problems. The cross-national research on the Kohn-Schooler hypothesis that self-directed work increases intellectual functioning, and self-directed orientations confirmed the generality of that hypothesis and established that the social status and social class differences in these psychological characteristics found within different countries are largely the result of social-structurally determined differences in the opportunity for occupational self-direction. Eric Wright's cross-national research program on class structure and class consciousness provides evidence that in a range of countries social classes directly affect political attitudes, while acting as tangible barriers to mobility and personal relationships. The research deriving from John Meyer's theories on institutionalization highlights the importance of institutions and socially constructed views of reality for the development and maintenance of cross-national differences and similarities in cultural values and their behavioral embodiment. All four of the programs provide evidence of the continuing importance of historically determined cultural differences. All are also congruent with the hypothesis that speed of change generally decreases as we go from psychological to social-structural to cultural levels of phenomena-a possibility whose confirmation would provide a valuable tool for understanding how culture and social structure affect cross-national differences in values and behavior. RP Schooler, C (reprint author), NIMH, LAB SOCIOENVIRONM STUDIES,NIH,FED BLDG,ROOM B1A14, 7550 WISCONSIN AVE, BETHESDA, MD 20892 USA. NR 65 TC 44 Z9 44 U1 2 U2 13 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0360-0572 J9 ANNU REV SOCIOL JI Annu. Rev. Sociol. PY 1996 VL 22 BP 323 EP 349 DI 10.1146/annurev.soc.22.1.323 PG 27 WC Sociology SC Sociology GA VD455 UT WOS:A1996VD45500013 ER PT J AU Morelli, S Alama, A Quattrone, A Gong, L Copreni, E Canti, G Nicolin, A AF Morelli, S Alama, A Quattrone, A Gong, L Copreni, E Canti, G Nicolin, A TI Oligonucleotides induce apoptosis restricted to the t(14;18) DHL-4 cell line SO ANTI-CANCER DRUG DESIGN LA English DT Article DE apoptosis; B-cell lymphoma; bcl-2 gene; oligodeoxynucleotides; t(14;18) ID CHROMOSOME-TRANSLOCATION; ANTISENSE OLIGODEOXYNUCLEOTIDES; BCL-2 PROTEIN; LEUKEMIA; LYMPHOMA; GENE; EXPRESSION; ONCOGENE; CANCER; GROWTH AB Most human follicular B-cell lymphomas are associated with t(14;18) chromosome translocation that joins the bcl-2 gene with the IgH locus. This hybrid gene causes upregulation of BCL-2 protein expression, endowing cells with survival advantage. Although early BCL-2 overexpression is definitely responsible for immortalization/transformation, its exact role in the overt transformation as well as in the maintenance of the tumor phenotype is not known. The capacity of oligodeoxynucleotides (ODN) to modulate gene expression specifically has been exploited to downregulate the overexpression of BCL-2 protein in the SU-DHL-4 human follicular B-cell lymphoma line by the use of sense ODN or antisense ODN designed to encompass the unique nucleotide sequence in the fusion region of the hybrid transcript. The specific downregulation of the bcl-2 transcript and of the relevant BCL-2 protein in the treated cells activated programed cell death and inhibited growing cells. The antitumor activity was restricted to the DHL-4 cell line carrying the specific nucleotide sequence at the bcl-2/IgH joining region. Thus, DHL-4 lymphoma cells derived from the acute phase of human follicular B-cell lymphoma, although endowed with additional activated oncogenes, were growth inhibited by bcl-2 downregulation in a genetically restricted fashion. The biological activity was exerted exclusively by ODNs synthesized in the sense orientation. The sense ODNs have been proposed to anneal the hybrid bcl-2/IgH antisense RNA as identified in this study. C1 UNIV MILAN,SCH MED,DEPT PHARMACOL,I-20129 MILAN,ITALY. NATL CANC INST,GENOA,ITALY. UNIV FLORENCE,INST GEN PATHOL,FLORENCE,ITALY. OI Quattrone, Alessandro/0000-0003-3333-7630 NR 41 TC 13 Z9 13 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0266-9536 J9 ANTI-CANCER DRUG DES JI Anti-Cancer Drug Des. PD JAN PY 1996 VL 11 IS 1 BP 1 EP 14 PG 14 WC Biochemistry & Molecular Biology; Oncology; Chemistry, Medicinal; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Oncology; Pharmacology & Pharmacy GA UC197 UT WOS:A1996UC19700002 PM 8639245 ER PT J AU Sun, Y Kim, H Parker, M StelerStevenson, WG Colburn, NH AF Sun, Y Kim, H Parker, M StelerStevenson, WG Colburn, NH TI Lack of suppression of tumor cell phenotype by overexpression of TIMP-3 in mouse JB6 tumor cells: Identification of a transfectant with increased tumorigenicity and invasiveness SO ANTICANCER RESEARCH LA English DT Article DE TIMP-3; tumor cell phenotype; DNA transfection; tumorigenicity; gene expression ID B16-F10 MELANOMA-CELLS; HUMAN-TISSUE INHIBITOR; NASOPHARYNGEAL CARCINOMA; METALLOPROTEINASES TIMP; INVASION; EXPRESSION; CHICKEN; MEMBER; FAMILY; P53 AB Background: We have recently cloned mouse tissue inhibitor of metalloproteinases-3 (mTIMP-3) by the differential display technique and found that mTIMP-3 was expressed in preneoplastic but not in neoplastic mouse JB6 epidermal cells (Sun et al. Cancer Res. 54:11139, 1994). This down regulation of the gene is attributable at least in part to alternation in gene methylation (Sun et al., J. Biol. Chem., 270:19312, 1995). Methods: To examine the potential role of TIMP-3 in this tumor model, we overexpressed mouse TIMP-3 in two JB6 tumor cell lines lacking endogenous mTIMP-3 expression. Stable transfectants from each line were selected and assayed for possible changes in tumor cell phenotype. Results: Our results showed that overexpression of mTIMP-3 in these two tumor lines did not change their ability to grow in soft agar, an assay for anchorage-independent growth, nor in nude mice, an in vivo tumorigenicity assay, nor to penetrate matrigel, an assay for invasiveness. We, however, isolated a clone which is highly malignant as demonstrated by a) very short latent period for tumor formation; b) very fast tumor growth; and c) highly invasive in the matrigel assay. Conclusion: We conclude from this study that although TIMP-3 is not expressed in mouse JB6 tumor cells, overexpression by DNA transfection did not reverse tumor cell phenotype, suggesting a complex role for TIMP-3 in tumorigenesis. The highly malignant transfectant isolated by this study can be used as a tool for the cloning of dominant oncogenes as well as tumor suppressor genes. C1 NCI,FREDERICK CANC RES & DEV CTR,CELL BIOL SECT,LAB VIRAL CARCINOGENESIS,FREDERICK,MD 21702. NCI,NIH,PATHOL LAB,EXTRACELLULAR MATRIX PATHOL SECT,BETHESDA,MD 20892. RP Sun, Y (reprint author), PARKE DAVIS PHARMACEUT RES,DEPT CANC RES,2800 PLYMOUTH RD,ANN ARBOR,MI 48105, USA. RI Stetler-Stevenson, William/H-6956-2012 OI Stetler-Stevenson, William/0000-0002-5500-5808 NR 29 TC 26 Z9 28 U1 0 U2 1 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDNTIOU-KALAMOU RD KAPANDRITI, POB 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD JAN-FEB PY 1996 VL 16 IS 1 BP 1 EP 7 PG 7 WC Oncology SC Oncology GA UF830 UT WOS:A1996UF83000001 PM 8615593 ER PT J AU Lindsay, CK Gomez, DE Thorgeirsson, UP AF Lindsay, CK Gomez, DE Thorgeirsson, UP TI Effect of flavone acetic acid on endothelial cell proliferation: Evidence for antiangiogenic properties SO ANTICANCER RESEARCH LA English DT Article DE FAA; endothelium; antiangiogenic; cytokines ID TUMOR-NECROSIS-FACTOR; ANTITUMOR-ACTIVITY; BLOOD-FLOW; XANTHENONE ANALOGS; INTERFERON-GAMMA; INVITRO MODEL; ANGIOGENESIS; MECHANISM; INDUCTION; MICE AB Flavone acetic acid (FAA) causes regression of a range of slow growing solid tumors implanted subcutaneously in mice. Although its precise mechanism of action is unknown, vascular collapse has been shown to precede tumor growth delay and regression. The aim of this study was to determine whether or not endothelial cell function was directly affected by clinically relevant concentrations of FAA. FAA at 100-250 mu g/ml inhibited endothelial cell proliferation in vitro, but did not compromise cellular function or viability. FAA abolished tubule formation in an in vitro angiogenesis assay and reduced vascular development of the chick embryo chorioallantoic membrane. In addition to targeting established tumor vasculature, FAA may also affect proliferating endothelium which may be involved in mediating the reduced tumor growth rate or stasis often observed after drug exposure. The chorioallantoic membrane of the chick embryo may represent an important model to elucidate more clearly the effect of FAA on a growing vascular network. C1 NCI,NIH,OFF DIRECTOR,TUMOR BIOL & CARCINOGENESIS SECT,BETHESDA,MD 20892. OI Gomez, Daniel E/0000-0002-8629-0787 NR 36 TC 11 Z9 11 U1 0 U2 0 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDNTIOU-KALAMOU RD KAPANDRITI, POB 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD JAN-FEB PY 1996 VL 16 IS 1 BP 425 EP 431 PG 7 WC Oncology SC Oncology GA UF830 UT WOS:A1996UF83000065 PM 8615648 ER PT J AU Padlan, EA AF Padlan, EA TI X-ray crystallography of antibodies SO ANTIGEN BINDING MOLECULES: ANTIBODIES AND T-CELL RECEPTORS SE ADVANCES IN PROTEIN CHEMISTRY LA English DT Review ID BENCE-JONES PROTEIN; IMMUNOGLOBULIN FAB FRAGMENT; LIGHT-CHAIN DIMER; HUMAN FC FRAGMENT; 2 CRYSTAL FORMS; INFLUENZA-VIRUS NEURAMINIDASE; SITE-DIRECTED MUTAGENESIS; ELECTRON-DENSITY MAP; 3-DIMENSIONAL STRUCTURE; NEUTRALIZING ANTIBODY RP Padlan, EA (reprint author), NIDDKD,MOL BIOL LAB,NIH,BETHESDA,MD 20892, USA. NR 171 TC 125 Z9 125 U1 2 U2 10 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0065-3233 J9 ADV PROTEIN CHEM JI Adv.Protein Chem. PY 1996 VL 49 BP 57 EP 133 DI 10.1016/S0065-3233(08)60488-X PG 77 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BG71H UT WOS:A1996BG71H00002 PM 8908297 ER PT J AU Piscitelli, SC Amantea, MA Vogel, S Bechtel, C Metcalf, JA Kovacs, JA AF Piscitelli, SC Amantea, MA Vogel, S Bechtel, C Metcalf, JA Kovacs, JA TI Effects of cytokines on antiviral pharmacokinetics: An alternative approach to assessment of drug interactions using bioequivalence guidelines SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID IMMUNODEFICIENCY-VIRUS INFECTION; PLACEBO-CONTROLLED TRIAL; AIDS-RELATED COMPLEX; INTERFERON-ALPHA; ZIDOVUDINE; AZIDOTHYMIDINE; INTERLEUKIN-2; EQUIVALENCE; DIDANOSINE; THERAPY AB The effects of cytokines on the pharmacokinetics of nucleoside analogs were evaluated in two separate studies using zidovudine in combination with interleukin-2 and didanosine in combination with alpha interferon. In each study, drug interactions were evaluated by using both a standard method (Student's t test) and bioequivalence testing. Serial blood samples were collected from human immunodeficiency virus-infected patients prior to and during cytokine therapy for determination of nucleoside analog concentrations. Concentrations were fit separately to a two-compartment model by using the iterative two-stage approach to population analysis. No alterations in area under the curve or oral clearance were observed for either drug during combination therapy. In general, there was good agreement between statistical methods for determining if antiviral pharmacokinetic parameters were altered by concomitant cytokine therapy. However, large individual changes in the maximum concentration of zidovudine in serum were detected by bioequivalence testing but no difference was found by Student's t test. For didanosine, significant but clinically irrelevant decreases determined by standard hypothesis testing were seen for both the volume of the central compartment (1.91 to 1.86 liters) and the absorption rate constant (0.79 to 0.73 h(-1)) in the presence of alpha interferon. No interaction was noted for these parameters by using bioequivalence guidelines. Bioequivalence testing may provide an alternative approach to assessment of drug interactions. Interleukin-2 and alpha interferon do not alter the pharmacokinetics of zidovudine and didanosine, respectively. C1 NIAID,DEPT PHARM,BETHESDA,MD 20892. NIAID,DEPT CRIT CARE MED,BETHESDA,MD 20892. NIAID,CTR CLIN,BETHESDA,MD 20892. NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. NR 25 TC 8 Z9 9 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD JAN PY 1996 VL 40 IS 1 BP 161 EP 165 PG 5 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA TN213 UT WOS:A1996TN21300032 PM 8787899 ER PT J AU Welsh, L Gaydos, C Quinn, TC AF Welsh, L Gaydos, C Quinn, TC TI In vitro activities of azithromycin, clarithromycin, erythromycin, and tetracycline against 13 strains of Chlamydia pneumoniae SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID INVITRO EVALUATION; TRACHOMATIS; TWAR; ANTIBIOTICS AB Thirteen strains of Chlamydia pneumoniae were evaluated for their in vitro susceptibilities to azithromycin, clarithromycin, erythromycin, and tetracycline. The MIC ranges were 0.125 to 0.5 mu g/ml for azithromycin, 0.031 to 1.0 mu g/ml for clarithromycin, 0.125 to 1.0 mu g/ml for erythromycin, and 0.125 to 1.0 mu g/ml for tetracycline, The ranges for the minimal lethal concentrations were 0.125 to 0.5 mu g/ml for azithromycin. 0.031 to 1.0 mu g/ml for clarithromycin, 0.125 to 1.0 mu g/ml for erythromycin, and 0.25 to 1.0 mu g/ml for tetracycline. Clarithromycin and azithromycin were the most active antibiotics against C. pneumoniae in vitro. C1 JOHNS HOPKINS UNIV,SCH MED,DIV INFECT DIS,BALTIMORE,MD 21205. NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. RI Gaydos, Charlotte/E-9937-2010 NR 16 TC 23 Z9 23 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD JAN PY 1996 VL 40 IS 1 BP 212 EP 214 PG 3 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA TN213 UT WOS:A1996TN21300040 PM 8787907 ER PT S AU McKenzie, R Straus, SE AF McKenzie, R Straus, SE BE Mills, J Volberding, PA Corey, L TI Therapeutic immunization for recurrent herpes simplex virus infections SO ANTIVIRAL CHEMOTHERAPY 4: NEW DIRECTIONS FOR CLINICAL APPLICATION AND RESEARCH SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Proceedings Paper CT 4th Triennial Symposium on New Directions in Antiviral Chemotherapy CY NOV 10-12, 1994 CL SAN FRANCISCO, CA SP Univ Calif San Francisco, Int Soc Antiviral Res, Macfarlane Burnet Ctr Med Res Melbourne, Austr, Australian Natl Ctr HIV Virol Res ID TYPE-1 GLYCOPROTEIN-D; HUMAN-LEUKOCYTE INTERFERON; GENITAL HERPES; GUINEA-PIGS; MONOCLONAL-ANTIBODIES; RECOMBINANT INTERLEUKIN-2; INTRANASAL IMMUNIZATION; SYNTHETIC PEPTIDES; SUBUNIT VACCINES; IMMUNE-RESPONSES RP McKenzie, R (reprint author), NIAID,CLIN INVEST LAB,BLDG 10,BETHESDA,MD 20892, USA. NR 90 TC 4 Z9 4 U1 0 U2 0 PU PLENUM PRESS DIV PLENUM PUBLISHING CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0065-2598 BN 0-306-45294-4 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 1996 VL 394 BP 67 EP 83 PG 17 WC Infectious Diseases; Medicine, Research & Experimental; Pharmacology & Pharmacy SC Infectious Diseases; Research & Experimental Medicine; Pharmacology & Pharmacy GA BF30J UT WOS:A1996BF30J00009 PM 8815711 ER PT S AU Litterst, C AF Litterst, C BE Mills, J Volberding, PA Corey, L TI Promising anti-HIV compounds in preclinical or early clinical development SO ANTIVIRAL CHEMOTHERAPY 4: NEW DIRECTIONS FOR CLINICAL APPLICATION AND RESEARCH SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Proceedings Paper CT 4th Triennial Symposium on New Directions in Antiviral Chemotherapy CY NOV 10-12, 1994 CL SAN FRANCISCO, CA SP Univ Calif San Francisco, Int Soc Antiviral Res, Macfarlane Burnet Ctr Med Res Melbourne, Austr, Australian Natl Ctr HIV Virol Res ID HUMAN-IMMUNODEFICIENCY-VIRUS; CD4-PSEUDOMONAS EXOTOXIN; REPLICATION; TYPE-1; CELLS RP Litterst, C (reprint author), NIAID,DIV AIDS,DRUG DEV & CLIN SCI BRANCH,DRUG DEV & SURVEILLANCE SECT,NIH,BETHESDA,MD 20892, USA. NR 16 TC 0 Z9 0 U1 0 U2 0 PU PLENUM PRESS DIV PLENUM PUBLISHING CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0065-2598 BN 0-306-45294-4 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 1996 VL 394 BP 397 EP 404 PG 8 WC Infectious Diseases; Medicine, Research & Experimental; Pharmacology & Pharmacy SC Infectious Diseases; Research & Experimental Medicine; Pharmacology & Pharmacy GA BF30J UT WOS:A1996BF30J00036 PM 8815704 ER PT S AU Sneller, MC AF Sneller, MC BE Mills, J Volberding, PA Corey, L TI Cytokine therapy of HIV infection SO ANTIVIRAL CHEMOTHERAPY 4: NEW DIRECTIONS FOR CLINICAL APPLICATION AND RESEARCH SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Proceedings Paper CT 4th Triennial Symposium on New Directions in Antiviral Chemotherapy CY NOV 10-12, 1994 CL SAN FRANCISCO, CA SP Univ Calif San Francisco, Int Soc Antiviral Res, Macfarlane Burnet Ctr Med Res Melbourne, Austr, Australian Natl Ctr HIV Virol Res ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; VIRUS TYPE-1 INFECTION; IMMUNE-DEFICIENCY SYNDROME; NECROSIS-FACTOR-ALPHA; RECOMBINANT INTERFERON-ALPHA; BLOOD MONONUCLEAR-CELLS; AIDS-RELATED COMPLEX; KAPOSI-SARCOMA; T-CELLS; REPLICATION INVITRO RP Sneller, MC (reprint author), NIAID,IMMUNOREGULAT LAB,NIH,BLDG 10,BETHESDA,MD 20892, USA. NR 53 TC 2 Z9 2 U1 0 U2 0 PU PLENUM PRESS DIV PLENUM PUBLISHING CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0065-2598 BN 0-306-45294-4 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 1996 VL 394 BP 411 EP 419 PG 9 WC Infectious Diseases; Medicine, Research & Experimental; Pharmacology & Pharmacy SC Infectious Diseases; Research & Experimental Medicine; Pharmacology & Pharmacy GA BF30J UT WOS:A1996BF30J00038 PM 8815707 ER PT J AU deJong, MD Boucher, CAB Galasso, GJ Hirsch, MS Kern, ER Lange, JMA Richman, DD AF deJong, MD Boucher, CAB Galasso, GJ Hirsch, MS Kern, ER Lange, JMA Richman, DD TI Consensus symposium on combined antiviral therapy SO ANTIVIRAL RESEARCH LA English DT Article; Proceedings Paper CT Consensus Symposium on Combined Antiviral Therapy CY JUL 25-27, 1995 CL LISBON, PORTUGAL SP Macrae Grp, New York, Int Soc Antiviral Res, NIAID ID HUMAN-IMMUNODEFICIENCY-VIRUS; CHRONIC HEPATITIS-C; PLACEBO-CONTROLLED TRIAL; RECOMBINANT INTERFERON-ALPHA; POLYMERASE CHAIN-REACTION; HUMAN LIVER-MICROSOMES; REVERSE-TRANSCRIPTASE; CYTOMEGALO-VIRUS; COMBINATION THERAPY; REPLICATION INVITRO C1 UNIV UTRECHT,EIKMAN WINKLER INST,ANTIVIRAL THERAPY LAB,UTRECHT,NETHERLANDS. NIH,BETHESDA,MD 20892. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,INFECT DIS UNIT,BOSTON,MA. UNIV ALABAMA,DEPT PEDIAT,BIRMINGHAM,AL. UNIV CALIF SAN DIEGO,DEPT PATHOL,LA JOLLA,CA 92093. UNIV CALIF SAN DIEGO,DEPT MED,LA JOLLA,CA 92093. UNIV CALIF SAN DIEGO,SAN DIEGO VET AFFAIRS MED CTR,LA JOLLA,CA 92093. RP deJong, MD (reprint author), UNIV AMSTERDAM,ACAD MED CTR,NATL AIDS THERAPY EVALUAT CTR,DEPT INFECT DIS TROP MED & AIDS,1105 AZ AMSTERDAM,NETHERLANDS. NR 126 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-3542 J9 ANTIVIR RES JI Antiviral Res. PD JAN PY 1996 VL 29 IS 1 BP 5 EP 29 DI 10.1016/0166-3542(95)00910-8 PG 25 WC Pharmacology & Pharmacy; Virology SC Pharmacology & Pharmacy; Virology GA UD272 UT WOS:A1996UD27200002 PM 8721539 ER PT J AU Reichelderfer, PS Coombs, RW AF Reichelderfer, PS Coombs, RW TI Cartesian coordinate analysis of viral burden and CD4+ cell count in HIV disease: Implications for clinical trial design and analysis SO ANTIVIRAL RESEARCH LA English DT Article; Proceedings Paper CT Consensus Symposium on Combined Antiviral Therapy CY JUL 25-27, 1995 CL LISBON, PORTUGAL SP Macrae Grp, New York, Int Soc Antiviral Res, NIAID DE viral burden; CD4+ cell; Cartesian coordinate plot; individual therapy response; virologic response modifier; immunologic response modifier; clinical trial design AB HIV-1 infection represents a dynamic interaction between the rapid turnover of virus, CD4+ cell proliferation and clearance. HIV-1 disease progression is assessed, in part, by the inverse relationship between virus burden and CD4+ cell count. However, there is enormous individual subject variability between virus burden in the peripheral blood and CD4+ cell count with subsequent disease progression, suggesting that there must be virologic and immunologic modifiers of the inverse relationship between virus load and CD4+ cell count. To investigate these modifiers, we have used a Cartesian coordinate plot analysis to describe the inverse relationship between viral burden and the peripheral blood CD4+ cell count. Subjects from several clinical studies with CD4+ cell counts ranging from < 50 to > 600 cells/mu L and varying viral burdens were studied. The analysis described the effect of various virologic and immunologic modifiers on this inverse relationship, for example, viral resistance, viral phenotype and the effect of very low CD4+ cell counts, and specifically addressed individual subject variation in assessing the association between the viral and immunologic parameters that define disease progression and response to antiretroviral therapy. As such, the Cartesian coordinate plot analysis method provides one approach to investigating the individual subject response to antiretroviral therapy. C1 UNIV WASHINGTON,DEPT LAB MED,PACIFIC MED CTR,SEATTLE,WA 98144. UNIV WASHINGTON,PACIFIC MED CTR,DEPT MED,SEATTLE,WA 98144. NIAID,NIH,DIV AIDS,BETHESDA,MD 20892. NR 10 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-3542 J9 ANTIVIR RES JI Antiviral Res. PD JAN PY 1996 VL 29 IS 1 BP 83 EP 86 DI 10.1016/0166-3542(95)00924-8 PG 4 WC Pharmacology & Pharmacy; Virology SC Pharmacology & Pharmacy; Virology GA UD272 UT WOS:A1996UD27200016 PM 8721553 ER PT J AU Collier, AC Coombs, RW Schoenfeld, DA Bassett, R Baruch, A Corey, L AF Collier, AC Coombs, RW Schoenfeld, DA Bassett, R Baruch, A Corey, L TI Combination therapy with zidovudine, didanosine and saquinavir SO ANTIVIRAL RESEARCH LA English DT Article; Proceedings Paper CT Consensus Symposium on Combined Antiviral Therapy CY JUL 25-27, 1995 CL LISBON, PORTUGAL SP Macrae Grp, New York, Int Soc Antiviral Res, NIAID DE Saquinavir; Zidovudine; Zalcitabine; phase II clinical trial; combination therapy; CD4+ cell; quantitative HIV-1 microculture; HIV-1 RNA C1 UNIV WASHINGTON,DEPT MED,PACIFIC MED CTR,SEATTLE,WA 98144. NIAID,AIDS CLIN TRIALS GRP,PROTOCOL 229 TEAM,BETHESDA,MD. F HOFFMANN LA ROCHE & CO LTD,NUTLEY,NJ. RP Collier, AC (reprint author), UNIV WASHINGTON,DEPT LAB MED,PACIFIC MED CTR,VIROL OFF,ROOM 9301,1200 12TH AVE S,SEATTLE,WA 98144, USA. NR 0 TC 30 Z9 30 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-3542 J9 ANTIVIR RES JI Antiviral Res. PD JAN PY 1996 VL 29 IS 1 BP 99 EP 99 DI 10.1016/0166-3542(95)00928-0 PG 1 WC Pharmacology & Pharmacy; Virology SC Pharmacology & Pharmacy; Virology GA UD272 UT WOS:A1996UD27200020 PM 8721557 ER PT J AU Sneller, MC AF Sneller, MC TI Consensus symposium on combined antiviral therapy; Overview of interferon and IL-2 combinations for the treatment of HIV infection SO ANTIVIRAL RESEARCH LA English DT Article; Proceedings Paper CT Consensus Symposium on Combined Antiviral Therapy CY JUL 25-27, 1995 CL LISBON, PORTUGAL SP Macrae Grp, New York, Int Soc Antiviral Res, NIAID DE alpha-interferon; interleukin-2; HIV; cytokine ID VIRUS TYPE-1 INFECTION; REPLICATION INVITRO; ALPHA; ZIDOVUDINE; INTERLEUKIN-2; INHIBITION; EFFICACY AB Among the immunomodulatory cytokines that have been evaluated for the treatment of HIV disease, alpha-interferon and interleukin-2 (IL-2) have been the most extensively studied. Monotherapy with alpha-interferon is effective therapy for HIV-associated Kaposi's sarcoma (KS) in patients with CD4 counts >150 cells/mm(3). However, the doses necessary to achieve a significant anti-tumor effect are often poorly tolerated. Combination therapy with alpha-interferon and zidovudine is associated with dose-limiting toxicities and an anti-tumor effect similar to that of higher dose alpha-interferon monotherapy. The combination of alpha-interferon and zidovudine can synergistically inhibit HIV replication in vitro; however, in vivo results suggest the anti-HIV effect of this combination is no greater than that seen with zidovudine monotherapy. Whether combination of interferon-alpha and other antiviral drugs will be useful in the treatment of HIV infection remains to be seen. Recent studies employing intermittent courses of IL-2 combined with continuous antiretroviral therapy indicate that sustained rises in CD4 counts can be achieved. The ability of IL-2 therapy to result in a sustained rise in CD4 counts is critically dependent on the pre-treatment CD4 count. The immunologic and clinical significance of these IL-2-induced increases in CD4 counts is unknown. Larger, controlled trials are currently underway to evaluate the role of intermittent IL-2 therapy in HIV infection. RP Sneller, MC (reprint author), NIAID,NIH,IMMUNOREGULAT LAB,BLDG 10,ROOM 11B-13,BETHESDA,MD 20892, USA. NR 18 TC 10 Z9 10 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-3542 J9 ANTIVIR RES JI Antiviral Res. PD JAN PY 1996 VL 29 IS 1 BP 105 EP 109 DI 10.1016/0166-3542(95)00930-2 PG 5 WC Pharmacology & Pharmacy; Virology SC Pharmacology & Pharmacy; Virology GA UD272 UT WOS:A1996UD27200022 PM 8721559 ER PT J AU Wiggs, CL Martin, A Altemus, M Murphy, DL AF Wiggs, CL Martin, A Altemus, M Murphy, DL TI Hypervigilance in patients with obsessive-compulsive disorder SO ANXIETY LA English DT Article DE obsessive-compulsive disorder (OCD); cognition; attention; memory; priming ID MEMORY; DISEASE AB The hypothesis that patients with obsessive-compulsive disorder (OCD) suffer from hypervigilant attention was investigated via explicit memory (incidental recall and recognition) and priming (reading speed) measures. OCD patients did not differ from normal controls on explicit measures of memory; specifically, recognition of unusual words (experiment 1) and recall and recognition of words and feature-specific information (experiment 2). Although both normal controls and OCD patients showed priming, the pattern of priming differed for the two groups (experiment 2). Specifically, patients with OCD failed to show feature-specific priming, suggesting they may have attended more focally on the priming task than did normal controls. These findings support previous reports of normal performance in OCD on explicit memory tasks, but suggest more sensitive measures may reflect differences in processing information. (C) 1996 Wiley-Liss, Inc.* C1 NIMH,CLIN SCI LAB,BETHESDA,MD 20892. RI martin, alex/B-6176-2009 NR 30 TC 3 Z9 3 U1 7 U2 7 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 1070-9797 J9 ANXIETY JI Anxiety PY 1996 VL 2 IS 3 BP 123 EP 129 PG 7 WC Psychiatry; Psychology SC Psychiatry; Psychology GA UQ489 UT WOS:A1996UQ48900003 PM 9160613 ER PT J AU Weise, RE Shear, MK Maser, JD AF Weise, RE Shear, MK Maser, JD TI On the need for standardization in panic disorder treatment research: Survey of the literature, 1980-1992 SO ANXIETY LA English DT Article DE panic; panic disorder; treatment; assessment; standardization ID PLACEBO-CONTROLLED TRIAL; MITRAL-VALVE PROLAPSE; SHORT-TERM TREATMENT; 2-YEAR FOLLOW-UP; IMIPRAMINE TREATMENT; ANXIETY DISORDERS; ALPRAZOLAM TREATMENT; GENERALIZED ANXIETY; DOUBLE-BLIND; PLASMA-CONCENTRATIONS AB A retrospective literature survey (1980-1992) was conducted to chronicle the development of panic disorder treatment research, Based on a National Institute of Mental Health conference on assessment standardization in this area (Shear and Maser, 1994), the results and implications of the survey are presented in terms of eight domains of measurement recommended as essential for high quality research. (C) 1996 Wiley-Liss, Inc.* RP Weise, RE (reprint author), NIMH,ROOM 10C-16,5600 FISHERIES LANE,ROCKVILLE,MD 20857, USA. NR 98 TC 5 Z9 5 U1 4 U2 5 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 1070-9797 J9 ANXIETY JI Anxiety PY 1996 VL 2 IS 6 BP 257 EP 264 PG 8 WC Psychiatry; Psychology SC Psychiatry; Psychology GA WA038 UT WOS:A1996WA03800002 PM 9160633 ER PT J AU Martinez, JM Papp, LA Coplan, JD Anderson, DE Mueller, CM Klein, DF Gorman, JM AF Martinez, JM Papp, LA Coplan, JD Anderson, DE Mueller, CM Klein, DF Gorman, JM TI Ambulatory monitoring of respiration in anxiety SO ANXIETY LA English DT Article; Proceedings Paper CT International-Society-for-the-Advancement-of-Respiratory-Psychophysiolog y Meeting CY OCT 09-11, 1995 CL TORONTO, CANADA SP Int Soc Adv Respiratory Psychophysiol DE anxiety; panic attack; ambulatory monitoring; respiration; breathing pattern ID PANIC DISORDER; CARBON-DIOXIDE; ALPRAZOLAM TREATMENT; ATTACKS AB An ambulatory monitor, body suit, and calibration procedure were developed to compare the respiration of seven patients with panic disorder and twelve normal volunteers. Subjects wore a body suit with Respitrace bands, connected to a portable respiratory monitor for a period of 24 hours. Breath by breath values for respiratory rate and tidal volume were computed every two minutes. There was a significant difference patients and controls in their patterns of minute ventilation during sleep. Tidal volume, rather that respiratory rate increases characterized the periods of anxiety and limited symptom attacks. (C) 1996 Wiley-Liss, Inc. C1 COLUMBIA UNIV,DEPT PSYCHIAT,NEW YORK,NY. NIA,BEHAV SCI LAB,NIH,CTR GERONTOL RES,BALTIMORE,MD 21224. RP Martinez, JM (reprint author), NEW YORK STATE PSYCHIAT INST & HOSP,UNIT 24,BIOL STUDIES UNIT,722 W 168TH ST,NEW YORK,NY 10032, USA. FU NIMH NIH HHS [MH-00416, MH-00858, MH-30960] NR 23 TC 54 Z9 56 U1 2 U2 5 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 1070-9797 J9 ANXIETY JI Anxiety PY 1996 VL 2 IS 6 BP 296 EP 302 PG 7 WC Psychiatry; Psychology SC Psychiatry; Psychology GA WA038 UT WOS:A1996WA03800006 PM 9160637 ER PT J AU Austin, RK McCann, UD AF Austin, RK McCann, UD TI Ballatrophobia: When clowns aren't funny SO ANXIETY LA English DT Letter C1 NIMH,BIOL PSYCHIAT BRANCH,UNIT ANXIETY DISORDERS,BETHESDA,MD 20892. NR 0 TC 2 Z9 2 U1 0 U2 0 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 1070-9797 J9 ANXIETY JI Anxiety PY 1996 VL 2 IS 6 BP 305 EP 305 PG 1 WC Psychiatry; Psychology SC Psychiatry; Psychology GA WA038 UT WOS:A1996WA03800008 PM 9160639 ER PT J AU Kawai, K Ohta, H Channing, MA Kubodera, A Eckelman, WC AF Kawai, K Ohta, H Channing, MA Kubodera, A Eckelman, WC TI Synthesis of polymer-bound 6-mercuric carboxylate DOPA precursors and solid phase labelling method of 6-radioiodinated L-DOPA SO APPLIED RADIATION AND ISOTOPES LA English DT Article AB In order to avoid separating unreacted mercury precursor and other mercury-containing compounds after the halodemercuration of a 6-mercury DOPA precursor, we developed a polymer-bound mercury precursor for the preparation of 6-halogenated DOPA. In this study, polymer-bound 6-mercuric carboxylate DOPA derivatives were synthesized from ion-exchange resin and Merrifield-type resin, Iododemercuration of polymer-bound 6-mercuric carboxylate DOPA derivatives gave higher yields (49-54%) compared with monomeric 6-mercuric trifluoroacetate protected DOPA. The radioiodination of the resin with no-carrier added iodine-125 afforded protected 6-[I-125]I-L-DOPA with labelling efficiency of 92-97% with both polymer-bound 6-mercuric carboxylate DOPA derivatives. C1 NIH,WARREN GRANT MAGNUSON CLIN CTR,DEPT PET,BETHESDA,MD 20892. RP Kawai, K (reprint author), SCI UNIV TOKYO,FAC PHARMACEUT SCI,DEPT RADIOPHARMACEUT CHEM,SHINJUKU KU,TOKYO 162,JAPAN. NR 8 TC 8 Z9 9 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0969-8043 J9 APPL RADIAT ISOTOPES JI Appl. Radiat. Isot. PD JAN PY 1996 VL 47 IS 1 BP 37 EP 44 PG 8 WC Chemistry, Inorganic & Nuclear; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Chemistry; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA TM585 UT WOS:A1996TM58500008 PM 8589672 ER PT J AU Sollitto, RB DiGiovanna, JJ AF Sollitto, RB DiGiovanna, JJ TI Failure of interferon alfa and isotretinoin combination therapy in the nevoid basal cell carcinoma syndrome SO ARCHIVES OF DERMATOLOGY LA English DT Article ID INTRALESIONAL INTERFERON RP Sollitto, RB (reprint author), NIAMS,DERMATOL CLIN RES UNIT,BLDG 10,ROOM 9N228,10 CTR DR,MSC 1820,BETHESDA,MD 20892, USA. NR 7 TC 6 Z9 7 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD JAN PY 1996 VL 132 IS 1 BP 94 EP 95 DI 10.1001/archderm.132.1.94 PG 2 WC Dermatology SC Dermatology GA TP702 UT WOS:A1996TP70200021 PM 8546496 ER PT J AU Wyatt, RJ AF Wyatt, RJ TI Neurodevelopmental abnormalities and schizophrenia - A family affair SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Editorial Material ID PRENATAL EXPOSURE; DISEASE; PREGNANCY RP Wyatt, RJ (reprint author), NIMH,NEUROSCI CTR ST ELIZABETHS,NEUROPSYCHIAT BRANCH,2700 MARTIN LUTHER KING JR AVE,WASHINGTON,DC 20032, USA. NR 35 TC 24 Z9 24 U1 1 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD JAN PY 1996 VL 53 IS 1 BP 11 EP 15 PG 5 WC Psychiatry SC Psychiatry GA TP700 UT WOS:A1996TP70000001 PM 8540772 ER PT J AU Taller, AM Asher, DM Pomeroy, KL Eldadah, BA Godec, MS Falkai, PG Bogert, B Kleinman, JE Stevens, JR Torrey, EF AF Taller, AM Asher, DM Pomeroy, KL Eldadah, BA Godec, MS Falkai, PG Bogert, B Kleinman, JE Stevens, JR Torrey, EF TI Search for viral nucleic acid sequences in brain tissues of patients with schizophrenia using nested polymerase chain reaction SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID HERPES-SIMPLEX VIRUS; VARICELLA-ZOSTER VIRUS; TROPICAL SPASTIC PARAPARESIS; HUMAN INFLUENZA-VIRUS; CYTOMEGALO-VIRUS; NUCLEOTIDE-SEQUENCE; DNA-SEQUENCE; ENZYMATIC AMPLIFICATION; GENOMIC SEQUENCES; ADULT SCHIZOPHRENIA AB Background: We used polymerase chain reaction to search for nucleic acid sequences of several viruses in DNA and RNA extracted from brain tissues of schizophrenic and control subjects. Methods: We extracted DNA and RNA templates from frozen brain specimens of 31 patients with schizophrenia and 23 nonschizophrenic control patients with other diseases. The extracts were subjected to polymerase chain reaction with oligonucleotide primers for 12 different viruses (cytomegalovirus, Epstein-Barr virus, herpes simplex virus type 1, human herpesvirus type 6, varicella-tester virus, measles virus, mumps virus, rubella virus, the picornavirus group, influenza A virus, human T-cell lymphotropic virus type I, and St Louis encephalitis virus), several of which have been suspected of involvement in schizophrenia. Nested primers were used to increase the sensitivity of the method. Results: No amplified nucleic acid sequences encoded by the selected viral genomes were detected in extracts of any brain specimens from either schizophrenic or control patients. Conclusions: These data agree with previous studies that failed to find sequences of a number of viruses in the cerebrospinal fluid or selected areas of the brains of schizophrenic patients. Additional efforts should be undertaken to identify other known and unknown pathogens in schizophrenia, sampling more areas of the brain from subjects with a variety of clinical types of schizophrenia. C1 NINCDS, CENT NERVOUS SYST STUDIES LAB, BETHESDA, MD 20892 USA. UNIV DUSSELDORF, DEPT PSYCHIAT, W-4000 DUSSELDORF, GERMANY. OTTO VONGUERICKE UNIV, DEPT PSYCHIAT, MAGDEBURG, GERMANY. NIMH, ST ELIZABETHS HOSP, CTR NEUROSCI, CLIN BRAIN DISORDERS BRANCH, WASHINGTON, DC 20032 USA. NR 87 TC 30 Z9 31 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD JAN PY 1996 VL 53 IS 1 BP 32 EP 40 PG 9 WC Psychiatry SC Psychiatry GA TP700 UT WOS:A1996TP70000004 PM 8540775 ER PT J AU Madden, PAF Heath, AC Rosenthal, NE Martin, NG AF Madden, PAF Heath, AC Rosenthal, NE Martin, NG TI Seasonal changes in mood and behavior - The role of genetic factors SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID AFFECTIVE-DISORDER; WINTER DEPRESSION; SUMMER DEPRESSION; LIGHT TREATMENT; BRIGHT LIGHT; PHOTOTHERAPY; PREVALENCE; SYMPTOMS; TWIN; POPULATION AB Background: Seasonal rhythms in mood and behavior (seasonality) have been reported to occur in the general population. Seasonal affective disorder, a clinically diagnosed syndrome, is believed to represent the morbid extreme of a spectrum of seasonality. Two types of seasonality have been clinically described: one characterized by a winter pattern and a second by a summer pattern of depressive mood disturbance. Methods: By using methods of univariate and multivariate genetic analysis, we examined the relative contribution of genetic and environmental factors to the risk of seasonality symptoms that were assessed by a mailed questionnaire of 4639 adult mins from a volunteer based registry in Australia. Results: Seasonality was associated with a winter ratherthan a summer pattern of mood and behavioral change. In each behavioral domain (ie, mood, energy, social activity, sleep, appetite, and weight), a significant genetic influence on the reporting of seasonal changes was found. Consistent with the hypothesis of a seasonal syndrome, genetic effects were found to exert a global influence across all behavioral changes, accounting for at least 29% of the variance in seasonality in men and women. Conclusions: There is a tendency for seasonal changes in mood and behavior to run in families, especially seasonality of the winter type, and this is largely due to a biological predisposition. These findings support continuing efforts to understand the role of seasonality in the development of mood disorders. C1 NIMH,CLIN PSYCHOBIOL BRANCH,BETHESDA,MD 20892. QUEENSLAND INST MED RES,BRISBANE,QLD 4006,AUSTRALIA. RP Madden, PAF (reprint author), WASHINGTON UNIV,SCH MED,DEPT PSYCHIAT,BOX 8134,4940 CHILDRENS PL,ST LOUIS,MO 63110, USA. OI Martin, Nicholas/0000-0003-4069-8020 FU NIAAA NIH HHS [AA07535]; NIDA NIH HHS [DA07261] NR 54 TC 107 Z9 108 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD JAN PY 1996 VL 53 IS 1 BP 47 EP 55 PG 9 WC Psychiatry SC Psychiatry GA TP700 UT WOS:A1996TP70000006 PM 8540777 ER PT J AU Ketter, TA Andreason, PJ George, MS Lee, C Gill, DS Parekh, PI Willis, MW Herscovitch, P Post, RM AF Ketter, TA Andreason, PJ George, MS Lee, C Gill, DS Parekh, PI Willis, MW Herscovitch, P Post, RM TI Anterior paralimbic mediation of procaine-induced emotional and psychosensory experiences SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article; Proceedings Paper CT 48th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 19-23, 1993 CL SAN FRANCISCO, CA SP Soc Biol Psychiat ID NICOTINIC ACETYLCHOLINE-RECEPTOR; CHOLINERGIC RECEPTORS; LOCAL-ANESTHETICS; LIMBIC SYSTEM; COMPUTED-TOMOGRAPHY; SEIZURE DEVELOPMENT; KINDLED SEIZURES; SMOOTH-MUSCLE; HUMAN-BRAIN; BLOOD-FLOW AB Background: Procaine activates limbic structures in animals. In humans, acute intravenous administration of procaine fields emotional and psychosensory experiences and temporal lobe fast activity. We studied procaine's acute effects on cerebral blood flow (CBF) in relationship to clinical responses. Methods: Cerebral blood flow was assessed by positron emission tomography with oxygen-15-labeled water in 32 healthy volunteers. Data were analyzed with statistical parametric mapping and magnetic resonance imaging-directed regions of interest. Results: Procaine increased global CBF and, to a greater extent, anterior paralimbic CBF. Subjects with intense procaine-induced fear compared with those with euphoria had greater increases in left amygdalar CBF. Absolute and normalized left amygdalar CBF changes tended to correlate positively with fear and negatively with euphoria intensity. Procaine-induced visual hallucinations appeared associated with greater global and occipital CBF increases. Absolute occipital CBF increases appeared to correlate positively with visual hallucination intensity. Conclusions: Procaine increased anterior paralimbic CBF, and different clinical responses appeared to be associated with different patterns of CBF changes. C1 NIAAA,BETHESDA,MD 20892. NIH,CTR CLIN,BETHESDA,MD 20892. NIH,BIOMED ENGN & IMPLEMENTAT BRANCH,BETHESDA,MD 20892. RP Ketter, TA (reprint author), NIMH,BIOL PSYCHIAT BRANCH,BLDG 10,ROOM 3N212,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 83 TC 169 Z9 171 U1 0 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD JAN PY 1996 VL 53 IS 1 BP 59 EP 69 PG 11 WC Psychiatry SC Psychiatry GA TP700 UT WOS:A1996TP70000007 PM 8540778 ER PT J AU Campo, E Jaffe, ES AF Campo, E Jaffe, ES TI Mantle cell lymphoma - Accurate diagnosis yields new clinical insights SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Editorial Material ID T(11-14) CHROMOSOME-TRANSLOCATION; LYMPHOCYTIC LYMPHOMA; CENTROCYTIC LYMPHOMA; T(11-14)(Q13-Q32) TRANSLOCATION; INTERMEDIATE DIFFERENTIATION; MOLECULAR-CLONING; BCL-1 LOCUS; GENE; BREAKPOINTS; REARRANGEMENT C1 UNIV BARCELONA,HOSP CLIN,DEPT PATHOL ANAT,BARCELONA,SPAIN. NCI,PATHOL LAB,HEMATOPATHOL SECT,BETHESDA,MD 20892. OI Campo, elias/0000-0001-9850-9793 NR 37 TC 19 Z9 19 U1 0 U2 1 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD JAN PY 1996 VL 120 IS 1 BP 12 EP 14 PG 3 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA TP695 UT WOS:A1996TP69500003 PM 8554438 ER PT J AU KrebsSmith, SM Cook, DA Subar, AF Cleveland, L Friday, J Kahle, LL AF KrebsSmith, SM Cook, DA Subar, AF Cleveland, L Friday, J Kahle, LL TI Fruit and vegetable intakes of children and adolescents in the United States SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE LA English DT Article ID NUTRITION AB Objectives: To identify the ways in which fruits and vegetables are consumed by children, to provide estimates of their intakes compared with recommendations, and to estimate the percentage of children meeting those recommendations. Design: We examined 3 days of dietary data from respondents in the US Department of Agriculture's 1989-1991 Continuing Survey of Food Intakes by Individuals. All foods reported in the survey were disaggregated into their component ingredients; all fruit and vegetable ingredients were assigned specific weights to correspond with a serving as defined by current dietary guidance materials; and the number of servings of each fruit and vegetable was tallied. Participants: A total of 3148 children and adolescents aged 2 to 18 years in the 48 conterminous United States. Main Outcome Measures: Percentages of fruit and vegetable servings consumed in various forms, mean number of servings consumed per day, and percentage of persons meeting various recommendations by sex/age, race/ethnicity, and household income. Results: Nearly one quarter of all vegetables consumed by children and adolescents were french fries. Their intakes of all fruits and of dark green and/or deep yellow vegetables were very low compared with recommendations. Only one in five children consumed five or more servings of fruits and vegetables per day. Conclusion: Pediatricians should encourage the consumption of fruits and vegetables, especially dark green and deep yellow vegetables, by children. C1 USDA,RIVERDALE,MD. INFORMAT MANAGEMENT SERV INC,SILVER SPRING,MD. RP KrebsSmith, SM (reprint author), NCI,DCPC,EXECUT PLAZA N,RM 313,6130 EXECUT BLVD,MSC 7344,BETHESDA,MD 20892, USA. NR 21 TC 248 Z9 257 U1 1 U2 10 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 1072-4710 J9 ARCH PEDIAT ADOL MED JI Arch. Pediatr. Adolesc. Med. PD JAN PY 1996 VL 150 IS 1 BP 81 EP 86 PG 6 WC Pediatrics SC Pediatrics GA TP037 UT WOS:A1996TP03700013 PM 8542012 ER PT J AU Chen, TL Chen, SH Tai, TY Chao, CC Park, SS Guengerich, FP Ueng, TH AF Chen, TL Chen, SH Tai, TY Chao, CC Park, SS Guengerich, FP Ueng, TH TI Induction and suppression of renal and hepatic cytochrome P450-dependent monooxygenases by acute and chronic streptozotocin diabetes in hamsters SO ARCHIVES OF TOXICOLOGY LA English DT Article DE diabetes; cytochrome P450; monooxygenase; hamster; streptozotocin ID MICROSOMAL CYTOCHROME-P-450; MONOCLONAL-ANTIBODIES; RAT-LIVER; ENZYMES; ETHANOL; ACETONE; PURIFICATION; PROTEINS; 3-METHYLCHOLANTHRENE; METABOLISM AB The acute and chronic effects of streptozotocin diabetes on kidney and liver microsomal monooxygenases were studied using hamsters 2 days and 6 weeks following treatment with the diabetogen, respectively. Acute diabetes increased aniline hydroxylation and N-nitrosodimethylamine demethylation, decreased pentoxyresorufin O-dealkylation, without affecting benzo(a)pyrene hydroxylation and 7-ethoxycoumarin O-deethylation in kidney and liver microsomes. The effects of chronic diabetes on the microsomal monooxygenases were similar to the effects of acute diabetes, except that the chronic diabetic condition markedly decreased benzo(a)pyrene and 7-ethoxycoumarin oxidations in kidney microsomes. Total cytochrome P450 content and NADPH-cytochrome P450 reductase activity in kidney and liver microsomes of the diabetic hamsters were similar to the controls. Gel electrophoresis of microsomes from control and streptozoptocin treated hamster tissues revealed that diabetes enhanced the intensity of protein band(s) in the P450 molecular weight region. Immunoblotting of microsomal proteins showed that acute and chronic streptozotocin diabetes induced proteins immunorelated to P450s 2E1 and 1A in kidney and liver. In marked contrast, the acute and chronic diabetic conditions decreased the level of a P450 2B-immunorelated protein(s) in kidney and liver. The present study demonstrates that acute and chronic streptozotocin diabetes has the ability to induce P450 2E1 and 1A and suppress P450 2B in hamster kidney and liver and that the hamster monooxygenase responds to diabetes differently from the rat enzyme. C1 NATL TAIWAN UNIV,COLL MED,INST TOXICOL,TAIPEI 10764,TAIWAN. NATL TAIWAN UNIV,COLL MED,INST CLIN MED,TAIPEI 10764,TAIWAN. NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21702. VANDERBILT UNIV,SCH MED,DEPT BIOCHEM,NASHVILLE,TN 37323. VANDERBILT UNIV,SCH MED,CTR MOLEC TOXICOL,NASHVILLE,TN 37323. FU NCI NIH HHS [CA 44353]; NIEHS NIH HHS [ES 00267] NR 49 TC 18 Z9 18 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0340-5761 J9 ARCH TOXICOL JI Arch. Toxicol. PD JAN PY 1996 VL 70 IS 3-4 BP 202 EP 208 DI 10.1007/s002040050261 PG 7 WC Toxicology SC Toxicology GA TR762 UT WOS:A1996TR76200010 PM 8825678 ER PT J AU Li, B Hoshino, Y Gorziglia, M AF Li, B Hoshino, Y Gorziglia, M TI Identification of a unique VP4 serotype that is shared by a human rotavirus (69M strain) and an equine rotavirus (H-2 strain) SO ARCHIVES OF VIROLOGY LA English DT Article ID OUTER CAPSID PROTEIN; AMINO-ACID-SEQUENCE; PROTECTION; ANTIBODIES; INFECTION; GENE AB A cDNA clone representing the VP4-encoding gene of human rotavirus strain 69M(VP7 serotype 8) was constructed and inserted into a baculovirus expression vector. Baculovirus recombinants that expressed the 64 M VP4 protein in Spodoptera frugiperda (Sf9) cells were screened by immunofluorescence With hyperimmune antiserum to the 69M strain and purified by terminal dilution. The expressed VP4 was detected by Coomassie blue staining of PAGE-separated proteins. The antigenic relationships between the VP4 of the 69M strain and those of various human and other animal rotavirus strains representing ten established VP4 serotypes were examined by plaque reduction neutralization. Hyperimmune antiserum produced in guinea pigs following immunization with a lysate of Sf9 cells infected with a 69M gene 4-baculovirus recombinant neutralized the infectivity of the homologous human rotavirus 69M strain as well as heterologous equine rotavirus H-2 strain to a high titer. The anti-69M VP4 hyperimmune antiserum did not neutralize significantly other rotavirus strains of human, simian, porcine, bovine, or murine origin. It thus appears that the human rotavirus 69M strain has a distinct VP4 serotype (designated as P serotype 4) which is closely related antigenically to equine rotavirus H-2 VP4. C1 NIH,NIAID,INFECT DIS LAB,EPIDEMIOL SECT,BETHESDA,MD 20892. NR 21 TC 14 Z9 14 U1 0 U2 1 PU SPRINGER-VERLAG WIEN PI VIENNA PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 VIENNA, AUSTRIA SN 0304-8608 J9 ARCH VIROL JI Arch. Virol. PY 1996 VL 141 IS 1 BP 155 EP 160 DI 10.1007/BF01718596 PG 6 WC Virology SC Virology GA TR997 UT WOS:A1996TR99700013 PM 8629943 ER PT J AU Lindquester, GJ Inoue, N Allen, RD Castelli, JW Stamey, FR Dambaugh, TR OBrian, JJ Danovich, RM Frenkel, N Pellett, PE AF Lindquester, GJ Inoue, N Allen, RD Castelli, JW Stamey, FR Dambaugh, TR OBrian, JJ Danovich, RM Frenkel, N Pellett, PE TI Restriction endonuclease mapping and molecular cloning of the human herpesvirus 6 variant B strain Z29 genome SO ARCHIVES OF VIROLOGY LA English DT Article ID GROWTH-PROPERTIES; VIRUS; SEQUENCE; DNA; DIFFERENTIATION; CYTOMEGALOVIRUS; IDENTIFICATION; REPLICATION; INFANTS; TROPISM AB Human herpesvirus 6 (HHV-6) variants A and B differ in cell tropism, reactivity with monoclonal antibodies, restriction endonuclease profiles, and epidemiology. Nonetheless, comparative nucleotide and amino acid sequences from several genes indicate that the viruses are very highly conserved genetically. The B variant is the major etiologic agent of exanthem subitum and is frequently isolated from children with febrile illness; no disease has been etiologically associated with HHV-6A. One HHV-6A strain has been cloned and sequenced, but similar information and reagents are not available for HHV-6B. We report here the determination of maps of the restriction endonuclease cleavage sites for BamHI, ClaI, HindIII, KpnI, and SalI, and the cloning in plasmids and bacteriophages of fragments representing over 95% of the HHV-6B strain Z29 [HHV-6B(Z29)] genome. Hybridization experiments and orientation of several blocks of nucleotide sequence information onto the genomic map indicate that HHV-6A and HHV-6B genomes are colinear. C1 CTR DIS CONTROL & PREVENT,DIV VIRAL & RICKETTSIAL DIS,ATLANTA,GA 30333. RHODES COLL,DEPT BIOL,MEMPHIS,TN 38112. DUPONT MERCK PHARMACEUT CO,WILMINGTON,DE 19880. NIH,BETHESDA,MD 20892. FU PHS HHS [1R15 A131189-01] NR 41 TC 16 Z9 32 U1 0 U2 1 PU SPRINGER-VERLAG WIEN PI VIENNA PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 VIENNA, AUSTRIA SN 0304-8608 J9 ARCH VIROL JI Arch. Virol. PY 1996 VL 141 IS 2 BP 367 EP 379 DI 10.1007/BF01718406 PG 13 WC Virology SC Virology GA TX863 UT WOS:A1996TX86300013 PM 8634027 ER PT J AU Leite, JPG Ando, T Noel, JS Jiang, B Humphrey, CD Lew, JF Green, KY Glass, RI Monroe, SS AF Leite, JPG Ando, T Noel, JS Jiang, B Humphrey, CD Lew, JF Green, KY Glass, RI Monroe, SS TI Characterization of Toronto virus capsid protein expressed in baculovirus SO ARCHIVES OF VIROLOGY LA English DT Article ID POLYMERASE CHAIN-REACTION; NORWALK VIRUS; ACUTE GASTROENTERITIS; SERUM ANTIBODY; YOUNG-CHILDREN; ANTIGEN; PREVALENCE; OUTBREAKS; ORGANIZATION; SPECIMENS AB Toronto virus (TV), previously called ''minireovirus,'' a human calicivirus classified as genogroup 2 and phylogenetic type P2-A, was originally described in association with diarrhea in children. The second open reading frame, encoding the capsid protein of TV24, was expressed in a baculovirus recombinant. The recombinant baculovirus produced a protein (rTV) with an apparent molecular mass of 58 kDa that self-assembled into virus-like particles similar to 30 nm in diameter with a density of 1.29 g/ml. Antigenic and immunogenic characteristics of these particles were determined by protein immunoblot, immunoprecipitation, and enzyme immunoassay. Seroconversion to the rTV protein was detected in 6 of 8 (75%) patients from a recent outbreak of gastroenteritis associated with a virus of similar phylogenetic type. These results confirm and extend the previous reports of the expression of the Norwalk and Mexico virus capsid proteins. C1 CDCP,VIRAL GASTROENTERITIS SECT,DIV VIRAL & RICKETTSIAL DIS,ATLANTA,GA 30333. OSWALDO CURZ INST,DEPT VIROL,RIO JANEIRO,BRAZIL. NIAID,INFECT DIS LAB,NIH,BETHESDA,MD 20892. OI Monroe, Stephan/0000-0002-5424-716X NR 30 TC 53 Z9 53 U1 1 U2 3 PU SPRINGER-VERLAG WIEN PI VIENNA PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 VIENNA, AUSTRIA SN 0304-8608 J9 ARCH VIROL JI Arch. Virol. PY 1996 VL 141 IS 5 BP 865 EP 875 DI 10.1007/BF01718161 PG 11 WC Virology SC Virology GA UM671 UT WOS:A1996UM67100007 PM 8678832 ER PT J AU Song, JW Baek, LJ Nagle, JW Schlitter, D Yanagihara, R AF Song, JW Baek, LJ Nagle, JW Schlitter, D Yanagihara, R TI Genetic and phylogenetic analyses of hantaviral sequences amplified from archival tissues of deer mice (Peromyscus maniculatus nubiterrae) captured in the eastern United States - Brief report SO ARCHIVES OF VIROLOGY LA English DT Article ID DIFFERENT GEOGRAPHICAL REGIONS; HUMAN PAPILLOMAVIRUS TYPE-16; ENCEPHALITIS-VIRUS; HETEROGENEITY; EVOLUTION; GENOTYPES; SPREAD AB The S and M segments of a hantavirus, enzymatically amplified from tissues of Cloudland deer mice (Peromyscus maniculatus nubiterrae) captured during 1985 in West Virginia, diverged from strains of Four Corners virus from the southwestern United States by more than 16% and 6% at the nucleotide and amino acid levels, respectively. Phylogenetic analysis suggested that this virus strain (designated Monongahela) forms a possible evolutionary link between the Four Corners and New York hantaviruses. C1 NINCDS,NEUROGENET SECT,NIH,BETHESDA,MD 20892. CARNEGIE MUSEUM NAT HIST PITTSBURGH,SECT MAMMALS,PITTSBURGH,PA. NINCDS,CENT NERVOUS SYST STUDIES LAB,NIH,BETHESDA,MD 20892. NR 43 TC 32 Z9 32 U1 1 U2 3 PU SPRINGER-VERLAG WIEN PI VIENNA PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 VIENNA, AUSTRIA SN 0304-8608 J9 ARCH VIROL JI Arch. Virol. PY 1996 VL 141 IS 5 BP 959 EP 967 DI 10.1007/BF01718170 PG 9 WC Virology SC Virology GA UM671 UT WOS:A1996UM67100016 PM 8678841 ER PT J AU Kapikian, AZ AF Kapikian, AZ TI Overview of viral gastroenteritis SO ARCHIVES OF VIROLOGY LA English DT Article; Proceedings Paper CT Sapporo International Symposium on Viral Gastroenteritis CY JUN 28-30, 1995 CL TOMAKOMAI HOKKAIDO, JAPAN ID INFECTIOUS NONBACTERIAL GASTROENTERITIS; DEVELOPING-COUNTRIES; DIARRHEAL DISEASE; YOUNG-CHILDREN; GLOBAL PROBLEM; NORWALK VIRUS; MAGNITUDE; ROTAVIRUS; INFANTS; MICROSCOPY AB Diarrheal illnesses in humans have been recognized since antiquity. Such illnesses continue to take a great toll of lives, with a disproportionately high mortality in infants and young children in developing countries. Bacteriologic and parasitologic advances made during the past century led to the discovery of the etiology of some of the diarrheal illnesses, but the etiology of the major portion remained unknown. It was assumed that viruses caused most of these illnesses because: (i) bacteria were recovered from only a small proportion of episodes, and (ii) bacteria-free filtrates were found to induce gastroenteritis in adult volunteer studies. However, an etiologic agent could not be recovered despite the ''golden age'' of virology in the 1950's and 1960's when tissue culture technology enabled the discovery of numerous cultivatable enteric viruses, none of which emerged as an important etiologic agent of gastroenteritis. The discoveries of the Norwalk virus in 1972, and of rotaviruses in 1973, both without the benefit of in vitro tissue culture systems, ushered in a new era in the study of the etiology of viral gastroenteritis. The Norwalk virus was found to be an important cause of non-bacterial epidemic gastroenteritis in adults and older children, and rotaviruses were shown to be the single most important etiologic agents of severe diarrheal illnesses of infants and young children in both developed and developing countries. With the major advances in the study of rotaviruses, there is a high degree of optimism that in the not-too-distant future, a rotavirus vaccine will be available. In addition, the recent molecular biologic advances in the study of the Norwalk and Norwalk-like viruses, now firmly established as caliviviruses, represent a major new horizon in the study of these viruses. RP Kapikian, AZ (reprint author), NIAID,INFECT DIS LAB,EPIDEMIOL SECT,NIH,BETHESDA,MD 20892, USA. NR 37 TC 14 Z9 15 U1 0 U2 1 PU SPRINGER-VERLAG WIEN PI VIENNA PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 VIENNA, AUSTRIA SN 0304-8608 J9 ARCH VIROL JI Arch. Virol. PY 1996 SU 12 BP 7 EP 19 PG 13 WC Virology SC Virology GA WE212 UT WOS:A1996WE21200003 ER PT J AU Hoshino, Y Kapikian, AZ AF Hoshino, Y Kapikian, AZ TI Classification of rotavirus VP4 and VP7 serotypes SO ARCHIVES OF VIROLOGY LA English DT Article; Proceedings Paper CT Sapporo International Symposium on Viral Gastroenteritis CY JUN 28-30, 1995 CL TOMAKOMAI HOKKAIDO, JAPAN ID POLYMERASE CHAIN-REACTION; MONOCLONAL-ANTIBODIES; GENOMIC CHARACTERIZATION; PASSIVE PROTECTION; RHESUS ROTAVIRUS; INDUCED DIARRHEA; P-SEROTYPES; PROTEIN; NEUTRALIZATION; STRAINS AB Rotaviruses, members of the Reoviridae family, are major etiologic agents of acute nonbacterial gastroenteritis of the young in a wide variety of mammalian and avian species, including humans. The need for effective immunoprophylaxis against rotaviral gastroenteritis has stimulated interest in the biochemical, molecular, genetic, and clinical aspects of these agents with the aim of developing safe and effective vaccines. Because neutralizing antibodies appear to play an important role in protection against many viral diseases, rotavirus antigens that induce neutralizing antibodies have played a central role in research and development of a rotavirus vaccine. The VP7 glycoprotein and VP4 spike protein that constitute the outer capsid of a complete rotavirus particle have been shown to be independent neutralization antigens. Since type specificity of the outer capsid proteins of a rotavirus appears to play an important role in protection against disease in experimental animal models, continued efforts have been made for classification and typing of neutralization specificities on the VP7 or VP4 capsid protein. Based on a criterion of >20-fold differences between the homologous and heterologous reciprocal neutralizing antibody titers, fourteen VP7 (G) serotypes have been established. Studies are underway to characterize and classify the VP4 (P) serotypes among the strains that exhibit the fourteen different G serotypes. Attempts to classify the VP4 serotypes based on the same criterion (i.e., >20-fold antibody differences) that is applied to classification of VP7 serotypes are in progress. This standard of >20-fold antibody differences can be applied with hyperimmune serum raised to a reassortant possessing the VP4 encoding gene (and an unrelated VP7 encoding gene). Genotypes can provide leads towards classification but the serotype of a strain should be based on neutralization. RP Hoshino, Y (reprint author), NIAID,INFECT DIS LAB,EPIDEMIOL SECT,NIH,BETHESDA,MD 20892, USA. NR 40 TC 11 Z9 11 U1 0 U2 0 PU SPRINGER-VERLAG WIEN PI VIENNA PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 VIENNA, AUSTRIA SN 0304-8608 J9 ARCH VIROL JI Arch. Virol. PY 1996 SU 12 BP 99 EP 111 PG 13 WC Virology SC Virology GA WE212 UT WOS:A1996WE21200013 ER PT J AU Kapikian, AZ Hoshino, Y Chanock, RM PerezSchael, I AF Kapikian, AZ Hoshino, Y Chanock, RM PerezSchael, I TI Jennerian and modified Jennerian approach to vaccination against rotavirus diarrhea using a quadrivalent rhesus rotavirus (RRV) and human-RRV reassortant vaccine SO ARCHIVES OF VIROLOGY LA English DT Article; Proceedings Paper CT Sapporo International Symposium on Viral Gastroenteritis CY JUN 28-30, 1995 CL TOMAKOMAI HOKKAIDO, JAPAN ID YOUNG-CHILDREN; INFANTS; REACTOGENICITY; RESTRICTION; SPECIFICITY; SEROTYPE-1; IMMUNITY; EFFICACY AB Rotaviruses are the single most important cause of severe diarrhea of infants and young children world-wide. Deaths from rotavirus diarrhea occur infrequently in developed countries; however, in developing countries, rotaviruses are estimated to cause over 870 000 deaths in the under five-year age group. There is, therefore, a vital need for a vaccine to prevent severe rotavirus diarrhea in infants and young children. The most extensively evaluated strategy for rotavirus vaccination has been the ''Jennerian'' approach in which an antigenically related rotavirus strain from an animal host (bovine or simian [rhesus monkey]) is used as the immunogen to induce protection against the four epidemiologically important group A human rotavirus serotypes. These orally administered vaccines were safe and immunogenic but had only limited success because serotype-specific immunity was not induced consistently in the under six-month age group. Therefore, a modified ''Jennerian'' approach was adopted with the goal of attaining broader antigenic coverage. In this approach, four serotypes are combined to form a quadrivalent vaccine comprised of: (i) rhesus rotavirus (RRV) which provides coverage for VP7 serotype 3, and (ii) three human-RRV reassortants each with ten RRV genes and a single human rotavirus gene that encodes VP7 serotype 1, 2, or 4 specificity. This modified ''Jennerian'' approach appears to be quite promising in preventing severe diarrhea in field trials. However, if this approach fails to yield an optimal level of protection consistently, additional modified ''Jennerian'' strategies are under development that consider not only human rotavirus VP7 but also human rotavirus VP4, the other outer capsid protein. In addition, a non- ''Jennerian'' approach includes the development of cold-adapted human rotavirus strains or cold-adapted human rotavirus reassortants as vaccine candidates. C1 CENT UNIV VENEZUELA,CARACAS,VENEZUELA. RP Kapikian, AZ (reprint author), NIAID,INFECT DIS LAB,NIH,BETHESDA,MD 20892, USA. NR 29 TC 5 Z9 5 U1 0 U2 2 PU SPRINGER-VERLAG WIEN PI VIENNA PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 VIENNA, AUSTRIA SN 0304-8608 J9 ARCH VIROL JI Arch. Virol. PY 1996 SU 12 BP 163 EP 175 PG 13 WC Virology SC Virology GA WE212 UT WOS:A1996WE21200019 ER PT J AU Cotch, MF Hoffman, GS Yerg, DE Kaufman, GI Targonski, P Kaslow, RA AF Cotch, MF Hoffman, GS Yerg, DE Kaufman, GI Targonski, P Kaslow, RA TI The epidemiology of Wegener's granulomatosis - Estimates of the five-year period prevalence, annual mortality, and geographic disease distribution from population-based data sources SO ARTHRITIS AND RHEUMATISM LA English DT Article ID SYSTEMIC VASCULITIS; POLYARTERITIS AB Objective. To estimate the prevalence, annual mortality, and geographic distribution of Wegener's granulomatosis. Methods. Analysis of national vital statistics data and hospitalization data from a national survey and from ail New York State inpatient facilities. Results. Between 1979 and 1988, 1,784 death certificates in the United States listed Wegener's granulomatosis as a cause of death, Nationally, an estimated 10,771 hospitalizations included Wegener's granulomatosis among the discharge diagnoses, In New York State, there were 978 hospitalizations among 571 individuals with Wegener's granulomatosis. Conclusion. The prevalence of Wegener's granulomatosis in the United States is approximately 3.0 per 100,000 persons, Clear differences in the geographic distribution of Wegener's granulomatosis are apparent when analyses consider rates of disease in individual counties. Contrary to previous reports, associations between disease exacerbations and season were not apparent. C1 CLEVELAND CLIN FDN,DEPT RHEUMAT & IMMUNOL DIS,CLEVELAND,OH 44195. NIAID,BETHESDA,MD 20892. NEW YORK STATE DEPT HLTH,ALBANY,NY. UNIV ILLINOIS,SCH PUBL HLTH,CHICAGO,IL. OI Cotch, Mary Frances/0000-0002-2046-4350 FU Intramural NIH HHS [Z99 EY999999] NR 16 TC 164 Z9 179 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD JAN PY 1996 VL 39 IS 1 BP 87 EP 92 DI 10.1002/art.1780390112 PG 6 WC Rheumatology SC Rheumatology GA TP969 UT WOS:A1996TP96900011 PM 8546743 ER PT S AU Montuori, N Sobel, ME AF Montuori, N Sobel, ME BE Gunthert, U Birchmeier, W TI The 67-kDa laminin receptor and tumor progression SO ATTEMPTS TO UNDERSTAND METASTASIS FORMATION I: METASTASIS-RELATED MOLECULES SE Current Topics in Microbiology and Immunology LA English DT Review ID BREAST-CANCER-CELLS; HUMAN COLON-CARCINOMA; MESSENGER-RNA; BINDING-PROTEIN; EXTRACELLULAR-MATRIX; DIFFERENTIAL EXPRESSION; MONOCLONAL-ANTIBODIES; RIBOSOMAL-PROTEIN; EMBRYONIC RETINA; MELANOMA-CELLS RP Montuori, N (reprint author), NCI, PATHOL LAB, MOL PATHOL SECT, NIH, ROOM 2A33, BETHESDA, MD 20892 USA. RI Montuori, Nunzia/J-8542-2013 NR 59 TC 25 Z9 27 U1 0 U2 4 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0070-217X BN 3-540-60680-7 J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 1996 VL 213 BP 205 EP 214 PN I PG 10 WC Immunology SC Immunology GA BJ66G UT WOS:A1996BJ66G00013 PM 8814988 ER PT S AU Freije, JMP MacDonald, NJ Steeg, PS AF Freije, JMP MacDonald, NJ Steeg, PS BE Gunthert, U Birchmeier, W TI Differential gene expression in tumor metastasis: Nm23 SO ATTEMPTS TO UNDERSTAND METASTASIS FORMATION II: REGULATORY FACTORS SE Current Topics in Microbiology and Immunology LA English DT Review ID NUCLEOSIDE DIPHOSPHATE KINASE; HUMAN BREAST-CANCER; LYMPH-NODE METASTASIS; PROTEIN EXPRESSION; DROSOPHILA DEVELOPMENT; BASEMENT-MEMBRANE; SUPPRESSOR GENES; MELANOMA-CELLS; GOOD PROGNOSIS; GROWTH ARREST RP Freije, JMP (reprint author), NCI, PATHOL LAB, WOMENS CANC SECT, BLDG 10, RM 2A33, BETHESDA, MD 20892 USA. RI Freije, Jose M.P./A-6535-2008 OI Freije, Jose M.P./0000-0002-4688-8266 NR 62 TC 16 Z9 17 U1 0 U2 1 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0070-217X BN 3-540-60681-5 J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 1996 VL 213 BP 215 EP 232 PN II PG 18 WC Immunology SC Immunology GA BJ66H UT WOS:A1996BJ66H00010 PM 9053292 ER PT S AU Alessandro, R Spoonster, J Wersto, RP Kohn, EC AF Alessandro, R Spoonster, J Wersto, RP Kohn, EC BE Gunthert, U Schlag, PM Birchmeier, W TI Signal transduction as a therapeutic target SO ATTEMPTS TO UNDERSTAND METASTASIS FORMATION III: THERAPEUTIC APPROACHES FOR METASTASIS TREATMENT SE Current Topics in Microbiology and Immunology LA English DT Review ID PROTEIN-KINASE-C; GROWTH-FACTOR-RECEPTOR; ETHER LIPID ANALOGS; TUMOR-CELL MOTILITY; INOSITOL PHOSPHATES; INTRACELLULAR CA2+; PHOSPHOLIPASE-C; CALCIUM INFLUX; FARNESYLTRANSFERASE INHIBITORS; PHOSPHATIDYLINOSITOL 3-KINASE RP Alessandro, R (reprint author), NCI, SIGNAL TRANSDUCT & PREVENT UNIT, PATHOL LAB, 10 CTR DR, MSC1500, BETHESDA, MD 20892 USA. NR 121 TC 10 Z9 10 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0070-217X BN 3-540-60682-3 J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 1996 VL 213 BP 167 EP 188 PN III PG 22 WC Immunology SC Immunology GA BJ66J UT WOS:A1996BJ66J00011 PM 8815004 ER PT J AU Brossi, A Pei, XF Greig, NH AF Brossi, A Pei, XF Greig, NH TI Invited review. Phenserine, a novel anticholinesterase related to physostigmine: Total synthesis and biological properties SO AUSTRALIAN JOURNAL OF CHEMISTRY LA English DT Review ID (-)-PHYSOSTIGMINE; (-)-ESEROLINE; (+)-PHYSOSTIGMINE; (-)-PHYSOVENOL; ALKALOIDS; OXINDOLES; ANALOGS AB Phenserine, the phenylcarbamate analogue of physostigmine, is a drug candidate of potential use for treating Alzheimer's disease. Phenserine inhibits acetylcholinesterase selectively, improves memory dramatically in experimental animals without toxicity, and reduces the production of beta-amyloid precursor protein, the source of the Alzheimer's toxin beta-amyloid. Phenserine was made from physostigmine in two steps, and it can be prepared in the required optically active form by total synthesis. For this purpose, the oxindole route developed by Julian in his total synthesis of physostigmine was vastly improved. Details of this work performed at the National Institutes of Health and at Institutions sponsored by this agency are presented herein. C1 NIDDK,BIOORGAN CHEM LAB,NIH,BETHESDA,MD 20892. NIA,LAB CELLULAR MOL BIOL,NIH,BALTIMORE,MD 21224. RP Brossi, A (reprint author), UNIV N CAROLINA,SCH PHARM,CHAPEL HILL,NC 27599, USA. NR 54 TC 42 Z9 42 U1 0 U2 6 PU C S I R O PUBLICATIONS PI COLLINGWOOD PA 150 OXFORD ST, PO BOX 1139, COLLINGWOOD VICTORIA 3066, AUSTRALIA SN 0004-9425 J9 AUST J CHEM JI Aust. J. Chem. PY 1996 VL 49 IS 2 BP 171 EP 181 PG 11 WC Chemistry, Multidisciplinary SC Chemistry GA UJ073 UT WOS:A1996UJ07300001 ER PT J AU LeRoith, D AF LeRoith, D TI Insulin-like growth factor receptors and binding proteins SO BAILLIERES CLINICAL ENDOCRINOLOGY AND METABOLISM LA English DT Review ID I IGF-I; MESSENGER-RIBONUCLEIC-ACID; BREAST-CANCER-CELLS; MANNOSE 6-PHOSPHATE RECEPTOR; NEURO-BLASTOMA CELLS; FOLLICLE-STIMULATING-HORMONE; OSTEOBLAST-LIKE CELLS; HUMAN GRANULOSA-CELLS; EARLY MOUSE EMBRYOS; BALB/C 3T3 CELLS RP LeRoith, D (reprint author), NIDDKD, DIABET BRANCH,NIH,BLDG 10,ROOM 8 SOUTH 239, 9000 ROCKVILLE PIKE, BETHESDA, MD 20892 USA. NR 186 TC 44 Z9 44 U1 0 U2 1 PU BAILLIERE TINDALL PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0950-351X J9 BAILLIERE CLIN ENDOC JI Baillieres Clin. Endocrinol. Metab. PD JAN PY 1996 VL 10 IS 1 BP 49 EP 73 DI 10.1016/S0950-351X(96)80298-9 PG 25 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA TW947 UT WOS:A1996TW94700005 PM 8734451 ER PT B AU Stratakis, CA Mitsiades, CS Pras, E Tsigos, C Carney, JA Chrousos, GP AF Stratakis, CA Mitsiades, CS Pras, E Tsigos, C Carney, JA Chrousos, GP BE Antypas, G TI Genomic instability in adrenal tumors of patients with Carney's complex SO BALKAN CONGRESS OF ONCOLOGY LA English DT Proceedings Paper CT 1st Congress of the Balkan-Union-of-Oncology CY JUL 03-07, 1996 CL ATHENS, GREECE SP Balkan Union Oncol C1 NICHHD,DEV ENDOCRINOL BRANCH,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MONDUZZI EDITORE PI 40128 BOLOGNA PA VIA FERRARESE 119/2, 40128 BOLOGNA, ITALY PY 1996 BP 543 EP 546 PG 4 WC Oncology SC Oncology GA BG40Z UT WOS:A1996BG40Z00095 ER PT B AU Stratakis, CA Mitsiades, CS South, S Carney, JA Chrousos, GP AF Stratakis, CA Mitsiades, CS South, S Carney, JA Chrousos, GP BE Antypas, G TI Clinical and genetic characteristics of Carney's complex, a familial multiple neoplasia syndrome. Analysis of a large kindred with familial history of acromegaly, as main manifestation of Carney's complex SO BALKAN CONGRESS OF ONCOLOGY LA English DT Proceedings Paper CT 1st Congress of the Balkan-Union-of-Oncology CY JUL 03-07, 1996 CL ATHENS, GREECE SP Balkan Union Oncol C1 NICHHD,DEV ENDOCRINOL BRANCH,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MONDUZZI EDITORE PI 40128 BOLOGNA PA VIA FERRARESE 119/2, 40128 BOLOGNA, ITALY PY 1996 BP 547 EP 550 PG 4 WC Oncology SC Oncology GA BG40Z UT WOS:A1996BG40Z00096 ER PT J AU Eschenhagen, T Friedrichsen, M Gsell, S Hollmann, A Mittmann, C Schmitz, W Scholz, H Weil, J Weinstein, LS AF Eschenhagen, T Friedrichsen, M Gsell, S Hollmann, A Mittmann, C Schmitz, W Scholz, H Weil, J Weinstein, LS TI Regulation of the human Gi alpha-2 gene promotor activity in embryonic chicken cardiomyocytes SO BASIC RESEARCH IN CARDIOLOGY LA English DT Article DE gene expression; reporter gene assay ID INHIBITORY G-PROTEIN; RAT-HEART; MEDIATED PATHWAYS; CROSS-REGULATION; SUBUNIT GENE; ALPHA; TRANSCRIPTION; STIMULATION; EXPRESSION; G(I-ALPHA-2) AB Increased expression of the inhibitory G protein Gi alpha-2 is assumed to contribute to desensitization of adenylyl cyclase in human heart failure. The mechanisms of upregulation involve increases in myocardial Gi alpha-2 protein, mRNA and gene transcriptional activity. To elucidate these mechanisms in more detail, the 5' flanking region of the human Gi alpha-2 gene (-1214/ + 115 bp) was cloned upstream of the bacterial chloramphenicol acetyltransferase (CAT) gene and transfected in embryonic chick cardiomyocytes, CAT activity was measured 48 h after transfection. Unstimulated activity of the -1214/ + 115 bp construct was about 10 fold higher than activity of the basal CAT-construct (pGEMCAT). 5' deletion from -1214/ + 115 to -85/ + 115 bp upstream of the transcriptional start site increased, further stepwise deletions to 46/ + 115 gradually decreased promotor activity. Deletion from -46/ + 115 to -33/ + 115 bp completely abolished promotor activity. Stimulation of cardiomyocytes that had been transfected with the -1214/ + 115 CAT-construct with isoprenaline (10 mu M), forskolin (10 mu M), forskolin (10 mu M) plus IBMX (10 mu M) or dibutyryl-cAMP (1 mM) for 24 h induced an increase in CAT activity to 139 +/- 12 % (n = 9), 211 +/- 18 % (n = 12), 256 +/- 20 % (n = 5) and 198 +/- 28 % (n = 7) of unstimulated values, respectively. We conclude: 1) In chicken cardiomyocytes a sequence clement of 52 bp between -85 and -33 bp is necessary to provide basal Gi alpha-2 promotor activity. 2) Elevation of cAMP has a stimulatory effect on the human Gi alpha-2 promotor, thereby offering a mechanism for beta-adrenoceptor-mediated increases in Gi alpha-2 in the heart. C1 NIDDK,METAB DIS BRANCH,BETHESDA,MD. RP Eschenhagen, T (reprint author), UNIV HAMBURG,KRANKENHAUS EPPENDORF,ABT ALLG PHARMAKOL,MARTINISTR 52,D-20246 HAMBURG,GERMANY. RI Weinstein, Lee/I-5575-2015 NR 17 TC 11 Z9 11 U1 0 U2 0 PU DR DIETRICH STEINKOPFF VERLAG PI BERLIN 33 PA C/O SPRINGER-VERLAG, HEIDELBERGER PLATZ 3, 1000 BERLIN 33, GERMANY SN 0300-8428 J9 BASIC RES CARDIOL JI Basic Res. Cardiol. PY 1996 VL 91 SU 2 BP 41 EP 46 DI 10.1007/BF00795361 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA VX751 UT WOS:A1996VX75100008 PM 8957543 ER PT J AU Acri, JB Serdikoff, SL Witkin, JM Sannerud, CA AF Acri, JB Serdikoff, SL Witkin, JM Sannerud, CA TI Discriminative stimulus effects of the benzodiazepine receptor partial agonist bretazenil in pigeons and in rats SO BEHAVIOURAL PHARMACOLOGY LA English DT Article DE benzodiazepines; bretazenil; diazepam-insensitive receptor subtype; drug discrimination; GABA(A); partial agonists; pigeon; rat ID ANTAGONIST RO-15-1788; FULL AGONISTS; RO 15-1788; MIDAZOLAM; CHLORDIAZEPOXIDE; DIAZEPAM; CUE; RO-16-6028; FLUMAZENIL; TOLERANCE AB Bretazenil is a partial agonist at diazepam-sensitive (DS) GABA(A) receptors, and it also binds with high affinity to diazepam-insensitive (DI) GABA(A) receptors. A unique discriminative stimulus effect transduced by binding at DI benzodiazepine (BZ) receptors has been reported in pigeons, but has not been established in rats. Further, differences have been observed between rats and pigeons in results of drug discrimination experiments utilizing BZ receptor partial agonists. Therefore, to examine the discriminative stimulus effects of bretazenil and to explore the possibility of species differences in substitution profiles, pigeons and rats were trained to discriminate 0.3 mg/kg bretazenil from vehicle. Flumazenil (0.03-1.0 mg/kg) did not substitute for bretazenil in pigeons, despite full substitution of bretazenil for flumazenil in this species. Flumazenil (0.03-10.0 mg/kg) also did not substitute for bretazenil in rats, despite the partial agonist effects of flumazenil in rats. Likewise, midazolam (0.3-1.0 mg/kg) did not substitute for bretazenil in pigeons, despite the fact that bretazenil partially substitutes for midazolam in pigeons. However in rats, midazolam produced full, dose-dependent substitution (0.03-3.2 mg/kg). Differences may result from different fractional receptor occupancy requirements for the mediation of discriminative stimulus effects through DS BZ receptors, and/or from a contribution of DI BZ receptor binding in pigeons. RP Acri, JB (reprint author), NIDA,ADDICT RES CTR,PRECLIN PHARMACOL LAB,POB 5180,BALTIMORE,MD 21224, USA. NR 39 TC 6 Z9 6 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0955-8810 J9 BEHAV PHARMACOL JI Behav. Pharmacol. PD JAN PY 1996 VL 7 IS 1 BP 72 EP 77 PG 6 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA TT374 UT WOS:A1996TT37400007 ER PT S AU Kim, HY Wang, TCL Ma, YC AF Kim, HY Wang, TCL Ma, YC BE Snyder, AP TI Characterization of polyunsaturated phospholipid remodeling in mammalian cells by high-performance liquid chromatography electrospray ionization mass spectrometry SO BIOCHEMICAL AND BIOTECHNOLOGICAL APPLICATIONS OF ELECTROSPRAY IONIZATION MASS SPECTROMETRY SE ACS SYMPOSIUM SERIES LA English DT Article; Proceedings Paper CT Symposium on Biochemical and Biotechnological Applications of Electrospray Ionization Mass Spectrometry, at the 209th National Meeting of the American-Chemical-Society CY APR 02-06, 1995 CL ANAHEIM, CA SP Amer Chem Soc AB Characteristics of cell membranes are greatly affected by the composition of phospholipid bilayers. The cellular membrane phospholipid composition is maintained by complex biosynthetic and remodeling processes, including phospholipase, base exchange and acyltransferase reactions. In order to understand these complex biochemical mechanisms, analysis of the phospholipid profile in biomembranes is necessary. Using electrospray mass spectrometry coupled to reversed phase HPLC, phospholipid molecular species of different head groups and fatty acyl compositions could be separated and detected in a single run. Sensitivity at the picomole level was attained with a linear response range over 2 orders of magnitude. Application of this technique to remodeling of polyunsaturated phospholipids in C-6 glia cells and the rodent brain is demonstrated. C1 NIMH,NIH,BETHESDA,MD 20892. RP Kim, HY (reprint author), NIAAA,NIH,BLDG 10,ROOM 3C-103,BETHESDA,MD 20892, USA. NR 19 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 SIXTEENTH ST NW, WASHINGTON, DC 20036 SN 0097-6156 BN 0-8412-3378-0 J9 ACS SYM SER PY 1996 VL 619 BP 267 EP 280 PG 14 WC Chemistry, Analytical; Spectroscopy SC Chemistry; Spectroscopy GA BE78K UT WOS:A1996BE78K00013 ER PT S AU Watts, JD Affolter, M Krebs, DL Wange, RL Samelson, LE Aebersold, R AF Watts, JD Affolter, M Krebs, DL Wange, RL Samelson, LE Aebersold, R BE Snyder, AP TI Electrospray ionization mass spectrometric investigation of signal transduction pathways - Determination of sites of inducible protein phosphorylation in activated T cells SO BIOCHEMICAL AND BIOTECHNOLOGICAL APPLICATIONS OF ELECTROSPRAY IONIZATION MASS SPECTROMETRY SE ACS SYMPOSIUM SERIES LA English DT Article; Proceedings Paper CT Symposium on Biochemical and Biotechnological Applications of Electrospray Ionization Mass Spectrometry, at the 209th National Meeting of the American-Chemical-Society CY APR 02-06, 1995 CL ANAHEIM, CA SP Amer Chem Soc ID MICE LACKING P56(LCK); ANTIGEN RECEPTOR-ZETA; TYROSINE KINASE; AFFINITY-CHROMATOGRAPHY; IL-2 RECEPTOR; TCR ZETA; P56LCK; IDENTIFICATION; ASSOCIATION; CHAIN AB We have developed methodologies for the determination of sites of protein phosphorylation by tandem microbore column chromatography, with on-line detection by electrospray ionization mass spectrometry (ESI-MS), of phosphopeptides recovered from two-dimensional (2D) phosphopeptide maps. We have applied these methods to the identification of sites of tyrosine phosphorylation induced on the lymphocyte-specific protein tyrosine kinase ZAP-70 and the T cell receptor (TCR) zeta subunit in vivo, following stimulation of T cells via their TCR. Our approach is generally applicable to the investigation of signal transduction pathways since it involves direct ESI-MS analysis of peptides recovered from 2D phosphopeptide maps, currently the analytical technique of choice for the detailed analysis of protein phosphorylation sites, and is fully adaptable for the analysis of serine- and threonine-phosphorylated peptides. C1 UNIV WASHINGTON,DEPT MOLEC BIOTECHNOL,SEATTLE,WA 98195. NESTEC LTD,RES CTR,CH-1000 LAUSANNE,SWITZERLAND. UNIV BRITISH COLUMBIA,DEPT MICROBIOL,VANCOUVER,BC V6T 1Z3,CANADA. NICHHD,NIH,CELL BIOL & METAB BRANCH,BETHESDA,MD 20892. NR 65 TC 6 Z9 6 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 SIXTEENTH ST NW, WASHINGTON, DC 20036 SN 0097-6156 BN 0-8412-3378-0 J9 ACS SYM SER PY 1996 VL 619 BP 381 EP 407 PG 27 WC Chemistry, Analytical; Spectroscopy SC Chemistry; Spectroscopy GA BE78K UT WOS:A1996BE78K00020 ER PT J AU Shetty, HU Holloway, HW Acevedo, LD Galdzicki, Z AF Shetty, HU Holloway, HW Acevedo, LD Galdzicki, Z TI Brain accumulation of myo-inositol in the trisomy 16 mouse, an animal model of Down's Syndrome SO BIOCHEMICAL JOURNAL LA English DT Article ID CELLS AB myo-Inositol and several other polyols were measured in the tissues of the trisomy 16 mouse (animal model of Down's Syndrome; human trisomy 21) and diploid controls. myo-Inositol was found to be selectively elevated in the brain of the trisomy 16 mouse. However, peripheral tissues showed no elevation. These results are consistent with the cerebrospinal fluid and plasma data reported previously on myo-inositol in Downs's Syndrome subjects. RP Shetty, HU (reprint author), NIA,NEUROSCI LAB,BETHESDA,MD 20892, USA. NR 18 TC 19 Z9 19 U1 0 U2 0 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON, ENGLAND W1N 3AJ SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD JAN 1 PY 1996 VL 313 BP 31 EP 33 PN 1 PG 3 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TN890 UT WOS:A1996TN89000002 PM 8546700 ER PT J AU Brozinick, JT Yaspelkis, BB Wilson, CM Grant, KE Gibbs, M Cushman, SW Ivy, JL AF Brozinick, JT Yaspelkis, BB Wilson, CM Grant, KE Gibbs, M Cushman, SW Ivy, JL TI Glucose transport and GLUT4 protein distribution in skeletal muscle of GLUT4 transgenic mice SO BIOCHEMICAL JOURNAL LA English DT Article ID INDUCED TRANSLOCATION AB The aim of the present investigation was to determine whether the subcellular distribution and insulin-stimulated translocation of the GLUT4 isoform of the glucose transporter are affected when GLUT4 is overexpressed in mouse skeletal muscle, and if the overexpression of GLUT4 alters maximal. insulin-stimulated glucose transport and metabolism. Rates of glucose transport and metabolism were assessed by hind-limb perfusion in GLUT4 transgenic (TG) mice and non-transgenic (NTG) controls. Glucose-transport activity was determined under basal (no insulin), submaximal (0.2 m-unit/ml) and maximal (10 m-units/ml) insulin conditions using a perfusate containing 8 mM 3-O-methyl-D-glucose. Glucose metabolism was quantified by perfusing the hind limbs for 25 min with a perfusate containing 8 mM glucose and 10 m-units/ml insulin. Under basal conditions, there was no difference in muscle glucose transport between TG (1.10+/-0.10 mu mol/h per g; mean+/-S.E.M.) and NTG (0.93+/-0.16 mu mol/h per g) mice. However, TG mice displayed significantly greater glucose-transport activity during submaximal (4.42+/-0.49 compared with 2.69+/-0.33 mu mol/h per g) and maximal (11.68+/-1.13 compared with 7.53+/-0.80 mu mol/h per g) insulin stimulation, Nevertheless, overexpression of the GLUT4 protein did not alter maximal rates of glucose metabolism. Membrane purification revealed that, under basal conditions, plasma-membrane (similar to 12-fold) and intracellular-membrane (similar to 4-fold) GLUT4 protein concentrations were greater in TG than NTG mice. Submaximal insulin stimulation did not increase plasma-membrane GLUT4 protein concentration whereas maximal insulin stimulation increased this protein in both NTG (4.1-fold) and TG (2.6-fold) mice. These results suggest that the increase in insulin-stimulated glucose transport following overexpression of the GLUT4 protein is limited by factors other than the plasma-membrane GLUT4 protein concentration. Furthermore, GLUT4 overexpression is not coupled to glucose-metabolic capacity. C1 NIDDK,DB,EXPTL DIABET METAB & NUTR SECT,BETHESDA,MD 20892. UNIV TEXAS,DEPT KINESIOL,EXERCISE PHYSIOL & METAB LAB,AUSTIN,TX 78712. PFIZER INC,CENT RES,GROTON,CT 06340. NR 27 TC 41 Z9 41 U1 0 U2 0 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON, ENGLAND W1N 3AJ SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD JAN 1 PY 1996 VL 313 BP 133 EP 140 PN 1 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TN890 UT WOS:A1996TN89000017 PM 8546674 ER PT J AU Yu, AE Hewitt, RE Kleiner, DE StetlerStevenson, WG AF Yu, AE Hewitt, RE Kleiner, DE StetlerStevenson, WG TI Molecular regulation of cellular invasion - Role of gelatinase A and TIMP-2 SO BIOCHEMISTRY AND CELL BIOLOGY-BIOCHIMIE ET BIOLOGIE CELLULAIRE LA English DT Article; Proceedings Paper CT 12th International Symposium on Cellular Endocrinology on the Extracellular Matrix: Its Synthesis, Function, and Degradation CY SEP 12-15, 1996 CL LAKE PLACID, NY DE tissue inhibitors of metalloproteinases; metalloproteinase; gelatinases; extracellular matrix; activation ID BASEMENT-MEMBRANE COLLAGEN; IN-SITU HYBRIDIZATION; METALLOPROTEINASE GENE-EXPRESSION; HUMAN COLON-CANCER; C-TERMINAL DOMAIN; IV COLLAGENASE; TISSUE INHIBITOR; MATRIX METALLOPROTEINASE; 72-KDA GELATINASE; MR 72,000 AB Extracellular matrix (ECM) turnover is an event that is tightly regulated. Much of the coordinate (physiological) or discoordinate (pathological) degradation of the ECM is catalyzed by a class of proteases known as the matrix metalloproteinases (MMPs) or matrixins. Matrixins are a family of homologous Zn atom dependent endopeptidases that are usually secreted from cells as inactive zymogens. Net degradative activity in the extracellular environment is regulated by specific activators and inhibitors. One member of the matrixin family, gelatinase A, is regulated differently from other MMPs, suggesting that it may play a unique role in cell-matrix interactions, including cell invasion. The conversion from the 72 kDa progelatinase A to the active 62 kDa species may be a key event in the acquisition of invasive potential. This discussion reviews some recent findings on the cellular mechanisms involved in progelatinase A activation and, in particular, the role of tissue inhibitor of matrix metalloproteinases-2 (TIMP-2) and transmembrane containing metalloproteinases (MT-MMP) in this process. C1 NCI,PATHOL LAB,NIH,BETHESDA,MD 20892. RI Stetler-Stevenson, William/H-6956-2012 OI Stetler-Stevenson, William/0000-0002-5500-5808 NR 76 TC 88 Z9 89 U1 0 U2 0 PU NATL RESEARCH COUNCIL CANADA PI OTTAWA PA RESEARCH JOURNALS, MONTREAL RD, OTTAWA ON K1A 0R6, CANADA SN 0829-8211 J9 BIOCHEM CELL BIOL JI Biochem. Cell Biol. PY 1996 VL 74 IS 6 BP 823 EP 831 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA WZ851 UT WOS:A1996WZ85100010 PM 9164651 ER PT J AU Negishi, M Uno, T Honkakoski, P Sueyoshi, T Darden, TA Pedersen, LP AF Negishi, M Uno, T Honkakoski, P Sueyoshi, T Darden, TA Pedersen, LP TI The roles of individual amino acids in altering substrate specificity of the P450 2a4/2a5 enzymes SO BIOCHIMIE LA English DT Article DE P450; substrate specificity; site-directed mutagenesis; computer modeling ID SITE-DIRECTED MUTAGENESIS; STEROID 15-ALPHA-HYDROXYLASE; COUMARIN 7-HYDROXYLASE; HYDROXYLASE-ACTIVITY; II P-45015-ALPHA; MUTATION; BINDING; REGIOSPECIFICITY; RESIDUE-209; PROTEINS AB A single amino acid substitution is sufficient to alter substrate specificity of P450 enzymes. Mouse P450 2a5, for example, has its substrate specificity converted from coumarin 7- to testosterone 15 alpha-hydroxylase activity by the substitution of Phe at position 209 to Leu. Furthermore, placing Asn at this position confers a novel corticosterone 15 alpha-hydroxylase activity to this P450. Recent site-directed mutational studies show the presence of the topologically common residues, each of which can determine the specificities of various mammalian P450s. For instance, residue 209 (in 2a5) corresponds to a residue at position 206 in rat P4502B1 that regulates its steroid hydroxylase activity. High substrate specificity often observed in an individual P450, therefore, can be determined and altered by the identities of a few critical residues. The structural flexibility of the substrate-heme pocket may also provide P450 enzymes with the ability to display a broad range of substrate specificities. Understanding the underlying principles whereby the flexible pocket determines P450 activities may lead us to the prediction of P450 activities based on the identities of key amino acid residues. C1 NIEHS,LAB QUANTITAT & COMPUTAT BIOL,NIH,RES TRIANGLE PK,NC 27709. RP Negishi, M (reprint author), NIEHS,PHARMACOGENET SECT,REPROD & DEV TOXICOL LAB,NIH,RES TRIANGLE PK,NC 27709, USA. RI Pedersen, Lee/E-3405-2013; OI Pedersen, Lee/0000-0003-1262-9861; Honkakoski, Paavo/0000-0002-4332-3577 NR 40 TC 18 Z9 19 U1 0 U2 2 PU EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS PA 141 RUE JAVEL, 75747 PARIS, FRANCE SN 0300-9084 J9 BIOCHIMIE JI Biochimie PY 1996 VL 78 IS 8-9 BP 685 EP 694 DI 10.1016/S0300-9084(97)82525-4 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VZ800 UT WOS:A1996VZ80000002 PM 9010596 ER PT J AU Koley, AP Robinson, RC Friedman, FK AF Koley, AP Robinson, RC Friedman, FK TI Cytochrome P450 conformation and substrate interactions as probed by CO binding kinetics SO BIOCHIMIE LA English DT Article DE cytochrome P450; kinetics; flash photolysis ID RAT-LIVER MICROSOMES; PSEUDOMONAS-PUTIDA CYTOCHROME-P-450; POLYCYCLIC AROMATIC-HYDROCARBONS; CARBON-MONOXIDE BINDING; ENDOPLASMIC-RETICULUM; FLASH-PHOTOLYSIS; PROTEIN ROTATION; HYDROXYLASE; FLAVONES; COMPLEX AB The kinetics of CO binding to cytochrome P450, as measured by the flash photolysis technique, is a powerful probe of P450 structure-function relationships. The kinetics are sensitive to P450 conformation and dynamics and are modulated by P450 interactions with substrates and other components of the microsomal membrane. Application of a difference method to kinetic data analysis distinguishes the kinetic behavior of individual P450 forms in the microsomal membrane. This approach shows that substrates differentially modulate the kinetics via: 1) changes in P450 conformation/dynamics that either accelerate or reduce the binding rate; and/or 2) steric effects that reduce the rate. Both mechanisms are observed, the relative contributions of each varying in a substrate- and P450-dependent manner. In addition to microsomes, substrate interactions with individual P450s can be similarly probed using expressed P450s. Experiments with baculovirus-expressed human P450 3A4 show that this P450 consists of multiple conformers with distinct substrate specificities, an observation which provides a basis for its recognition of a wide array of structurally diverse substrates. These studies thus demonstrate the utility of CO binding kinetics in elucidating fundamental P450-substrate interactions in a biological membrane environment. C1 NCI,MOL CARCINOGENESIS LAB,NIH,BETHESDA,MD 20892. RI Friedman, Fred/D-4208-2016 NR 32 TC 41 Z9 41 U1 2 U2 5 PU EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS PA 141 RUE JAVEL, 75747 PARIS, FRANCE SN 0300-9084 J9 BIOCHIMIE JI Biochimie PY 1996 VL 78 IS 8-9 BP 706 EP 713 DI 10.1016/S0300-9084(97)82528-X PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VZ800 UT WOS:A1996VZ80000005 PM 9010599 ER PT J AU Prior, TI Kunwar, S Pastan, I AF Prior, TI Kunwar, S Pastan, I TI Studies on the activity of barnase toxins in vitro and in vivo SO BIOCONJUGATE CHEMISTRY LA English DT Article ID PSEUDOMONAS EXOTOXIN-A; EPIDERMAL GROWTH-FACTOR; DOMAIN-II; RIBONUCLEASE CHIMERAS; CYTOTOXIC ACTIVITY; TRANSLOCATION; IMMUNOTOXINS; AERUGINOSA; RECEPTOR; FRAGMENT AB Pseudomonas exotoxin A (PE) is a protein toxin composed of three structural domains which are responsible for cell binding (domain Ia, amino acids 1-252), translocation into the cytosol (domain II, amino acids 253-364) and ADP-ribosylation activity (domain III, amino acids 405-613). We have previously described (Prior, T. I., FitzGerald, D. J., and Pastan, I. (1992) Biochem. 31, 3555-3559) a molecule composed of amino acids 1-412 of PE and the extracellular ribonuclease of Bacillus amyloliquefaciens, barnase (Bar), and shown that this protein (PE(1-412)-Bar) is toxic to cells due to its ribonuclease activity, which had been delivered to the cytosol. We have now used this model to evaluate the role played by the carboxyl end of domain II (amino acids 347-364), domain Ib, and the amino end of domain III (amino acids 405-412) in the translocation event. Toxins completely lacking domain III, termed PE(1-380)-Bar, or both domains Ib and III, termed pE(1-364)-Bar, were equally cytotoxic to a murine fibroblast cell line (L929) as was PE(1-412)-Bar. Extending the deletion to include part of the E-helix and all of the F-helix of domain II (amino acids 347-364) resulted in a toxin (pE(1-346)-Bar) that was 10-fold less toxic. Previously tested on only murine cell lines, we demonstrate that barnase toxins are cytotoxic also to a variety of human cell lines. Cytotoxicity was assessed by measuring inhibition of DNA synthesis. Surprisingly, PE(1-380)-Bar is not lethal when injected into mice, either intraperitoneally or intravenously, at 9 nmol, which is 2200-fold more than the amount required for killing by PE (4 pmol). In cell culture these barnase-containing toxins are 100-fold less toxic to murine fibroblast cells than PE. Barnase toxin has a greater survival time in the blood of mice than PE, with a half-life of 102 min. We conclude that domain II is sufficient to transport proteins into the cytosol. Further, since domain Ia can be replaced with other cell targeting moieties, we propose that barnase-toxins should be evaluated for utility in targeted cancer therapy. C1 NCI,DCBDC,MOLEC BIOL LAB,BETHESDA,MD 20892. NR 36 TC 15 Z9 18 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 1043-1802 J9 BIOCONJUGATE CHEM JI Bioconjugate Chem. PD JAN-FEB PY 1996 VL 7 IS 1 BP 23 EP 29 DI 10.1021/bc9500655 PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA TT950 UT WOS:A1996TT95000006 PM 8741987 ER PT J AU Pozsgay, V Trinh, L Shiloach, J Robbins, JB DonohueRolfe, A Calderwood, SB AF Pozsgay, V Trinh, L Shiloach, J Robbins, JB DonohueRolfe, A Calderwood, SB TI Purification of subunit B of Shiga toxin using a synthetic trisaccharide-based affinity matrix SO BIOCONJUGATE CHEMISTRY LA English DT Article ID SHIGELLA-DYSENTERIAE TYPE-1; CELL-SURFACE GLYCANS; TRI-SACCHARIDE; OLIGOSACCHARIDES; DERIVATIVES; GLYCOSIDES; DETERMINANT; ANTIGEN; POLYSACCHARIDE; RECEPTOR AB The blood group P-1 antigenic trisaccharide (3), which is the receptor-binding ligand of Shiga-like toxins, is synthesized in a spacer-equipped form (32) from 2-(trimethylsilyl)ethyl glucoside 5 and the 1-thiogalactoside building blocks 10 and 22 in a stereocontrolled, stepwise fashion. Covalent attachment of 32 to hydrazine group-containing agarose gel by reductive amination provided the P-1 trisaccharide-containing affinity sorbent which was used for preparative scale isolation of subunit B of Shiga toxin. C1 NIDDKD,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. TUFTS UNIV,SCH VET MED,DEPT COMPARAT MED,N GRAFTON,MA 01536. MASSACHUSETTS GEN HOSP,INFECT DIS UNIT,BOSTON,MA 02114. RP Pozsgay, V (reprint author), NICHHD,DEV & MOLEC IMMUN LAB,BETHESDA,MD 20892, USA. NR 47 TC 12 Z9 12 U1 1 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 1043-1802 J9 BIOCONJUGATE CHEM JI Bioconjugate Chem. PD JAN-FEB PY 1996 VL 7 IS 1 BP 45 EP 55 DI 10.1021/bc9500711 PG 11 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA TT950 UT WOS:A1996TT95000009 PM 8741990 ER PT B AU Smith, JC AF Smith, JC BE Khoo, MCK TI Realistic computational models of respiratory neurons and networks SO BIOENGINEERING APPROACHES TO PULMONARY PHYSIOLOGY AND MEDICINE LA English DT Proceedings Paper CT 12th Biomedical Simulations Resource Short Course on Bioengineering Approaches to Pulmonary Physiology and Medicine CY MAY 20, 1995 CL SEATTLE, WA C1 NINCDS,NEURAL CONTROL LAB,NIH,BETHESDA,MD 20892. NR 0 TC 4 Z9 4 U1 0 U2 0 PU PLENUM PRESS DIV PLENUM PUBLISHING CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 BN 0-306-45370-3 PY 1996 BP 77 EP 92 DI 10.1007/978-0-585-34964-0_5 PG 16 WC Engineering, Biomedical SC Engineering GA BG08M UT WOS:A1996BG08M00005 ER PT B AU Kraemer, KH AF Kraemer, KH BE Holick, MF Jung, EG TI Sunlight and melanoma: Studies of human genetic disorders SO BIOLOGIC EFFECTS OF LIGHT 1995 LA English DT Proceedings Paper CT 4th International Arnold Rikli Symposium on Biologic Effects of Light CY OCT 09-11, 1995 CL ATLANTA, GA SP Inst Friedrich Wolff AG, Light Symp Fdn RP Kraemer, KH (reprint author), NCI,MOL CARCINOGENESIS LAB,BLDG 37,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WALTER DE GRUYTER PI BERLIN 30 PA GENTHINER STRASSE 13, W-1000 BERLIN 30, GERMANY BN 3-11-014899-4 PY 1996 BP 252 EP 255 PG 4 WC Biophysics; Dermatology SC Biophysics; Dermatology GA BH54R UT WOS:A1996BH54R00043 ER PT B AU Braun, MM Tucker, MA AF Braun, MM Tucker, MA BE Holick, MF Jung, EG TI Do photoproducts of vitamin D play a role in the etiology of cutaneous melanoma? SO BIOLOGIC EFFECTS OF LIGHT 1995 LA English DT Proceedings Paper CT 4th International Arnold Rikli Symposium on Biologic Effects of Light CY OCT 09-11, 1995 CL ATLANTA, GA SP Inst Friedrich Wolff AG, Light Symp Fdn RP Braun, MM (reprint author), NCI,EPIDEMIOL & BIOSTAT PROGRAM,NIH,EPN 443,6130 EXECUT BLVD,ROCKVILLE,MD 20852, USA. RI Tucker, Margaret/B-4297-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WALTER DE GRUYTER PI BERLIN 30 PA GENTHINER STRASSE 13, W-1000 BERLIN 30, GERMANY BN 3-11-014899-4 PY 1996 BP 293 EP 300 PG 8 WC Biophysics; Dermatology SC Biophysics; Dermatology GA BH54R UT WOS:A1996BH54R00048 ER PT B AU Tangrea, J Taylor, P Albanes, D Helzlsouer, K Pietinen, P Virtamo, J AF Tangrea, J Taylor, P Albanes, D Helzlsouer, K Pietinen, P Virtamo, J BE Holick, MF Jung, EG TI Prediagnostic serum levels of vitamin D metabolites and the subsequent risk of large bowel cancer SO BIOLOGIC EFFECTS OF LIGHT 1995 LA English DT Proceedings Paper CT 4th International Arnold Rikli Symposium on Biologic Effects of Light CY OCT 09-11, 1995 CL ATLANTA, GA SP Inst Friedrich Wolff AG, Light Symp Fdn RP Tangrea, J (reprint author), NCI,NIH,BETHESDA,MD 20892, USA. RI Albanes, Demetrius/B-9749-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WALTER DE GRUYTER PI BERLIN 30 PA GENTHINER STRASSE 13, W-1000 BERLIN 30, GERMANY BN 3-11-014899-4 PY 1996 BP 301 EP 308 PG 8 WC Biophysics; Dermatology SC Biophysics; Dermatology GA BH54R UT WOS:A1996BH54R00049 ER PT B AU Rosenthal, NE AF Rosenthal, NE BE Holick, MF Jung, EG TI The mechanism of action of light in the treatment of seasonal affective disorder (SAD) SO BIOLOGIC EFFECTS OF LIGHT 1995 LA English DT Proceedings Paper CT 4th International Arnold Rikli Symposium on Biologic Effects of Light CY OCT 09-11, 1995 CL ATLANTA, GA SP Inst Friedrich Wolff AG, Light Symp Fdn RP Rosenthal, NE (reprint author), NIMH,CLIN PSYCHOBIOL BRANCH,BETHESDA,MD 20892, USA. NR 0 TC 3 Z9 3 U1 0 U2 1 PU WALTER DE GRUYTER PI BERLIN 30 PA GENTHINER STRASSE 13, W-1000 BERLIN 30, GERMANY BN 3-11-014899-4 PY 1996 BP 317 EP 324 PG 8 WC Biophysics; Dermatology SC Biophysics; Dermatology GA BH54R UT WOS:A1996BH54R00051 ER PT J AU Castellanos, FX Fine, EJ Kaysen, D Marsh, WL Rapoport, JL Hallett, M AF Castellanos, FX Fine, EJ Kaysen, D Marsh, WL Rapoport, JL Hallett, M TI Sensorimotor gating in boys with Tourette's syndrome and ADHD: Preliminary results SO BIOLOGICAL PSYCHIATRY LA English DT Article DE prepulse inhibition; gating; attention-deficit hyperactivity disorder; Tourette's syndrome; blink reflex ID ATTENTION-DEFICIT DISORDER; INDUCED STARTLE MODULATION; HYPERACTIVITY DISORDER; BASAL GANGLIA; BLINK REFLEX; SCHIZOPHRENIC-PATIENTS; CHILDREN; INHIBITION; PRESTIMULATION; MATURATION AB Deficits in sensorimotor gating, defined by prepulse inhibition (PPI), have been associated with subcortical dopaminergic overactivity in animal and clinical studies, Utilizing supraorbital nerve electrical stimulation, we produced adequate blink responses and measured decreases in amplitude resulting from electric prestimuli just above sensory threshold. Seven boys comorbid for attention-deficit hyperactivity disorder (ADHD) and a tic disorder had significantly reduced PPI, compared to 14 screened controls and seven boys with ADHD alone. If independently replicated, these results may reflect greater neurologic immaturity in these comorbid subjects. Alternatively, these findings, together with other converging lines of evidence, suggest that deficient pallidal inhibition may be etiologically related so tic and movement disorders. C1 VET ADM MED CTR,DEPT NEUROL,BUFFALO,NY. SUNY BUFFALO,BUFFALO,NY. NINCDS,MED NEUROL BRANCH,BETHESDA,MD 20892. RP Castellanos, FX (reprint author), NIMH,CHILD PSYCHIAT BRANCH,BLDG 10 ROOM 6N240,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. OI Castellanos, Francisco/0000-0001-9192-9437 NR 68 TC 264 Z9 266 U1 3 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD JAN 1 PY 1996 VL 39 IS 1 BP 33 EP 41 DI 10.1016/0006-3223(95)00101-8 PG 9 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA TM611 UT WOS:A1996TM61100007 PM 8719124 ER PT S AU Osawa, Y Nakatsuka, K Williams, MS Kindt, JT Nakatsuka, M AF Osawa, Y Nakatsuka, K Williams, MS Kindt, JT Nakatsuka, M BE Snyder, R Kocsis, JJ Sipes, IG Kalf, GF Jollow, DJ Greim, H Monks, TJ Witmer, CM TI Reactions of reactive metabolites with hemoproteins - Toxicological implications - Covalent alteration of hemoproteins SO BIOLOGICAL REACTIVE INTERMEDIATES V: BASIC MECHANISTIC RESEARCH IN TOXICOLOGY AND HUMAN RISK ASSESSMENT SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Proceedings Paper CT 5th International Symposium on Biological Reactive Intermediates CY JAN 04-08, 1995 CL MUNICH, GERMANY SP Deut Forschungsgemeinsch, Deut Gesell Exptl & Klin Pharmakol & Toxicol, BASF AG, Basotherm, Bayer AG, Bohringer Ingelheim, Bohringer Mannheim, Hoechst AG, E Merck AG, Schering Forschungsgesell Gmbh, Rutgers, The State Univ New Jersey, Environm & Occupat Hlth Sci Inst, Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Joint Grad Program Toxicol ID NITRIC-OXIDE SYNTHASE; PROSTHETIC HEME; CYTOCHROME-P450 2B1; HEMOGLOBIN ADDUCTS; CROSS-LINKING; MYOGLOBIN; MECHANISM; INACTIVATION; BRCCL3; IDENTIFICATION RP Osawa, Y (reprint author), NHLBI,LAB MOLEC IMMUNOL,MOLEC & CELLULAR TOXICOL SECT,BETHESDA,MD 20892, USA. NR 35 TC 5 Z9 5 U1 0 U2 0 PU PLENUM PRESS DIV PLENUM PUBLISHING CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0065-2598 BN 0-306-45197-2 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 1996 VL 387 BP 37 EP 45 PG 9 WC Biochemistry & Molecular Biology; Public, Environmental & Occupational Health; Medicine, Research & Experimental; Toxicology SC Biochemistry & Molecular Biology; Public, Environmental & Occupational Health; Research & Experimental Medicine; Toxicology GA BF83V UT WOS:A1996BF83V00006 PM 8794192 ER PT S AU Keefer, LK Wink, DA AF Keefer, LK Wink, DA BE Snyder, R Kocsis, JJ Sipes, IG Kalf, GF Jollow, DJ Greim, H Monks, TJ Witmer, CM TI DNA damage and nitric oxide SO BIOLOGICAL REACTIVE INTERMEDIATES V: BASIC MECHANISTIC RESEARCH IN TOXICOLOGY AND HUMAN RISK ASSESSMENT SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Proceedings Paper CT 5th International Symposium on Biological Reactive Intermediates CY JAN 04-08, 1995 CL MUNICH, GERMANY SP Deut Forschungsgemeinsch, Deut Gesell Exptl & Klin Pharmakol & Toxicol, BASF AG, Basotherm, Bayer AG, Bohringer Ingelheim, Bohringer Mannheim, Hoechst AG, E Merck AG, Schering Forschungsgesell Gmbh, Rutgers, The State Univ New Jersey, Environm & Occupat Hlth Sci Inst, Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Joint Grad Program Toxicol ID NITROUS-ACID; L-ARGININE; INHIBITION; CELLS; SUPEROXIDE; OXIDATION; KINETICS; PROTEIN; OXYGEN; AGENT RP Keefer, LK (reprint author), NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,CHEM SECT,FREDERICK,MD 21702, USA. RI Keefer, Larry/N-3247-2014 OI Keefer, Larry/0000-0001-7489-9555 NR 30 TC 28 Z9 28 U1 0 U2 0 PU PLENUM PRESS DIV PLENUM PUBLISHING CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0065-2598 BN 0-306-45197-2 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 1996 VL 387 BP 177 EP 185 PG 9 WC Biochemistry & Molecular Biology; Public, Environmental & Occupational Health; Medicine, Research & Experimental; Toxicology SC Biochemistry & Molecular Biology; Public, Environmental & Occupational Health; Research & Experimental Medicine; Toxicology GA BF83V UT WOS:A1996BF83V00024 PM 8794210 ER PT S AU Buchanan, JR Portier, CJ AF Buchanan, JR Portier, CJ BE Snyder, R Kocsis, JJ Sipes, IG Kalf, GF Jollow, DJ Greim, H Monks, TJ Witmer, CM TI The use of data on biologically reactive intermediates in risk assessment SO BIOLOGICAL REACTIVE INTERMEDIATES V: BASIC MECHANISTIC RESEARCH IN TOXICOLOGY AND HUMAN RISK ASSESSMENT SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Proceedings Paper CT 5th International Symposium on Biological Reactive Intermediates CY JAN 04-08, 1995 CL MUNICH, GERMANY SP Deut Forschungsgemeinsch, Deut Gesell Exptl & Klin Pharmakol & Toxicol, BASF AG, Basotherm, Bayer AG, Bohringer Ingelheim, Bohringer Mannheim, Hoechst AG, E Merck AG, Schering Forschungsgesell Gmbh, Rutgers, The State Univ New Jersey, Environm & Occupat Hlth Sci Inst, Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Joint Grad Program Toxicol ID NAPHTHALENE METABOLITES; METHYLENE-CHLORIDE; MODELS; VARIABILITY RP Buchanan, JR (reprint author), NIEHS,LAB QUANTITAT & COMPUTAT BIOL,RES TRIANGLE PK,NC 27709, USA. NR 18 TC 0 Z9 0 U1 0 U2 0 PU PLENUM PRESS DIV PLENUM PUBLISHING CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0065-2598 BN 0-306-45197-2 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 1996 VL 387 BP 429 EP 437 PG 9 WC Biochemistry & Molecular Biology; Public, Environmental & Occupational Health; Medicine, Research & Experimental; Toxicology SC Biochemistry & Molecular Biology; Public, Environmental & Occupational Health; Research & Experimental Medicine; Toxicology GA BF83V UT WOS:A1996BF83V00051 PM 8794237 ER PT J AU Enomoto, K Furuya, K Moore, RC Yamagishi, S Oka, T Maeno, T AF Enomoto, K Furuya, K Moore, RC Yamagishi, S Oka, T Maeno, T TI Expression cloning and signal transduction pathway of P-2U receptor in mammary tumor cells SO BIOLOGICAL SIGNALS LA English DT Article DE ATP; UTP; P-2U receptor; inositol-1,4,5-trisphosphate; calcium; mammary cell ID GUANINE-NUCLEOTIDE-BINDING; HYBRID NG108-15 CELLS; EXTRACELLULAR ATP; PERTUSSIS TOXIN; INTRACELLULAR CALCIUM; ENDOTHELIAL-CELLS; EPITHELIAL-CELLS; HL60 CELLS; RELEASE; BRADYKININ AB Extracellularly applied ATP, UTP and UDP induce a transient increase in the intracellular Ca2+ concentration of mammary cells via a P-2U receptor. The P-2U receptor in the mammary tumor cell line MMT060562 was cloned and expressed in the human leukemia cell line K-562. The deduced amino acid sequence of the mammary tumor cell P-2U receptor was 98% homologous with that of mouse NG108-15 cells. It was a member of the superfamily of GTP-binding-protein-coupled receptors. ATP and UTP induced the increase in the intracellular concentrations of Ca2+ and inositol-1,4,5-trisphosphate in both mammary tumor cells and P-2U-receptor-expressed K562 cells. Dose-response curves on the production of inositol-1,4,5-trisphosphate and Ca2+ by ATP and UTP were consistently similar. Injection of GTP enhanced the ATP-induced outward current and injection of GTP gamma S induced a repetitive outward current. Both pertussis and cholera toxins did not affect ATP-induced calcium increase. It was suggested that the P-2U receptor coupled with pertussis- and cholera-toxin-insensitive GTP-binding proteins and activated phosphoinositide turnover. C1 NATL INST PHYSIOL SCI,DEPT CELL PHYSIOL,OKAZAKI,AICHI 444,JAPAN. NIH,MOLEC & CELL BIOL LAB,BETHESDA,MD. RP Enomoto, K (reprint author), SHIMANE MED UNIV,DEPT PHYSIOL,IZUMO,SHIMANE 693,JAPAN. NR 35 TC 10 Z9 11 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1016-0922 J9 BIOL SIGNAL JI Biol. Signals PD JAN-FEB PY 1996 VL 5 IS 1 BP 9 EP 21 PG 13 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA UK565 UT WOS:A1996UK56500002 PM 8739319 ER PT B AU Clore, GM Werner, MH Huth, JR Gronenborn, AM AF Clore, GM Werner, MH Huth, JR Gronenborn, AM BE Sarma, RH Sarma, MH TI Understanding SRY related 46X,Y sex reversal at the atomic level SO BIOLOGICAL STRUCTURE AND DYNAMICS, VOL 1 LA English DT Proceedings Paper CT 9th Conversation in the Discipline Biomolecular Stereodynamics CY JUN 20-24, 1995 CL SUNY ALBANY, ALBANY, NY SP SUNY Albany, Dept Chem, SUNY Albany, Inst Biomolec Stereodynam HO SUNY ALBANY C1 NIDDK,CHEM PHYS LAB,NATL INST HLTH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ADENINE PRESS PI SCHENECTADY PA 2066 CENTRAL AVE, SCHENECTADY, NY 12304 BN 0-940030-47-0 PY 1996 BP 35 EP & PG 7 WC Biochemistry & Molecular Biology; Biophysics; Spectroscopy SC Biochemistry & Molecular Biology; Biophysics; Spectroscopy GA BF89A UT WOS:A1996BF89A00004 ER PT B AU Vinson, C Olive, M Mikhailenko, I Krylov, D AF Vinson, C Olive, M Mikhailenko, I Krylov, D BE Sarma, RH Sarma, MH TI Stability and specificity of coiled coils: Extending the interface into the bZIP basic region SO BIOLOGICAL STRUCTURE AND DYNAMICS, VOL 1 LA English DT Proceedings Paper CT 9th Conversation in the Discipline Biomolecular Stereodynamics CY JUN 20-24, 1995 CL SUNY ALBANY, ALBANY, NY SP SUNY Albany, Dept Chem, SUNY Albany, Inst Biomolec Stereodynam HO SUNY ALBANY C1 NCI,BIOCHEM LAB,NATL INST HLTH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ADENINE PRESS PI SCHENECTADY PA 2066 CENTRAL AVE, SCHENECTADY, NY 12304 BN 0-940030-47-0 PY 1996 BP 225 EP & PG 10 WC Biochemistry & Molecular Biology; Biophysics; Spectroscopy SC Biochemistry & Molecular Biology; Biophysics; Spectroscopy GA BF89A UT WOS:A1996BF89A00019 ER PT S AU Kawai, N McCarron, RM Spatz, M AF Kawai, N McCarron, RM Spatz, M BE Couraud, PO Scherman, D TI Hypoxia augments Na+-K+-Cl- cotransport activity in cultured brain capillary endothelial cells of the rat SO BIOLOGY AND PHYSIOLOGY OF THE BLOOD-BRAIN BARRIER: TRANSPORT, CELLULAR INTERACTIONS, AND BRAIN PATHOLOGIES SE ADVANCES IN BEHAVIORAL BIOLOGY LA English DT Proceedings Paper CT Cerebral Vascular Biology Symposium CY JUL 10-12, 1995 CL PARIS, FRANCE SP CNRS, INSERM, French Minist Educ & Res, Soc Neurosci, European Concerted Action Biomed, Assoc Naturalia & Biol, Amersham, Becton Dickinson, Glaxo, Rhone Poulenc Rorer, Roussel, Sanofi AB The effect of hypoxia on K+ uptake activity in cultured rat brain capillary endothelial cells (RBEC) was investigated by using Rb-86(+) as a tracer for K+. Exposure of RBEC to hypoxia (95% N-2/5% CO2, 24 hr) reduced Na+,K+-ATPase activity by 39%, whereas it significantly increased Na+-K+-Cl- cotransport activity by 48%. Exposure of RBEC to oligomycin, a metabolic inhibitor, led to a complete inhibition of Na+,K+-ATPase and a coordinated increase of Na+-K+-Cl- cotransport activity up to 2-fold. Oligomycin also increased the rate of K+ efflux. The reduction of oligomycin-augmented Na+-K+-Cl- cotransport activity by protein-tyrosine kinase inhibitors (genistein, 50 mu M; herbimycin A, 10 mu M) and the ineffectiveness of inhibitors of either protein kinase C (bisindolylmaleimide, 500 nM) or protein kinase A (H8, 20 mu M) indicate the involvement of protein-tyrosine phosphorylation in this event. The data suggest that under hypoxic conditions when Na+,K+-ATPase activity is reduced, RBEC have the ability to increase K+ uptake through activation of Na+-K+-Cl- cotransport. RP Kawai, N (reprint author), NINCDS,STROKE BRANCH,NIH,BLDG 36,RM 4D04,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PLENUM PRESS DIV PLENUM PUBLISHING CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0099-9962 BN 0-306-45362-2 J9 ADV BEHAV BIOL PY 1996 VL 46 BP 235 EP 240 PG 6 WC Behavioral Sciences; Physiology SC Behavioral Sciences; Physiology GA BG97F UT WOS:A1996BG97F00039 ER PT S AU McCarron, RM Yoshihide, Y Spatz, M Hallenbeck, J AF McCarron, RM Yoshihide, Y Spatz, M Hallenbeck, J BE Couraud, PO Scherman, D TI Hypertensive versus normotensive monocyte adhesion to cultured cerebral microvascular endothelial cells SO BIOLOGY AND PHYSIOLOGY OF THE BLOOD-BRAIN BARRIER: TRANSPORT, CELLULAR INTERACTIONS, AND BRAIN PATHOLOGIES SE ADVANCES IN BEHAVIORAL BIOLOGY LA English DT Proceedings Paper CT Cerebral Vascular Biology Symposium CY JUL 10-12, 1995 CL PARIS, FRANCE SP CNRS, INSERM, French Minist Educ & Res, Soc Neurosci, European Concerted Action Biomed, Assoc Naturalia & Biol, Amersham, Becton Dickinson, Glaxo, Rhone Poulenc Rorer, Roussel, Sanofi AB Hypertension may predispose to the development of thrombotic vascular disease by promoting interactions between circulating blood monocytes (mo) and vascular endothelial cells (EC). The adherence of mo from spontaneously hypertensive (SHR), normotensive Wistar-Kyoto (WKY) and Sprague-Dawley (SD) rats to cultures of activated and untreated homologous cerebral microvascular EC was examined. There were no significant differences in the percent of monocytes from all three strains adhering to untreated EC. Mo binding was inhibited (approx. 50%) by antibodies against beta 2-integrin molecules (CD11a, CD11b, CD18) and intercellular adhesion molecule-1 (ICAM-1). Treatment of EC with LPS, IL-1 beta, TNF alpha or IFN gamma dose-dependently upregulated mo adhesion. The level of syngeneic and allogeneic mo adhesion to stimulated SHR EC was significantly more upregulated than was observed with identically treated WKY or SD EC (p < 0.001). Mo adhesion to stimulated EC was inhibited (10 - 20%) by antibodies to the beta 1-integrin, VLA-4 and antibodies to the beta 2-integrins and ICAM-1 (20 - 25%). These results demonstrated that treated SHR EC exhibited significantly higher adhesivity and suggest that hypertension may enhance responsiveness of endothelium to factors which promote mo adhesion. Subsequent mo interactions, via cytokines, may be important in the genesis of stroke. RP McCarron, RM (reprint author), NINCDS,STROKE BRANCH,NIH,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PLENUM PRESS DIV PLENUM PUBLISHING CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0099-9962 BN 0-306-45362-2 J9 ADV BEHAV BIOL PY 1996 VL 46 BP 299 EP 302 PG 4 WC Behavioral Sciences; Physiology SC Behavioral Sciences; Physiology GA BG97F UT WOS:A1996BG97F00048 ER PT S AU Ambs, S Forrester, K Lupold, SE Merriam, WG Geller, DA Billiar, TR Harris, CC AF Ambs, S Forrester, K Lupold, SE Merriam, WG Geller, DA Billiar, TR Harris, CC BE Moncada, S Stamler, J Gross, S Higgs, EA TI Regulation of human inducible NOS2 expression by the tumor suppressor gene p53 SO BIOLOGY OF NITRIC OXIDE, PT 5 SE PORTLAND PRESS PROCEEDINGS LA English DT Proceedings Paper CT 4th International Meeting on the Biology of Nitric Oxide CY SEP, 1995 CL AMELIA ISL, FL C1 NCI,HUMAN CARCINOGENESIS LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 1 PU PORTLAND PRESS LTD PI LONDON PA 59 PORTLAND PL, LONDON, ENGLAND W1N 3AJ SN 0966-4068 BN 1-85578-102-6 J9 PORTL PR P PY 1996 VL 10 BP 7 EP 7 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Chemistry, Medicinal; Pharmacology & Pharmacy; Physiology SC Biochemistry & Molecular Biology; Cell Biology; Pharmacology & Pharmacy; Physiology GA BE95M UT WOS:A1996BE95M00007 ER PT S AU Wink, DA Liebmann, J Pacelli, R Cook, JA DeLuca, AM Coffin, D DeGraff, W Gamson, J Krishna, MC Mitchell, JB AF Wink, DA Liebmann, J Pacelli, R Cook, JA DeLuca, AM Coffin, D DeGraff, W Gamson, J Krishna, MC Mitchell, JB BE Moncada, S Stamler, J Gross, S Higgs, EA TI Possible roles for NO donors in cancer treatment SO BIOLOGY OF NITRIC OXIDE, PT 5 SE PORTLAND PRESS PROCEEDINGS LA English DT Proceedings Paper CT 4th International Meeting on the Biology of Nitric Oxide CY SEP, 1995 CL AMELIA ISL, FL C1 NCI,RADIAT BIOL BRANCH,TUMOR BIOL SECT,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PORTLAND PRESS LTD PI LONDON PA 59 PORTLAND PL, LONDON, ENGLAND W1N 3AJ SN 0966-4068 BN 1-85578-102-6 J9 PORTL PR P PY 1996 VL 10 BP 39 EP 39 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Chemistry, Medicinal; Pharmacology & Pharmacy; Physiology SC Biochemistry & Molecular Biology; Cell Biology; Pharmacology & Pharmacy; Physiology GA BE95M UT WOS:A1996BE95M00039 ER PT S AU Witteveen, CFB Giovanelli, J Kaufman, S AF Witteveen, CFB Giovanelli, J Kaufman, S BE Moncada, S Stamler, J Gross, S Higgs, EA TI Nitric oxide synthase catalyzes the reduction of quinonoid dihydrobiopterin to tetrahydrobiopterin SO BIOLOGY OF NITRIC OXIDE, PT 5 SE PORTLAND PRESS PROCEEDINGS LA English DT Proceedings Paper CT 4th International Meeting on the Biology of Nitric Oxide CY SEP, 1995 CL AMELIA ISL, FL C1 NIMH,NEUROCHEM LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PORTLAND PRESS LTD PI LONDON PA 59 PORTLAND PL, LONDON, ENGLAND W1N 3AJ SN 0966-4068 BN 1-85578-102-6 J9 PORTL PR P PY 1996 VL 10 BP 81 EP 81 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Chemistry, Medicinal; Pharmacology & Pharmacy; Physiology SC Biochemistry & Molecular Biology; Cell Biology; Pharmacology & Pharmacy; Physiology GA BE95M UT WOS:A1996BE95M00080 ER PT S AU Rafferty, S Domachowske, J Malech, H AF Rafferty, S Domachowske, J Malech, H BE Moncada, S Stamler, J Gross, S Higgs, EA TI Effects of nitric oxide production on hemoglobin expression in the erythroleukemic cell line K562 SO BIOLOGY OF NITRIC OXIDE, PT 5 SE PORTLAND PRESS PROCEEDINGS LA English DT Proceedings Paper CT 4th International Meeting on the Biology of Nitric Oxide CY SEP, 1995 CL AMELIA ISL, FL C1 NIAID,HOST DEF LAB,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PORTLAND PRESS LTD PI LONDON PA 59 PORTLAND PL, LONDON, ENGLAND W1N 3AJ SN 0966-4068 BN 1-85578-102-6 J9 PORTL PR P PY 1996 VL 10 BP 124 EP 124 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Chemistry, Medicinal; Pharmacology & Pharmacy; Physiology SC Biochemistry & Molecular Biology; Cell Biology; Pharmacology & Pharmacy; Physiology GA BE95M UT WOS:A1996BE95M00123 ER PT S AU Keefer, LK Daniel, JS Pulfer, S Hanson, SR Saavedra, JE Billiar, TR Roller, PP AF Keefer, LK Daniel, JS Pulfer, S Hanson, SR Saavedra, JE Billiar, TR Roller, PP BE Moncada, S Stamler, J Gross, S Higgs, EA TI Tissue-selective delivery of nitric oxide using diazeniumdiolates (formerly ''NONOates'') SO BIOLOGY OF NITRIC OXIDE, PT 5 SE PORTLAND PRESS PROCEEDINGS LA English DT Proceedings Paper CT 4th International Meeting on the Biology of Nitric Oxide CY SEP, 1995 CL AMELIA ISL, FL C1 NCI,CHEM SECT,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21702. RI Keefer, Larry/N-3247-2014 OI Keefer, Larry/0000-0001-7489-9555 NR 0 TC 2 Z9 2 U1 0 U2 1 PU PORTLAND PRESS LTD PI LONDON PA 59 PORTLAND PL, LONDON, ENGLAND W1N 3AJ SN 0966-4068 BN 1-85578-102-6 J9 PORTL PR P PY 1996 VL 10 BP 335 EP 335 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Chemistry, Medicinal; Pharmacology & Pharmacy; Physiology SC Biochemistry & Molecular Biology; Cell Biology; Pharmacology & Pharmacy; Physiology GA BE95M UT WOS:A1996BE95M00330 ER PT J AU Bagavandoss, P StetlerStevenson, W AF Bagavandoss, P StetlerStevenson, W TI Immunofluorescent localization of gelatinases and tissue inhibitor of metalloproteinase-1 in the rat ovary. SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract C1 KENT STATE UNIV,DEPT BIOL SCI,CANTON,OH. NCI,PATHOL LAB,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 1996 VL 54 SU 1 BP 13 EP 13 PG 1 WC Reproductive Biology SC Reproductive Biology GA VF099 UT WOS:A1996VF09900019 ER PT J AU Roberts, RL Wolf, KN Wildt, DE Kleiman, DG Rall, WF AF Roberts, RL Wolf, KN Wildt, DE Kleiman, DG Rall, WF TI Impact of mating duration on ovulation and embryo development in the prairie vole (Microtus ochrogaster). SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract C1 SMITHSONIAN INST,NATL ZOOL PK,DEPT ZOOL RES,WASHINGTON,DC 20008. SMITHSONIAN INST,NATL ZOOL PK,DEPT REPROD PHYSIOL,WASHINGTON,DC 20008. NIH,NATL CTR RES RESOURCES,VET RESOURCES BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 3 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 1996 VL 54 SU 1 BP 47 EP 47 PG 1 WC Reproductive Biology SC Reproductive Biology GA VF099 UT WOS:A1996VF09900052 ER PT J AU Tilly, JL Flaws, JA DeSanti, AM Hughes, FM Tilly, KI Maravei, DV Trbovich, AM Cidlowski, JA Hirshfield, AN AF Tilly, JL Flaws, JA DeSanti, AM Hughes, FM Tilly, KI Maravei, DV Trbovich, AM Cidlowski, JA Hirshfield, AN TI Biochemical and morphological investigation of apoptosis and atresia in rat ovarian antral follicles incubated in vitro. SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT OBSTET & GYNECOL,VINCENT CTR REPROD BIOL,BOSTON,MA. UNIV MARYLAND,SCH MED,DEPT ANAT,BALTIMORE,MD 21201. NIEHS,LAB INTEGRAT BIOL,RES TRIANGLE PK,NC 27709. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 1996 VL 54 SU 1 BP 124 EP 124 PG 1 WC Reproductive Biology SC Reproductive Biology GA VF099 UT WOS:A1996VF09900129 ER PT J AU Sakata, H Izumi, SI Mah, KA Slayden, OD Rubin, J Brenner, RM AF Sakata, H Izumi, SI Mah, KA Slayden, OD Rubin, J Brenner, RM TI Keratinocyte growth factor (KGF) inhibits progesterone-induced apoptosis in the mouse uterine luminal epithelium. SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract C1 NCI,CELLULAR & MOL BIOL LAB,BETHESDA,MD 20892. NAGASAKI UNIV,SCH MED,DEPT ANAT 3,NAGASAKI 852,JAPAN. OREGON REG PRIMATE RES CTR,DIV REPROD SCI,BEAVERTON,OR 97006. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 1996 VL 54 SU 1 BP 127 EP 127 PG 1 WC Reproductive Biology SC Reproductive Biology GA VF099 UT WOS:A1996VF09900131 ER PT J AU Fields, PA Lee, VH Jetten, AM Chang, SMT Fields, MJ AF Fields, PA Lee, VH Jetten, AM Chang, SMT Fields, MJ TI Rabbit placental relaxin: Amino acid sequence of the B-chain and in situ hybridization in syncytiotrophoblast. SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract C1 UNIV S ALABAMA,MOBILE,AL 36688. NIEHS,RES TRIANGLE PK,NC 27709. TEXAS TECH UNIV,LUBBOCK,TX 79409. UNIV FLORIDA,GAINESVILLE,FL 32611. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 1996 VL 54 SU 1 BP 268 EP 268 PG 1 WC Reproductive Biology SC Reproductive Biology GA VF099 UT WOS:A1996VF09900270 ER PT J AU HildPetito, S Blye, RP Larner, JM Reel, JR AF HildPetito, S Blye, RP Larner, JM Reel, JR TI Biological activity profile of the antiprogestin, CDB 2914 (17 alpha-acetoxy-11 beta-[4-N,N-dimethylaminophenyl]-19 norpregna-4,9-diene-3,20-dione). SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract C1 BIOQUAL INC,ROCKVILLE,MD. NICHHD,CONTRACEPT DEV BRANCH,ROCKVILLE,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 1996 VL 54 SU 1 BP 310 EP 310 PG 1 WC Reproductive Biology SC Reproductive Biology GA VF099 UT WOS:A1996VF09900312 ER PT B AU Kleinman, JE Nawroz, S AF Kleinman, JE Nawroz, S BE Watson, SJ TI Schizophrenia: Postmortem studies SO BIOLOGY OF SCHIZOPHRENIA AND AFFECTIVE DISEASE LA English DT Proceedings Paper CT 73rd Meeting of the Association-for-Research-in-Nervous-and-Mental-Disease on Biology of Schizophrenia and Affective Disease CY DEC, 1993 CL NEW YORK, NY SP Assoc Res Nervous & Mental Dis C1 NIMH,CTR NEUROSCI,CLIN BRAIN DISORDERS BRANCH,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 BN 0-88048-746-1 PY 1996 BP 223 EP 237 PG 15 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA BG03A UT WOS:A1996BG03A00009 ER PT B AU VanHorn, JD Berman, KF Weinberger, DR AF VanHorn, JD Berman, KF Weinberger, DR BE Watson, SJ TI Pathophysiology of schizophrenia: Insights from neuroimaging SO BIOLOGY OF SCHIZOPHRENIA AND AFFECTIVE DISEASE LA English DT Proceedings Paper CT 73rd Meeting of the Association-for-Research-in-Nervous-and-Mental-Disease on Biology of Schizophrenia and Affective Disease CY DEC, 1993 CL NEW YORK, NY SP Assoc Res Nervous & Mental Dis C1 NIMH,INTRAMURAL RES PROGRAM,NEUROSCI CTR ST ELIZABETHS,BETHESDA,MD. NR 0 TC 3 Z9 3 U1 0 U2 0 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 BN 0-88048-746-1 PY 1996 BP 393 EP 419 PG 27 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA BG03A UT WOS:A1996BG03A00014 ER PT J AU Lujan, HD Mowatt, MR Conrad, JT Nash, TE AF Lujan, HD Mowatt, MR Conrad, JT Nash, TE TI Increased expression of the molecular chaperone BiP/GRP78 during the differentiation of a primitive eukaryote SO BIOLOGY OF THE CELL LA English DT Article DE endoplasmic reticulum; eukaryotic evolution; giardiasis; stress response; Golgi apparatus ID GLUCOSE-REGULATED PROTEIN; HEAT-SHOCK PROTEINS; CHAIN BINDING-PROTEIN; GIARDIA-LAMBLIA; ENDOPLASMIC-RETICULUM; SECRETORY PATHWAY; CALCIUM IONOPHORE; MAMMALIAN-CELLS; GRP78 PROMOTER; ER AB Giardia lamblia, a major cause of intestinal disease worldwide, is a parasitic protozoan that represents the earliest branch of the eukaryotic lineage. Trophozoites, which possess two nuclei but lack mitochondria, peroxisomes and a typical Golgi apparatus, colonize the small intestine of the vertebrate host where they may differentiate into infective cysts. Encystation is a regulated process characterized by the biosynthesis, secretion and formation of a protective extracellular cyst wall. In previous studies, we demonstrated the biogenesis of the Golgi apparatus during encystation and identified two leucine-rich proteins (CWPs), which localize within encystation-specific secretory granules before their incorporation into the cyst wall. Here, we used immunological, biochemical and molecular biological approaches to analyze the expression of BiP/GRP78, an endoplasmic reticulum (ER)-resident chaperone, during the Giardia life cycle. A monoclonal antibody specific for Giardia BiP permitted the visualization of the ER of this protozoan and showed that BiP expression increased simultaneously with the increased expression of CWPs during encystation. However, in contrast to the 140-fold increase in levels of CWP transcripts, the steady-state level of BiP mRNA did not increase during encystation. Furthermore, potent inducers of BiP expression in higher eukaryotic cells, including agents that perturb the ER environment, did not affect BiP expression in Giardia. These results, when considered together with the profound changes that occur in the secretory pathway during Giardia encystation, indicate an important role for this molecular chaperone during the differentiation of this primitive eukaryote. RP Lujan, HD (reprint author), NIAID,PARASIT DIS LAB,NATL INST HLTH,BLDG 4,ROOM 126,BETHESDA,MD 20892, USA. NR 55 TC 44 Z9 44 U1 0 U2 2 PU EDITIONS SCIENTIFIQUES ELSEVIER PI PARIS CEDEX 15 PA 141 RUE JAVEL, 75747 PARIS CEDEX 15, FRANCE SN 0248-4900 J9 BIOL CELL JI Biol. Cell PY 1996 VL 86 IS 1 BP 11 EP 18 DI 10.1016/0248-4900(96)89519-0 PG 8 WC Cell Biology SC Cell Biology GA UY392 UT WOS:A1996UY39200002 PM 8688827 ER PT J AU Wendler, D AF Wendler, D TI Innateness as an explanatory concept SO BIOLOGY & PHILOSOPHY LA English DT Article DE innateness; explanation AB Although many of the issues surrounding innateness have received a good deal of attention lately, the basic concept of token innateness has been largely ignored. In the present paper, I try to correct this imbalance by offering an account of the innateness of token traits. I begin by explaining Stephen Stich's account of token innateness and offering a counterexample to that account. I then clarify why the contemporary biological approaches to innateness will not be able to resolve the problems that beset Stich's account. From there, I develop an alternative understanding of the innateness of token traits, what I call a 'causal/explanatory' account. The argument to be made is that token innateness is both a causal, and an explanatory, concept. After clarifying this understanding of innateness, and showing how it handles several counterexamples to other accounts,I end with some comments on what the causal/explanatory account suggests for our understanding of innateness in general. RP Wendler, D (reprint author), NIH,BIOETH PROGRAM,BETHESDA,MD 20892, USA. NR 12 TC 2 Z9 2 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0169-3867 J9 BIOL PHILOS JI Biol. Philos. PD JAN PY 1996 VL 11 IS 1 BP 89 EP 116 DI 10.1007/BF00127473 PG 28 WC History & Philosophy Of Science SC History & Philosophy of Science GA UG404 UT WOS:A1996UG40400006 ER PT S AU Kirk, KL Filler, R AF Kirk, KL Filler, R BE Ojima, I McCarthy, JR Welch, JT TI Recent advances in the biomedicinal chemistry of fluorine-containing compounds SO BIOMEDICAL FRONTIERS OF FLUORINE CHEMISTRY SE ACS SYMPOSIUM SERIES LA English DT Article; Proceedings Paper CT Symposium on Fluro-Amino Acids and Peptides in Medicinal Chemistry / Symposium on Fluorine in Drug Design, at the 210 ACS National Meeting CY 1995 CL CHICAGO, IL SP Amer Chem Soc, Div Fluorine Chem, Amer Chem Soc, Div Medicinal Chem ID HUMAN-LEUKOCYTE ELASTASE; GLCNAC ENOLPYRUVYL TRANSFERASE; HUMAN NEUTROPHIL ELASTASE; SOLID-PHASE SYNTHESIS; TRIFLUOROMETHYL KETONES; NONPEPTIDIC INHIBITORS; PROTEASE INHIBITORS; O-PHOSPHOTYROSINE; RENIN INHIBITORS; HIV-1 PROTEASE AB Recent developments in biomedicinal applications of fluorine-containing compounds are reviewed. Biochemical and mechanistic aspects of this field are discussed first. The development of enzyme inhibitors and other pharmacological tools and medicinal agents is considered from the point of view of how the special properties of fluorine can be exploited in analogue design. In the second part of this review, an array of recent medicinal candidates is described, encompassing drugs that show promise for the treatment of a variety of diseases. In both sections, the emphasis has been on material published within the past five years. C1 IIT,DEPT BIOL CHEM & PHYS SCI,CHICAGO,IL 60616. RP Kirk, KL (reprint author), NIDDK,NIH,BIOORGAN CHEM LAB,BLDG 8A,ROOM B1A-02,BETHESDA,MD 20892, USA. NR 77 TC 32 Z9 32 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 SIXTEENTH ST NW, WASHINGTON, DC 20036 SN 0097-6156 BN 0-8412-3442-6 J9 ACS SYM SER PY 1996 VL 639 BP 1 EP 24 PG 24 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Chemistry, Inorganic & Nuclear SC Pharmacology & Pharmacy; Chemistry GA BG35X UT WOS:A1996BG35X00001 ER PT S AU Kirk, KL Nie, JY AF Kirk, KL Nie, JY BE Ojima, I McCarthy, JR Welch, JT TI Fluorinated amino acids in nerve systems SO BIOMEDICAL FRONTIERS OF FLUORINE CHEMISTRY SE ACS SYMPOSIUM SERIES LA English DT Article; Proceedings Paper CT Symposium on Fluro-Amino Acids and Peptides in Medicinal Chemistry / Symposium on Fluorine in Drug Design, at the 210 ACS National Meeting CY 1995 CL CHICAGO, IL SP Amer Chem Soc, Div Fluorine Chem, Amer Chem Soc, Div Medicinal Chem ID ORTHOSTATIC HYPOTENSION; O-METHYLATION; DOPAMINE; DL-THREO-3,4-DIHYDROXYPHENYLSERINE; NOREPINEPHRINES; SUBSTITUTION; SITE AB Fluorinated analogues of amino acid precursors of amine neurotransmitters have had many applications related to biochemistry and neuropharmacology. We have studied the effects of ring-fluorination on the biological properties of a series of aromatic (tyrosine, dihydroxyphenylalanine, dihydroxyphenylserine) and heteroaromatic amino acids (histidine) that function as precursors of amine neurotransmitters. In addition, we have synthesized fluorinated neurotransmitter amines (tyramine, dopamine, norepinephrine, epineprhine, serotonin, histamine) and have examined the effects of fluorine on such properties as receptor interactions and interaction with metabolic enzymes. Studies with monofluorinated analogues have now been extended to di- and trifluoro-substituted analogues. RP Kirk, KL (reprint author), NIDDK,NIH,BIOORGAN CHEM LAB,BLDG 8A,ROOM B1A-02,BETHESDA,MD 20892, USA. NR 40 TC 3 Z9 3 U1 1 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 SIXTEENTH ST NW, WASHINGTON, DC 20036 SN 0097-6156 BN 0-8412-3442-6 J9 ACS SYM SER PY 1996 VL 639 BP 312 EP 327 PG 16 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Chemistry, Inorganic & Nuclear SC Pharmacology & Pharmacy; Chemistry GA BG35X UT WOS:A1996BG35X00022 ER PT J AU Haverkos, HW Drotman, DP AF Haverkos, HW Drotman, DP TI NIDA technical review: Nitrite inhalants SO BIOMEDICINE & PHARMACOTHERAPY LA English DT Review DE AIDS; HIV infection; immunosuppression; Kaposi's sarcoma; nitrite inhalants; sexual behavior ID MULTICENTER AIDS COHORT; ISOBUTYL NITRITE; KAPOSIS-SARCOMA; HOMOSEXUAL MEN; RISK; INFECTION AB Nitrite inhalants are commonly abused substances in the US and Europe. ''Nitrite inhalants and AIDS'' was a popular topic in the early 1980s when the cause of AIDS was not known. With the discovery of HIV, concern about nitrite use wained. However, nitrite inhalant use is associated with behavioral relapse and HIV transmission among gay men, with decreased lymphocyte counts and natural killer cell activity in laboratory studies, and remains a candidate ''cofactor'' in the pathogenesis of AIDS-related Karposi sarcoma. Discouraging nitrite use continues to be a worthwhile public health goal. Participants recommend specific research efforts. C1 CTR DIS CONTROL & PREVENT,CTR INFECT DIS,ATLANTA,GA. RP Haverkos, HW (reprint author), NIDA,NIH,OFF AIDS,ROOM 9A-30,5600 FISHERS LANE,ROCKVILLE,MD 20857, USA. NR 18 TC 6 Z9 6 U1 0 U2 0 PU EDITIONS SCIENTIFIQUES ELSEVIER PI PARIS CEDEX 15 PA 141 RUE JAVEL, 75747 PARIS CEDEX 15, FRANCE SN 0753-3322 J9 BIOMED PHARMACOTHER JI Biomed. Pharmacother. PY 1996 VL 50 IS 5 BP 228 EP 230 DI 10.1016/0753-3322(96)87663-3 PG 3 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA VF942 UT WOS:A1996VF94200005 PM 8949404 ER PT J AU Haverkos, HW AF Haverkos, HW TI Is Kaposi's sarcoma caused by new herpesvirus? SO BIOMEDICINE & PHARMACOTHERAPY LA English DT Letter ID DNA-SEQUENCES; AIDS; NITRITE; EPIDEMIOLOGY RP Haverkos, HW (reprint author), NIDA,NIH,ROOM 9A,5600 FISHERS LANE,ROCKVILLE,MD 20857, USA. NR 15 TC 6 Z9 6 U1 0 U2 0 PU EDITIONS SCIENTIFIQUES ELSEVIER PI PARIS CEDEX 15 PA 141 RUE JAVEL, 75747 PARIS CEDEX 15, FRANCE SN 0753-3322 J9 BIOMED PHARMACOTHER JI Biomed. Pharmacother. PY 1996 VL 50 IS 6-7 BP 318 EP 319 DI 10.1016/0753-3322(96)84834-7 PG 2 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA VN338 UT WOS:A1996VN33800016 PM 8952876 ER PT J AU Nam, JM AF Nam, JM TI Detection of cyclic trends in incidence data using the efficiency score method SO BIOMETRICAL JOURNAL LA English DT Article DE cyclic trends; score test; asymptotic power; sample size AB In studies involving a cyclic regularity, researchers usually have a good working knowledge regarding the peak time in the cycle. Capitalizing on this information we derive the asymptotically uniformly most powerful unbiased test for detecting a cyclic trend using the likelihood score, and present the asymptotic power function of the test and the approximate formula for sample size. Numerical studies demonstrate great advantages of the proposed test over the standard test in terms of power and sample size. Asymptotic power of the score test is satisfactorily close to actual power We also generalize this method so that it is applicable for incidence data from unequally spaced intervals or risk populations of unequal size. C1 NCI,BIOSTAT BRANCH,BETHESDA,MD 20892. NR 17 TC 0 Z9 0 U1 0 U2 0 PU AKADEMIE VERLAG GMBH PI BERLIN PA MUHLENSTRASSE 33-34, D-13187 BERLIN, GERMANY SN 0323-3847 J9 BIOMETRICAL J JI Biom. J. PY 1996 VL 38 IS 6 BP 661 EP 668 DI 10.1002/bimj.4710380604 PG 8 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA VV953 UT WOS:A1996VV95300003 ER PT J AU Rengarajan, K deSmet, MD Wiggert, BB AF Rengarajan, K deSmet, MD Wiggert, BB TI Removal of albumin from multiple human serum samples SO BIOTECHNIQUES LA English DT Article RP Rengarajan, K (reprint author), NEI,RETINAL CELL & MOLEC BIOL LAB,BLDG 6,RM 338,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. OI de Smet, Marc/0000-0002-9217-5603 NR 4 TC 17 Z9 19 U1 0 U2 1 PU EATON PUBLISHING CO PI NATICK PA 154 E. CENTRAL ST, NATICK, MA 01760 SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD JAN PY 1996 VL 20 IS 1 BP 30 EP & PG 2 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TP294 UT WOS:A1996TP29400005 PM 8770400 ER PT B AU Wlodawer, A AF Wlodawer, A BE Rudolph, FB McIntire, LV TI Structural biology as it applies to biotechnology SO BIOTECHNOLOGY: SCIENCE, ENGINEERING, AND ETHICAL CHALLENGES FOR THE TWENTY-FIRST CENTURY LA English DT Proceedings Paper CT 2nd DeLange Conference on Biotechnology - Science, Engineering, and Ethical Challenges for the 21st-Century CY FEB 28-MAR 02, 1994 CL RICE UNIV, HOUSTON, TX SP Rice Univ, Inst Biosci & Bioengn HO RICE UNIV C1 NCI,FREDERICK CANC RES & DEV CTR,MACROMOL STRUCT LAB,FREDERICK,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOSEPH HENRY PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 BN 0-309-05282-3 PY 1996 BP 28 EP 42 PG 15 WC Biotechnology & Applied Microbiology; Health Policy & Services; Multidisciplinary Sciences SC Biotechnology & Applied Microbiology; Health Care Sciences & Services; Science & Technology - Other Topics GA BF44C UT WOS:A1996BF44C00003 ER PT J AU Levine, PH AF Levine, PH TI The use of transfer factors in chronic fatigue syndrome: Prospects and problems SO BIOTHERAPY LA English DT Article; Proceedings Paper CT Xth International Symposium on Transfer Factor - Transfer Factor in the Era of AIDS CY JUN 22-24, 1995 CL BOLOGNA, ITALY DE chronic fatigue syndrome; herpes viruses; transfer factor ID EPSTEIN-BARR-VIRUS; BURKITTS-LYMPHOMA; INFECTION; ILLNESS; PERSISTENT; RELAPSE AB Chronic fatigue syndrome (CFS) is a heterogeneous disorder characterized by severe prolonged unexplained fatigue and a variety of associated symptoms such as arthralgias, myalgias, cognitive dysfunction, and severe sleep disturbances. Many patients initially present with an acute onset of apparent infectious origin with either an upper respiratory or gastrointestinal illness, fever, chills, tender lymphadenopathy, and malaise suggestive of a flu-like illness. In some cases, specific viral infections can be identified at the outset, particularly herpes viruses such as Epstein-Barr virus (EBV), human herpes virus-6 (HHV-6), and cytomegalovirus (CMV). Transfer factors (TF) with specific activity against these herpes viruses has been documented. With some studies suggesting that persistent viral activity may play a role in perpetuation of CFS symptoms, there appears to be a rationale for the use of TF in patients with CFS and recent reports have suggested that transfer factor may-play a beneficial role in this disorder. This report focuses on the heterogeneity of CFS, the necessity for randomized coded studies, the importance of patient selection and sub-classification in clinical trials, and the need to utilize specific end-points for determining efficacy of treatment. C1 GEORGE WASHINGTON CANC CTR,WASHINGTON,DC. RP Levine, PH (reprint author), NCI,VIRAL EPIDEMIOL BRANCH,EPN 434,BETHESDA,MD 20892, USA. NR 22 TC 0 Z9 0 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0921-299X J9 BIOTHERAPY JI Biotherapy PY 1996 VL 9 IS 1-3 BP 77 EP 79 DI 10.1007/BF02628661 PG 3 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA WB046 UT WOS:A1996WB04600014 PM 8993762 ER PT J AU Ablashi, DV Levine, PH DeVinci, C Whitman, JE Pizza, G Viza, D AF Ablashi, DV Levine, PH DeVinci, C Whitman, JE Pizza, G Viza, D TI Use of anti HHV-6 transfer factor for the treatment of two patients with chronic fatigue syndrome (CFS). Two case reports SO BIOTHERAPY LA English DT Article; Proceedings Paper CT Xth International Symposium on Transfer Factor - Transfer Factor in the Era of AIDS CY JUN 22-24, 1995 CL BOLOGNA, ITALY DE chronic fatigue syndrome; human herpes virus type 6; transfer factor ID HUMAN HERPESVIRUS-6; IN-VITRO; INFECTION; VIRUS; DISORDERS AB Specific Human Herpes virus-6 (HHV-6) transfer factor (TF) preparation, administered to two chronic fatigue syndrome patients, inhibited the HHV-6 infection. Prior to treatment, both patients exhibited an activated HHV-6 infection. TF treatment significantly improved the clinical manifestations of CFS in one patient who resumed normal duties within weeks, whereas no clinical improvement was observed in the second patient. It is concluded that HHV-6 specific TF may be of significant value in controlling HHV-6 infection and related illnesses. C1 GEORGETOWN UNIV,SCH MED,DEPT MICROBIOL & IMMUNOL,WASHINGTON,DC 20007. NCI,VIRAL EPIDEMIOL BRANCH,ROCKVILLE,MD 20892. S ORSOLA M MALPIGHI HOSP,DIV UROL 1,IMMUNOTHERAPY UNIT,BOLOGNA,ITALY. FAC MED ST PERES,IMMUNOBIOL LAB,CNRS,URA 1294,PARIS,FRANCE. RP Ablashi, DV (reprint author), ADV BIOTECHNOL INC,9108 GUILFORD RD,COLUMBIA,MD 21046, USA. NR 22 TC 4 Z9 5 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0921-299X J9 BIOTHERAPY JI Biotherapy PY 1996 VL 9 IS 1-3 BP 81 EP 86 DI 10.1007/BF02628662 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA WB046 UT WOS:A1996WB04600015 PM 8993763 ER PT J AU Prasad, U binJalaludin, MA Rajadurai, P Pizza, G DeVinci, C Viza, D Levine, PH AF Prasad, U binJalaludin, MA Rajadurai, P Pizza, G DeVinci, C Viza, D Levine, PH TI Transfer factor with anti-EBV activity as an adjuvant therapy for nasopharyngeal carcinoma: A pilot study SO BIOTHERAPY LA English DT Article; Proceedings Paper CT Xth International Symposium on Transfer Factor - Transfer Factor in the Era of AIDS CY JUN 22-24, 1995 CL BOLOGNA, ITALY DE cell-mediated immunity; Epstein-Barr virus; nasopharyngeal carcinoma; transfer factor ID VIRUS; INFECTIONS AB Overall survival of nasopharyngeal carcinoma (NPC) at UICC stage IV still remains unsatisfactory even with combination chemotherapy (CT) and radio-therapy (RT). In view of the association of reactivation of Epstein-Barr virus (EBV) with the development and recurrence of NPC, immunotherapy in the form of transfer factor (TF) with specific activity against EBV (TF-BI) was suggested as an adjuvant to a combination of CT and RT in order to improve survival. In the present study, 6 UICC Stage IV patients received TF-B1 and another 6 patients matched for disease stage were given TF prepared from peripheral blood leucocytes (TF-PBL). Results were compared with another 18 patients matched by age, sex, and stage of disease who received standard therapy without TF during the same period (C group). After a median follow up of 47.5 months, the survival for the TF-B1 group was found to be significantly better (P=<0.05) than the PBL and C group. While the 8 patients with distant metastasis (DM), not treated with TF-B1 (6 in the control and 2 in the PBL group), died due to progressive disease (average survival being 14.3 months), both patients with DM in the TF-B1 group had complete remission: one died of tuberculosis after surviving for 3.5 years and another is still alive, disease free, after 4.2 years. Although the series involved a small number of cases, the apparent effect of adjuvant immunotherapy in the form of TF with anti-EBV activity is of considerable interest. C1 S ORSOLA M MALPIGHI HOSP,BOLOGNA,ITALY. FAC MED ST PERES,CNRS,URA 1294,IMMUNOBIOL LAB,PARIS,FRANCE. NIH,BETHESDA,MD 20892. GEORGE WASHINGTON UNIV,CTR CANC,WASHINGTON,DC. RP Prasad, U (reprint author), UNIV MALAYA,FAC MED,DEPT OTORHINOLARYNGOL,PANTAI VALLEY,KUALA LUMPUR 59100,MALAYSIA. NR 19 TC 4 Z9 7 U1 1 U2 2 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0921-299X J9 BIOTHERAPY JI Biotherapy PY 1996 VL 9 IS 1-3 BP 109 EP 115 DI 10.1007/BF02628667 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA WB046 UT WOS:A1996WB04600020 PM 8993768 ER PT J AU Usui, N Matsushima, K Pilaro, AM Longo, DL Wiltrout, RH AF Usui, N Matsushima, K Pilaro, AM Longo, DL Wiltrout, RH TI Antitumor effects of human recombinant interleukin-1 alpha and etoposide against human tumor cells: Mechanism for synergism in vitro and activity in vivo SO BIOTHERAPY LA English DT Article DE interleukin 1 alpha; etoposide (VP-16); interleukin-1 receptor antagonist; synergistic antitumor effects ID HUMAN-MELANOMA CELLS; MANGANESE SUPEROXIDE-DISMUTASE; RECEPTOR ANTAGONIST; NECROSIS-FACTOR; TOPOISOMERASE-II; ANTICANCER DRUG; IL-1 RECEPTOR; DNA; EXPRESSION; VP-16-213 AB Recombinant human interleukin 1 alpha (rhIL-1 alpha) and etoposide (VP-16) synergize for direct growth inhibition of several human tumor cell lines in vitro. Our previous studies demonstrated that VP-16 increased the number of membrane-associated IL-1 receptors (IL-1Rs) and also enhanced the internalization of receptor-bound rhIL-1 alpha. The purposes of this study were to test our hypothess that these events were critical to the synergy between rhIL-1 alpha and VP-16, to determine whether rhIL-1 alpha and VP-16 synergize to increase superoxide (SO) anion radical production in vitro since SO anion has been implicated in the toxic effects of IL-1, and to investigate the antitumor efficacy of the combination against tumors in vivo. A375/C6 melanoma cells and OVCAR-3 ovarian carcinoma cells were tested with IL-1 receptor antagonist (IL-1ra) before exposure to rhIL-1 alpha, VP-16 and rhIL-1 alpha plus VP-16. The synergistic or antagonistic effects were assessed by MTT assay. SO production was measured by reduction of cytochrome C. Athymic female mice bearing the A375/C6 melanoma were treated by rhIL-1 alpha, VP-16, and rhIL-1 alpha+VP-16. The antitumor effects were evaluated by quantitating tumor growth and survival time. Pretreatment with the IL-1ra abrogated the synergistic effects of rhIL-1 alpha and VP-16. The production of SO radical by A375/C6 cells was increased 2.5 fold by the combination of rhIL-1 alpha and VP-16, and the addition of exogenous SOD blocked the synergy between rhIL-1 alpha and VP-16. However, when A375/SOD15 cells which over-expressed manganese superoxide dismutase (MnSOD) after MnSOD cDNA transfection were exposed to rhIL-1 alpha and VP-16, in vitro antagonism was observed. In vivo studies demonstrated that the combination of rhIL-1 alpha and VP-16 delayed tumor growth better than either agent alone, although long-term survival was not improved because of substantial toxicity. Our results suggest that the synergistic antitumor effects of IL-1 alpha and VP-16 may be due to IL-1R modulation and increased internalization of IL-1-IL-1R complex by VP-16 treatment, as well as to a subsequent increase in SO anion radical production from the tumor cells exposed to both drugs. Thus, the combination of IL-1 alpha and VP-16 might prove useful for the treatment of malignant disease in vivo, if the increased toxicity can be reduced or managed. C1 NCI,EXPT IMMUNOL LAB,DIV CANC TREATMENT,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. NCI,BIOL RESPONSE MODIFIERS PROGRAM,DIV CANC TREATMENT,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. KANAZAWA UNIV,CANC RES INST,DEPT PHARMACOL,KANAZAWA,ISHIKAWA 920,JAPAN. NR 41 TC 5 Z9 5 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0921-299X J9 BIOTHERAPY JI Biotherapy PY 1996 VL 9 IS 4 BP 199 EP 208 DI 10.1007/BF02620733 PG 10 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA WC522 UT WOS:A1996WC52200002 PM 9012539 ER PT J AU Samuel, CE Ozato, K AF Samuel, CE Ozato, K TI Induction of interferons and interferon-induced genes SO BIOTHERAPY LA English DT Article C1 NICHHD,NIH,LAB MOL GROWTH REGULAT,BETHESDA,MD 20892. RP Samuel, CE (reprint author), UNIV CALIF SANTA BARBARA,DEPT BIOL SCI,GRAD PROGRAM BIOCHEM & MOL BIOL,SANTA BARBARA,CA 93106, USA. NR 29 TC 4 Z9 4 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0921-299X J9 BIOTHERAPY JI Biotherapy PY 1996 VL 8 IS 3-4 BP 183 EP 187 DI 10.1007/BF01877203 PG 5 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA UV952 UT WOS:A1996UV95200006 PM 8962798 ER PT J AU Sokolic, RA Sekhsaria, S Sugimoto, Y WhitingTheobald, N Linton, GF Li, F Gottesman, MM Malech, HL AF Sokolic, RA Sekhsaria, S Sugimoto, Y WhitingTheobald, N Linton, GF Li, F Gottesman, MM Malech, HL TI A bicistronic retrovirus vector containing a picornavirus internal ribosome entry site allows for correction of X-linked CGD by selection for MDR1 expression SO BLOOD LA English DT Article ID CHRONIC GRANULOMATOUS-DISEASE; CAP-INDEPENDENT TRANSLATION; MULTIDRUG-RESISTANCE GENE; P-GLYCOPROTEIN; ENCEPHALOMYOCARDITIS VIRUS; BONE-MARROW; SUPEROXIDE GENERATION; RESPIRATORY BURST; TRANSGENIC MICE; MESSENGER-RNA AB Chronic granulomatous disease (CGD) is an inherited hematologic disorder involving failure of phagocytic cell oxidase to produce superoxide (O-2(-.)), resulting in recurrent infections. The success of retrovirus gene therapy for hematopoietic diseases will be limited both by the efficiency of ex vivo transduction of target cells and by the ability of corrected cells to replace uncorrected cells in vivo. Using MFG-based retrovirus vectors containing oxidase genes, we have previously demonstrated in vitro correction of CGD, but transduction rates were low. In the present study we explore a strategy for providing a selective growth advantage to transduced cells, while retaining the single promoter feature of MFG responsible for high virus titer and enhanced protein production. We constructed a bicistronic retrovirus producing a single mRNA encoding both the therapeutic gene for the X-linked form of CGD (X-CGD), gp91(phox), and the selectable human multidrug resistance gene, MDR1 linked together by the encephalomyocarditis virus internal ribosome entry site (IRES). As a control we constructed a bicistronic vector with the polio virus IRES element and using the bacterial neomycin resistance gene (neo(r)) as the selective element. In Epstein-Barr virus transformed B (EBV-B) cells from an X-CGD patient, a tissue culture model of CGD, we show correction of the CGD defect and complete normalization of the cell population using either of these vectors and appropriate selection (vincristine for MDR1 and G418 for neo(r)). Using a chemiluminescence assay of O-2(-.) production, populations of cells transduced with either vector demonstrated initial correction levels of from less than 0.1% up to 2.7% of normal EBV-B cell oxidase activity. With either construct, cell growth under appropriate selection enriched the population of transduced cells, resulting in correction of X-CGD EBV-B cells to a level of O-2(-.) production equalling or exceeding that of normal EBV-B cells. These studies show that a therapeutic gene can be linked to a resistance gene by an IRES element, allowing for selective enrichment of cells expressing the therapeutic gene. Furthermore, the use of MDR1 as a selective element in our studies validates an important approach to gene therapy that could allow in vivo selection and is generalizable to a number of therapeutic settings. C1 NIAID,HOST DEF LAB,BETHESDA,MD 20892. NCI,DIV CANC BIOL DIAG & CTR,CELL BIOL LAB,BETHESDA,MD 20892. BROWN UNIV,SCH MED,PROVIDENCE,RI 02912. RI Sokolic, Robert/I-6072-2012 NR 55 TC 55 Z9 55 U1 1 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD JAN 1 PY 1996 VL 87 IS 1 BP 42 EP 50 PG 9 WC Hematology SC Hematology GA TN441 UT WOS:A1996TN44100007 PM 8547675 ER PT J AU Hoang, T Paradis, E Brady, G Billia, F Nakahara, K Iscove, NN Kirsch, IR AF Hoang, T Paradis, E Brady, G Billia, F Nakahara, K Iscove, NN Kirsch, IR TI Opposing effects of the basic helix-loop-helix transcription factor SCL on erythroid and monocytic differentiation SO BLOOD LA English DT Article ID T-CELL LEUKEMIA; ACUTE LYMPHOBLASTIC-LEUKEMIA; GENE-PRODUCT; EXPRESSION; TRANSLOCATION; LINE; PROTEINS; TAL-1; HEMATOPOIESIS; INVOLVEMENT AB The SCL gene (also called Tal-1 or TCL5) was identified because of its association with chromosomal translocations in childhood T-cell lymphoid leukemias. SCL codes for a basic helix-loop-helix (bHLH) factor that can function as a transcriptional activator or repressor. In the adult, SCL expression is restricted to hematopoietic cells and tissues, hut its function in the process of lineage commitment is unknown. The present study was designed to address the role of SCL in hematopoietic cell differentiation. SCL expression was determined in primary hematopoietic cells through the screening of cDNA samples obtained by reverse transcription-polymerase chain reaction (RT-PCR) from single cells at different stages of differentiation. SCL RNA expression was highest in bipotential and committed erythroid precursors and diminished with subsequent maturation to proerythroblasts and normoblasts. In contrast, SCL mRNA was low to undetectable in precursors of granulocytes and monocytes and their maturing progeny. The same pattern of expression was observed after erythroid or monocytic differentiation of a bipotent cell line, TF-1, in that SCL mRNA levels remained elevated during erythroid differentiation and were downregulated with monocytic differentiation. Accordingly, TF-1 was chosen as a model to investigate the functional significance of this divergent pattern of SCL expression in the two lineages. four independent clones stably transfected with an SCL expression vector exhibited enhanced spontaneous and delta-aminolevulinic acid-induced erythroid differentiation as measured by glycophorin expression and hemoglobinization, consistent with the view that SCL is a positive regulator of erythroid differentiation. Furthermore, constitutive SCL expression interfered with monocytic differentiation, as assessed by the generation of adherent cells and the expression of Fc gamma RII in response to TPA. These results suggest that the downregulation of SCL may be required for monocytic differentiation. (C) 1996 by The American Society of Hematology. C1 UNIV MONTREAL,DEPT PHARMACOL,MONTREAL,PQ H3C 3J7,CANADA. UNIV MONTREAL,PROGRAM MOLEC BIOL,MONTREAL,PQ H3C 3J7,CANADA. ONTARIO CANC INST,TORONTO,ON M4X 1K9,CANADA. UNIV TORONTO,DEPT MED BIOPHYS,TORONTO,ON,CANADA. UNIV MANCHESTER,SCH BIOL SCI,MANCHESTER,LANCS,ENGLAND. NCI,NAVAL MED ONCOL BRANCH,BETHESDA,MD. RP Hoang, T (reprint author), CLIN RES INST MONTREAL,HEMOPOIESIS & LEUKEMIA LAB,110 PINE AVE W,MONTREAL,PQ H2W 1R7,CANADA. NR 48 TC 80 Z9 80 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD JAN 1 PY 1996 VL 87 IS 1 BP 102 EP 111 PG 10 WC Hematology SC Hematology GA TN441 UT WOS:A1996TN44100014 PM 8547631 ER PT J AU Beckwith, M Fenton, RG Katona, IM Longo, DL AF Beckwith, M Fenton, RG Katona, IM Longo, DL TI Phosphatidylinositol-3-kinase activity is required for the anti-Ig-mediated growth inhibition of a human B-lymphoma cell line SO BLOOD LA English DT Article ID PROTEIN-TYROSINE KINASES; GTPASE-ACTIVATING PROTEIN; MURINE LYMPHOCYTES-B; CROSS-LINKING; RECEPTOR COMPLEX; SRC FAMILY; MEMBRANE IMMUNOGLOBULIN; PHOSPHOLIPASE C-GAMMA-2; SIGNAL TRANSDUCTION; PHOSPHORYLATION AB Stimulation of B lymphocytes through the Ig receptor initiates a cascade of biochemical changes, which can ultimately lead to either activation and growth, or cell-cycle arrest and cell death. One of the critical events that occurs in both cases is the activation of tyrosine kinases, and the resulting phosphorylation of a variety of proteins on tyrosine residues. In this report we identify one of the substrates of phosphorylation as the 85-kD subunit of the enzyme phosphatidylinositol-3 kinase (PI3K), and show that both anti-IgM and anti-IgD stimulation results in an increase in the antiphosphotyrosine-precipitable PI3K activity Furthermore, we show that the potent and specific inhibitor of PI3K, Wortmannin, can completely abrogate anti-Ig-mediated growth inhibition without affecting tyrosine kinase induction or protein kinase C (PKC) activation. Treatment of intact cells with Wortmannin results in an irreversible decrease in anti-Ig-induced PI3K activity, suggesting that the effect of Wortmannin on anti-Ig-mediated growth inhibition is caused by its inactivation of PI3K activity. Taken together, these data show that activation of PI3K is a critical component of the anti-Ig-initiated signaling cascade, that leads to growth inhibition of human B lymphoma cells. C1 SCI APPLICAT INT CORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD. UNIFORMED SERV UNIV HLTH SCI,DEPT PEDIAT,BETHESDA,MD 20814. UNIFORMED SERV UNIV HLTH SCI,DEPT MED,BETHESDA,MD 20814. RP Beckwith, M (reprint author), NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,BIOL RESPONSE MODIFIERS PROGRAM,BLDG 567,FREDERICK,MD 21702, USA. NR 53 TC 25 Z9 26 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD JAN 1 PY 1996 VL 87 IS 1 BP 202 EP 210 PG 9 WC Hematology SC Hematology GA TN441 UT WOS:A1996TN44100024 PM 8547643 ER PT J AU Myers, AH Young, Y Langlois, JA AF Myers, AH Young, Y Langlois, JA TI Prevention of falls in the elderly SO BONE LA English DT Article; Proceedings Paper CT International Symposium on Physical Loading, Exercise, and Bone CY NOV 17-19, 1994 CL UKK INST, TAMPERE, FINLAND SP Minist Educ Finland, Minist Hlth & Social Welf Finland, Orion yhtyma Oy, Farmos Tutkimus, Finland, Glaxo Wellcome Inc, NC, Sandoz Oy, Finland, STRATEC Medizintech GmbH, Germany HO UKK INST DE elderly; falls; injurious; interventions; prevention; recurrent ID NURSING-HOME RESIDENTS; LONG-TERM-CARE; RISK-FACTORS; RECURRENT FALLS; INJURIOUS FALLS; COMMUNITY; PEOPLE; POPULATION; MEDICATIONS; PREDICTORS AB The purpose of these symposium presentations was to examine the role of physical activity as a means of preventing hip fractures through the prevention of falls, Risk factor identification is necessary to develop preventive strategies, Risk factors related to physical activity and other risk factors for falls were identified, Intervention studies aimed at reducing, preventing or delaying falls were identified and discussed, A literature search from 1976-1994, identified 52 studies examining risk factors for falls, recurrent falls and/or falls resulting in injury, Nine intervention studies were identified with the primary outcome of falls, Physical activity-related risk factors for falls include limitations in general functioning, such as ambulation and mobility problems, difficulty or dependence in activities of daily living, and exposures to the risks of falling as indicated by the nature and frequency of daily activities, Impairments in gait and balance as well as neuromuscular and musculoskeletal impairments frequently underlie changes in physical activity in old age. Reduced activity level may occur as a result of these impairments, leading to further declines in physical functioning and an increased risk of falls, A relatively high level of activity in old age is also associated with risk of falls, Other risk factors for falls, such as cognitive impairment, visual deficits and medication use, may combine with physical activity-related risk factors to increase the risk of falls, Intervention studies directed at nursing home populations did not prevent fails but had other statistically and clinically significant outcomes, Studies among the community dwelling that targeted potential or current risk factors and included an exercise component reported a significant reduction in falls, prevented the onset of new disabilities and reduced baseline risk factors, Prevention of falls and subsequent injuries in the institutionalized population remains a challenge, Further development of interventions for community-dwelling elders that facilitate maintenance of physical activity without unduly increasing the risk of falls is also critical, The potential for maintenance of benefits gained from all fall interventions needs further examination. C1 UNIV MARYLAND,SCH MED,DEPT EPIDEMIOL & PREVENT MED,BALTIMORE,MD 21201. NIA,NIH,EPIDEMIOL DEMOG & BIOMETRY PROGRAM,BALTIMORE,MD 21224. RP Myers, AH (reprint author), NIA,GERONTOL RES CTR,BEHAV SCI LAB,NIH,RM 3B-03,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. NR 67 TC 50 Z9 50 U1 5 U2 25 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 8756-3282 J9 BONE JI Bone PD JAN PY 1996 VL 18 IS 1 SU S BP S87 EP S101 DI 10.1016/8756-3282(95)00384-3 PG 15 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA TT812 UT WOS:A1996TT81200013 PM 8717552 ER PT B AU Colby, CL Duhamel, JR Goldberg, ME AF Colby, CL Duhamel, JR Goldberg, ME BE Aertsen, A Braitenberg, V TI Multiple parietal representations of space SO BRAIN THEORY: BIOLOGICAL BASIS AND COMPUTATIONAL PRINCIPLES LA English DT Proceedings Paper CT 5th International Meeting on Brain Theory CY APR 05-07, 1994 CL IST RIC SCI & TECNOL, TRENT, ITALY SP European Commiss DG XII, Fritz Thyssen Stift, Ist Ric Sci & Tecnol HO IST RIC SCI & TECNOL RP Colby, CL (reprint author), NEI,SENSORIMOTOR RES LAB,BLDG 49,ROOM 2A50,BETHESDA,MD 20892, USA. NR 0 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE PUBL B V PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 0-444-82046-9 PY 1996 BP 37 EP 52 DI 10.1016/B978-044482046-4/50047-X PG 16 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA BJ27L UT WOS:A1996BJ27L00003 ER PT J AU Breen, N Kessler, LG Brown, ML AF Breen, N Kessler, LG Brown, ML TI Breast cancer control among the underserved - An overview SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE ethnicity; female; health promotion; health services access; mammography; mass screening; race; socioeconomic factors ID BLACK-WHITE DIFFERENCES; SCREENING MAMMOGRAPHY; NATIONAL SURVEY; UNITED-STATES; SOCIOECONOMIC-FACTORS; ETHNIC-GROUPS; MEDICAL-CARE; SOCIAL-CLASS; PAP SMEAR; WOMEN AB This paper explores barriers to the use of standard screening and breast cancer treatment that result in systematic differences in health outcomes. We review available data on individual, socioeconomic, and health system determinants of access to standard breast cancer care, including screening, diagnostic, and treatment services. Based on this review, we discuss the combination of factors which result in underservice. We argue that a broad framework which considers health system and social class as well as individual factors is useful for analyzing how structures of health care delivery tend to provide less than standard care to women who are older, have less income, or are less educated, black, or Hispanic. Data collection efforts which do not include structural and socioeconomic variables may result in an incomplete or misleading understanding of the determinants of underservice. These factors also need to be considered in the design and evaluation of public health policies and interventions meant to ameliorate the effects of underservice. RP Breen, N (reprint author), NCI,APPL RES BRANCH,DIV CANC PREVENT & CONTROL,EPN-313,BETHESDA,MD 20892, USA. NR 76 TC 45 Z9 45 U1 4 U2 4 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PY 1996 VL 40 IS 1 BP 105 EP 115 DI 10.1007/BF01806006 PG 11 WC Oncology SC Oncology GA VG043 UT WOS:A1996VG04300009 PM 8888156 ER PT J AU Das, R Vonderhaar, BK AF Das, R Vonderhaar, BK TI Activation of raf-1 MEK, and MAP kinase in prolactin responsive mammary cells SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE breast cancer; prolactin; signal transduction ID GROWTH-HORMONE RECEPTOR; HUMAN-BREAST-CANCER; XENOPUS-OOCYTE MATURATION; PROTEIN-TYROSINE KINASE; TRANSCRIPTION FACTOR; SIGNAL-TRANSDUCTION; IN-VITRO; PHOSPHORYLATION; JAK2; PATHWAYS AB The polypeptide hormone prolactin (Prl), acting through its cell surface receptors, promotes growth and differentiation in normal and malignant breast cells. We demonstrate herein that two Prl-responsive cell lines, NOG-8 normal mouse mammary epithelial and T47D human breast cancer cells, respond to Prl by rapid and transient activation of a series of kinases. Raf-1 was activated within 2-5 min of Prl treatment. This was followed rapidly by activation of MEK (MAP kinase kinase) and MAP kinase activity in these cells. Increased MAP kinase activity was accompanied by tyrosine phosphorylation of both the 42 kDa and 44 kDa isoforms. The tyrosine kinase inhibitors genestein and tyrphostin blocked the increase in MAP kinase activity as well as Prl induced growth of the T47D cells. These results indicate that the Prl receptor, after binding to Prl in mammary cells, activates the raf-MEK-MAP kinase pathway for signal transduction leading to mitogenesis. C1 NCI,TUMOR IMMUNOL & BIOL LAB,NIH,BETHESDA,MD 20892. NR 46 TC 77 Z9 78 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PY 1996 VL 40 IS 2 BP 141 EP 149 DI 10.1007/BF01806209 PG 9 WC Oncology SC Oncology GA VG045 UT WOS:A1996VG04500003 PM 8879680 ER PT J AU Smith, GH AF Smith, GH TI Experimental mammary epithelial morphogenesis in an in vivo model: Evidence for distinct cellular progenitors of the ductal and lobular phenotype SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE mammary epithelial development; lobular progenitors; ductal progenitors; morphogenesis; mammary fat pad; animal transplantation model ID MOUSE; CELLS; INVIVO; GLAND; EXPRESSION; DIFFERENTIATION; MICE; TRANSGENE; TISSUES; INVITRO AB An in vivo transplantation system has been used to evaluate the developmental capacities of specific mouse mammary epithelial cell populations. Specifically, mouse mammary epithelial cells with distinctly limited developmental potentials have been identified using this procedure. Two distinct epithelial cell progenitors have been identified by experiments designed to determine whether basal lobular and ductal phenotypes could develop independently under conditions imposed by a limiting dilution. The prediction that these separate epithelial progenitors must exist was based upon the results from transplantation experiments carried out in epithelium-divested mammary fat pads of syngeneic mice with mammary epithelium from two different transgenic mouse models. The results presented here demonstrate the following points: 1) lobular, i.e. secretory, progenitor cells are present as distinct entities among the mammary epithelial cells found in immature virgin female mice; 2) similarly, ductal epithelial progenitors are present within the same population; 3) lobular progenitors are present in greater numbers, although both cell populations are extremely small; 4) as expected, some inocula produce outgrowths with simultaneous development of both lobular and ductal phenotypes - it is not known whether this indicates cooperative interaction between the two epithelial progenitors or signals the presence of a third progenitor type capable of producing both ductular and lobular committed daughters; 5) these findings have important consequences in the design of experiments aimed at testing the effects of known and putative mammary oncogenes and tumor suppressor genes, using techniques which include cellular transformation in vitro followed by in vivo cultivation and evaluation. RP Smith, GH (reprint author), NCI,ONCOGENET SECT,TUMOR IMMUNOL & BIOL LAB,BLDG 10-8B07,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 31 TC 167 Z9 170 U1 0 U2 3 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PY 1996 VL 39 IS 1 BP 21 EP 31 DI 10.1007/BF01806075 PG 11 WC Oncology SC Oncology GA UK921 UT WOS:A1996UK92100003 PM 8738603 ER PT J AU Callahan, R AF Callahan, R TI MMTV-induced mutations in mouse mammary tumors: Their potential relevance to human breast cancer SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE mouse model system; mutations; MMTV ID TRANSGENIC MICE; GROWTH-FACTORS; PROVIRAL INSERTION; EPITHELIAL-CELLS; NOTCH-GENE; VIRUS; INT-2; HETEROZYGOSITY; EXPRESSION; CARCINOGENESIS AB In mouse mammary tumor virus (MMTV) infected mice, three identifiable stages of mammary tumorigenesis cad be biologically defined: preneoplastic hyperplastic nodules, malignant tumor, and distant metastatic lesions (primarily in the lung). MMTV is a biological carcinogen which induces somatic mutations as consequence of its integration into the host cellular genome. Each stage of mammary tumorigenesis appears to result from the clonal outgrowth of cells containing additional integrated proviral MMTV genomes. This phenomenon has provided the basis for an approach to identify genes which, when affected, may contribute to progression through the different stages of mammary tumorigenesis. Eight different genes (Wnt1, Wnt3, Wnt10b, Fgf3, Fgf4, Fgf8, lnt3, and lnt6) have been shown to be genetically altered in multiple mammary tumors as a consequence of MMTV integration. Although the significance of the human homologs of these genes as targets for somatic mutation during human breast carcinogenesis is only now being explored, it is clear that this work has led to a new appreciation of the complexity of the genetic circuitry that is involved in the control of normal mammary gland growth and development. It seems likely that some of the mutations induced by MMTV, and the signaling pathways in which these target genes take part, will be relevant to the progression from preneoplastic lesions to distant metastasis in human breast cancer. RP Callahan, R (reprint author), NCI, ONCOGENET SECT, TUMOR IMMUNOL & BIOL LAB, BLDG 10, ROOM 5B50, BETHESDA, MD 20892 USA. NR 82 TC 47 Z9 47 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PY 1996 VL 39 IS 1 BP 33 EP 44 DI 10.1007/BF01806076 PG 12 WC Oncology SC Oncology GA UK921 UT WOS:A1996UK92100004 PM 8738604 ER PT J AU Amundadottir, LT Merlino, G Dickson, RB AF Amundadottir, LT Merlino, G Dickson, RB TI Transgenic mouse models of breast cancer SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE breast tumorigenesis; cell cycle genes; growth factors and receptors; growth suppressing genes; int genes; multiple transgenes; nuclear oncogenes; ras genes; transgenic mice; viral oncogenes ID TRANSFORMING GROWTH-FACTOR; C-MYC AMPLIFICATION; NEU ONCOGENE; FACTOR-RECEPTOR; DNA-BINDING; FACTOR-ALPHA; TYROSINE KINASES; MAMMARY-TUMORS; TGF-ALPHA; SIGNAL TRANSDUCTION AB Although valuable initial information can be gathered about transformation from in vitro studies, human cancer occurs in the context of a complex interaction with its environment and must ultimately be studied in living animals. Transgenic animal models have been used to study breast transformation for a number of years and have yielded valuable information on the subject. In this paper, we will summarize results from our laboratories, and others, regarding the use of transgenic mice to study breast tumorigenesis. We will also suggest future directions for the use of transgenic models to understand, and hopefully, one day to cure the disease. C1 GEORGETOWN UNIV,VINCENT T LOMBARDI CANC RES CTR,WASHINGTON,DC 20007. GEORGETOWN UNIV,DEPT CELL BIOL,WASHINGTON,DC 20007. NCI,NIH,MOLEC BIOL LAB,BETHESDA,MD 20892. RI Amundadottir, Laufey/L-7656-2016 OI Amundadottir, Laufey/0000-0003-1859-8971 NR 89 TC 45 Z9 45 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PY 1996 VL 39 IS 1 BP 119 EP 135 DI 10.1007/BF01806083 PG 17 WC Oncology SC Oncology GA UK921 UT WOS:A1996UK92100011 PM 8738611 ER PT J AU Pastan, I Pai, LH Brinkmann, U FitzGerald, D AF Pastan, I Pai, LH Brinkmann, U FitzGerald, D TI Recombinant immunotoxins SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article; Proceedings Paper CT Symposium on New Approaches in the Therapy of Breast Cancer CY OCT, 1994 CL GEORGETOWN UNIV MED CTR, WASHINGTON, DC SP Bristol Myers Squibb HO GEORGETOWN UNIV MED CTR DE breast cancer; cancer treatment; colon cancer; Pseudomonas exotoxin ID EPIDERMAL GROWTH-FACTOR; PSEUDOMONAS EXOTOXIN-A; MONOCLONAL-ANTIBODY; FACTOR RECEPTOR; COLON-CANCER; CARCINOMA; CELLS; MICE; EXPRESSION; PROTEINS AB Pseudomonas exotoxin has been genetically modified so that it targets cancer cells. This was accomplished by deleting its cell binding domain and replacing it with Fv fragments of antibodies that react with breast, colon, and other cancers. Several recombinant immunotoxins are now in clinical trials. RP Pastan, I (reprint author), NCI,DIV CANC BIOL DIAG & CTR,NIH,MOLEC BIOL LAB,37 CONVENT DR MSC 4255,BETHESDA,MD 20892, USA. NR 25 TC 16 Z9 16 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PY 1996 VL 38 IS 1 BP 3 EP 9 DI 10.1007/BF01803778 PG 7 WC Oncology SC Oncology GA TU162 UT WOS:A1996TU16200002 PM 8825117 ER PT J AU Schlom, J Kantor, J Abrams, S Tsang, KY Panicali, D Hamilton, JM AF Schlom, J Kantor, J Abrams, S Tsang, KY Panicali, D Hamilton, JM TI Strategies for the development of recombinant vaccines for the immunotherapy of breast cancer SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article; Proceedings Paper CT Symposium on New Approaches in the Therapy of Breast Cancer CY OCT, 1994 CL GEORGETOWN UNIV MED CTR, WASHINGTON, DC SP Bristol Myers Squibb HO GEORGETOWN UNIV MED CTR DE carcinoembryonic antigen (CEA); immunotherapy; Phase I trial; recombinant vaccines; vaccinia virus ID HUMAN CARCINOEMBRYONIC-ANTIGEN; EPITHELIAL TUMOR-ANTIGEN; PLUS DETOX ADJUVANT; IMMUNE-RESPONSES; VIRUS-VACCINE; LYMPHOCYTES-T; CELLS; GENE; COSTIMULATION; IMMUNIZATION AB The development of recombinant vaccines for specific immunotherapy of carcinoma represents a novel approach for the treatment of breast cancer and other tumor types. This article reviews the various parameters that should be considered in the development of recombinant vaccines. Several breast cancer associated antigens are also discussed which may provide potential target molecules. The human carcinoembryonic antigen (CEA), which is expressed on approximately 50% of breast cancers, represents one such target for immunotherapy. To enhance the immunogenicity of this antigen, a recombinant CEA-vaccinia vaccine, designated rV-CEA, was produced. To study the effects of this vaccine in an animal model, a murine colon carcinoma cell line was transduced with CEA and transplanted into immunocompetent mice for protection and therapy studies. Pre-clinical toxicity studies were also conducted in non-human primates. The results of these studies showed the rV-CEA vaccine to be immunogenic and safe in both rodents and primates, and to elicit good anti-tumor responses in the rodent model. In a Phase I clinical trial in metastatic breast, lung, and colorectal cancer patients involving three immunizations of rV-CEA, at three dose levels, enhancement of T-cell and antibody responses to vaccinia virus proteins were observed with no toxicity. Specific T-cell responses were studied via stimulation of peripheral blood lymphocytes with specific peptide epitopes from the CEA molecule. These studies demonstrated clear cut differences in establishment of T-cell lines pre- versus post-immunization. The T-cell lines were shown to be CD8(+) and/or CD4(+)/CD8(+), to lyse EBV transformed B-cells transduced with the CEA gene, and to lyse CEA positive carcinoma cells in a HLA restricted manner. Thus, in a Phase I clinical trial the rV-CEA vaccine has been shown to stimulate a CTL response specific for CEA defined epitopes in cancer patients. C1 THERION BIOL CORP,CAMBRIDGE,MA 02142. NCI,USN,ONCOL BRANCH,NIH,BETHESDA,MD 20892. RP Schlom, J (reprint author), NCI,TUMOR IMMUNOL & BIOL LAB,NIH,BLDG 10,ROOM 8B07,BETHESDA,MD 20892, USA. NR 36 TC 35 Z9 35 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PY 1996 VL 38 IS 1 BP 27 EP 39 DI 10.1007/BF01803781 PG 13 WC Oncology SC Oncology GA TU162 UT WOS:A1996TU16200005 PM 8825120 ER PT J AU Sheng, ZM Marchetti, A Buttitta, F Champeme, MH Campani, D Bistocchi, M Lidereau, R Callahan, R AF Sheng, ZM Marchetti, A Buttitta, F Champeme, MH Campani, D Bistocchi, M Lidereau, R Callahan, R TI Multiple regions of chromosome 6q affected by loss of heterozygosity in primary human breast carcinomas SO BRITISH JOURNAL OF CANCER LA English DT Article DE breast cancer; deletion; chromosome 6q; tumour suppressor gene ID CANCER; ABNORMALITIES; DELETION; DISEASE AB A total of 80 primary human breast carcinoma DNAs were analysed for loss of heterozygosity (LOH) on the long arm of chromosome 6, using microsatellite markers whose location has been defined physically and by linkage analysis. Loss of heterozygosity was observed in 38 of 80 (48%) tumours that were informative for at least one locus. The analysis revealed partial or interstitial deletions of chromosome 6q. Detailed mapping of chromosome 6q in these tumour DNAs identified two and perhaps three commonly deleted regions. One of these is located between markers D6S251 and D6S252 (6q14-q16.2), another between D6S268 and D6S261 (6q16.3-q23) and a third between D6S287 and D6S270 (6q22.3-q23.1). C1 NCI,TUMOR IMMUNOL & BIOL LAB,BETHESDA,MD 20892. UNIV PISA,INST PATHOL ANAT & HISTOL,PISA,ITALY. CTR RENE HUGUENIN,INSERM,F-92211 ST CLOUD,FRANCE. NR 18 TC 64 Z9 64 U1 0 U2 3 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD JAN PY 1996 VL 73 IS 2 BP 144 EP 147 DI 10.1038/bjc.1996.27 PG 4 WC Oncology SC Oncology GA TP078 UT WOS:A1996TP07800003 PM 8546898 ER PT J AU Leonessa, F Green, D Licht, T Wright, A WingateLegette, K Lippman, J Gottesman, MM Clarke, R AF Leonessa, F Green, D Licht, T Wright, A WingateLegette, K Lippman, J Gottesman, MM Clarke, R TI MDA435/LCC6 and MDA435/LCC6(MDR1): Ascites models of human breast cancer SO BRITISH JOURNAL OF CANCER LA English DT Article DE breast cancer; MDR1, P-glycoprotein; animal models; drug screening ID P-GLYCOPROTEIN EXPRESSION; MULTIDRUG RESISTANCE; ESTROGEN-RECEPTOR; CELL-LINES; PLEURAL EFFUSIONS; NUDE-MICE; DOXORUBICIN; CARCINOMA; GROWTH; TUMORIGENICITY AB We have established a novel ascites tumour model (MDA435/LCC6) from the oestrogen receptor-negative, invasive and metastatic MDA-MB-435 human breast cancer cell line. MDA435/LCC6 cells grow as both malignant ascites and solid tumours in vivo in nude mice and nude rats, with a tumour incidence of approximately 100%. Untreated mice develop ascites following i.p. inoculation of 1x10(6) cells and have a reproducible life span of approximately 30 days, with all animals dying within a 48 h period. The in vivo response of MDA435/LCC6 ascites to several cytotoxic drugs, including doxorubicin, etoposide (VP-16), BCNU and mitomycin C, closely reflects the activity of these single agents in previously untreated breast cancer patients. MDA435/LCC6 cells also retain the anchorage-dependent and anchorage-independent in vitro growth properties of the parental MDA-MB-435 cells, and can be used in standard in vitro drug screening assays. The drug resistance pattern of the MDA435/LCC6 cells suggests that they may have few active endogenous drug resistance mechanisms. To generate a model for the screening of MDR1-reversing agents, MDA435/LCC6 were transduced with a retroviral vector directing the constitutive expression of the MDR1 cDNA, producing a cell line with a classical MDR1 resistance pattern (MDA435/LCC6(MDRI)). These ascites models may be a viable alternative to the murine leukaemia ascites (L1210, P388) and, in conjunction with other breast cancer cell lines, facilitate the in vitro and in vivo screening of new cytotoxic drugs and drug combinations. C1 GEORGETOWN UNIV,SCH MED,CTR CANC,WASHINGTON,DC 20007. GEORGETOWN UNIV,SCH MED,DEPT PHYSIOL & BIOPHYS,WASHINGTON,DC 20007. NCI,MOLEC BIOL LAB,BETHESDA,MD 20892. NCI,CELL BIOL LAB,BETHESDA,MD 20892. RI Clarke, Robert/A-6485-2008 OI Clarke, Robert/0000-0002-9278-0854 FU NCI NIH HHS [UO1-CA51908, P50-CA58185, R01-CA58022] NR 52 TC 88 Z9 88 U1 0 U2 3 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD JAN PY 1996 VL 73 IS 2 BP 154 EP 161 DI 10.1038/bjc.1996.29 PG 8 WC Oncology SC Oncology GA TP078 UT WOS:A1996TP07800005 PM 8546900 ER PT J AU AlDamluji, S Kopin, IJ AF AlDamluji, S Kopin, IJ TI Functional properties of the uptake of amines in immortalised peptidergic neurones (transport-P) SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Article DE amine uptake; hypothalamus; prazosin; neurones; biological transport ID GONADOTROPIN-RELEASING-HORMONE; HIGH-AFFINITY UPTAKE; ISOLATED RAT-HEART; HYPOTHALAMIC NEURONS; EXPRESSION CLONING; CELL-FUNCTION; NORADRENALINE; INHIBITION; ATPASES; AGENTS AB 1 Most neurotransmitters are inactivated by uptake into presynaptic nerve terminals and into glial cells. We recently provided evidence for uptake of amines in postsynaptic neurones. Uptake was evident at nanomolar concentrations of prazosin, but at concentrations of unlabelled prazosin greater than 10(-7) M, there was a further activation of uptake, manifested by a paradoxical increase in accumulation of the radioligand. We have now studied further characteristics of amine uptake in immortalised gonadotrophin-releasing hormone (GnRH) neurones. Control cells included SK-N-SH neuroblastoma cells (which possess presynaptic type amine transporters) and non-neuronal (COS-7) cells. 2 [H-3]-prazosin bound to intact GnRH cells and was displaced by unlabelled prazosin in concentrations of 10(-9) to 10(-7) M. However, at higher concentrations of unlabelled prazosin, there was an increase in apparent [H-3]-prazosin binding, as we had previously described. This paradoxical increase in accumulation of the radioligand was abolished by desipramine. 3 Desipramine had no effect on the association of prazosin with COS-7 cells. There was no paradoxical increase in accumulation of [H-3]-prazosin in COS-7 cells, indicating that this effect requires the presence of a desipramine-blockable uptake process. 4 The increase in binding of the radioligand that was observed in the GnRH cells is not a general property of neuronal transporters; in SK-N-SH cells, there was no increase in accumulation of (-)-[H-3]-noradrenaline in the presence of concentrations of unlabelled (-)-noradrenaline greater than 10(-7) M. 5 The uptake of prazosin and the increase in accumulation of [H-3]-prazosin were abolished in the cold, indicating that this is an active, energy-requiring process. 6 Desipramine-sensitive uptake of prazosin was demonstrable in the GnRH cells in the absence of sodium. Further, the Na+/K+-ATPase inhibitor, vanadate, abolished noradrenaline uptake in SK-N-SH cells but had no effect on prazosin uptake in GnRH cells. Thus, the uptake of prazosin does not derive its energy from the sodium pump. 7 Prazosin uptake was inhibited by the V-ATPase inhibitor bafilomycin A(1), the H+/Na+ ionophore, monensin and the organic base, chloroquine, indicating that uptake derives its energy from a proton pump. In contrast to other proton-dependent amine transporters, the uptake of prazosin was unaffected by reserpine. 8 Increasing extracellular pH did not increase the uptake of prazosin into GnRH cells, indicating that it is unlikely to be due to non-specific diffusion and concentration of a lysosomotropic drug into intracellular acidic particles. 9 The uptake of prazosin was unaffected by steroid hormones. 10 In COS-7 cells transfected with alpha(1)-adrenoceptor cDNA, [H-3]-prazosin was displaced by unlabelled prazosin without causing an increase in binding of the radioligand. This indicated that the increase in accumulation of the radioligand is unlikely to be due simply to some function of alpha(1)-adrenoceptors. 11 Thus, peptidergic neurones possess an uptake process with properties that are distinguishable from known amine transporters. C1 NINCDS,NIH,CLIN NEUROSCI BRANCH,BETHESDA,MD 20892. NR 40 TC 11 Z9 11 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0007-1188 J9 BRIT J PHARMACOL JI Br. J. Pharmacol. PD JAN PY 1996 VL 117 IS 1 BP 111 EP 118 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA TY674 UT WOS:A1996TY67400017 PM 8825351 ER PT J AU Ren, K Iadarola, MJ Dubner, R AF Ren, K Iadarola, MJ Dubner, R TI An isobolographic analysis of the effects of N-methyl-D-aspartate and NK1 tachykinin receptor antagonists on inflammatory hyperalgesia in the rat SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Article DE NMDA receptor antagonist; dextrorphan; tachykinin receptors; NK1 tachykinin receptor antagonists; CP-96,345; WIN 51,708; isobologram; hyperalgesia ID SUBSTANCE-P RECEPTOR; DORSAL HORN NEURONS; ADJUVANT-INDUCED INFLAMMATION; EXCITATORY AMINO-ACIDS; SPINAL-CORD; UNILATERAL INFLAMMATION; BEHAVIORAL HYPERALGESIA; NONPEPTIDE ANTAGONIST; NOCICEPTIVE RESPONSES; POSSIBLE INVOLVEMENT AB 1 The interaction between N-methyl-D-aspartate (NMDA) and NK1 tachykinin receptors was analyzed isobolographically in rats with inflammatory hyperalgesia induced by intraplantar injection of complete Freund's adjuvant-saline emulsion (CFA, 100 mu g Mycobacterium tuberculosis). 2 Thermal hyperalgesia of the inflamed paw, determined by paw withdrawal response to a heat stimulus, was dose-dependently attenuated by intrathecal administration of an NMDA receptor antagonist, dextrorphan (2.5-40 mu g, ED(50)=7.2 mu g), and two NK1 tachykinin receptor antagonists, WIN 51,708 (0.01-200 mu g, ED(50)=10.4 mu g) or CP-96,345 (5-200 mu g, ED(50)=82.1 mu g). There was no effect of these agents on the nociceptive threshold of the non-inflamed paw. CP-96,344, an enantiomer of CP-96,345 that is inactive as an NK, tachykinin receptor antagonist, slightly attenuated hyperalgesia at a dose of 200 mu g. 3 Combinations of dextrorphan and WIN 51,708 were administered at fixed ratios (10%:90%; 41%:59%; 90%:10%). Isobolographic analysis revealed that the ED(50)s obtained from the three combination ratios were not significantly different from those that were expected from a simple additive effect. 4 Thus, an additive interaction was demonstrated between NMDA and NK1 tachykinin receptor systems at the spinal level. These results suggest that both NMDA and NK1 tachykinin receptors are activated in response to peripheral inflammation, but that they may contribute independently to development of hyperalgesia. C1 NIDR, NIH, NEUROBIOL & ANESTHESIOL BRANCH, BETHESDA, MD 20892 USA. NR 63 TC 35 Z9 35 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0007-1188 J9 BRIT J PHARMACOL JI Br. J. Pharmacol. PD JAN PY 1996 VL 117 IS 1 BP 196 EP 202 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA TY674 UT WOS:A1996TY67400029 PM 8825363 ER PT B AU Jensen, P Friesen, B Sanger, C AF Jensen, P Friesen, B Sanger, C BE Exo, KJ Friesen, BJ TI Plenary session: Implications of research advances in children's mental health SO BUILDING ON FAMILY STRENGTHS: RESEARCH AND PROGRAMS IN SUPPORT OF CHILDREN AND THEIR FAMILIES, CONFERENCE PROCEEDINGS LA English DT Proceedings Paper CT National Conference on Building on Family - Research and Programs in Support of Children and Their Families CY JUN 01-03, 1995 CL PORTLAND, OR SP Portland State Univ, Res & Training Ctr Family Support & Childrens Mental Hlth C1 NIMH, Div Clin Res, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PORTLAND STATE UNIV PI PORTLAND PA P O BOX 751, PORTLAND, OR 97207 USA PY 1996 BP 34 EP 54 PG 21 WC Family Studies SC Family Studies GA BL36G UT WOS:000075265500002 ER PT J AU Colaianni, LA AF Colaianni, LA TI Health information for the global village - Introduction SO BULLETIN OF THE MEDICAL LIBRARY ASSOCIATION LA English DT Editorial Material RP Colaianni, LA (reprint author), NATL LIB MED,8600 ROCKVILLE PIKE,BETHESDA,MD 20894, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MED LIBRARY ASSN PI CHICAGO PA SUITE 300 6 N MICHIGAN AVE, CHICAGO, IL 60602 SN 0025-7338 J9 B MED LIBR ASSOC JI Bull. Med. Libr. Assoc. PD JAN PY 1996 VL 84 IS 1 BP 81 EP 81 PG 1 WC Information Science & Library Science SC Information Science & Library Science GA TV825 UT WOS:A1996TV82500010 ER PT J AU Lindberg, DAB AF Lindberg, DAB TI The modern library: Lost and found SO BULLETIN OF THE MEDICAL LIBRARY ASSOCIATION LA English DT Article; Proceedings Paper CT 7th International Congress on Medical Librarianship CY MAY 10-11, 1995 CL WASHINGTON, D.C. AB The modern library, a term that was heard frequently in the mid-twentieth century, has fallen into disuse. The over-promotion of computers and all that their enthusiasts promised probably hastened its demise. Today, networking is transforming how libraries provide-and users seek-information. Although the Internet is the natural environment for the health sciences librarian, it is going through growing pains as we face issues of censorship and standards. Today's ''modern librarian'' must not only be adept at using the Internet but must become familiar with digital information in all its forms-images, full text, and factual data banks. Most important, to stay ''modern,'' today's librarians must embark on a program of lifelong learning that will enable them to make optimum use of the advantages offered by modern technology. RP Lindberg, DAB (reprint author), NATL LIB MED, 8600 ROCKVILLE PIKE, BETHESDA, MD 20894 USA. NR 6 TC 2 Z9 2 U1 0 U2 0 PU MEDICAL LIBRARY ASSOC PI CHICAGO PA 65 EAST WACKER PLACE, STE 1900, CHICAGO, IL 60601-7298 USA SN 0025-7338 J9 B MED LIBR ASSOC JI Bull. Med. Libr. Assoc. PD JAN PY 1996 VL 84 IS 1 BP 86 EP 90 PG 5 WC Information Science & Library Science SC Information Science & Library Science GA TV825 UT WOS:A1996TV82500013 PM 8938334 ER PT J AU Bart, KJ Foulds, J Patriarca, P AF Bart, KJ Foulds, J Patriarca, P TI Global eradication of poliomyelitis: Benefit-cost analysis SO BULLETIN OF THE WORLD HEALTH ORGANIZATION LA English DT Article AB A benefit-cost analysis of the Poliomyelitis Eradication Initiative was undertaken to facilitate national and international decision-making with regard to financial support. The base case examined the net costs and benefits during the period 1986-2040; the model assumed differential costs for oral poliovirus vaccine (OPV) and vaccine delivery in industrialized and developing countries, and ignored all benefits aside from reductions in direct costs for treatment and rehabilitation. The model showed that the ''break-even'' point at which benefits exceeded costs was the year 2007, with a saving of US$ 13 600 million by the year 2040. Sensitivity analyses revealed only small differences in the break-even point and in the dollars saved, when compared with the base case, even with large variations in the target age group for vaccination, the proportion of case-patients seeking medical attention, and the cost of vaccine delivery. The technical feasibility of global eradication is supported by the availability of an easily administered, inexpensive vaccine (OPV), the epidemiological characteristics of poliomyelitis, and the successful experience in the Americas with elimination of wild poliovirus infection. This model demonstrates that the Poliomyelitis Eradication Initiative is economically justified. C1 US DEPT HHS,NIAID,DIV MICROBIOL & INFECT DIS,NIH,BETHESDA,MD. US FDA,CTR BIOL EVALUAT & RES,DIV VIRAL PROD,OFF VACCINES,BETHESDA,MD. RP Bart, KJ (reprint author), US DEPT HHS,OFF INT HLTH,OFF SECRETARY,ROOM 18-74,5600 FISHERS LANE,ROCKVILLE,MD 20878, USA. NR 23 TC 49 Z9 50 U1 0 U2 0 PU WORLD HEALTH ORGANIZATION PI GENEVA 27 PA DISTRIBUTION AND SALES, CH-1211 GENEVA 27, SWITZERLAND SN 0042-9686 J9 B WORLD HEALTH ORGAN JI Bull. World Health Organ. PY 1996 VL 74 IS 1 BP 35 EP 45 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA UN911 UT WOS:A1996UN91100004 PM 8653814 ER PT J AU Goldschmidt, R AF Goldschmidt, R TI Of WAIS, WebSite, and Windows NT SO BYTE LA English DT Letter RP Goldschmidt, R (reprint author), NIH,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BYTE PUBL INC PI PETERBOROUGH PA 70 MAIN ST, PETERBOROUGH, NH 03458 SN 0360-5280 J9 BYTE JI Byte PD JAN PY 1996 VL 21 IS 1 BP 18 EP 18 PG 1 WC Computer Science, Hardware & Architecture; Computer Science, Software Engineering SC Computer Science GA TK781 UT WOS:A1996TK78100010 ER PT S AU Pommier, Y Gupta, M Valenti, M NievesNeira, W AF Pommier, Y Gupta, M Valenti, M NievesNeira, W BE Pantazis, P Giovanella, BC Rothenberg, ML TI Cellular resistance to camptothecins SO CAMPTOTHECINS: FROM DISCOVERY TO THE PATIENT SE Annals of the New York Academy of Sciences LA English DT Review CT Conference on the Camptothecins - From Discovery to the Patient CY FEB 07-10, 1996 CL BETHESDA, MD SP New York Acad Sci, Pharmacia & Upjohn Inc, Janssen Pharm, NCI, Rhone Poulenc Rorer, SmithKline Beecham Pharm, RGK Fdn, Yakult Honsha Co Ltd, Boehringer Ingelheim KG, Daiichi Pharm Corp, Genentech Inc, Marion Merrell Dow Inc, Rhone Poulenc Rorer Fdn, Stehlin Fdn Canc Res ID DNA TOPOISOMERASE-I; STRAND-BREAK-REPAIR; DEPENDENT PROTEIN-KINASE; ATAXIA-TELANGIECTASIA GENE; P-GLYCOPROTEIN EXPRESSION; CROSS-LINKING AGENTS; HAMSTER DC3F CELLS; MAMMALIAN-CELLS; LUNG-CANCER; SCID MUTATION RP Pommier, Y (reprint author), NCI, MOL PHARMACOL LAB,DIV BASIC SCI,NIH,BLDG 37, ROOM 5C25, BETHESDA, MD 20892 USA. NR 125 TC 27 Z9 27 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-057-3 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1996 VL 803 BP 60 EP 73 DI 10.1111/j.1749-6632.1996.tb26377.x PG 14 WC Oncology; Multidisciplinary Sciences; Pharmacology & Pharmacy SC Oncology; Science & Technology - Other Topics; Pharmacology & Pharmacy GA BH28S UT WOS:A1996BH28S00007 PM 8993501 ER PT S AU Muggia, FM Dimery, I Arbuck, SG AF Muggia, FM Dimery, I Arbuck, SG BE Pantazis, P Giovanella, BC Rothenberg, ML TI Camptothecin and its analogs - An overview of their potential in cancer therapeutics SO CAMPTOTHECINS: FROM DISCOVERY TO THE PATIENT SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT Conference on the Camptothecins - From Discovery to the Patient CY FEB 07-10, 1996 CL BETHESDA, MD SP New York Acad Sci, Pharmacia & Upjohn Inc, Janssen Pharm, NCI, Rhone Poulenc Rorer, SmithKline Beecham Pharm, RGK Fdn, Yakult Honsha Co Ltd, Boehringer Ingelheim KG, Daiichi Pharm Corp, Genentech Inc, Marion Merrell Dow Inc, Rhone Poulenc Rorer Fdn, Stehlin Fdn Canc Res ID CELL LUNG-CANCER; TOPOISOMERASE-I INHIBITOR; PHASE-I; CPT-11; TOPOTECAN; CISPLATIN; INVITRO; CYTOTOXICITY; COMBINATION; NSC-100880 C1 UNIV SO CALIF, KENNETH NORRIS JR COMPREHENS CANC CTR, DEV THERAPEUT PROGRAM, LOS ANGELES, CA 90033 USA. NCI, INVEST DRUG BRANCH, CANC THERAPY EVALUAT PROGRAM, DIV CANC DIAG TREATMENT & CTR, BETHESDA, MD 20205 USA. RP Muggia, FM (reprint author), UNIV SO CALIF, KENNETH NORRIS JR COMPREHENS CANC CTR, DEPT MED, LOS ANGELES, CA 90033 USA. NR 72 TC 29 Z9 29 U1 2 U2 4 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-057-3 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1996 VL 803 BP 213 EP 223 DI 10.1111/j.1749-6632.1996.tb26391.x PG 11 WC Oncology; Multidisciplinary Sciences; Pharmacology & Pharmacy SC Oncology; Science & Technology - Other Topics; Pharmacology & Pharmacy GA BH28S UT WOS:A1996BH28S00021 PM 8993515 ER PT S AU Potmesil, M Arbuck, SG Takimoto, CH Liebes, L Hochster, H AF Potmesil, M Arbuck, SG Takimoto, CH Liebes, L Hochster, H BE Pantazis, P Giovanella, BC Rothenberg, ML TI 9-Aminocamptothecin and beyond - Preclinical and clinical studies SO CAMPTOTHECINS: FROM DISCOVERY TO THE PATIENT SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT Conference on the Camptothecins - From Discovery to the Patient CY FEB 07-10, 1996 CL BETHESDA, MD SP New York Acad Sci, Pharmacia & Upjohn Inc, Janssen Pharm, NCI, Rhone Poulenc Rorer, SmithKline Beecham Pharm, RGK Fdn, Yakult Honsha Co Ltd, Boehringer Ingelheim KG, Daiichi Pharm Corp, Genentech Inc, Marion Merrell Dow Inc, Rhone Poulenc Rorer Fdn, Stehlin Fdn Canc Res ID TOPOISOMERASE-I INHIBITOR; PLANT ANTITUMOR AGENTS; PHASE-I; CAMPTOTHECIN ANALOGS; GROWTH-INHIBITION; CANCER; TOPOTECAN; INFUSION; CPT-11; TRIAL C1 NYU, SCH MED, KAPLAN CANC CTR, DEPT MED, NEW YORK, NY 10016 USA. NCI, DIV CANC TREAMENT DIAG & CTR, NIH, BETHESDA, MD 20889 USA. NCI, NAVY MED ONCOL BRANCH, DIV CLIN SCI, NATL NAVAL MED CTR, BETHESDA, MD 20889 USA. RP Potmesil, M (reprint author), NYU, SCH MED, KAPLAN CANC CTR, DEPT RADIOL, 550 1ST AVE, NEW YORK, NY 10016 USA. FU NCI NIH HHS [P01 CA 50529, P03 CA 16087, R01 CA 54484] NR 47 TC 22 Z9 23 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-057-3 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1996 VL 803 BP 231 EP 246 DI 10.1111/j.1749-6632.1996.tb26393.x PG 16 WC Oncology; Multidisciplinary Sciences; Pharmacology & Pharmacy SC Oncology; Science & Technology - Other Topics; Pharmacology & Pharmacy GA BH28S UT WOS:A1996BH28S00023 PM 8993517 ER PT S AU Goldwasser, F Shimizu, T Pommier, Y AF Goldwasser, F Shimizu, T Pommier, Y BE Pantazis, P Giovanella, BC Rothenberg, ML TI Failure in DNA elongation predicts sensitivity to camptothecin in the colon cell lines of the NCI anticancer drug screen SO CAMPTOTHECINS: FROM DISCOVERY TO THE PATIENT SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT Conference on the Camptothecins - From Discovery to the Patient CY FEB 07-10, 1996 CL BETHESDA, MD SP New York Acad Sci, Pharmacia & Upjohn Inc, Janssen Pharm, NCI, Rhone Poulenc Rorer, SmithKline Beecham Pharm, RGK Fdn, Yakult Honsha Co Ltd, Boehringer Ingelheim KG, Daiichi Pharm Corp, Genentech Inc, Marion Merrell Dow Inc, Rhone Poulenc Rorer Fdn, Stehlin Fdn Canc Res ID TOPOISOMERASE C1 NCI, MOL PHARMACOL LAB, DIV BASIC SCI, NIH, BETHESDA, MD 20892 USA. NR 5 TC 1 Z9 1 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-057-3 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1996 VL 803 BP 308 EP 309 DI 10.1111/j.1749-6632.1996.tb26401.x PG 2 WC Oncology; Multidisciplinary Sciences; Pharmacology & Pharmacy SC Oncology; Science & Technology - Other Topics; Pharmacology & Pharmacy GA BH28S UT WOS:A1996BH28S00031 PM 8993525 ER PT S AU Takimoto, CH Dahut, W Harold, N Nakashima, H Lieberman, R Liang, MD Arbuck, SG Chen, AP Hamilton, JM Cantilena, LR Allegra, CJ Grem, JL AF Takimoto, CH Dahut, W Harold, N Nakashima, H Lieberman, R Liang, MD Arbuck, SG Chen, AP Hamilton, JM Cantilena, LR Allegra, CJ Grem, JL BE Pantazis, P Giovanella, BC Rothenberg, ML TI Clinical pharmacology of 9-aminocamptothecin SO CAMPTOTHECINS: FROM DISCOVERY TO THE PATIENT SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT Conference on the Camptothecins - From Discovery to the Patient CY FEB 07-10, 1996 CL BETHESDA, MD SP New York Acad Sci, Pharmacia & Upjohn Inc, Janssen Pharm, NCI, Rhone Poulenc Rorer, SmithKline Beecham Pharm, RGK Fdn, Yakult Honsha Co Ltd, Boehringer Ingelheim KG, Daiichi Pharm Corp, Genentech Inc, Marion Merrell Dow Inc, Rhone Poulenc Rorer Fdn, Stehlin Fdn Canc Res ID PHASE C1 US FDA, CTR DRUG EVALUAT & RES, ROCKVILLE, MD 20857 USA. NCI, CANC THERAPY EVALUAT PROGRAM, BETHESDA, MD 20892 USA. UNIFORMED SERV UNIV HLTH SCI, DEPT INTERNAL MED, DIV CLIN PHARMACOL, BETHESDA, MD 20814 USA. RP Takimoto, CH (reprint author), USN, BETHESDA HOSP,NCI,MED ONCOL BRANCH,DIV CLIN SCI, BLDG 8, ROOM 5101, BETHESDA, MD 20889 USA. NR 3 TC 6 Z9 6 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-057-3 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1996 VL 803 BP 324 EP 326 DI 10.1111/j.1749-6632.1996.tb26407.x PG 3 WC Oncology; Multidisciplinary Sciences; Pharmacology & Pharmacy SC Oncology; Science & Technology - Other Topics; Pharmacology & Pharmacy GA BH28S UT WOS:A1996BH28S00037 PM 8993530 ER PT J AU Lynch, HT Drouhard, T Vasen, HFA Cavalieri, J Lynch, J Nord, S Smyrk, T Lanspa, S Murphy, P Whelan, KL Peters, J delaChapelle, A AF Lynch, HT Drouhard, T Vasen, HFA Cavalieri, J Lynch, J Nord, S Smyrk, T Lanspa, S Murphy, P Whelan, KL Peters, J delaChapelle, A TI Genetic counseling in a Navajo hereditary nonpolyposis colorectal cancer kindred SO CANCER LA English DT Article DE cross-cultural genetic counseling; Navajo; MLH1 mutation; hereditary nonpolyposis colorectal cancer ID FAMILY AB BACKGROUND. Cross-cultural genetic counseling was provided to an estended Navajo Indian family in which the MLH1 gene mutation for hereditary nonpolyposis colorectal cancer (HNPCC) had been identified. The family had been observed by the authors since 1983 and over the years had been provided with intensive education regarding the natural history, of HNPCC as well as recommendations for cancer surveillance and management that was responsive to this natural history. METHODS. Following identification of the MLH1 mutation, DNA from family members was evaluated by a reference laboratory (OncorMed, Gaithersburg, MD), where sequences were checked in both the forward and reverse directions against the published sequence for MLH1. The 4bp deletion beginning at the first nucleotide of codon 727 was easily visualized in the heterozygous condition in both affected and predispositional individuals. The family was reeducated as a group and then provided further education individually during genetic counseling sessions, at which time they were appraised of potential penalties, such as insurance and employer discrimination, and psychological sequelae that could result from knowledge of the MLH1 mutation. Strict confidentiality of this information was assured. RESULTS. DNA testing was performed on 51 family members. Twenty-three individuals were counseled, seven of whom were positive for MLH1. Reactions ranged from full acceptance of the genetic implications to traditional Navajo reasoning such as the family had been cursed. CONCLUSIONS. DNA-based genetic counseling requires compassion and empathy, coupled with intensive preeducation regarding potential penalties and advantages that might emanate from this knowledge. Special care must be given to patients' culture, beliefs, and traditions. (C) 1996 American Cancer Society. C1 CREIGHTON UNIV,SCH MED,DEPT PREVENT MED,OMAHA,NE 68178. TUBA CITY INDIAN MED CTR,TUBA CITY,AZ. NETHERLANDS FDN DETECT HEREDITARY TUMOURS,LEIDEN,NETHERLANDS. CREIGHTON UNIV,SCH MED,DEPT GASTROENTEROL,OMAHA,NE. ONCORMED LABS,GAITHERSBURG,MD. CLARKSON HOSP,DEPT PATHOL,OMAHA,NE. NIH,MED GENET BRANCH,HUMAN GENOME RES PROJECT,BETHESDA,MD. UNIV HELSINKI,FAC MED,HELSINKI,FINLAND. NR 14 TC 20 Z9 20 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD JAN 1 PY 1996 VL 77 IS 1 BP 30 EP 35 DI 10.1002/(SICI)1097-0142(19960101)77:1<30::AID-CNCR7>3.0.CO;2-R PG 6 WC Oncology SC Oncology GA TL670 UT WOS:A1996TL67000007 PM 8630936 ER PT J AU Potischman, N Brinton, LA AF Potischman, N Brinton, LA TI Nutrition and cervical neoplasia SO CANCER CAUSES & CONTROL LA English DT Review DE cervical cancer; diet; epidemiology; human papillomavirus; review ID CERVICOVAGINAL EPITHELIAL-CELLS; BETA-CAROTENE LEVELS; INTRAEPITHELIAL NEOPLASIA; ASCORBIC-ACID; VITAMIN-A; RISK-FACTORS; FOLIC-ACID; ALPHA-TOCOPHEROL; CANCER INCIDENCE; NUTRIENT STATUS AB Epidemiologic evidence on the relation between nutrition and cervical cancer is reviewed. Cervical cancer is the leading cancer among women in many developing countries, and remains a major public health problem worldwide. This review of nutritional research on cervical neoplasia encompasses the range of epithelial abnormalities from early preneoplastic lesions to invasive cancer. Identified risk factors for cervical neoplasia suggest a multifactorial etiology with several cancer-associated human papillomaviruses (HPV) as the central cause. Studies of nutritional predictors of cervical neoplasia to date, however, have been limited by inadequate HPV measures,which compromise the interpretations of findings. Current research using accurate measures of HPV will be most revealing. Nonetheless, agreement in findings from previous studies suggest a role for nutritional factors in some or all stages of cervical neoplasia. Low vitamin C and carotenoid status are associated fairly consistently with both cervical cancer and precursors, whereas results for vitamin E status are less consistent. The effect of folate status may be restricted to early preneoplastic cervical lesions and not to more advanced disease. Current research is addressing nutritional influences on HPV infection and persistence and on progression of cervical disease. Limitations and recommendations for future research directions are discussed in light of methodologic issues related to nutritional and HPV research. RP Potischman, N (reprint author), NCI, DIV CANC EPIDEMIOL & GENET, ENVIRONM EPIDEMIOL BRANCH, NUTR EPIDEMIOL SECT, EXECUT PLAZA N, BETHESDA, MD 20892 USA. RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 NR 79 TC 61 Z9 63 U1 0 U2 4 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD JAN PY 1996 VL 7 IS 1 BP 113 EP 126 DI 10.1007/BF00115643 PG 14 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA TV618 UT WOS:A1996TV61800011 PM 8850440 ER PT J AU Ziegler, RG Mayne, ST Swanson, CA AF Ziegler, RG Mayne, ST Swanson, CA TI Nutrition and lung cancer SO CANCER CAUSES & CONTROL LA English DT Review DE diet; epidemiology; lung cancer; smoking; review ID DIETARY VITAMIN-A; SERUM BETA-CAROTENE; FOLLOW-UP; SUBSEQUENT RISK; EPIDEMIOLOGIC EVIDENCE; CIGARETTE-SMOKING; FINNISH MEN; NEW-JERSEY; INTERVENTION TRIAL; PROSPECTIVE BASEL AB Epidemiologic evidence on the relationship between nutrition and lung cancer is reviewed. Observational studies of diet and lung cancer, both prospective and retrospective, continue to suggest strongly that increased vegetable and fruit intake is associated with reduced risk in men and women; in various countries; in smokers, ex-smokers, and never-smokers; and for all histologic types of lung cancer. Prospective studies of blood beta-carotene levels, arguably the best available biomarker of vegetable and fruit intake, indicate that low levels are predictive of increased lung cancer incidence. However, in a randomized, placebo-controlled clinical trial in male smokers, lung cancer incidence and total mortality were increased significantly among the men receiving beta-carotene supplements. If beta-carotene can prevent lung carcinogenesis,which the trial cannot rule out, then the dosage, duration of use, method of administration, and/or subpopulation are critical. Ongoing clinical trials, some of which include women, will provide much-needed information. Other carotenoids, other phytochemicals, and associated dietary patterns may explain the beneficial effects of vegetables and fruits and have not been explored adequately in epidemiologic work. Several observational epidemiologic studies, both prospective and retrospective, have indicated that diets high in fat, saturated fat, and cholesterol may increase the risk of lung cancer and that the effect is not mediated through vegetable and fruit intake. The relationship, although not yet established, merits further investigation. Since beta-carotene can function as an antioxidant, other micronutrients with this potential, specifically vitamins E and C and selenium, also have been proposed to reduce lung cancer risk. However, the totality of the epidemiologic evidence is not, at present, persuasive for any one of these micronutrients. C1 YALE UNIV, SCH MED, DEPT EPIDEMIOL & PUBL HLTH, NEW HAVEN, CT 06510 USA. YALE UNIV, CTR CANC, NEW HAVEN, CT 06510 USA. RP Ziegler, RG (reprint author), NCI, DIV CANC EPIDEMIOL & GENET, NUTR EPIDEMIOL SECT, EXECUT PLAZA N 443, BETHESDA, MD 20892 USA. NR 161 TC 250 Z9 254 U1 1 U2 15 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 EI 1573-7225 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD JAN PY 1996 VL 7 IS 1 BP 157 EP 177 DI 10.1007/BF00115646 PG 21 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA TV618 UT WOS:A1996TV61800014 PM 8850443 ER PT J AU Brunda, MJ Luistro, L Rumennik, L Wright, RB Dvorozniak, M Aglione, A Wigginton, JM Wiltrout, RH Hendrzak, JA Palleroni, AV AF Brunda, MJ Luistro, L Rumennik, L Wright, RB Dvorozniak, M Aglione, A Wigginton, JM Wiltrout, RH Hendrzak, JA Palleroni, AV TI Antitumor activity of interleukin 12 in preclinical models SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article; Proceedings Paper CT 11th Bristol-Myers-Squibb Nagoya International Cancer Treatment Symposium - Cytokines and New Anticancer Agents on the Horizon of Oncology CY NOV 24-25, 1995 CL NAGOYA, JAPAN SP Bristol Myers Squibb DE antitumor activity; cytokine; interleukin 12; interleukin 2; interferon ID CELL STIMULATORY FACTOR; LYMPHOCYTE MATURATION FACTOR; NATURAL-KILLER-CELLS; IN-VIVO; T-CELLS; INTERFERON-GAMMA; HETERODIMERIC CYTOKINE; MURINE TUMORS; IL-12; MICE AB Interleukin 12 (IL-12) is a heterodimeric cytokine with a number of biological effects that are consistent with its potential role as an antitumor agent. The antimetastatic and antitumor activities of IL-12 have been demonstrated in a number of murine tumor models. Both the inhibition of established experimental pulmonary or hepatic metastases and a reduction in spontaneous metastases have been achieved by treatment with murine IL-12. Systemic treatment of mice bearing subcutaneous tumors with IL-12 results in tumor growth inhibition, prolongation of survival, and, in some models, tumor regression. The antitumor effect of IL-12 in these models is dose-dependent and can be initiated against well-established tumors. Mice cured of their tumor by IL-12 treatment are specifically immune to rechallenge with the same tumor. A series of experiments have demonstrated that both T-cells and interferon-gamma (IFN-gamma) induction are necessary for the optimal antitumor effects of IL-12. However, the antitumor efficacy of IL-12 has not been observed after exogenous administration of murine IFN-gamma, suggesting that additional factors may be important for the antitumor effects of IL-12. In several tumor models, IL-12 is more active or has a larger therapeutic window than either IL-2 or IFN-alpha, two cytokines with demonstrated antitumor activity against human malignancies. Combining IL-12 with other cytokines or chemotherapeutic drugs can improve antitumor effects. C1 SAIC FREDERICK,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD. NCI,FREDERICK CANC RES & DEV CTR,DIV BASIC SCI,EXPT IMMUNOL LAB,FREDERICK,MD. RP Brunda, MJ (reprint author), HOFFMANN LA ROCHE INC,DEPT ONCOL,340 KINGSLAND ST,NUTLEY,NJ 07110, USA. NR 51 TC 57 Z9 57 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PY 1996 VL 38 SU S BP S16 EP S21 DI 10.1007/s002800051031 PG 6 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA VC785 UT WOS:A1996VC78500004 PM 8765410 ER PT J AU Garry, VF Tarone, RE Long, L Griffith, J Kelly, JT Burroughs, B AF Garry, VF Tarone, RE Long, L Griffith, J Kelly, JT Burroughs, B TI Pesticide appliers with mixed pesticide exposure: G-banded analysis and possible relationship to non-Hodgkin's lymphoma SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID 7-14 TRANSLOCATIONS; CHROMOSOME REARRANGEMENTS; NONRANDOM OCCURRENCE; FRAGILE SITES; LYMPHOCYTES; INVERSION; CULTURES; ANGELMAN; CELL AB To further investigate the possible relationships between agricultural pesticide exposure and the increased risk of non-Hodgkin's Lymphoma among farm workers in the north central United States, we performed G-banded chromosome analyses of peripheral blood from workers classified according to primary types of pesticide exposure: herbicides (n = 20), insecticides (n = 18), fumigants (n = 23), and occupationally unexposed controls (n = 33). Significantly increased rearrangement frequencies were demonstrated in fumigant and insecticide appliers compared to control subjects. At certain chromosome bands there were significant excesses of breaks observed in pesticide appliers, but no breaks were observed in controls. Some of these bands contained genes with potential implications for cancer risk, including oncogenes and genes involved in tumor suppression and apoptosis. Of particular interest with regard to lymphoma risk were the excess rearrangements and breaks involving band 14q32 in fumigant appliers and the excess breaks involving band 18q21 in herbicide appliers; translocations linking 14q32 and 18q21 are the most common rearrangements observed in non-Hodgkin's lymphoma patients. The potential pathobiological relevance of these cytogenetic events warrants additional investigation at the molecular level. C1 NCI,BETHESDA,MD 20892. US EPA,RES TRIANGLE PK,NC 27711. UNIV MINNESOTA,DEPT FAMILY PRACTICE & COMMUNITY HLTH,MINNEAPOLIS,MN 55455. RP Garry, VF (reprint author), UNIV MINNESOTA,LAB ENVIRONM MED & PATHOL,STONE LAB 1,421 29TH AVE SE,MINNEAPOLIS,MN 55414, USA. NR 39 TC 36 Z9 36 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JAN PY 1996 VL 5 IS 1 BP 11 EP 16 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA TP311 UT WOS:A1996TP31100003 PM 8770460 ER PT J AU Chow, WH McLaughlin, JK Mandel, JS Wacholder, S Niwa, S Fraumeni, JF AF Chow, WH McLaughlin, JK Mandel, JS Wacholder, S Niwa, S Fraumeni, JF TI Obesity and risk of renal cell cancer SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID CIGARETTE-SMOKING; CARCINOMA; WOMEN; KIDNEY; HYPERTENSION; HAMSTER; WEIGHT; MEN; ESTROGEN; DISEASE AB In a population-based case control study including 449 directly interviewed cases and 707 controls, we assessed the risk of renal cell cancer associated with height, weight, body mass index (BMI), and frequency of weight changes. Odds ratios and 95% confidence intervals were estimated by using logistic regression models. Among women, risk increased with increasing usual BMI (P for trend < 0.001). A nearly 4-fold risk was found among the 10% of women with the highest usual BMI (odds ratio = 3.8; confidence interval = 1.7-8.4). Among men, no clear trend was observed with usual weight or BMI, although the highest risk (30-50%) generally was seen among those in the upper deciles of weight or BMI. There was no clear indication that excess BMI early or late in life disproportionately affected risk. Risk also was not related to patterns of weight fluctuations or use of diet pills. Our study supports previous observations linking renal cell cancer risk to increased BMI among women and suggests a weaker association in men. Given the increasing prevalence of obesity and the rising incidence of renal cell cancer in the United States, additional studies are needed to disentangle the effects of BMI from various correlates and to identify the mechanisms by which obesity affects risk. C1 NCI,DIV CANC EPIDEMIOL & GENET,ROCKVILLE,MD 20852. UNIV MINNESOTA,SCH PUBL HLTH,DIV ENVIRONM & OCCUPAT HLTH,MINNEAPOLIS,MN 55455. WESTAT CORP,ROCKVILLE,MD 20850. NR 50 TC 54 Z9 56 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JAN PY 1996 VL 5 IS 1 BP 17 EP 21 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA TP311 UT WOS:A1996TP31100004 PM 8770461 ER PT J AU You, WC Zhang, L Yang, CS Chang, YS Issaq, H Fox, SD Utermahlen, WE Zhao, L Keefer, L Liu, WD Chow, WH Ma, JL Kneller, R Ho, MYK Fraumeni, JF Xu, GW Blot, WJ AF You, WC Zhang, L Yang, CS Chang, YS Issaq, H Fox, SD Utermahlen, WE Zhao, L Keefer, L Liu, WD Chow, WH Ma, JL Kneller, R Ho, MYK Fraumeni, JF Xu, GW Blot, WJ TI Nitrite, N-nitroso compounds, and other analytes in physiological fluids in relation to precancerous gastric lesions SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID HIGH-RISK; STOMACH-CANCER; ENDOGENOUS FORMATION; URINARY-EXCRETION; BIOLOGICAL-FLUIDS; CARCINOGENESIS; NITRATE; JUICE; NITROSAMINES; HYPOTHESIS AB Levels of gastric juice nitrite, several urinary N-nitroso compounds, and other analytes were examined among nearly 600 residents in an area of Shandong, China, where precancerous gastric lesions are common and rates of stomach cancer are among the world's highest. Gastric juice nitrite levels were considerably higher among those with gastric juice pH values above 2.4 versus below 2.4. Nitrite was detected more often and at higher levels among persons with later stage gastric lesions, especially when gastric pH was high. Of those with intestinal metaplasia, 17.5% had detectable levels of gastric nitrite, while this analyte was detected in only 7.2% of those with less advanced lesions. Relative to those with undetectable nitrite, the odds of intestinal metaplasia increased from 1.5 (95% confidence interval = 0.6-4.1) to 4.1 (95% confidence interval = 1.8-9.3) among those with low and high nitrite concentrations, respectively. Urinary acetaldehyde and formaldehyde levels also tended to be higher among those with more advanced pathology, particularly dysplasia. However, urinary excretion levels of total N-nitroso compounds and several nitrosamino acids differed little among those with chronic atrophic gastritis and intestinal metaplasia and dysplasia, consistent with findings from recent studies in the United Kingdom, France, and Colombia. The data from this high-risk population suggest that elevated levels of gastric nitrite, especially in a high pH environment, are associated with advanced precancerous gastric lesions, although specific N-nitroso compounds were not implicated. C1 BEIJING MED UNIV,BEIJING INST CANC RES,BEIJING 100034,PEOPLES R CHINA. BEIJING MED UNIV,SCH ONCOL,BEIJING 100034,PEOPLES R CHINA. WEIFANG MED INST,WEIFANG 261041,SHANDONG,PEOPLES R CHINA. LINQU PUBL HLTH,SHANDONG 262600,PEOPLES R CHINA. RUTGERS STATE UNIV,CANC RES LAB,PISCATAWAY,NJ 08855. PRI DYNCORP,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21702. NCI,BETHESDA,MD 20892. INT EPIDEMIOL INST LTD,ROCKVILLE,MD 20850. FU NCI NIH HHS [N01-CP-15620, N01-CP-21009, N01-CP-05631] NR 37 TC 20 Z9 23 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JAN PY 1996 VL 5 IS 1 BP 47 EP 52 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA TP311 UT WOS:A1996TP31100009 PM 8770466 ER PT J AU Longo, DL AF Longo, DL TI The case against the routine use radiation therapy in advanced-stage Hodgkin's disease SO CANCER INVESTIGATION LA English DT Article ID COMBINED MODALITY THERAPY; LOW-DOSE RADIATION; COMBINATION CHEMOTHERAPY; FOLLOW-UP; MEDIASTINAL INVOLVEMENT; MOPP CHEMOTHERAPY; RANDOMIZED TRIAL; FIELD RADIATION; RISK; RADIOTHERAPY RP Longo, DL (reprint author), NIA,NIH,BALTIMORE,MD 21224, USA. NR 49 TC 6 Z9 6 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 SN 0735-7907 J9 CANCER INVEST JI Cancer Invest. PY 1996 VL 14 IS 4 BP 353 EP 360 DI 10.3109/07357909609012163 PG 8 WC Oncology SC Oncology GA UY225 UT WOS:A1996UY22500010 PM 8689431 ER PT J AU Figg, WD Ammerman, K Patronas, N Steinberg, SM Walls, RG Dawson, N Reed, E Sartor, O AF Figg, WD Ammerman, K Patronas, N Steinberg, SM Walls, RG Dawson, N Reed, E Sartor, O TI Lack of correlation between prostate-specific antigen and the presence of measurable soft tissue metastases in hormone-refractory prostate cancer SO CANCER INVESTIGATION LA English DT Article AB Appropriate staging procedures for patients with hormone-refractory prostate cancer are poorly defined. In particular, there are no studies correlating prostate-specific antigen (PSA) with more traditional methods of staging. We have evaluated the abdominal/pelvic CT scan, bone scan, and PSA results following initial diagnosis of hormone-refractory prostate cancer in 177 consecutive patients (median age = 63.1 years, range 45-80). Thirty-four patients (19.2%) had measurable lesions (greater than or equal to 2 cm) on CT scan compatible with metastatic disease. Of the patients with measurable lesions, 29/34 (85.3%) had retroperitoneal and/or pelvic adenopathy; 5 patients (14.7%) had measurable lesions in the liver. Other sites of metastatic disease were detected in less than 1% of the patients receiving scans. All patients had bone scan abnormalities compatible with metastatic disease. Results of these imaging studies were then compared to PSA serum concentration (Abbott IMx). The mean PSA concentration was not different in those patients with soft tissue disease as compared to those without soft tissue involvement and there was no correlation between PSA concentration and the presence or absence of measurable soft tissue disease. In contrast to previously published studies in hormone-naive prostate cancer patients, these studies in hormone-refractory patients indicate that the detection of metastatic disease by standard radiological procedures cannot be predicted by measurement of serum PSA. C1 NCI, DEPT DIAGNOST RADIOL, NIH, BETHESDA, MD 20892 USA. NCI, BIOSTAT & DATA MANAGEMENT SECT, NIH, DIV CLIN SCI, BETHESDA, MD 20892 USA. RP Figg, WD (reprint author), NCI, CLIN PHARMACOL BRANCH,NIH,BLDG 10,ROOM 5A01, 9000 ROCKVILLE PIKE, BETHESDA, MD 20892 USA. RI Figg Sr, William/M-2411-2016 NR 12 TC 34 Z9 35 U1 0 U2 0 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0735-7907 EI 1532-4192 J9 CANCER INVEST JI Cancer Invest. PY 1996 VL 14 IS 6 BP 513 EP 517 DI 10.3109/07357909609076896 PG 5 WC Oncology SC Oncology GA VW262 UT WOS:A1996VW26200002 PM 8951355 ER PT J AU Kuettel, MR Thraves, PJ Jung, M Varghese, SP Prasad, SC Rhim, JS Dritschilo, A AF Kuettel, MR Thraves, PJ Jung, M Varghese, SP Prasad, SC Rhim, JS Dritschilo, A TI Radiation-induced neoplastic transformation of human prostate epithelial cells SO CANCER RESEARCH LA English DT Article ID K-RAS; IONIZING-RADIATION; ALLELIC LOSS; CANCER; DNA; ACTIVATION; ONCOGENE; GENES; MUTATIONS AB We report the malignant transformation of human prostate epithelial cells (267B1) after multiple exposures to ionizing radiation. Carcinogenic progression of cells from immortal growth to anchorage-independent growth in soft agar to tumorigenicity in athymic mice resulted after a cumulative X-ray dose of 30 Gy. The tumors were characterized histologically as poorly differentiated adenocarcinomas, expressed prostate-specific antigen, and stained positive for keratin. No p53 or ras mutations were observed. Numerous chromosomal defects were noted on karyotypes after radiation exposure. However, chromosome 3 and 8 translocations were observed predominantly in the tumor outgrowths. These findings provide the first evidence of malignant transformation of human prostate epithelial cells exposed to ionizing radiation. C1 NCI,MOLEC ONCOL LAB,FREDERICK,MD 21702. RP Kuettel, MR (reprint author), GEORGETOWN UNIV,SCH MED,VINCENT T LOMBARDI CANC RES CTR,DEPT RADIAT MED,WASHINGTON,DC 20007, USA. FU NCI NIH HHS [R01-CA45408, CA52954] NR 33 TC 44 Z9 44 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 1 PY 1996 VL 56 IS 1 BP 5 EP 10 PG 6 WC Oncology SC Oncology GA TM481 UT WOS:A1996TM48100003 PM 8548774 ER PT J AU Liu, Y Martindale, JL Gorospe, M Holbrook, NJ AF Liu, Y Martindale, JL Gorospe, M Holbrook, NJ TI Regulation of p21(WAF1/CIP1) expression through mitogen-activated protein kinase signaling pathway SO CANCER RESEARCH LA English DT Article ID DIFFERENTIATION AB p21(WAF1/CIP1) is a cyclin-dependent kinase inhibitor whose expression in mammalian tissues is highly induced in response to stress as well as during normal development and differentiation. Induction of p21(WAF1/CIP1) in response to DNA damage occurs through a transcriptional mechanism that is dependent on the activation of the tumor suppressor protein p53. Recent evidence indicates that p21(WAF1/CIP1),an also be induced independent of p53, but the signal transduction mechanisms involved in regulating p21(WAF1/CIP1) expression in these situations have not been elucidated. In this study, we have addressed the role of the mitogen-activated protein kinase signaling pathway in the induction of p21(WAF1/CIP1) in response to growth factor treatment. Using an experimental approach involving cotransfection of a p21(WAF1/CIP1) promoter-luciferase construct with a variety of plasmids expressing dominant positive or dominant negative mutant proteins involved in this signaling pathway, we provide evidence to support a role for mitogen-activated protein kinase in the transcriptional activation of p21(WAF1/CIP1) by growth factor stimulation. C1 NIA,GERONTOL RES CTR,CELLULAR & MOLEC BIOL LAB,GENE EXPRESS & AGING SECT,BALTIMORE,MD 21224. RI Liu, Yusen/E-3527-2011 NR 23 TC 191 Z9 194 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 1 PY 1996 VL 56 IS 1 BP 31 EP 35 PG 5 WC Oncology SC Oncology GA TM481 UT WOS:A1996TM48100008 PM 8548769 ER PT J AU Minnick, DT Kunkel, TA AF Minnick, DT Kunkel, TA TI DNA synthesis errors, mutators and cancer SO CANCER SURVEYS LA English DT Article ID TYPE-1 REVERSE-TRANSCRIPTASE; 5' EXONUCLEASE ACTIVITY; HAMSTER OVARY CELLS; ESCHERICHIA-COLI; CRYSTAL-STRUCTURE; POLYMERASE-I; SACCHAROMYCES-CEREVISIAE; EXCISION-REPAIR; AMINO-ACID; DEOXYNUCLEOSIDE TRIPHOSPHATE RP Minnick, DT (reprint author), NIEHS, MOL GENET LAB, RES TRIANGLE PK, NC 27709 USA. NR 94 TC 27 Z9 27 U1 0 U2 1 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 0261-2429 J9 CANCER SURV JI Cancer Surv. PY 1996 VL 28 BP 3 EP 20 PG 18 WC Oncology SC Oncology GA WC238 UT WOS:A1996WC23800002 PM 8977025 ER PT J AU Woodgate, R Levine, A AF Woodgate, R Levine, A TI Damage inducible mutagenesis: Recent insights into the activities of the Umu family of mutagenesis proteins SO CANCER SURVEYS LA English DT Article ID DNA-POLYMERASE-III; RECA-MEDIATED CLEAVAGE; ULTRAVIOLET-LIGHT MUTAGENESIS; UV-INDUCED MUTATIONS; ESCHERICHIA-COLI; SOS MUTAGENESIS; SALMONELLA-TYPHIMURIUM; CHEMICAL MUTAGENESIS; EPSILON-SUBUNIT; SAMAB OPERONS RP Woodgate, R (reprint author), NICHHD,SECT DNA REPLICAT REPAIR & MUTAGENESIS,NIH,BETHESDA,MD 20892, USA. NR 98 TC 48 Z9 48 U1 0 U2 2 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 0261-2429 J9 CANCER SURV JI Cancer Surv. PY 1996 VL 28 BP 117 EP 140 PG 24 WC Oncology SC Oncology GA WC238 UT WOS:A1996WC23800009 PM 8977032 ER PT J AU Wang, XW Harris, CC AF Wang, XW Harris, CC TI TP53 tumour suppressor gene: Clues to molecular carcinogenesis and cancer therapy SO CANCER SURVEYS LA English DT Review ID WILD-TYPE P53; DNA-BINDING FUNCTION; CELL-CYCLE CONTROL; LI-FRAUMENI SYNDROME; PROTEIN-KINASE-C; TRANSCRIPTIONAL ACTIVATION; IN-VIVO; P53-DEFICIENT MICE; T-ANTIGEN; HEPATOCELLULAR-CARCINOMA RP Wang, XW (reprint author), NCI,HUMAN CARCINOGENESIS LAB,DIV BASIC SCI,NIH,BETHESDA,MD 20892, USA. RI Wang, Xin/B-6162-2009 NR 234 TC 33 Z9 34 U1 0 U2 0 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 0261-2429 J9 CANCER SURV JI Cancer Surv. PY 1996 VL 28 BP 169 EP 196 PG 28 WC Oncology SC Oncology GA WC238 UT WOS:A1996WC23800012 PM 8977035 ER PT J AU Kirsch, IR Lista, F AF Kirsch, IR Lista, F TI Transrearrangements as biomarkers for risk of lymphoid malignancy SO CANCER SURVEYS LA English DT Article ID DEPENDENT PROTEIN-KINASE; T-CELL TUMORS; IMMUNOGLOBULIN GENE REARRANGEMENT; ATAXIA-TELANGIECTASIA LYMPHOCYTES; GLYCOPHORIN-A MUTATIONS; BROKEN DNA-MOLECULES; V(D)J RECOMBINATION; HODGKINS-DISEASE; CHROMOSOME-14 INVERSION; SCID MICE RP Kirsch, IR (reprint author), USN,NCI,MED ONCOL BRANCH,BETHESDA,MD 20889, USA. NR 81 TC 2 Z9 2 U1 1 U2 1 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 0261-2429 J9 CANCER SURV JI Cancer Surv. PY 1996 VL 28 BP 311 EP 327 PG 17 WC Oncology SC Oncology GA WC238 UT WOS:A1996WC23800020 PM 8977043 ER PT S AU Shtern, F AF Shtern, F BE Lemke, HU Vannier, MW Inamura, K Farman, AG TI Novel digital technologies for improved control of breast cancer SO CAR '96: COMPUTER ASSISTED RADIOLOGY SE INTERNATIONAL CONGRESS SERIES LA English DT Proceedings Paper CT International Symposium on Computer and Communication Systems for Image Guided Diagnosis and Therapy (CAR 96) CY JUN, 1996 CL PARIS, FRANCE RP Shtern, F (reprint author), NCI,DIV CANC TREATMENT,DIAGNOSIS & CTR,NIH,RM 3A44,BLDG 31,BETHESDA,MD 20892, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE PUBL B V PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0531-5131 BN 0-444-82497-9 J9 INT CONGR SER PY 1996 VL 1124 BP 357 EP 361 PG 5 WC Engineering, Biomedical; Medical Informatics; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Medical Informatics; Radiology, Nuclear Medicine & Medical Imaging GA BG22F UT WOS:A1996BG22F00062 ER PT J AU Diwan, BA Henneman, JR Rice, JM Nims, RW AF Diwan, BA Henneman, JR Rice, JM Nims, RW TI Enhancement of thyroid and hepatocarcinogenesis by 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene in rats at doses that cause maximal induction of CYP2B SO CARCINOGENESIS LA English DT Article ID PHENOBARBITAL-LIKE INDUCER; MONO-OXYGENASE ACTIVITY; N-NITROSODIETHYLAMINE; HORMONE LEVELS; METABOLISM; PROMOTION; LIVER; MICE; CARCINOGENESIS; SUSCEPTIBILITY AB To investigate the promoting effects of 1,4-bis[2-(3,5-dichlorspyridyloxy)]benzene (TCPOBOP) on liver and thyroid carcinogenesis of rats at doses that cause maximal induction of hepatic CYP2B, 5-week-old male F344 rats were given either a single i.p. dose of 75 mg N-nitrosodiethylamine (NDEA)/kg body wt in saline or saline alone. After 2 weeks the rats were fed control diet or a diet containing 330 or 1000 p.p.m. TCPOBOP or 500 p.p.m. phenobarbital (PB; a positive control group). A total of four sequential sacrifices (9, 30, 52 and 79 weeks of age) was performed. At 30 weeks the mean volume (mm(3)) of hepatocellular foci in NDEA-initiated rats exposed to either dose of TCPOBOP or to PB was significantly increased as compared with rats exposed to NDEA followed by control diet (P < 0.05). In addition, the volume percentage of liver occupied by foci was significantly greater in NDEA-initiated/1000 p.p.m. TCPOBOP-promoted rats as compared with rats exposed to NDEA alone (P < 0.05, n = 6). At 52 weeks of age the incidences (and multiplicities, in units of tumors per tumor-bearing rat) of hepatocellular adenomas were 0, 83 (2.6 +/- 1.3), 100 (3.4 +/- 2.1) or 67% (2.5 +/- 1.9) in rats exposed to NDEA alone or NDEA followed by 330 or 1000 p.p.m. TCPOBOP or 500 p.p.m. PB respectively (n = 12). Hepatocellular carcinomas were found only in rats given 1000 p.p.m. TCPOBOP (17% incidence) or PB (8% incidence) following NDEA initiation. The incidences of thyroid follicular cell adenomas were 0, 17, 33 or 8% in rats exposed to NDEA alone or NDEA followed by 330 or 1000 p.p.m. TCPOBOP or 500 p.p.m. PB respectively. Between 53 and 79 weeks of age 38% of rats treated with NDEA alone developed multiple (1.5 +/- 0.8) hepatocellular adenomas. This incidence was enhanced to 100% in rats exposed to NDEA followed by either 330 or 1000 p.p.m. TCPOBOP. Multiplicities of hepatocellular adenomas were also increased significantly (10.5 +/- 3.9, 10.4 +/- 7.0 and 10.1 +/- 6.7 respectively) in rats promoted with 330 or 1000 p.p.m. TCPOBOP or 500 p.p.m. PB. None of the rats exposed to NDEA alone developed hepatocellular carcinomas, while multiple hepatocellular carcinomas occurred in 38% of the rats exposed to 330 p.p.m. and 78% of the rats given 1000 p.p.m. TCPOBOP following NDEA initiation. Thyroid follicular cell tumors occurred at 79 weeks in more than 40 and 50% incidences in rats exposed to NDEA followed by 330 or 1000 p.p.m. TCPOBOP respectively. Also, a significant decrease in serum levels of triiodothyronine and thyroxine were observed in non-initiated 79-week-old rats fed 1000 p.p.m. TCPOBOP, compared with age-matched untreated controls (n = 6). Increases in hepatic CYP2B-mediated benzyloxy-resorufin O-dealkylase activity detected in rats exposed to 330 and 1000 p.p.m. TCPOBOP for 2 or 23 weeks were similar in magnitude to those caused by 500 p.p.m. PB. Thus TCPOBOP at maximal CYP2B induction doses exhibits a strong promoting activity for both liver and thyroid of rats. C1 NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21702. RP Diwan, BA (reprint author), NCI,FREDERICK CANC RES & DEV CTR,BIOL CARCINOGENESIS & DEV PROGRAM,SAIC FREDERICK,FREDERICK,MD 21702, USA. NR 24 TC 26 Z9 26 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JAN PY 1996 VL 17 IS 1 BP 37 EP 43 DI 10.1093/carcin/17.1.37 PG 7 WC Oncology SC Oncology GA UC148 UT WOS:A1996UC14800007 PM 8565134 ER PT J AU DeBenedetti, VMG Welsh, JA Yu, MC Bennett, WP AF DeBenedetti, VMG Welsh, JA Yu, MC Bennett, WP TI p53 mutations in hepatocellular carcinoma related to oral contraceptive use SO CARCINOGENESIS LA English DT Article ID HUMAN CANCER; EXOGENOUS HORMONES; FEMALE RATS; LIVER; GENE; POLYMORPHISM; HEPATOCARCINOGENESIS; CARCINOGENESIS; EPIDEMIOLOGY; ESTRADIOL AB Oral contraceptives (OCs) are implicated in the development of hepatocellular carcinoma (HCC). Mitogenic stimulation may be the primary mechanism of tumorigenesis, but other factors may also contribute. Mutational spectrum analysis can provide insights into pathogenesis, therefore we analyzed the p53 tumor suppressor gene in 10 HCCs from women with a history of OC use, All were non-Asians whose average OC use was 6.7 years (range 2 months-13 years) and whose mean age at HCC diagnosis was 48.8 years (range 21-67 years), Each tumor was analyzed by immunohistochemistry, DNA sequencing and allelic deletion analysis, Three tumors were positive by p53 immunohistochemistry; allelic deletion analysis identified loss of heterozygosity in one of four informative cases, Two p53 point mutations were found in one tumor containing moderately and well-differentiated components; this patient was negative for all serological markers of hepatitis B and C infections. Both components showed p53 protein accumulation and a GTT(val)-->GCT(ala) mutation at codon 274, In addition, a silent mutation (ACC(thr)-->ACT(thr)) at codon 140 of the p53 gene was detected in the moderately differentiated component of the tumor. These preliminary data indicate that p53 mutations are uncommon in OC-related HCCs. One of the two detected mutations was a G:C-->A:T transition at a non-CpG site, which is characteristic of DNA damage by free radicals, These data support a model whereby estrogens contribute to HCC development primarily through mitogen stimulation and secondarily by mutagenesis via hydroxyl radicals produced during estrogen metabolism, Confirmational analysis of a larger series is warranted. C1 NCI,HUMAN CARCINOGENESIS LAB,NIH,BETHESDA,MD 20892. UNIV SO CALIF,KENNETH NORRIS JR COMPREHENS CANC CTR,LOS ANGELES,CA 90033. NR 43 TC 15 Z9 15 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JAN PY 1996 VL 17 IS 1 BP 145 EP 149 DI 10.1093/carcin/17.1.145 PG 5 WC Oncology SC Oncology GA UC148 UT WOS:A1996UC14800023 PM 8565124 ER PT J AU Konig, R Fleury, S Germain, RN AF Konig, R Fleury, S Germain, RN TI The structural basis of CD4-MHC class 11 interactions: Coreceptor contributions to T cell receptor antigen recognition and oligomerization-dependent signal transduction SO CD4 MOLECULE SE CURRENT TOPICS IN MICROBIOLOGY AND IMMUNOLOGY LA English DT Review ID CLASS-II MHC; HUMAN-IMMUNODEFICIENCY-VIRUS; TOXIC LYMPHOCYTES-T; HISTOCOMPATIBILITY COMPLEX-MOLECULES; MONOCLONAL-ANTIBODY GK1.5; PROTEIN KINASE P56LCK; CD4 BINDING-SITE; ENVELOPE GLYCOPROTEIN; LOW-AFFINITY; PHYSICAL ASSOCIATION C1 NIAID,IMMUNOL LAB,LYMPHOCYTE BIOL SECT,BETHESDA,MD 20892. RP Konig, R (reprint author), UNIV TEXAS,MED BRANCH,DEPT MICROBIOL & IMMUNOL,SEALY CTR MOL SCI,301 UNIV BLVD,ROUTE J-19,GALVESTON,TX 77555, USA. RI Konig, Rolf/B-3128-2008 NR 93 TC 30 Z9 31 U1 1 U2 3 PU SPRINGER-VERLAG BERLIN PI BERLIN 33 PA HEIDELBERGER PLATZ 3, W-1000 BERLIN 33, GERMANY SN 0070-217X J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 1996 VL 205 BP 19 EP 46 PG 28 WC Immunology; Microbiology SC Immunology; Microbiology GA BJ47G UT WOS:A1996BJ47G00002 PM 8575196 ER PT J AU LacazVieira, F Kachar, B AF LacazVieira, F Kachar, B TI Tight junction dynamics in the frog urinary bladder SO CELL ADHESION AND COMMUNICATION LA English DT Article DE tight junction; frog urinary bladder; paracellular permeability; calcium; protein kinase C; H7; diC8 ID PROTEIN-KINASE-C; ADHESION MOLECULE UVOMORULIN; PANCREATIC ACINAR CELLS; EPITHELIAL MDCK CELLS; EXTRACELLULAR CALCIUM; OCCLUDING JUNCTIONS; APICAL MEMBRANE; AMPHIBIAN EPITHELIA; ZONULAE OCCLUDENTES; PLASMA-MEMBRANE AB In a previous study in frog skin (Castro et al., J. Memb. Biol. 134:15-29, 1993), it was shown that TJs experimentally disrupted by a selective deposition of BaSO4 could be resealed upon addition of Ca2+ to the apical solution; in the absence of apical Ca2+, the normal Ca2+ activity of the Na2SO4-Ringer's bathing the basolateral side was not able to induce TJ resealing. We now show that apical Ca2+ also activates the TJ sealing mechanism in frog urinary bladders. Three known procedures were utilized to increase TJ permeability, all in the absence of apical Ca2+: (i) exposure to high positive transepithelial clamping potentials; (ii) exposure of the apical surface to hypertonic solutions; and (iii) selective deposition of BaSO4 in the TJs. The resealing of the TJs was promoted by raising the concentration of Ca2+ in the apical solution. This effect of Ca2+ is not impaired by the presence of Ca2+ channel blockers (nifedipine, verapamil, Mn2+ or Cd2+) in the apical solution, indicating that junction resealing does not depend on Ca2+ entering the cells through the apical membrane. TJ resealing that occurs in response to raised apical Ca2+ most likely results from a direct effect of Ca2+, entering the disrupted TJs from the apical solution and reaching the zonula adhaerens Ca2+ receptors (E-cadherins), Protein kinase C (PKC) must play a significant role in the control of TJ assembly in this tight epithelia since the PKC inhibitor (H7) and the activator (diC8) markedly affect TJ recovery after disruption by apical hypertonicity. H7 treated tissues show marked recuperation of conductance even in the absence of apical Ca2+. In contrast, diC8 prevents tissue recuperation which normally occurs after addition of Ca2+ to the apical solution. C1 NIDCD,LAB CELLULAR BIOL,NIH,ROCKVILLE,MD 20850. UNIV SAO PAULO,INST BIOMED SCI,DEPT PHYSIOL & BIOPHYS,BR-05508 SAO PAULO,BRAZIL. NR 71 TC 10 Z9 10 U1 0 U2 0 PU HARWOOD ACAD PUBL GMBH PI READING PA C/O STBS LTD, PO BOX 90, READING, BERKS, ENGLAND RG1 8JL SN 1061-5385 J9 CELL ADHES COMMUN JI Cell Adhes. Commun. PY 1996 VL 4 IS 1 BP 53 EP 68 DI 10.3109/15419069609010763 PG 16 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA VE784 UT WOS:A1996VE78400005 PM 8870973 ER PT J AU Anderson, SS Wu, KJ Nagase, H StettlerStevenson, WG Kim, YK Tsilibary, EC AF Anderson, SS Wu, KJ Nagase, H StettlerStevenson, WG Kim, YK Tsilibary, EC TI Effect of matrix glycation on expression of type IV collagen, MMP-2, MMP-9 and TIMP-1 by human mesangial cells SO CELL ADHESION AND COMMUNICATION LA English DT Article DE mesangial cells; nonenzymatic glycosylation; type IV collagen; matrix metalloproteinases; diabetes ID MESSENGER-RNA LEVELS; EXTRACELLULAR-MATRIX; DIABETES-MELLITUS; GLOMERULAR MESANGIUM; ENDOTHELIAL-CELLS; END-PRODUCTS; VI COLLAGEN; PROTEINS; GLUCOSE; RATS AB Human mesangial cells grown in either 5 or 25 mM glucose were cultured on type IV collagen which had been previously control-incubated or in vitro glycated. Northern blot analysis revealed that after 3-7 days in culture mesangial cells on glycated type IV collagen expressed similar to 25-200% more alpha 1(IV), similar to 20-50%, less matrix metalloproteinase 2 (MMP-2), and 65-75% more tissue inhibitor of metalloproteinase 1 (TIMP-1). Decreased immunoreactivity (similar to 30-40%) and collagenolytic activity (similar to 10-40%) corresponding to MMP-2 was also detected in media conditioned during the third day of culture on glycated type IV collagen, These effects on cell function were related to the extent of type IV collagen modification and were similar for cells cultured in 5 or 25mM glucose. Elevated glucose (25 vrs 5mM) increased expression of alpha 1(IV) mRNA (similar to 40-70%) and in conjunction with matrix glycation resulted in detectable levels of MMP-9 message by northern blot although collagenolytic activity corresponding to MMP-9 was not detectable by zymography. We conclude that glucose and matrix glycation may each alter mesangial cell function, perhaps leading to an imbalance in mesangial matrix synthesis and degradation which could contribute to mesangial expansion characteristic of diabetic renal disease. C1 UNIV KANSAS,SCH MED,DEPT BIOCHEM & MOL BIOL,KANSAS CITY,KS 66160. NCI,PATHOL LAB,NIH,BETHESDA,MD 20892. UNIV MINNESOTA,SCH MED,DEPT PEDIAT,MINNEAPOLIS,MN 55455. RP Anderson, SS (reprint author), UNIV MINNESOTA,SCH MED,DEPT LAB MED & PATHOL,BOX 609 UMHC,420 DELAWARE ST SE,MINNEAPOLIS,MN 55455, USA. FU NIDDK NIH HHS [DK-43574]; PHS HHS [NIDOK-39216] NR 48 TC 34 Z9 40 U1 1 U2 3 PU HARWOOD ACAD PUBL GMBH PI READING PA C/O STBS LTD, PO BOX 90, READING, BERKS, ENGLAND RG1 8JL SN 1061-5385 J9 CELL ADHES COMMUN JI Cell Adhes. Commun. PY 1996 VL 4 IS 2 BP 89 EP 101 DI 10.3109/15419069609010765 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA VQ180 UT WOS:A1996VQ18000002 PM 8937745 ER PT J AU Tarasova, NI Romanov, VL DaSilva, PP Michejda, CJ AF Tarasova, NI Romanov, VL DaSilva, PP Michejda, CJ TI Numerous cell targets for gastrin in the guinea pig stomach revealed by gastrin CCKB receptor localization SO CELL AND TISSUE RESEARCH LA English DT Article DE parietal cells; gastric mucosa; secretion; receptor; gastrin; gastrointestinal hormones; guinea pig ID PARIETAL-CELLS; ACID-SECRETION; DISTINCT RECEPTORS; ENDOCRINE-CELLS; ANTIULCER DRUGS; CHOLECYSTOKININ; HISTAMINE; BINDING; MUCOSA AB The localization of the gastrin/CCKB receptor (GR) has recently become a subject of debate, especially since the publication of evidence for its presence in an unsuspected location, namely in the lamina propria, the submucosal layer of the stomach lining. Knowledge of the receptor localization is important because of the critical role of gastrin secretion and its trophic effects on the gastric epithelium. The present study, which utilizes immunohistochemistry and electron microscopy as primary tools, provides unequivocal data concerning the localization of GR in the guinea pig stomach. GR is expressed in parietal cells, on chief cells, and in previously unreported endocrine cells of the stomach. It is not found in the lamina propria. The predominant localization of the receptor in the endocrine cells is on the membranes of cytoplasmic electron-dense secretory granules. The positioning of these cells in the gastric glands suggests that they may be involved in;the uptake of gastrin from the circulation. The distribution of GR implies that it may be involved in the regulation of various processes and may mediate various effects of gastrin in the stomach. C1 NCI,FREDERICK CANC RES & DEV CTR,MATH BIOL LAB,MEMBRANE STRUCT SECT,FREDERICK,MD 21702. RP Tarasova, NI (reprint author), NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MOLEC ASPECTS DRUG DESIGN SECT,POB B,FREDERICK,MD 21702, USA. NR 33 TC 30 Z9 30 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0302-766X J9 CELL TISSUE RES JI Cell Tissue Res. PD JAN PY 1996 VL 283 IS 1 BP 1 EP 6 PG 6 WC Cell Biology SC Cell Biology GA TN882 UT WOS:A1996TN88200001 PM 8581949 ER PT J AU VandeWoude, GF AF VandeWoude, GF TI Untitled SO CELL GROWTH & DIFFERENTIATION LA English DT Editorial Material RP VandeWoude, GF (reprint author), NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,POB B,BLDG 469,FREDERICK,MD 21702, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1044-9523 J9 CELL GROWTH DIFFER JI Cell Growth Differ. PD JAN PY 1996 VL 7 IS 1 BP 1 EP 1 PG 1 WC Cell Biology SC Cell Biology GA TN638 UT WOS:A1996TN63800001 ER PT J AU Li, ML Hu, JD Heermeier, K Hennighausen, L Furth, PA AF Li, ML Hu, JD Heermeier, K Hennighausen, L Furth, PA TI Expression of a viral oncoprotein during mammary gland development alters cell fate and function: Induction of p53-independent apoptosis is followed by impaired milk protein production in surviving cells SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID WHEY ACIDIC PROTEIN; LARGE T-ANTIGEN; DEATH; GENE AB The disruption of cell cycle regulation is associated with developmental abnormalities and tumorigenesis. The SV40 large T antigen (Tag) interferes with cell cycle control by interacting with the pRb family and p53. Mice carrying a transgene composed of the whey acidic protein (WAR) gene promoter and the Tag coding sequence express Tag during pregnancy and are unable to nurse their young. Tag expression induced apoptosis in mammary epithelial cells during late pregnancy, At least 5% of mammary epithelial cells were undergoing apoptosis at any one time. In contrast, less than 0.2% of mammary epithelial cells in nontransgenic littermates was undergoing apoptosis. Apoptosis in Tag mice was associated with increased steady-state RNA levels of bar and bcl-x(L+S), with a relative increase in bcl-x(S) expression, Since p53 was sequestered by Tag, it is likely that p53-independent mechanisms precipitated apoptosis, The Tag-expressing mammary alveolar cells that did not undergo apoptosis continued to differentiate through late pregnancy, as measured by the sequential activation of milk protein gene expression, However, milk protein production, processing, and secretion was impaired, resulting in lactation failure. C1 UNIV MARYLAND,SCH MED,DEPT MED,DIV INFECT DIS,BALTIMORE,MD 21201. VET ADM MED CTR,BALTIMORE,MD 21201. NIDDKD,BIOCHEM & METAB LAB,BETHESDA,MD 20892. NR 36 TC 53 Z9 53 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1044-9523 J9 CELL GROWTH DIFFER JI Cell Growth Differ. PD JAN PY 1996 VL 7 IS 1 BP 3 EP 11 PG 9 WC Cell Biology SC Cell Biology GA TN638 UT WOS:A1996TN63800002 PM 8788028 ER PT J AU Li, ML Hu, JD Heermeier, K Hennighausen, L Furth, PA AF Li, ML Hu, JD Heermeier, K Hennighausen, L Furth, PA TI Apoptosis and remodeling of mammary gland tissue during involution proceeds through p53-independent pathways SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID WHEY ACIDIC PROTEIN; CELL-DEATH; GENE AB Mammary gland involution is a physiological process that follows lactation and results in the rapid disappearance of the entire lobulo-alveolar compartment. Coincident with the onset of involution, milk protein gene expression ceases and alveolar cells undergo programmed cell death, In mammary epithelial tissue culture cells in vitro, both p53-dependent and p53-independent apoptosis pathways have been identified. We investigated whether p53 induces apoptosis during mammary gland involution in vivo and participates in tissue remodeling. Toward this end, we examined the process of involution in the presence and absence of functional p53 in mouse models: wild-type, transgenic mice that express SV40 T-antigen specifically in mammary tissue during pregnancy; and mice that carry nonfunctional p53 alleles in their germ line, Mammary gland whole-mount and histological analyses revealed that involution and remodeling, with the concomitant disappearance of the lobulo-alveolar structures, proceeded normally in the absence of functional p53, In addition, the absence of functional p53 did not alter the involution related pattern of bar (death inducer) gene expression or the ratio of RNAs encoding bcl-x(S) (death inducer) to bcl-x(L) (survival inducer), C1 UNIV MARYLAND,SCH MED,DEPT MED,BALTIMORE VA MED CTR,DIV INFECT DIS,BALTIMORE,MD 21201. VET ADM MED CTR,BALTIMORE,MD. NIDDKD,BIOCHEM & METAB LAB,BETHESDA,MD 20892. NR 28 TC 87 Z9 87 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1044-9523 J9 CELL GROWTH DIFFER JI Cell Growth Differ. PD JAN PY 1996 VL 7 IS 1 BP 13 EP 20 PG 8 WC Cell Biology SC Cell Biology GA TN638 UT WOS:A1996TN63800003 PM 8788029 ER PT J AU Wadsworth, P Bottaro, DP AF Wadsworth, P Bottaro, DP TI Microtubule dynamic turnover is suppressed during polarization and stimulated in hepatocyte growth factor scattered Madin-Darby canine kidney epithelial cells SO CELL MOTILITY AND THE CYTOSKELETON LA English DT Article DE microtubule dynamics; polarized cells; MDCK epithelial cells ID REAL-TIME OBSERVATIONS; INDIVIDUAL MICROTUBULES; INTERPHASE CELLS; LIVING CELLS; FIBROBLAST LOCOMOTION; STABLE MICROTUBULES; INSTABILITY INVITRO; SURFACE POLARITY; TYROSINE KINASE; GTP HYDROLYSIS AB The dynamic behavior of microtubules has been measured in non-polarized, polarized, and hepatocyte growth factor treated Madin-Darby canine kidney epithelial cells. In a nocodazole disassembly assay, microtubules in polarized cells were more resistant to depolymerization than microtubules in non-polarized cells; microtubules in scattered cells were nearly completely disassembled. Analysis of fluorescent microtubules in living cells further revealed that individual microtubules in polarized cells were kinetically stabilized and microtubules in scattered cells were highly dynamic. Individual microtubule behavior in polarized cells was characterized by a suppression of the average rate of shortening, an increase in the average duration of pause, a decrease in the frequency of catastrophe transitions, and an increase in the frequency of rescue transitions, when compared with microtubules in non-polarized cells. In contrast, microubule behavior in epithelial cells treated with hepatocyte growth factor was characterized by increases in the average rates of microtubule growth and shortening, a decrease in the frequency of rescue transitions, and an increase in the frequency of catastrophe transitions, when compared with polarized cells. Dynamicity, a measure of the gain and loss of subunits from microtubule plus ends, was 2.7 mu m/min in polarized cells and 11.1 mu m/min in scattered cells. These results demonstrate that individual microtubule dynamic behavior is markedly suppressed in polarized epithelial cells. Our results further demonstrate that in addition to its previously characterized effects on cell locomotion, hepatocyte growth factor stimulates microtubule dynamic turnover in lamellar regions of living cells. (C) 1996 Wiley-Liss, Inc. C1 UNIV MASSACHUSETTS,PROGRAM MOL & CELLULAR BIOL,AMHERST,MA 01003. NCI,CELLULAR & MOL BIOL LAB,BETHESDA,MD 20892. RP Wadsworth, P (reprint author), UNIV MASSACHUSETTS,DEPT BIOL,CB 35810,AMHERST,MA 01003, USA. RI Bottaro, Donald/F-8550-2010 OI Bottaro, Donald/0000-0002-5057-5334 FU NICHD NIH HHS [N01-HD-2-3144] NR 74 TC 20 Z9 21 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0886-1544 J9 CELL MOTIL CYTOSKEL JI Cell Motil. Cytoskeleton PY 1996 VL 35 IS 3 BP 225 EP 236 DI 10.1002/(SICI)1097-0169(1996)35:3<225::AID-CM5>3.0.CO;2-7 PG 12 WC Cell Biology SC Cell Biology GA VP950 UT WOS:A1996VP95000005 PM 8913643 ER PT J AU Terasaki, M AF Terasaki, M TI Actin filament translocations in sea urchin eggs SO CELL MOTILITY AND THE CYTOSKELETON LA English DT Article DE phalloidin; confocal microscopy ID CULTURED ANIMAL-CELLS; ENDOPLASMIC-RETICULUM; F-ACTIN; CONTRACTILE RING; FERTILIZATION; PHALLOIDIN; POLYMERIZATION; MECHANISM; ORGANIZATION; MICROFILAMENTS AB Rhodamine (rh) phalloidin was used as a probe for actin filaments in living eggs and was observed using confocal microscopy. Exogenous, rh phalloidin labeled actin filaments were injected into eggs and were observed to translocate in the cytoplasm. At fertilization, filaments accumulated at the fertilization cone. Rh phalloidin alone, injected at concentrations that did not interfere with fertilization or mitosis, labeled filaments in the interior of unfertilized eggs, some of which translocated. At fertilization, staining increased dramatically at the fertilization cone and to a lesser degree around the entire cortex. At about 9 min, many filaments appeared to detach and translocated away from the egg surface. This study shows that there are mechanisms that can translocate actin filaments within the egg cytoplasm (at approximately 0.2-0.3 mu m/sec), and raises the possibility that at least some of the changes in actin filament organization after fertilization are due to translocation of filaments. (C) 1996 Wiley-Liss, Inc. C1 MARINE BIOL LAB,WOODS HOLE,MA 02543. NINCDS,NEUROBIOL LAB,NIH,BETHESDA,MD 20892. NR 50 TC 26 Z9 26 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0886-1544 J9 CELL MOTIL CYTOSKEL JI Cell Motil. Cytoskeleton PY 1996 VL 34 IS 1 BP 48 EP 56 DI 10.1002/(SICI)1097-0169(1996)34:1<48::AID-CM5>3.0.CO;2-E PG 9 WC Cell Biology SC Cell Biology GA UH908 UT WOS:A1996UH90800005 PM 8860231 ER PT J AU Bearer, EL DeGiorgis, JA Medeiros, NA Reese, TS AF Bearer, EL DeGiorgis, JA Medeiros, NA Reese, TS TI Actin-based motility of isolated axoplasmic organelles SO CELL MOTILITY AND THE CYTOSKELETON LA English DT Article DE motility; organelles; myosin ID FAST AXONAL-TRANSPORT; SQUID GIANT-AXON; RATE CONSTANTS; MYOSIN-I; FILAMENTS; KINESIN; MOVEMENT; ENDS; MICROFILAMENTS; PURIFICATION AB We previously showed that axoplasmic organelles from the squid giant axon move toward the barbed ends of actin filaments and that KI-washed organelles separated from soluble proteins by sucrose density fractionation retain a 235-kDa putative myosin. Here, we examine the myosin-like activities of KI-washed organelles after sucrose density fractionation to address the question whether the myosin on these organelles is functional. By electron microscopy KI-washed organelles bound to actin filaments in the absence of ATP but not in its presence. Analysis of organelle-dependent ATPase activity over time and with varying amounts of organelles revealed a basal activity of 350 (range: 315-384) nmoles Pi/mg/min and an actin-activated activity of 774 (range: 560-988) nmoles/mg/min, a higher specific activity than for the other fractions. By video microscopy washed organelles moved in only one direction on actin filaments with a net velocity of 1.11 +/- .03 mu m/s and an instantaneous velocity of 1.63 +/- 0.29 mu m/s. By immunogold electronmicroscopy, 7% of KI-washed organelles were decorated with an antimyosin antibody as compared to 0.5% with non-immune serum. Thus, some axoplasmic organelles have a tightly associated myosin-like activity. (C) 1996 Wiley-Liss, Inc. C1 BIOL MARINE LAB,WOODS HOLE,MA. NINCDS,NIH,NEUROBIOL LAB,BETHESDA,MD 20892. RP Bearer, EL (reprint author), BROWN UNIV,DEPT PATHOL & LAB MED,DIV BIOL & MED,BOX G,PROVIDENCE,RI 02912, USA. FU NIGMS NIH HHS [R01 GM047368-05, R01 GM047368, GM47368] NR 37 TC 16 Z9 16 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0886-1544 J9 CELL MOTIL CYTOSKEL JI Cell Motil. Cytoskeleton PY 1996 VL 33 IS 2 BP 106 EP 114 DI 10.1002/1097-0169(1996)33:2<106::AID-CM970330202>3.0.CO;2-N PG 9 WC Cell Biology SC Cell Biology GA TW079 UT WOS:A1996TW07900004 PM 8635200 ER PT S AU Sheng, PL Cerruti, C Ali, S Cadet, JL AF Sheng, PL Cerruti, C Ali, S Cadet, JL BE Ali, SF Takahashi, Y TI Nitric oxide is a mediator of methamphetamine (METH)-induced neurotoxicity - In vitro evidence from primary cultures of mesencephalic cells SO CELLULAR AND MOLECULAR MECHANISMS OF DRUGS OF ABUSE: COCAINE, IBOGAINE, AND SUBSTITUTED AMPHETAMINES SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Cellular and Molecular Mechanisms of Drugs of Abuse - Cocaine, Ibogaine, and Substituted Amphetamines CY JUN 29-30, 1995 CL NIIGATA, JAPAN SP Int Soc Neurochem, Niigata Univ, Niigata City, Niigate Prefecture Med Assoc, Niigate Prefecture, Denkaseiken Ltd, Jujisawa Pharm Co, Perkin Elmer Japan, ABI Div, Ikeda Med Electr Co, Kyowa Hakko Co, Sumitomo Pharm Co, Pfizer Pharm Co, Brain Res Inst, Dept Neuropharm, Colleagues, Niigate Univ Sch Med, Dept Psychiat, Colleagues, Servier Amer, Matsuhama Hosp, Seki Hosp, Itsukamachi Hosp, Shima Hosp, Natl Saigata Hosp, Niigata & Niitsu Shinai Hosp, Suehirobashi Hosp, Tamiya Hosp, Mishima Hosp, Sagatasoh Hosp, Murakami Hosp, Haryugaoka Hosp, Ohshima Hosp, Nagaoka Hoyoin Hosp, Usuki Hosp, Lizuka Hosp, Kurokawa Hosp, Inazuki Hosp, Sanko Hosp, Minamihama Hosp, Aska Hoyoen Hosp, Hoshi Hosp, Ichiyokai Hosp, Arita Hosp, US FDA, Natl Ctr Toxicol Res ID TYROSINE-HYDROXYLASE ACTIVITY; DNA STRAND-BREAKS; DOPAMINERGIC-NEURONS; STRIATAL DOPAMINE; RAT-BRAIN; INDUCED DEPRESSION; HYDROGEN-PEROXIDE; OXIDATIVE STRESS; TRANSGENIC MICE; UPTAKE SITES C1 NIDA, IRP, Mol Neuropsychiat Sect, NIH, Baltimore, MD 21224 USA. Natl Ctr Toxicol Res, Neurochem Lab, Jefferson, AR 72079 USA. RP Cadet, JL (reprint author), NIDA, IRP, Mol Neuropsychiat Sect, NIH, POB 5180, Baltimore, MD 21224 USA. NR 42 TC 39 Z9 40 U1 0 U2 2 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-036-0 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1996 VL 801 BP 174 EP 186 DI 10.1111/j.1749-6632.1996.tb17440.x PG 13 WC Substance Abuse; Multidisciplinary Sciences; Neurosciences; Pharmacology & Pharmacy SC Substance Abuse; Science & Technology - Other Topics; Neurosciences & Neurology; Pharmacology & Pharmacy GA BK04B UT WOS:000070968400014 PM 8959032 ER PT S AU Kitayama, S Morita, K Dohi, T Wang, JB Davis, SC Uhl, GR AF Kitayama, S Morita, K Dohi, T Wang, JB Davis, SC Uhl, GR BE Ali, SF Takahashi, Y TI Dissection of dopamine and cocaine binding sites on the rat dopamine transporter expressed in COS cells SO CELLULAR AND MOLECULAR MECHANISMS OF DRUGS OF ABUSE: COCAINE, IBOGAINE, AND SUBSTITUTED AMPHETAMINES SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Cellular and Molecular Mechanisms of Drugs of Abuse - Cocaine, Ibogaine, and Substituted Amphetamines CY JUN 29-30, 1995 CL NIIGATA, JAPAN SP Int Soc Neurochem, Niigata Univ, Niigata City, Niigate Prefecture Med Assoc, Niigate Prefecture, Denkaseiken Ltd, Jujisawa Pharm Co, Perkin Elmer Japan, ABI Div, Ikeda Med Electr Co, Kyowa Hakko Co, Sumitomo Pharm Co, Pfizer Pharm Co, Brain Res Inst, Dept Neuropharm, Colleagues, Niigate Univ Sch Med, Dept Psychiat, Colleagues, Servier Amer, Matsuhama Hosp, Seki Hosp, Itsukamachi Hosp, Shima Hosp, Natl Saigata Hosp, Niigata & Niitsu Shinai Hosp, Suehirobashi Hosp, Tamiya Hosp, Mishima Hosp, Sagatasoh Hosp, Murakami Hosp, Haryugaoka Hosp, Ohshima Hosp, Nagaoka Hoyoin Hosp, Usuki Hosp, Lizuka Hosp, Kurokawa Hosp, Inazuki Hosp, Sanko Hosp, Minamihama Hosp, Aska Hoyoen Hosp, Hoshi Hosp, Ichiyokai Hosp, Arita Hosp, US FDA, Natl Ctr Toxicol Res ID PARKINSONISM-INDUCING NEUROTOXIN; NOREPINEPHRINE TRANSPORTERS; CLONING; SUBSTRATE; TOXICITY; DOMAINS; MPP+ C1 Hiroshima Univ, Sch Dent, Dept Pharmacol, Minami Ku, Hiroshima 734, Japan. NIDA, Mol Neurobiol Branch, Div Intramural Program, NIH, Baltimore, MD 21224 USA. RP Kitayama, S (reprint author), Hiroshima Univ, Sch Dent, Dept Pharmacol, Minami Ku, Kasumi 1-2-3, Hiroshima 734, Japan. NR 13 TC 21 Z9 21 U1 1 U2 2 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-036-0 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1996 VL 801 BP 388 EP 393 DI 10.1111/j.1749-6632.1996.tb17460.x PG 6 WC Substance Abuse; Multidisciplinary Sciences; Neurosciences; Pharmacology & Pharmacy SC Substance Abuse; Science & Technology - Other Topics; Neurosciences & Neurology; Pharmacology & Pharmacy GA BK04B UT WOS:000070968400034 PM 8959052 ER PT J AU Hallenbeck, JM AF Hallenbeck, JM TI Inflammatory reactions at the blood-endothelial interface in acute stroke SO CELLULAR AND MOLECULAR MECHANISMS OF ISCHEMIC BRAIN DAMAGE SE ADVANCES IN NEUROLOGY LA English DT Review ID PLATELET-ACTIVATING-FACTOR; TUMOR-NECROSIS-FACTOR; GROWTH-FACTOR-BETA; HUMAN VASCULAR ENDOTHELIUM; FOCAL CEREBRAL-ISCHEMIA; LEUKOCYTE ADHESION MOLECULES; TRANSIENT FOREBRAIN ISCHEMIA; TISSUE FACTOR EXPRESSION; CENTRAL-NERVOUS-SYSTEM; PLASMINOGEN-ACTIVATOR RP Hallenbeck, JM (reprint author), NINCDS,STROKE BRANCH,NIH,BETHESDA,MD 20892, USA. NR 152 TC 70 Z9 73 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA E WASHINGTON SQ, PHILADELPHIA, PA 19105 SN 0091-3952 J9 ADV NEUROL JI Adv.Neurol. PY 1996 VL 71 BP 281 EP 300 PG 20 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA BG71K UT WOS:A1996BG71K00021 PM 8790806 ER PT J AU Pritchard, JB Miller, DS AF Pritchard, JB Miller, DS TI Intracellular compartmentation of organic anions and cations during renal secretion SO CELLULAR PHYSIOLOGY AND BIOCHEMISTRY LA English DT Review DE kidney; choroid plexus; membrane transport; intracellular organelles; confocal microscopy; fluorescein; tetraethylammonium; quinacrine; nocodazole; microtubules ID CELLS; RAT; TRANSPORT; CORTEX AB Although plasma membrane events mediating organic anion and cation secretion have been intensively investigated, intracellular events associated with transcellular fluxes of secreted solutes have received much less attention. Recent data obtained through epifluorescence and confocal microscopy in renal tissue of mammals, teleosts, and crustaceans indicates that sequestration within intracellular organelles is intimately Quinacrine involved in secretion of both organic anions (OA) and cations Nocodazole (OC). For OA, one compartment is mitochondrial and a second is smaller and more mobile. OA-loaded vesicles were shown to move in a basolateral-to-apical direction in crustacean urinary bladder. This movement was reversibly blocked by nocodazole, a microtubule-disrupting agent. Furthermore, secretion into the lumen of teleost proximal tubule was also reversibly inhibited by nocodazole. For OA, the small mobile vesicles have yet to be identified or isolated. For OC, a population of acidifying endosomes was identified which accumulated tetraethylammonium (TEA) by TEA/proton exchange. Finally, in cultured monolayers of choroid plexus, an epithelium which transports both OA and OC from cerebrospinal fluid to blood, fusion of vesicles with the basolateral membrane and concomitant release of OC was seen during transepithelial transport. This process was also blocked by nocodazole. The roles of sequestration in transepithelial transport are as yet uncertain, but these data argue that such roles are likely. RP Pritchard, JB (reprint author), NIEHS,CELLULAR & MOL PHARMACOL LAB,NIH,COMPARAT MEMBRANE PHARMACOL SECT,MD 19-01,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 13 TC 6 Z9 6 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-8987 J9 CELL PHYSIOL BIOCHEM JI Cell. Physiol. Biochem. PY 1996 VL 6 IS 1-2 BP 50 EP 59 DI 10.1159/000154794 PG 10 WC Cell Biology; Physiology SC Cell Biology; Physiology GA UZ691 UT WOS:A1996UZ69100006 ER PT J AU Reddy, BVB Bartoszewicz, Z Rebois, RV AF Reddy, BVB Bartoszewicz, Z Rebois, RV TI Modification of the sialic acid residues of choriogonadotropin affects signal transduction SO CELLULAR SIGNALLING LA English DT Article DE choriogonadotropin; N-acetylneuraminic acid; signal transduction; adenylyl cyclase ID HUMAN CHORIONIC-GONADOTROPIN; GLYCOSIDIC CARBOHYDRATE UNITS; N-ACETYLNEURAMINIC ACID; TUMOR-CELL LINE; BIOLOGICAL PROPERTIES; LINKED OLIGOSACCHARIDES; GALACTOSE RESIDUES; ALPHA-SUBUNIT; BETA-SUBUNIT; HORMONE AB Human choriogonadotropin (hCG) is a glycoprotein hormone that activates adenylyl cyclase. The carbohydrate moieties of hCG ate required for biological activity, but not for binding to the gonadotropin receptors. We modified N-acetylneuraminic acid (NeuAc) on the oligosaccharide moieties of hCG, and determined the effect on its biological activity by measuring hormone-stimulated adenylyl cyclase. Treating hCG with sodium periodate to remove two carbon atoms from NeuAc or quantitatively removing NeuAc from hCG reduced its biological activity by 36% and 50%, respectively. The galactose residues of asialo-hCG were reacted with NeuAc-hydrazone or a hydrazone of the oligosaccharide from the ganglioside G(M1) (Gal(beta 1-3)GalNAc(beta 1-4)[NeuAc(alpha 2-3)]Gal(beta 1-4)Glc). The gonadotropin receptor had high affinity for both derivatives, but their biological activity was less than that of hCG. These results suggest that several structural aspects of NeuAc including carbon side chain, an intact ring structure, and the position of NeuAc relative to other carbohydrate residues are important for full biological activity of hCG. C1 NINCDS,NIH,MOLEC & CELLULAR BIOL LAB,MEMBRANE BIOCHEM SECT,BETHESDA,MD 20892. NINCDS,NIH,MOLEC & CELLULAR BIOL LAB,BRAIN DEV SECT,BETHESDA,MD 20892. NR 30 TC 13 Z9 13 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0898-6568 J9 CELL SIGNAL JI Cell. Signal. PD JAN PY 1996 VL 8 IS 1 BP 35 EP 41 DI 10.1016/0898-6568(95)02013-6 PG 7 WC Cell Biology SC Cell Biology GA TV631 UT WOS:A1996TV63100006 PM 8777139 ER PT J AU Warner, DR Okuya, S Rebois, RV AF Warner, DR Okuya, S Rebois, RV TI Altered G(s)alpha N-terminus affects G(s) activity and interaction with the G beta gamma subunit complex in cell membranes but not in solution SO CELLULAR SIGNALLING LA English DT Article DE G protein subunit interaction; amino terminus of G(s)alpha; adenylylcyclase; choleragen ID SEQUENCE-SPECIFIC PROTEOLYSIS; PROTEIN ALPHA-SUBUNITS; ADENYLATE-CYCLASE; GTP-BINDING; REGULATORY COMPONENT; GUANINE-NUCLEOTIDES; ESCHERICHIA-COLI; TRANSDUCIN; PURIFICATION; TRANSLATION AB The stimulatory G protein (G(s)) mediates activation of adenylylcyclase by a ligand-receptor complex. G(s) is heterotrimeric (alpha beta gamma) and activation can be accomplished by dissociation of the alpha-subunit (G(s) alpha) from the beta gamma-subunit complex (G beta gamma). G(s) alpha is also a substrate for choleragen catalyzed ADP-ribosylation when it is associated with G beta gamma but not as free G(s) alpha. Using recombinant DNA techniques we modified the cDNA for the 52,000 M(r) form of Gsa (G(s) alpha(52)) to produce a protein with a 2,400 M(r) N-terminal extension (G(s) alpha(54.4)). This N-terminal extension could be removed with the protease Factor Xa. In vitro transcription and translation of the recombinant plasmid containing the cDNA's for G(s) alpha(52) and G(s) alpha(54.4) produced a 52,000 M(r) and a 54,000 M(r) protein, respectively. In solution the properties of G(s) alpha(52) and G(s) alpha(51.4) were indistinguishable. Both proteins: (a) formed a heterotrimer with G beta gamma and their affinities for the subunit complex were the same; (b) could be ADP-ribosylated by choleragen in the presence but not in the absence of G beta gamma; (c) bound the non-hydrolyzable GTP analogue, GTP gamma S, and were protected from chymotryptic proteolysis by the guanine nucleotide; and (d) could activate in vitro translated type IV adenylylcyclase. G(s) alpha(54.4) and G(s) alpha(52) were incorporated into S49 cyc(-) membranes, which lack Gsa. After incorporation, both G(s) alpha(52) and G(s) alpha(54.4) were protected from chymotryptic proteolysis when GTP gamma S was present, revealing that both proteins were able to bind the nucleotide and undergo a conformational change characteristic of Gsa activation. When G(s) alpha(52) was incorporated into cyc(-) membranes it could mediate both hormone and GTP gamma S stimulation of adenylylcyclase and could be ADP-ribosylated by choleragen, but Gs alpha(54.4) could do neither of these things, indicating that the properties of G(s) alpha(54.4) were altered by the membrane. Deletion of the N-terminal extension by treatment with Factor Xa in solution converted G(s) alpha(54.4) to G(s) alpha(52), and upon incorporation into cyc(-) membranes it behaved like G(s) alpha(52) in every regard, showing that the effect of the N-terminal extension was reversible. A lack of other differences in the functional properties of G(s) alpha(52) and G(s) alpha(54.4) suggests a correlation between the interaction of G(s) alpha with G beta gamma and its ability to activate adenylylcyclase. C1 NINCDS,NIH,MEMBRANE BIOCHEM SECT,MOLEC & CELLULAR NEUROBIOL LAB,BETHESDA,MD 20892. NR 34 TC 8 Z9 8 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0898-6568 J9 CELL SIGNAL JI Cell. Signal. PD JAN PY 1996 VL 8 IS 1 BP 43 EP 53 DI 10.1016/0898-6568(95)02017-9 PG 11 WC Cell Biology SC Cell Biology GA TV631 UT WOS:A1996TV63100007 PM 8777140 ER PT J AU Courtney, SM Ungerleider, LG Keil, K Haxby, JV AF Courtney, SM Ungerleider, LG Keil, K Haxby, JV TI Object and spatial visual working memory activate separate neural systems in human cortex SO CEREBRAL CORTEX LA English DT Article ID POSITRON EMISSION TOMOGRAPHY; INFERIOR TEMPORAL CORTEX; FRONTAL-LOBE LESIONS; PREFRONTAL CORTEX; RHESUS-MONKEY; PET IMAGES; DISSOCIATION; PRIMATE; CONNECTIONS; (H2O)-O-15 AB Human and nonhuman primate visual systems are divided into object and spatial information processing pathways, In the macaque, it has been shown that these pathways project to separate areas in the frontal lobe and that the ventral and dorsal frontal areas are, respectively, involved in working memory for objects and spatial locations. A positron emission tomography (PET) study was done to determine if a similar anatomical segregation exists in humans for object and spatial visual working memory. Face working memory demonstrated significant increases in regional cerebral blood flow (rCBF), relative to location working memory, in fusiform, parahippocampal, inferior frontal, and anterior cingulate cortices, and in right thalamus and midline cerebellum. Location working memory demonstrated significant increases in rCBF relative to face working memory, in superior and inferior parietal cortex, and in the superior frontal sulcus. Our results show that the neural systems involved in working memory for faces and for spatial location are functionally segregated, with different areas recruited in both extrastriate and frontal cortices for processing the two types of visual information. RP Courtney, SM (reprint author), NIMH,LPP,SECT FUNCT BRAIN IMAGING,BLDG 10,ROOM 4C110,10 CTR DR,MSC 1366,BETHESDA,MD 20892, USA. NR 62 TC 610 Z9 617 U1 2 U2 27 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 SN 1047-3211 J9 CEREB CORTEX JI Cereb. Cortex PD JAN-FEB PY 1996 VL 6 IS 1 BP 39 EP 49 DI 10.1093/cercor/6.1.39 PG 11 WC Neurosciences SC Neurosciences & Neurology GA TW392 UT WOS:A1996TW39200006 PM 8670637 ER PT S AU Rick, SW McCoy, JD Haymet, ADJ AF Rick, SW McCoy, JD Haymet, ADJ BE Laird, BB Ross, RB Ziegler, T TI Density-functional theory of quantum freezing and the helium isotopes SO CHEMICAL APPLICATIONS OF DENSITY-FUNCTIONAL THEORY SE ACS SYMPOSIUM SERIES LA English DT Article; Proceedings Paper CT Conference on Chemical Applications of Density-Functional Theory, at the 209th National Meeting of the American-Chemical-Society CY APR 02-06, 1995 CL ANAHEIM, CA SP Amer Chem Soc, Div Phys Chem, Amer Chem Soc, Div Comp Chem ID ZERO TEMPERATURE; HIGH-PRESSURE; MELTING CURVE; SYSTEMS; CRYSTALLIZATION; EQUATION; LIQUID; FLUIDS; STATE; HE-4 C1 NEW MEXICO INST MIN & TECHNOL,DEPT MAT ENGN,SOCORRO,NM 87801. UNIV SYDNEY,SCH CHEM,SYDNEY,NSW 2006,AUSTRALIA. RP Rick, SW (reprint author), NCI,FREDERICK CANC RES & DEV CTR,FREDERICK BIOMED SUPERCOMP CTR,STRUCT BIOCHEM PROGRAM,FREDERICK,MD 21702, USA. RI McCoy, John/B-3846-2010; Haymet, Anthony/A-9881-2009 OI McCoy, John/0000-0001-5404-1404; Haymet, Anthony/0000-0002-5617-2106 NR 39 TC 0 Z9 0 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 SIXTEENTH ST NW, WASHINGTON, DC 20036 SN 0097-6156 BN 0-8412-3403-5 J9 ACS SYM SER PY 1996 VL 629 BP 286 EP 296 PG 11 WC Chemistry, Multidisciplinary; Chemistry, Physical SC Chemistry GA BF67B UT WOS:A1996BF67B00020 ER PT B AU Schneider, TD AF Schneider, TD BE ChelaFlores, J Raulin, F TI New approaches in mathematical biology: Information theory and molecular machines SO CHEMICAL EVOLUTION: PHYSICS OF THE ORIGIN AND EVOLUTION OF LIFE LA English DT Proceedings Paper CT 4th Trieste Conference on Chemical Evolution - Physics of the Origin and Evolution of Life CY SEP 04-08, 1995 CL TRIESTE, ITALY SP Int Ctr Theoret Phys, Int Ctr Genet Engn & Biotechnol, UNESCO, Univ Paris 12, Val de Marne AB qMy research uses classical information theory to study genetic systems. Information theory, founded by Claude Shannon in the 1940's, has had an enormous impact on communications engineering and computer sciences. Shannon found a way to measure information. We use this measure to precisely characterize the sequence conservation at nucleic-acid binding sites. The resulting methods completely replace the use of ''consensus sequences'', and therefore provide better models for molecular biologists. An excess of sequence conservation at bacteriophage T7 promoters and at F plasmid IncD repeats led us to predict the existence of proteins that bind the DNA. In another application of information theory, the wonderful fidelity of telephone communications and compact disk (CD) music can be traced directly to Shannon's channel capacity theorem. When rederived for molecular biology, this theorem explains the surprising precision of many molecular events. Through connections with the Second Law of Thermodynamics and Maxwell's Demon, this approach also has implications for the development of technology at the molecular level. The theory of molecular machines describes molecular interactions by using the mathematics of information theory [1, 2]. For convenience, I have divided the theory into three levels, which are characterized by these topics: Level 0. Sequence Logos: patterns in genetic sequences. Level 1. Machine Capacity: energetics of macromolecules. Level 2. The Second Law: Maxwell's Demon and the limits of computers. RP Schneider, TD (reprint author), NCI,FREDERICK CANC RES & DEV CTR,MATH BIOL LAB,POB B,FREDERICK,MD 21702, USA. NR 0 TC 3 Z9 4 U1 0 U2 2 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS BN 0-7923-4111-2 PY 1996 BP 313 EP 321 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA BH48F UT WOS:A1996BH48F00028 ER PT J AU Chen, CN Wang, PC Song, HF Liu, YC Chen, CS AF Chen, CN Wang, PC Song, HF Liu, YC Chen, CS TI Non-invasive detection of ibuprofen in vivo C-13-NMR signals in rats SO CHEMICAL & PHARMACEUTICAL BULLETIN LA English DT Article DE ibuprofen metabolism; in vivo C-13-NMR; xenobiotics ID METABOLIC CHIRAL INVERSION; ANTI-INFLAMMATORY DRUGS; 2-PHENYLPROPIONIC ACID; 2-ARYLPROPIONIC ACIDS; STEREOSELECTIVE METABOLISM; STEREOISOMERIC INVERSION; OPTICAL ISOMERIZATION; RENAL-FAILURE; ENANTIOMERS; MECHANISM AB A non-invasive in vivo C-13-NMR experiment is performed to follow the metabolic pathway of ibuprofen in rats. Detection of possible intermediates and the stereoselectivity of ibuprofen chiral inversion process are discussed. C1 HOWARD UNIV HOSP, DEPT RADIOL, WASHINGTON, DC USA. UNIV RHODE ISL, DEPT PHARMACOGNOSY & ENVIRONM HLTH SCI, KINGSTON, RI 02881 USA. RP Chen, CN (reprint author), NIH, NCRR, BIOMED ENGN & INSTRUMENTAT PROGRAM, BLDG 13, RM 3N-17, BETHESDA, MD USA. NR 27 TC 4 Z9 4 U1 0 U2 1 PU PHARMACEUTICAL SOC JAPAN PI TOKYO PA 2-12-15 SHIBUYA, SHIBUYA-KU, TOKYO, 150-0002, JAPAN SN 0009-2363 J9 CHEM PHARM BULL JI Chem. Pharm. Bull. PD JAN PY 1996 VL 44 IS 1 BP 204 EP 207 PG 4 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA TR785 UT WOS:A1996TR78500033 PM 8582039 ER PT J AU Rouzer, CA Sabourin, M Skinner, TL Thompson, EJ Wood, TO Chmurny, GN Klose, JR Roman, JM Smith, RH Michejda, CJ AF Rouzer, CA Sabourin, M Skinner, TL Thompson, EJ Wood, TO Chmurny, GN Klose, JR Roman, JM Smith, RH Michejda, CJ TI Oxidative metabolism of 1-(2-chloroethyl)-3-alkyl-3-(methylcarbamoyl) triazenes: Formation of chloroacetaldehyde and relevance to biological activity SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID VINYL-CHLORIDE; ALKYLATING-AGENTS; 1,3-DIALKYL-3-ACYLTRIAZENES; PRODUCTS; DECOMPOSITION; 1,3-DIALKYLTRIAZENES; 2-CHLOROACETALDEHYDE; MUTAGENICITY; RATES; DNA AB (Methylcarbamoyl)triazenes have been shown to be effective cancer chemotherapeutic agents in a number of biological systems. Because of their chemical stability, it is likely that their activity in vivo is the result of a metabolic activation process. Previous studies have shown that 1-(2-chloroethyl)-3-methyl-3-(methylcarbamoyl)triazene (CMM) and 1-(2-chloroethyl)-3-benzyl-3-(methylcarbamoyl)triazene (CBzM) are metabolized by rat liver microsomes in the presence of NADPH to yield the ((hydroxymethyl)carbamoyl)triazene analogs of the parent compounds. The present studies show that both compounds are also oxidized at the chloroethyl substituent to yield chloroacetaldehyde and a substituted urea. In the case of CBzM metabolism, 47% of the metabolized parent compound was recovered as benzylmethylurea, 8% was recovered as benzylurea, and 26% was recovered as the ((hydroxymethyl)carbamoyl)-triazene and carbamoyltriazene metabolites. These results suggest that the chloroethyl group is the favored initial site of metabolism. In reaction mixtures containing intitial concentrations of 300 mu M CBzM, 78 mu M chloroacetaldehyde was produced, as compared to 58 mu M chloroacetaldehyde produced from the metabolism of 300 mu M CMM. The formation of chloroacetaldehyde, a known mutagenic DNA alkylating agent, may explain the biological activity of these compounds. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MOLEC ASPECTS DRUG DESIGN SECT,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,SAIC,CHEM SYNTH & ANAL LAB,FREDERICK,MD 21702. RP Rouzer, CA (reprint author), WESTERN MARYLAND COLL,DEPT CHEM,2 COLL HILL,WESTMINSTER,MD 21157, USA. FU NCI NIH HHS [N01-CO-46000] NR 23 TC 34 Z9 34 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD JAN-FEB PY 1996 VL 9 IS 1 BP 172 EP 178 DI 10.1021/tx9500639 PG 7 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA TU002 UT WOS:A1996TU00200024 PM 8924588 ER PT J AU Barr, DP Martin, MV Guengerich, FP Mason, RP AF Barr, DP Martin, MV Guengerich, FP Mason, RP TI Reaction of cytochrome P450 with cumene hydroperoxide: ESR spin trapping evidence for the homolytic scission of the peroxide O-O bond by ferric cytochrome P450 1A2 SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID LIVER MICROSOMAL CYTOCHROME-P-450; SUBSTRATE HYDROXYLATION; LIPID-PEROXIDATION; REDUCTIVE CLEAVAGE; ALKOXYL RADICALS; TUMOR PROMOTERS; OXYGEN-TRANSFER; MECHANISM; HEME; OXIDATION AB ESR spin trapping was used to investigate the reaction of rabbit cytochrome P450 (P450) 1A2 with cumene hydroperoxide. Cumene hydroperoxide-derived peroxyl, alkoxyl, and carbon-centered radicals were formed and trapped during the reaction. The relative contributions of each radical adduct to the composite ESR spectrum were influenced by the concentration of the spin trap. Computer simulation of the experimental data obtained at various 5,5-dimethyl-1-pyrroline N-oxide (DMPO) concentrations was used to quantitate the contributions of each radical adduct to the composite ESR spectrum. The alkoxyl radical was the initial radical produced during the reaction. Experiments with 2-methyl-2-nitrosopropane identified the carbon-centered adducts as those of the methyl radical, hydroxymethyl radical, and a secondary carbon-centered radical. The reaction did not require NADPH-cytochrome P450 reductase or NADPH. It is concluded that the reaction involves the initial homolytic scission of the peroxide O-O bond to produce the cumoxyl radical. Methyl radicals were produced from the beta-scission of the cumoxyl radical. The peroxyl adduct was not observed in the absence of molecular oxygen. We conclude that the DMPO peroxyl radical adduct detected in the presence of oxygen was due to the methylperoxyl radical formed by the reaction of the methyl radical with oxygen. At a higher P450 concentration, a protein-derived radical adduct was also detected. C1 VANDERBILT UNIV,DEPT BIOCHEM,NASHVILLE,TN 37232. VANDERBILT UNIV,CTR MOLEC TOXICOL,NASHVILLE,TN 37232. RP Barr, DP (reprint author), NIEHS,NIH,MOLEC BIOPHYS LAB,RES TRIANGLE PK,NC 27709, USA. NR 47 TC 51 Z9 53 U1 0 U2 9 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD JAN-FEB PY 1996 VL 9 IS 1 BP 318 EP 325 DI 10.1021/tx9501501 PG 8 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA TU002 UT WOS:A1996TU00200044 PM 8924611 ER PT J AU Misra, RR Hochadel, JF Smith, GT Cook, JC Waalkes, MP Wink, DA AF Misra, RR Hochadel, JF Smith, GT Cook, JC Waalkes, MP Wink, DA TI Evidence that nitric oxide enhances cadmium toxicity by displacing the metal from metallothionein SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID C-MYC; CELL-GROWTH; DNA DAMAGE; AGENTS; ACTIVATION; MECHANISM; COMPLEXES; INFECTION; KINETICS; NITRATE AB Cadmium is carcinogenic in humans and rodents. Although extensive evidence indicates that the toxicity and genotoxicity of Cd is ameliorated by binding to cysteine clusters in metallothionein (MT), the factors governing Cd release at intracellular target sites remain unknown. Nitric oxide is a pollutant gas and an important intercellular messenger in the inflammatory immune response. When growing Chinese hamster ovary cells were treated for 24 h with 0.5, 0.75, or 1.0 mM CdC12 followed by a 1-h exposure to 1.0, 1.5, or 2.0 mM 1,1-diethyl-2-hydroxy-2-nitrosohydrazine (DEA/NO), an NO-generating sodium salt, NO enhanced Cd-induced inhibition of colony forming ability without affecting Cd-induced cytolethality. In experiments designed to determine whether NO acts by displacing Cd from cellular MT, cells treated with 2.0 mM CdCl2 followed by 1.5 or 3.0 mM DEA/NO exhibited 29 and 38% reductions, respectively, in the amount of Cd bound to MT. When purified rat liver MT was used to further characterize NO-induced release of Cd from MT, dose-related increases in Cd displacement were observed at DEA/NO concentrations between 0.1 and 0.5 mM, and a plateau was reached at 3 mol of Cd displaced/mol of MT at higher DEA/NO concentrations. Compared to cells exposed to Cd or DEA/NO alone, cells treated with Cd followed by DEA/NO also exhibited a transient 2-3-fold decrease in c-myc proto-oncogene expression. Taken together, our results support the hypothesis that NO mediates Cd release from MT in vivo and suggest that intracellular generation of free Cd may induce DNA damage and force cells into a period of growth arrest. Such findings may have particular relevance with regard to the etiology of Cd-induced carcinogenesis in human populations. C1 NCI,FREDERICK CANC RES & DEV CTR,DIV CANC ETIOL,LAB COMPARAT CARCINOGENESIS,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,SAIC FREDERICK,BCDP,FREDERICK,MD 21702. NCI,RADIAT BIOL BRANCH,TUMOR BIOL SECT,BETHESDA,MD 20892. NR 43 TC 115 Z9 118 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD JAN-FEB PY 1996 VL 9 IS 1 BP 326 EP 332 DI 10.1021/tx950109y PG 7 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA TU002 UT WOS:A1996TU00200045 PM 8924612 ER PT J AU Smith, MBK Taneyhill, LA Michejda, CJ Smith, RH AF Smith, MBK Taneyhill, LA Michejda, CJ Smith, RH TI Base sequence selectivity in the alkylation of DNA by 1,3-dialkyl-3-acyltriazenes SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID INTERSTRAND CROSS-LINKING; AGENTS; DECOMPOSITION; (2-HALOETHYL)NITROSOUREAS; SPECIFICITY; MECHANISM; RATS AB The base sequence selectivity of DNA alkylation for a series of structurally related 1,3-dialkyl-3-acyltriazenes was examined with calf thymus DNA or polymers containing the sequences GGG, CGC, TGT, and AGA. The reaction products at the N7 and the O-6 positions of guanine were identified, quantitated, and then correlated with the decomposition rates of the triazenes, 1-(2-chloroethyl)-3-methyl-3-carbethoxy-(CMC), 1-(2-chloroethyl)-3-methyl-3-acetyl-(CMA), 1-(2-hydroxyethyl)-3-methyl-3-carbethoxy-(HMC), 1-(2-hydroxyethyl)-3-methyl-3-acetyl-(HMA), and 1,3-dimethyl-3-acetyl- (DMA). The results of these studies revealed that DNA sequences with runs of purines were more reactive toward alkylation by all of the triazenes tested, irrespective of whether the alkylation was measured by N7, O-6, or total guanine adducts. Within this generalization, the (hydroxyethyl)triazenes showed a preference for the AGA sequence, while the (chloroethyl)triazenes favored the GGG sequence. The structure of the 3-acyl group of the triazene also played a role in the extent of alkylation of a particular sequence of DNA. Both the (chloroethyl)- and the (hydroxyethyl)triazenes produced higher alkylation product yields for the 3-carbethoxytriazenes as compared with the 3-acetyl derivatives for most of the sequences examined. These overall patterns correlated well with the order of decomposition of the triazenes at 37 degrees C: HMC > DMA > HMA > CMC > CMA. This study has demonstrated how varying the structure of 1,3-dialkyl-3-acyltriazenes can modulate DNA alkylation, a finding which may be important in the design of new triazene antitumor agents. C1 WESTERN MARYLAND COLL,DEPT CHEM,WESTMINSTER,MD 21157. RP Smith, MBK (reprint author), NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MACROMOLEC STRUCT LAB,FREDERICK,MD 21702, USA. RI Taneyhill, Lisa/K-1815-2013 NR 25 TC 4 Z9 4 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD JAN-FEB PY 1996 VL 9 IS 1 BP 341 EP 348 PG 8 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA TU002 UT WOS:A1996TU00200047 ER PT J AU Rosenfeld, MA Collins, FS AF Rosenfeld, MA Collins, FS TI Gene therapy for cystic fibrosis SO CHEST LA English DT Review DE airway; cystic fibrosis; epithelial cells; gene therapy; vectors ID TRANSMEMBRANE CONDUCTANCE REGULATOR; RESPIRATORY EPITHELIAL-CELLS; ION-TRANSPORT DEFECT; CHLORIDE CHANNEL; ADENOASSOCIATED VIRUS; TRANSGENIC MICE; EXPRESSION; IDENTIFICATION; RECEPTOR; INVIVO RP Rosenfeld, MA (reprint author), NIH,NATL CTR HUMAN GENOME RES,DIV INTRAMURAL RES,LAB GENE TRANSFER,ROOM 3A14,BLDG 49,BETHESDA,MD 20892, USA. NR 102 TC 32 Z9 32 U1 0 U2 1 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 SN 0012-3692 J9 CHEST JI Chest PD JAN PY 1996 VL 109 IS 1 BP 241 EP 252 DI 10.1378/chest.109.1.241 PG 12 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA TP054 UT WOS:A1996TP05400046 PM 8549191 ER PT J AU Belov, YP Aksinenko, AY Blessington, B Newman, AH AF Belov, YP Aksinenko, AY Blessington, B Newman, AH TI Chiral aminophosphonate eluent for enantiomeric analysis of amino acids SO CHIRALITY LA English DT Article; Proceedings Paper CT 6th International Symposium on Chiral Discrimination CY APR 26-28, 1995 CL ST LOUIS, MO DE aminophosphonic acids; asymmetric synthesis; chiral HPLC; ligand-ex change chromatography; enantiomeric analysis ID CHROMATOGRAPHY AB An aqueous solution of the (+)-monoethyl ester of N-(1'-hydroxymethyl)propyl-alpha-aminobenzylphosphonic acid has been proposed as a suitable chiral eluent for enantiomeric analysis of amino acids by ligand-exchange chromatography. Asymmetric synthesis of the chiral selector using (-)-(R)-2-aminobutan-1-ol as a starting reactant is described. The dependence of the parameters of separation of valine enantiomers on concentration of the complexing ion, pH, and temperature has been investigated. It is shown that the order in which enantiomers are eluted from a column depends on the concentration of the complexing ion and pH. (C) 1996 Wiley-Liss, Inc. C1 UNIV BRADFORD,BRADFORD BD7 1DP,W YORKSHIRE,ENGLAND. NIDA,NIH,BALTIMORE,MD. RP Belov, YP (reprint author), RUSSIAN ACAD SCI,INST PHYSIOL ACT SUBST,CHERNOGOLOVKA 142432,RUSSIA. OI Aksinenko, Alexey/0000-0002-7281-9467 NR 6 TC 4 Z9 4 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0899-0042 J9 CHIRALITY JI Chirality PY 1996 VL 8 IS 1 BP 122 EP 125 PG 4 WC Chemistry, Medicinal; Chemistry, Analytical; Chemistry, Organic; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA TY396 UT WOS:A1996TY39600017 PM 8845275 ER PT J AU Yang, SK Bao, ZP Shou, MG AF Yang, SK Bao, ZP Shou, MG TI Stereoselective nucleophilic substitution of oxazepam and racemization in acidic methanol and ethanol SO CHIRALITY LA English DT Article DE oxazepam; racemization; reversed-phase and chiral stationary phase highperformance liquid chromatography; circular dichroism spectropolarimetry; mass spectrometry ID ENANTIOMERS; 1,4-BENZODIAZEPINES; KINETICS AB Enantiomeric and racemic oxazepam (OX), 3-O-methyloxazepam (MeOX), and 3-O-ethyloxazepam (EtOX) were used to study racemization, heteronucleophilic, and homonucleophilic substitution reactions in anhydrous acidic methanol and ethanol. Kinetics of racemization and nucleophilic substitution reactions in nondeuterated and deuterated solvents were determined by circular dichroism spectropolarimetry, chiral stationary phase high-performance liquid chromatography (HPLC), reversed-phase HPLC, and mass spectrometry, Several reactions occurred when (S)-OX, for example, was dissolved in acidic methanol: (1) (S)-OX itself underwent spontaneous racemization, (2) the 3-hydroxyl group of (S)-OX was stereoselectively substituted by the methoxy group of methanol to form MeOX enriched in (S)-MeOX, (3) the 3-methoxy group of (S)-MeOX was stereoselectively substituted by the methoxy group of methanol to form MeOX enriched in (S)-MeOX, and (4) the 3-methoxy group of (R)-MeOX was stereoselectively substituted by the methoxy group of methanol to form MeOX enriched in (R)-MeOX. Repetitive reactions 3 and 4 eventually resulted in a racemic MeOX. Similar reactions occurred for an enantiomeric OX in acidic ethanol. (C) 1996 Wiley-Liss, Inc. C1 NCI,NIH,MOLEC CARCINOGENESIS LAB,BETHESDA,MD 20892. RP Yang, SK (reprint author), UNIFORMED SERV UNIV HLTH SCI,F EDWARD HERBERT SCH MED,DEPT PHARMACOL,BETHESDA,MD 20814, USA. NR 21 TC 8 Z9 8 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0899-0042 J9 CHIRALITY JI Chirality PY 1996 VL 8 IS 2 BP 214 EP 223 PG 10 WC Chemistry, Medicinal; Chemistry, Analytical; Chemistry, Organic; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA UF363 UT WOS:A1996UF36300007 PM 8857183 ER PT S AU Erickson, JD Weihe, E Schafer, MKM Neale, E Williamson, L Bonner, TI TaoCheng, JH Eiden, LE AF Erickson, JD Weihe, E Schafer, MKM Neale, E Williamson, L Bonner, TI TaoCheng, JH Eiden, LE BE Klein, J Loffelholz, K TI The VAChT/ChAT ''cholinergic gene locus'': New aspects of genetic and vesicular regulation of cholinergic function SO CHOLINERGIC MECHANISMS: FROM MOLECULAR BIOLOGY TO CLINICAL SIGNIFICANCE SE Progress in Brain Research LA English DT Review CT 9th International Cholinergic Symposium (ISCM) CY JUN 07-10, 1995 CL MAINZ, GERMANY SP Johannes Gutenberg Univ Mainz, State Rheinland Pfalz, Deut Forschungsgemeinsch, Deut Gesell Exptl & Klin Pharm & Toxikol, Int Soc Neurochem, Bayer Ag, Germany, Boehringer Ingelheim, Germany, MSD, Germany, Byk Gulden, Germany, Hoffmann La Roche, Germany, Labotec, Germany, Madaus, Germany, Marion Merrell, Germany, Merz & Co, Germany, Pharmacia, Germany, Pharmacia Biotech, Germany, Roland, Germany, Schwabe, Germany, SmithKline Beecham, Germany, Upjohn, US ID ADRENAL PHEOCHROMOCYTOMA CELLS; VESICLE MONOAMINE TRANSPORTER; NERVE GROWTH-FACTOR; ACETYLCHOLINE TRANSPORTER; CAENORHABDITIS-ELEGANS; SYNAPTIC VESICLES; ACETYLTRANSFERASE GENE; CHROMAFFIN GRANULES; MOLECULAR-CLONING; AMINE TRANSPORTER C1 NICHHD, DEV NEUROBIOL LAB, NIH, BETHESDA, MD 20892 USA. NINCDS, NEUROBIOL LAB, NIH, BETHESDA, MD 20892 USA. UNIV MARBURG, DEPT ANAT & CELL BIOL, D-3550 MARBURG, GERMANY. RP Erickson, JD (reprint author), NIMH, MOL NEUROSCI SECT, CELL BIOL LAB, NIH, BETHESDA, MD 20892 USA. OI Eiden, Lee/0000-0001-7524-944X NR 50 TC 25 Z9 26 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0079-6123 BN 0-444-82166-X J9 PROG BRAIN RES JI Prog. Brain Res. PY 1996 VL 109 BP 69 EP 82 PG 14 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA BJ05X UT WOS:A1996BJ05X00006 PM 9009694 ER PT S AU Wess, J Blin, N Yun, J Schoneberg, T Liu, J AF Wess, J Blin, N Yun, J Schoneberg, T Liu, J BE Klein, J Loffelholz, K TI Molecular aspects of muscarinic receptor assembly and function SO CHOLINERGIC MECHANISMS: FROM MOLECULAR BIOLOGY TO CLINICAL SIGNIFICANCE SE Progress in Brain Research LA English DT Review CT 9th International Cholinergic Symposium (ISCM) CY JUN 07-10, 1995 CL MAINZ, GERMANY SP Johannes Gutenberg Univ Mainz, State Rheinland Pfalz, Deut Forschungsgemeinsch, Deut Gesell Exptl & Klin Pharm & Toxikol, Int Soc Neurochem, Bayer Ag, Germany, Boehringer Ingelheim, Germany, MSD, Germany, Byk Gulden, Germany, Hoffmann La Roche, Germany, Labotec, Germany, Madaus, Germany, Marion Merrell, Germany, Merz & Co, Germany, Pharmacia, Germany, Pharmacia Biotech, Germany, Roland, Germany, Schwabe, Germany, SmithKline Beecham, Germany, Upjohn, US ID PROTEIN-COUPLED RECEPTORS; SITE-DIRECTED MUTAGENESIS; BETA-ADRENERGIC RECEPTORS; ACETYLCHOLINE-RECEPTOR; INTRAMOLECULAR INTERACTIONS; ANTAGONIST-BINDING; SYNTHETIC PEPTIDES; PHOSPHOLIPASE-C; AMINO-ACIDS; SPECIFICITY RP Wess, J (reprint author), NIDDKD, BIOORGAN CHEM LAB, BETHESDA, MD 20892 USA. NR 46 TC 10 Z9 11 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0079-6123 BN 0-444-82166-X J9 PROG BRAIN RES JI Prog. Brain Res. PY 1996 VL 109 BP 153 EP 162 PG 10 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA BJ05X UT WOS:A1996BJ05X00014 PM 9009702 ER PT S AU SingerLahat, D Rojas, E Felder, CC AF SingerLahat, D Rojas, E Felder, CC BE Klein, J Loffelholz, K TI Muscarinic receptor activated Ca2+ channels in non-excitable cells SO CHOLINERGIC MECHANISMS: FROM MOLECULAR BIOLOGY TO CLINICAL SIGNIFICANCE SE Progress in Brain Research LA English DT Review CT 9th International Cholinergic Symposium (ISCM) CY JUN 07-10, 1995 CL MAINZ, GERMANY SP Johannes Gutenberg Univ Mainz, State Rheinland Pfalz, Deut Forschungsgemeinsch, Deut Gesell Exptl & Klin Pharm & Toxikol, Int Soc Neurochem, Bayer Ag, Germany, Boehringer Ingelheim, Germany, MSD, Germany, Byk Gulden, Germany, Hoffmann La Roche, Germany, Labotec, Germany, Madaus, Germany, Marion Merrell, Germany, Merz & Co, Germany, Pharmacia, Germany, Pharmacia Biotech, Germany, Roland, Germany, Schwabe, Germany, SmithKline Beecham, Germany, Upjohn, US ID INTRACELLULAR CALCIUM; ACETYLCHOLINE-RECEPTORS; SIGNAL-TRANSDUCTION; NEURONAL CELLS; INFLUX; PHOSPHOLIPASE-A2; STIMULATION; STORES; GLAND C1 NIMH, CELL BIOL LAB, BETHESDA, MD 20892 USA. RP SingerLahat, D (reprint author), NIDDKD, CELL BIOL & GENET LAB, BETHESDA, MD 20892 USA. NR 23 TC 6 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0079-6123 BN 0-444-82166-X J9 PROG BRAIN RES JI Prog. Brain Res. PY 1996 VL 109 BP 195 EP 199 PG 5 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA BJ05X UT WOS:A1996BJ05X00019 PM 9009707 ER PT J AU Allikmets, R Kashuba, VI Huebner, K LaForgia, S Kisselev, LL Klein, G Dean, M Zabarovsky, ER AF Allikmets, R Kashuba, VI Huebner, K LaForgia, S Kisselev, LL Klein, G Dean, M Zabarovsky, ER TI Mapping of 22 NotI linking clones on human chromosome 3 by polymerase chain reaction and somatic cell hybrid panels SO CHROMOSOME RESEARCH LA English DT Article DE chromosome 3; NotI linking clones; sequence tagged sites; somatic cell hybrids ID HUMAN GENOME; CPG ISLANDS; JUMPING LIBRARIES; GENE MARKERS; CONSTRUCTION; CARCINOMA; SEQUENCE; CLONING; MAP AB Twenty-two human chromosome 3 derived and partially sequenced Notl linking clones were mapped using two somatic cell hybrid panels. Somatic cell hybrid mapping was performed by Southern hybridization and/or by polymerase chain reaction (PCR), using 300-500 bp CpG-rich sequences surrounding Notl sites. Thus, 22 new Notl site-tagged (sequence tagged sites) STSs were created, distributed over the entire human chromosome 3. The majority of these linking clones tag known or unknown expressed sequences (genes). Together with other physical and genetic mapping methods, localization of Notl linking clones facilitates the construction of a long-range physical map and, at the same time, a transcriptional map of human chromosome 3. C1 KAROLINSKA INST,DEPT TUMOR BIOL,S-10401 STOCKHOLM,SWEDEN. UKRAINIAN ACAD SCI,INST MOLEC BIOL & GENET,KIEV 252627,UKRAINE. JEFFERSON MED COLL,JEFFERSON CANC INST,PHILADELPHIA,PA 19103. VA ENGELHARDT MOLEC BIOL INST,MOSCOW 117984,RUSSIA. RP Allikmets, R (reprint author), NCI,FREDERICK CANC RES & DEV CTR,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21702, USA. RI Zabarovsky, Eugene/A-6645-2010; Dean, Michael/G-8172-2012 OI Dean, Michael/0000-0003-2234-0631 FU NCI NIH HHS [R01 CA14054-15] NR 20 TC 6 Z9 6 U1 0 U2 1 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0967-3849 J9 CHROMOSOME RES JI Chromosome Res. PD JAN PY 1996 VL 4 IS 1 BP 33 EP 37 DI 10.1007/BF02254942 PG 5 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA TN068 UT WOS:A1996TN06800006 PM 8653266 ER PT J AU Jacques, PF Bostom, AG Williams, RR Ellison, RC Eckfeldt, JH Rosenberg, IH Selhub, J Rozen, R AF Jacques, PF Bostom, AG Williams, RR Ellison, RC Eckfeldt, JH Rosenberg, IH Selhub, J Rozen, R TI Relation between folate status, a common mutation in methylenetetrahydrofolate reductase, and plasma homocysteine concentrations SO CIRCULATION LA English DT Article DE enzymes; homocysteine; amino acids; metabolism; genetics AB Background Methylenetetrahydrofolate reductase (MTHFR) synthesizes 5-methyltetrahydrofolate, the major carbon donor in remethylation of homocysteine to methionine. A common MTHFR mutation, an alanine-to-valine substitution, renders the enzyme thermolabile and may cause elevated plasma levels of the amino acid homocysteine. Methods and Results To assess the potential interaction between this mutation and vitamin coenzymes in homocysteine metabolism, we screened 365 individuals from the NHLBI Family Heart Study. Among individuals with lower plasma folate concentrations (<15.4 nmol/L), those with the homozygous mutant genotype had total fasting homocysteine levels that were 24% greater (P<.05) than individuals with the normal genotype. A difference between genotypes was not seen among individuals with folate levels greater than or equal to 15.4 nmol/L. Conclusions Individuals with thermolabile MTHFR may have a higher folate requirement for regulation of plasma homocysteine concentrations; folate supplementation may be necessary to prevent fasting hyperhomocysteinemia in such persons. C1 MCGILL UNIV,CHILDRENS HOSP,DEPT HUMAN GENET,MONTREAL,PQ H3H 1P3,CANADA. MCGILL UNIV,CHILDRENS HOSP,DEPT PEDIAT,MONTREAL,PQ H3H 1P3,CANADA. MCGILL UNIV,CHILDRENS HOSP,DEPT BIOL,MONTREAL,PQ H3H 1P3,CANADA. TUFTS UNIV,USDA,HUMAN NUTR RES CTR AGING,BOSTON,MA 02111. UNIV UTAH,NHLBI FAMILY HEART STUDY,CARDIOVASC GENET RES CLIN,SALT LAKE CITY,UT. NHLBI FAMILY HEART STUDY,FRAMINGHAM,MA. UNIV MASSACHUSETTS,SCH MED,BOSTON,MA. UNIV MINNESOTA,NHLBI FAMILY HEART STUDY CENT LAB,DEPT LAB MED & PATHOL,MINNEAPOLIS,MN 55455. FU NHLBI NIH HHS [N01-HC-25106] NR 11 TC 1066 Z9 1105 U1 6 U2 25 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD JAN 1 PY 1996 VL 93 IS 1 BP 7 EP 9 PG 3 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA TL997 UT WOS:A1996TL99700003 PM 8616944 ER PT J AU Liu, K Ruth, KJ Flack, JM JonesWebb, R Burke, G Savage, PJ Hulley, SB AF Liu, K Ruth, KJ Flack, JM JonesWebb, R Burke, G Savage, PJ Hulley, SB TI Blood pressure in young black and whites: Relevance of obesity and lifestyle factors in determining differences - The CARDIA study SO CIRCULATION LA English DT Article DE blood pressure; lifestyle; obesity; race ID LONGITUDINAL DATA-ANALYSIS; RISK-FACTORS; ALCOHOL-CONSUMPTION; ETHNIC-DIFFERENCES; SCHOOL-CHILDREN; SKIN COLOR; HYPERTENSION; HEART; AMERICANS; SMOKERS AB Background Middle-aged black men and women have higher blood pressure, on average, than whites. However, this pattern is inconsistent in children and adolescents. This study explores how differences in lifestyle factors in young adulthood may influence blood pressure patterns in the two races. Methods and Results The Coronary Artery Risk Development in Young Adults (CARDIA) study is an ongoing collaborative investigation of lifestyle and the evolution of cardiovascular disease risk factors in a random sample of young adults ages 18 to 30 years at baseline (1985 to 1986). Data from four examinations over 7 years were analyzed with the use of a method that simultaneously examined cross-sectional and longitudinal relationships bf lifestyle factors and blood pressure. This study included 1154 black women, 853 black men, 1126 white women, and 1013 white men. Blacks had higher systolic blood pressure and diastolic blood pressure than whites at every examination. Racial differences were much greater in women than in men and increased over time. Within each sex-race group, average diastolic blood pressure over four examinations was positively associated with baseline age, body mass index, and alcohol intake and negatively associated with physical activity, cigarette use, and intake of potassium and protein. Longitudinal change in diastolic blood pressure was positively associated with changes in body mass index and alcohol intake. After adjustment for obesity and other lifestyle factors, black-white diastolic blood pressure differences were reduced substantially: 21% to 75% for men and 49% to 129% for women. Results for systolic blood pressure were similar. Conclusions Differences in obesity and other lifestyle factors in young adults largely explain the higher baseline blood pressure and greater increase over time of blacks relative to whites. C1 BOWMAN GRAY SCH MED,CTR HYPERTENS,WINSTON SALEM,NC. UNIV MINNESOTA,SCH PUBL HLTH,DIV EPIDEMIOL,MINNEAPOLIS,MN. BOWMAN GRAY SCH MED,DEPT PUBL HLTH SCI,WINSTON SALEM,NC. NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,BETHESDA,MD 20892. UNIV CALIF SAN FRANCISCO,DEPT EPIDEMIOL & BIOSTAT,SAN FRANCISCO,CA 94143. RP Liu, K (reprint author), NORTHWESTERN UNIV,SCH MED,DEPT PREVENT MED,680 N LAKE SHORE DR,SUITE 1102,CHICAGO,IL 60611, USA. FU NHLBI NIH HHS [N01-HC-48048, N01-HC-48047, N01-HC-48049] NR 38 TC 79 Z9 80 U1 1 U2 8 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD JAN 1 PY 1996 VL 93 IS 1 BP 60 EP 66 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA TL997 UT WOS:A1996TL99700012 PM 8616942 ER PT J AU Madore, DV Anderson, P Baxter, BD Carlone, GM Edwards, KM Hamilton, RG Holder, P Kayhty, H Phipps, DC Peeters, CCA Schneerson, R Siber, GR Ward, JI Frasch, CE AF Madore, DV Anderson, P Baxter, BD Carlone, GM Edwards, KM Hamilton, RG Holder, P Kayhty, H Phipps, DC Peeters, CCA Schneerson, R Siber, GR Ward, JI Frasch, CE TI Interlaboratory study evaluating quantitation of antibodies to Haemophilus influenzae type b polysaccharide by enzyme-linked immunosorbent assay SO CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY LA English DT Article ID RADIOANTIGEN BINDING ASSAY; HEMOPHILUS-INFLUENZAE; CAPSULAR POLYSACCHARIDE; BACTERICIDAL ACTIVITY; ELISA; POLYRIBOPHOSPHATE; IMMUNIZATION; VACCINES; CHILDREN; ANTIGEN AB An interlaboratory study was conducted to determine whether an enzyme-linked immunosorbent assay (ELISA) with an antigen preparation composed of various-sized fragments of Haemophilus influenzae type b polysaccharide conjugated to human serum albumin could be standardized across laboratories and whether the ELISA-derived results from different laboratories are equivalent to those obtained by the standard radioactive antigen binding assay (RABA) for quantitation of anti-H, influenza type b polysaccharide antibodies. Twenty coded human serum samples were qnantitated by ELISA in 11 laboratories and by RABA in 5 laboratories. The mean RABA-derived values served as the basis for all comparisons. While the overall correspondence of antibody values between the two methods was good, significant differences were found among some of the 11 ELISA data sets and among the mean RABA values. Seven laboratories generated higher ELISA antibody values for lo rv-titered sera. Four laboratories generated antibody concentrations that were not statistically different between the two assay methods. The results therefore indicate that the ELISA can tolerate substantial variations in protocol, such as the use of different plates and different antibody reagents, without affecting the quantitation of serum antibodies. However, attention should be focused on low-titered sera, as some assay conditions may yield spurious results. This ELISA is a serologic assay which can serve as an alternative to the RABA for quantitation of antibodies to H. influenzae type b polysaccharide. C1 LEDERLE PRAXIS BIOL,W HENRIETTA,NY. UNIV ROCHESTER,MED CTR,ROCHESTER,NY 14642. BAYLOR COLL MED,INFLUENZA RES CTR,HOUSTON,TX 77030. CTR DIS CONTROL & PREVENT,ATLANTA,GA 30341. VANDERBILT UNIV,SCH MED,NASHVILLE,TN 37212. JOHNS HOPKINS UNIV HOSP,JOHNS HOPKINS ASTHMA & ALLERGY CTR,SCH MED,BALTIMORE,MD 21205. NICHHD,BETHESDA,MD 20892. CTR BIOL EVALUAT & RES,LAB BACTERIAL POLYSACCHARIDES,BETHESDA,MD. NATL PUBL HLTH INST,HELSINKI,FINLAND. NATL INST PUBL HLTH & ENVIRONM,BILTHOVEN,NETHERLANDS. MASSACHUSETTS PUBL HLTH BIOL LABS,BOSTON,MA. UNIV CALIF LOS ANGELES,HARBOR MED SCH,TORRANCE,CA 90509. NR 19 TC 41 Z9 42 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 1071-412X J9 CLIN DIAGN LAB IMMUN JI Clin. Diagn. Lab. Immunol. PD JAN PY 1996 VL 3 IS 1 BP 84 EP 88 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA TP777 UT WOS:A1996TP77700015 PM 8770509 ER PT J AU Gbakima, AA Nutman, TB Bradley, JE McReynolds, LA Winget, MD Hong, Y Scott, AL AF Gbakima, AA Nutman, TB Bradley, JE McReynolds, LA Winget, MD Hong, Y Scott, AL TI Immunoglobulin G subclass responses of children during infection with Onchocerca volvulus SO CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY LA English DT Article ID HAITIAN PEDIATRIC POPULATION; HUMAN FILARIASIS; BANCROFTIAN FILARIASIS; WUCHERERIA-BANCROFTI; RECOMBINANT ANTIGEN; ANTIBODY-RESPONSES; IGG SUBCLASSES; IMMUNITY; PROTEIN; RESPONSIVENESS AB To characterize the patterns of immunoglobulin G (IgG) subclass and IgE reactivity during the early stages of onchocerciasis, sera were collected from 224 children (age groups, 2 to 5, 6 to 10, and II to 15 years) residing in a region of Sierra Leone a-here Onchocerca volvulus is endemic, and these samples were tested by enzyme-linked immunosorbent assay for their reactivity to adult antigens (OvAg) and against four recombinant proteins (OV11, OV27, OV29, and OV16), Over 88% of the samples contained detectable levels of anti-OvAg IgG, In samples from microfilaria (MF)-positive children, IgG4 responses were significantly elevated and constituted on average 39, 35, and 289 of the total IgG responses for the age groups of 2 to 5, 6 to 10, and II to 15 Scars, respectively, For MF-negative individuals, the mean contributions of IgG4 to the total IgG response sere 11% (2 to 5 years), 27% (6 to 10 years), and 56% (11 to 15 years), OvAg-specific IgE was detectable in the sera from both MF-negative and ME-positive individuals, To increase the specificity of the response, recombinant antigens OV11, OV27, and OV29 were tested individually or as a cocktail, Nearly 50% of the MF-negative children and 85% of the ME-positive children had detectable levels of IgG against at least one of the recombinant antigens, Only a small portion of the IgG against the recombinant peptides was IgG4. The prevalence of IgG against OV16 in samples from MF-negative children was 51%, and that for MF-positive children was 75%. The general profile of the humoral immune responses mounted by both ME-positive and a large percentage of the MF-negative children during the initial phases of infection with O, volvulus is similar to the profile reported for adults harboring chronic O. volvulus infections, These results suggest that very quickly after infection, the interactions between parasite and host result in an immunological environment that may contribute to the maintenance of a long-term, chronic infection. C1 JOHNS HOPKINS UNIV, SCH HYG & PUBL HLTH, DEPT MOLEC MICROBIOL & IMMUNOL, BALTIMORE, MD 21205 USA. UNIV SIERRA, NJALA UNIV COLL, DEPT BIOL SCI, TROP DIS RES UNIT, FREETOWN, SIERRA LEONE. NIAID, PARASIT DIS LAB, BETHESDA, MD 20892 USA. UNIV LONDON IMPERIAL COLL SCI & TECHNOL, DEPT PURE & APPL BIOL, LONDON SW7 2BB, ENGLAND. NEW ENGLAND BIOLABS INC, BEVERLY, MA 01915 USA. NATL UNIV SINGAPORE, INST MOLEC & CELL BIOL, SINGAPORE 117548, SINGAPORE. JOHNS HOPKINS UNIV, SCH HYG & PUBL HLTH, DEPT EPIDEMIOL, BALTIMORE, MD 21205 USA. RI ASTAR, IMCB/E-2320-2012; Hong, Yan/D-5106-2014; OI Hong, Yan/0000-0002-2954-8788; Bradley, Janette/0000-0003-3973-7977 NR 48 TC 4 Z9 4 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1071-412X J9 CLIN DIAGN LAB IMMUN JI Clin. Diagn. Lab. Immunol. PD JAN PY 1996 VL 3 IS 1 BP 98 EP 104 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA TP777 UT WOS:A1996TP77700018 PM 8770512 ER PT J AU Chiu, JJ Sgagias, MK Cowan, KH AF Chiu, JJ Sgagias, MK Cowan, KH TI Interleukin 6 acts as a paracrine growth factor in human mammary carcinoma cell lines SO CLINICAL CANCER RESEARCH LA English DT Article ID RECEPTOR EXPRESSION; STIMULATING FACTOR; SIGNAL TRANSDUCER; EPITHELIAL-CELLS; BREAST-CANCER; DIFFERENTIATION; INVITRO; ASSOCIATION; PROTEIN; PURIFICATION AB The effect of interleukin 6 (IL-6) on normal and human mammary carcinoma epithelial cells was studied, IL-6 inhibited the growth of estrogen receptor-positive [ER(+)] breast cancer cell lines, which underwent apoptosis with prolonged treatment. In contrast, ER(-) breast cancer cell lines were resistant to IL-6-mediated growth inhibition. By examining the components of the IL-6 receptor (IL-6R) system, we found that ER(+) breast cancer cells expressed predominantly soluble IL-6R alpha, whereas the ER(-) breast cancer cells expressed primarily the transmembrane form of the IL-6R, gp130. In addition, detectable levels of IL-6 were secreted into the medium by ER(-) but not ER(+) breast cancer cells. Furthermore, the supernatant obtained from IL-6-secreting, ER(-) cells suppressed the growth of IL-6-sensitive, ER(+) breast cancer cells in a paracrine fashion. Although IL-6 is secreted by ER(-) breast cancer cells, this cytokine does not seem to stimulate the proliferation of these cells in an autocrine fashion, These studies indicate that IL-6 can regulate the growth of normal and transformed human mammary epithelial cells differentially, and that IL-6 secretion by some ER(-) breast cancer cells can function as a paracrine growth factor, suppressing the growth of ER(+) breast cancer cells irt vitro. RP Chiu, JJ (reprint author), NCI,MED BRANCH,BLDG 10,ROOM 12N226,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 37 TC 56 Z9 57 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JAN PY 1996 VL 2 IS 1 BP 215 EP 221 PG 7 WC Oncology SC Oncology GA TN878 UT WOS:A1996TN87800028 PM 9816109 ER PT J AU Rao, JS Yamamoto, M Mohaman, S Gokaslan, ZL Fuller, GN StetlerStevenson, WG Rao, VH Liotta, LA Nicolson, GL Sawaya, RE AF Rao, JS Yamamoto, M Mohaman, S Gokaslan, ZL Fuller, GN StetlerStevenson, WG Rao, VH Liotta, LA Nicolson, GL Sawaya, RE TI Expression and localization of 92 kDa type IV collagenase gelatinase B (MMP-9) in human gliomas SO CLINICAL & EXPERIMENTAL METASTASIS LA English DT Article DE 92 kDa type IV collagenase; astrocytoma; glioblastoma multiforme; invasiveness; matrix-metalloproteinase ID SQUAMOUS-CELL-CARCINOMA; BASEMENT-MEMBRANE; TISSUE INHIBITOR; MATRIX METALLOPROTEINASES; 92-KDA GELATINASE; BRAIN-TUMORS; METASTASIS; INVASION; LUNG; SECRETION AB Matrix metalloproteinases play an important regulatory role in tissue morphogenesis, cell differentiation and motility, and tumor cell invasiveness, We have recently demonstrated elevated activity of the 92 kDa type IV collagenase (MMP-9) in human glioblastoma and in the present study examine the relative amounts of MMP-9 protein and mRNA in human gliomas and as well as the distribution of MMP-9 in human glioma tumors in vivo. Using an enzyme-linked immunosorbent assay for the quantitative determination of MMP-9 protein, we found that levels were significantly higher in malignant astrocytomas, especially in glioblastoma multiforme, than in normal brain tissues and low-grade gliomas. In addition, the amount of MMP-9 mRNA, as determined by northern blot analysis was higher in anaplastic astrocytomas and glioblastoma multiforme than in normal brain tissue and low-grade gliomas. Immunocytochemical staining for MMP-9 showed strong cytoplasmic immunoreactivity in the tumor cells and the proliferating endothelial cells of glioblastoma multiforme and anaplastic astrocytomas, The staining intensity was lower in low-grade astrocytomas, and was undetectable or very low in normal brain astrocytes, The results indicate that expression of MMP-9 is dramatically upregulated in highly malignant gliomas and correlates with the highly malignant progression of human gliomas in vivo, and support a role for the MMP-9 in facilitating the invasiveness seen in malignant gliomas in vivo. C1 UNIV TEXAS,MD ANDERSON CANC CTR,DEPT PATHOL,HOUSTON,TX 77030. UNIV TEXAS,MD ANDERSON CANC CTR,DEPT TUMOR BIOL,HOUSTON,TX 77030. NCI,PATHOL LAB,BETHESDA,MD 20892. MEYER REHABIL INST,MATRIX RES LAB,OMAHA,NE. RP Rao, JS (reprint author), UNIV TEXAS,MD ANDERSON CANC CTR,DEPT NEUROSURG,BOX 064,1515 HOLCOMBE BLVD,HOUSTON,TX 77030, USA. RI Stetler-Stevenson, William/H-6956-2012; OI Stetler-Stevenson, William/0000-0002-5500-5808; Fuller, Gregory/0000-0001-9447-2647 FU NCI NIH HHS [CA 56792] NR 34 TC 128 Z9 136 U1 0 U2 3 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0262-0898 J9 CLIN EXP METASTAS JI Clin. Exp. Metastasis PD JAN PY 1996 VL 14 IS 1 BP 12 EP 18 DI 10.1007/BF00157681 PG 7 WC Oncology SC Oncology GA TK860 UT WOS:A1996TK86000002 PM 8521611 ER PT J AU Sivaparvathi, M Yamamoto, M Nicolson, GL Gokaslan, ZL Fuller, GN Liotta, LA Sawaya, R Rao, JS AF Sivaparvathi, M Yamamoto, M Nicolson, GL Gokaslan, ZL Fuller, GN Liotta, LA Sawaya, R Rao, JS TI Expression and immunohistochemical localization of cathepsin L during the progression of human gliomas SO CLINICAL & EXPERIMENTAL METASTASIS LA English DT Article DE cathepsins; cysteine proteases; cysteine protease inhibitors; glioblastoma multiforme; invasiveness ID CYSTEINE PROTEINASE; STRUCTURAL PROTEINS; MURINE FIBROBLASTS; MICROSOMAL LUMEN; CANCER-CELLS; DEGRADATION; MEMBRANE; IDENTIFICATION; INHIBITORS; ACTIVATION AB Recent studies suggest that cysteine proteinase cathepsin L is involved in the process of tumor invasion and metastasis, We examined cathepsin L activity in brain tumor tissue samples by an enzymatic assay, and cathepsin L protein content by enzyme-linked immunoadsorbent assays and Western blotting to determine whether increased levels of cathepsin L correlate with the progression of human gliomas, Native and acid-activatable cathepsin L activities were highest in glioblastomas followed by anaplastic astrocytomas and were lowest in low-grade gliomas and normal brain tissues, Significantly higher amounts of an M(r) 29 000 cathepsin L were present in glioblastomas and anaplastic astrocytomas than in normal brain tissues and low-grade glioma tissue extracts, Using specific antibodies to cathepsin L, we also studied its cellular distribution by immunohistochemical procedures, Higher diffuse cathepsin L immunoreactivity was found in glioblastomas than in low-grade gliomas and normal brain tissue samples. Finally, the addition of cathepsin L antibody inhibits the invasion of glioblastoma cell lines through Matrigel invasion assay. These results suggest the expression of cathepsin L is dramatically upregulated in malignant gliomas and correlates with the malignant progression of human gliomas in vivo. C1 UNIV TEXAS,MD ANDERSON CANC CTR,DEPT NEUROSURG,HOUSTON,TX 77030. UNIV TEXAS,MD ANDERSON CANC CTR,DEPT TUMOR BIOL,HOUSTON,TX 77030. UNIV TEXAS,MD ANDERSON CANC CTR,DEPT NEUROPATHOL,HOUSTON,TX 77030. NCI,PATHOL LAB,BETHESDA,MD 20892. OI Fuller, Gregory/0000-0001-9447-2647 FU NCI NIH HHS [CA 56792] NR 38 TC 51 Z9 52 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0262-0898 J9 CLIN EXP METASTAS JI Clin. Exp. Metastasis PD JAN PY 1996 VL 14 IS 1 BP 27 EP 34 DI 10.1007/BF00157683 PG 8 WC Oncology SC Oncology GA TK860 UT WOS:A1996TK86000004 PM 8521613 ER PT J AU Sawaya, RE Yamamoto, M Gokaslan, ZL Wang, SW Mohanam, S Fuller, GN McCutcheon, IE StetlerStevenson, WG Nicolson, GL Rao, JS AF Sawaya, RE Yamamoto, M Gokaslan, ZL Wang, SW Mohanam, S Fuller, GN McCutcheon, IE StetlerStevenson, WG Nicolson, GL Rao, JS TI Expression and localization of 72 kDa type IV collagenase (MMP-2) in human malignant gliomas in vivo SO CLINICAL & EXPERIMENTAL METASTASIS LA English DT Article DE glioblastoma multiforme; invasiveness; malignant astrocytoma; matrix metalloproteinase; 72 kDa type IV collagenase ID TISSUE INHIBITOR; MATRIX METALLOPROTEINASES; PLASMINOGEN-ACTIVATOR; MESSENGER-RNA; BRAIN-TUMORS; MR 72,000; CELLS; INVASION; ANGIOGENESIS; METASTASIS AB The 72 kDa type IV collagenase (gelatinase), a matrix metalloproteinase (MMP-2), has been proposed to potentiate the invasion and metastasis of malignant tumors, To determine the potential role of the MMP-2 in human gliomas and normal brain tissue, we examined the relative amounts of protein, mRNA, and distribution, Using gelatin zymography, densitometry, and an enzyme-linked immunosorbent assay for the quantitative determination of the MMP-2 we found that the enzyme's activity was significantly elevated in malignant astrocytomas, especially in glioblastoma multiforme, compared to low-grade glioma and normal brain tissues, As determined by Northern blot analysis, the amount of MMP-2 mRNA transcript was higher in anaplastic astrocytomas and glioblastoma multiforme tumors than in normal brain tissues or low-grade gliomas, a finding that was consistent with the amounts of MMP-2 protein detected in these tissues, Immunohistochemical studies demonstrated that MMP-2 was localized in tumor cells and vasculature cells of malignant astrocytomas, Staining intensity was clearly lower in low-grade astrocytomas, and immunoreactivity was very low or undetectable in normal brain astrocytes, The results suggest that expression of the MMP-2 is dramatically upregulated in malignant gliomas, correlating with the malignant progression of human gliomas in vivo. C1 UNIV TEXAS,MD ANDERSON CANC CTR,DEPT NEUROSURG,HOUSTON,TX 77030. UNIV TEXAS,MD ANDERSON CANC CTR,DEPT PATHOL,HOUSTON,TX 77030. UNIV TEXAS,MD ANDERSON CANC CTR,DEPT TUMOR BIOL,HOUSTON,TX 77030. NCI,PATHOL LAB,BETHESDA,MD 20892. RI Stetler-Stevenson, William/H-6956-2012; OI Stetler-Stevenson, William/0000-0002-5500-5808; Fuller, Gregory/0000-0001-9447-2647 FU NCI NIH HHS [CA 56792] NR 37 TC 137 Z9 140 U1 0 U2 3 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0262-0898 J9 CLIN EXP METASTAS JI Clin. Exp. Metastasis PD JAN PY 1996 VL 14 IS 1 BP 35 EP 42 DI 10.1007/BF00157684 PG 8 WC Oncology SC Oncology GA TK860 UT WOS:A1996TK86000005 PM 8521615 ER PT J AU LekstromHimes, JA Dale, JK Kingma, DW Diaz, PS Jaffe, ES Straus, SE AF LekstromHimes, JA Dale, JK Kingma, DW Diaz, PS Jaffe, ES Straus, SE TI Periodic illness associated with Epstein-Barr virus infection SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID FAMILIAL MEDITERRANEAN FEVER; RENAL-TRANSPLANT RECIPIENTS; NUCLEAR ANTIGEN; OROPHARYNGEAL EXCRETION; ANTIBODY-RESPONSES; INTERFERON; COMPLEX; DISEASE; ADULT AB A 15-year-old boy with a 13-year history of periodic fevers, lymphadenopathy, and leukocytosis showed virological, serological, immunohistologic, and molecular evidence of persistent, active, Epstein-Barr virus (EBV) infection. Acyclovir and several other agents failed to alter his clinical course. Comprehensive immunological studies could not identify a defined immune deficiency syndrome to explain the persistent infection, although he does continue to have circulating polymeric EBV-specific immunoglobulin type A, as is seen in individuals during acute EBV infections. In vitro work suggests that this polymeric antibody prevents B cell infection by EBV. Cumulative data suggest that this patient suffers from a novel form of EBV infection. C1 NIAID,CLIN INVEST LAB,BETHESDA,MD 20892. NIH,WARREN GRANT MAGNUSON CLIN CTR,DEPT PATHOL,BETHESDA,MD 20892. UNIV CHICAGO,DEPT PEDIAT INFECT DIS,CHICAGO,IL 60637. NR 34 TC 18 Z9 18 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JAN PY 1996 VL 22 IS 1 BP 22 EP 27 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA TP780 UT WOS:A1996TP78000004 PM 8824960 ER PT J AU Ferguson, JH AF Ferguson, JH TI Research syntheses in the form of meta-analysis in the NIH consensus development conference SO CLINICAL RESEARCH AND REGULATORY AFFAIRS LA English DT Proceedings Paper CT 1st National Meeting on Research Synthesis - Applications to Drug Regulatory Policy and Health Care Policy CY DEC 05, 1994 CL HARVARD SCH PUBLIC HLTH, BOSTON, MA SP Harvard Sch Public Hlth, Technol Assessment Grp HO HARVARD SCH PUBLIC HLTH RP Ferguson, JH (reprint author), NIH,OFF MED APPLICAT & RES,FED BLDG,ROOM 618,BETHESDA,MD 20892, USA. NR 10 TC 0 Z9 0 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 SN 1060-1333 J9 CLIN RES REGUL AFF JI Clin. Res. Regul. Affairs PY 1996 VL 13 IS 1 BP 31 EP 35 DI 10.3109/10601339609019627 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA TX935 UT WOS:A1996TX93500005 ER PT J AU Klar, AJS AF Klar, AJS TI A single locus, RGHT, specifies preference for hand utilization in humans SO COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY LA English DT Article; Proceedings Paper CT 61st Cold Spring Harbor Symposium on Function and Dysfunction in the Nervous System CY 1996 CL COLD SPRING HARBOR, NY SP Alza Corp, Amgen Inc, BASF Biores Corp, Becton Dickinson & Co, Boehringer Mannheim Corp, Bristol Myers Squibb Co, Chiron Corp, Chugal Res Inst Molec Med Inc, Diagnost Prod Corp, Dupont Merck Pharmaceut Co, Forest Labs Inc, Genentech Inc, Hoeshst Marion Roussel Inc, Hoffmann La Roche Inc, Johnson & Johnson, Kyowa Hakko Kogyo Co Ltd, Life Technol Inc, Eli Lilly & Co, Oncogene Sci Inc, Pall Corp, Perkin Elmer Corp, Appl Biosyst Div, Pfizer Inc, Pharmacia & Upjohn Inc, Res Genet Inc, Sandoz Res Inst, Schering Plough Corp, Sumitomo Pharmaceut Co Ltd, Wyeth Ayerst Res, Zeneca Grp PLC ID HUMAN HANDEDNESS; SKILL; MODEL; LATERALITY; POPULATION RP NCI, FREDERICK CANC RES & DEV CTR, ABL BASIC RES PROGRAM, GENE REGULAT & CHROMOSOME BIOL LAB, FREDERICK, MD 21702 USA. FU NCI NIH HHS [N01-CO-46000] NR 28 TC 59 Z9 61 U1 0 U2 0 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 0091-7451 J9 COLD SPRING HARB SYM JI Cold Spring Harbor Symp. Quant. Biol. PY 1996 VL 61 BP 59 EP 65 PG 7 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA XD580 UT WOS:A1996XD58000008 PM 9246435 ER PT J AU Wang, ZZ Fuhrer, C Shtrom, S Sugiyama, JE Ferns, MJ Hall, ZW AF Wang, ZZ Fuhrer, C Shtrom, S Sugiyama, JE Ferns, MJ Hall, ZW TI The nicotinic acetylcholine receptor at the neuromuscular junction: Assembly and tyrosine phosphorylation SO COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY LA English DT Article; Proceedings Paper CT 61st Cold Spring Harbor Symposium on Function and Dysfunction in the Nervous System CY 1996 CL COLD SPRING HARBOR, NY SP Alza Corp, Amgen Inc, BASF Biores Corp, Becton Dickinson & Co, Boehringer Mannheim Corp, Bristol Myers Squibb Co, Chiron Corp, Chugal Res Inst Molec Med Inc, Diagnost Prod Corp, Dupont Merck Pharmaceut Co, Forest Labs Inc, Genentech Inc, Hoeshst Marion Roussel Inc, Hoffmann La Roche Inc, Johnson & Johnson, Kyowa Hakko Kogyo Co Ltd, Life Technol Inc, Eli Lilly & Co, Oncogene Sci Inc, Pall Corp, Perkin Elmer Corp, Appl Biosyst Div, Pfizer Inc, Pharmacia & Upjohn Inc, Res Genet Inc, Sandoz Res Inst, Schering Plough Corp, Sumitomo Pharmaceut Co Ltd, Wyeth Ayerst Res, Zeneca Grp PLC ID ENDOPLASMIC-RETICULUM; TERMINAL DOMAINS; XENOPUS OOCYTES; COS CELLS; PROTEIN; AGRIN; KINASES; GLYCOPROTEIN; BINDING; SUBUNIT C1 UNIV CALIF SAN FRANCISCO,DEPT PHYSIOL,SAN FRANCISCO,CA 94143. RP Wang, ZZ (reprint author), NIMH,NIH,BETHESDA,MD 20892, USA. NR 50 TC 5 Z9 5 U1 0 U2 2 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 0091-7451 J9 COLD SPRING HARB SYM JI Cold Spring Harbor Symp. Quant. Biol. PY 1996 VL 61 BP 363 EP 371 PG 9 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA XD580 UT WOS:A1996XD58000038 PM 9246465 ER PT J AU Pichel, JG Shen, L Sheng, HZ Granholm, AC Drago, J Grinberg, A Lee, EJ Huang, SP Saarma, M Hoffer, BJ Sariola, H Westphal, H AF Pichel, JG Shen, L Sheng, HZ Granholm, AC Drago, J Grinberg, A Lee, EJ Huang, SP Saarma, M Hoffer, BJ Sariola, H Westphal, H TI GDNF is required for kidney development and enteric innervation SO COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY LA English DT Article; Proceedings Paper CT 61st Cold Spring Harbor Symposium on Function and Dysfunction in the Nervous System CY 1996 CL COLD SPRING HARBOR, NY SP Alza Corp, Amgen Inc, BASF Biores Corp, Becton Dickinson & Co, Boehringer Mannheim Corp, Bristol Myers Squibb Co, Chiron Corp, Chugal Res Inst Molec Med Inc, Diagnost Prod Corp, Dupont Merck Pharmaceut Co, Forest Labs Inc, Genentech Inc, Hoeshst Marion Roussel Inc, Hoffmann La Roche Inc, Johnson & Johnson, Kyowa Hakko Kogyo Co Ltd, Life Technol Inc, Eli Lilly & Co, Oncogene Sci Inc, Pall Corp, Perkin Elmer Corp, Appl Biosyst Div, Pfizer Inc, Pharmacia & Upjohn Inc, Res Genet Inc, Sandoz Res Inst, Schering Plough Corp, Sumitomo Pharmaceut Co Ltd, Wyeth Ayerst Res, Zeneca Grp PLC ID MIDBRAIN DOPAMINERGIC-NEURONS; GROWTH FACTOR/SCATTER FACTOR; TYROSINE KINASE RECEPTOR; NEUROTROPHIC FACTOR GDNF; EMBRYONIC STEM-CELLS; IN-VIVO; RET PROTOONCOGENE; NERVOUS-SYSTEM; MESSENGER-RNA; NEURAL CREST C1 UNIV COLORADO,HLTH SCI CTR,DEPT PHARMACOL,DENVER,CO 80262. UNIV COLORADO,HLTH SCI CTR,DEPT BASIC DENT SCI,DENVER,CO 80262. MONASH UNIV,DEPT ANAT,CLAYTON,VIC 3168,AUSTRALIA. UNIV HELSINKI,INST BIOTECHNOL,PROGRAM DEV BIOL,BIOCTR 1,FIN-00014 HELSINKI,FINLAND. UNIV HELSINKI,INST BIOTECHNOL,PROGRAM MOL NEUROBIOL,BIOCTR 1,FIN-00014 HELSINKI,FINLAND. UNIV HELSINKI,CHILDRENS HOSP,LAB PEDIAT PATHOL,FIN-00380 HELSINKI,FINLAND. RP Pichel, JG (reprint author), NCI,LAB MAMMALIAN GENES & DEV,BETHESDA,MD 20892, USA. NR 85 TC 28 Z9 28 U1 1 U2 1 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 0091-7451 J9 COLD SPRING HARB SYM JI Cold Spring Harbor Symp. Quant. Biol. PY 1996 VL 61 BP 445 EP 457 PG 13 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA XD580 UT WOS:A1996XD58000046 PM 9246473 ER PT J AU Wickner, RB Masison, DC Edskes, HK Maddelein, ML AF Wickner, RB Masison, DC Edskes, HK Maddelein, ML TI Prions of yeast, [PSI] and [URE3], as models for neurodegenerative diseases SO COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY LA English DT Article; Proceedings Paper CT 61st Cold Spring Harbor Symposium on Function and Dysfunction in the Nervous System CY 1996 CL COLD SPRING HARBOR, NY SP Alza Corp, Amgen Inc, BASF Biores Corp, Becton Dickinson & Co, Boehringer Mannheim Corp, Bristol Myers Squibb Co, Chiron Corp, Chugal Res Inst Molec Med Inc, Diagnost Prod Corp, Dupont Merck Pharmaceut Co, Forest Labs Inc, Genentech Inc, Hoeshst Marion Roussel Inc, Hoffmann La Roche Inc, Johnson & Johnson, Kyowa Hakko Kogyo Co Ltd, Life Technol Inc, Eli Lilly & Co, Oncogene Sci Inc, Pall Corp, Perkin Elmer Corp, Appl Biosyst Div, Pfizer Inc, Pharmacia & Upjohn Inc, Res Genet Inc, Sandoz Res Inst, Schering Plough Corp, Sumitomo Pharmaceut Co Ltd, Wyeth Ayerst Res, Zeneca Grp PLC ID SACCHAROMYCES-CEREVISIAE; TRANSGENIC MICE; SUP35 GENE; PROTEIN HSP104; SCRAPIE PRION; MUTATION; SUPPRESSION; PROPAGATION; TRANSLATION; TERMINATION RP Wickner, RB (reprint author), NIDDKD,SECT GENET SIMPLE EUKARYOTES,NIH,BETHESDA,MD 20892, USA. RI MADDELEIN, Marie-Lise/G-5395-2010 NR 57 TC 4 Z9 4 U1 0 U2 1 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 0091-7451 J9 COLD SPRING HARB SYM JI Cold Spring Harbor Symp. Quant. Biol. PY 1996 VL 61 BP 541 EP 550 PG 10 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA XD580 UT WOS:A1996XD58000053 PM 9246480 ER PT J AU Hall, ZW AF Hall, ZW TI Summary: Function and dysfunction of the nervous system SO COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY LA English DT Article; Proceedings Paper CT 61st Cold Spring Harbor Symposium on Function and Dysfunction in the Nervous System CY 1996 CL COLD SPRING HARBOR, NY SP Alza Corp, Amgen Inc, BASF Biores Corp, Becton Dickinson & Co, Boehringer Mannheim Corp, Bristol Myers Squibb Co, Chiron Corp, Chugal Res Inst Molec Med Inc, Diagnost Prod Corp, Dupont Merck Pharmaceut Co, Forest Labs Inc, Genentech Inc, Hoeshst Marion Roussel Inc, Hoffmann La Roche Inc, Johnson & Johnson, Kyowa Hakko Kogyo Co Ltd, Life Technol Inc, Eli Lilly & Co, Oncogene Sci Inc, Pall Corp, Perkin Elmer Corp, Appl Biosyst Div, Pfizer Inc, Pharmacia & Upjohn Inc, Res Genet Inc, Sandoz Res Inst, Schering Plough Corp, Sumitomo Pharmaceut Co Ltd, Wyeth Ayerst Res, Zeneca Grp PLC RP Hall, ZW (reprint author), NINCDS,NIH,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 0091-7451 J9 COLD SPRING HARB SYM JI Cold Spring Harbor Symp. Quant. Biol. PY 1996 VL 61 BP 851 EP 861 PG 11 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA XD580 UT WOS:A1996XD58000083 ER PT B AU Renyi, I Barsony, J AF Renyi, I Barsony, J BE Tarnay, K Fazekas, Z TI Fluorescent imaging and fluorometry techniques to study hormone binding to vitamin D receptors in live cells SO COMBIO'96 - SUMMER WORKSHOP ON COMPUTATIONAL MODELLING, IMAGING AND VISUALIZATION IN BIOSCIENCES SE KFKI PREPRINT/REPORT SERIES LA English DT Proceedings Paper CT Summer Workshop on Computational Modelling, Imaging and Visualization in Biosciences (COMBIO 96) CY AUG 29-31, 1996 CL SOPRON, HUNGARY SP Hungarian Acad Sci, Natl Comm Technol Dev, IEEE, Hungarian Sect C1 NIDDK,LAB CELL BIOL & BIOCHEM,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KFKI - ATOMIC ENERGY RESEARCH INST, APPL REACTOR PHYSICS PI BUDAPEST PA PO BOX 49, H-1525 BUDAPEST, HUNGARY J9 KFKI PREP R PY 1996 VL 1996 IS 6 BP 23 EP 30 PN M,H PG 8 WC Computer Science, Interdisciplinary Applications; Medical Informatics; Medicine, Research & Experimental SC Computer Science; Medical Informatics; Research & Experimental Medicine GA BG36D UT WOS:A1996BG36D00004 ER PT J AU Chen, TT Simon, R AF Chen, TT Simon, R TI Extension of two-sided test to multiple treatment trials SO COMMUNICATIONS IN STATISTICS-THEORY AND METHODS LA English DT Article DE multiple comparison; multiple range test; sample size; subset selection; slippage test ID SELECTION AB In a two-treatment trial, a two-sided test is often used to reach a conclusion. Usually we are interested in doing a two-sided test because of no prior preference between the two treatments and we want a three-decision framework. When a standard control is just as good as the new experiment-al treatment (which has the same toxicity and cost), then we will accept both treatments. Only when the standard control is clearly worse or better than the new experimental treatment, then we choose only one treatment. In this paper, we extend the concept of a two-sided test to the multiple treatment trial where three or more treatments are involved. The procedure turns out to be a subset selection procedure; however, the theoretical framework and performance requirement are different from the existing subset selection procedures. Two procedures (exclusion or inclusion) are developed here for the case of normal data with equal known variance. If the sample size is large, they can be applied with unknown variance and with the binomial data or survival data with random censoring. C1 NCI,BIOMETR RES BRANCH,BETHESDA,MD 20892. NR 20 TC 2 Z9 2 U1 0 U2 1 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 SN 0361-0926 J9 COMMUN STAT THEORY JI Commun. Stat.-Theory Methods PY 1996 VL 25 IS 5 BP 947 EP 965 DI 10.1080/03610929608831742 PG 19 WC Statistics & Probability SC Mathematics GA UE425 UT WOS:A1996UE42500004 ER PT J AU Madden, TL Tatusov, RL Zhang, JH AF Madden, TL Tatusov, RL Zhang, JH TI Applications of network BLAST server SO COMPUTER METHODS FOR MACROMOLECULAR SEQUENCE ANALYSIS SE METHODS IN ENZYMOLOGY LA English DT Review RP Madden, TL (reprint author), NIH,NATL CTR BIOTECHNOL INFORMAT,NATL LIB MED,BETHESDA,MD 20894, USA. NR 0 TC 217 Z9 227 U1 0 U2 4 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0076-6879 J9 METHOD ENZYMOL JI Methods Enzymol. PY 1996 VL 266 BP 131 EP 141 PG 11 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BF77C UT WOS:A1996BF77C00009 PM 8743682 ER PT J AU Schuler, GD Epstein, JA Ohkawa, H Kans, JA AF Schuler, GD Epstein, JA Ohkawa, H Kans, JA TI Entrez: Molecular biology database and retrieval system SO COMPUTER METHODS FOR MACROMOLECULAR SEQUENCE ANALYSIS SE METHODS IN ENZYMOLOGY LA English DT Review RP Schuler, GD (reprint author), NIH,NATL CTR BIOTECHNOL INFORMAT,NATL LIB MED,BETHESDA,MD 20894, USA. NR 0 TC 231 Z9 237 U1 1 U2 5 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0076-6879 J9 METHOD ENZYMOL JI Methods Enzymol. PY 1996 VL 266 BP 141 EP 162 PG 22 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BF77C UT WOS:A1996BF77C00010 PM 8743683 ER PT J AU Koonin, EV Tatusov, RL Rudd, KE AF Koonin, EV Tatusov, RL Rudd, KE TI Protein sequence comparison at genome scale SO COMPUTER METHODS FOR MACROMOLECULAR SEQUENCE ANALYSIS SE METHODS IN ENZYMOLOGY LA English DT Review RP Koonin, EV (reprint author), NIH,NATL CTR BIOTECHNOL INFORMAT,NATL LIB MED,BETHESDA,MD 20894, USA. NR 0 TC 70 Z9 70 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0076-6879 J9 METHOD ENZYMOL JI Methods Enzymol. PY 1996 VL 266 BP 295 EP 322 PG 28 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BF77C UT WOS:A1996BF77C00018 PM 8743691 ER PT J AU Altschul, SF Gish, W AF Altschul, SF Gish, W TI Local alignment statistics SO COMPUTER METHODS FOR MACROMOLECULAR SEQUENCE ANALYSIS SE METHODS IN ENZYMOLOGY LA English DT Review C1 WASHINGTON UNIV,SCH MED,DEPT GENET,ST LOUIS,MO 63108. RP Altschul, SF (reprint author), NIH,NATL CTR BIOTECHNOL INFORMAT,NATL LIB MED,BETHESDA,MD 20894, USA. RI Gish, Warren/C-8123-2012 NR 0 TC 450 Z9 463 U1 0 U2 10 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0076-6879 J9 METHOD ENZYMOL JI Methods Enzymol. PY 1996 VL 266 BP 460 EP 480 PG 21 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BF77C UT WOS:A1996BF77C00027 PM 8743700 ER PT J AU Wootton, JC Federhen, S AF Wootton, JC Federhen, S TI Analysis of compositionally biased regions in sequence databases SO COMPUTER METHODS FOR MACROMOLECULAR SEQUENCE ANALYSIS SE METHODS IN ENZYMOLOGY LA English DT Review RP Wootton, JC (reprint author), NIH,NATL CTR BIOTECHNOL INFORMAT,NATL LIB MED,BETHESDA,MD 20894, USA. NR 0 TC 501 Z9 520 U1 0 U2 10 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0076-6879 J9 METHOD ENZYMOL JI Methods Enzymol. PY 1996 VL 266 BP 554 EP 571 PG 18 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BF77C UT WOS:A1996BF77C00033 PM 8743706 ER PT J AU Shkarin, P Spencer, RGS AF Shkarin, P Spencer, RGS TI Direct simulation of spin echoes by summation of isochromats SO CONCEPTS IN MAGNETIC RESONANCE LA English DT Article AB Numerous methods have been used to illustrate and simulate complex spin-echo phenomena for noninteracting spins. Our approach is to reconstruct the time domain signal by what amounts to a finite Fourier series, the terms of which correspond to spin isochromats. The coefficients of the series evolve in response to pulses and periods of free precession. This permits explicit calculation of echo timings and amplitudes for a sequence of strong pulses of arbitrary number, timing, flip angle, and phase. The effects of the shape and density of the isochromat distribution on echo formation are investigated, as are the effects of spin-spin and spin-lattice relaxation. In addition, we identify explicitly the magnetization components that contribute to echo formation in complex sequences. Further, the effect of pulse errors on echo amplitudes is readily simulated. (C) 1996 John Wiley & Sons, inc. C1 NIA,NIH,BALTIMORE,MD 21224. NR 11 TC 9 Z9 10 U1 0 U2 0 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 1043-7347 J9 CONCEPT MAGNETIC RES JI Concepts Magn. Resonance PY 1996 VL 8 IS 4 BP 253 EP 268 DI 10.1002/(SICI)1099-0534(1996)8:4<253::AID-CMR2>3.0.CO;2-Y PG 16 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy SC Chemistry; Physics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy GA UR187 UT WOS:A1996UR18700002 ER PT J AU Werbelow, L London, RE AF Werbelow, L London, RE TI Dynamic frequency shift SO CONCEPTS IN MAGNETIC RESONANCE LA English DT Article ID HIGHER-RANK MULTIPOLES; HALF-MOLECULES; SPIN RELAXATION; LINE-SHAPES; NMR; NUCLEI; QUADRUPOLAR; OVOTRANSFERRIN; SYSTEMS; BINDING AB The relationship between the measured relaxation characteristics of nuclear spin polarization or coherence and molecular dynamics invariably is analyzed via the calculation of spectral density functions derived from single-sided Fourier transforms of time-dependent, angular correlation functions. Consequently, the associated spectral densities and hence, all derived relaxation parameters, are intrinsically complex-valued. The imaginary part of the spectral density, commonly associated with a ''dynamic'' frequency shift, generally has been considered negligible. However, an increasing number of situations have been noted in which these dynamic frequency shins introduce readily measured and quantifiable spectral perturbations. In this review, the origin, characteristics, and, most important, the relevance of the dynamic frequency shift are discussed. (C) 1996 John Wiley & Sons, Inc. C1 NEW MEXICO INST MIN & TECHNOL,SOCORRO,NM 87801. NIEHS,MOL BIOPHYS LAB,RES TRIANGLE PK,NC 27709. NR 64 TC 32 Z9 32 U1 2 U2 9 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 1043-7347 J9 CONCEPT MAGNETIC RES JI Concepts Magn. Resonance PY 1996 VL 8 IS 5 BP 325 EP 338 DI 10.1002/(SICI)1099-0534(1996)8:5<325::AID-CMR2>3.0.CO;2-0 PG 14 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy SC Chemistry; Physics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy GA UZ789 UT WOS:A1996UZ78900004 ER PT J AU Robey, PG AF Robey, PG TI Vertebrate mineralized matrix proteins: Structure and function SO CONNECTIVE TISSUE RESEARCH LA English DT Article; Proceedings Paper CT 5th International Conference on the Chemistry and Biology of Mineralized Tissues CY OCT 22-27, 1995 CL KOHLER, WI DE collagen; glycosaminoglycans; proteoglycans; glycoproteins; gla-proteins ID ENAMEL AB The mineralized matrices of enamel, cementum, dentin, calcified cartilage and bone are similar in their ability to form a microenvironment that facilitates deposition of hydroxyapatite. However, they are not identical, as witnessed by the nature of apatite crystals that are formed. Enamel is devoid of collagen, and is composed of enamelins, amelogenins, tuftelin and ameloblastin, first described at this meeting. Cementum, dentin and bone matrices are composed primarily of type I collagen, however, each matrix may also contain unique moieties. The exact composition of cementum is not fully known, but in dentin there are unique matrix proteins, phosphophoryn (dentin phosphoprotein, DPP), a distinctive dentin matrix protein (DMP-1), and dentin sialoprotein (DSP). In bone, dentin and cementum, the matrix proteins include proteoglycans (versican, decorin, biglycan) and hyaluronan, glycoproteins which are often phosphorylated and sulfated (osteonectin, RGD-containing proteins) and gla-containing proteins (matrix gla protein, protein S, osteocalcin). The exact nature of all the non-collagenous proteins of calcified cartilage is not yet fully known. While there are no definitive functions for any of the mineralized matrix proteins to date, they most likely participate in regulation of cell metabolism, matrix deposition and mineralization, and bone turnover. C1 NIDR, BONE RES BRANCH, NIH, BETHESDA, MD 20892 USA. RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 NR 6 TC 93 Z9 96 U1 1 U2 10 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0300-8207 J9 CONNECT TISSUE RES JI Connect. Tissue Res. PY 1996 VL 35 IS 1-4 BP 131 EP 136 DI 10.3109/03008209609029183 PG 6 WC Cell Biology; Orthopedics SC Cell Biology; Orthopedics GA WL094 UT WOS:A1996WL09400023 PM 9084650 ER PT J AU Stubbs, JT AF Stubbs, JT TI Generation and use of recombinant human bone sialoprotein and osteopontin for hydroxyapatite studies SO CONNECTIVE TISSUE RESEARCH LA English DT Article; Proceedings Paper CT 5th International Conference on the Chemistry and Biology of Mineralized Tissues CY OCT 22-27, 1995 CL KOHLER, WI DE hydroxyapatite; recombinant proteins; human bone sialoprotein; human osteopontin; extracellular matrix ID SECRETED PHOSPHOPROTEIN-1; CRYSTAL-FORMATION; MATRIX; PROTEINS; BSP; LOCALIZATION; BIOSYNTHESIS; ASSOCIATION; MODULATION; NUCLEATION AB Bone sialoprotein (BSP) and osteopontin (OPN) are two extracellular bone matrix proteins that have the ability to modulate the growth of hydroxyapatite in vitro, Studies of BSP/OPN hydroxyapatite interactions in the past have been directed toward the identification of essential structural elements that allow these two proteins to modulate hydroxyapatite growth, However, these studies are limited by the finite quantities of purified extracellular matrix proteins, I have utilized a recombinant E. coli expression system to obtain milligram quantities of human bone sialoprotein and human osteopontin that may be used to study extracellular matrix protein interactions with hydroxyapatite. RP Stubbs, JT (reprint author), NIDR, BONE RES BRANCH, NIH, BETHESDA, MD 20892 USA. NR 20 TC 14 Z9 14 U1 0 U2 1 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0300-8207 J9 CONNECT TISSUE RES JI Connect. Tissue Res. PY 1996 VL 35 IS 1-4 BP 393 EP 399 DI 10.3109/03008209609029217 PG 7 WC Cell Biology; Orthopedics SC Cell Biology; Orthopedics GA WL094 UT WOS:A1996WL09400057 PM 9084680 ER PT J AU Gahl, WA McDowell, G KaiserKupfer, MI AF Gahl, WA McDowell, G KaiserKupfer, MI TI Benign cystinosis patients SO CORNEA LA English DT Letter ID NEPHROPATHIC CYSTINOSIS; CYSTEAMINE; CHILDREN RP Gahl, WA (reprint author), NICHHD,HUMAN BIOCHEM GENET SECT,BLDG 10,RM 9S-241,10 CTR DR,MSC 1830,BETHESDA,MD 20892, USA. NR 10 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0277-3740 J9 CORNEA JI Cornea PD JAN PY 1996 VL 15 IS 1 BP 101 EP 102 DI 10.1097/00003226-199601000-00019 PG 2 WC Ophthalmology SC Ophthalmology GA TN069 UT WOS:A1996TN06900019 PM 8907390 ER PT J AU Ruttimann, UE Pollack, MM Fiser, DH AF Ruttimann, UE Pollack, MM Fiser, DH TI Prediction of three outcome states from pediatric intensive care SO CRITICAL CARE MEDICINE LA English DT Article DE severity of illness index; logistic regression; quality assessment; patient outcome assessment; intensive care unit; mortality prediction; pediatrics; critical illness ID SEVERE HEAD-INJURY; NON-TRAUMATIC COMA; EVOKED-POTENTIALS; PROGNOSTIC VALUE; PROLONGED COMA; CHILDHOOD; CHILDREN; TOMOGRAPHY; PRESSURE AB Objective: To develop a method based on admission day data for predicting patient outcome status as independently functional, compromised functional, or dead. Design: Prospectively acquired development and validation samples. Setting: A pediatric intensive care unit located in a tertiary care center. Patients: Consecutive admissions (n = 1,663) for predictor development, and consecutive admissions (n = 1,153) for predictor validation. Methods: Pediatric Risk of Mortality score, baseline Pediatric Overall Performance Category score, age, operative status, and primary diagnosis classified into ten organ systems and nine etiologies were recorded at the time of intensive care unit admission. Predictor was developed by stepwise polychotomous logistic regression analysis for the outcomes functional, compromised, and dead. Model fit was evaluated by chi-square statistics; prediction performance was measured by the area under the receiver operating characteristic curve, and classification table analysis of observed vs, predicted outcomes. Measurements and Main Results: The resulting predictor in eluded Pediatric Risk of Mortality, baseline Pediatric Overall Performance Category, operative status, age, and diagnostic factors from four systems (cardiovascular, respiratory, neurologic, gastrointestinal), and six etiologies (infection, trauma, drug overdose, allergy/immunology, diabetes, miscellaneous/undetermined). Its application to the validation sample yielded good agreement between the total number expected and the observed outcomes for each state (chi-square = 3.16, 2 degrees of freedom, p = .206), with area indices of 0.96 +/- 0.01 for discrimination of fully functional vs. the combination of the two poor outcome states (compromised or death), and 0.94 +/- 0.02 for discrimination of fully or compromised functional vs, death. The 3 x 3 classification resulted in correct classification rates of 83.2%, 74.4%, and 81.3%, for the outcomes functional, compromised, and death, respectively. Conclusions: Prediction of three outcome states using physiologic status, baseline functional level, and broad-based diagnostic groupings at admission is feasible and may improve the relevance of quality of care assessment. C1 GEORGE WASHINGTON UNIV,SCH MED,DEPT PEDIAT,WASHINGTON,DC 20052. CHILDRENS NATL MED CTR,DEPT CRIT CARE MED,WASHINGTON,DC 20010. CHILDRENS NATL MED CTR,CTR HLTH SERV & CLIN RES,WASHINGTON,DC 20010. UNIV ARKANSAS MED SCI HOSP,DEPT PEDIAT CRIT CARE MED,LITTLE ROCK,AR. UNIV ARKANSAS MED SCI HOSP,DEPT HLTH SERV RES,LITTLE ROCK,AR. ARKANSAS CHILDRENS HOSP,LITTLE ROCK,AR 72202. RP Ruttimann, UE (reprint author), NIAAA,NIH,BLDG 10-3C102,BETHESDA,MD 20892, USA. NR 28 TC 12 Z9 12 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD JAN PY 1996 VL 24 IS 1 BP 78 EP 85 DI 10.1097/00003246-199601000-00014 PG 8 WC Critical Care Medicine SC General & Internal Medicine GA TT354 UT WOS:A1996TT35400014 PM 8565543 ER PT J AU Tsai, CJ Lin, SL Wolfson, HJ Nussinov, R AF Tsai, CJ Lin, SL Wolfson, HJ Nussinov, R TI Protein-protein interfaces: Architectures and interactions in protein-protein interfaces and in protein cores. Their similarities and differences SO CRITICAL REVIEWS IN BIOCHEMISTRY AND MOLECULAR BIOLOGY LA English DT Review DE protein-protein interfaces; protein architectures; structural motifs; protein-protein interactions; interface-dataset ID CRYSTAL-STRUCTURE; DATA-BANK; 3-DIMENSIONAL STRUCTURE; ANGSTROM RESOLUTION; SECONDARY STRUCTURE; MOLECULAR-SURFACES; RECOGNITION; SUBUNIT; DOCKING; BINDING AB Protein structures generally consist of favorable folding motifs formed by specific arrangements of secondary structure elements. Similar architectures can be adopted by different amino acids sequences, although the details of the structures vary. It has long been known that despite the sequence variability, there is a striking preferential conservation of the hydrophobic character of the amino acids at the buried positions of these folding motifs. Differences in the sizes of the side-chains are accommodated by movements of the secondary structure elements with respect to each other, leading to compact packing. Scanning protein-protein interfaces reveals that similar architectures are also observed at and around their interacting surfaces, with preservation of the hydrophobic character, although not to the same extent. The general forces that determine the origin of the native structures of proteins have been investigated intensively. The major non-bonded forces operating on a protein chain as it folds into a three-dimensional structure are likely to be packing, the hydrophobic effect, and electrostatic interactions. While the substantial hydrophobic forces lead to a compact conformation, they are also nonspecific and cannot serve as a guide to a conformationally unique structure. For the general folding problem, it thus appears that packing is a prime candidate for determining a particular fold. Specific hydrogen-bonding patterns and salt-bridges have also been proposed to play a role. Inspection of protein-protein interfaces reveals that the hallmarks governing single chain protein structures also determine their interactions, suggesting that similar principles underlie protein folding and protein-protein associations. This review focuses on some aspects of protein-protein interfaces, particularly on the architectures and their interactions. These are compared with those present in protein monomers. This task is facilitated by the recently compiled, non-redundant structural dataset of protein-protein interfaces derived from the crystallographic database. In particular, although current view holds that protein-protein interfaces and interactions are similar to those found in the conformations of single-chain proteins, this review brings forth the differences as well. Not only is it logical that such differences would exist, it is these differences that further illuminate protein folding on the one hand and protein-protein recognition on the other. These are also particularly important in considering inhibitor (ligand) design. C1 NCI,FREDERICK CANC RES & DEV CTR,MATH BIOL LAB,SAIC,FREDERICK,MD 21702. TEL AVIV UNIV,SCH MATH SCI,DEPT COMP SCI,IL-69978 TEL AVIV,ISRAEL. TEL AVIV UNIV,SACKLER INST MOL MED,IL-69978 TEL AVIV,ISRAEL. RI Wolfson, Haim/A-1837-2011 FU NCI NIH HHS [1-CO-74102] NR 75 TC 86 Z9 87 U1 3 U2 19 PU CRC PRESS INC PI BOCA RATON PA 2000 CORPORATE BLVD NW, BOCA RATON, FL 33431 SN 1040-9238 J9 CRIT REV BIOCHEM MOL JI Crit. Rev. Biochem. Mol. Biol. PY 1996 VL 31 IS 2 BP 127 EP 152 DI 10.3109/10409239609106582 PG 30 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UJ240 UT WOS:A1996UJ24000002 PM 8740525 ER PT J AU Wess, J AF Wess, J TI Molecular biology of muscarinic acetylcholine receptors SO CRITICAL REVIEWS IN NEUROBIOLOGY LA English DT Review DE mutagenesis; receptor assembly; ligand binding site; receptor/G protein coupling; receptor desensitization; receptor phosphorylation ID BETA-ADRENERGIC-RECEPTOR; PROTEIN-COUPLED RECEPTORS; SITE-DIRECTED MUTAGENESIS; HUMAN BETA-2-ADRENERGIC RECEPTOR; AGONIST-INDUCED PHOSPHORYLATION; 3RD INTRACELLULAR LOOP; SUBTYPE-SPECIFIC ANTIBODIES; CEREBELLAR GRANULE CELLS; INDUCED DOWN-REGULATION; CHOLINERGIC RECEPTORS AB Following the molecular cloning of five distinct muscarinic acetylcholine receptor (mAChR) genes, the last decade has witnessed an explosion of new knowledge about how mAChRs function at a molecular level. These studies have been greatly facilitated by the molecular characterization of the many components of the signal transduction pathways activated upon mAChR stimulation. Molecular genetic and biochemical approaches have considerably advanced our knowledge about how mAChRs are assembled, how they bind ligands, and which structural elements on the mAChRs are critical for G protein coupling. In addition, the molecular mechanisms involved in the regulation of mAChR activity (including mAChR sequestration, down-regulation, and phosphorylation) have been explored in great detail. Since the mAChRs are typical members of the super-family of C protein-coupled receptors, the information gathered with this class of receptors should be of broad general relevance. C1 NIDDKD,BIOORGAN CHEM LAB,BETHESDA,MD 20892. NR 196 TC 344 Z9 353 U1 1 U2 34 PU BEGELL HOUSE INC PI NEW YORK PA 79 MADISON AVE, SUITE 1205, NEW YORK, NY 10016-7892 SN 0892-0915 J9 CRIT REV NEUROBIOL JI Crit. Rev. Neurobiol. PY 1996 VL 10 IS 1 BP 69 EP 99 PG 31 WC Neurosciences SC Neurosciences & Neurology GA VB919 UT WOS:A1996VB91900004 PM 8853955 ER PT J AU Wise, SP Murray, EA Gerfen, CR AF Wise, SP Murray, EA Gerfen, CR TI The frontal cortex basal ganglia system in primates SO CRITICAL REVIEWS IN NEUROBIOLOGY LA English DT Review DE striatum; pallidum; prefrontal; premotor; dopamine ID PREFRONTAL UNIT-ACTIVITY; SUPPLEMENTARY EYE FIELD; MOVEMENT-RELATED ACTIVITY; PRIMARY MOTOR CORTEX; CARD SORTING TEST; DELAYED-RESPONSE PERFORMANCE; MONKEY GLOBUS-PALLIDUS; VISUALLY GUIDED ARM; OBSESSIVE-COMPULSIVE DISORDER; POSITRON EMISSION TOMOGRAPHY AB The primate basal ganglia receives information from most of the cerebrum, including the frontal cortex, but projects (via the dorsal thalamus) primarily to the frontal lobe, perhaps in its entirety. As such, the frontal cortex and basal ganglia constitute an integrated, distributed neuronal architecture. We review evidence that the frontal lobe and basal ganglia specialize in different, but related, aspects of response learning. Frontal cortex acts when new rules need to be learned and older ones rejected, whereas the basal ganglia potentiate previously learned rules based on environmental context and reinforcement history. Such potentiation increases the probability that the central nervous system will select a particular rule to guide behavior. We outline a possible mechanism for the basal ganglia's proposed role in rule potentiation, one that involves both the direct and indirect striatal output pathways and their dopaminergic input. It has previously been proposed that direct-pathway neurons recognize a pattern of corticostriatal inputs, which promotes activity in recurrent, positive-feedback modules (or loops) of which they are an integral part. We propose that this recurrent activity potentiates a rule associated with those modules. If so, then the dopaminergic system is well situated and organized to modulate rule potentiation in both the short and long term. Dopaminergic neurons of the midbrain increase activity during learning and other periods of relatively unpredictable reinforcement. Dopamine enhances gene expression and other forms of activity in striatal neurons of the direct pathway, while suppressing neurons of the indirect pathway. In the short term, then, dopamine may augment the activity of modules triggered by a recognized context, whereas in the long term it may promote context-dependent activation of the same modules. Together, these modulatory influences could support both rule potentiation and learning the context for potentiating that rule. C1 NIMH, NEUROPHYSIOL LAB, ANIM CTR, NIH, POOLESVILLE, MD 20837 USA. NIMH, NEUROPSYCHOL LAB, BETHESDA, MD 20892 USA. OI Murray, Elisabeth/0000-0003-1450-1642 NR 441 TC 310 Z9 311 U1 13 U2 22 PU BEGELL HOUSE INC PI REDDING PA 50 CROSS HIGHWAY, REDDING, CT 06896 USA SN 0892-0915 J9 CRIT REV NEUROBIOL JI Crit. Rev. Neurobiol. PY 1996 VL 10 IS 3-4 BP 317 EP 356 PG 40 WC Neurosciences SC Neurosciences & Neurology GA VZ239 UT WOS:A1996VZ23900003 PM 8978985 ER PT J AU Guedez, L Lim, MS StetlerStevenson, WG AF Guedez, L Lim, MS StetlerStevenson, WG TI The role of metalloproteinases and their inhibitors in hematological disorders SO CRITICAL REVIEWS IN ONCOGENESIS LA English DT Review DE ECM; extracellular matrix; TIMPs; tissue inhibitors of metalloproteinases; leukocyte-metalloproteinases; hematopoiesis; inflammation; soluble ligand-receptors ID ERYTHROID-POTENTIATING ACTIVITY; ACUTE LYMPHOBLASTIC-LEUKEMIA; HUMAN MONONUCLEAR PHAGOCYTES; ACTIVITY TISSUE INHIBITOR; B16-F10 MELANOMA-CELLS; NECROSIS-FACTOR-ALPHA; MARROW STROMAL CELLS; HUMAN T-LYMPHOCYTES; TIMP GENE FAMILY; HUMAN FAS LIGAND AB The balance between the activities of matrix metalloproteinases (MMPs) and the tissue inhibitors of metalloproteinases (TIMPs) is an important control point during the turnover of the extracellular matrix. Previous studies have demonstrated that an uncontrolled rate of production of these proteins leads to various pathological conditions. Overexpression of MMPs by malignant cells can increase the invasive behavior of solid tumors and their metastatic potential. In an increasing number of reports, it has become evident that expression of MMPs and TIMPs is not restricted to solid tumors. Normal and malignant hematological cells also express these proteins and play a pivotal role in the hematological-cell physiology. In addition to modifying the extracellular matrix, MMPs and TIMPs exert other functions in hematological cells, including growth-factor activity, removal of cell-surface receptors, and autoimmunity. The goal of this review is to gather recent studies concerning the properties of MMPs and TIMPs in hematological cells, their regulation of gene expression, their cellular distribution, and their potential role in the pathogenesis of hematological disorders such as inflammation and neoplasia. RP Guedez, L (reprint author), NCI,PATHOL LAB,NCI,BLDG 10,ROOM 2A-33,BETHESDA,MD 20892, USA. RI Guedez, Liliana/H-4951-2012; Stetler-Stevenson, William/H-6956-2012 OI Stetler-Stevenson, William/0000-0002-5500-5808 NR 177 TC 42 Z9 42 U1 0 U2 2 PU BEGELL HOUSE INC PI NEW YORK PA 79 MADISON AVE, SUITE 1205, NEW YORK, NY 10016-7892 SN 0893-9675 J9 CRIT REV ONCOGENESIS JI Crit. Rev. Oncog. PY 1996 VL 7 IS 3-4 BP 205 EP 225 PG 21 WC Biochemistry & Molecular Biology; Oncology; Cell Biology SC Biochemistry & Molecular Biology; Oncology; Cell Biology GA XP291 UT WOS:A1996XP29100004 PM 9258603 ER PT J AU Wolff, L AF Wolff, L TI Myb-induced transformation SO CRITICAL REVIEWS IN ONCOGENESIS LA English DT Review DE differentiation; protooncogene; transcription factor; leukemia ID MURINE LEUKEMIA-VIRUS; B-CELL LYMPHOMAS; INDUCED PROMONOCYTIC LEUKEMIA; NEGATIVE REGULATORY DOMAIN; COLONY-STIMULATING FACTOR; ETS PROTEINS COOPERATE; C-MYB; V-MYB; HEMATOPOIETIC-CELLS; TRANSCRIPTIONAL ACTIVATION AB The c-myb protooncogene has been implicated in the development of avian and murine hematopoietic neoplasms of the myeloid and lymphoid lineages. The transcription factor encoded by this gene has a dual function in oncogenesis because it regulates genes that prevent apoptosis and genes involved in cellular proliferation. c-myb has repeatedly been a target of retroviral insertional mutagenesis. The most common mechanism by which retroviruses activate c-myb's oncogenic potential is by providing transcriptional control that results in constitutive expression, a feature that is consistent with the demonstration that ectopic expression of c-myb can prevent growth arrest of differentiating hematopoietic cells. In a less common mechanism of activation, carboxyl(C)-terminal truncation renders the c-Myb protein more stable and active in transcriptional transactivation. Interestingly, the ability of v-Myb, a product of the avian myeloblastosis virus (AMV), to cause rapid transformation of cells in vivo and in vitro can be explained by the combined effects of deregulated expression through the retroviral LTR, N- and C-terminal truncation, and activating mutations in its DNA binding domain. Although c-myb's involvement in human leukemia has been suggested, it has never been clearly established and should be investigated further. C1 NCI,CELLULAR ONCOL LAB,BETHESDA,MD 20892. NR 126 TC 58 Z9 58 U1 0 U2 2 PU BEGELL HOUSE INC PI NEW YORK PA 79 MADISON AVE, SUITE 1205, NEW YORK, NY 10016-7892 SN 0893-9675 J9 CRIT REV ONCOGENESIS JI Crit. Rev. Oncog. PY 1996 VL 7 IS 3-4 BP 245 EP 260 PG 16 WC Biochemistry & Molecular Biology; Oncology; Cell Biology SC Biochemistry & Molecular Biology; Oncology; Cell Biology GA XP291 UT WOS:A1996XP29100006 PM 9258605 ER PT B AU Fierer, DS Challberg, MD AF Fierer, DS Challberg, MD BE Jameel, S Wagner, EK TI Enzymology of herpes simplex virus 1 DNA replication: Viral DNA replication in the context of the eukaryotic DNA replication machinery SO CURRENT DEVELOPMENTS IN ANIMAL VIROLOGY LA English DT Proceedings Paper CT 1st ICGEB-UCI Virology Symposium on Current Developments in Animal Virology CY FEB 19-23, 1995 CL INT CTR GENET ENGN & BIOTECHNOL, NEW DELHI, INDIA SP Int Ctr Genet Engn & Biotechnol, Univ Calif Irvine, Program Anim Virol HO INT CTR GENET ENGN & BIOTECHNOL RP Fierer, DS (reprint author), NIAID,VIRAL DIS LAB,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SCIENCE PUBLISHERS INC PI LEBANON PA 52 LABOMBARD ROAD NORTH, LEBANON, NH 03766 BN 1-886106-61-4 PY 1996 BP 43 EP 58 PG 16 WC Public, Environmental & Occupational Health; Virology SC Public, Environmental & Occupational Health; Virology GA BJ32C UT WOS:A1996BJ32C00003 ER PT J AU Datiles, MB Lasa, MSM Freidlin, V AF Datiles, MB Lasa, MSM Freidlin, V TI A longitudinal study of cortical cataracts using retroillumination photographs SO CURRENT EYE RESEARCH LA English DT Article DE cataract photography; cortical cataracts; longitudinal study; ocular image analysis; statistical analysis ID CLASSIFICATION SYSTEM-II; LENS OPACITIES; EYE AB The National Eye Institute (NEI) computer planimetry system has been shown to have good reproducibility in assessing the size of cortical cataracts from retroilluminatin photographs. In this study, we determined the usefulness of this system in monitoring cortical cataract changes over time. Using the Neitz Kawara retroillumination camera, retroillumination photographs of cortical cataracts in 81 eyes were obtained every six months for an average of 31 months. As previously described, the cortical cataract outlines were traced in a masked fashion onto transparent plastic overlays, and the tracings then digitized into a Macintosh Quadra computer using a computer scanner. Cortical cataract area was then determined using a specially developed software program. For each eye, the rate of cortical area change was determined by the slope of the regression line fitted to the follow-up measurements. Cataract progression was classified to be significant if the slope exceeded a critical value. Of the 81 eyes, 24 (30%) had significant cataract progression, while 57 (70%) did not progress. This study presents data on progression of the area of cortical cataracts and suggests the usefulness of the NEI computer planimetry system for monitoring such changes from retroillumination photographs. The slope-based test can also play a useful part in longitudinal studies with irregular time intervals and variable number of visits. C1 NEI,NIH,DIV BIOMETRY & EPIDEMIOL,BETHESDA,MD 20892. RP Datiles, MB (reprint author), NEI,NIH,CATARACT & CORNEA SECT,OPHTHALM GENET & CLIN SERV BRANCH,BLDG 10,RM 10N226,10 CTR DR,BETHESDA,MD 20892, USA. OI Datiles, Manuel III B./0000-0003-4660-1664 NR 25 TC 1 Z9 2 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0271-3683 J9 CURR EYE RES JI Curr. Eye Res. PD JAN PY 1996 VL 15 IS 1 BP 53 EP 61 DI 10.3109/02713689609017611 PG 9 WC Ophthalmology SC Ophthalmology GA TT983 UT WOS:A1996TT98300007 PM 8631204 ER PT J AU Manganiello, VC Degerman, E Taira, M Kono, T Belfrage, P AF Manganiello, VC Degerman, E Taira, M Kono, T Belfrage, P TI Type III cyclic nucleotide phosphodiesterases and insulin action SO CURRENT TOPICS IN CELLULAR REGULATION, VOL 34 SE CURRENT TOPICS IN CELLULAR REGULATION LA English DT Review ID INHIBITED CAMP-PHOSPHODIESTERASE; DEPENDENT PROTEIN-KINASE; EPIDERMAL GROWTH-FACTOR; PHOTORECEPTOR CGMP PHOSPHODIESTERASE; POSITIVE INOTROPIC AGENTS; CONGESTIVE HEART-FAILURE; ADENOSINE-MONOPHOSPHATE PHOSPHODIESTERASE; RECENT CLINICAL DEVELOPMENTS; GTPASE-ACTIVATING PROTEIN; RECEPTOR TYROSINE KINASES C1 CHIBA UNIV,SCH MED,DEPT MED 2,CHIBA 280,JAPAN. LUND UNIV,SCH MED,DEPT MED & PHYSIOL CHEM,LUND,SWEDEN. VANDERBILT UNIV,SCH MED,NASHVILLE,TN 37240. RP Manganiello, VC (reprint author), NHLBI,CELLULAR METAB LAB,NIH,BETHESDA,MD 20892, USA. NR 266 TC 19 Z9 19 U1 1 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0070-2137 J9 CURR TOP CELL REGUL PY 1996 VL 34 BP 63 EP 100 DI 10.1016/S0070-2137(96)80003-3 PG 38 WC Cell Biology; Physiology SC Cell Biology; Physiology GA BF07U UT WOS:A1996BF07U00003 PM 8646851 ER PT J AU Wink, DA Hanbauer, I Grisham, MB Laval, F Nims, RW Lavals, J Cook, J Pacelli, R Liebmann, J Krishna, M Ford, PC Mitchell, JB AF Wink, DA Hanbauer, I Grisham, MB Laval, F Nims, RW Lavals, J Cook, J Pacelli, R Liebmann, J Krishna, M Ford, PC Mitchell, JB TI Chemical biology of nitric oxide: Regulation and protective and toxic mechanisms SO CURRENT TOPICS IN CELLULAR REGULATION, VOL 34 SE CURRENT TOPICS IN CELLULAR REGULATION LA English DT Review ID ISCHEMIA-REPERFUSION INJURY; LOW-DENSITY-LIPOPROTEIN; GUINEA-PIG HEART; NITROGEN-DIOXIDE; GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE; MYOCARDIAL-ISCHEMIA; HYDROGEN-PEROXIDE; HISTAMINE-RELEASE; ADP-RIBOSYLATION; AQUEOUS-SOLUTION C1 NHLBI,LAB MOL IMMUNOL,BETHESDA,MD 20892. LOUISIANA STATE UNIV,MED CTR,DEPT PHYSIOL,SHREVEPORT,LA 71130. INSERM,U347,GRP RADIOCHIM ADN,F-94276 LE KREMLIN BICETR,FRANCE. INST GUSTAVE ROUSSY,CNRS,URA 147,GRP REPARAT LESIONS RADIO & CHIMIOINDUITES,F-94805 VILLEJUIF,FRANCE. NCI,RADIAT BIOL BRANCH,BETHESDA,MD 20892. UNIV CALIF SANTA BARBARA,DEPT CHEM,SANTA BARBARA,CA 93106. RP Wink, DA (reprint author), NCI,CHEM SECT,COMPARAT CARCINOGENESIS LAB,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702, USA. RI Ford, Peter/D-1826-2011 OI Ford, Peter/0000-0002-5509-9912 NR 122 TC 230 Z9 233 U1 2 U2 9 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0070-2137 J9 CURR TOP CELL REGUL PY 1996 VL 34 BP 159 EP 187 DI 10.1016/S0070-2137(96)80006-9 PG 29 WC Cell Biology; Physiology SC Cell Biology; Physiology GA BF07U UT WOS:A1996BF07U00006 PM 8646847 ER PT J AU Shi, YB IshizuyaOka, A AF Shi, YB IshizuyaOka, A TI Biphasic intestinal development in amphibians: Embryogenesis and remodeling during metamorphosis SO CURRENT TOPICS IN DEVELOPMENTAL BIOLOGY, VOL 32 SE CURRENT TOPICS IN DEVELOPMENTAL BIOLOGY LA English DT Review ID THYROID-HORMONE RECEPTOR; ACID-BINDING-PROTEIN; EPITHELIAL-MESENCHYMAL INTERACTIONS; XENOPUS-LAEVIS; GENE-EXPRESSION; BRUSH-BORDER; REGIONAL EXPRESSION; DUODENAL MESENCHYME; VILLIN EXPRESSION; CONNECTIVE-TISSUE C1 DOKKYO UNIV,SCH MED,DEPT ANAT,MIBU,TOCHIGI 32102,JAPAN. RP Shi, YB (reprint author), NICHHD,MOLEC EMBRYOL LAB,NIH,BETHESDA,MD 20892, USA. NR 117 TC 114 Z9 114 U1 1 U2 4 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0070-2153 J9 CURR TOP DEV BIOL PY 1996 VL 32 BP 205 EP 235 PG 31 WC Developmental Biology SC Developmental Biology GA BF07L UT WOS:A1996BF07L00007 PM 8929670 ER PT J AU Goldstein, JA Blaisdell, J AF Goldstein, JA Blaisdell, J TI Genetic tests which identify the principal defects in CYP2C19 responsible for the polymorphism in mephenytoin metabolism SO CYTOCHROME P450, PT B SE METHODS IN ENZYMOLOGY LA English DT Review ID HUMANS RP Goldstein, JA (reprint author), NIEHS,BIOCHEM RISK ANAL LAB,POB 12233,RES TRIANGLE PK,NC 27709, USA. RI Goldstein, Joyce/A-6681-2012 NR 16 TC 101 Z9 105 U1 0 U2 4 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0076-6879 J9 METHOD ENZYMOL JI Methods Enzymol. PY 1996 VL 272 BP 210 EP 218 DI 10.1016/S0076-6879(96)72025-6 PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BG35K UT WOS:A1996BG35K00023 PM 8791779 ER PT J AU FernandezSalguero, PM Gonzalez, FJ AF FernandezSalguero, PM Gonzalez, FJ TI Targeted disruption of specific cytochromes P450 and xenobiotic receptor genes SO CYTOCHROME P450, PT B SE METHODS IN ENZYMOLOGY LA English DT Review ID EMBRYONIC STEM-CELLS; MICE LACKING; CYSTIC-FIBROSIS; HOMOLOGOUS RECOMBINATION; REPLACEMENT VECTORS; APOLIPOPROTEIN-E; EGF RECEPTOR; MOUSE; CHIMERAS; MODEL RP FernandezSalguero, PM (reprint author), NCI,DIV BASIC SCI,NIH,BETHESDA,MD 20892, USA. OI Fernandez-Salguero, Pedro M./0000-0003-2839-5027 NR 46 TC 1 Z9 1 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0076-6879 J9 METHOD ENZYMOL JI Methods Enzymol. PY 1996 VL 272 BP 412 EP 430 DI 10.1016/S0076-6879(96)72046-3 PG 19 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BG35K UT WOS:A1996BG35K00044 PM 8791800 ER PT J AU Bentz, M Bergerheim, USR Li, C Joos, S Werner, CA Baudis, M Gnarra, J Merino, MJ Zbar, B Linehan, WM Lichter, P AF Bentz, M Bergerheim, USR Li, C Joos, S Werner, CA Baudis, M Gnarra, J Merino, MJ Zbar, B Linehan, WM Lichter, P TI Chromosome imbalances in papillary renal cell carcinoma and first cytogenetic data of familial cases analyzed by comparative genomic hybridization SO CYTOGENETICS AND CELL GENETICS LA English DT Article ID DNA-SEQUENCES; TUMORS AB We used comparative genomic hybridization to analyze 17 tumor samples from 11 patients with papillary renal cell carcinoma (RCC), including three patients with hereditary papillary RCC. Whereas the most frequent aberrations confirmed data obtained by banding analyses, copy number increases on 5q, which previously were considered characteristic of nonpapillary RCC, were identified in two cases. In two complex cases belonging to the same family, a characteristic pattern of chromosomal aberrations was found: five of the six imbalances present in the less complex case were included in the karyotype of the other case, suggesting a genetically determined mechanism resulting in genomic instability of specific chromosomes or chromosomal subregions and/or selection of specific mutations. C1 DEUTSCH KREBSFORSCHUNGSZENTRUM,ABT ORG KOMPLEXER GENOME,D-69120 HEIDELBERG,GERMANY. UNIV HEIDELBERG,MED KLIN & POLIKLIN 5,HEIDELBERG,GERMANY. KAROLINSKA HOSP,DEPT UROL,S-10401 STOCKHOLM,SWEDEN. NCI,SURG BRANCH,BETHESDA,MD 20892. NCI,IMMUNOBIOL LAB,FREDERICK,MD 21701. RI Baudis, Michael/J-4602-2012 OI Baudis, Michael/0000-0002-9903-4248 NR 16 TC 42 Z9 43 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-0171 J9 CYTOGENET CELL GENET JI Cytogenet. Cell Genet. PY 1996 VL 75 IS 1 BP 17 EP 21 DI 10.1159/000134448 PG 5 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA WB528 UT WOS:A1996WB52800005 PM 8995481 ER PT J AU Ivanov, SV Modi, WS AF Ivanov, SV Modi, WS TI Molecular characterization of the complex sex-chromosome heterochromatin in the rodent Microtus chrotorrhinus SO CYTOGENETICS AND CELL GENETICS LA English DT Article ID TANDEM SATELLITE ARRAY; ALPHA-SATELLITE; TRANSCRIPTIONAL ACTIVITY; DNA-SEQUENCES; HUMAN GENOME; EVOLUTION; BINDING; MOUSE; ELEMENTS; FAMILY AB The sex chromosomes of Microtus chrotorrhinus are unusually large compared to those of other mammals, comprising about 20 % of the karyotype and containing substantial amounts of constitutive heterochromatin. Previous studies have described two highly repeated DNA families (MSAT-160 and MSAT-2570) that localize to this heterochromatin (Modi, 1992, 1993c). The present report describes a third satellite DNA family (termed MSAT-21) in M. chrotorrhinus that is also located in the sex heterochromatin. This repeat consists of diverged copies (average similarity = 75 %) of a tandemly repeated 21-mer. Southern blotting of MSAT-21 revealed that although some higher order (5-20 kb) repeats do exist, none has spread throughout an appreciable portion of the genome. Pulsed field gel experiments indicated that most of the larger arrays (50-700 kb) of all three satellite families are distributed across numerous size classes, suggesting that the three repeats are interspersed with one another in this heterochromatin. Analysis of a boundary between MSAT-21 and MSAT-160 showed that the junction monomers of each satellite are intact and that a pentanucleotide has apparently been transferred from MSAT-21 to MSAT-160 via recombination. Sequence comparisons of MSAT-160 with another rodent satellite and with the U3 region of the Rous sarcoma virus (RSV) long terminal repeat identified inverted repeats and similarities with viral enhancer domains in the rodent sequences, Additionally, the MSAT-21 consensus was found to be similar to the R region of RSV, suggesting a retroviral ancestor for these rodent repeated DNA families. C1 NCI,BIOL CARCINOGENESIS & DEV PROGRAM,SAIC FREDERICK,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. NR 34 TC 21 Z9 21 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-0171 J9 CYTOGENET CELL GENET JI Cytogenet. Cell Genet. PY 1996 VL 75 IS 1 BP 49 EP 56 DI 10.1159/000134456 PG 8 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA WB528 UT WOS:A1996WB52800013 PM 8995489 ER PT J AU Filie, JD Kozak, CA AF Filie, JD Kozak, CA TI Linkage and synteny homologies between human chromosome 13 and mouse chromosomes 5, 8 and 14 SO CYTOGENETICS AND CELL GENETICS LA English DT Meeting Abstract C1 NIAID,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-0171 J9 CYTOGENET CELL GENET JI Cytogenet. Cell Genet. PY 1996 VL 75 IS 2-3 BP 107 EP 107 PG 1 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA WG954 UT WOS:A1996WG95400009 ER PT J AU Tachibana, M Iwata, N Watanabe, A Nobukuni, Y Ploplis, B Kajigaya, S AF Tachibana, M Iwata, N Watanabe, A Nobukuni, Y Ploplis, B Kajigaya, S TI Assignment of the gene for a ubiquitin-conjugating enzyme (UBE2I) to human chromosome band 16p13.3 by in situ hybridization SO CYTOGENETICS AND CELL GENETICS LA English DT Article ID DEGRADATION C1 NHLBI,HEMATOL BRANCH,NIH,BETHESDA,MD 20892. NATL INST NEUROSCI,DEPT INHERITED METAB DIS,KODAIRA,TOKYO,JAPAN. RP Tachibana, M (reprint author), NIDCD,MOL GENET LAB,NIH,5 RES COURT,ROCKVILLE,MD 20850, USA. NR 12 TC 3 Z9 4 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-0171 J9 CYTOGENET CELL GENET JI Cytogenet. Cell Genet. PY 1996 VL 75 IS 4 BP 222 EP 223 DI 10.1159/000134487 PG 2 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA WN578 UT WOS:A1996WN57800004 PM 9067428 ER PT J AU Shows, TB Alders, M Bennett, S Burbee, D Cartwright, P Chandrasekharappa, S Cooper, P Courseaux, A Davies, C Devignes, MD Devilee, P Elliott, R Evans, G Fantes, J Garner, H Gaudray, P Gerhard, DS Gessler, M Higgins, M Hummerich, H James, M Lagercrantz, J Litt, M Little, P Mannens, M Munroe, D Nowak, N OBrien, S Parker, N Perlin, M Reid, L Richard, C Sawicki, M Swallow, D Thakker, R vanHeyningen, V vanSchothorst, E Vorechovsky, I Wadelius, C Weber, B Zabel, B AF Shows, TB Alders, M Bennett, S Burbee, D Cartwright, P Chandrasekharappa, S Cooper, P Courseaux, A Davies, C Devignes, MD Devilee, P Elliott, R Evans, G Fantes, J Garner, H Gaudray, P Gerhard, DS Gessler, M Higgins, M Hummerich, H James, M Lagercrantz, J Litt, M Little, P Mannens, M Munroe, D Nowak, N OBrien, S Parker, N Perlin, M Reid, L Richard, C Sawicki, M Swallow, D Thakker, R vanHeyningen, V vanSchothorst, E Vorechovsky, I Wadelius, C Weber, B Zabel, B TI Report of the fifth international workshop on human chromosome 11 mapping (1996) SO CYTOGENETICS AND CELL GENETICS LA English DT Editorial Material ID FAMILIAL HYPERTROPHIC CARDIOMYOPATHY; PROTEIN-C GENE; SUSCEPTIBILITY LOCUS; HUMAN GENOME; MAP; LOCALIZATION; REGION; SITE; HUMAN-CHROMOSOME-11; SEQUENCE C1 UNIV AMSTERDAM,ACAD MED CTR,NL-1105 AZ AMSTERDAM,NETHERLANDS. UNIV OXFORD,WELLCOME TRUST CTR HUMAN GENET,OXFORD OX3 7BN,ENGLAND. UNIV TEXAS,SW MED CTR,DALLAS,TX 75235. UNIV UTAH,DEPT HUMAN GENET,SALT LAKE CITY,UT 84112. NCHGR,LGT,NIH,BETHESDA,MD 20892. FAC MED,LGMCH,CNRS URA 1462,F-06717 NICE 2,FRANCE. CNRS UPR 420,F-94801 VILLEJUIF,FRANCE. LEIDEN UNIV,DEPT HUMAN GENET,NL-2333 AL LEIDEN,NETHERLANDS. ROSWELL PK CANC INST,DEPT MOL & CELL BIOL,BUFFALO,NY 14263. WESTERN GEN HOSP,MRC,HUMAN GENET UNIT,EDINBURGH EH4 2XU,MIDLOTHIAN,SCOTLAND. FAC MED NICE,CNRS URA 1462,F-06107 NICE 2,FRANCE. WASHINGTON UNIV,SCH MED,DEPT GENET,ST LOUIS,MO 63110. THEODOR BOVERI INST BIOWISSENSCH,LEHRSTUHL PHYSIOL CHEM,D-97074 WURZBURG,GERMANY. UNIV LONDON IMPERIAL COLL SCI TECHNOL & MED,DEPT BIOCHEM,LONDON SW7 2AZ,ENGLAND. NUFFIELD ORTHOPAED CTR,WELLCOME TRUST CTR HUMAN GENET,OXFORD OX3 7LD,ENGLAND. KAROLINSKA HOSP,DEPT CLIN GENET,S-10401 STOCKHOLM,SWEDEN. OREGON HLTH SCI UNIV,DEPT BIOCHEM,PORTLAND,OR 97201. OREGON HLTH SCI UNIV,DEPT MED GENET,PORTLAND,OR 97201. MIT,CTR CANC RES,CAMBRIDGE,MA 02139. NCI,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21702. ROYAL CHILDRENS HOSP,DEPT HAEMATOL ONCOL,PARKVILLE,VIC 3052,AUSTRALIA. CARNEGIE MELLON UNIV,DEPT COMP SCI,PITTSBURGH,PA 15213. UNIV N CAROLINA,LINEBERGER CANC CTR,CHAPEL HILL,NC 27599. UNIV PITTSBURGH,WESTERN PSYCHIAT INST & CLIN,DEPT PSYCHIAT,PITTSBURGH,PA 15213. W LOS ANGELES VET AFFAIRS MED CTR,DEPT GEN SURG,LOS ANGELES,CA 90073. UNIV LONDON UNIV COLL,GALTON LAB,MRC,HUMAN BIOCHEM GENET UNIT,LONDON NW1 2HE,ENGLAND. HAMMERSMITH HOSP,ROYAL POSTGRAD MED SCH,MRC,MOL ENDOCRINOL GRP,LONDON W12 0NN,ENGLAND. LEIDEN UNIV,RUL,LEIDEN,NETHERLANDS. KAROLINSKA INST,NOVUM,DEPT BIOSCI,S-14157 HUDDINGE,SWEDEN. UNIV UPPSALA HOSP,S-75185 UPPSALA,SWEDEN. BIOCTR,INST HUMAN GENET,D-97074 WURZBURG,GERMANY. UNIV MAINZ,DEPT PEDIAT,D-55101 MAINZ,GERMANY. RP Shows, TB (reprint author), ROSWELL PK CANC INST,DEPT HUMAN GENET,BUFFALO,NY 14263, USA. RI van Heyningen, Veronica/B-8039-2008 OI van Heyningen, Veronica/0000-0003-0359-0141 NR 42 TC 1 Z9 1 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-0171 J9 CYTOGENET CELL GENET JI Cytogenet. Cell Genet. PY 1996 VL 74 IS 1-2 BP 2 EP 52 PG 51 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA VN347 UT WOS:A1996VN34700001 ER PT J AU Dutra, AS Mignot, E Puck, JM AF Dutra, AS Mignot, E Puck, JM TI Gene localization and syntenic mapping by FISH in the dog SO CYTOGENETICS AND CELL GENETICS LA English DT Article ID SEVERE COMBINED IMMUNODEFICIENCY; CANIS-FAMILIARIS; DOMESTIC DOG; CHROMOSOMES; GENOME; HYBRIDIZATION; MAMMALS; CELLS AB To begin development of a canine gene map and to define syntenic regions between the canine and human genomes, the technique of fluorescence in situ hybridization (FISH) was adapted to localize specific DNA sequences in canine metaphases. Genomic clones of canine origin as well as human yeast artificial chromosome clones were used to map canine loci. The immunoglobulin heavy-chain region was localized to canine chromosome 4qtel; the canine major histocompatibility locus, DLA, was found to be on chromosome 12qtel. Of particular interest, the canine X chromosome, which morphologically is highly similar to the human X, also showed syntenic localization of the clotting factor VIII (F8C) and factor IX (F9) genes to Xq28 and Xq26.3-->q27.1, respectively. C1 NIH,NATL CTR HUMAN GENOME RES,LAB GENE TRANSFER,BETHESDA,MD 20892. STANFORD UNIV,MED CTR,CTR STUDY SLEEP DISORDERS,PALO ALTO,CA 94304. STANFORD UNIV,MED CTR,DEPT NEUROL,PALO ALTO,CA 94304. NR 26 TC 47 Z9 47 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-0171 J9 CYTOGENET CELL GENET JI Cytogenet. Cell Genet. PY 1996 VL 74 IS 1-2 BP 113 EP 117 DI 10.1159/000134395 PG 5 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA VN347 UT WOS:A1996VN34700013 PM 8893815 ER PT J AU Altomare, DA Kozak, CA Sonoda, G Testa, JR AF Altomare, DA Kozak, CA Sonoda, G Testa, JR TI Chromosome mapping of the mouse Akt2 gene and Akt2 pseudogene SO CYTOGENETICS AND CELL GENETICS LA English DT Article ID FLUORESCENCE INSITU HYBRIDIZATION; C-AKT; ONCOGENE; LOCALIZATION; KINASE; EXPRESSION; CARCINOMAS; PROTEINS; OVARIAN AB We previously reported the cloning of a murine cDNA encoding the protein-serine/threonine kinase Akt2, and we used this clone to map the Akt2 gene to mouse chromosome (MMU) 7B1 by fluorescence in situ hybridization. We now have cloned and partially sequenced a mouse Akt2 pseudogene. An analysis of two sets of multilocus crosses revealed that the Akt2 gene is closely linked to the Cyp2a locus in proximal MMU7. The Akt2 pseudogene was mapped to proximal MMU11 by both multilocus mapping and fluorescence in situ hybridization. C1 FOX CHASE CANC CTR,DEPT MED ONCOL,PHILADELPHIA,PA 19111. NIH,BETHESDA,MD 20892. FU NCI NIH HHS [CA-06927, P30 CA006927, R01 CA077429] NR 24 TC 6 Z9 6 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-0171 J9 CYTOGENET CELL GENET JI Cytogenet. Cell Genet. PY 1996 VL 74 IS 4 BP 248 EP 251 DI 10.1159/000134426 PG 4 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA VW615 UT WOS:A1996VW61500002 PM 8976376 ER PT J AU Lee, HH Farber, JM AF Lee, HH Farber, JM TI Localization of the gene for the human MIG cytokine on chromosome 4q21 adjacent to INP10 reveals a chemokine ''mini-cluster'' SO CYTOGENETICS AND CELL GENETICS LA English DT Article ID BETA-THROMBOGLOBULIN; MESSENGER-RNA; CELL-LINE; INTERFERON; CLONING; MAPS AB MIG is a gamma interferon-inducible T cell chemoattractant that is a member of the chemokine family of cytokines. P1 clones containing the MIG gene were found also to contain the gene of a related chemokine, INP10. We localized MIG and INP10 to 4q21 by FISH, demonstrated by pulsed field gel electrophoresis that MIG and INP10 are distant from the tight cluster of other CXC chemokine genes at 4q12 --> q13, and determined that MIG and INP10 are oriented head to tail with their start codons separated by less than 16 kb. C1 NIAID,CLIN INVEST LAB,NIH,BETHESDA,MD 20892. NR 18 TC 23 Z9 23 U1 1 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-0171 J9 CYTOGENET CELL GENET JI Cytogenet. Cell Genet. PY 1996 VL 74 IS 4 BP 255 EP 258 DI 10.1159/000134428 PG 4 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA VW615 UT WOS:A1996VW61500004 PM 8976378 ER PT J AU Huang, B Crolla, JA Christian, SL WolfLedbetter, ME Macha, ME Papenhausen, PN Ledbetter, DH AF Huang, B Crolla, JA Christian, SL WolfLedbetter, ME Macha, ME Papenhausen, PN Ledbetter, DH TI Identification of two classes of breakpoints in small inv dup(15) chromosomes confirms ''hotspots'' for chromosome 15 rearrangements SO CYTOGENETICS AND CELL GENETICS LA English DT Meeting Abstract C1 WESSEX REG GENET LAB,SALISBURY,WILTS,ENGLAND. LAB CORP AMER,RES TRIANGLE PK,NC. NIH,NATL CTR HUMAN GENOME RES,DIAGNOST DEV BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-0171 J9 CYTOGENET CELL GENET JI Cytogenet. Cell Genet. PY 1996 VL 74 IS 4 BP 303 EP 303 PG 1 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA VW615 UT WOS:A1996VW61500017 ER PT J AU Gollin, SM Lese, CM Rossie, KM Khanna, P Jackson, TR Ried, T Wilson, J Michalides, R Myers, EN Johnson, JT AF Gollin, SM Lese, CM Rossie, KM Khanna, P Jackson, TR Ried, T Wilson, J Michalides, R Myers, EN Johnson, JT TI Amplification of 11q13 in oral squamous cell carcinoma: Karyotyping, CGH, and altered cyclin D1 expression SO CYTOGENETICS AND CELL GENETICS LA English DT Meeting Abstract C1 UNIV PITTSBURGH,PITTSBURGH,PA 15260. NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. NETHERLANDS CANC INST,AMSTERDAM,NETHERLANDS. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-0171 J9 CYTOGENET CELL GENET JI Cytogenet. Cell Genet. PY 1996 VL 74 IS 4 BP 308 EP 308 PG 1 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA VW615 UT WOS:A1996VW61500037 ER PT J AU Cargile, CB Ried, T Guan, XY Schrock, E Taetle, R Meltzer, PS Trent, JM AF Cargile, CB Ried, T Guan, XY Schrock, E Taetle, R Meltzer, PS Trent, JM TI Chromosome microdissection and spectral karyotyping applied to identify DNA sequence amplifications in human ovarian tumors SO CYTOGENETICS AND CELL GENETICS LA English DT Meeting Abstract C1 UNIV MARYLAND,DEPT OBSTET & GYNECOL,DIV HUMAN GENET,BALTIMORE,MD 21201. NIH,NATL CTR HUMAN GENOME RES,CANC GENET LAB,BETHESDA,MD 20892. NIH,NATL CTR HUMAN GENOME RES,DIAGNOST DEV BRANCH,BETHESDA,MD 20892. ARIZONA CANC CTR,TUCSON,AZ. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-0171 J9 CYTOGENET CELL GENET JI Cytogenet. Cell Genet. PY 1996 VL 74 IS 4 BP 309 EP 309 PG 1 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA VW615 UT WOS:A1996VW61500039 ER PT J AU Stratakis, CA Pras, E Lin, JP Kastner, DL Carney, JA Chrousos, GP AF Stratakis, CA Pras, E Lin, JP Kastner, DL Carney, JA Chrousos, GP TI Carney complex, a multiple endocrine neoplasia and familial lentiginosis syndrome, maps to the D2S123 locus (chromosome 2p16) SO CYTOGENETICS AND CELL GENETICS LA English DT Meeting Abstract C1 NICHHD,DEV ENDOCRINOL BRANCH,BETHESDA,MD. NIAMS,ARTHRIT RHEUMATISM BRANCH,BETHESDA,MD. NIAMS,SKIN BIOL LAB,GENET STUDIES S,NIH,BETHESDA,MD. MAYO CLIN,DEPT LAB MED & PATHOL,ROCHESTER,MN. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-0171 J9 CYTOGENET CELL GENET JI Cytogenet. Cell Genet. PY 1996 VL 73 IS 4 BP 14 EP 14 PG 1 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA VD191 UT WOS:A1996VD19100015 ER PT J AU Cummings, LM Trent, JM Marchuk, DA AF Cummings, LM Trent, JM Marchuk, DA TI Identification and mapping of type 1 neurofibromatosis (NF1) homologous loci SO CYTOGENETICS AND CELL GENETICS LA English DT Article; Proceedings Paper CT 4th International Workshop on Human Chromosome 2 Mapping 1996 CY APR 10, 1996 CL IMPERIAL CANC RES FUND LABS, LONDON, ENGLAND SP European Commiss HUGO, NIH, Imperial Canc Res Fund HO IMPERIAL CANC RES FUND LABS ID ALPHA-SATELLITE DNA; GENE; SEQUENCE; CHROMOSOMES; TRANSLOCATION; GENERATION; MUTATIONS; CLONING; PROBES AB During the establishment of a YAC contig for the type 1 neurofibromatosis (NF1) region on human chromosome 17q11.2, several YAC clones were isolated which originated from a different chromosome but which retained strong homology to NF1 coding regions (Marchuk et al., 1992). Fluorescence in situ hybridization (FISH) using these clones has identified NF1-homologous loci on several human chromosomes, including 2, 14, 15, 21, and 22. PCR amplification using primers originally designed to amplify NF1 exons has confirmed these chromosome localizations and, in addition, has revealed NF1-homologous sequences on chromosomes 12 and 20. Sequence analysis of the amplified products has demonstrated that (1) most of these loci have > 90% identity with NF1 sequences; (2) most of these loci represent nonprocessed pseudogenes; and (3) for the chromosome 12 locus, the two described regions of homology with NF1 have open reading frames. Finally, we have identified two novel alpha-satellite DNA repeat units in proximity to NF1-homologous sequences on chromosome 14. Their association suggests a mechanism for dispersion of the NF1-homologous loci based on alpha-satellite-mediated exchange between nonhomologous chromosomes. C1 DUKE UNIV,MED CTR,DEPT GENET,DURHAM,NC 27710. NIH,NATL CTR HUMAN GENOME RES,CANC GENET LAB,BETHESDA,MD 20892. NR 27 TC 15 Z9 15 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-0171 J9 CYTOGENET CELL GENET JI Cytogenet. Cell Genet. PY 1996 VL 73 IS 4 BP 334 EP 340 DI 10.1159/000134370 PG 7 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA VD191 UT WOS:A1996VD19100032 PM 8751390 ER PT J AU Sood, R Aksentijevich, I Altherr, M Apostolou, S Balow, JE Blake, T Callen, DF Centola, M Chen, X Chen, X Collins, FS Doggett, NA FischelGhodsian, N Gardner, D Gumucio, D Krizman, DB Kruglyak, L Levy, E Liu, P Marrone, BL Pras, E Pras, M Richards, RI Rotter, JI Shelton, D Shohat, M Wood, G Kastner, DL AF Sood, R Aksentijevich, I Altherr, M Apostolou, S Balow, JE Blake, T Callen, DF Centola, M Chen, X Chen, X Collins, FS Doggett, NA FischelGhodsian, N Gardner, D Gumucio, D Krizman, DB Kruglyak, L Levy, E Liu, P Marrone, BL Pras, E Pras, M Richards, RI Rotter, JI Shelton, D Shohat, M Wood, G Kastner, DL TI High-resolution physical map of the region spanning the MEF locus at 16p13 SO CYTOGENETICS AND CELL GENETICS LA English DT Meeting Abstract C1 NIAMS,NIH,ARB,BETHESDA,MD 20892. LOS ALAMOS NATL LAB,LOS ALAMOS,NM 87545. WOMENS & CHILDRENS HOSP,ADELAIDE,SA,AUSTRALIA. NIH,NATL CTR HUMAN GENOME RES,LGT,BETHESDA,MD 20892. CEDARS SINAI MED CTR,LOS ANGELES,CA 90048. UNIV MICHIGAN,ANN ARBOR,MI 48109. MIT,WHITEHEAD INST,CAMBRIDGE,MA. CHAIM SHEBA MED CTR,HELLER INST MED RES,IL-52621 TEL HASHOMER,ISRAEL. BEILINSON MED CTR,IL-49100 PETAH TIQWA,ISRAEL. RI Liu, Paul/A-7976-2012; Callen, David/G-1975-2012 OI Liu, Paul/0000-0002-6779-025X; NR 0 TC 0 Z9 0 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-0171 J9 CYTOGENET CELL GENET JI Cytogenet. Cell Genet. PY 1996 VL 72 IS 4 BP 21 EP 21 PG 1 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA UF197 UT WOS:A1996UF19700023 ER PT J AU Vojta, PJ Kato, H Barett, JC AF Vojta, PJ Kato, H Barett, JC TI Generation of a subchromosomal transferable fragment library for human chromosome 1 SO CYTOGENETICS AND CELL GENETICS LA English DT Meeting Abstract C1 UNIV N CAROLINA,CURRICULUM GENET & MOLEC BIOL,CHAPEL HILL,NC. NIEHS,NIH,RES TRIANGLE PK,NC 27709. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-0171 J9 CYTOGENET CELL GENET JI Cytogenet. Cell Genet. PY 1996 VL 72 IS 2-3 BP 153 EP 153 PG 1 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA TX310 UT WOS:A1996TX31000031 ER PT J AU Wang, MG Yi, H Guerini, D Klee, CB McBride, OW AF Wang, MG Yi, H Guerini, D Klee, CB McBride, OW TI Calcineurin A alpha (PPP3CA), calcineurin A beta (PPP3CB) and calcineurin B (PPP3R1) are located on human chromosomes 4, 10q21->q22 and 2p16->p15 respectively SO CYTOGENETICS AND CELL GENETICS LA English DT Article ID DEPENDENT PROTEIN PHOSPHATASE; CATALYTIC SUBUNIT; INSITU HYBRIDIZATION; REGULATORY SUBUNIT; COLORECTAL-CANCER; MOLECULAR-CLONING; BINDING-PROTEIN; CDNA CLONE; CALMODULIN; GENE AB Calcineurin (also called protein phosphatase-2B) is a calmodulin-regulated protein phosphatase which plays an important role in signal transduction. The enzyme is a heterodimer of a 58-59 kDa calmodulin-binding catalytic subunit (calcineurin A) and a small(i.e. 19 kDa) Ca2+-binding regulatory subunit (calcineurin B). The highly conserved calcineurin B is encoded by a single gene in all tissues except testes, whereas there are three isoforms of calcineurin A (alpha, beta and gamma) encoded by genes on three different chromosomes. This enzyme can play a critical role in transcriptional regulation and growth control in T lymphocytes by a mechanism believed to involve dephosphorylation of the nuclear factor NF-AT which is essential for transcription of the interleukin-2 gene. To better evaluate the potential role of the calcineurin genes in human genetic disorders, we have studied their chromosome locations. Calcineurin B (PPP3R1) is located on human chromosome 2p16 --> p15 and calcineurin A beta(PPP3CB, previous gene symbol CALNB) is present on 10q21 --> q22. We confirm the localization of calcineurin A alpha (PPP3CA, previous gene symbol CALNA) to chromosome 4 without regional localization. C1 NCI,BIOCHEM LAB,NIH,BETHESDA,MD 20892. NR 44 TC 31 Z9 34 U1 0 U2 6 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-0171 J9 CYTOGENET CELL GENET JI Cytogenet. Cell Genet. PY 1996 VL 72 IS 2-3 BP 236 EP 241 DI 10.1159/000134198 PG 6 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA TX310 UT WOS:A1996TX31000061 PM 8978785 ER PT J AU Altherr, MR Auerbach, AD Biggs, PO Burn, TC Breuning, MH Peters, DJM Taschner, P Giles, R vanderReijden, B Callen, DF CletonJansen, AM Daniels, R Doggett, NA DorionBonnet, F Driouch, K Gibson, R Ingvarsson, S Kastner, DL KwitekBlack, AE Landegent, JE Loder, B Matthijs, G Mole, SE Olsson, PG Porter, CJ Pronk, JC Ricke, DO Sandford, R Savoia, A Siciliano, MJ Sood, R AF Altherr, MR Auerbach, AD Biggs, PO Burn, TC Breuning, MH Peters, DJM Taschner, P Giles, R vanderReijden, B Callen, DF CletonJansen, AM Daniels, R Doggett, NA DorionBonnet, F Driouch, K Gibson, R Ingvarsson, S Kastner, DL KwitekBlack, AE Landegent, JE Loder, B Matthijs, G Mole, SE Olsson, PG Porter, CJ Pronk, JC Ricke, DO Sandford, R Savoia, A Siciliano, MJ Sood, R TI Report of the fourth international workshop on human chromosome 16 mapping 1995 - Held on 12-14 November 1995 at the University of Leiden, The Netherlands SO CYTOGENETICS AND CELL GENETICS LA English DT Editorial Material ID DNA GLYCOSYLASE CDNA; GENE MAPS; MOUSE; CLONING; DIPEPTIDASE; ASSIGNMENT; REGION; FAMILY C1 LOS ALAMOS NATL LAB,DIV LIFE SCI,LOS ALAMOS,NM 87545. LOS ALAMOS NATL LAB,CTR HUMAN GENOME STUDIES,LOS ALAMOS,NM 87545. LEIDEN UNIV,INST HUMAN GENET,LEIDEN,NETHERLANDS. WOMENS & CHILDRENS HOSP,DEPT CYTOGENET & MOLEC GENET,ADELAIDE,SA,AUSTRALIA. ROCKEFELLER UNIV,LAB HUMAN GENET & HEMATOL,NEW YORK,NY 10021. INST CANC RES,MOLEC CARCINOGENESIS SECT,SUTTON SM2 5NG,SURREY,ENGLAND. INTEGRATED GENET INC,FRAMINGHAM,MA 01701. LEIDEN STATE UNIV,DEPT HUMAN GENET,2333 AL LEIDEN,NETHERLANDS. LEIDEN UNIV,DEPT PATHOL,2300 RC LEIDEN,NETHERLANDS. JOHN RADCLIFFE HOSP,INST MOLEC MED,OXFORD OX3 9DU,ENGLAND. INST BERGONIE,MOLEC ONCOL LAB,F-33076 BORDEAUX,FRANCE. CTR RENE HUGUENIN,LAB ONCOLOGENET,F-92210 ST CLOUD,FRANCE. UNITED MED & DENT SCH,GUYS HOSP,DIV MED & MOLEC GENET,LONDON SE1 9RT,ENGLAND. UNIV ICELAND,DEPT PATHOL,IS-121 REYKJAVIK,ICELAND. NATL HOSP ICELAND,IS-121 REYKJAVIK,ICELAND. NCI,BETHESDA,MD 20892. UNIV IOWA,DEPT PEDIAT,IOWA CITY,IA 52242. ACAD HOSP LEIDEN,DEPT HEMATOL,2333 AL LEIDEN,NETHERLANDS. RI Ingvarsson, Sigurdur/E-7448-2011; Callen, David/G-1975-2012; van der Reijden, Bert/A-3543-2014; Savoia, Anna/B-6463-2014; Biggs, Patrick/H-3355-2014 OI Savoia, Anna/0000-0002-2407-2696; Biggs, Patrick/0000-0002-0285-4101 NR 45 TC 13 Z9 13 U1 0 U2 4 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-0171 J9 CYTOGENET CELL GENET JI Cytogenet. Cell Genet. PY 1996 VL 72 IS 4 BP 271 EP 285 PG 15 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA UF197 UT WOS:A1996UF19700002 ER PT J AU Roilides, E Lyman, CA Mertins, SD Cole, DJ Venzon, D Pizzo, PA Chanock, SJ Walsh, TJ AF Roilides, E Lyman, CA Mertins, SD Cole, DJ Venzon, D Pizzo, PA Chanock, SJ Walsh, TJ TI Ex vivo effects of macrophage colony-stimulating factor on human monocyte activity against fungal and bacterial pathogens SO CYTOKINE LA English DT Article DE Aspergillus; Candida; M-CSF; monocyte; Staphylococcus ID ASPERGILLUS-FUMIGATUS HYPHAE; MURINE MACROPHAGES; CANDIDA-ALBICANS; RECOMBINANT; INFECTIONS; EXPRESSION; ENHANCEMENT; RECEPTORS; THERAPY; CANCER AB The ex vivo effects of macrophage colony-stimulating factor (M-CSF) on antifungal and antibacterial activities of human elutriated monocytes were studied. Cells were isolated prior to the initiation of therapy, on day 3 and at week 7, in six patients with an advanced malignancy receiving M-CSF in a phase I study, Superoxide anion production by monocytes in response to N-formyl methionyl leucyl phenylalanine was enhanced at day 3 of therapy (P = 0.011). In addition, at day 3, fungicidal activity against blastoconidia of Candida albicans was enhanced by M-CSF treatment (P = 0.026), whereas antifungal activity against hyphae of Aspergillus fumigatus was not significantly changed. Bactericidal activity against Staphylococcus aureus was increased at day 3 (P = 0.004). By Northern blot analysis, M-CSF does not upregulate the expression of components of the NADPH-oxidase, the multicomponent enzyme system responsible for generation of superoxide radicals by monocytes. Instead, the predominant effect of M-CSF on circulating monocytes is probably a post-transcriptional effect. In conclusion, these findings suggest that administration of M-CSF to patients may enhance microbicidal activities and thus may provide a useful adjunct to conventional antimicrobial therapy. (C) 1996 Academic Press Limited C1 NCI,PEDIAT BRANCH,BETHESDA,MD 20892. NCI,INFECT DIS SECT,BETHESDA,MD 20892. NCI,SURG BRANCH,BETHESDA,MD 20892. NCI,BIOSTAT & DATA MANAGEMENT SECT,BETHESDA,MD 20892. RI Venzon, David/B-3078-2008 NR 30 TC 34 Z9 34 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 1043-4666 J9 CYTOKINE JI Cytokine PD JAN PY 1996 VL 8 IS 1 BP 42 EP 48 DI 10.1006/cyto.1996.0006 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA TT982 UT WOS:A1996TT98200006 PM 8742065 ER PT J AU Izquierdo, MA Scheffer, GL Flens, MJ Shoemaker, RH Rome, LH Scheper, RJ AF Izquierdo, MA Scheffer, GL Flens, MJ Shoemaker, RH Rome, LH Scheper, RJ TI Relationship of LRP-human major vault protein to in vitro and clinical resistance to anticancer drugs SO CYTOTECHNOLOGY LA English DT Article; Proceedings Paper CT International Meeting on Drug Resistance in Cancer CY SEP 20-23, 1995 CL NATL CELL & TISSUE CULTURE CTR, DUBLIN, IRELAND SP European Tissue Culture Soc, Italian Branch, European Tissue Culture Soc, Irish Branch HO NATL CELL & TISSUE CULTURE CTR DE drug resistance; lung resistance-related protein; multidrug resistance; multidrug resistance-associated protein; P-glycoprotein; vaults ID MEDIATED MULTIDRUG-RESISTANCE; P-GLYCOPROTEIN; MRP; CARCINOMA; LINES; RNA AB Multidrug resistance (MDR) has been related to two members of the ABC-superfamily of transporters, P-glycoprotein (Pgp) and Multidrug Resistance-associated Protein (MRP). We have described a 110 kD protein termed the Lung Resistance-related Protein (LRP) that is overexpressed in several non-Pgp MDR cell lines of different histogenetic origin. Reversal of MDR parallels a decrease in LRP expression. In a panel of 61 cancer cell Lines which have not been subjected to laboratory drug selection, LRP was a superior predictor for in vitro resistance to MDR-related drugs when compared to Pgp and MRP, and LRP's predictive value extended to MDR unrelated drugs, such as platinum compounds. LRP is widely distributed in clinical cancer specimens, but the frequency of LRP expression inversely correlates with the known chemosensitivity of different tumour types. Furthermore, LRP expression at diagnosis has been shown to be a strong and independent prognostic factor for response to chemotherapy and outcome in acute myeloid leukemia and ovarian carcinoma (platinum-based treatment) patients. Recently, LRP has been identified as the human major protein. Vaults are novel cellular organelles broadly distributed and highly conserved among diverse eukaryotic cells, suggesting that they play a role in fundamental cell processes. Vaults localise to nuclear pore complexes and may be the central plug of the nuclear pore complexes. Vaults structure and localisation support a transport function for this particle which could involve a variety of substrates. Vaults may therefore play a role in drug resistance by regulating the nucleocytoplasmic transport of drugs. C1 FREE UNIV AMSTERDAM HOSP,DEPT PATHOL,NL-1081 HV AMSTERDAM,NETHERLANDS. NCI,LAB DRUG DISCOVERY RES & DEV,DEV THERAPEUT PROGRAM,DIV CANC TREATMENT,FREDERICK,MD 21702. UNIV CALIF LOS ANGELES,SCH MED,DEPT BIOL CHEM,LOS ANGELES,CA 90024. RI Rome, Leonard/E-8786-2016 OI Rome, Leonard/0000-0002-1236-2063 NR 26 TC 40 Z9 45 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0920-9069 J9 CYTOTECHNOLOGY JI Cytotechnology PY 1996 VL 19 IS 3 BP 191 EP 197 DI 10.1007/BF00744212 PG 7 WC Biotechnology & Applied Microbiology; Cell Biology SC Biotechnology & Applied Microbiology; Cell Biology GA VG029 UT WOS:A1996VG02900005 PM 8862006 ER PT J AU Boni, R Zhuang, Z Albuquerque, A Vortmeyer, A Duray, P AF Boni, R Zhuang, Z Albuquerque, A Vortmeyer, A Duray, P TI Detection of allelic loss on chromosomes 1p and 9p in dysplastic nevi using the microdissection technique SO DERMATOLOGY LA English DT Article; Proceedings Paper CT 78th Annual Meeting of the Swiss-Society-for-Dermatology-and-Venereology CY SEP 19-21, 1996 CL GENEVA, SWITZERLAND SP Swiss Soc Dermatol & Venereol C1 UNIV ZURICH HOSP,DEPT DERMATOL,CH-8091 ZURICH,SWITZERLAND. RP Boni, R (reprint author), NCI,DEPT PATHOL,NIH,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1018-8665 J9 DERMATOLOGY JI Dermatology PY 1996 VL 193 IS 2 BP 169 EP 169 PG 1 WC Dermatology SC Dermatology GA VH955 UT WOS:A1996VH95500057 ER PT J AU Itin, PH Bohn, S Mathys, D Guggenheim, R Richard, G AF Itin, PH Bohn, S Mathys, D Guggenheim, R Richard, G TI Trichorhinophalangeal syndrome type III SO DERMATOLOGY LA English DT Article DE trichorhinophalangeal syndrome type III; scanning electron microscopy of hair ID LANGER-GIEDION SYNDROME; CHROMOSOME-8 LONG ARM; INTERSTITIAL DELETION; REGION AB Trichorhinophalangeal syndrome (TRPS) type III is a newly defined clinical entity. This symptom complex is inherited as an autosomal dominant trait and clinically characterized by growth retardation, craniofacial abnormalities, severe brachydactyly and sparse hair. In addition, absence of mental retardation and cartilaginous exostoses are required for the diagnosis of TRPS III. To further delineate this newly recognized entity, we report on a patient from a Turkish family segregating TRPS III in 7 family members. The patient had a very short stature (147 cm, <3rd standard deviation), a thin upper lip and a prominent lower lip, a pear-shaped nose, stubby fingers and toes with cone-shaped epiphyses and sparse scalp hair. Scanning electron microscopy findings and results of energy-dispersive X-ray microanalysis are presented in such a patient for the first time. C1 UNIV BASEL,LAB SCANNING ELECTRON MICROSCOPY,CH-4031 BASEL,SWITZERLAND. NIAMS,SKIN BIOL LAB,GENET STUDIES SECT,BETHESDA,MD. RP Itin, PH (reprint author), UNIV BASEL,DERMATOL KLIN,PETERSGRABEN 4,CH-4031 BASEL,SWITZERLAND. NR 13 TC 15 Z9 16 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1018-8665 J9 DERMATOLOGY JI Dermatology PY 1996 VL 193 IS 4 BP 349 EP 352 PG 4 WC Dermatology SC Dermatology GA WB517 UT WOS:A1996WB51700021 PM 8993967 ER PT S AU Milne, GWA Wang, S Fung, V AF Milne, GWA Wang, S Fung, V BE DeVito, SC Garrett, RL TI Use of computers in toxicology and chemical design SO DESIGNING SAFER CHEMICALS: GREEN CHEMISTRY FOR POLLUTION PREVENTION SE ACS SYMPOSIUM SERIES LA English DT Article; Proceedings Paper CT Session on Designing Safer Chemicals, at the 208th National Meeting of the American-Chemical-Society CY AUG, 1994 CL WASHINGTON, DC SP Amer Chem Soc ID AUTOMATED STRUCTURE EVALUATION; SALMONELLA MUTAGENICITY; ARTIFICIAL-INTELLIGENCE; RODENT CARCINOGENICITY; QSAR MODEL; DATA-BASES; PREDICTION; PROGRAM; BIOASSAYS; BIPHENYLS AB Experimental determination of the acute or chronic toxicity of chemicals has traditionally been carried out by treating animals with different doses of the compound and determining the effects. This procedure requires that a sample of the material be available. The testing is expensive, particularly if chronic toxicity is to be examined and as the testing is done in animals, the extrapolation of the results to humans is often of dubious reliability. For these reasons, efforts have been expended in recent years to develop computer programs which can predict toxicity from chemical composition. The accuracy of such predictions is improving steadily and currently they offer an alternative to traditional toxicological methods. Further, they can be used to predict the toxicities of chemicals which do not exist and thus can be used as a guide to ecologically sensitive chemical development. RP Milne, GWA (reprint author), NCI,MED CHEM LAB,NIH,BLDG 37,ROOM 5B29,BETHESDA,MD 20892, USA. NR 53 TC 2 Z9 2 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 SIXTEENTH ST NW, WASHINGTON, DC 20036 SN 0097-6156 BN 0-8412-3443-4 J9 ACS SYM SER PY 1996 VL 640 BP 138 EP 155 PG 18 WC Chemistry, Multidisciplinary SC Chemistry GA BG22P UT WOS:A1996BG22P00007 ER PT J AU Hermesz, E Mackem, S Mahon, KA AF Hermesz, E Mackem, S Mahon, KA TI Rpx: A novel anterior-restricted homeobox gene progressively activated in the prechordal plate, anterior neural plate and Rathke's pouch of the mouse embryo SO DEVELOPMENT LA English DT Article DE homeobox; pituitary; adenohypophysis; gastrulation; prechordal plate; anterior neural plate; endoderm; Rathke's pouch; mouse ID HOMEODOMAIN PROTEIN; TRANSCRIPTION FACTOR; DEVELOPING FOREBRAIN; XENOPUS EMBRYOS; GROWTH-HORMONE; EARLY CHICK; EXPRESSION; DOMAIN; DROSOPHILA; PITUITARY AB We have isolated a new murine homeobox gene, Rpx (for Rathke's pouch homeobox), that is dynamically expressed in the prospective cephalic region of the embryo during gastrulation. Early expression is seen in the anterior midline endoderm and prechordal plate precursor. Expression is subsequently activated in the overlying ectoderm of the cephalic neural plate, suggesting that inductive contact with Rpx-expressing mesendoderm is required for this expression. Subsequently, Rpx expression is extinguished in the mesendoderm while remaining in the prospective prosencephalic region of the neural plate ectoderm, Ultimately, transcripts become restricted to Rathke's pouch, the primordium of the pituitary, which is known to be derived from the most anterior ectoderm of the early embryo. Down regulation of Rpx in the pouch coincides with the differentiation of pituitary-specific cell types, Rpx is the earliest known marker for the pituitary primordium, suggestive of a role in the early determination or differentiation of the pituitary. Since Rpx is expressed so dynamically and so early in the anterior region of the embryo, and since its early expression domain is much more extensive than the region fated to form the pituitary, it is likely that Rpx is involved in the initial determination of the anterior (prechordal) region of the embryo. C1 NICHHD,LAB MAMMALIAN GENES & DEV,BETHESDA,MD 20892. NCI,NIH,PATHOL LAB,BETHESDA,MD 20892. NR 83 TC 243 Z9 247 U1 0 U2 0 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0950-1991 J9 DEVELOPMENT JI Development PD JAN PY 1996 VL 122 IS 1 BP 41 EP 52 PG 12 WC Developmental Biology SC Developmental Biology GA TY516 UT WOS:A1996TY51600005 PM 8565852 ER PT S AU Fauci, AS AF Fauci, AS BE Giraldo, G Bolognesi, DP Salvatore, M BethGiraldo, E TI Host factors in the pathogenesis of HIV disease SO DEVELOPMENT AND APPLICATIONS OF VACCINES AND GENE THERAPY IN AIDS SE ANTIBIOTICS AND CHEMOTHERAPY LA English DT Proceedings Paper CT International Workshop on the Development and Applications of Vaccines and Gene Therapy in AIDS CY JUN 15-16, 1995 CL NAPLES, ITALY SP Ist Nazl Tumori, Fdn G Pascale Naples, Lega Italiana Lotta Tumori, Commiss European Communities, Italian Minist Hlth, Italian Assoc AIDS, Assessorato Sanita, Campania ID IMMUNODEFICIENCY-VIRUS TYPE-1; FOLLICULAR DENDRITIC CELLS; T-CELLS; INFECTION; REPLICATION; EXPRESSION; APOPTOSIS; DEATH RP Fauci, AS (reprint author), NIAID,NIH,BETHESDA,MD 20892, USA. NR 32 TC 17 Z9 17 U1 0 U2 0 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0066-4758 BN 3-8055-6256-X J9 ANTIBIOT CHEMOTHER PY 1996 VL 48 BP 4 EP 12 PG 9 WC Infectious Diseases; Medicine, Research & Experimental; Pharmacology & Pharmacy SC Infectious Diseases; Research & Experimental Medicine; Pharmacology & Pharmacy GA BF56F UT WOS:A1996BF56F00002 PM 8726500 ER PT S AU Nara, PL AF Nara, PL BE Giraldo, G Bolognesi, DP Salvatore, M BethGiraldo, E TI Immunotyping HIV-1 in the 1990s SO DEVELOPMENT AND APPLICATIONS OF VACCINES AND GENE THERAPY IN AIDS SE ANTIBIOTICS AND CHEMOTHERAPY LA English DT Proceedings Paper CT International Workshop on the Development and Applications of Vaccines and Gene Therapy in AIDS CY JUN 15-16, 1995 CL NAPLES, ITALY SP Ist Nazl Tumori, Fdn G Pascale Naples, Lega Italiana Lotta Tumori, Commiss European Communities, Italian Minist Hlth, Italian Assoc AIDS, Assessorato Sanita, Campania ID HUMAN-IMMUNODEFICIENCY-VIRUS RP Nara, PL (reprint author), NCI,FCRDC,TUMOR CELL BIOL LAB,VIRUS BIOL SECT,BLDG 560,ROOM 12-92,FREDERICK,MD 21702, USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0066-4758 BN 3-8055-6256-X J9 ANTIBIOT CHEMOTHER PY 1996 VL 48 BP 56 EP 62 PG 7 WC Infectious Diseases; Medicine, Research & Experimental; Pharmacology & Pharmacy SC Infectious Diseases; Research & Experimental Medicine; Pharmacology & Pharmacy GA BF56F UT WOS:A1996BF56F00008 PM 8726506 ER PT S AU Vogel, FR AF Vogel, FR BE Giraldo, G Bolognesi, DP Salvatore, M BethGiraldo, E TI Role of adjuvants in HIV vaccine design SO DEVELOPMENT AND APPLICATIONS OF VACCINES AND GENE THERAPY IN AIDS SE ANTIBIOTICS AND CHEMOTHERAPY LA English DT Proceedings Paper CT International Workshop on the Development and Applications of Vaccines and Gene Therapy in AIDS CY JUN 15-16, 1995 CL NAPLES, ITALY SP Ist Nazl Tumori, Fdn G Pascale Naples, Lega Italiana Lotta Tumori, Commiss European Communities, Italian Minist Hlth, Italian Assoc AIDS, Assessorato Sanita, Campania ID RECOMBINANT GAMMA-INTERFERON; IMMUNOLOGICAL ADJUVANTS; ANTIBODY-RESPONSE; CHOLERA-TOXIN; PERTUSSIS TOXIN; VIRUS-VACCINE; CELL SUBSETS; IMMUNIZATION; LIPOSOMES; INDUCTION RP Vogel, FR (reprint author), NIAID,DIV AIDS,VACCINE & PREVENT RES PROGRAM,MSC 7620,6003 EXECUT BLVD,ROOM 2A28A,BETHESDA,MD 20892, USA. NR 48 TC 3 Z9 3 U1 0 U2 0 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0066-4758 BN 3-8055-6256-X J9 ANTIBIOT CHEMOTHER PY 1996 VL 48 BP 84 EP 91 PG 8 WC Infectious Diseases; Medicine, Research & Experimental; Pharmacology & Pharmacy SC Infectious Diseases; Research & Experimental Medicine; Pharmacology & Pharmacy GA BF56F UT WOS:A1996BF56F00011 PM 8726509 ER PT S AU Hoff, R Lawrence, DN AF Hoff, R Lawrence, DN BE Giraldo, G Bolognesi, DP Salvatore, M BethGiraldo, E TI Preparation for HIV vaccine efficacy trials SO DEVELOPMENT AND APPLICATIONS OF VACCINES AND GENE THERAPY IN AIDS SE ANTIBIOTICS AND CHEMOTHERAPY LA English DT Proceedings Paper CT International Workshop on the Development and Applications of Vaccines and Gene Therapy in AIDS CY JUN 15-16, 1995 CL NAPLES, ITALY SP Ist Nazl Tumori, Fdn G Pascale Naples, Lega Italiana Lotta Tumori, Commiss European Communities, Italian Minist Hlth, Italian Assoc AIDS, Assessorato Sanita, Campania RP Hoff, R (reprint author), NIAID,NIH,DIV AIDS,VACCINE & PREVENT RES PROGRAM,ROOM 2A12,BETHESDA,MD 20892, USA. NR 19 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0066-4758 BN 3-8055-6256-X J9 ANTIBIOT CHEMOTHER PY 1996 VL 48 BP 155 EP 160 PG 6 WC Infectious Diseases; Medicine, Research & Experimental; Pharmacology & Pharmacy SC Infectious Diseases; Research & Experimental Medicine; Pharmacology & Pharmacy GA BF56F UT WOS:A1996BF56F00022 PM 8726520 ER PT S AU Gallo, RC AF Gallo, RC BE Giraldo, G Bolognesi, DP Salvatore, M BethGiraldo, E TI Some novel approaches to the control of HIV and select aspects of HIV pathogenesis SO DEVELOPMENT AND APPLICATIONS OF VACCINES AND GENE THERAPY IN AIDS SE ANTIBIOTICS AND CHEMOTHERAPY LA English DT Proceedings Paper CT International Workshop on the Development and Applications of Vaccines and Gene Therapy in AIDS CY JUN 15-16, 1995 CL NAPLES, ITALY SP Ist Nazl Tumori, Fdn G Pascale Naples, Lega Italiana Lotta Tumori, Commiss European Communities, Italian Minist Hlth, Italian Assoc AIDS, Assessorato Sanita, Campania ID VIRUS TYPE-1 REPLICATION; KAPOSIS SARCOMA; GROWTH-FACTOR; CELLS RP Gallo, RC (reprint author), NCI,TUMOR CELL BIOL LAB,BLDG 37,ROOM 6A09,37 CONVENT DR MSC 4255,BETHESDA,MD 20892, USA. NR 17 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0066-4758 BN 3-8055-6256-X J9 ANTIBIOT CHEMOTHER PY 1996 VL 48 BP 188 EP 191 PG 4 WC Infectious Diseases; Medicine, Research & Experimental; Pharmacology & Pharmacy SC Infectious Diseases; Research & Experimental Medicine; Pharmacology & Pharmacy GA BF56F UT WOS:A1996BF56F00026 PM 8726524 ER PT S AU Bridges, SH AF Bridges, SH BE Giraldo, G Bolognesi, DP Salvatore, M BethGiraldo, E TI Immune reconstitution for HIV disease SO DEVELOPMENT AND APPLICATIONS OF VACCINES AND GENE THERAPY IN AIDS SE ANTIBIOTICS AND CHEMOTHERAPY LA English DT Proceedings Paper CT International Workshop on the Development and Applications of Vaccines and Gene Therapy in AIDS CY JUN 15-16, 1995 CL NAPLES, ITALY SP Ist Nazl Tumori, Fdn G Pascale Naples, Lega Italiana Lotta Tumori, Commiss European Communities, Italian Minist Hlth, Italian Assoc AIDS, Assessorato Sanita, Campania ID T-CELL CLONES; TRANSPLANTATION; CD4+ RP Bridges, SH (reprint author), NIAID,NIH,DIV AIDS,SOLAR BLDG,ROOM 2C03,BETHESDA,MD 20892, USA. NR 21 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0066-4758 BN 3-8055-6256-X J9 ANTIBIOT CHEMOTHER PY 1996 VL 48 BP 233 EP 239 PG 7 WC Infectious Diseases; Medicine, Research & Experimental; Pharmacology & Pharmacy SC Infectious Diseases; Research & Experimental Medicine; Pharmacology & Pharmacy GA BF56F UT WOS:A1996BF56F00032 PM 8726530 ER PT J AU Lana, DP Leferovich, JM Kelly, AM Hughes, SH AF Lana, DP Leferovich, JM Kelly, AM Hughes, SH TI Selective expression of a ski transgene affects IIb past muscles and skeletal structure SO DEVELOPMENTAL DYNAMICS LA English DT Article DE c-ski; development; transgene; in situ hybridization; skeleton; muscle ID RAT HINDLIMB; ONCOGENE; MYOSIN; MICE; CELLS; GENE; DIFFERENTIATION; EMBRYOGENESIS; OSTEOPETROSIS; SEQUENCE AB The expression of a ski transgene in the hind leg muscles of mice follows a spatial and temporal pattern reminiscent of the pattern of myogenic development, Anterior muscles, which are formed earliest during development, are also the first muscles to express ski mRNA. Muscles derived from the posterior muscle group, formed later during development, exhibit delayed expression of ski mRNA. In addition, there is regional variation in ski mRNA levels within a particular muscle. Superficial regions of fast muscles, which contain a large percentage of type IIb fibers and have a high ATPase activity, express a higher level of ski mRNA than the deep portions of the same muscles. The deep regions contain a lower percentage of type IIb fibers and lower ATPase activity, The soleus, a slow muscle composed predominantly of type I fibers, expresses low ATPase activity and contains much lower levels of ski mRNA, mRNA from the ski transgene is also expressed at high levels in the osteocytes of the leg bones of 15-day and older transgenic mice. High levels of Ski protein is present in the osteocytes of the leg bones, ski expression appears to cause remodeling of the tibia and fibula, The cross-sectional area of the tibia and fibula of ski transgenic mice is significantly decreased compared to controls, X-rays of the skeletons of ski transgenic mice suggest that the bones of the entire skeleton are thinner than the bones in normal mice, Pathological stress fractures were found in several bones in the ski transgenic mice, (C) 1996 Wiley-Liss, Inc. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. UNIV PENN,SCH VET MED,DEPT PATHOBIOL,PHILADELPHIA,PA 19104. FU NHLBI NIH HHS [HL 15835] NR 44 TC 14 Z9 14 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD JAN PY 1996 VL 205 IS 1 BP 13 EP 23 DI 10.1002/(SICI)1097-0177(199601)205:1<13::AID-AJA2>3.0.CO;2-8 PG 11 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA TN085 UT WOS:A1996TN08500002 PM 8770548 ER PT J AU Buonanno, A Rosenthal, N AF Buonanno, A Rosenthal, N TI Molecular control of muscle diversity and plasticity SO DEVELOPMENTAL GENETICS LA English DT Review ID TROPONIN-I GENE; MYOGENIC REGULATORY GENES; ENHANCER-BINDING FACTOR; ADULT SKELETAL-MUSCLE; LIGHT CHAIN ENHANCER; FAST-TWITCH MUSCLE; TRANSGENIC MICE; FIBER-TYPE; TRANSCRIPTION FACTOR; MYOD FAMILY C1 MASSACHUSETTS GEN HOSP EAST,CARDIOVASC RES CTR,BOSTON,MA. RP Buonanno, A (reprint author), NIH,BLDG 49,ROOM 5A-38,BETHESDA,MD 20892, USA. NR 140 TC 50 Z9 52 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0192-253X J9 DEV GENET JI Dev. Genet. PY 1996 VL 19 IS 2 BP 95 EP 107 DI 10.1002/(SICI)1520-6408(1996)19:2<95::AID-DVG1>3.0.CO;2-V PG 13 WC Developmental Biology; Genetics & Heredity SC Developmental Biology; Genetics & Heredity GA VQ330 UT WOS:A1996VQ33000001 PM 8900042 ER PT J AU Calvo, S Stauffer, J Nakayama, M Buonanno, A AF Calvo, S Stauffer, J Nakayama, M Buonanno, A TI Transcriptional control of muscle plasticity: Differential regulation of troponin I genes by electrical activity SO DEVELOPMENTAL GENETICS LA English DT Article DE fiber-type; skeletal muscle; myotube; Sol8; denervation ID HUMAN MYOGLOBIN PROMOTER; ENHANCER-BINDING FACTOR; ADULT SKELETAL-MUSCLE; MYOD FAMILY; TRANSGENIC MICE; HUMAN ALDOLASE; C GENE; EXPRESSION; MYOGENIN; ELEMENT AB Plasticity of the skeletal muscle phenotype can result from the selective repression and activation of gene expression in response to innervation patterns. Motoneurons, eliciting different patterns of depolarization, regulate the contractile properties of the myofibers they innervate by selectively activating expression of genes encoding fiber-type-specific (fast vs. slow) contractile proteins. We have analyzed the regulation of the troponin I slow (TnIs) and fast (TnIf) genes as a model to study the molecular mechanisms regulating fiber-type plasticity. We found that expression of the two TnI isoforms is downregulated by denervation. Moreover, TnI expression is upregulated by specific patterns of electrical activity (10 Hz vs. 100 Hz) used to depolarize muscle. We previously isolated the rat TnIs gene and demonstrated that regulatory sequences reside in its upstream region and second intron [Banerjee-Basu S, Buonanno A (1993), Mol Cell Biol 12:5024-5032]. Using transgenic mice, we show that the upstream region of the TnIs gene extending from -949 to +50 is sufficient to confer transcription specifically in slow-twitch muscles. Serial deletions of the TnIs upstream and intronic regions were generated in a CAT reporter vector to delineate transcriptional regulatory elements in transiently transfected SoI8 myotubes. Sequences necessary to confer the highest levels of TnIs transcription mapped to the upstream region between -0.95 and -0.72 kb, and to a 56 bp sequence located in the second intron. Comparison of the rat sequence between -0.95 and -0.72 to the human TnIs gene identified a highly homologous region of 128 bp that we named the TnI SURE (slow upstream regulatory element). Alignment of these two SURE sequences with the quail TnI fast intronic regulatory element identified common motifs, namely, two ATT-rich sequences (A/T1 and A/T2) with homology to homeotic protein and MEF2 binding sites, a CACC box, an E box, and a novel motif (GCAGGCA) that we denoted the CAGG box. Mutation of either the A/T2 site, E box, or CAGG box practically abolish the SURE function in transfected myotubes; mutation of the A/T1 and CACC sites has a lesser effect. Using competitive electrophoretic mobility shift assays with nuclear extracts derived from SoI8 myotubes, we demonstrate specific binding to these motifs. The A/T1 and A/T2 sites are shown to form different complexes. The A/T2 site, which bares extensive homology to a MEF2 site, forms complexes that are super shifted by MEF2A antisera and that are competed by a consensus MEF2 site present in the MCK enhancer. Our results demonstrate that the linear arrangement of DNA sequence motifs is conserved in the regulatory elements of the TnI slow and fast genes and suggest that the interaction of multiple protein-DNA complexes are necessary for enhancer function. (C) 1996 Wiley-Liss, Inc. C1 NICHHD,MOL NEUROBIOL UNIT,NIH,BETHESDA,MD 20892. NR 60 TC 28 Z9 29 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0192-253X J9 DEV GENET JI Dev. Genet. PY 1996 VL 19 IS 2 BP 169 EP 181 DI 10.1002/(SICI)1520-6408(1996)19:2<169::AID-DVG9>3.0.CO;2-7 PG 13 WC Developmental Biology; Genetics & Heredity SC Developmental Biology; Genetics & Heredity GA VQ330 UT WOS:A1996VQ33000009 PM 8900050 ER PT J AU Eddy, EM AF Eddy, EM TI The germ line and development SO DEVELOPMENTAL GENETICS LA English DT Review ID CAENORHABDITIS-ELEGANS; CELL SPECIFICATION; DROSOPHILA; PLASM; LOCALIZATION; EMBRYOS RP Eddy, EM (reprint author), NIEHS,NIH,LRDT,GAMETE BIOL SECT,C4-01,RES TRIANGLE PK,NC 27709, USA. NR 22 TC 11 Z9 11 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0192-253X J9 DEV GENET JI Dev. Genet. PY 1996 VL 19 IS 4 BP 287 EP 289 DI 10.1002/(SICI)1520-6408(1996)19:4<287::AID-DVG1>3.0.CO;2-5 PG 3 WC Developmental Biology; Genetics & Heredity SC Developmental Biology; Genetics & Heredity GA WF908 UT WOS:A1996WF90800001 PM 9023981 ER PT J AU Ghosh, S Schork, NJ AF Ghosh, S Schork, NJ TI Perspectives in diabetes - Genetic analysis of NIDDM - The study of quantitative traits SO DIABETES LA English DT Review ID INSULIN SENSITIVITY INDEX; AFFECTED RELATIVE PAIRS; PEDIGREE-MEMBER METHOD; FASTING BLOOD-GLUCOSE; LINKAGE ANALYSIS; GLUCOKINASE GENE; PIMA-INDIANS; COMPLEX TRAITS; SUSCEPTIBILITY GENES; FAMILY RESEMBLANCE AB Many studies are in progress worldwide to elucidate the genetics of NIDDM. Nevertheless, few articles are available that combine the interdisciplinary fields of medicine, genetics, physiology, and statistics in order to provide the scientific rationale for such an endeavor, Here are describe the methodology and background necessary to study the genetics of NIDDM and discuss how to analyze the data, We also provide a detailed bibliography for researchers and a glossary for those who are not experts in the field. In particular, we wish to emphasize the analysis of intermediate quantitative traits as a means to dissect the genetic basis of NIDDM. C1 CASE WESTERN RESERVE UNIV,SCH MED,DEPT GENET,CLEVELAND,OH. CASE WESTERN RESERVE UNIV,SCH MED,CTR HUMAN GENET,CLEVELAND,OH. UNIV HOSP CLEVELAND,CLEVELAND,OH. RP Ghosh, S (reprint author), NATL CTR HUMAN GENOME RES,LAB GENE TRANSFER,ROOM 1S125,BLDG 9,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 153 TC 87 Z9 89 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0012-1797 J9 DIABETES JI Diabetes PD JAN PY 1996 VL 45 IS 1 BP 1 EP 14 DI 10.2337/diabetes.45.1.1 PG 14 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA TM677 UT WOS:A1996TM67700001 PM 8522051 ER PT J AU Drass, JA Feldman, RHL AF Drass, JA Feldman, RHL TI Knowledge about hypoglycemia in young women with type I diabetes and their supportive others SO DIABETES EDUCATOR LA English DT Article ID CHILDREN; PARENTS AB Hypoglycemia is a common stressful occurrence for people with type I diabetes, is disruptive to daily activities, and is a source of embarrassment, fear and anxiety. Adequate knowledge about hypoglycemia is needed to recognize, treat, and prevent this condition. Families and friends also need adequate knowledge about hypoglycemia to provide helpful support. In this study, the Hypoglycemia Knowledge Questionnaire was used to measure knowledge about hypoglycemia in a convenience sample of 94 young women with type I diabetes and 94 supportive others. Knowledge about hypoglycemia was significantly higher for the young women with diabetes than for their supportive others, although knowledge deficits were evident for the young women on selected questionnaire items. Because normalization of blood glucose is associated with an increased risk of hypoglycemia, comprehensive evaluation of knowledge about hypoglycemia is critical to self-care. Additional studies are needed to validate the reliability and evaluate the usefulness of the Hypoglycemia Knowledge Questionnaire in clinical and research applications. C1 NIH,CTR CLIN,DEPT NURSING,BETHESDA,MD 20892. NR 16 TC 3 Z9 3 U1 1 U2 1 PU AMER ASSOC DIABETES EDUCATORS PI CHICAGO PA STE 1240, 444 NORTH MICHIGAN AVE, CHICAGO, IL 60611-3901 SN 0145-7217 J9 DIABETES EDUCATOR JI Diabetes Educ. PD JAN-FEB PY 1996 VL 22 IS 1 BP 34 EP 38 DI 10.1177/014572179602200105 PG 5 WC Endocrinology & Metabolism; Public, Environmental & Occupational Health SC Endocrinology & Metabolism; Public, Environmental & Occupational Health GA TT505 UT WOS:A1996TT50500005 PM 8697954 ER PT J AU Harris, MI AF Harris, MI TI Impaired glucose tolerance - Prevalence and conversion to NIDDM SO DIABETIC MEDICINE LA English DT Article; Proceedings Paper CT Expert Workshop on Impaired Glucose Tolerance CY MAR 29, 1995 CL LONDON, ENGLAND SP Bayer AG DE impaired glucose tolerance; epidemiology; diabetes prevention; international studies ID UNITED-STATES POPULATION; DIABETES-MELLITUS; RISK-FACTORS; NAURUANS AB Impaired glucose tolerance (IGT) has been investigated in a large number of populations from different parts of the world and with differing lifestyles. The occurrence of IGT varies widely. IGT prevalence tends to increase with age, but there is no consistent relationship with gender. Prevalence is lower in groups with less obesity and having physically active lifestyles, such as those living in rural areas and having traditional lifestyles, even when subjects with the same genetic background are compared. Risk factors for IGT are similar to those for non-insulin dependent diabetes mellitus (NIDDM). IGT, characterized by hyperglycaemia and insulin resistance, is probably a stage in the pathogenesis of NIDDM. Therapies aimed at improving glucose tolerance and decreasing insulin resistance in subjects with IGT may, therefore, be able to delay or prevent the development of NIDDM. RP Harris, MI (reprint author), NIDDK,NIH,NATL DIABET DATA GRP,NATCHER BLDG,ROOM 5AN24,45 CTR DR MSC 6600,BETHESDA,MD 20892, USA. NR 14 TC 46 Z9 52 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0742-3071 J9 DIABETIC MED JI Diabetic Med. PY 1996 VL 13 IS 3 SU 2 BP S9 EP S11 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA UB895 UT WOS:A1996UB89500003 PM 8689862 ER PT J AU Spraul, M Ravussin, E Baron, AD AF Spraul, M Ravussin, E Baron, AD TI Lack of relationship between muscle sympathetic nerve activity and skeletal muscle vasodilation in response to insulin infusion SO DIABETOLOGIA LA English DT Article DE sympathetic nervous system; microneurography; leg blood flow; insulin sensitivity; insulin-mediated glucose uptake ID MEDIATED GLUCOSE-UPTAKE; BLOOD-FLOW; ESSENTIAL-HYPERTENSION; DIABETES-MELLITUS; HYPERINSULINEMIA; RESISTANCE; HUMANS; METABOLISM; ACTIVATION; RECORDINGS AB Increases in plasma insulin concentration result in vasodilation in skeletal muscle but also in an increase in muscle sympathetic nerve activity (MSNA) which is thought to cause vasoconstriction. The increase in MSNA could therefore be a response to vasodilation (baroreflex), or MSNA could cause vasodilation via putative sympathetic vasodilatory fibres. To examine the relationship between vasodilation, MSNA and insulin action we studied nine nondiabetic Pima Indian men (age 29 +/- 7 years, weight 91 +/- 19 kg, 29 +/- 6% body fat, mean +/- SD) during sequential euglycaemic clamps at low and high insulin doses (80 and 600 mU . m(-2) min(-1)). Leg blood flow was measured by thermodilution, leg glucose uptake by the balance technique, arterial pressure by invasive monitoring and MSNA by microneurography of the peroneal nerve. Whole body glucose uptake (M) ranged from 6.7 to 48.3 during low dose and from 9.4 to 67.7 mu mol . kg fat free mass(-1) . min(-1) during high dose insulin infusion. At both insulin doses, incremental leg blood flow correlated with M (r = 0.63 and 0.71, respectively). No correlation was found between incremental MSNA and leg blood flow, M or leg glucose uptake. Blood pressure was unchanged throughout the study. MSNA increased after 15-40 min of insulin infusion in all the subjects, whereas leg blood flow started to increase only after 45 min in the most insulin sensitive but not in the most insulin resistant subjects. Thus, insulin stimulates MSNA more rapidly than vasodilation. In conclusion, insulin-mediated MSNA: 1) is neither a response to nor a cause of the vasodilation observed in insulin sensitive men, 2) has no net presser effect even in the most insulin resistant men in whom insulin-mediated vasodilation was impaired. We conclude that the effect of insulin to stimulate MSNA is dissociated from its acute haemodynamic action. C1 NIDDKD,CLIN DIABET & NUTR SECT,PHOENIX,AZ 85016. INDIANA UNIV,MED CTR,RICHARD L ROUDEBUSH VET AFFAIRS MED CTR,DEPT MED,INDIANAPOLIS,IN. RP Spraul, M (reprint author), UNIV DUSSELDORF,KLIN STOFFWECHSELKRANKHEITEN & ERNAHRUNG,MOORENSTR 5,POSTFACH 101007,D-40061 DUSSELDORF,GERMANY. NR 26 TC 20 Z9 21 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD JAN PY 1996 VL 39 IS 1 BP 91 EP 96 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA TR709 UT WOS:A1996TR70900013 PM 8720608 ER PT S AU Heimendinger, J Chapelsky, D AF Heimendinger, J Chapelsky, D GP AMER INST CANC RES TI The national 5 a day for Better Health Program SO DIETARY PHYTOCHEMICALS IN CANCER PREVENTION AND TREATMENT SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Proceedings Paper CT 6th Annual Research Conference of the American-Institute-for-Cancer-Research on Dietary Phytochemicals in Cancer Prevention and Treatment CY AUG 31-SEP 01, 1995 CL WASHINGTON, DC SP Amer Inst Canc Res ID CANCER RISK; MASS-MEDIA; FRUIT; VEGETABLES; COMMUNITY; EDUCATION; CAMPAIGN; PROJECT; PREVENTION; PROMOTION RP Heimendinger, J (reprint author), NCI,BETHESDA,MD 20892, USA. NR 29 TC 21 Z9 21 U1 0 U2 1 PU PLENUM PRESS DIV PLENUM PUBLISHING CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0065-2598 BN 0-306-45365-7 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 1996 VL 401 BP 199 EP 206 PG 8 WC Oncology; Cell Biology; Nutrition & Dietetics SC Oncology; Cell Biology; Nutrition & Dietetics GA BG31G UT WOS:A1996BG31G00017 PM 8886138 ER PT J AU Desilva, MG Lu, J Donadel, G Modi, WS Xie, H Notkins, AL Lan, MS AF Desilva, MG Lu, J Donadel, G Modi, WS Xie, H Notkins, AL Lan, MS TI Characterization and chromosomal localization of a new protein disulfide isomerase, PDIp, highly expressed in human pancreas SO DNA AND CELL BIOLOGY LA English DT Article ID HORMONE-BINDING-PROTEIN; ENDOPLASMIC-RETICULUM PROTEIN; MOLECULAR-CLONING; PROLYL 4-HYDROXYLASE; BETA-SUBUNIT; PEPTIDE BINDING; SEQUENCE; GENE; CDNA; ISOMERIZATION AB Protein disulfide isomerase (PDI) catalyzes protein folding and thiol-disulfide interchange reactions, The enzyme is localized in the lumen of endoplasmic reticulum (ER) and is abundant in secretory cells of various tissues. In this study we describe the isolation and characterization from human pancreas of a new protein, PDIp, that is structurally and functionally related to PDIs, PDIp, cDNA is 1,659 bp in length and predicts a protein with an open reading frame of 511 amino acids. PDIp, amino acid sequence shows 46% identity and 66% similarity to that of human PDI, PDIp, possesses two thioredoxin-like active sites (WCGHCQ and WCTHCK) and an endoplasmic reticulum retention signal sequence, KEEL, at the carboxyl terminus, Northern analysis of normal human tissues and various human tumor cell lines revealed PDIp mRNA (2.0 kb) expression only in the normal pancreas, Recombinant PDIp, protein catalyzed reductive cleavage of insulin and renaturation of reduced RNaseA, Somatic cell genetics and fluorescence in situ hybridization localized the PDIp gene to the short arm of human chromosome 16. It is concluded that PDIp is a new member of the PDI family and is highly expressed in human pancreas. C1 NIDR,ORAL MED LAB,BETHESDA,MD 20892. NCI,FREDERICK CANC RES & DEV CTR,DYNCORP,BIOL CARCINOGENESIS DEV PROGRAM,FREDERICK,MD 21702. NR 41 TC 54 Z9 57 U1 0 U2 4 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1044-5498 J9 DNA CELL BIOL JI DNA Cell Biol. PD JAN PY 1996 VL 15 IS 1 BP 9 EP 16 DI 10.1089/dna.1996.15.9 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity GA TQ820 UT WOS:A1996TQ82000002 PM 8561901 ER PT J AU Morelli, C Sherratt, T Greaves, MJ Iwanejko, L Trabanelli, C Rimessi, P Gualandi, F Negrini, M BarbantiBrodano, G Trent, JM Boyle, JM AF Morelli, C Sherratt, T Greaves, MJ Iwanejko, L Trabanelli, C Rimessi, P Gualandi, F Negrini, M BarbantiBrodano, G Trent, JM Boyle, JM TI Physical analysis of part of band 6q21 harboring a putative tumor suppressor gene and a putative senescence gene SO DNA SEQUENCE LA English DT Article C1 UNIV FERRARA,INST MICROBIOL,I-44100 FERRARA,ITALY. PATERSON INST CANC RES,CANC GENET DEPT,MANCHESTER M20 9BX,LANCS,ENGLAND. NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. RI Negrini, Massimo/J-2377-2016; Gualandi, Francesca/K-7513-2016 OI Negrini, Massimo/0000-0002-0007-1920; Gualandi, Francesca/0000-0001-9551-057X NR 3 TC 2 Z9 2 U1 0 U2 0 PU HARWOOD ACAD PUBL GMBH PI READING PA C/O STBS LTD, PO BOX 90, READING, BERKS, ENGLAND RG1 8JL SN 1042-5179 J9 DNA SEQUENCE JI DNA Seq. PY 1996 VL 7 IS 1 BP 43 EP 45 DI 10.3109/10425179609015646 PG 3 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA WE658 UT WOS:A1996WE65800011 PM 9063637 ER PT J AU vanRhee, AM Jacobson, KA AF vanRhee, AM Jacobson, KA TI Molecular architecture of G protein-coupled receptors SO DRUG DEVELOPMENT RESEARCH LA English DT Review DE G protein-coupled receptors; GPCRs; transmembrane domains; mutagenesis; sequence alignment; identifiers; molecular architecture; molecular structure ID SITE-DIRECTED MUTAGENESIS; BETA-ADRENERGIC-RECEPTOR; MUSCARINIC ACETYLCHOLINE-RECEPTOR; SINGLE AMINO-ACID; NEPHROGENIC DIABETES-INSIPIDUS; PLATELET-ACTIVATING-FACTOR; 3RD CYTOPLASMIC LOOP; NUCLEOTIDE REGULATORY PROTEINS; CONSTITUTIVELY ACTIVE MUTANTS; LIGAND-BINDING SPECIFICITY AB This review of the current literature on mutations in G protein-coupled receptors (GPCRs) of the rhodopsin-related family intends to draw inferences from amino acid sequences for single receptors and multiple sequence alignments with regard to the molecular architecture of this class of receptors. For this purpose a comprehensive list of mutations within the transmembrane helical regions (TMs; over 390 mutations from 38 different receptor subtypes) and their effects on function was compiled, and an alignment of known GPCR sequences (over 150 separate sequences) was made. Regions most prominently involved in ligand binding are located in TMs 3, 5, 6, and 7. Position 3.32 in TM3 is occupied by a D in all biogenic amine receptors (sequence conservation) but may be occupied by uncharged residues in other receptors while its role in ligand binding is analogous (function conservation). TMs 5, 6, and 7 display considerable sequence conservation throughout the majority of GPCRs investigated, but not necessarily at those positions involved in ligand binding. However, considerable function conservation is observed for positions 5.42 (frequently hydrophilic), 5.46 (small amino acids required for agonist binding to ''small ligand'' receptors), 6.52 and 7.39 (high variability), and 7.43 (frequently aromatic). A general conclusion of this review is that there is overwhelming conservation of structure-function correlates among GPCRs. Thus, it is now possible to cross-correlate the results of mutagenesis studies between GPCRs of different subfamilies, and to use those results to predict the function of specific residues in new GPCR sequences. (C) 1996 Wiley-Liss, Inc.* C1 NIDDK,NIH,LBC,MOL RECOGNIT SECT,BETHESDA,MD 20892. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS [Z01 DK031117-20, Z99 DK999999, ZIA DK031115-26] NR 311 TC 146 Z9 147 U1 0 U2 10 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0272-4391 J9 DRUG DEVELOP RES JI Drug Dev. Res. PD JAN PY 1996 VL 37 IS 1 BP 1 EP 38 DI 10.1002/(SICI)1098-2299(199601)37:1<1::AID-DDR1>3.0.CO;2-S PG 38 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA TX942 UT WOS:A1996TX94200001 PM 21921973 ER PT J AU Acri, JB Shah, JH Newman, AH Belov, YP Basile, AS Sharpe, LG Witkin, JM AF Acri, JB Shah, JH Newman, AH Belov, YP Basile, AS Sharpe, LG Witkin, JM TI Behavioral effects and dopamine antagonist properties of N-alkylaminobenzazepines SO DRUG DEVELOPMENT RESEARCH LA English DT Article DE dopamine D-1 receptors; dopamine antagonists; benzazepines; apomorphine; cocaine; locomotor activity; stereotypy; nucleus accumbens; mice; rats ID COCAINE; RECEPTOR; SCH-23390; RATS; D1; AMPHETAMINE; HALOPERIDOL; PROFILE; MONKEYS; AGONIST AB Blockade of dopamine D-1 receptors has been suggested as a novel therapeutic approach to psychotic disorders and to psychomotor stimulant dependencies. Peripheral D-1 receptors have also been implicated in the acute lethal effects of cocaine. Attempts to synthesize a D-1 antagonist that does not penetrate the central nervous system led to the discovery of a novel series of N-alkylaminobenzazepine D-1 antagonists. In the present study, the most potent compound of that series, JHS 271, suppressed locomotor activity, and blocked cocaine-stimulated activity, apomorphine-induced stereotypies, and the lethal effects of cocaine in mice. Structural analogs of JHS 271 were also evaluated in selected assays. Potencies in these tests demonstrated a significant positive correlation with affinities for the D-1 receptor. These results implicate D-1 receptor blockade as a mechanism of action for JHS 271 and related compounds. Comparative studies of central vs. systemic administration and determination of blood/brain concentrations indicated that JHS 271, like SCH 23390, can readily access central sites upon systemic application. (C) 1996 Wiley-Liss, Inc.* C1 NIDA,ADDICT RES CTR,MOLEC GENET SECT,BALTIMORE,MD 21224. NIH,BALTIMORE,MD. RP Acri, JB (reprint author), NIDA,ADDICT RES CTR,DRUG DEV GRP PSYCHOBIOL SECT,POB 5180,BALTIMORE,MD 21224, USA. NR 36 TC 1 Z9 1 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0272-4391 J9 DRUG DEVELOP RES JI Drug Dev. Res. PD JAN PY 1996 VL 37 IS 1 BP 39 EP 47 DI 10.1002/(SICI)1098-2299(199601)37:1<39::AID-DDR2>3.0.CO;2-N PG 9 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA TX942 UT WOS:A1996TX94200002 ER PT B AU Brewer, HB SantamarinaFojo, S Hoeg, JM AF Brewer, HB SantamarinaFojo, S Hoeg, JM BE Gotto, AM Paoletti, R Smith, LC Catapano, AL Jackson, AS TI Role of gene therapy in the treatment of the genetic dyslipoproteinemias SO DRUGS AFFECTING LIPID METABOLISM: RISK FACTORS AND FUTURE DIRECTIONS SE MEDICAL SCIENCE SYMPOSIA SERIES LA English DT Proceedings Paper CT XII International Symposium of Drugs Affecting Lipid Metabolism (DALM XII) CY NOV 06-10, 1995 CL HOUSTON, TX SP Fdn Giovanni Lorenzini, Milan, Giovanni Lorenzini Med Fdn, Houston C1 NHLBI,MOL DIS BRANCH,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS BN 0-7923-4167-8 J9 MED SCI SYMP SER PY 1996 VL 10 BP 297 EP 309 PG 13 WC Cardiac & Cardiovascular Systems; Pharmacology & Pharmacy SC Cardiovascular System & Cardiology; Pharmacology & Pharmacy GA BG62C UT WOS:A1996BG62C00036 ER PT B AU SantamarinaFojo, S ApplebaumBowden, D Kobayashi, J Dugi, KA Maeda, N AF SantamarinaFojo, S ApplebaumBowden, D Kobayashi, J Dugi, KA Maeda, N BE Gotto, AM Paoletti, R Smith, LC Catapano, AL Jackson, AS TI Replacement of endothelial-bound lipolytic enzymes in lipase-deficient mice using recombinant adenovirus SO DRUGS AFFECTING LIPID METABOLISM: RISK FACTORS AND FUTURE DIRECTIONS SE MEDICAL SCIENCE SYMPOSIA SERIES LA English DT Proceedings Paper CT XII International Symposium of Drugs Affecting Lipid Metabolism (DALM XII) CY NOV 06-10, 1995 CL HOUSTON, TX SP Fdn Giovanni Lorenzini, Milan, Giovanni Lorenzini Med Fdn, Houston C1 NHLBI,MOL DIS BRANCH,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS BN 0-7923-4167-8 J9 MED SCI SYMP SER PY 1996 VL 10 BP 329 EP 335 PG 7 WC Cardiac & Cardiovascular Systems; Pharmacology & Pharmacy SC Cardiovascular System & Cardiology; Pharmacology & Pharmacy GA BG62C UT WOS:A1996BG62C00038 ER PT B AU Suomi, SJ AF Suomi, SJ BE Hertzman, C Kelly, S Bobak, M TI Biological, maternal, and life style interactions with the psychosocial environment: Primate models SO EAST-WEST LIFE EXPECTANCY GAP IN EUROPE: ENVIRONMENTAL AND NON-ENVIRONMENTAL DETERMINANTS SE NATO ADVANCED SCIENCES INSTITUTE SERIES, SER 2 LA English DT Proceedings Paper CT NATO Advanced Research Workshop on Environmental and Non-Environmental Determinants of the East/West Life Expectancy Gap CY MAR 20-22, 1995 CL SURREY, ENGLAND SP NATO, Int Sci Exchange Programme C1 NICHHD,COMPARAT ETHOL LAB,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS BN 0-7923-4207-0 J9 NATO ASI 2 PY 1996 VL 19 BP 133 EP 142 PG 10 WC Environmental Studies; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA BG48N UT WOS:A1996BG48N00010 ER PT S AU Rabin, O Chang, MCJ Grange, E Drieu, K Rapoport, SI AF Rabin, O Chang, MCJ Grange, E Drieu, K Rapoport, SI BE Christen, Y DroyLefaix, MT MaciasNunez, JF TI Effects of Ginkgo biloba extract (EGb 761) on cerebral postischemic lipid metabolism SO EFFECTS OF GINKGO BILOBA EXTRACT (EGB 761) ON NEURONAL PLASTICITY SE ADVANCES IN GINKGO BILOBA EXTRACT RESEARCH LA English DT Proceedings Paper CT 5th International Symposium on Effects of Ginkgo Biloba Extract (EGB 761) on Neuronal Plasticity CY SEP 30, 1996 CL SALAMANCA, SPAIN SP Ispen Inst DE ischemia; fatty acids; phospholipids; Ginkgo biloba extract RP Rabin, O (reprint author), NIA,NEUROSCI LAB,NATL INST HLTH,BLDG 10,ROOM 6C103,BETHESDA,MD 20892, USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER EDITIONS SCIENTIFIQUES PI PARIS PA 29 RUE BUFFON, 75005 PARIS, FRANCE SN 0927-9407 BN 2-906077-81-X J9 ADV GINKGO PY 1996 VL 5 BP 7 EP 19 PG 13 WC Neurosciences SC Neurosciences & Neurology GA BG02F UT WOS:A1996BG02F00002 ER PT J AU Gerloff, C Altenmuller, E Dichgans, J AF Gerloff, C Altenmuller, E Dichgans, J TI Disintegration and reorganization of cortical motor processing in two patients with cerebellar stroke SO ELECTROENCEPHALOGRAPHY AND CLINICAL NEUROPHYSIOLOGY LA English DT Article DE movement-related potentials; topographic mapping; cerebello-cerebral interaction; cerebellar stroke; recovery; plasticity ID CEREBRAL DIASCHISIS; PARKINSONS-DISEASE; NEURAL DISCHARGE; BRAIN POTENTIALS; MOVEMENT; CORTEX; INFARCTION; SCALP; RECOVERY; MONKEY AB Cerebello-cerebral interaction plays a fundamental role in movement processing. Extensively studied in monkeys, cerebello-thalamo-cerebral information processing is less clear in humans. Taking advantage of the tight linkage between cerebellum and cerebral motor cortex, the objective of this experiment was to gain information on cerebellar function, dysfunction and recovery by analyzing movement-related cortical potentials (MRCPs). MRCPs were recorded prior to voluntary repetitive finger movements from two cerebellar stroke patients, in the acute phase of cerebellar stroke and after clinical recovery. Ten normal subjects served as controls. The main result was a significant depression of late MRCP components over the contralateral motor cortex when patients performed index finger movements of the affected side in the acute phase, and improvement of depressed components after clinical recovery, 8-10 months later. Topographic maps of late MRCP components showed diffusely enlarged potential fields with ataxic movements in the acute phase, and re-focused fields on follow-up. We conclude that (1) late MRCP components are particularly sensitive to cerebellar input in humans and can reflect different functional states of the cerebellum, (2) disturbance of motor cortex function after cerebellar stroke (diaschisis) can occur as a temporary phenomenon that reverses with good clinical recovery. C1 UNIV TUBINGEN,DEPT NEUROL,D-72076 TUBINGEN,GERMANY. RP Gerloff, C (reprint author), NINDS,NIH,HMCS,BLDG 10,BETHESDA,MD 20892, USA. NR 46 TC 19 Z9 19 U1 0 U2 2 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0013-4694 J9 ELECTROEN CLIN NEURO JI Electroencephalogr. Clin. Neurophysiol. PD JAN PY 1996 VL 98 IS 1 BP 59 EP 68 DI 10.1016/0013-4694(95)00204-9 PG 10 WC Engineering, Biomedical; Clinical Neurology SC Engineering; Neurosciences & Neurology GA TY685 UT WOS:A1996TY68500010 PM 8689996 ER PT J AU Chang, HT Chrambach, A AF Chang, HT Chrambach, A TI Application of gels of 0.5 mm thickness to electrophoresis in the automated HPGE-1000 apparatus: Improved resolution SO ELECTROPHORESIS LA English DT Article DE automated gel electrophoresis apparatus; resolution; gel thickness AB Gel electrophoresis in commercial automated apparatus (HPGE-1000, LabIntelligence, Menlo Park, CA) is conventially conducted in gels of 3 mm thickness at about 15 V/cm. Since the intermittent scanning of the gel allows one to measure band width as a Function of migration time, resolution may be evaluated quantitatively. Comparing the value of resolution between two proteins in electrophoresis on agarose gels of 0.5 and 3.0 mm thickness and at various field strengths, it was found that within the given Joule heat dissipation capacity of the apparatus, resolution between the proteins is improved when the gel thickness is reduced from 3.0 to 0.5 mm, which allows for an increase in field strength from 15 V/cm, conventional for that apparatus, to 45 V/cm. C1 NICHHD,MACROMOLEC ANAL SECT,THEORET & PHYS BIOL LAB,NIH,BETHESDA,MD 20892. RI Chang, Huan-Tsung/C-1183-2011; OI Chang, Huan-Tsung/0000-0002-5393-1410 NR 10 TC 7 Z9 7 U1 0 U2 2 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0173-0835 J9 ELECTROPHORESIS JI Electrophoresis PD JAN PY 1996 VL 17 IS 1 BP 80 EP 83 DI 10.1002/elps.1150170114 PG 4 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA UD135 UT WOS:A1996UD13500013 PM 8907522 ER PT J AU Zakharov, SF Chang, HT Chrambach, A AF Zakharov, SF Chang, HT Chrambach, A TI Reproducibility of mobility in gel electrophoresis SO ELECTROPHORESIS LA English DT Article DE electrophoretic mobility; reproducibility; sodium dodecyl sulfate-polyacrylamide gel electrophoresis ID CONVEX FERGUSON PLOTS; PARTICLES; SIZE; FRAGMENTS; CHARGE; DNA AB The quantitative exploitation of gel electrophoresis to yield molecular and gel fiber properties rests on the assumption that mobility is characteristic of the macromolecule migrating as a band and is a physical constant for any system defined by pH, ionic strength and temperature. This assumption has not been tested intra-experimentally in previous literature. With the commercial introduction of automated gel electrophoresis apparatus, the collection of multiple mobility data during a single run without additional expense of labor has made it possible to test the assumption. As a start, we undertook that test for three proteins and their sodium dodecyl sulfate (SDS) derivatives, in agarose and polyacrylamide gel electrophoresis, various field strengths, continuous and discontinuous buffers, as well as intra- and interexperimentally. It was found that In agarose gel electrophoresis conducted in a single buffer, the standard deviation of mobility over a wide concentration range ranges intra-experimentally from 0.2 to 1.3% for two globular proteins and 1.4 to 5.3% for the same proteins derivatized with SDS. Interexperimentally, it was 3% in the single case tested to date. The standard deviation in polyacrylamide appears to be higher, Varies in inverse relation to the mobility value, i.e. increases with gel concentration in the range of 11 to 19% T, and varies substantially between the two SDS-proteins investigated. Mobility in a discontinuous buffer system decreases continuously due to the decreasing leading phase/trailing phase ratio along the migration path. The decrease is sharpest in the ''nonrestrictive'' stacking gel. C1 NICHHD,MACROMOLEC ANAL SECT,THEORET & PHYS BIOL LAB,NIH,BETHESDA,MD 20892. RI Chang, Huan-Tsung/C-1183-2011 NR 22 TC 11 Z9 11 U1 0 U2 3 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0173-0835 J9 ELECTROPHORESIS JI Electrophoresis PD JAN PY 1996 VL 17 IS 1 BP 84 EP 90 DI 10.1002/elps.1150170115 PG 7 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA UD135 UT WOS:A1996UD13500014 PM 8907523 ER PT J AU Stratakis, CA Mastorakos, G Magiakou, MA Papavasiliou, EC PanitsaFaflia, C Georgiadis, E Batrinos, ML AF Stratakis, CA Mastorakos, G Magiakou, MA Papavasiliou, EC PanitsaFaflia, C Georgiadis, E Batrinos, ML TI 24-hour secretion of growth hormone (GH), insulinlike growth factors-I and -II (IGF-I, -II), prolactin (PRL) and thyrotropin (TSH) in young adults of normal and tall stature. SO ENDOCRINE RESEARCH LA English DT Article ID IDIOPATHIC SHORT STATURE; SERUM SOMATOMEDIN-C; BINDING-PROTEIN; HEALTHY-CHILDREN; HUMAN-PLASMA; NORMAL BOYS; BODY-MASS; DEFICIENCY; AGE; ADOLESCENTS AB Studies of the growth hormone (GH) secretory dynamics of children with normal and idiopathic short stature (ISS) have revealed that the regulation of the GH-somatomedin (GHS) axis can differ significantly among normal individuals. Information on the GA secretion in idiopathic tall stature (ITS) is scarce. We previously showed that the GH response td stimulation with GH-releasing hormone (GHRH) in male, late adolescents and young adults with ITS is significantly greater than that of their sex and age-matched controls of average height. In the present study, we studied the 24-hour (hr) GH, insulin-like growth factor-I and -II (IGF-I and -II), prolactin (PRL) and thyroid-stimulating hormone (TSH) secretion by every 30 minutes (min) sampling in 12 young, healthy male Greek army recruits. Group I [n=6, age 22+1.4 years (y.), mean + standard deviation (SD)] had a height of 198.5+4.2cm, at least 3 SD's above the mean of the Greek male population. Group II (n=6, age 20.5+1.05 y.) had a height of 169.2+3.4cm, within 2SD's of the normal mean. Serum IGF-l levels were determined in both unextracted and extracted samples. Our results indicated that the number of secretory bursts and the circadian panel of GA, IGF-I and -II, PRL and TSH were similar in the two groups. Both the amplitude of the secretory GA peaks (5.08+3.07 vs. 3.3+0.8 ng/ml, p=0.19,) and the area under the curve (AUG) of the 24-hour GH secretion (9.8+5.5 vs. 6.6+1.3 ng/ml/hr, p=0.2) were higher in group I than in group II, but the difference was not significant. A significant nocturnal increase of both IGF-I and -II levels was found only in extracted human plasma (p<0.001), whereas measurements of IGF-I in unextracted samples failed to reveal circadian variation (p<0.1). We conclude that no significant differences were found in this pilot study of the neurosecretory regulation of the GAS axis between individuals of tall and normal stature. A tendency for greater amount of GH secretion per secretory peak was found in persons with tall stature; however, this finding needs to be confirmed in a larger study. IGF-I and -II levels had a significant circadian variation with a large nocturnal surge, when measured in extracted plasma. The latter, might be explained by circadian variation of the circulating IGF-binding proteins and its detection appears to be method of extraction-dependent. C1 NICHHD,DEB,SECT PEDIAT ENDOCRINOL,NIH,BETHESDA,MD 20892. RP Stratakis, CA (reprint author), UNIV ATHENS,EVGENIDON HOSP,ENDOCRINE UNIT,DEPT EXPT PHARMACOL 2,401 MIL HOSP,GR-11527 ATHENS,GREECE. NR 40 TC 12 Z9 12 U1 0 U2 1 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 SN 0743-5800 J9 ENDOCR RES JI Endocr. Res. PY 1996 VL 22 IS 3 BP 261 EP 276 PG 16 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VF504 UT WOS:A1996VF50400004 PM 8875138 ER PT J AU Aguilera, G Kiss, A Lu, A Camacho, C AF Aguilera, G Kiss, A Lu, A Camacho, C TI Regulation of adrenal steroidogenesis during chronic stress SO ENDOCRINE RESEARCH LA English DT Article; Proceedings Paper CT 7th Conference on the Adrenal Cortex CY JUN 27-30, 1996 CL CRIEFF, SCOTLAND ID ZONA GLOMERULOSA; HYPERRENINEMIC HYPOALDOSTERONISM; SECRETION; ADRENOCORTICOTROPIN AB The mechanism of the altered adrenal responsiveness during chronic stress was studied by analysis of ACTH and Ang II responses and the expression and activity of steroidogenic enzymes in the adrenal cortex of rats subjected to repeated immobilization (2 hr/day for 14 days), or repeated i.p. injection of 1.5 M NaCl. Concomitant with increased pregnenolone production and reduced aldosterone secretion by isolated adrenal glomerulosa cells of chronically stressed rats, P-450scc mRNA were increased and P-450aldo mRNA levels were decreased in adrenal zona glomerulosa. Consistent with elevated plasma corticosterone levels, isolated adrenal fasciculata cells from stressed rats showed higher cAMP, pregnenolone and corticosterone responses to ACTH. Adrenal fasciculata area and levels of P-450scc, but not those of P-450(11 beta) hydroxylase were significantly increased. The effects of repeated stress on adrenal steroidogenesis were mimicked by repeated ACTH injections. The half life of corticosterone in plasma measured with [H-3]corticosterone was increased in stressed rats but not in ACTH injected rats. This study shows that chronic stress leads to a) inhibition of mineralocorticoid secretion due to inhibition of the late biosynthetic pathway, and b) increased circulating glucocorticoids due to increased ACTH receptor activity, expression and activity of the early pathway, and decreased glucocorticoid clearance. Altered adrenal glomerulosa and fasciculata function, but not changes in glucocorticoid clearance, are probably mediated by increased ACTH secretion during chronic stress. RP Aguilera, G (reprint author), NICHHD,SECT ENDOCRINE PHYSIOL,DEB,NIH,BETHESDA,MD 20892, USA. NR 14 TC 23 Z9 24 U1 0 U2 4 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 SN 0743-5800 J9 ENDOCR RES JI Endocr. Res. PY 1996 VL 22 IS 4 BP 433 EP 443 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VX774 UT WOS:A1996VX77400017 PM 8969894 ER PT J AU Alavanja, MCR Brownson, RC Benichou, J Boice, J AF Alavanja, MCR Brownson, RC Benichou, J Boice, J TI Estimating the attributable risk of residential radon among nonsmoking women: Initial results and methodologic challenges SO ENVIRONMENT INTERNATIONAL LA English DT Article; Proceedings Paper CT 6th International Symposium on The Natural Radiation Environment (NRE-VI) CY JUN 05-09, 1995 CL MONTREAL, CANADA ID LUNG-CANCER; UNITED-STATES; DESIGN ISSUES; EXPOSURE; MISSOURI; RN; SMOKING; GLASS AB A population-based, case-control study of incident lung cancer among women in Missouri (United States) who were lifetime nonsmokers and long-term exsmokers was conducted between 1986 and 1992. The study included 538 lung cancer cases and 1183 population-based, age matched controls. Information on lung cancer risk factors was obtained by interviewing cases, next-of-kin of cases, and controls. Year-long radon measurements were also sought in every dwelling occupied for the previous 5-30 y. The Missouri study was among the first studies specifically-designed to evaluate the effects of residential radon on lung cancer risk. The mean radon lever found in homes was 1.6 pCi/L. This level of radon exposure is somewhat higher than that observed in the United States as a whole (mean 1.25 pCi/L). A small nonsignificant risk was found for study subjects exposed to a median domestic radon concentration of 4 pCi/L (25 y time-weight average). Since only a small fraction of the population is exposed at this level, it is estimated that the population attributable risk (PAR) for domestic radon is between 1 and 4% in Missouri. The growing body of residential studies has not clearly shown an elevation in lung cancer risk due to low-level, long-term radon exposure. It may be difficult to demonstrate a statistically significant increase in risk due in part to the inherent methodologic difficulties associated with assessing the potential carcinogenic effect of low-level radon exposure, errors in reconstructing past radon exposures, and population mobility which tends to homogenize exposures. A complementary method of radon exposure measurement, now being used in a second epidemiologic evaluation of lung cancer in Missouri, which uses heirloom grass to assess actual historic cumulative dose, is discussed, and may help strengthen future studies. Copyright (C) 1996 Elsevier Science Ltd. RP Alavanja, MCR (reprint author), NCI,DEPT HLTH & HUMAN SERV,NIH,BETHESDA,MD 20892, USA. NR 33 TC 1 Z9 1 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0160-4120 J9 ENVIRON INT JI Environ. Int. PY 1996 VL 22 SU 1 BP S1005 EP S1013 DI 10.1016/S0160-4120(96)00213-9 PG 9 WC Environmental Sciences SC Environmental Sciences & Ecology GA XK592 UT WOS:A1996XK59200131 ER PT J AU Zeiger, E Tennant, RW AF Zeiger, E Tennant, RW TI New animals, new uses, and old issues SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Editorial Material DE transgenic; mutagenesis; carcinogenesis; genetic engineering; genetic toxicity testing C1 NIEHS,LAB ENVIRONM CARCINOGENESIS & MUTAGENESIS,RES TRIANGLE PK,NC 27709. NR 0 TC 1 Z9 1 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PY 1996 VL 28 IS 1 BP 3 EP 4 DI 10.1002/(SICI)1098-2280(1996)28:1<3::AID-EM2>3.0.CO;2-I PG 2 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA UZ821 UT WOS:A1996UZ82100002 PM 8698044 ER PT J AU Nutley, EV Tcheong, AC Allen, JW Collins, BW Ma, M Lowe, XR Bishop, JB Moore, DH Wyrobek, AJ AF Nutley, EV Tcheong, AC Allen, JW Collins, BW Ma, M Lowe, XR Bishop, JB Moore, DH Wyrobek, AJ TI Micronuclei induced in round spermatids of mice after stem-cell treatment with chloral hydrate: Evaluations with centromeric DNA probes and kinetochore antibodies SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article DE mouse; spermatid; micronuclei; chloral hydrate; centromere; kinetochore; FISH; chromosome-specific DNA probes; X chromosome; cot-1 DNA ID IN-SITU HYBRIDIZATION; MOUSE BONE-MARROW; MALE GERM-CELLS; FLUORESCENCE INSITU HYBRIDIZATION; CHEMICALLY-INDUCED ANEUPLOIDY; RADIATION-INDUCED MICRONUCLEI; CHINESE-HAMSTER CELLS; GAMMA-SATELLITE DNA; CHROMOSOMAL INSTABILITY; HUMAN-LYMPHOCYTES AB The chromosomal effects of chloral hydrate (CH) on germ cells of male mice were investigated using two methods to detect and characterize spermatid micronuclei (SMN): (a) anti-kinetochore immunofluorescence (SMN-CREST) and (b) multicolor fluorescence in situ hybridization with DNA probes for centromeric DNA and repetitive sequences on chromosome X (SMN-FISH). B6C3F1 mice received single intraperitoneal (i.p.) injections of 82.7, 165.4, or 413.5 mg/kg and round spermatids were sampled at three time intervals representing cells treated in late meiosis, early meiosis, or as spermatogonial stem cells. No increases in the frequencies of SMN were detected for cells treated during meiosis using either SMN-CREST or SMN-FISH methods. After spermatogonial stem-cell treatment, however, elevated frequencies of SMN were detected by both methods. With SMN-FISH, dose trends were observed both in the frequencies of spermatids containing micronuclei and in the frequency of spermatids carrying centromeric label. These findings corroborate the recent report by Alien and colleagues [Alien JW et al.(1994): Mutat. Res. 323:81-88] that CH treatment of spermatogenic stem cells induced SMN. Furthermore, our findings suggest that chromosomal malsegregation or loss may occur in spermatids long after CH treatment of stem cells. Further studies are needed to understand the mechanism of action of the CH effect on stem cells and to determine whether similar effects are induced in human males treated with CH. (C) 1996 Wiley-Liss, Inc. C1 LAWRENCE LIVERMORE NATL LAB,BIOL & BIOTECHNOL RES PROGRAM,LIVERMORE,CA 94550. US EPA,DIV ENVIRONM CARCINOGENESIS,RES TRIANGLE PK,NC 27711. NATL INST ENVIRONM HLTH SCI,RES TRIANGLE PK,NC. FU NIEHS NIH HHS [Y01-ES-10203-00] NR 64 TC 11 Z9 11 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PY 1996 VL 28 IS 2 BP 80 EP 89 DI 10.1002/(SICI)1098-2280(1996)28:2<80::AID-EM3>3.0.CO;2-I PG 10 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA VM419 UT WOS:A1996VM41900003 PM 8844988 ER PT J AU Spencer, DL Caspary, WJ Hines, KC Tindall, KR AF Spencer, DL Caspary, WJ Hines, KC Tindall, KR TI 5-azacytidine-induced 6-thioguanine resistance at the gpt locus in AS52 cells: Cellular response SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article DE AS52 cells; 5-azacytidine; expression; gpt gene; mutagenesis; 6-thioguanine resistance ID CANCER CHEMOTHERAPEUTIC-AGENTS; SISTER-CHROMATID EXCHANGES; MAMMALIAN-CELLS; DNA-SYNTHESIS; MORPHOLOGICAL TRANSFORMATION; SALMONELLA-TYPHIMURIUM; C3H-10T1/2 CLONE-8; ESCHERICHIA-COLI; MUTAGENICITY; INDUCTION AB Treatment of AS52 cells with 5-azacytidine resulted in an induction of 6-thioguanine-resistant (6TG') colonies, which reached a maximum by an expression time of 9 days. Dose responses for both cytotoxicity and mutation induction were determined following treatment with 5-azacytidine. At 20 mu M treatment, 5-azacytidine exposure resulted in about 50% survival. Mutant frequency reached a maximum at 10 mu M At concentrations between 10 and 20 mu M, 5-azacytidine was a potent mutagen but did not exhibit a dose response. Although many compounds both induce cell death and affect the growth rate of cells, 5-azacytidine specifically induced cell death and did not affect the doubling time of the surviving treated cell population. (C) 1996 Wiley-Liss, Inc. C1 NIEHS,LAB ENVIRONM CARCINOGENESIS & MUTAGENESIS,RES TRIANGLE PK,NC 27709. NR 33 TC 2 Z9 2 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PY 1996 VL 28 IS 2 BP 100 EP 106 PG 7 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA VM419 UT WOS:A1996VM41900005 PM 8844990 ER PT J AU Bishop, JB Dellarco, VL Hassold, T Ferguson, LR Wyrobek, AJ Friedman, JM AF Bishop, JB Dellarco, VL Hassold, T Ferguson, LR Wyrobek, AJ Friedman, JM TI Aneuploidy in germ cells: Etiologies and risk factors SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Editorial Material DE toxicology; disease; genetics; reproduction; development ID BALANCED TRANSLOCATION; CYTOGENETICS; PREGNANCY; MICE AB A 2 1/2-day workshop on germ cell aneuploidy was convened September 11-13, 1995 at the National Institute of Environmental Health Sciences in Research Triangle Park, North Carolina to discuss current understandings of the etiology and origin of human aneuploidy, especially in regard to potential environmental causes, and to identify gaps in our research knowledge. The workshop was designed to facilitate interactions among research experts conducting studies on the fundamental biology of chromosomal movement and segregation, on aneuploidy as a human clinical problem, and on toxicological aspects of aneuploidy induction. Overview presentations provided perspectives on aneuploidy as a human clinical problem, the genetics of aneuploidy, and the issues of concern in toxicological testing and regulatory risk assessment. The four choirs introduced the topics for each of their workgroups, setting the stage for subsequent, in-depth discussions on (1) chromosome mover components, (2) altered recombination, (3) parental age effects, and (4) differential chromosome susceptibility. From these discussions, gaps in our research knowledge related to the role of the environment in the etiology of aneuploidy and associated molecular, cellular, and genetic processes involved were identified, and will be used to establish a research agenda for filling those gaps. (C) 1996 Wiley-Liss, Inc.(star) C1 US EPA,NATL CTR ENVIRONM ASSESSMENT,WASHINGTON,DC 20460. CASE WESTERN RESERVE UNIV,DEPT GENET,CLEVELAND,OH 44106. CASE WESTERN RESERVE UNIV,CTR HUMAN GENET,CLEVELAND,OH 44106. UNIV HOSP CLEVELAND,CLEVELAND,OH. AUCKLAND MED SCH,AUCKLAND,NEW ZEALAND. LAWRENCE LIVERMORE NATL LAB,LIVERMORE,CA. UNIV BRITISH COLUMBIA,DEPT MED GENET,VANCOUVER,BC,CANADA. RP Bishop, JB (reprint author), NIEHS,POB 12233,A2-10,RES TRIANGLE PK,NC 27709, USA. RI Ferguson, Lynnette/F-5989-2011 NR 28 TC 16 Z9 17 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PY 1996 VL 28 IS 3 BP 159 EP 166 PG 8 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA VR377 UT WOS:A1996VR37700001 PM 8908176 ER PT J AU Ferguson, LR Allen, JW Mason, JM AF Ferguson, LR Allen, JW Mason, JM TI Meiotic recombination and germ cell aneuploidy SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article; Proceedings Paper CT Workshop on Germ Cell Aneuploidy CY SEP 11-13, 1995 CL NATL INST ENVIRONM HLTH SCI, RES TRIANGLE PK, NC HO NATL INST ENVIRONM HLTH SCI DE recombination; meiosis; aneuploidy ID SISTER-CHROMATID COHESION; DOUBLE-STRAND BREAKS; SYNAPTONEMAL COMPLEX DAMAGE; DNA TOPOISOMERASE-II; DROSOPHILA-MELANOGASTER FEMALES; MICROTUBULE MOTOR PROTEIN; SACCHAROMYCES-CEREVISIAE; GENETIC-ANALYSIS; CROSSING-OVER; MEIOSIS-I AB Data on human trisomic conceptuses suggest that the extra chromosome commonly has a maternal origin, and the amount and position of crossing-over on nondisjoined chromosomes is commonly altered. These observations may provide important clues to the etiology of human germ cell aneuploidy, especially in regard to evaluating whether environmental factors play a role. There is concordance of effects of environmental agents on fungi, plants, and animals, which suggests that the overall process of meiosis is well conserved and that chemical and physical agents con affect meiotic recombination, leading to aneuploidy. It seems likely that meiosis in humans will fit the general pattern of meiosis in terms of sensitivity to radiation and chemicals. Thus studies on other organisms provide some insight into the procedures necessary for obtaining useful human date. For example, frequencies of spontaneous meiotic recombination ore not uniform per physical length in Drosophila, and different regions of a chromosome respond differently to treatment. Treatments that relieve constraints on the distribution of meiotic exchange, without changing greatly the overall frequency of exchange, may increase the number of univalents and give the impression that there are chromosome-specific responses. Recombination studies that monitor one or a few relatively short genetic regions may also give a false impression of the effects of a treatment on recombination. In addition, meiotic mutants in Saccharomyces and Drosophila highlight a number of processes that are important for production of an exchange event and the utility of that event in the proper segregation of both homologues and sisters. They also suggest that tests for pairing at pachytene, chiasmata at diplotene, and genetic crossing-over may give different results. (C) 1996 Wiley-Liss, Inc(star) C1 NIEHS,MOL GENET LAB,RES TRIANGLE PK,NC 27709. UNIV AUCKLAND,SCH MED,CANC RES LAB,AUCKLAND,NEW ZEALAND. US EPA,DIV ENVIRONM CARCINOGENESIS,RES TRIANGLE PK,NC 27711. RI Ferguson, Lynnette/F-5989-2011 NR 178 TC 21 Z9 21 U1 1 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PY 1996 VL 28 IS 3 BP 192 EP 210 PG 19 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA VR377 UT WOS:A1996VR37700005 PM 8908180 ER PT J AU Gorelick, NJ Tindall, KR Glickman, BW AF Gorelick, NJ Tindall, KR Glickman, BW TI Introduction: State of the art in transgenic animals in mutation research SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Editorial Material ID LACL C1 NATL INST ENVIRONM HLTH SCI,LAB ENVIRONM CARCINOGENESIS & MUTAGENESIS,RES TRIANGLE PK,NC. UNIV VICTORIA,DEPT BIOL,VICTORIA,BC,CANADA. RP Gorelick, NJ (reprint author), PROCTER & GAMBLE CO,IVORYDALE TECH CTR,MIAMI VALLEY LABS,5299 SPRING GROVE AVE,CINCINNATI,OH 45217, USA. NR 8 TC 6 Z9 6 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PY 1996 VL 28 IS 4 BP 295 EP 298 PG 4 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA XK218 UT WOS:A1996XK21800001 PM 8991056 ER PT J AU deBoer, JG Mirsalis, JC Provost, GS Tindall, KR Glickman, BW AF deBoer, JG Mirsalis, JC Provost, GS Tindall, KR Glickman, BW TI Spectrum of mutations in kidney, stomach, and liver from lacl transgenic mice recovered after treatment with tris(2,3-dibromopropyl)phosphate SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article; Proceedings Paper CT Satellite Meeting on the State of the Art in Transgenic Animals in Mutation Research, at the 1996 Annual Meeting of the Environmental-Mutagen-Society CY 1996 CL VANCOUVER ISL, CANADA SP Environm Mutagen Soc DE Big Blue(R); mutational spectra; DNA sequencing; tissue specificity; mutational frequency ID FLAME-RETARDANT; REACTIVE METABOLITE; COVALENT BINDING; PROLIFERATION; MUTAGENICITY; GENOTOXICITY; PHOSPHATE; INVITRO; RAT AB The flame retardant tris (2,3-dibromopropyl)phosphate (TDBP), once used in cotton sleepware for children, is presently banned from commerce. it produces tumors in rodents in both a sex- and tissue-specific manner. The kidney is the main target for tumor formation in male and female rats, as well as in male mice. In contrast, tumors are formed in the liver of female animals. We have used lacl transgenic male B6C3F1 mice (Big Blue(R)) to examine the induction of mutation in kidney, liver, and stomach after exposure to 150 mg/kg (2 days), 300 mg/kg (4 days), and 600 mg/kg (4 days) of TDBP. At the highest dose, the mutant frequency was approximately 50% above control values in the kidney (P < 0.01). A smaller increase was observed in the liver (P = 0.07), while no increase was seen in the stomach (P = 0.28). Sequence analysis of the recovered mutants showed a TDBP-specific change in mutation spectrum in kidney, which was not observed in liver and stomach. In kidney, a dose-dependent decrease in G:C --> A:T transitions, including at 5'-CpG3' sites, was observed. This was accompanied by an increase in the loss of single G:C base pairs from approximately 3% to 15%. These results illustrate both the sensitivity and specificity of the lacl transgenic system in the analysis of tissue-specific mutation. This study also reinforces the importance of examining mutational spectra when mutant induction levels are low. (C) 1996 Wiley-Liss, Inc. C1 SRI INT, MENLO PK, CA 94025 USA. STRATOGENE INC, LA JOLLA, CA USA. NATL INST ENVIRONM HLTH SCI, LAB ENVIRONM CARCINOGENESIS & MUTAGENIS, RES TRIANGLE PK, NC USA. RP deBoer, JG (reprint author), UNIV VICTORIA, DEPT BIOL, CTR ENVIRONM HLTH, VICTORIA, BC V8W 3N5, CANADA. FU NIEHS NIH HHS [N01-ES-35365] NR 24 TC 27 Z9 27 U1 1 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PY 1996 VL 28 IS 4 BP 418 EP 423 PG 6 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA XK218 UT WOS:A1996XK21800017 PM 8991072 ER PT J AU Chan, PC AF Chan, PC TI Effect of ethanol on urethane carcinogenesis SO ENVIRONMENTAL CARCINOGENESIS & ECOTOXICOLOGY REVIEWS-PART C OF JOURNAL OF ENVIRONMENTAL SCIENCE AND HEALTH LA English DT Review ID ETHYL CARBAMATE URETHANE; SISTER-CHROMATID EXCHANGES; BLOOD-ALCOHOL CONCENTRATIONS; UPPER ALIMENTARY-TRACT; FISCHER 344 RATS; VINYL CARBAMATE; N-NITROSODIMETHYLAMINE; BONE-MARROW; POSSIBLE RELEVANCE; EXPOSURE OCCURS RP Chan, PC (reprint author), NIEHS,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 130 TC 0 Z9 0 U1 0 U2 1 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 SN 1059-0501 J9 ENVIRON CARCIN ECO R JI Environ. Carcinog. Ecotoxical. Rev.-Pt. C J. Env. Sci. Health PY 1996 VL 14 IS 1 BP 43 EP 62 PG 20 WC Oncology; Environmental Sciences; Toxicology SC Oncology; Environmental Sciences & Ecology; Toxicology GA UR057 UT WOS:A1996UR05700002 ER PT J AU Cannon, DJ Fung, VA AF Cannon, DJ Fung, VA TI alpha,beta-unsaturated ketones class study: Development of chemical nominations for carcinogenicity testing SO ENVIRONMENTAL CARCINOGENESIS & ECOTOXICOLOGY REVIEWS-PART C OF JOURNAL OF ENVIRONMENTAL SCIENCE AND HEALTH LA English DT Review ID SALMONELLA-TYPHIMURIUM; CARBONYL-COMPOUNDS; AMES TEST; MUTAGENICITY; GENOTOXICITY; IDENTIFICATION; CONSTITUENTS; GLUTATHIONE; MECHANISMS; SUBSTANCES C1 NCI,US DEPT HHS,BETHESDA,MD 20892. RP Cannon, DJ (reprint author), TECH RESOURCES INT INC,3202 TOWER OAKS BLVD,ROCKVILLE,MD 20852, USA. NR 51 TC 1 Z9 1 U1 1 U2 2 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 SN 1059-0501 J9 ENVIRON CARCIN ECO R JI Environ. Carcinog. Ecotoxical. Rev.-Pt. C J. Env. Sci. Health PY 1996 VL 14 IS 2 BP 139 EP 157 PG 19 WC Oncology; Environmental Sciences; Toxicology SC Oncology; Environmental Sciences & Ecology; Toxicology GA VQ214 UT WOS:A1996VQ21400003 ER PT B AU Bouville, A AF Bouville, A BE Till, JE TI Reconstructing doses to downwinders from fallout SO ENVIRONMENTAL DOSE RECONSTRUCTION AND RISK IMPLICATIONS: NCRP - PROCEEDINGS OF THE THIRTY-FIRST ANNUAL MEETING, 12-13 APRIL, 1995, AS PRESENTED AT THE CRYSTAL CITY MARRIOTT, ARLINGTON, MA, ISSUED OCTOBER 1, 1996 SE PROCEEDINGS OF THE NATIONAL COUNCIL ON RADIATION PROTECTION AND MEASUREMENTS LA English DT Proceedings Paper CT 31st Annual Meeting of the National-Council-on-Radiation-Protection-and-Measurement on Environmental Dose Reconstruction and Risk Implications CY APR 12-13, 1995 CL ARLINGTON, VA SP Natl Council Radiat Protect & Measurements RP Bouville, A (reprint author), NCI,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATL COUNCIL RADIATION PROTECTION MEASUREMENTS PI BETHESDA PA 7910 WOODMONT AVE, SUITE 1016, BETHESDA, MD 20814 BN 0-929600-53-3 J9 P NAT C RAD PY 1996 IS 17 BP 171 EP 189 PG 19 GA BH67M UT WOS:A1996BH67M00010 ER PT B AU Land, CE AF Land, CE BE Till, JE TI Epidemiological studies of downwinders SO ENVIRONMENTAL DOSE RECONSTRUCTION AND RISK IMPLICATIONS: NCRP - PROCEEDINGS OF THE THIRTY-FIRST ANNUAL MEETING, 12-13 APRIL, 1995, AS PRESENTED AT THE CRYSTAL CITY MARRIOTT, ARLINGTON, MA, ISSUED OCTOBER 1, 1996 SE PROCEEDINGS OF THE NATIONAL COUNCIL ON RADIATION PROTECTION AND MEASUREMENTS LA English DT Proceedings Paper CT 31st Annual Meeting of the National-Council-on-Radiation-Protection-and-Measurement on Environmental Dose Reconstruction and Risk Implications CY APR 12-13, 1995 CL ARLINGTON, VA SP Natl Council Radiat Protect & Measurements AB There have been numerous epidemiological studies of cancer risk among residents of areas downwind from the Nevada Test Site where atmospheric weapons tests were conducted during 1951-1963. These studies were of varying quality, but at least two were major undertakings involving individual radiation dosimetry. Although some innovative and sophisticated approaches were employed, the overall scientific value of the studies is limited by the fact that radiation doses were so low as to almost preclude the possibility of learning anything new about risk. The sole, arguable exception concerns thyroid cancer risk from childhood exposure to I-131, a question about which very little is known. RP Land, CE (reprint author), NCI,BETHESDA,MD 20892, USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU NATL COUNCIL RADIATION PROTECTION MEASUREMENTS PI BETHESDA PA 7910 WOODMONT AVE, SUITE 1016, BETHESDA, MD 20814 BN 0-929600-53-3 J9 P NAT C RAD PY 1996 IS 17 BP 311 EP 328 PG 18 GA BH67M UT WOS:A1996BH67M00020 ER PT B AU Beebe, G AF Beebe, G BE Till, JE TI Epidemiologic studies based on the Chernobyl accident SO ENVIRONMENTAL DOSE RECONSTRUCTION AND RISK IMPLICATIONS: NCRP - PROCEEDINGS OF THE THIRTY-FIRST ANNUAL MEETING, 12-13 APRIL, 1995, AS PRESENTED AT THE CRYSTAL CITY MARRIOTT, ARLINGTON, MA, ISSUED OCTOBER 1, 1996 SE PROCEEDINGS OF THE NATIONAL COUNCIL ON RADIATION PROTECTION AND MEASUREMENTS LA English DT Proceedings Paper CT 31st Annual Meeting of the National-Council-on-Radiation-Protection-and-Measurement on Environmental Dose Reconstruction and Risk Implications CY APR 12-13, 1995 CL ARLINGTON, VA SP Natl Council Radiat Protect & Measurements RP Beebe, G (reprint author), NCI,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATL COUNCIL RADIATION PROTECTION MEASUREMENTS PI BETHESDA PA 7910 WOODMONT AVE, SUITE 1016, BETHESDA, MD 20814 BN 0-929600-53-3 J9 P NAT C RAD PY 1996 IS 17 BP 339 EP 350 PG 12 GA BH67M UT WOS:A1996BH67M00022 ER PT B AU Cantor, KP AF Cantor, KP BE Bertollini, R Lebowitz, MD Saracci, R Savitz, DA TI Epidemiologic research priorities on the health risk of drinking water contaminants SO ENVIRONMENTAL EPIDEMIOLOGY: EXPOSURE AND DISEASE LA English DT Proceedings Paper CT International Workshop on Priorities in Environmental Epidemiology CY JAN, 1993 CL ROME, ITALY SP WHO, European Ctr Environm & Hlth, Rome Div RP Cantor, KP (reprint author), NCI,ENVIRONM EPIDEMIOL BRANCH,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LEWIS PUBLISHERS INC PI BOCA RATON PA 2000 CORPORATE BLVD NW, BOCA RATON, FL 33431 BN 1-56670-067-1 PY 1996 BP 63 EP 82 PG 20 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA BG84C UT WOS:A1996BG84C00005 ER PT B AU Blair, A Zahm, SH AF Blair, A Zahm, SH BE Bertollini, R Lebowitz, MD Saracci, R Savitz, DA TI Pesticides and cancer: Status and priorities SO ENVIRONMENTAL EPIDEMIOLOGY: EXPOSURE AND DISEASE LA English DT Proceedings Paper CT International Workshop on Priorities in Environmental Epidemiology CY JAN, 1993 CL ROME, ITALY SP WHO, European Ctr Environm & Hlth, Rome Div RP Blair, A (reprint author), NCI,OCCUPAT STUDIES SECT,BETHESDA,MD 20892, USA. RI Zahm, Shelia/B-5025-2015 NR 0 TC 2 Z9 2 U1 0 U2 0 PU LEWIS PUBLISHERS INC PI BOCA RATON PA 2000 CORPORATE BLVD NW, BOCA RATON, FL 33431 BN 1-56670-067-1 PY 1996 BP 83 EP 97 PG 15 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA BG84C UT WOS:A1996BG84C00006 ER PT J AU Corcoran, ML Hewitt, RE Kleiner, DE StetlerStevenson, WG AF Corcoran, ML Hewitt, RE Kleiner, DE StetlerStevenson, WG TI MMP-2: Expression, activation and inhibition SO ENZYME & PROTEIN LA English DT Article DE invasion; metastasis; gelatinase; activation ID ERYTHROID-POTENTIATING ACTIVITY; STROMELYSIN GENE-EXPRESSION; CONSERVED PEPTIDE SEQUENCE; GROWTH-PROMOTING ACTIVITY; MESSENGER-RNA EXPRESSION; HUMAN FIBROSARCOMA CELLS; HUMAN-TISSUE INHIBITOR; IV COLLAGENASE GENE; MATRIX METALLOPROTEINASE; PLASMINOGEN-ACTIVATOR AB Remodeling of the extracellular matrix (ECM), which occurs during many physiological and pathological processes, is one of the requisite events of cellular invasion. The matrix metalloproteinases (MMPs) are a family of zinc-dependent proteases that are responsible for proteolytic degradation of specific ECM components. Regulating the activity of the MMPs at both mRNA and/or protein levels modulates the degradation of the ECM components which in turn alter cellular invasion. Although most MMPs are regulated via similar mechanisms at the mRNA and protein levels, the modulation of gelatinase A is unique. Understanding the mechanisms that regulate gelatinase A is important since expression and activation of this particular MMP is consistently correlated with a majority of malignant phenotypes. In this report, we will contrast the mechanisms that regulate the expression, activation and inhibition of gelatinase A with the mechanisms that modulate the rest the MMP family. C1 NCI,EXTRACELL MATRIX PATHOL SECT,PATHOL LAB,DIV CLIN SCI,NIH,BETHESDA,MD 20892. RI Stetler-Stevenson, William/H-6956-2012; OI Stetler-Stevenson, William/0000-0002-5500-5808; Kleiner, David/0000-0003-3442-4453 NR 79 TC 161 Z9 165 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1019-6773 J9 ENZYME PROTEIN JI Enzyme Protein PY 1996 VL 49 IS 1-3 BP 7 EP 19 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VD919 UT WOS:A1996VD91900002 PM 8796994 ER PT J AU Hewitt, R Dano, K AF Hewitt, R Dano, K TI Stromal cell expression of components of matrix-degrading protease systems in human cancer SO ENZYME & PROTEIN LA English DT Article DE cancer; stroma; proteases; invasion ID IN-SITU HYBRIDIZATION; HUMAN COLON-CANCER; UROKINASE PLASMINOGEN-ACTIVATOR; COLLAGENASE GENE-EXPRESSION; TIMP-2 MESSENGER-RNAS; IV COLLAGENASE; STROMELYSIN-3 GENE; TISSUE INHIBITOR; BREAST-CANCER; GELATINASE-A AB Components of matrix-degrading protease systems are in human cancer often expressed by tumour-infiltrating stromal cells. The cellular pattern of expression of these molecules appears to be unique for each type of cancer. In several cases there are similarities with patterns observed in nonmalignant remodelling processes in the same tissue. These findings indicate that the stromal cells actively participate in the process of cancer invasion. The implications of this new paradigm for cancer biology and cancer treatment are discussed. RP Hewitt, R (reprint author), NCI, PATHOL LAB,NIH,BLDG 10,RM B1B58, 10 CTR DR MSC 1500, BETHESDA, MD 20892 USA. NR 88 TC 64 Z9 66 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1019-6773 J9 ENZYME PROTEIN JI Enzyme Protein PY 1996 VL 49 IS 1-3 BP 163 EP 173 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VD919 UT WOS:A1996VD91900012 PM 8797004 ER PT J AU Cocco, P Ward, MH Buiatti, E AF Cocco, P Ward, MH Buiatti, E TI Occupational risk factors for gastric cancer: An overview SO EPIDEMIOLOGIC REVIEWS LA English DT Review ID NITRATE FERTILIZER WORKERS; CAUSE-SPECIFIC MORTALITY; HELICOBACTER-PYLORI INFECTION; BRITISH RUBBER INDUSTRY; REDUCTION PLANT WORKERS; ETHYLENE-OXIDE WORKERS; TEXAS OIL REFINERIES; PEST-CONTROL WORKERS; STOMACH-CANCER; LUNG-CANCER C1 NCI, OCCUPAT EPIDEMIOL BRANCH, DIV CANC EPIDEMIOL, BETHESDA, MD 20892 USA. UNIV CAGLIARI, IST MED LAVORO, CAGLIARI, ITALY. CTR STUDIO & PREVENZ ONCOL, UNITA EPIDEMIOL USL 17E, I-50131 FLORENCE, ITALY. NR 231 TC 35 Z9 35 U1 3 U2 5 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0193-936X EI 1478-6729 J9 EPIDEMIOL REV JI Epidemiol. Rev. PY 1996 VL 18 IS 2 BP 218 EP 234 PG 17 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA WF379 UT WOS:A1996WF37900009 PM 9021314 ER PT J AU Stein, U Shoemaker, RH Schlag, PM AF Stein, U Shoemaker, RH Schlag, PM TI MDR1 gene expression: Evaluation of its use as a molecular marker for prognosis and chemotherapy of bone and soft tissue sarcomas SO EUROPEAN JOURNAL OF CANCER LA English DT Article DE multidrug resistance; MDR1 gene; P-glycoprotein; bone and soft tissue sarcomas ID MULTIDRUG-RESISTANCE GENE; PRODUCT P-GLYCOPROTEIN; MONOCLONAL-ANTIBODIES; DRUG-RESISTANCE; IMMUNOHISTOCHEMICAL DETECTION; CELL-LINES; TOPOISOMERASE-II; CLINICAL-TRIALS; HUMAN CANCERS; HUMAN-TUMORS AB Successful chemotherapeutic treatment of malignant tumours is often limited by the intrinsic or acquired multidrug resistance (MDR). The classical MDR phenotype is characterised by reduced drug accumulation within the cell, caused by overexpression of the MDR1 gene encoded P-glycoprotein. Some reports have been published evaluating MDR1 expression as a molecular marker for response to chemotherapy in human bone and soft tissue sarcomas. In this review, an attempt is made to summarise the accuracy of the measurement of MDR1 expression for use in prognosis, as well as in decisions on chemotherapeutic treatment of sarcomas. In addition, general problems for the performance of such studies is discussed. C1 NCI,FREDERICK CANC RES & DEV CTR,FREDERICK,MD. UNIV KLINIKUM RUDOLF VIRCHOW,MAX DELBRUCK CENTRUM MOLEK MED,ROBERT ROSSLE KLIN ONKOL,BERLIN,GERMANY. RP Stein, U (reprint author), MAX DELBRUCK CENTRUM MOLEK MED,ROBERT ROSSLE STR 10,D-13122 BERLIN,GERMANY. NR 82 TC 24 Z9 25 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD JAN PY 1996 VL 32A IS 1 BP 86 EP 92 DI 10.1016/0959-8049(95)00478-5 PG 7 WC Oncology SC Oncology GA TZ633 UT WOS:A1996TZ63300019 PM 8695249 ER PT J AU Xu, X Azumi, N Skelton, HG Hearing, VJ Gersten, DM AF Xu, X Azumi, N Skelton, HG Hearing, VJ Gersten, DM TI Immunostaining of human melanomas by a monoclonal antibody to B700 mouse melanoma antigen SO EUROPEAN JOURNAL OF CANCER LA English DT Article DE melanoma; B700; diagnosis; monoclonal antibody ID HUMAN-MALIGNANT-MELANOMA; BOVINE SERUM-ALBUMIN; MURINE MELANOMA; NEURO-BLASTOMA; CELLS; REACTIVITY; DIAGNOSIS; PROTEINS; TUMORS AB Previous studies have shown that B700, an albumin-like murine melanoma antigen, has a human homologue termed H700. Polyclonal antibodies to B700 also bind to all cultured human, swine and hamster melanoma cells, suggesting that B700 is a ''pan-melanoma'' antigen. The objects of this investigation were: (a) to determine if 2-3-3, a monoclonal antibody to B700, can be used to identify human melanomas in formalin-fixed, paraffin-embedded tissues, and (b) to determine the specificity and potential diagnostic value of 2-3-3. Forty-eight of the 49 human melanomas, including spindle melanoma cells, stained positively, as did five of the eight pigmented naevi including cellular spindle naevi. Twenty-six of the 32 human non-melanomatous lesions were negative for 2-3-3 staining (weakly positive on one breast carcinoma and positive on five neural tumours). These results indicate that 2-3-3, a monoclonal antibody to the mouse melanoma antigen B700, can be used to identify H700 in archival specimens. 2-3-3 may have an advantage over HMB45, which is the most commonly used antibody for melanoma diagnosis, because of its immunoreactivity with spindle melanocytic lesions. Antibodies to B700 may prove to be a useful adjunct in the diagnosis of human melanoma and related lesions. C1 GEORGETOWN UNIV,MED CTR,DEPT PATHOL,WASHINGTON,DC 20007. ARMED FORCES INST PATHOL,DEPT DERMATOPATHOL,WASHINGTON,DC 20306. NCI,CELL BIOL LAB,NIH,BETHESDA,MD 20892. NR 30 TC 4 Z9 4 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD JAN PY 1996 VL 32A IS 1 BP 168 EP 173 DI 10.1016/0959-8049(95)00546-3 PG 6 WC Oncology SC Oncology GA TZ633 UT WOS:A1996TZ63300032 PM 8695227 ER PT J AU Young, NS AF Young, NS TI Introduction SO EUROPEAN JOURNAL OF HAEMATOLOGY LA English DT Editorial Material RP Young, NS (reprint author), NHLBI,HEMATOL BRANCH,BETHESDA,MD 20892, USA. NR 7 TC 1 Z9 1 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0902-4441 J9 EUR J HAEMATOL JI Eur. J. Haematol. PY 1996 VL 57 SU 60 BP 6 EP 8 PG 3 WC Hematology SC Hematology GA VX757 UT WOS:A1996VX75700002 ER PT J AU Kaufman, DW Kelly, JP Jurgelon, JM Anderson, T Issaragrisil, S Wiholm, BE Young, NS Leaverton, P Levy, M Shapiro, S AF Kaufman, DW Kelly, JP Jurgelon, JM Anderson, T Issaragrisil, S Wiholm, BE Young, NS Leaverton, P Levy, M Shapiro, S TI Drugs in the aetiology of agranulocytosis and aplastic anaemia SO EUROPEAN JOURNAL OF HAEMATOLOGY LA English DT Article; Proceedings Paper CT Workshop on Drug-Related Blood Dyscrasias CY OCT 12-14, 1995 CL SALTSJOBADEN, SWEDEN SP Astra DE agranulocytosis; aplastic anaemia; IAAAS; drug-induced ID ANEMIA AB Agranulocytosis and aplastic anaemia are rare but serious conditions known to be caused by numerous drugs. Most of what is known or suspected about the aetiology is based on case reports, with only a few formal epidemiological studies that provide quantitative estimates of risk. Updated results have been obtained from a combined analysis of data from 3 case-control studies that used similar methods: the International Agranulocytosis and Aplastic Anemia Study (IAAAS), conducted in Israel and Europe; a study conducted in the northeast US; and a study conducted in Thailand, Totals of 362 cases of agranulocytosis, 454 cases of aplastic anaemia and 6458 controls were included in the analyses. The IAAAS and Thai study were population-based, providing estimates of the incidence of the 2 dyscrasias. The overall annual incidence of agranulocytosis in the ambulatory population was 3.4/10(6) in the IAAAS and 0.8/10(6) in Thailand; by contrast the incidence of aplastic anaemia was 2.0/10(6) in the IAAAS and 4.1/10(6) in Thailand. A total of 21 compounds were significantly associated with an increased risk of agranulocytosis in the IAAAS and US studies. Excess risks ranged from 0.06 to 13 cases/10(6) users/wk; the most strongly associated drugs were procainamide, anti-thyroid drugs and sulphasalazine. An association with drugs that had previously been suspected was also seen in Thailand. The overall aetiologic fractions of agranulocytosis due to drug use were 62% in the IAAAS, 72% in the US and 70% in Thailand. Eleven drugs were significantly associated with an increased risk of aplastic anaemia, with excess risks ranging from 1.4 to 60 cases/10(6) users in a 5-month period. The most strongly associated drugs were penicillamine, gold and carbamazepine. Aetiologic fractions were 27% in the IAAAS, 17% in the US and 2% in Thailand, which paralleled the prevalence of use of associated drugs in the 3 populations. The present results confirm that agranulocytosis is largely a drug-induced disease, with similar proportions accounted for in 3 disparate geographic regions. By contrast, although many of the expected associations were observed for aplastic anaemia, most of the aetiology is not explained by drugs. For all associated drugs, the excess risks are sufficiently low that blood dyscrasias should not figure prominently in the balancing of risks and benefits. C1 MAHIDOL UNIV,SRIRAJ HOSP,DIV HEMATOL,DEPT MED,BANGKOK 10700,THAILAND. NATL BOARD HLTH & WELF,DEPT MED,UPPSALA,SWEDEN. NHLBI,CLIN HEMATOL BRANCH,BETHESDA,MD 20892. UNIV S FLORIDA,COLL PUBL HLTH,DEPT BIOSTAT & EPIDEMIOL,TAMPA,FL. HADASSAH UNIV HOSP,DEPT MED,CLIN PHARMACOL UNIT,IL-91240 JERUSALEM,ISRAEL. RP Kaufman, DW (reprint author), BOSTON UNIV,SCH MED,SLONE EPIDEMIOL UNIT,1371 BEACON ST,BROOKLINE,MA 02146, USA. OI Issaragrisil, Surapol/0000-0002-8924-0646 NR 8 TC 21 Z9 23 U1 2 U2 2 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0902-4441 J9 EUR J HAEMATOL JI Eur. J. Haematol. PY 1996 VL 57 SU 60 BP 23 EP 30 PG 8 WC Hematology SC Hematology GA VX757 UT WOS:A1996VX75700005 ER PT J AU Young, NS AF Young, NS TI Immune pathophysiology of acquired aplastic anaemia SO EUROPEAN JOURNAL OF HAEMATOLOGY LA English DT Article; Proceedings Paper CT Workshop on Drug-Related Blood Dyscrasias CY OCT 12-14, 1995 CL SALTSJOBADEN, SWEDEN SP Astra DE aplastic anaemia; autoimmunity; stem cells; apoptosis; immunosuppression ID HEMATOPOIETIC PROGENITOR CELLS; NECROSIS-FACTOR-ALPHA; BONE-MARROW FAILURE; INTERFERON-GAMMA; FAS ANTIGEN; ANTILYMPHOCYTE GLOBULIN; GENE-EXPRESSION; ANEMIA PATIENTS; STEM-CELL; IN-VITRO AB Clinical observations and laboratory studies have supported an immune basis for most acquired aplastic anaemias, with the majority of patients responding to immunosuppressive therapy. In vitro, interferon (IFN) and tumour necrosis factor (TNF) inhibit haematopoiesis, including colony formation by early and late progenitor cells and the generation of long-term culture initiating cells (LTCIC). These lymphokines induce Fas antigen expression on CD34(+) cells and apoptosis within the haematopoietic cell compartment. Local secretion of cytokines is far more potent than addition to long-term bone marrow cultures. Activated cytotoxic lymphocytes, high levels of INF gamma and TNF alpha, and increased Fas expression an CD34(+) marrow cells are present in patients. Haematopoiesis is severely diminished in severe aplastic anaemia on presentation: CD34(+) cell numbers, colony forming cells and LTCIC are all markedly decreased. LTCIC numbers do not predict recovery. Blood cell counts increase in some cases in the absence of changed numbers of LTCIC, but recovered patients have higher and sometimes normal LTCIC numbers. The mechanism by which chemical and biological agents incite altered immunity remains unclear. Drug associations have been inferred from case reports and formal epidemiological studies, but have remained refractory to systematic laboratory study. Whatever the initial events, immune system destruction of haematopoiesis plays a central role in the development of acquired aplastic anaemia. C1 NHLBI,HEMATOL BRANCH,BETHESDA,MD 20892. NR 38 TC 8 Z9 12 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0902-4441 J9 EUR J HAEMATOL JI Eur. J. Haematol. PY 1996 VL 57 SU 60 BP 55 EP 59 PG 5 WC Hematology SC Hematology GA VX757 UT WOS:A1996VX75700010 ER PT J AU Pohl, LR Pumford, NR Martin, JL AF Pohl, LR Pumford, NR Martin, JL TI Mechanisms, chemical structures and drug metabolism SO EUROPEAN JOURNAL OF HAEMATOLOGY LA English DT Article; Proceedings Paper CT Workshop on Drug-Related Blood Dyscrasias CY OCT 12-14, 1995 CL SALTSJOBADEN, SWEDEN SP Astra DE idiosyncratic drug toxicity; drug allergy; protein adducts; reactive metabolites; halothane hepatitis; autoantibodies ID ENDOPLASMIC-RETICULUM ANTIBODIES; HALOTHANE HEPATITIS PATIENTS; PROTEIN DISULFIDE-ISOMERASE; SERUM ANTIBODIES; HUMAN-LIVER; NONCOVALENT INTERACTIONS; NEOANTIGENS; EXPRESSION; COVALENT; ANTIGENS AB From the studies that have been done by many laboratories over the last 2 decades, it is now clear that the toxicities produced by many drugs are due to their reactive metabolites. It is thought that, in many cases, reactive metabolites cause toxicity by binding covalently to tissue proteins, However, until recently it was difficult to identify these protein targrts. Due to the development of an immunochemical approach, this problem has been overcome, as is illustrated here by studies that have been conducted on the metabolic basis of the idiosyncratic hepatitis caused by the inhalation anaesthetic halothane. The major problem to solve in the future will be to determine how protein adduct formation leads to toxicity. It is possible that protein adduct formation may alter an important cellular function or may lead to immunopathology, as is thought to occur in the case of halothane hepatitis. If an allergic reaction is suspected, purified protein targets or reactive metabolites can sct?ie as antigens for identifying sensitized individuals, This information can be used to prevent not only an allergic reaction to the drug, but possibly cross-reactions to other drugs that are structurally related. Another important application of these studies is the design of safer alternative drugs that will not produce structurally similar toxic reactive metabolites. C1 UNIV ARKANSAS MED SCI HOSP,DIV TOXICOL,LITTLE ROCK,AR 72205. JOHNS HOPKINS MED INST,DEPT ANESTHESIOL & CRIT CARE MED,BALTIMORE,MD 21205. RP Pohl, LR (reprint author), NHLBI,MOL & CELLULAR TOXICOL SECT,LAB MOL IMMUNOL,NIH,BLDG 10,ROOM 8N 110,BETHESDA,MD 20892, USA. NR 46 TC 11 Z9 11 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0902-4441 J9 EUR J HAEMATOL JI Eur. J. Haematol. PY 1996 VL 57 SU 60 BP 98 EP 104 PG 7 WC Hematology SC Hematology GA VX757 UT WOS:A1996VX75700018 ER PT J AU Keisu, M Young, N AF Keisu, M Young, N TI Drug-related blood dyscrasias workshop - Discussion SO EUROPEAN JOURNAL OF HAEMATOLOGY LA English DT Editorial Material C1 NHLBI,HEMATOL BRANCH,BETHESDA,MD 20892. RP Keisu, M (reprint author), ASTRA ARCUS AB,SODERTALJE,SWEDEN. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0902-4441 J9 EUR J HAEMATOL JI Eur. J. Haematol. PY 1996 VL 57 SU 60 BP 125 EP 129 PG 5 WC Hematology SC Hematology GA VX757 UT WOS:A1996VX75700022 ER PT J AU Lanza, F Moretti, S Latorraca, A Papa, S Castoldi, GL Shaw, S AF Lanza, F Moretti, S Latorraca, A Papa, S Castoldi, GL Shaw, S TI Moving towards the definition of new clusters of designation at the 6th International Workshop on Human Leukocyte Differentiation Antigens. SO EUROPEAN JOURNAL OF HISTOCHEMISTRY LA English DT Article; Proceedings Paper CT European School of Cytometry - Immunophenotyping Haematological Malignancies CY JUN 12-15, 1995 CL URBINO, ITALY SP CNR DE cluster of designation; new surface molecules; cytokine receptors C1 UNIV FERRARA,INST HEMATOL,I-44100 FERRARA,ITALY. UNIV URBINO,INST MORPHOL SCI,I-61029 URBINO,ITALY. NIH,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LUIGI PONZIO E FIGLIO PI PAVIA PA VIA D DA CATALOGNA 1/3, 27100 PAVIA, ITALY SN 1121-760X J9 EUR J HISTOCHEM JI Eur. J. Histochem. PY 1996 VL 40 SU 1 BP 63 EP 74 PG 12 WC Cell Biology SC Cell Biology GA UG206 UT WOS:A1996UG20600008 PM 8839701 ER PT J AU Lisignoli, G Monaco, MCG Facchini, A Toneguzzi, S Cattini, L Hilbert, DM Lavaroni, S Belvedere, O Degrassi, A AF Lisignoli, G Monaco, MCG Facchini, A Toneguzzi, S Cattini, L Hilbert, DM Lavaroni, S Belvedere, O Degrassi, A TI In vitro cultured stromal cells from human tonsils display a distinct phenotype and induce B cell adhesion and proliferation SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE stromal cells; phenotype; follicular dendritic cells; cytokine ID FOLLICULAR DENDRITIC CELLS; LYMPHOID-TISSUES; RETICULUM CELLS; LOCALIZATION; NODES AB Peripheral lymphoid tissues contain a fibroblastic cell type referred to as stromal cells or reticulum cells which interact with lymphocytes as part of the lymphoid microenvironment. After isolation from human tonsils and expansion in vitro we analyzed the surface phenotype, extracellular matrix components, cytoskeletal products, cytokine production, binding and functional interaction with B lymphocytes of in vitro cultured stromal cells (HTSC) both in resting condition and after activation with tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma. Our results show that HTSC do not express specific myeloid, lymphoid, endothelial or epithelial markers. HTSC express CD54 (ICAM-1), CD49a (VLA-1). CD49b (VLA-2), CD49c (VLA-3), CD49e (VLA-5), CD49f (VLA-6), CD29, CD51, CD44 and produce vinculin, beta-tubulin, alpha-actin, vimentin, fibronectin, laminin and collagen types I, III and IV. Activation of HTSC up-regulated CD54 (ICAM-1) and induced HLA-DR and CD106 (VCAM-1). HTSC constitutively produce interleukin (IL)-6 which is enhanced upon activation with TNF-alpha. IL-8 and granulocyte/macrophage colony-stimulating factor are detected only in the supernatants of activated HTSC. Reverse transcriptase polymerase chain reaction analysis revealed that HTSC display mRNA for IL-1 alpha, leukemia inhibitory factor and IL-7. The adhesion of tonsillar B lymphocytes to activated HTSC is mediated by CD11a/CD18 and CD54. Furthermore. HTSC can induce maximal proliferation of IL-2-activated B lymphocytes cocultured in direct cell-cell contact with HTSC. These results clearly distinguish in vitro cultured HTSC from common fibroblasts and other non-lymphoid elements present in the lymphoid parenchyma, such as follicular dendritic cells, and show that HTSC actively participate in the lymphoid microenvironment. In vitro cultures of HTSC could therefore be a useful model system for detailed analysis of the interactions between stromal cells and lymphocytes under physiological and pathological conditions. C1 IOR,IST RIC CODIVILLA PUTT,LAB IMMUNOL & GENET,I-40136 BOLOGNA,ITALY. UNIV BOLOGNA,INST CLIN MED & GASTROENTEROL,I-40126 BOLOGNA,ITALY. NCI,NIH,GENET LAB,BETHESDA,MD 20892. UNIV UDINE,CONSORZIO RIC BIOMED,I-33100 UDINE,ITALY. UNIV UDINE,DIPARTIMENTO PATOL & MED SPERIMENTAL & CLIN,I-33100 UDINE,ITALY. NR 26 TC 30 Z9 30 U1 0 U2 0 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD JAN PY 1996 VL 26 IS 1 BP 17 EP 27 DI 10.1002/eji.1830260104 PG 11 WC Immunology SC Immunology GA UD138 UT WOS:A1996UD13800003 PM 8566062 ER PT J AU Borkowski, TA Nelson, AJ Farr, AG Udey, MC AF Borkowski, TA Nelson, AJ Farr, AG Udey, MC TI Expression of gp40, the murine homologue of human epithelial cell adhesion molecule (Ep-CAM), by murine dendritic cells SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE dendritic cells; Langerhans cells; gp40; epithelial cell adhesion molecule; subpopulations ID EPIDERMAL LANGERHANS CELLS; MONOCLONAL-ANTIBODY; PROTEIN ANTIGENS; LYMPH-NODE; GLYCOPROTEIN; CDNA; CLONING; SKIN AB Dendritic cells (DC) can be distinguished from other antigen-presenting cells (APC) by their morphology, motility and ability to initiate primary responses in naive T cells. Certain cell surface proteins (e.g. major histocompatibility complex antigens, co-stimulatory/adhesion molecules and DEC205) are selectively expressed by DC, and may contribute to the potent APC activity of these leukocytes. As an outgrowth of studies of adhesion molecules expressed by epithelia and Langerhans cells (LC), we examined DC from murine epidermis and various lymphoid tissues for evidence of expression of gp40, a glycoprotein recently identified as the murine homologue of human epithelial cell adhesion molecule (Ep-CAM). gp40 was detected on freshly-obtained LC, cultured LC and LC that migrated from skin explants, as well as on keratinocytes. In skin-associated lymph nodes, gp40 was selectively expressed by some DC in T cell-dependent areas. DC-enriched preparations from skin-associated lymph nodes and spleen contained many cells that co-expressed DC markers (CD11c and DEC205) and high levels of gp40. Lower levels of gp40 were present on DC from gut-associated lymph nodes. These results demonstrate that the putative homophilic adhesion molecule gp40 is expressed by subpopulations of DC in selected tissues: we propose that gp40 expression may have functional consequences for DC. C1 NCI, DERMATOL BRANCH, BETHESDA, MD 20892 USA. UNIV WASHINGTON, DEPT BIOL STRUCT, SEATTLE, WA 98195 USA. FU NIA NIH HHS [AG-04360]; NIAID NIH HHS [AI-24137] NR 36 TC 56 Z9 57 U1 0 U2 0 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD JAN PY 1996 VL 26 IS 1 BP 110 EP 114 DI 10.1002/eji.1830260117 PG 5 WC Immunology SC Immunology GA UD138 UT WOS:A1996UD13800016 PM 8566052 ER PT J AU Blottner, D Wolf, N Lachmund, A Flanders, KC Unsicker, K AF Blottner, D Wolf, N Lachmund, A Flanders, KC Unsicker, K TI TGF-beta rescues target-deprived preganglionic sympathetic neurons in the spinal cord SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE TGF-beta; neuroprotection; preganglionic sympathetic spinal cord neurons; adrenal medullary chromaffin cells; growth factors ID FIBROBLAST GROWTH-FACTOR; NITRIC-OXIDE SYNTHASE; RAT ADRENAL-GLAND; FIMBRIA-FORNIX TRANSECTION; NADPH-DIAPHORASE; RETROGRADE TRANSPORT; HORSERADISH-PEROXIDASE; CHOLINERGIC NEURONS; NERVOUS-SYSTEM; MESSENGER-RNA AB Transforming growth factors beta (TGF-beta), a family of pleiotropic cytokines, are widely distributed in the developing and adult nervous system. in order to further determine the neural functions of TGF-beta, we have localized the TGF-beta isoforms 1, 2 and 3 in the adult rat adrenal medulla and studied the neuroprotective capacity of one representative family member, TGF-beta 2, for those spinal cord neurons which innervate adrenal chromaffin cells and which die after destruction of the adrenal medulla. Unilateral electrothermal destruction of the adrenal medulla led to the disappearance of 25% of sympathetic preganglionic neurons, which are located in the intermediolateral (IML) column of thoracic spinal cord segments 7-10 and can be selectively marked by NADPH-diaphorase. The neurons which disappeared following adrenomedullectomy constitute the full set of neurons that innervate the adrenal medulla. Implantation of gelfoam soaked with 0.5 mu g TGF-beta 2 into the adrenal wound cavity rescued all spinal cord neurons in the IML ipsilaterally to the lesioned side. Cytochrome c was not effective. Injections of [I-125]TGF-beta 2 into the adrenal medulla did not result in retrograde transport and subsequent labelling of spinal cord neurons, suggesting that TGF-beta may exert its neuroprotective actions by indirect mechanisms. TGF-beta applied to cultured adrenocortical cells did not overtly increase the amount of mRNA for fibroblast growth factor-2, an established trophic molecule for sympathetic preganglionic spinal cord neurons. The mechanisms by which TGF-beta exerts its neurotrophic effect are therefore unclear. Even so, our data provide the first evidence that TGF-beta may play an important role in vivo in the control of maintenance of a population of spinal cord neurons. C1 UNIV HEIDELBERG,DEPT ANAT & CELL BIOL,D-69120 HEIDELBERG,GERMANY. FREE UNIV BERLIN,DEPT ANAT,D-14195 BERLIN,GERMANY. NCI,CHEMOPREVENT LAB,BETHESDA,MD 20892. RI Wolf, Nicole/H-3943-2014 OI Wolf, Nicole/0000-0003-1721-0728 NR 58 TC 33 Z9 33 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD JAN PY 1996 VL 8 IS 1 BP 202 EP 210 DI 10.1111/j.1460-9568.1996.tb01181.x PG 9 WC Neurosciences SC Neurosciences & Neurology GA TR960 UT WOS:A1996TR96000021 PM 8713464 ER PT B AU Friedman, L AF Friedman, L BE Fracchia, GN Haavisto, KH TI Financing of clinical trials SO EUROPEAN MEDICINES RESEARCH: PERSPECTIVES IN CLINICAL TRIALS LA English DT Proceedings Paper CT Workshop on European Medicines Research - Perspectives in Clinical Trials CY DEC, 1994 CL BRUSSELS, BELGIUM SP European Commiss DGXII Sci Res & Dev RP Friedman, L (reprint author), NIH,DEPT HLTH & HUMAN SERV,BETHESDA,MD 20892, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU EUROPEAN CONFERENCE PUBLICATIONS PI CAMBRIDGE CB4 4RT PA PO BOX 806 COTTENHAM, CAMBRIDGE CB4 4RT, ENGLAND BN 0-9526643-0-5 PY 1996 BP 89 EP 93 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BH89N UT WOS:A1996BH89N00014 ER PT J AU Beerpoot, LJ Lipska, BK Weinberger, DR AF Beerpoot, LJ Lipska, BK Weinberger, DR TI Neurobiology of treatment-resistant schizophrenia: New insights and new models SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Article; Proceedings Paper CT Symposium on Managing the Life Cycle of Schizophrenia - First Episode, Stabilised and Treatment-Resistant Patients, at the ECNP Meeting CY SEP-OCT -, 1995 CL VENICE, ITALY SP European Coll Neuropsychopharm DE schizophrenia; neurobiology; development; gene expression; antipsychotic drugs; dopaminergic systems ID POSITRON EMISSION TOMOGRAPHY; D2 DOPAMINE-RECEPTORS; PREFRONTAL CORTEX; CEREBRAL-CORTEX; BRAIN; ABNORMALITIES; DEFICITS; PSYCHOSIS; ORGANIZATION; AMPHETAMINE AB In an attempt to understand schizophrenia, four important fields have been implicated in the disease process and are reviewed here. Early findings that antipsychotic drugs were dopamine antagonists led to a dopaminergic theory of schizophrenia. However, it now appears that a primary dopaminergic abnormality is an unlikely explanation. The cortex has always been thought to be involved in the development of schizophrenia and recent data from neuropsychological, postmortem and imaging studies have indicated that connections between the prefrontal and temporolimbic areas within the brain may be abnormal. Traditionally, schizophrenia has been considered to be a disease with an adult onset pathology. This theory has now been challenged by data suggesting that in schizophrenia, anatomical changes in the adult brain are non-progressive and occurred prior to the onset of illness. Finally, studies on neuronal gene expression have indicated that all antipsychotic drugs modulate DNA transcription in the shell of the nucleus accumbens and that newer antipsychotics produce a quite different pattern of expression from conventional neuroleptics. These recent approaches provide new opportunities in the understanding of schizophrenia, its treatment and prevention. C1 NIMH,CLIN BRAIN DISORDERS BRANCH,CTR NEUROSCI,ST ELIZABETHS HOSP,INTRAMURAL RES PROGRAM,WASHINGTON,DC 20032. NR 107 TC 7 Z9 7 U1 2 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PY 1996 VL 6 SU 2 BP 27 EP 34 DI 10.1016/0924-977X(96)00008-9 PG 8 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA UQ613 UT WOS:A1996UQ61300006 ER PT J AU Hampel, H Schneider, C Hock, C MullerSpahn, F Ackenheil, M AF Hampel, H Schneider, C Hock, C MullerSpahn, F Ackenheil, M TI CNS demyelination in monoclonal gammopathy of undetermined significance (MGUS): Possible cause of a dementia syndrome SO EUROPEAN PSYCHIATRY LA English DT Article DE dementia; chronic polyneuropathies; monoclonal gammopathy of undetermined significance (MGUS); demyelinating disease; white matter lesions (WMLs); CNS autoantibodies ID CENTRAL NERVOUS-SYSTEM; PERIPHERAL NEUROPATHY; LEUKO-ARAIOSIS; IGM; LESIONS; MRI AB In acquired peripheral demyelinating disease only few publications point out the possibility of simultaneous involvement of the CNS. We describe two patients with chronic polyneuropathy and monoclonal gammopathy of undetermined significance (MGUS) developing a progressive dementia syndrome with extensive cerebral white matter alterations. RP Hampel, H (reprint author), NIA,NEUROSCI LAB,NATL INST HLTH,BLDG 10,ROOM 6C414,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 15 TC 1 Z9 1 U1 0 U2 1 PU EDITIONS SCIENTIFIQUES ELSEVIER PI PARIS CEDEX 15 PA 141 RUE JAVEL, 75747 PARIS CEDEX 15, FRANCE SN 0924-9338 J9 EUR PSYCHIAT JI Eur. Psychiat. PY 1996 VL 11 IS 1 BP 46 EP 49 DI 10.1016/0924-9338(96)80458-5 PG 4 WC Psychiatry SC Psychiatry GA TV813 UT WOS:A1996TV81300008 PM 19698421 ER PT J AU Hampel, H Berger, C MullerSpahn, F AF Hampel, H Berger, C MullerSpahn, F TI Psychodrug-induced and EDTA associated thrombocytopenia: Important factors in the differential diagnosis of low platelet counts SO EUROPEAN PSYCHIATRY LA English DT Article DE thrombocytopenia; psychodrug-induced thrombocytopenia; EDTA-associated pseudothrombocytopenia AB We report the case of a 68-year-old depressive patient who developed severe thrombocytopenia during hospitalization. EDTA-associated thrombocytopenia and psychodrug-induced thrombocytopenia are illustrated as potential causes of low platelet counts, particularly in regard to psychiatric patients. RP Hampel, H (reprint author), NIA,NEUROSCI LAB,NIH,BLDG 10,ROOM 6C414,BETHESDA,MD 20892, USA. NR 11 TC 0 Z9 0 U1 0 U2 1 PU EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS PA 141 RUE JAVEL, 75747 PARIS, FRANCE SN 0924-9338 J9 EUR PSYCHIAT JI Eur. Psychiat. PY 1996 VL 11 IS 8 BP 416 EP 418 DI 10.1016/S0924-9338(97)82581-3 PG 3 WC Psychiatry SC Psychiatry GA VZ894 UT WOS:A1996VZ89400009 PM 19698494 ER PT J AU Schuppert, F Hiller, W Weinland, G HoangVu, C vonzurMuhlen, A Kohn, LD AF Schuppert, F Hiller, W Weinland, G HoangVu, C vonzurMuhlen, A Kohn, LD TI Iodide, cytokines and TSH-receptor expression in Graves' disease SO EXPERIMENTAL AND CLINICAL ENDOCRINOLOGY & DIABETES LA English DT Article; Proceedings Paper CT Molecular Aspects in the Pathogenesis and Diagnostics of Thyroid Diseases Conference of the Thyroid Gland Section of the Deutschen-Gesellschaft-fur-Endokrinologie CY NOV 22-23, 1996 CL CASTROP RAUXEL, GERMANY SP Deut Gesell Endokrinol DE iodide; cytokine; TSH receptor; autoimmune disease; thyroid ID FRTL-5 THYROID-CELLS; THYROTROPIN RECEPTOR; GENE-EXPRESSION; INTERFERON-GAMMA; HUMAN THYROCYTES; MESSENGER-RNA; METHIMAZOLE; AGENTS; GROWTH; DOG AB The present study was initiated to characterize thyrotropin receptor (TSH-R) expression in thyroids from patients with Graves' disease, as well as parameters that influence TSH-R expression either causally, such as interferon-gamma (IFN-gamma), the leading candidate among the cytokines thought to play a key role in the initiation of autoimmune thyroid disease, or therapeutically, such as iodide, which is used to prepare patients for surgery. Our data show that there is an average 4-fold increase of TSH-R mRNA levels in the thyroids of Graves' patients coming to surgery, which is paralleled by an increase in TSH-R protein levels and TSH binding capacity. The increase does not appear to be related to IFN-gamma since IFN-gamma transcripts are barely detectable in most Graves' patients. Iodide treatment causes a 2-fold decrease in TSH-R expression in association with significant decreases in major histocompatibility complex (MHC) class I and class II gene expression. These last data are compatible with a recently enunciated ''transcription factor hypothesis'' according to which abnormally high TSH-R and MHC class I and class II gene expression in Graves' thyroids are the result of a loss of the normal negative regulation of these genes necessary to allow the normal growth and function of the gland, yet preserve self-tolerance. C1 UNIV HANNOVER,SCH MED,DEPT ABDOMINAL & TRANSPLANT SURG,D-30625 HANNOVER,GERMANY. ISRAELIT HOSP,DEPT SURG,HAMBURG,GERMANY. UNIV HALLE WITTENBERG,DEPT SURG,HALLE,SAALE,GERMANY. NIDDK,METAB DIS BRANCH,NIH,BETHESDA,MD. RP Schuppert, F (reprint author), UNIV HANNOVER,SCH MED,DEPT CLIN ENDOCRINOL,KONSTANTY GUTSCHOW STR 8,D-30625 HANNOVER,GERMANY. NR 28 TC 8 Z9 10 U1 0 U2 1 PU JOHANN AMBROSIUS BARTH VERLAG PI HEIDELBERG PA IM WEIHER 10, D-69121 HEIDELBERG, GERMANY SN 0947-7349 J9 EXP CLIN ENDOCR DIAB JI Exp. Clin. Endocrinol. Diabet. PY 1996 VL 104 SU 4 BP 68 EP 74 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VY149 UT WOS:A1996VY14900017 PM 8981006 ER PT J AU Nagata, H Worobec, AS Metcalfe, DD AF Nagata, H Worobec, AS Metcalfe, DD TI Identification of a polymorphism in the transmembrane domain of the protooncogene c-kit in healthy subjects SO EXPERIMENTAL AND CLINICAL IMMUNOGENETICS LA English DT Article DE protein tyrosine kinase; c-kit; mastocytosis; stem cell factor ID TYROSINE KINASE; RECEPTOR; MUTATIONS; ZAP-70; CELLS AB c-Kit is the receptor for stem cell factor (SCF) and is found on hematopoietic stem cells, mast cells, melanocytes, and germ cells. Aggregation of c-Kit by SCF regulates cell proliferation, differentiation, and survival. In the process of examining c-Kit, a polymorphism in the transmembrane domain of the protooncogene c-kit was identified. This polymorphism consisted of an A-to-C transversion at nucleotide (nt) 1642, and was deduced to substitute leucine for methionine at codon 541. The frequency of the allele with 'C' at nt 1642 was 0.09 in 64 unrelated subjects. Analysis of a two-generation family with the polymorphism suggested that this polymorphism did not result in disease. This is the first report of a polymorphism in the transmembrane domain of c-kit, and may be of value in understanding and following the function of c-Kit in normal subjects and in those with other abnormalities of c-Kit. C1 NIAID, NIH, LAD, BETHESDA, MD 20892 USA. NR 22 TC 20 Z9 20 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0254-9670 J9 EXP CLIN IMMUNOGENET JI Exp. Clin. Immunogenet. PY 1996 VL 13 IS 3-4 BP 210 EP 214 PG 5 WC Biochemistry & Molecular Biology; Genetics & Heredity; Immunology SC Biochemistry & Molecular Biology; Genetics & Heredity; Immunology GA WY739 UT WOS:A1996WY73900011 PM 9165275 ER PT J AU PascualLeone, A Wassermann, EM Grafman, J Hallett, M AF PascualLeone, A Wassermann, EM Grafman, J Hallett, M TI The role of the dorsolateral prefrontal cortex in implicit procedural learning SO EXPERIMENTAL BRAIN RESEARCH LA English DT Article DE transcranial magnetic stimulation; learning and memory; cortical physiology; human ID TRANSCRANIAL MAGNETIC STIMULATION; ALZHEIMERS-DISEASE; PARKINSONS-DISEASE; MEMORY-SYSTEMS; KNOWLEDGE; AMNESIA; TASK AB We studied the role of the dorsolateral prefrontal cortex in procedural learning. Normal subjects completed several blocks of a serial reaction time task using only one hand without or with concurrent non-invasive repetitive transcranial magnetic stimulation. To disrupt their function transiently, stimulation was applied at low intensity over the supplementary motor area or over the dorsolateral prefrontal cortex contralateral or ipsilateral to the hand used for the test. Stimulation to the contralateral dorsolateral prefrontal cortex markedly impaired procedural implicit learning, as documented by the lack of significant change in response times during the task. Stimulation over the other areas did not interfere with learning. These results support the notion of a critical role of contralateral dorsolateral prefrontal structures in learning of motor sequences. C1 NINCDS,HUMAN MOTOR CONTROL SECT,MED NEUROL BRANCH,BETHESDA,MD. NINCDS,COGNIT NEUROSCI SECT,MED NEUROL BRANCH,BETHESDA,MD. RP PascualLeone, A (reprint author), UNIV VALENCIA,DEPT FISIOL,UNIDAD NEUROBIOL,CSIC,AVDA BLASCO IBANEZ 17,E-46010 VALENCIA,SPAIN. RI Pascual-Leone, Alvaro/G-6566-2011; OI Grafman, Jordan H./0000-0001-8645-4457 NR 32 TC 127 Z9 129 U1 1 U2 11 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0014-4819 J9 EXP BRAIN RES JI Exp. Brain Res. PD JAN PY 1996 VL 107 IS 3 BP 479 EP 485 PG 7 WC Neurosciences SC Neurosciences & Neurology GA TR692 UT WOS:A1996TR69200012 PM 8821387 ER PT J AU Duncan, MK BanerjeeBasu, S McDermott, JB Piatigorsky, J AF Duncan, MK BanerjeeBasu, S McDermott, JB Piatigorsky, J TI Sequence and expression of chicken beta A2- and beta B3-crystallins SO EXPERIMENTAL EYE RESEARCH LA English DT Article DE crystallins; evolution; gene expression; gene duplication; eye; development ID CRYSTALLIN GENE FAMILY; X-RAY-ANALYSIS; EYE LENS; NUCLEOTIDE-SEQUENCE; DELTA-CRYSTALLIN; CELL ELONGATION; MESSENGER-RNAS; CDNA; EVOLUTION; POLYPEPTIDE AB Crystallins are a diverse group of proteins that contribute to the transparency and refractive properties of the eye lens. Previously, the chicken orthologs of four out of the six known bovine beta-crystallin genes have been cloned and sequenced. In the present study, cDNAs corresponding to the chicken orthologs of beta A2- and beta B3-crystallin, the two previously unidentified chicken beta-crystallins, have been isolated. In addition, sequence analysis of three independent chicken beta B2-crystallin cDNAs yielded a deduced connecting peptide sequence which is considerably shorter than that reported previously. Thus, direct homologs of all of the known bovine beta-crystallins are expressed in the chicken lens. This demonstrates that the duplications giving rise to the known vertebrate beta-crystallins occurred over 300 million years ago. beta B2- and beta B3/A1-crystallin are the most highly conserved of the beta-crystallins suggesting that these genes may be important for other functions besides their refractive role in the lens. By Northern blot hybridization analysis, both beta A2- and beta B3-crystallin were shown to be lens-specific in the chicken embryo. The relative levels of beta A2-crystallin remained stable from five days of embryogenesis until adulthood, while the relative amounts of beta B3-crystallin increased until hatching and were appreciably lower in the adult lens, Approximately equal relative amounts of beta A2-crystallin mRNA were found in the lens epithelia and fibers of 5 day embryonic chicken embryos; by contrast, beta B3-crystallin mRNA was detected preferentially in the lens fibers. These data in combination with previous studies suggest that beta-crystallin genes are regulated independently from each other in the developing chicken lens. The elucidation of the primary structures for all seven chicken beta-crystallin polypeptides will facilitate future studies on the structure/function relationships responsible for lens transparency and on the molecular basis for beta-crystallin gene expression during development. (C) 1996 Academic Press Limited C1 NEI,MOLEC & DEV BIOL LAB,BETHESDA,MD 20892. NR 54 TC 11 Z9 13 U1 0 U2 2 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0014-4835 J9 EXP EYE RES JI Exp. Eye Res. PD JAN PY 1996 VL 62 IS 1 BP 111 EP 119 DI 10.1006/exer.1996.0013 PG 9 WC Ophthalmology SC Ophthalmology GA TT612 UT WOS:A1996TT61200013 PM 8674507 ER PT J AU Howard, BH AF Howard, BH TI Replicative senescence: Considerations relating to the stability of heterochromatin domains SO EXPERIMENTAL GERONTOLOGY LA English DT Article DE senescence; heterochromatin; cell cycle ID HUMAN-DIPLOID FIBROBLASTS; POSITION-EFFECT VARIEGATION; CELLULAR SENESCENCE; SODIUM-BUTYRATE; 5-AZACYTIDINE-INDUCED DEMETHYLATION; TRANSCRIPTIONAL STATES; HISTONE DEACETYLATION; INVITRO LIFESPAN; TELOMERE LENGTH; DNA METHYLATION AB Replicative senescence of human diploid fibroblasts (HDF) cultured in vitro is characterized by a progressive and irreversible loss of responsiveness to mitogenic stimulation by serum. While some constraints have been placed on the nature of HDF senescence, its underlying molecular mechanism(s) remain obscure. Here, the possibility is considered that defects in cell cycle-coupled reassembly of repressive chromatin domains may contribute to HDF senescence. Features of this model are discussed in relation to established models of HDF senescence based on telomere shortening and loss of DNA methylation. RP Howard, BH (reprint author), NICHHD,NIH,LAB MOLEC GROWTH REGULAT,BETHESDA,MD 20892, USA. NR 79 TC 57 Z9 60 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0531-5565 J9 EXP GERONTOL JI Exp. Gerontol. PD JAN-APR PY 1996 VL 31 IS 1-2 BP 281 EP 293 DI 10.1016/0531-5565(95)00022-4 PG 13 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA TX426 UT WOS:A1996TX42600025 PM 8706797 ER PT J AU Badolato, R Sacks, DL Savoia, D Musso, T AF Badolato, R Sacks, DL Savoia, D Musso, T TI Leishmania major: Infection of human monocytes induces expression of IL-8 and MCAF SO EXPERIMENTAL PARASITOLOGY LA English DT Article DE Leishmania; chemokines ID EXPERIMENTAL VISCERAL LEISHMANIASIS; IFN-GAMMA; CUTANEOUS LEISHMANIASIS; BLOOD MONOCYTES; GENE-EXPRESSION; MACROPHAGES; INVITRO; MICE; MECHANISM; DONOVANI AB Leishmania major, the causative agent of cutaneous leishmaniasis, is an intracellular parasite of monocytic cells. Leishmania lesions are characterized by recruitment of neutrophils, eosinophils, and blood monocytes. To clarify the mechanism of this cellular influx we examined the expression of IL-8 and MCAF, cytokines chemotactic for neutrophils and monocytes, respectively, in human monocytes infected by L. major Supernatants of monocytes infected with L. major had chemotactic activity for neutrophils and monocytes that was neutralized by anti-IL-8 and anti-MCAF antibodies. Both IL-8 and MCAF mRNAs were induced within 1 hr of infection. Furthermore we showed that infection of monocytes with L. major induces IL-8 and MCAF but not the proinflammatory cytokines IL-1 beta and TNF alpha. These data suggest that the expression of chemokines may contribute to the cellular recruitment in Leishmania lesions. (C) 1996 Academic Press, Inc. C1 NIAID,PARASIT DIS LAB,NIH,BETHESDA,MD 20892. UNIV TURIN,DEPT CLIN & BIOL SCI,TURIN,ITALY. INST MICROBIOL,I-10126 TURIN,ITALY. RP Badolato, R (reprint author), NCI,BIOL CARCINOGENESIS & DEV PROGRAM,PROGRAM RESOURCES INC,DYN CORP,FCRDC,FREDERICK,MD 21702, USA. RI Badolato, Raffaele/A-8081-2010; Savoia, Dianella/F-9183-2013 OI Badolato, Raffaele/0000-0001-7375-5410; Savoia, Dianella/0000-0002-8963-7889 NR 27 TC 52 Z9 52 U1 0 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0014-4894 J9 EXP PARASITOL JI Exp. Parasitol. PD JAN PY 1996 VL 82 IS 1 BP 21 EP 26 DI 10.1006/expr.1996.0003 PG 6 WC Parasitology SC Parasitology GA UB426 UT WOS:A1996UB42600003 PM 8617327 ER PT S AU Rauschecker, JP AF Rauschecker, JP BE Norita, M Bando, T Stein, BE TI Substitution of visual by auditory inputs in the cat's anterior ectosylvian cortex SO EXTRAGENICULOSTRIATE MECHANISMS UNDERLYING VISUALLY-GUIDED ORIENTATION BEHAVIOR SE Progress in Brain Research LA English DT Review CT Satellite Meeting on Extrageniculostriate Mechanisms Underlying Visually-Guided Orientation Behavior at the 4th World Congress of Neuroscience CY 1996 CL NIIGATA, JAPAN SP Int Brain Res Org ID CEREBRAL-CORTEX; RETINOTOPIC ORGANIZATION; CORTICAL CONNECTIONS; SUPERIOR COLLICULUS; EARLY BLINDNESS; FIELD; PLASTICITY; AREA; NEURONS; FLOW C1 NIMH, COGNIT NEUROSCI SECT, NEUROPSYCHOL LAB, NIH, BETHESDA, MD 20892 USA. RP Rauschecker, JP (reprint author), GEORGETOWN INST COGNIT & COMPUTAT SCI, 3970 RESERVOIR RD NW, WASHINGTON, DC 20007 USA. RI Rauschecker, Josef/A-4120-2013 NR 66 TC 16 Z9 16 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0079-6123 BN 0-444-82347-6 J9 PROG BRAIN RES JI Prog. Brain Res. PY 1996 VL 112 BP 313 EP 323 PG 11 WC Neurosciences SC Neurosciences & Neurology GA BJ08P UT WOS:A1996BJ08P00022 PM 8979838 ER PT J AU Mosher, WD Bachrach, CA AF Mosher, WD Bachrach, CA TI Understanding US fertility: Continuity and change in the national survey of family growth, 1988-1995 SO FAMILY PLANNING PERSPECTIVES LA English DT Article ID SEXUALLY-TRANSMITTED DISEASES; UNITED-STATES; REPRODUCTIVE AGE; WOMEN; INFERTILITY; BEHAVIOR; PATTERNS; ADOPTION; RISK AB About 50 studies based on the 1988 National Survey of Family Growth (NSFG) and a telephone reinterview conducted with the same women two years later provide continuing information about the fertility and health of American women. Among the findings of these studies are that black women have almost twice as many pregnancies as do white women (5.1 vs. 2.8), with nearly all of the difference being unintended pregnancies. Unwanted births increased between 1982 and 1988, particularly among less-educated, poor and minority women. This increase in the proportion of unwanted births may have prompted the increase in female sterilization among these groups. Concern with the AIDS epidemic led to increases in condom use between 1982 and 1990, especially among the partners of teenagers and college-educated women. Rates of teenage pregnancy were fairly stable during the period 1980-1988, as increases in the proportion of teenagers having intercourse were offset by increases in condom use. Rates of infertility did not change significantly in the 1980s, but because of delayed childbearing and the aging of the baby-boom cohort, the number of older childless women increased substantially The 1995 NSFG was redesigned in a number of ways in order to answer a new generation of questions about fertility and women's health in the United States. C1 NICHHD,DEMOG & BEHAV SCI BRANCH,BETHESDA,MD 20892. RP Mosher, WD (reprint author), NCHS,FAMILY GROWTH SURV BRANCH,HYATTSVILLE,MD, USA. NR 70 TC 63 Z9 66 U1 1 U2 5 PU ALAN GUTTMACHER INST PI NEW YORK PA 120 WALL STREET, NEW YORK, NY 10005 SN 0014-7354 J9 FAM PLANN PERSPECT JI Fam. Plann. Perspect. PD JAN-FEB PY 1996 VL 28 IS 1 BP 4 EP 12 DI 10.2307/2135956 PG 9 WC Demography; Family Studies SC Demography; Family Studies GA TU264 UT WOS:A1996TU26400001 PM 8822409 ER PT J AU Ptitsyn, OB AF Ptitsyn, OB TI A determinable but unresolved problem SO FASEB JOURNAL LA English DT Editorial Material ID CHYMOTRYPSIN INHIBITOR-2; PROTEIN CHAINS; PRINCIPLES; TRANSITION; STATE C1 NCI,MATH BIOL LAB,BETHESDA,MD 20892. RP Ptitsyn, OB (reprint author), RUSSIAN ACAD SCI,INST PROT RES,PUSHCHINO 142292,RUSSIA. NR 34 TC 10 Z9 11 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD JAN PY 1996 VL 10 IS 1 BP 3 EP 4 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TR328 UT WOS:A1996TR32800001 PM 8566544 ER PT J AU Lee, B Kurochkina, N Kang, HS AF Lee, B Kurochkina, N Kang, HS TI Protein folding by a biased Monte Carlo procedure in the dihedral angle space SO FASEB JOURNAL LA English DT Review DE conformational search; hydrophobic potential ID SECONDARY STRUCTURE; GLOBULAR-PROTEINS; HELIX; MODEL; PREDICTION; CRAMBIN; PEPTIDE AB A straightforward method for predicting the protein structure is to find conformations that have the lowest energy along a chosen folding pathway, One approach in this direction is to produce a large number of structures by varying the dihedral angles of the molecule more or less randomly and then to screen each one using a suitable energy function, This procedure is computationally demanding, but by using a more realistic model, one hopes that the folding behavior one observes in calculations may better mimic the actual folding process in nature, The method is beginning to yield interesting results, thanks to the increase in the computational power but also to the intelligent selection of the folding pathway, This article reviews general features of this method, some important highlights of the particular procedure we used, and some of the more significant results obtained to date in our laboratory, The results are highly encouraging and indicate the direction of future effort that is most likely to be fruitful. RP Lee, B (reprint author), NCI, DIV BASIC SCI,MOLEC BIOL LAB,RM 4B15,BLDG 37, 37 CONVENT DR, MSC 4255, BETHESDA, MD 20892 USA. NR 43 TC 14 Z9 15 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JAN PY 1996 VL 10 IS 1 BP 119 EP 125 PG 7 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TR328 UT WOS:A1996TR32800016 PM 8566532 ER PT J AU Petzke, F Heppner, C Mbulamberi, D Winkelmann, W Chrousos, GP Allolio, B Reincke, M AF Petzke, F Heppner, C Mbulamberi, D Winkelmann, W Chrousos, GP Allolio, B Reincke, M TI Hypogonadism in Rhodesian sleeping sickness: Evidence for acute and chronic dysfunction of the hypothalamic-pituitary-gonadal axis SO FERTILITY AND STERILITY LA English DT Article DE Trypanosoma brucei rhodesiense; hypothalamic-pituitary-gonadal axis; testosterone; LH; FSH; hypogonadism ID BRUCEI-GAMBIENSE INFECTION; TRYPANOSOMA-BRUCEI; AFRICAN TRYPANOSOMIASIS; BINDING GLOBULIN; TESTOSTERONE; DISORDERS; HUMANS; SYSTEM AB Objective: To investigate acute and long-term effects of Rhodesian sleeping sickness on the function of the hypothalamic-pituitary-gonadal (HPG) axis in men. Design: An observational, cross-sectional study. Setting: Primary health care centers under care of the National Sleeping Sickness Control Program in southeast Uganda. Participants: Fifty-two male patients with sleeping sickness at different stages of treatment and 11 clinically healthy male volunteers recruited from health care personnel. Interventions: Patients and controls were questioned about loss of libido and impotence. All received 100 mu g GnRH IV. Blood was drawn before and 30 minutes after GnRH administration. Main Outcome Measures: Frequency of loss of libido and impotence. Baseline T and sex hormone-binding globulin baseline and GnRH-stimulated serum LH and FSH concentrations. Results: Loss of libido and/or impotence were present in 39% of men with active disease before therapy, whereas 84% were biochemically hypogonadal. After cure, 45% of men still were symptomatic and 45% were biochemically hypogonadal. Compared with controls (806 +/- 59 pg/mt [conversion factor to SI unit, 0.03467]; mean +/- SEM), T concentrations were decreased substantially in patients before (249 +/- 48 ng/dL), during treatment (429 +/- 56 ng/dL), and after cure (431 +/- 58 ng/dL). Corresponding baseline LH concentrations were inappropriately low and the relative LH response to GnRH was reduced both before and during treatment (794% +/- 131% versus 322% +/- 68%). Follicle-stimulating hormone concentrations increased gradually up to 8.0 +/- 1.3 mIU/mL (conversion factor to SI unit, 1.00) at the end of treatment, returning to 4.2 +/- 0.6 mIU/mL after cure. Conclusions: Rhodesian sleeping sickness causes acute and chronic HPG axis dysfunction. The clinical and biochemical picture suggest a combined central and peripheral hypogonadism. This is only in part reversible after cure and most likely due to direct parasitic infiltration and/or secondary inflammation causing necrosis and/or fibrosis at the pituitary and gonadal levels. C1 UNIV WURZBURG,MED KLIN,DEPT MED,D-90780 WURZBURG,GERMANY. NICHHD,DEV ENDOCRINOL BRANCH,BETHESDA,MD 20892. UNIV COLOGNE,DEPT MED 2,W-5000 COLOGNE,GERMANY. NATL SLEEPING SICKNESS CONTROL PROGRAM,JINJA,UGANDA. NR 25 TC 8 Z9 8 U1 0 U2 0 PU AMER SOC REPRODUCTIVE MEDICINE PI BIRMINGHAM PA 1209 MONTGOMERY HIGHWAY, BIRMINGHAM, AL 35216-2809 SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD JAN PY 1996 VL 65 IS 1 BP 68 EP 75 PG 8 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA TL626 UT WOS:A1996TL62600012 PM 8557157 ER PT J AU Uversky, VN Ptitsyn, OB AF Uversky, VN Ptitsyn, OB TI All-or-none solvent-induced transitions between native, molten globule and unfolded states in globular proteins SO FOLDING & DESIGN LA English DT Article DE molten globule; phase transitions; protein denaturation; protein unfolding ID SIZE-EXCLUSION CHROMATOGRAPHY; COOPERATIVE TRANSITIONS; ALPHA-LACTALBUMIN; COMPACT STATE; STABILITY; MOLECULES AB Background: It has long been established that temperature-induced melting of small globular proteins is an all-or-none transition. Little was known, however, about the degree of cooperativity of denaturant-induced transitions in proteins, especially in those cases in which the proteins unfold through the molten globule state. Results: We have processed data on the equilibrium urea-induced and guanidinium chloride (GdmCl)-induced unfolding of globular proteins from the native to the unfolded state, from the native to the molten globule stale and from the molten globule to the unfolded state. We show that in ail these cases, the cooperativity of unfolding increases linearly with the increase of the molecular weight of the protein up to 25-30 kDa. Conclusions: The cooperative unit of the urea-induced and GdmCl-induced equilibrium transitions of small proteins between the native, molten globule and unfolded states includes the protein molecule as a whole. In other words, both native and molten globule proteins are unfolded by strong denaturing solvents according to an all-or-none mechanism. C1 RUSSIAN ACAD SCI,INST PROT RES,PUSHCHINO 142292,MOSCOW REG,RUSSIA. NCI,MATH BIOL LAB,NIH,BETHESDA,MD 20892. RI Uversky, Vladimir/F-4515-2011 OI Uversky, Vladimir/0000-0002-4037-5857 NR 28 TC 57 Z9 60 U1 2 U2 4 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 1359-0278 J9 FOLD DES JI Fold. Des. PY 1996 VL 1 IS 2 BP 117 EP 122 DI 10.1016/S1359-0278(96)00020-X PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA WC403 UT WOS:A1996WC40300006 PM 9079371 ER PT J AU Bahar, I Jernigan, RL AF Bahar, I Jernigan, RL TI Coordination geometry of nonbonded residues in globular proteins SO FOLDING & DESIGN LA English DT Article DE coordination geometry; residue packing; specificity of interresidue interactions ID SIDE-CHAIN; PACKING; STABILITY; SEQUENCES; FEATURES; FOLD AB Background: Two opposite Views have been advanced for the packing of sidechains in globular proteins. The first is the jigsaw puzzle model, in which the complementarity of size and shape is essential. The second, the nuts-and-bolts model, suggests that constraints induced by steric complementarity or pairwise specificity have little influence. Here, the angular distributions of sidechains around amino acids of different types are analyzed, in order to capture the preferred (if any) coordination loci in the neighborhood of a given type of amino acid. Results: Some residue pairs select specific coordination states with probabilities about ten times higher than expected for random distributions. This selectivity becomes more pronounced at closer separations leading to an effective free energy of stabilization as large as -2 RT for some sidechain pairs. A list of the most probable coordination sites around each residue type is presented, along with their statistical weights. Conclusions: These data provide guidance as to how to pack selectively the nonbonded sidechains in the neighborhood of a central residue for computer generation of unknown protein structures. (C) Current Biology Ltd C1 NCI,MOL STRUCT SECT,MATH BIOL LAB,DIV BASIC SCI,NIH,BETHESDA,MD 20892. BOGAZICI UNIV,DEPT CHEM ENGN,TR-80815 BEBEK,ISTANBUL,TURKEY. BOGAZICI UNIV,POLYMER RES CTR,TR-80815 BEBEK,ISTANBUL,TURKEY. TUBITAK ADV POLYMER MAT RES CTR,TR-80815 BEBEK,ISTANBUL,TURKEY. RI Jernigan, Robert/A-5421-2012 NR 28 TC 61 Z9 62 U1 2 U2 3 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 1359-0278 J9 FOLD DES JI Fold. Des. PY 1996 VL 1 IS 5 BP 357 EP 370 DI 10.1016/S1359-0278(96)00051-X PG 14 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA WC406 UT WOS:A1996WC40600006 PM 9080182 ER PT J AU Osawa, Y Williams, MS AF Osawa, Y Williams, MS TI Covalent crosslinking of the heme prosthetic group to myoglobin by H2O2: Toxicological implications SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE heme; H2O2; covalent alteration; myoglobin; ischemia reperfusion injury; oxidative modification; toxicity; free radicals ID POTENTIAL PROTECTIVE MECHANISM; OXYGEN RADICALS; LIPID-PEROXIDATION; PROTEIN DAMAGE; CYTOCHROME-P-450 HEME; SUICIDE INACTIVATION; HEMOGLOBIN ADDUCTS; REPERFUSION INJURY; HYDROGEN-PEROXIDE; FERRYL-MYOGLOBIN AB It is known that treatment of myoglobin with H2O2 leads to covalent alteration of the heme prosthetic group with concomitant formation of a protein bound heme adduct and transforms myoglobin from an Oxygen storage protein to an oxidase. In the current study it was shown, with the use of C-14-labeled heme reconstituted into apomyoglobin, that up to 88% of the oxidatively altered heme can be accounted for by the protein bound product. Furthermore, a partially purified preparation of the protein hound heme adduct was introduced into human fibroblasts using the method of osmotic lysis of pinosomes and found to cause cell death (40%) within 1 h, as evidenced by trypan blue exclusion. Native myoglobin introduced into cells in the same manner or extracellular treatment by the protein bound heme adduct had no effect on cell viability. The extent of cell death could be decreased (50%) by N-acetyl-L-cysteine, indicating a potential role for reactive oxygen intermediates in this Process These results show that the covalently altered myoglobin can elicit cellular damage and suggests that similar processes may occur in vivo in pathologic conditions such as that involving cardiac ischemia and reperfusion injury, where covalently altered myoglobin may form. C1 NCI,EXPTL IMMUNOL BRANCH,NIH,BETHESDA,MD 20892. NHLBI,LAB MOL IMMUNOL,NIH,BETHESDA,MD 20892. NR 63 TC 38 Z9 38 U1 2 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 1996 VL 21 IS 1 BP 35 EP 41 DI 10.1016/0891-5849(95)02215-5 PG 7 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA UT321 UT WOS:A1996UT32100006 PM 8791091 ER PT J AU Ayala, A Cutler, RG AF Ayala, A Cutler, RG TI The utilization of 5-hydroxyl-2-amino valeric acid as a specific marker of oxidized arginine and proline residues in proteins SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE oxidized amino acids; glutamyl semialdehyde; GC/MS/SIM; HAVA; carbonyl; free radicals ID MIXED-FUNCTION OXIDATION; COLI GLUTAMINE-SYNTHETASE; OXYGEN RADICALS; AMINO-ACIDS; LEUCONOSTOC-MESENTEROIDES; SUPEROXIDE-DISMUTASE; CATALYZED OXIDATION; HISTIDINE-RESIDUES; TURBATRIX-ACETI; CARBONYL GROUPS AB Alteration of cellular proteins by oxidative modification could represent an important mechanism leading to cellular dysdifferentiation and age-related diseases. There is difficulty in testing this hypothesis because of a lack of specific assays that can measure the extent proteins are oxidized in nonpurified tissue preparations. Some methods used to measure carbonyl groups in nonpurified samples have serious limitations because of interference from other sources of carbonyl groups not being a product of oxidation-mediated damage. Oxidation of arginine and proline residues has been reported to produce gamma-glutamyl semialdehyde, which on reduction and acid hydrolysis, was predicted to form 5-hydroxy-2-amino valeric acid (HAVA). In this article we confirm this prediction using a GC/MS/SIM technique, and carry out additional experiments to determine if HAVA may be a useful marker of oxidative damage in proteins, These experiments utilized purified preparations of arginine, proline, histidine, and lysine amino acid homopolymers and six different purified proteins preparations in nonoxidized and oxidized states. Results demonstrate that HAVA compares well with the carbonyl group formation as a specific marker of oxidized protein, and that the GC/MS/SIM technique can detect HAVA reliably to 150 femtomoles per injection. Thus, HAVA as a specific marker of oxidized arginine and proline could prove to be a useful assay in pure and nonpurified samples. C1 NIA,GERONTOL RES CTR,NIH,BALTIMORE,MD 21224. NR 42 TC 34 Z9 34 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 1996 VL 21 IS 1 BP 65 EP 80 DI 10.1016/0891-5849(95)02220-1 PG 16 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA UT321 UT WOS:A1996UT32100009 PM 8791094 ER PT J AU Rauhala, P Sziraki, I Chiueh, CC AF Rauhala, P Sziraki, I Chiueh, CC TI Peroxidation of brain lipids in vitro: Nitric oxide versus hydroxyl radicals SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE nitric oxide; peroxidation of brain lipids; S-nitroso-N-acetylpenicillamine SNAP; ferrous ion; penicillamine; hydroxyl radical; free radicals ID PEROXYNITRITE; SUPEROXIDE AB The pro-oxidant effects of hydroxyl radical (. OH, ferrous ammonium sulfate/Fe2+) or nitric oxide (NO ., S-nitroso-N-acetylpenicillamine/SNAP) generating compounds were studied in rat brain homogenate preparations. Submicromolar concentrations of Fe2+, but not SNAP (up to 100 mu M), increased the formation of fluorescent products of malondialdehyde in cortical homogenates. In fact, iron-catalyzed brain lipid peroxidation was inhibited by SNAP (100 mu M), but not by light-exposed SNAP or its degradation product penicillamine (100 mu M). This study provides relevant evidence to suggest that submicromolar concentrations of Fe2+ can potentiate lipid peroxidation in disrupted brain tissue. NO . released from SNAP did not stimulate, but rather inhibited brain lipid peroxidation. These results support the hypothesis that NO ., as opposed to . OH radicals, is not a pro-oxidant but rather an antioxidant. C1 NIMH,UNIT NEUROTOXICOL & NEUROPROTECT,CLIN SCI LAB,NIH CLIN CTR,BETHESDA,MD 20892. OI Rauhala, Pekka/0000-0003-2036-3522 NR 17 TC 37 Z9 37 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 1996 VL 21 IS 3 BP 391 EP 394 DI 10.1016/0891-5849(96)00043-3 PG 4 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA VB873 UT WOS:A1996VB87300016 PM 8855451 ER PT J AU Ayala, A Cutler, RG AF Ayala, A Cutler, RG TI Comparison of 5-hydroxy-2-amino valeric acid with carbonyl group content as a marker of oxidized protein in human and mouse liver tissues SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE 5-hydroxy-2-amino-valeric acid; protein oxidation; hyperoxia; P450 cytochrome; aging; free radicals ID OXIDATIVELY MODIFIED PROTEINS; GLUTAMINE-SYNTHETASE; SELECTIVE PROTEOLYSIS; GENE-EXPRESSION; CYTOCHROME-P-450; INACTIVATION; CARCINOGENS; DITYROSINE; HEMOGLOBIN; SYSTEM AB Previous studies indicate that 5-hydroxy-2-amino valeric acid (HAVA) is an excellent marker of oxidized arginine and proline in purified proteins. We report here experiments testing the specificity of the HAVA assay a technique using the unpurified 100,000 x g supernatant fraction prepared from mice and human liver tissue. Results are compared to carbonyl group analysis on the same tissue samples. Mice at ages 3, 12, and 30 months were exposed to 100% oxygen. Results showed a significant increase of HAVA content in each age group. No significant changes were found in carbonyl group content. Because it has been reported that carbonyl group content increases with age, we applied the HAVA assay to reexamine this question. Using mice of 1 to 30 months of age, we failed to detect any significance difference in either HAVA or carbonyl group content. However, on using human liver samples a significant decrease from age 16 to 40 years and then an increase to 85 years of age was found for both HAVA and carbonyl groups. Liver proteins may be oxidized from hydrogen peroxide produced from the cytochrome P450 detoxification system. This possibility was supported by a significant positive correlation found between HAVA and cytochrome P450 content in 18 human individuals of different ages. C1 NIA,CTR GERONTOL RES,NIH,BALTIMORE,MD 21224. NR 26 TC 11 Z9 11 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 1996 VL 21 IS 4 BP 551 EP 558 DI 10.1016/0891-5849(96)00125-6 PG 8 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA VH624 UT WOS:A1996VH62400017 PM 8886807 ER PT J AU Liu, YS Guyton, KZ Gorospe, M Xu, QB Lee, JC Holbrook, NJ AF Liu, YS Guyton, KZ Gorospe, M Xu, QB Lee, JC Holbrook, NJ TI Differential activation of ERK, JNK/SAPK and p38/CSBP/RK map kinase family members during the cellular response to arsenite SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE oxidative stress; stress response; arsenite; mitogen-activated protein kinase; Ras; free radicals ID SIGNAL-TRANSDUCTION PATHWAY; GROWTH-FACTOR RECEPTOR; PROTEIN-KINASE; C-JUN; MAMMALIAN-CELLS; MEK KINASE; PC12 CELLS; HA-RAS; PHOSPHORYLATION; STRESS AB Exposure of cells to either proliferative or stressful stimuli elicits a complex response involving one or more distinct phosphorylation cascades culminating in the activation of multiple members of the mitogen-activated protein kinase (MAPK) family, including extracellular signal regulated kinase (ERK), stress-activated c-Jun N-terminal kinase (JNK/SAPK), and p38/RK/CSBP protein kinase. While the pathways transducing mitogenic stimuli to these kinases are relatively well established, the early signalling events leading to their activation in response to stress are poorly understood. In the present study, we examined ERK, JNK/SAPK, and p38 activation in cells treated with the sulfhydryl-reactive agent sodium arsenite. Arsenite treatment potently activated both JNK/SAPK and p38, but only moderately activated ERK. Activation of all three kinases was prevented by the free radical scavenger N-Acetyl-L-cysteine, suggesting that an oxidative signal initiates the responses. Suramin, a growth factor receptor poison, significantly inhibited ERK activation by arsenite, but had little effect on either JNK/SAPK or p38 activity. In contrast, suramin inhibited the activation of all three kinases by snort wavelength ultraviolet light (UVC) irradiation. In addition, comparative studies with wild-type PC12 cells and PC12 cells expressing a dominant negative Ras mutant allele indicated that arsenite activates ERK primarily through a Ras-dependent pathway(s), while activation of both JNK/SAPK and p38 occurs through a mechanism relatively independent of Ras. These results suggest that JNK/SAPK and p38 may share common upstream regulators distinct from those involved in ERK activation. C1 NIA,GERONTOL RES CTR,GENE EXPRESS & AGING SECT,BALTIMORE,MD 21224. SMITHKLINE BEECHAM PHARMACEUT,DEPT CELLULAR BIOCHEM,KING OF PRUSSIA,PA 19406. RI Liu, Yusen/E-3527-2011 NR 53 TC 168 Z9 170 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 1996 VL 21 IS 6 BP 771 EP 781 DI 10.1016/0891-5849(96)00176-1 PG 11 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA VM926 UT WOS:A1996VM92600004 PM 8902523 ER PT J AU Reszka, KJ Bilski, P Chignell, CF Dillon, J AF Reszka, KJ Bilski, P Chignell, CF Dillon, J TI Free radical reactions photosensitized by the human lens component, kynurenine: An EPR and spin trapping investigation SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE kynurenine; cysteine; EPR; free radical; lens injury; photochemistry; photoreduction; spin trapping; superoxide radical ID O-BETA-GLUCOSIDE; EYE LENS; 3-HYDROXYKYNURENINE; ACID; 5,5-DIMETHYL-1-PYRROLINE-1-OXIDE; CONSTITUENTS; SUPEROXIDE; PROTEINS; OXYGEN AB We have undertaken electron paramagnetic resonance and spin trapping investigations of the photochemistry of kynurenine (KN), a natural component of the human eye and close analog of the principal chromophore in the young human lens 3-OH-kynurenine O-glucoside (3HKG). 5,5-Dimethyl-1-pyrroline N-oxide (DMPO) was employed as a spin trap. We found that upon UV irradiation (> 300 nm) KN photoreduces oxygen to superoxide radical (in DMSO) and nitromethane (CH3NO2) to a nitromethane radical anion (CH3NO2.-) (in air-free buffers, pH 7 and 9.5). KN also sensitized photooxidation of cysteine, NADH, EDTA, azide, and ascorbate; oxygen greatly accelerated this process. Oxidation of cysteine, NADH, and EDTA was accompanied by superoxide radical formation. Cysteinyl and azidyl radicals were detected as DMPO adducts. We also observed that KN undergoes photodegradation to a product(s) whose photosensitizing capacity is greater than that of KN itself. We postulate that: (i) 3HKG may be able to photoinitiate free radical reactions in vivo, and (ii) oxygen is an important factor determining the yields of free radical processes initiated by lenticular chromophores. C1 COLUMBIA UNIV,DEPT OPHTHALMOL,NEW YORK,NY 10027. RP Reszka, KJ (reprint author), NIEHS,MOLEC BIOPHYS LAB,POB 12233,MD 17-05,104 ALEXANDER DR,RES TRIANGLE PK,NC 27709, USA. NR 34 TC 25 Z9 26 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 1996 VL 20 IS 1 BP 23 EP 34 DI 10.1016/0891-5849(95)02018-7 PG 12 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA TM326 UT WOS:A1996TM32600003 PM 8903676 ER PT J AU Misik, V Riesz, P AF Misik, V Riesz, P TI Peroxyl radical formation in aqueous solutions of N,N-dimethylformamide, N-methylformamide, and dimethylsulfoxide by ultrasound: Implications for sonosensitized cell killing SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE ultrasound; sonodynamic therapy; N,N-dimethyl formamide; N-methyl formamide; dimethylsulfoxide; peroxyl radicals; spin trapping; EPR; free radicals ID WATER MIXTURES; RATE CONSTANTS; SONOCHEMISTRY; ADRIAMYCIN AB Sonodynamic therapy, which refers to a synergistic effect of drugs and ultrasound, is a promising new modality for cancer treatment. The sonodynamic effect was found for a number of structurally unrelated compounds, and the underlying mechanisms are still unknown. Recently, Jeffers et al. (J. Acoust. Sec. Am. 97:669-676; 1995) have shown that the sonodynamic action of nontoxic concentrations of N,N-dimethylformamide (DMF), N-methyl formamide (MMF), and dimethylsulfoxide (DMSO) combined with ultrasound, on killing of cultured HL-60 human promyelocytic leukemia cells, and attributed this toxic effect to unknown short lived reactive species produced from these solutes by ultrasonic cavitation. Using the spin trap 3,5-dibromo-4-nitrosobenzene sulfonate (DBNBS) in nitrogen-saturated aqueous solutions of DMF, MMF, or DMSO exposed to 50 kHz ultrasound, we detected formation of (CH3)-C-. and (CH2N)-C-.(CH3)CHO radical adducts for DMF, mostly (CH2NHCHO)-C-. adducts for MMF, and (CH3)-C-. adducts for DMSO. These radicals were formed either by reactions of the solutes with ultrasound-generated H-. and (OH)-O-. radicals (such as (.)CH(2)R-type radicals in DMF and MMF, and (CH3)-C-. radicals in DMSO), or by direct pyrolysis of the weak bonds in the solute molecules (e.g., (CH3)-C-. radicals from DMF). In air-saturated sonicated solutions these carbon centered radicals were converted to the corresponding peroxyl radicals and spin trapped with 5,5-dimethyl-1-pyrroline-N-oxide (DMPO); (OOCH2N)-O-.(CH3)CHO radicals were identified in DMF, (OOCH2NHCHO)-O-. radicals in MMF, and (OOCH3)-O-. radicals in DMSO solutions. We suggest that these radical species by virtue of their longer lifetimes and higher selectivity, compared to (OH)-O-. radicals, which are also formed in sonicated solutions, are the species responsible for sonodynamic cell killing by the combined effect of ultrasound with DMF, MMF, or DMSO. C1 NCI, RADIAT BIOL BRANCH, BETHESDA, MD 20892 USA. NR 43 TC 36 Z9 41 U1 1 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 1996 VL 20 IS 1 BP 129 EP 138 PG 10 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA TM326 UT WOS:A1996TM32600016 PM 8903689 ER PT J AU VanderZee, J Barr, DP Mason, RP AF VanderZee, J Barr, DP Mason, RP TI ESR spin trapping investigation of radical formation from the reaction between hematin and tert-butyl hydroperoxide SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE hematin; tert-butyl hydroperoxide; radical; ESR; spin trapping; free radicals ID ALKOXYL RADICALS; ORGANIC HYDROPEROXIDES; CUMENE HYDROPEROXIDE; AQUEOUS-SOLUTION; PEROXY-RADICALS; RESONANCE; ALKYL; DECOMPOSITION; SPECTROSCOPY; SUPEROXIDE AB Various mechanisms have been proposed for the reaction between heme proteins and organic hydroperoxides, including a peroxidase-type mechanism and homolytic cleavage. We used electron spin resonance (ESR) spectroscopy to investigate the formation of radicals in a hematin/tert-butyl hydroperoxide system. Spin trapping studies, using 5,5-dimethyl-1-pyrroline N-oxide (DMPO), showed the formation of peroxyl and alkoxyl radicals in this system. At higher hematin concentrations an alkyl radical adduct could also be detected, which was identified as the methyl radical by using the spin trap 2-methyl-2-nitrosopropane. Furthermore, the relative contribution of the peroxyl and alkoxyl radical adducts was determined at various DMPO concentrations using computer simulation. It was found that at low DMPO concentrations both the alkoxyl and the peroxyl radical adducts could be detected. At higher DMPO concentrations, on the other hand, the alkoxyl radical dominated, whereas the peroxyl radical adduct decreased to a small portion of the total radical adduct population. Thus, the alkoxyl radical was the initial radical, produced by homolytic scission of the O-O bond of the hydroperoxide by ferric hematin. Although some tert-butyl peroxyl radicals could be detected by direct ESR, the majority of the peroxyl radicals detected by spin trapping were methyl peroxyl radicals, formed in the reaction between methyl radicals (formed by p-scission of the alkoxyl radicals) and Oxygen. C1 NIEHS,MOLEC BIOPHYS LAB,RES TRIANGLE PK,NC 27709. RP VanderZee, J (reprint author), LEIDEN STATE UNIV,DEPT MED BIOCHEM,SYLVIUS LAB,POB 9503,2300 RA LEIDEN,NETHERLANDS. NR 29 TC 87 Z9 89 U1 3 U2 13 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 1996 VL 20 IS 2 BP 199 EP 206 DI 10.1016/0891-5849(95)02031-4 PG 8 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA TN600 UT WOS:A1996TN60000004 PM 8746440 ER PT J AU Snell, JC Colton, CA Chernyshev, ON Gilbert, DL AF Snell, JC Colton, CA Chernyshev, ON Gilbert, DL TI Location-dependent artifact for no measurement using multiwell plates SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE air pollution; cell culture; Griess reaction; multiwell plates; nitric oxide; free radicals ID L-ARGININE; NITRITE; OXIDATION; NITRATE AB The Griess reaction is widely used to measure the cellular production of NO by detecting the supernatant levels of nitrite. Ordinarily, background levels of nitrite in the media are subtracted from the levels of nitrite produced by the cells by preparing a ''blank'' during the determination of the standard curve. Although this method is adequate for most experimental conditions, it cannot be used when cell supernatants are collected from multiwell dishes, particularly when low amounts of NO are produced and when long incubation periods are required to induce NO production. Our data show that a highly variable level of nitrite is found in the absence of cells in the media from wells at the edges of the 96-well plate while media from interior wells shows no detectable nitrite accumulation. The most likely source of this noncellular NO is from nitric oxides (NOx) found in the ambient air and reduction of air exchange or regulation of the gaseous environment eliminates this ''border effect.'' C1 NINCDS,UNIT REACT OXYGEN SPECIES,BIOPHYS SECT,BNP,NIH,BETHESDA,MD 20892. GEORGETOWN UNIV,SCH MED,DEPT PHYSIOL & BIOPHYS,WASHINGTON,DC 20007. NR 7 TC 11 Z9 11 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 1996 VL 20 IS 3 BP 361 EP 363 DI 10.1016/0891-5849(96)02083-7 PG 3 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA TY878 UT WOS:A1996TY87800012 PM 8720906 ER PT J AU Guyton, KZ Spitz, DR Holbrook, NJ AF Guyton, KZ Spitz, DR Holbrook, NJ TI Expression of stress response genes GADD153, c-jun, and heme oxygenase H2O2- and O-2-resistant fibroblasts SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE H2O2; oxidative stress; adaptation; stress response; gene expression; free radicals ID INCREASED CATALASE ACTIVITY; HYDROGEN-PEROXIDE; CELLULAR-RESISTANCE; OXIDATIVE STRESS; OXIDANT STRESS; GROWTH ARREST; DNA DAMAGE; CIS-FOS; INDUCTION; CELLS AB In the present study, the expression of the stress-inducible genes GADD153, c-jun, heme oxygenase-1 (HO-1), and HSP70 was compared among parental hamster diploid fibroblasts (HA-1), and cell lines isolated for resistance to either H2O2 (OC14) or O-2 (O(2)R95). Both OC14 and O(2)R95 cell lines are known to have significantly augmented cellular antioxidant defenses, including increased glutathione content, as well as enhanced catalase, superoxide dismutase, and glutathione peroxidase activities. Northern analysis indicated that basal expression of HO-1 and c-jun is also elevated in these resistant cell lines. Relative to HA-1 values, basal GADD153 mRNA expression was approximately threefold higher in O(2)R95, but twofold lower in OC14 cells. HSP70 mRNA expression was comparable among parental and resistant cell lines. Both OC14 and O(2)R95 cells showed greatly enhanced survival following H2O2 exposure. The H2O2 doses that induced 50% toxicity in parental and resistant cells (3 vs. 30-60 x 10(-13) mel/cell, respectively) differed by more than an order of magnitude. Similarly, GADD153, c-jun, and HO-1 mRNA were elevated in control cells following exposure to doses of H2O2 an order of magnitude lower than is required for gene activation in resistant cell lines. Nonetheless, at equitoxic doses, the level of induction of GADD153 and HO-1 was greater in resistant than in parental cell lines. Taken together, our results suggest that alterations in the basal level of expression of certain stress-responsive genes, including HO-1, c-jun, and GADD153, may contribute to the H2O2-resistant phenotype in these fibroblast cell lines. Further, changes in the regulation of these genes in response to adverse stimuli may provide an additional mechanism for enhanced cell survival following oxidative stress. C1 NIA,GERONTOL RES CTR,SECT GENE EXPRESS & AGING,BALTIMORE,MD 21224. WASHINGTON UNIV,MED CTR,MALLINCKRODT INST RADIOL,RADIAT ONCOL CTR,SECT CANC BIOL,ST LOUIS,MO 63110. FU NCI NIH HHS [P01CA51116]; NHLBI NIH HHS [R01HL51469] NR 37 TC 28 Z9 28 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 1996 VL 20 IS 5 BP 735 EP 741 DI 10.1016/0891-5849(95)02151-5 PG 7 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA UD144 UT WOS:A1996UD14400009 PM 8721617 ER PT J AU Joseph, JA VillalobosMolina, R Denisova, N Erat, S Cutler, R Strain, J AF Joseph, JA VillalobosMolina, R Denisova, N Erat, S Cutler, R Strain, J TI Age differences in sensitivity to H2O2- or NO-induced reductions in K+-evoked dopamine release from superfused striatal slices: Reversals by PBN or Trolox SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE aging; striatum; oxidative stress; dopamine release; Trolox; PBN; NO.; H2O2; free radicals ID HEAVY-PARTICLE IRRADIATION; BETA-ADRENERGIC-RECEPTOR; NITRIC-OXIDE; LIPID-PEROXIDATION; SENESCENCE; SUPEROXIDE; MEMBRANES; DAMAGE; BRAIN; RAT AB Previous research has indicated that many age-related functional alterations may be the result of a decreased ability of the organism to respond to oxidative stress (OS). However, this hypothesis is based on indirect indices of function (e.g., increased vulnerability of hepatocytes from senescent animals to H2O2-induced DNA damage, increases in lipofuscin accumulation). More direct tests of this hypothesis, especially as it relates to brain aging, have not been extensively undertaken. Present experiments were carried out to make such tests by examining age differences in the sensitivity to OS on reductions in striatal dopamine (DA) release. Thus, K+- evoked DA (K+-ERDA) release from superfused striatal slices from young (6-8 month) and old (24-25 month) animals was examined following either: (a) application of the NO-generator sodium nitroprusside or (b) preincubation with H2O2. in order to assess the specific effects of OS on muscarinic (mAChR) sensitivity, oxotremorine-enhancement of K+-ERDA was examined following incubation with H2O2. Results showed that the striatal tissue from the old animals showed greater sensitivity to both H2O2 and NO than young animals, and stimulated DA decreased at lower concentrations of these agents (e.g., NO-100 mu M young, 30 mu M old). In addition, H2O2 was also effective in reducing oxo-enhanced K+-ERDA and was more effective as a function of age. If the striatal tissue was incubated in either Trolox (alpha-tocopherol) or alpha-phenyl-n-tert-butyl nitrone (PEN) prior to OS, the negative effects of NO. and H2O2 were reversed in both age groups, Results are discussed in terms of age-related membrane and endogenous antioxidant alterations that could induce increases in sensitivity to OS and the specificity of antioxidants in reducing this sensitivity in key functional systems. C1 IPN,CINVESTAV,DEPT PHARMACOL & TOXICOL,MEXICO CITY 14000,DF,MEXICO. NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. RP Joseph, JA (reprint author), TUFTS UNIV,USDA,HUMAN NUTR RES CTR AGING,ARS,ROOM 919,711 WASHINGTON ST,BOSTON,MA 02111, USA. NR 52 TC 57 Z9 60 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 1996 VL 20 IS 6 BP 821 EP 830 DI 10.1016/0891-5849(95)02225-2 PG 10 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA UE965 UT WOS:A1996UE96500008 PM 8728030 ER PT J AU Misik, V Miyoshi, N Riesz, P AF Misik, V Miyoshi, N Riesz, P TI EPR spin trapping study of the decomposition of azo compounds in aqueous solutions by ultrasound: Potential for use as sonodynamic sensitizers for cell killing SO FREE RADICAL RESEARCH LA English DT Article DE free radicals; azo compounds; ultrasound; sonodynamic therapy; sonosensitization; EPR ID PHOTOCHEMICAL DECOMPOSITION; HYDROGEN-ATOMS; RADICALS; HEMATOPORPHYRIN; THERMOLYSIS; AZIDE AB Sonodynamic therapy, a promising new approach to cancer treatment, is based on synergistic cell killing by combination of certain drugs (sonosensitizers) and ultrasound. Although the mechanism of sonodynamic action is not understood, the role of free radicals produced from sonosensitizers by ultrasound is im plicated. In this work, we studied formation of free radicals during the decomposition of several water-soluble azo compounds by 50 kHz ultrasound in aqueous solutions. Using the spin trap 3,5-dibromo-4-nitrosobenzene sulfonate (DBNBS) tertiary carbon-centered radicals from 2,2'-azobis (N,N'-dimethyleneisobutyramidine) dihydrochloride (VA-044), 2-(carbamoylazo)-isobutyronitrile (V-30), and 2,2'-azobis (2-amidinopropane) dihydrochloride (AAPH) and (.)CH3 radicals from 1,1'-azobis (N,N'-dimethylformamide) (AAMF) were detected in argon-saturated solutions and the corresponding oxygen-centered radicals (alkoxyl and peroxyl) from VA-044, V-30, and AAPH were identified using the spin trap 5,5'-dimethyl-1-pyrroline-N-oxide (DMPO) in aerated sonicated solutions. No free radicals from 4,4'-dihydroxyazobenzene-3,3'-dicarboxyl acid, disodium salt (DHAB) could be found in either system. While VA-044 and AAPH could also be readily decomposed by heat (42.5 degrees C and 80 degrees C), V-30 decomposition only occurred in the ultrasound-exposed solutions. The most likely mechanism of decomposition of azo compounds by ultrasound is their thermolysis in the heated shell of the liquid surrounding cavitating bubbles driven by ultrasound and/or by pyrolysis inside these bubbles. Experiments using scavengers of (OH)-O-. and H-., which are produced by sonolysis in aqueous solutions, demonstrated that these radicals are not involved in the ultrasound-mediated radical production from the azo compounds. Due to the known cytotoxic potential of free radicals produced from azo compounds, the use of these compounds as ultrasound sensitizers appears to be a promising approach for sonodynamic cell killing. C1 NCI,RADIAT BIOL BRANCH,NIH,BETHESDA,MD 20892. FUKUI MED SCH,DEPT PATHOL,MATSUOKA,FUKUI,JAPAN. NR 32 TC 17 Z9 21 U1 0 U2 4 PU HARWOOD ACAD PUBL GMBH PI READING PA C/O STBS LTD, PO BOX 90, READING, BERKS, ENGLAND RG1 8JL SN 1071-5762 J9 FREE RADICAL RES JI Free Radic. Res. PY 1996 VL 25 IS 1 BP 13 EP 22 DI 10.3109/10715769609145652 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UV863 UT WOS:A1996UV86300003 PM 8814440 ER PT J AU Iwahashi, H Deterding, LJ Parker, CE Mason, RP Tomer, KB AF Iwahashi, H Deterding, LJ Parker, CE Mason, RP Tomer, KB TI Identification of radical adducts formed in the reactions of unsaturated fatty acids with soybean lipoxygenase using continuous flow fast atom bombardment with tandem mass spectrometry SO FREE RADICAL RESEARCH LA English DT Article DE linoleic acid; linolenic acid; arachidonic acid; lipid peroxidation; HPLC/EPR; spin trapping; continuous flow fast atom bombardment combined with tandem mass; spectrometry ID PERFORMANCE LIQUID-CHROMATOGRAPHY; ELECTRON-SPIN RESONANCE; LINOLEIC-ACID; LIPID-PEROXIDATION; ANAEROBIC REACTION; TRAPPED RADICALS; HYDROPEROXIDES; DECOMPOSITION; BIOMOLECULES; SEPARATION AB Structures of alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone (4-POBN) radical adducts formed in the reactions of soybean lipoxygenase with linoleic acid, linolenic acid, and arachidonic acid were determined using continuous flow fast atom bombardment (CF-FAB) combined with tandem mass spectrometry. The radical adducts of these lipoxygenase-dependent reactions were: n-octanoic acid radical, 12,13-dihydroxylinoleic acid radical, 12,13-epoxylinoleic acid radical, and n-pentyl radical from linoleic acid; n-octanoic acid radical, ethyl radical, and cis/trans and/or positional isomers (1- and S-pentenyl) of pentenyl radical from linolenic acid; and 14,15-epoxyarachidonic acid radical and n-pentyl radical from arachidonic acid. Of these radical adducts, the n-octanoic acid radical from linoleic and linolenic acid, the ethyl radical from linolenic acid, and the 12,13-dihydroxylinoleic acid radical are identified for the first time in the reactions of soybean lipoxygenase. Thus the CF-FAB combined with tandem mass spectrometry employed here, by which both radical adducts and their fragment ions can be detected, is shown to be a powerful tool in the structural identification of free radicals. C1 NIEHS,MOL BIOPHYS LAB,NIH,RES TRIANGLE PK,NC 27709. RP Iwahashi, H (reprint author), WAKAYAMA MED COLL,DEPT CHEM,651 HIRONISHI,WAKAYAMA 64963,JAPAN. RI Tomer, Kenneth/E-8018-2013 NR 56 TC 34 Z9 36 U1 0 U2 5 PU HARWOOD ACAD PUBL GMBH PI READING PA C/O STBS LTD, PO BOX 90, READING, BERKS, ENGLAND RG1 8JL SN 1071-5762 J9 FREE RADICAL RES JI Free Radic. Res. PY 1996 VL 25 IS 3 BP 255 EP 274 DI 10.3109/10715769609149051 PG 20 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VJ973 UT WOS:A1996VJ97300007 PM 8889492 ER PT S AU Gauda, EB Gerfen, CR AF Gauda, EB Gerfen, CR BE Zapata, P Eyzaguirre, C Torrance, RW TI Expression and localization of enkephalin, substance P, and substance P receptor genes in the rat carotid body SO FRONTIERS IN ARTERIAL CHEMORECEPTION SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Proceedings Paper CT XIIIth International Symposium on Arterial Chemoreceptors CY MAR 25-29, 1996 CL CATHOLIC UNIV CHILE, EXPTL CTR, SANTIAGO, CHILE SP Int Soc Arterial Chemorecept, Catholic Univ Chile, Natl Commiss Sci & Technol Res, Chile, Andes Fdn, 3rd World Acad Sci, Merck, Chile, Nestle, Chile HO CATHOLIC UNIV CHILE, EXPTL CTR ID NEUROKININ-A; CAT; HYPOXIA; CHEMORECEPTORS; NEUROPEPTIDES; ANTAGONIST C1 NIMH,NEUROPHYSIOL LAB,BETHESDA,MD 20892. RP Gauda, EB (reprint author), JOHNS HOPKINS MED INST,DEPT PEDIAT,BALTIMORE,MD 21287, USA. NR 22 TC 1 Z9 1 U1 0 U2 0 PU PLENUM PRESS DIV PLENUM PUBLISHING CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0065-2598 BN 0-306-45490-4 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 1996 VL 410 BP 313 EP 318 PG 6 WC Cardiac & Cardiovascular Systems; Physiology SC Cardiovascular System & Cardiology; Physiology GA BH18J UT WOS:A1996BH18J00047 PM 9030317 ER PT B AU Lands, WEM AF Lands, WEM BE Vanderhoek, JY TI Control of eicosanoid response intensity SO FRONTIERS IN BIOACTIVE LIPIDS SE GWUMC DEPARTMENT OF BIOCHEMISTRY ANNUAL SPRING SYMPOSIA LA English DT Proceedings Paper CT 16th Washington International Spring Symposium on Health Science CY MAY 06-09, 1996 CL GEORGE WASHINGTON UNIV, WASHINGTON, DC SP ITT Continental Baking Co Inc, Merck Res Lab, Merck Frosst Canada Inc, Searle Tech Support & Adm, Avanti Polar Lipids Inc, Biomol Res Labs Inc, Ciba Geigy Corp Pharm Div, Quest Int Sci & Regulatory Affairs, Pfizer Inc, Cent Res Div, Alza Corp, Assay Designs Inc, Cascade Biochem Ltd, Matreya Inc HO GEORGE WASHINGTON UNIV RP Lands, WEM (reprint author), NIAAA,NIH,6000 EXECUT BLVD,MSC 7003,BETHESDA,MD 20892, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU PLENUM PRESS DIV PLENUM PUBLISHING CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 BN 0-306-45505-6 J9 GWUMC DEPT PY 1996 BP 23 EP 30 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BG91Q UT WOS:A1996BG91Q00004 ER PT B AU Felder, CC Nielsen, A Briley, EM Palkovits, M Richardson, M Riggin, RM Becker, GW AF Felder, CC Nielsen, A Briley, EM Palkovits, M Richardson, M Riggin, RM Becker, GW BE Vanderhoek, JY TI The role of anandamide and related fatty acid ethanolamides as endogenous ligands for the CB1 and CB2 cannabinoid receptors SO FRONTIERS IN BIOACTIVE LIPIDS SE GWUMC DEPARTMENT OF BIOCHEMISTRY ANNUAL SPRING SYMPOSIA LA English DT Proceedings Paper CT 16th Washington International Spring Symposium on Health Science CY MAY 06-09, 1996 CL GEORGE WASHINGTON UNIV, WASHINGTON, DC SP ITT Continental Baking Co Inc, Merck Res Lab, Merck Frosst Canada Inc, Searle Tech Support & Adm, Avanti Polar Lipids Inc, Biomol Res Labs Inc, Ciba Geigy Corp Pharm Div, Quest Int Sci & Regulatory Affairs, Pfizer Inc, Cent Res Div, Alza Corp, Assay Designs Inc, Cascade Biochem Ltd, Matreya Inc HO GEORGE WASHINGTON UNIV RP Felder, CC (reprint author), NIMH,CELL BIOL LAB,BETHESDA,MD 20892, USA. RI Palkovits, Miklos/F-2707-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU PLENUM PRESS DIV PLENUM PUBLISHING CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 BN 0-306-45505-6 J9 GWUMC DEPT PY 1996 BP 157 EP 164 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BG91Q UT WOS:A1996BG91Q00022 ER PT J AU Chapin, RE Stevens, JT Hughes, CL Kelce, WR Hess, RA Daston, GP AF Chapin, RE Stevens, JT Hughes, CL Kelce, WR Hess, RA Daston, GP TI Endocrine modulation of reproduction SO FUNDAMENTAL AND APPLIED TOXICOLOGY LA English DT Article ID HYPOTHALAMIC ARCUATE NUCLEUS; SERTOLI-CELL PROLIFERATION; MICRODISSECTED BRAIN-AREAS; INCREASED TESTIS GROWTH; AGING FEMALE RATS; SPERM PRODUCTION; NEONATAL-HYPOTHYROIDISM; ADULT-RATS; LUTEINIZING-HORMONE; BINDING-SITES AB The ability of foreign compounds to affect the functioning of various endocrine systems is currently thought responsible for a wide variety of effects. The presentations in this symposium reviewed the evidence for and against the involvement of endocrine systems in several different aspects of reproduction. The mechanism behind the ability of a triazine herbicide to cause enhanced appearance of mammary tumors in one strain of female rats is reviewed by Stevens. The data suggest that enhanced aging, not direct mammary modulation, is responsible. Dietary phytoestrogens, the mediators of their actions, their effects in various biological systems, and the relationships between phytoestrogen producers and consumers are all provocatively and succinctly reviewed by Hughes. Kelce presents the strategy used to dissect the mode and mechanisms of action of a fungicide that opened a new awareness in reproductive toxicology: the possibility of xenobiotics being antiandrogens. Finally, to heighten our understanding of the interplay among hormonal systems in vivo, Hess reviews the data that show that androgens are not the only hormones important in the development of the male reproductive system: the pituitary is shown to play a critical role at specific stages of development. The breadth of these presentations, and the implications of their findings, should make us pause and realize how much there is still to discover about the interaction between the reproductive system and anthropogenic compounds. C1 CIBA GEIGY CORP,CROP PROTECT DIV,DEPT TOXICOL,GREENSBORO,NC. WAKE FOREST UNIV,BOWMAN GRAY SCH MED,DEPT COMPARAT MED,COMPARAT MED CLIN RES CTR,WINSTON SALEM,NC 27109. WAKE FOREST UNIV,BOWMAN GRAY SCH MED,DEPT OBSTET & GYNECOL,WINSTON SALEM,NC 27109. US EPA,HLTH EFFECTS RES LAB,DIV DEV TOXICOL,REPROD TOXICOL BRANCH,RES TRIANGLE PK,NC 27711. UNIV ILLINOIS,DEPT VET BIOSCI,URBANA,IL 61801. PROCTER & GAMBLE CO,CINCINNATI,OH 45239. RP Chapin, RE (reprint author), NIEHS,NATL TOXICOL PROGRAM,REPROD TOXICOL GRP,POB 12233,RES TRIANGLE PK,NC 27709, USA. OI Chapin, Robert/0000-0002-5997-1261 NR 87 TC 55 Z9 65 U1 2 U2 10 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0272-0590 J9 FUND APPL TOXICOL JI Fundam. Appl. Toxicol. PD JAN PY 1996 VL 29 IS 1 BP 1 EP 17 DI 10.1006/faat.1996.0001 PG 17 WC Toxicology SC Toxicology GA TQ836 UT WOS:A1996TQ83600001 PM 8838635 ER PT J AU Griffin, RJ Dudley, CN Cunningham, ML AF Griffin, RJ Dudley, CN Cunningham, ML TI Biochemical effects of the mouse hepatocarcinogen oxazepam: Similarities to phenobarbital SO FUNDAMENTAL AND APPLIED TOXICOLOGY LA English DT Article ID RAT-LIVER; METABOLISM; INDUCTION; MICE; PROLIFERATION; DIAZEPAM; BINDING; CELLS AB The National Toxicology Program (NTP) recently determined that the commonly prescribed sedative hypnotic agent oxazepam is a mouse liver carcinogen, Many other benzodiazepines are metabolized to oxazepam resulting in further human exposure to this drug, This has resulted in considerable interest in the mechanism of oxazepam-mediated mouse liver carcinogenesis for use in human risk assessment. Several directions for mechanistic research were examined in this study, B6C3F1 mice were treated with oxazepam-dosed feed at 125 (noncarcinogenic) and 2500 ppm (carcinogenic) for 3, 7, 10, and 21 days. Cell proliferation in liver, cytochrome P450 induction, free radical formation, GSH depletion, and levels of circulating thyroid-stimulating hormone (TSH) were analyzed at these time points, Increased levels of hepatic cell proliferation were observed by 7 days at 125 ppm and by 10 days at 2500 ppm. Microsomal enzyme induction also occurred and was associated with elevated plasma TSH levels. Hepatic GSH levels were slightly depressed but there was no evidence of increased oxidative stress. A similar pattern of biochemical events has been observed to occur during dosed feed treatment with phenobarbital, These results suggest that oxazepam and phenobarbital may induce carcinogenesis by similar mechanisms in mice. RP Griffin, RJ (reprint author), NIEHS, CHEM BRANCH, RES TRIANGLE PK, NC 27709 USA. NR 39 TC 28 Z9 28 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0272-0590 J9 FUND APPL TOXICOL JI Fundam. Appl. Toxicol. PD JAN PY 1996 VL 29 IS 1 BP 147 EP 154 DI 10.1006/faat.1996.0016 PG 8 WC Toxicology SC Toxicology GA TQ836 UT WOS:A1996TQ83600016 PM 8838650 ER PT B AU Wivel, NA AF Wivel, NA GP OECD TI Clinical overview of human gene transfer trials SO GENE DELIVERY SYSTEMS: A STATE-OF-THE-ART REVIEW LA English DT Proceedings Paper CT OECD Ottawa 95 Workshop on Gene Delivery Systems CY JUN 28-30, 1995 CL OTTAWA, CANADA SP OECD C1 NIH,OFF RECOMBINANT DNA ACT,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ORGANIZATION ECONOMIC COOPERATION & DEVELOPMENT PI PARIS PA 2, RUE ANDRE PASCAL, CEDEX 16, 75775 PARIS, FRANCE BN 92-64-14887-6 PY 1996 BP 43 EP 49 PG 7 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA BG56E UT WOS:A1996BG56E00002 ER PT B AU Karlsson, S Medin, JA Migita, M Stahl, SK Schiffmann, R AF Karlsson, S Medin, JA Migita, M Stahl, SK Schiffmann, R GP OECD TI Gene therapy of Gaucher disease SO GENE DELIVERY SYSTEMS: A STATE-OF-THE-ART REVIEW LA English DT Proceedings Paper CT OECD Ottawa 95 Workshop on Gene Delivery Systems CY JUN 28-30, 1995 CL OTTAWA, CANADA SP OECD C1 NIH,MOL & MED GENET SECT,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ORGANIZATION ECONOMIC COOPERATION & DEVELOPMENT PI PARIS PA 2, RUE ANDRE PASCAL, CEDEX 16, 75775 PARIS, FRANCE BN 92-64-14887-6 PY 1996 BP 237 EP 244 PG 8 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA BG56E UT WOS:A1996BG56E00024 ER PT J AU Rao, MS Yukawa, M Omori, M Thorgeirsson, SS Reddy, JK AF Rao, MS Yukawa, M Omori, M Thorgeirsson, SS Reddy, JK TI Expression of transcription factors and stem cell factor precedes hepatocyte differentiation in rat pancreas SO GENE EXPRESSION LA English DT Article DE oval cell; pancreatic hepatocytes; stem cell factor; C/EBP HNF ID ENHANCER-BINDING-PROTEIN; ADULT-RAT; GENE-EXPRESSION; LIVER; PROLIFERATION; REGENERATION; APOPTOSIS; PATTERNS; RECEPTOR; EMBRYOS AB Multiple foci of morphologically and functionally differentiated hepatocytes are induced in the pancreas of adult rats subjected to a copper depletion-repletion regimen. Differentiation of hepatocytes in pancreas is preceded by irreversible depletion of over 90% of pancreatic acinar cells. Progressive acinar cell loss during 4-6 weeks of copper deficiency results in the proliferation of oval cells, some of which may serve as the hepatocyte precursor or stem cells. Albumin mRNA is detected in oval cells at 5 and 6 weeks by in situ hybridization at which time no morphologically identifiable hepatocytes are evident in the pancreas. Immunocytochemical analysis demonstrated the presence of stem cell factor (SCF) in proliferating oval cells during 6 weeks of copper depletion, and Northern blot analysis revealed the expression of liver-enriched transcription factors in the rat pancreas during this 4-6-week period of copper deficiency. CCAAT/enhancer binding protein alpha (C/EBP alpha) mRNA was detected first at 4 weeks of copper deficiency. By 5 and 6 weeks of copper deficiency, the expression of mRNAs of C/EBP alpha, beta, and delta, and hepatocyte nuclear factor-3 beta (HNF-3 beta) was markedly enhanced. This enhanced expression of liver-enriched transcription factors and the SCF during oval cell proliferation in the pancreas preceding the expression of albumin mRNA and subsequent differentiation of hepatocyte phenotype further supports the identity of these oval cells as hepatocyte precursors or stem cells. C1 NCI,EXPT CARCINOGENESIS LAB,NIH,BETHESDA,MD 20892. RP Rao, MS (reprint author), NORTHWESTERN UNIV,SCH MED,DEPT PATHOL,303 E CHICAGO AVE,CHICAGO,IL 60611, USA. FU NIDDK NIH HHS [DK37958] NR 40 TC 23 Z9 24 U1 0 U2 2 PU COGNIZANT COMMUNICATION CORP PI ELMSFORD PA 3 HARTSDALE ROAD, ELMSFORD, NY 10523-3701 SN 1052-2166 J9 GENE EXPRESSION JI Gene Expr. PY 1996 VL 6 IS 1 BP 15 EP 22 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA VT131 UT WOS:A1996VT13100002 PM 8931988 ER PT J AU Humphrey, GW Englander, EW Howard, BH AF Humphrey, GW Englander, EW Howard, BH TI Specific binding sites for a Pol III transcriptional repressor and Pol II transcription Factor YY1 within the internucleosomal spacer region in primate Alu repetitive elements SO GENE EXPRESSION LA English DT Article DE adenovirus; Alu repetitive sequence; chromatin; DNA binding proteins; Pol III ID RNA-POLYMERASE-III; ACID SEQUENCE-ANALYSIS; POLYACRYLAMIDE GELS; CONSENSUS SEQUENCE; GENE-TRANSCRIPTION; PROMOTER ELEMENTS; FAMILY REPEAT; 7SL RNA; C-FOS; DNA AB Alu interspersed repetitive elements possess internal RNA polymerase III promoters that are transcribed in vitro and in transfected mouse cells but are nearly silent in human HeLa cells. Transcriptional repression of these elements is to some extent reversible, as pol III-dependent Alu expression can be induced with herpes simplex or adenovirus. To assess whether sequence-specific DNA binding proteins might contribute to Alu transcriptional silencing, we examined the internucleosomal spacer region surrounding the B box of the Alu pol III promoter in HeLa cell nuclei for evidence of proteins bound at specific sites in vivo. We identified a DNase I-hypersensitive site 5' to the B box and a DNase I-resistant region 3' to the B box in nuclei. An Alu-specific repressor binds to a 5-bp inverted repeat motif overlapping the 5' end of the TFIIIC binding site and may inhibit pol III transcription through competitive displacement. The level of Alu-specific pol III repressor activity is significantly reduced in adenovirus-infected HeLa cells, suggesting that the repressor may contribute to Alu transcriptional silencing in vivo. The 3' DNase I-resistant region coincided with a binding site for the pol II transcription factor YY1 in vitro. YY1 is one of the major proteins in HeLa cells having binding specificity for Alu elements. YY1 bound to tandem arrays of genomic Alu elements may play a role in chromatin organization and silencing. C1 NICHHD,LAB MOL GROWTH REGULAT,NATL INST HLTH,BETHESDA,MD 20892. NR 56 TC 19 Z9 19 U1 0 U2 2 PU COGNIZANT COMMUNICATION CORP PI ELMSFORD PA 3 HARTSDALE ROAD, ELMSFORD, NY 10523-3701 SN 1052-2166 J9 GENE EXPRESSION JI Gene Expr. PY 1996 VL 6 IS 3 BP 151 EP 168 PG 18 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA WK220 UT WOS:A1996WK22000003 PM 9041122 ER PT J AU Gatignol, A Duarte, M Daviet, L Chang, YN Jeang, KT AF Gatignol, A Duarte, M Daviet, L Chang, YN Jeang, KT TI Sequential steps in tat Trans-activation of HIV-1 mediated through cellular DNA, RNA, and protein binding factors SO GENE EXPRESSION LA English DT Article DE Tat; Trans-activation; HIV; cellular factors; RNA binding proteins ID HUMAN-IMMUNODEFICIENCY-VIRUS; LONG TERMINAL REPEAT; HUMAN CHROMOSOME-12; NUCLEAR-PROTEIN; INDEPENDENT ACTIVATION; TRANSACTIVATING REGION; RODENT CELLS; NASCENT RNA; IN-VITRO; TYPE-1 AB The regulation of HIV expression is controlled by the activity of the Long Terminal Repeat (LTR). Trans-activation by the virally encoded Tat protein is one of the main mechanisms of LTR activation. Tat binds to its target, TAR RNA, and cellular proteins that bind the LTR, Tat, or TAR RNA are important components of the trans-activation process. We will review the factors that have been characterized for a possible involvement in this mechanism. Whereas LTR binding proteins consist of Sp1 and TBP, a large number of factors that bind TAR RNA have been isolated. We have previously cloned two of them by RNA probe recognition: TRBP and La. We have shown that the in vitro and in vivo binding of TRBP to TAR RNA correlates with a constant expression of the protein during HIV-1 infection. Several proteins that interact with Tat have mainly positive, but some negative, effects on trans-activation. Genetic studies have defined that human chromosome 12 encodes a protein that will allow trans-activation in rodent cells. The binding and the functional data about these proteins suggest sequential steps for the Tat transactivation mechanism. Each of these intracellular molecular events could be the target for molecular intervention against the virus. C1 INST COCHIN GENET MOLEC,UNITE 322 INSERM,F-75014 PARIS,FRANCE. NIAID,NIH,MOLEC MICROBIOL LAB,BETHESDA,MD 20892. RI Jeang, Kuan-Teh/A-2424-2008 NR 82 TC 36 Z9 38 U1 0 U2 1 PU COGNIZANT COMMUNICATION CORP PI ELMSFORD PA 3 HARTSDALE ROAD, ELMSFORD, NY 10523-3701 SN 1052-2166 J9 GENE EXPRESSION JI Gene Expr. PY 1996 VL 5 IS 4-5 BP 217 EP 228 PG 12 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA UJ748 UT WOS:A1996UJ74800003 PM 8723388 ER PT J AU Rost, K AF Rost, K TI Practice variation in rural mental health care delivery systems SO GENERAL HOSPITAL PSYCHIATRY LA English DT Editorial Material RP Rost, K (reprint author), UNIV ARKANSAS MED SCI HOSP,DEPT PSYCHIAT,NIMH CTR RURAL MENTAL HEALTHCARE RES,SLOT 554,LITTLE ROCK,AR 72205, USA. NR 8 TC 0 Z9 0 U1 2 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0163-8343 J9 GEN HOSP PSYCHIAT JI Gen. Hosp. Psych. PD JAN PY 1996 VL 18 IS 1 BP 1 EP 2 DI 10.1016/0163-8343(95)00131-X PG 2 WC Psychiatry SC Psychiatry GA TX636 UT WOS:A1996TX63600001 PM 8666207 ER PT J AU Kimura, S Hara, Y Pineau, T FernandezSalguero, P Fox, CH Ward, JM Gonzalez, FJ AF Kimura, S Hara, Y Pineau, T FernandezSalguero, P Fox, CH Ward, JM Gonzalez, FJ TI The T/ebp null mouse thyroid-specific enhancer-binding protein is essential for the organogenesis of the thyroid, lung, ventral forebrain, and pituitary SO GENES & DEVELOPMENT LA English DT Article DE T/EBP; gene targeting; thyroid; lung; ventral forebrain; pituitary ID RAT ADENOHYPOPHYSIS; PEROXIDASE GENE; EXPRESSION; PROMOTER; INVITRO; CELLS; DIFFERENTIATION; POUCH; TTF-1; BRAIN AB The thyroid-specific enhancer-binding protein (T/ebp) gene was disrupted by homologous recombination in embryonic stem cells to generate mice lacking T/EBP expression. Heterozygous animals developed normally, whereas mice homozygous for the disrupted gene were born dead and lacked the lung parenchyma. Instead, they had a rudimentary bronchial tree associated with an abnormal epithelium in their pleural cavities. Furthermore, the homozygous mice had no thyroid gland but had a normal parathyroid. In addition, extensive defects were found in the brain of the homozygous mice, especially in the ventral region of the forebrain. The entire pituitary, including the anterior, intermediate, and posterior pituitary, was also missing. In situ hybridization showed that the T/ebp gene is expressed in the normal thyroid, lung bronchial epithelium, and specific areas of the forebrain during early embryogenesis. These results establish that the expression of T/EBP, a transcription factor known to control thyroid-specific gene transcription, is also essential for organogenesis of the thyroid, lung, ventral forebrain, and pituitary. C1 NHLBI,BIOCHEM GENET LAB,BETHESDA,MD 20892. MOLEC HISTOL LAB,GAITHERSBURG,MD 20897. NCI,OFF LAB ANIM SCI,VET & TUMOR PATHOL SECT,FREDERICK,MD 21702. RP Kimura, S (reprint author), NCI,MOLEC CARCINOGENESIS LAB,BETHESDA,MD 20892, USA. OI Fernandez-Salguero, Pedro M./0000-0003-2839-5027 NR 31 TC 775 Z9 788 U1 0 U2 4 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 0890-9369 J9 GENE DEV JI Genes Dev. PD JAN 1 PY 1996 VL 10 IS 1 BP 60 EP 69 DI 10.1101/gad.10.1.60 PG 10 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA TR986 UT WOS:A1996TR98600006 PM 8557195 ER PT S AU Shields, PG AF Shields, PG BE Walker, C Groopman, J Slaga, TJ KleinSzanto, A TI Molecular epidemiology SO GENETICS AND CANCER SUSCEPTIBILITY: IMPLICATIONS FOR RISK ASSESSMENT SE PROGRESS IN CLINICAL AND BIOLOGICAL RESEARCH LA English DT Article; Proceedings Paper CT 8th International Conference on Carcinogenesis and Risk Assessment CY NOV 30-DEC 03, 1994 CL AUSTIN, TX SP NIEHS, NCI, Environm Protect Agcy, Proctor & Gamble, Rohm & Haas, Univ Texas M D Anderson Canc Ctr, Sci Park Res Div, Amer Petr Inst, ILSI, Hlth Environm Sci Inst, Allied Signal, E I Dupont De Nemours, Amer Ind Hlth Council, Hoffman LaRoche, Merck Res Labs, Bristol Myers Squibb Pharm Res Inst, Dermigen ID GLUTATHIONE-S-TRANSFERASE; LUNG-CANCER RISK; SQUAMOUS-CELL CARCINOMA; COMMON GENETIC-DEFECT; HEME-BINDING REGION; GSTM1 NULL GENOTYPE; CYP2D6 ALLELE; POOR METABOLIZERS; CYTOCHROME-P450IA1 GENE; FUNCTIONAL-SIGNIFICANCE RP Shields, PG (reprint author), NCI, HUMAN CARCINOGENESIS LAB, MOL EPIDEMIOL SECT, BLDG 37, ROOM 2C16, BETHESDA, MD 20892 USA. NR 57 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS, INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0361-7742 BN 0-471-13777-4 J9 PROG CLIN BIOL RES JI Prog.Clin.Biol.Res. PY 1996 VL 395 BP 141 EP 157 PG 17 WC Biology; Medicine, Research & Experimental SC Life Sciences & Biomedicine - Other Topics; Research & Experimental Medicine GA BJ03J UT WOS:A1996BJ03J00009 PM 8895987 ER PT S AU Goldman, D Lappalainen, J Ozaki, N AF Goldman, D Lappalainen, J Ozaki, N BE Bock, GR Goode, JA TI Direct analysis of candidate genes in impulsive behaviours SO GENETICS OF CRIMINAL AND ANTISOCIAL BEHAVIOUR SE CIBA FOUNDATION SYMPOSIA LA English DT Article; Proceedings Paper CT Symposium on Genetics of Criminal and Antisocial Behaviour CY FEB 14-16, 1995 CL CIBA FDN, LONDON, ENGLAND SP Ciba Fdn HO CIBA FDN ID DOPAMINE-RECEPTOR GENE; MONOAMINE OXIDASE-A; CEREBROSPINAL-FLUID; ALLELIC ASSOCIATION; 5-HYDROXYINDOLEACETIC ACID; AMINE METABOLITES; SEVERE ALCOHOLISM; VIOLENT BEHAVIOR; D2 RECEPTOR; SEROTONIN AB Antisocial behaviour is both heterogeneous and the product of interacting genetic and environmental factors acting at different levels of causation. Heritability studies show that individual differences in predisposition to antisocial behaviour are transmitted vertically in families by genetic mechanisms. Owing to aetiological heterogeneity and complexity, study of a variety of other behavioural phenotypes may shed more light on the antecedents of antisocial behaviour than direct studies on antisocial behaviour. Identification of genetic vulnerability factors would clarify mechanisms of vulnerability and the role of the environment. Direct gene analysis and genetic linkage analysis have identifed structural variants in genes involved in neurotransmitter function, and some progress has been made towards relating these genetic variants to antisocial personality and other behaviours. Thyroid hormone receptor variants can cause attention deficit/hyperactivity disorder, and a monoamine oxidase A variant leads to aggressive behaviour in one family. Direct gene analyses have revealed nonconservative amino acid substitutions and structural variants (generally rare) at DRD2, DRD3 and DRD4 dopamine receptors and 5-HT1A, 5-HT2A, 5-HT2C and 5-HT7 serotonin receptors. The stage is set to identify the phenotypic significance of these as well as genetic variants at other loci which may be relevant as candidate genes for antisocial behaviour and related behavioural differences. RP Goldman, D (reprint author), NIAAA, NIH, NEUROGENET LAB, 12501 WASHINGTON AVE, ROCKVILLE, MD 20852 USA. RI Ozaki, Norio/M-8908-2014; Goldman, David/F-9772-2010 OI Ozaki, Norio/0000-0002-7360-4898; Goldman, David/0000-0002-1724-5405 NR 71 TC 8 Z9 8 U1 2 U2 5 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, WEST SUSSEX, ENGLAND SN 0300-5208 BN 0-471-95719-4 J9 CIBA F SYMP PY 1996 VL 194 BP 139 EP 152 PG 14 WC Genetics & Heredity; Medicine, General & Internal; Psychiatry SC Genetics & Heredity; General & Internal Medicine; Psychiatry GA BF13Y UT WOS:A1996BF13Y00018 PM 8862874 ER PT S AU Virkkunen, M Goldman, D Linnoila, M AF Virkkunen, M Goldman, D Linnoila, M BE Bock, GR Goode, JA TI Serotonin in alcoholic violent offenders SO GENETICS OF CRIMINAL AND ANTISOCIAL BEHAVIOUR SE CIBA FOUNDATION SYMPOSIA LA English DT Article; Proceedings Paper CT Symposium on Genetics of Criminal and Antisocial Behaviour CY FEB 14-16, 1995 CL CIBA FDN, LONDON, ENGLAND SP Ciba Fdn HO CIBA FDN ID IMPULSIVE FIRE SETTERS; CEREBROSPINAL-FLUID; MONOAMINE METABOLITES; PLATELET MAO; BEHAVIOR; PREDICTION; ABUSE; GENE AB Finnish alcoholic, impulsive, habitually violent offenders have been found to have low brain serotonin (5-hydroxytryptamine; 5-HT) turnover which is associated with impaired impulse control, a history of suicide attempts, hypoglycaemic tendency after an oral glucose load and diurnal activity rhythm dysregulation or hyperactivity. Relatively high cerebrospinal fluid (CSF) free testosterone concentration is a further characteristic of the offenders with antisocial personality disorder. The impulsive offenders may represent a behaviourally extreme group of type 2 alcoholics as defined by Cloninger. A large cohort of 800 subjects, including alcoholic violent offenders, their relatives and male controls, has now been gathered from Finland with support from the National Institute on Alcohol Abuse and Alcoholism. About 200 subjects have provided CSF samples. Leukocytes from the whole cohort have been harvested and immortalized. Genes regulating 5-HT functions are now being systematically analysed from these samples. Thus far, polymorphisms of the tryptophan hydroxylase (TPH) and 5-HT2C receptor genes have been the most informative findings. C1 NIAAA,DIV INTRAMURAL CLIN & BIOL RES,BETHESDA,MD 20892. RP Virkkunen, M (reprint author), UNIV HELSINKI,CENT HOSP,DEPT PSYCHIAT,SF-00180 HELSINKI,FINLAND. RI Goldman, David/F-9772-2010 OI Goldman, David/0000-0002-1724-5405 NR 38 TC 32 Z9 34 U1 1 U2 1 PU JOHN WILEY & SONS LTD PI CHICHESTER PA BAFFINS LANE, CHICHESTER, WEST SUSSEX, ENGLAND PO19 1UD SN 0300-5208 BN 0-471-95719-4 J9 CIBA F SYMP PY 1996 VL 194 BP 168 EP 177 PG 10 WC Genetics & Heredity; Medicine, General & Internal; Psychiatry SC Genetics & Heredity; General & Internal Medicine; Psychiatry GA BF13Y UT WOS:A1996BF13Y00022 PM 8862876 ER PT J AU Boguski, M Chakravarti, A Gibbs, R Green, E Myers, R AF Boguski, M Chakravarti, A Gibbs, R Green, E Myers, R TI Untitled SO GENOME RESEARCH LA English DT Editorial Material C1 CASE WESTERN RESERVE UNIV,CLEVELAND,OH 44106. BAYLOR COLL MED,HOUSTON,TX 77030. NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. STANFORD UNIV,SCH MED,STANFORD,CA 94305. RP Boguski, M (reprint author), NIH,NATL CTR BIOTECHNOL INFORMAT,BETHESDA,MD, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 1054-9803 J9 GENOME RES JI Genome Res. PD JAN PY 1996 VL 6 IS 1 BP U5 EP U5 PG 1 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA TW662 UT WOS:A1996TW66200001 ER PT B AU Lyons, LA OBrien, SJ AF Lyons, LA OBrien, SJ BE Gustafson, JP Flavell, RB TI Prospects for comparative genome analyses among mammals SO GENOMES OF PLANTS AND ANIMALS: 21ST STADLER GENETICS SYMPOSIUM SE STADLER GENETICS SYMPOSIA SERIES LA English DT Proceedings Paper CT 21st Stadler Genetics Symposium - Genomes of Plants and Animals CY MAY 22-24, 1995 CL UNIV MISSOURI, COLUMBIA, MO SP Univ Missouri Columbia, USDA, Agr Res Serv, Anheuser Busch Co Inc, Northrup King Co, Monsanto Co HO UNIV MISSOURI C1 NCI,FREDERICK CANC RES & DEV CTR,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21702. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PLENUM PRESS DIV PLENUM PUBLISHING CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 BN 0-306-45372-X J9 STADLER GEN PY 1996 BP 115 EP 125 PG 11 WC Agronomy; Plant Sciences; Genetics & Heredity; Zoology SC Agriculture; Plant Sciences; Genetics & Heredity; Zoology GA BF84R UT WOS:A1996BF84R00009 ER PT B AU Koonin, EV Tatusov, RL Rudd, KE AF Koonin, EV Tatusov, RL Rudd, KE BE Gustafson, JP Flavell, RB TI Escherichia coli - Functional and evolutionary implications of genome scale computer-aided protein sequence analysis SO GENOMES OF PLANTS AND ANIMALS: 21ST STADLER GENETICS SYMPOSIUM SE STADLER GENETICS SYMPOSIA SERIES LA English DT Proceedings Paper CT 21st Stadler Genetics Symposium - Genomes of Plants and Animals CY MAY 22-24, 1995 CL UNIV MISSOURI, COLUMBIA, MO SP Univ Missouri Columbia, USDA, Agr Res Serv, Anheuser Busch Co Inc, Northrup King Co, Monsanto Co HO UNIV MISSOURI C1 NATL INST HLTH,NATL CTR BIOTECHNOL INFORMAT,NATL LIB MED,BETHESDA,MD 20894. NR 0 TC 3 Z9 3 U1 0 U2 0 PU PLENUM PRESS DIV PLENUM PUBLISHING CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 BN 0-306-45372-X J9 STADLER GEN PY 1996 BP 177 EP 210 PG 34 WC Agronomy; Plant Sciences; Genetics & Heredity; Zoology SC Agriculture; Plant Sciences; Genetics & Heredity; Zoology GA BF84R UT WOS:A1996BF84R00014 ER PT J AU Reynolds, AB Jenkins, NA Gilbert, DJ Copeland, NG Shapiro, DN Wu, J Daniel, JM AF Reynolds, AB Jenkins, NA Gilbert, DJ Copeland, NG Shapiro, DN Wu, J Daniel, JM TI The gene encoding p120(cas), a novel catenin, localizes on human chromosome 11q11 (CTNND) and mouse chromosome 2 (Catns) SO GENOMICS LA English DT Article ID TYROSINE PHOSPHORYLATION; BOX PROTEIN; SUBSTRATE; CELLS AB The p120(cas) gene encodes a protein tyrosine kinase substrate that associates with the cell-cell adhesion protein complex containing E-cadherin and its cytoplasmic cofactors alpha-catenin, beta-catenin, and plakoglobin. Like other components of the cadherin/catenin complex, defects in p120(cas) may contribute to cell malignancy. We have determined the chromosomal location of the p120(cas) gene in human and mouse using fluorescence in situ hybridization and interspecific backcross analysis, respectively. The human p120(cas) gene (CTNND) is localized immediately adjacent to the centromere on the long arm of chromosome 11 in band 11q11. The murine p120(cas) gene (Catns) was assigned to the middle of chromosome 2. Neither locus is currently known to be associated with disease or malignancy. (C) 1996 Academic Press, Inc C1 ST JUDE CHILDRENS RES HOSP, DEPT EXPTL ONCOL, MEMPHIS, TN 38105 USA. NCI, FREDERICK CANC RES & DEV CTR, ABL BASIC RES PROGRAM, MAMMALIAN GENET LAB, FREDERICK, MD 21702 USA. RP Reynolds, AB (reprint author), ST JUDE CHILDRENS RES HOSP, DEPT TUMOR CELL BIOL, 332 N LAUDERDALE ST, MEMPHIS, TN 38105 USA. FU NCI NIH HHS [P30 CA21756, CA55724, N01-CO-46000] NR 17 TC 19 Z9 21 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD JAN 1 PY 1996 VL 31 IS 1 BP 127 EP 129 DI 10.1006/geno.1996.0020 PG 3 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA TR637 UT WOS:A1996TR63700020 PM 8808291 ER PT J AU Saeki, T Salomon, DS Gullick, WJ Nagasako, K Futami, S Mandai, K Yamagami, K Moriwaki, S Nishikawa, Y Takashima, S Tahara, E AF Saeki, T Salomon, DS Gullick, WJ Nagasako, K Futami, S Mandai, K Yamagami, K Moriwaki, S Nishikawa, Y Takashima, S Tahara, E TI Expression of cripto-1 in nonpolypoid adenomas and carcinomas of the human colon SO GI CANCER LA English DT Article DE cripto-1; epidermal growth factor receptor; transforming growth factor alpha; nonpolypoid growth adenomas; human colon carcinomas ID GROWTH-FACTOR-ALPHA; HUMAN GASTROINTESTINAL CARCINOMAS; FLAT COLORECTAL ADENOMAS; CELL-LINE; CANCER-CELLS; FACTOR-RECEPTOR; MESSENGER-RNA; GENE; AMPHIREGULIN; EGF AB Epidermal growth factor (EGF)-related peptides have been implicated in the pathogenesis of colon cancer. The purpose of this study was to evaluate the frequency of expression of a novel EGF-related peptide, cripto-1 (CR-1) in nonpolypoid and polypoid colon adenomas and carcinomas. Methods: CR-1 was assessed by immunocytochemistry in colon specimens. Results: Twenty-six of 36 (72.2%) nonpolypoid, flat adenomas versus 21 of 46 (45.6%) polypoid adenoma samples were positive for CR-1 expression. In the carcinomas, 18 of 23 (78.2%) nonpolypoid growth carcinomas (NPG-carcinomas) and 30 of 41 (73.1%) polypoid growth carcinomas (PG-carcinomas) were positive for CR-1 expression. Only 6 of 102 (5.9%) noninvolved colon mucosa samples exhibited CR-1 expression. In adenomas with a moderate degree of atypia, CR-1 was expressed at a significantly higher frequency in flat, nonpolypoid adenomas than in corresponding polypoid adenomas (p < 0.05). Finally, CR-1 was expressed at a significantly higher frequency in nonpolypoid lesions that were less than 10 mm than in polypoid lesions of the same size (p < 0.05-.01). Conclusions: These data demonstrate that CR-1 may be involved in the early stages of colon cancer development especially from flat, nonpolypoid adenomas. C1 NATL SHIKOKU CANC CTR HOSP,DEPT CLIN RES PATHOL SURG & INTERNAL MED,MATSUYAMA,EHIME 790,JAPAN. NATL CANC INST,NIH,TUMOR GROWTH FACTOR SECT,TUMOR IMMUNOL & BIOL LAB,BETHESDA,MD. HAMMERSMITH HOSP,IMPERIAL CANC RES FUND,MOL ONCOL UNIT,LONDON,ENGLAND. TOKYO WOMENS MED COLL,DEPT INTERNAL MED,TOKYO 162,JAPAN. HIROSHIMA UNIV,SCH MED,DEPT PATHOL,HIROSHIMA,JAPAN. NR 54 TC 0 Z9 0 U1 0 U2 0 PU HARWOOD ACAD PUBL GMBH PI READING PA C/O STBS LTD, PO BOX 90, READING, BERKS, ENGLAND RG1 8JL SN 1064-9700 J9 GI CANCER JI GI Cancer PY 1996 VL 1 IS 4 BP 257 EP & PG 14 WC Oncology; Gastroenterology & Hepatology SC Oncology; Gastroenterology & Hepatology GA VY140 UT WOS:A1996VY14000006 ER PT J AU Handa, JT Berkowitz, BA Wilson, CA Ando, N Sen, HA Jaffe, GJ AF Handa, JT Berkowitz, BA Wilson, CA Ando, N Sen, HA Jaffe, GJ TI Hypoxia precedes the development of experimental preretinal neovascularization SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY LA English DT Article ID PROLIFERATIVE DIABETIC-RETINOPATHY; OXYGEN-TENSION; F-19 NMR; RABBIT; VITREORETINOPATHY; ANGIOGENESIS; DEGENERATION; MACROPHAGES; EYE AB Background: Although the mechanism of preretinal neovascular growth in the cell-injected rabbit eye model is not known, it has been proposed that the initial vasodilation and eventual development of neovascularization may be attributable to inflammatory mediators. However, an alternative explanation involving hypoxia has not been considered. The purpose of this study was to measure preretinal oxygen tension prior to the development of preretinal neovascularization in the cell-injected rabbit eye. Methods: In the rabbit, intravitreous injections of 250 000 homologous dermal fibroblasts were performed on one eye; the fellow (control) eye was injected with vehicle. Preretinal oxygen tension over the myelin wing was measured using F-19-NMR spectroscopy of a 30-mu l droplet of perfluorocarbon previously injected into the preretinal vitreous. Results: Compared to control eyes, fibroblast-injected eyes showed a 1.7-fold decrease in preretinal oxygen tension from the first time studied (1 day after cell injection) through the development of visible neovascularization. Hypoxia occurred without coexisting ophthalmoscopic evidence of vascular occlusion or, on days 1 and 3 after cell injection, retinal detachment. Conclusion: This result demonstrates for the first time that preretinal hypoxia precedes the development of preretinal neovascularization in the fibroblast-injected rabbit eye. C1 UNIV TEXAS,SW MED CTR,DEPT OPHTHALMOL,DALLAS,TX 75235. DUKE EYE CTR,DURHAM,NC. NIEHS,RES TRIANGLE PK,NC 27709. NR 18 TC 8 Z9 8 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0721-832X J9 GRAEF ARCH CLIN EXP JI Graefes Arch. Clin. Exp. Ophthalmol. PD JAN PY 1996 VL 234 IS 1 BP 43 EP 46 DI 10.1007/BF00186517 PG 4 WC Ophthalmology SC Ophthalmology GA TJ786 UT WOS:A1996TJ78600006 PM 8750849 ER PT J AU Li, LP Darden, T Hiskey, R Pedersen, LG AF Li, LP Darden, T Hiskey, R Pedersen, LG TI Computational studies of human prothrombin fragment 1, the Gla domain of factor IX and several biological interesting mutants SO HAEMOSTASIS LA English DT Article; Proceedings Paper CT 3rd Symposium on New Aspects of Haemophilia Treatment CY SEP 21-23, 1995 CL COPENHAGEN, DENMARK DE prothrombin; Gla domain; kringle domain; factor IX; mutant; molecular dynamics ID CARBOXYGLUTAMIC ACID RESIDUES; MEMBRANE-BINDING; PROTEINS; SIMULATION; ION AB We have employed molecular dynamics simulations to understand the properties of the gamma-carboxyglutamic acid (Gla) domains of human prothrombin fragment 1 (residues 1-144) and factor IX (residues 1-47). The simulations are based on (1) the crystal structure of bovine prothrombin fragment 1 in the presence of calcium and (2) our subsequent simulation of the solution structure for which we found accommodation of the long range ionic forces critical. In addition, we have estimated the solution structures for key mutant proteins [prothrombin (Gla6 to Asp and Gla16 to Asp) and factor IX (Gly 12 to Ala)]. The simulations for the latter two mutants do not stabilize, a result in concert with the known biological data. C1 UNIV N CAROLINA,DEPT CHEM,CHAPEL HILL,NC 27599. NIEHS,RES TRIANGLE PK,NC 27709. RI Pedersen, Lee/E-3405-2013 OI Pedersen, Lee/0000-0003-1262-9861 FU NHLBI NIH HHS [HL-06350] NR 17 TC 2 Z9 3 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-0147 J9 HAEMOSTASIS JI Haemostasis PD JAN PY 1996 VL 26 SU 1 BP 54 EP 59 PG 6 WC Hematology SC Hematology GA TZ689 UT WOS:A1996TZ68900012 PM 8904174 ER PT S AU Steinert, P Tarcsa, E Lee, SC Jang, SI Andreoli, J Markova, N AF Steinert, P Tarcsa, E Lee, SC Jang, SI Andreoli, J Markova, N BE vanNeste, D Randall, VA TI Human trichohyalin SO HAIR RESEARCH FOR THE NEXT MILLENIUM SE INTERNATIONAL CONGRESS SERIES LA English DT Proceedings Paper CT 1st Tricontinental Meeting of Hair Research Societies CY OCT 08-10, 1995 CL BRUSSELS, BELGIUM SP Barbara Jordan, US, Bioderma, France, Canfield Sci, US, Clairol, US, Eli Lilly, US, Galderma Belgilux, Belgium, Glaxo, US, Hoyu Co Ltd, Japan, Johnson & Johnson, US, KAO Corp, Japan, L Oreal, France, Lundbeck N V, Belgium, Merck, US, NAAF, US, Neutrogena, US, Oclassen, US, Pierre Fabre Cosmet, France, Pola Labs, Jap, Procter & Gamble, UK, Roussel Uclaf, France, Sandoz, US, Schering, US, Shiseido, Japan, Taisho Pharm Co Ltd, Japan, Soc Hair Sci Res, Unilever, UK, Upjohn, US C1 NIAMSD,SKIN BIOL BRANCH,NATL INST HLTH,BETHESDA,MD 20892. NR 0 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE PUBL B V PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0531-5131 BN 0-444-82336-0 J9 INT CONGR SER PY 1996 VL 1111 BP 169 EP 173 PG 5 WC Dermatology SC Dermatology GA BG40T UT WOS:A1996BG40T00033 ER PT S AU Hansen, LA Lichti, U Tennenbaum, T Dlugosz, AA Threadgill, DW Magnuson, T Yuspa, SH AF Hansen, LA Lichti, U Tennenbaum, T Dlugosz, AA Threadgill, DW Magnuson, T Yuspa, SH BE vanNeste, D Randall, VA TI Altered hair follicle morphogenesis in epidermal growth factor receptor deficient mice SO HAIR RESEARCH FOR THE NEXT MILLENIUM SE INTERNATIONAL CONGRESS SERIES LA English DT Proceedings Paper CT 1st Tricontinental Meeting of Hair Research Societies CY OCT 08-10, 1995 CL BRUSSELS, BELGIUM SP Barbara Jordan, US, Bioderma, France, Canfield Sci, US, Clairol, US, Eli Lilly, US, Galderma Belgilux, Belgium, Glaxo, US, Hoyu Co Ltd, Japan, Johnson & Johnson, US, KAO Corp, Japan, L Oreal, France, Lundbeck N V, Belgium, Merck, US, NAAF, US, Neutrogena, US, Oclassen, US, Pierre Fabre Cosmet, France, Pola Labs, Jap, Procter & Gamble, UK, Roussel Uclaf, France, Sandoz, US, Schering, US, Shiseido, Japan, Taisho Pharm Co Ltd, Japan, Soc Hair Sci Res, Unilever, UK, Upjohn, US C1 NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BETHESDA,MD 20892. NR 0 TC 7 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE PUBL B V PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0531-5131 BN 0-444-82336-0 J9 INT CONGR SER PY 1996 VL 1111 BP 425 EP 431 PG 7 WC Dermatology SC Dermatology GA BG40T UT WOS:A1996BG40T00088 ER PT J AU Mosnaim, AD Freitag, FG Ignacio, R Salas, MA Karoum, F Wolf, ME Diamond, S AF Mosnaim, AD Freitag, FG Ignacio, R Salas, MA Karoum, F Wolf, ME Diamond, S TI Apparent lack of correlation between tyramine and phenylethylamine content and the occurrence of food-precipitated migraine - Reexamination of a variety of food products frequently consumed in the United States and commonly restricted in tyramine-free diets SO HEADACHE QUARTERLY-CURRENT TREATMENT AND RESEARCH LA English DT Article DE tyramine; phenylethylamine; diet-precipitated headaches ID MONOAMINE-OXIDASE INHIBITORS; PRESSOR AMINES; PHENELZINE; HEADACHES; EPISODE AB Objective: There is abundant evidence to support the assumption that vasoactive substances present in food are, at least in part, responsible for the etiology of diet-precipitated vascular headaches. However, the data currently available concerning the food contents of individual, suspected substances such as p-tyramine (TYR) and phenylethylamine (PEA), and upon which most clinical decisions are currently made, are based on studies performed mostly in European countries and Canada. In many cases, this information is up to 30 years old. The development of sophisticated analytical procedures to measure these vasoactive amines, changes in food manufacturing techniques, and the availability of a vast array of new dietary choices, make a compelling case for the reexamination of the content of these substances in various commonly consumed foods in the United States. Design: A variety of food samples, eg selected beers, liquors, wines, various cheeses, meat and seafood products, as well as miscellaneous foodstuffs, were bought from the two largest grocery chains in the Chicago area and assayed for TYR, m-TYR and PEA content using mass fragmentography analysis. This procedure is highly specific, sensitive, accurate, and reproducible. The use of deuterated compounds allows for correction of differences in the relative percentage of extraction of the studied amines from the various food samples, for possible amine losses during their derivatization procedure, and to control for any inconsistencies that may influence experimental reproducibility. Results: This study indicated that the content of TYR in ''usual portions'' of a variety of fresh, non-spoiled foods and beverages commonly consumed in the United States is too small (mostly nanogram to microgram amounts; rarely over 1 mg and never more than 5 mg) to trigger migraine. However, the levels of this amine increases significantly in some poorly conserved products, particularly in those containing meat and fish. The contents of either m-TYR or PEA never exceeded 10 ng per mt or g of the various foodstuffs studied. This information will hopefully lead to a more rational design of friendly-diets for food sensitive migraine patients, thus increasing the patient's quality of life. Conclusions: Although most clinicians would agree to the existence of ''diet-triggered migraine,'' attempts to link the occurrence of vascular headaches in vulnerable patients with the ingestion of specific foods ''allegedly rich in NR and/or PEA'' content have failed to yield consistent, reproducible results. In spite of these findings, and helping to further confuse the patients, there is a great number of sometimes widely different so-called TYR-free dials currently recommended by clinicians as migraine-friendly. Our results should encourage a reexamination of the TYR and PEA contents in foods labeled as restricted in currently used TYR-free diets, and a reevaluation of the possible role of these amines, if any, in the etiology of food-precipitated vascular headaches. C1 FINCH UNIV HLTH SCI CHICAGO MED SCH,DEPT MOL BIOL & PHARMACOL,N CHICAGO,IL 60064. DIAMOND HEADACHE CLIN LTD,CHICAGO,IL. CHICAGO COLL OSTEOPATH MED,DEPT FAMILY MED,DOWNERS GROVE,IL. ST ELIZABETH HOSP,NIMH,CTR NEUROSCI,WASHINGTON,DC 20032. LOYOLA UNIV,STRITCH SCH MED,MAYWOOD,IL 60153. COLUMBUS HOSP,DIAMOND HEADACHE CLIN,CHICAGO,IL. COLUMBUS HOSP,INPATIENT HEADACHE PROGRAM,CHICAGO,IL. VET AFFAIRS MED CTR,TARDIVE DYSKINESIA PROGRAM,N CHICAGO,IL. NR 43 TC 4 Z9 4 U1 2 U2 4 PU INT UNIV PRESS INC PI MADISON PA 59 BOSTON POST RD PO BOX 1524, MADISON, CT 06443-1524 J9 HEADACHE Q-CURR TREA JI Headache Q.-Curr. Treat. Res. PY 1996 VL 7 IS 3 BP 239 EP 249 PG 11 WC Neurosciences SC Neurosciences & Neurology GA VE855 UT WOS:A1996VE85500008 ER PT J AU Delahanty, DL Dougall, AL Schmitz, JB Hawken, L Trakowski, JH Jenkins, FJ Baum, A AF Delahanty, DL Dougall, AL Schmitz, JB Hawken, L Trakowski, JH Jenkins, FJ Baum, A TI Time course of natural killer cell activity and lymphocyte proliferation in response to two acute stressors in healthy men SO HEALTH PSYCHOLOGY LA English DT Article DE stress; psychoneuroimmunology; immune; natural killer cells; lymphocyte proliferation ID PSYCHOLOGICAL STRESS; IMMUNE FUNCTION; CYTO-TOXICITY; HUMANS; CANCER; IMMUNOCOMPETENCE; SUSCEPTIBILITY; MEDIATION; DISEASE; EMOTION AB To clarify the time course of immune system activity during and after acute stresser exposure, this study collected immune measures from 31 men at 6 times (before, during, and after 2 common laboratory stressors; mental arithmetic with harassment or a cold presser task). The 6-min stresser period was associated with increased self-report of pain and distress in both stresser groups and with increased systolic and diastolic blood pressure and heart rate in the mental arithmetic group. Increased natural killer cell activity in this group was observed during the task (2 and 5 min into the task) and 5 min after the task ended. A significant Group x Time effect was observed for lymphocyte proliferation to pokeweed mitogen, and a significant Group x Time x Dilution effect was observed for proliferation to concanavalin A. Inspection of the data suggested that this interaction was due to a reduction in proliferation in both stresser groups during the task period. C1 UNIFORMED SERV UNIV HLTH SCI,DEPT MED & CLIN PSYCHOL,BETHESDA,MD. NIH,BETHESDA,MD 20892. RP Delahanty, DL (reprint author), UNIV PITTSBURGH,MED CTR,PITTSBURGH CANC INST,DIV BEHAV MED & ONCOL,405 IROQUOIS BLDG,PITTSBURGH,PA 15213, USA. RI Jenkins, Frank/A-8529-2009 FU NIMH NIH HHS [MH 40106] NR 40 TC 35 Z9 35 U1 1 U2 1 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 0278-6133 J9 HEALTH PSYCHOL JI Health Psychol. PD JAN PY 1996 VL 15 IS 1 BP 48 EP 55 DI 10.1037/0278-6133.15.1.48 PG 8 WC Psychology, Clinical; Psychology SC Psychology GA TP896 UT WOS:A1996TP89600006 PM 8788540 ER PT J AU Han, JY Wee, JH Kim, JM Kim, JY Kim, IH Rodgers, GP AF Han, JY Wee, JH Kim, JM Kim, JY Kim, IH Rodgers, GP TI A new observation of Hb Yamagata with a different nucleotide substitution: beta 132AAA->AAT SO HEMOGLOBIN LA English DT Article ID HEMOGLOBIN C1 NIDDK,NIH,BIOL CHEM LAB,BETHESDA,MD 20892. RP Han, JY (reprint author), DONG A UNIV,COLL MED,LIFE SCI RES INST,PUSAN 602103,SOUTH KOREA. NR 6 TC 4 Z9 4 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 SN 0363-0269 J9 HEMOGLOBIN JI Hemoglobin PY 1996 VL 20 IS 2 BP 165 EP 168 DI 10.3109/03630269609027924 PG 4 WC Biochemistry & Molecular Biology; Hematology SC Biochemistry & Molecular Biology; Hematology GA UV073 UT WOS:A1996UV07300011 PM 8811322 ER PT J AU Bisgaard, HC Nagy, P SantoniRugiu, E Thorgeirsson, SS AF Bisgaard, HC Nagy, P SantoniRugiu, E Thorgeirsson, SS TI Proliferation, apoptosis, and induction of hepatic transcription factors are characteristics of the early response of biliary epithelial (oval) cells to chemical carcinogens SO HEPATOLOGY LA English DT Article ID RAT-LIVER; ALPHA-FETOPROTEIN; HEPATOCYTES; HEPATOCARCINOGENESIS; EXPRESSION AB In this study, we used [H-3]thymidine labeling of newly synthesized DNA to examine the earliest effects of 2-acetylaminofluorene (2-AAF) on the mitotic activation of cells in the adult rat liver, and in situ hybridization analysis to study the expression of three transcription factors (HNF1 beta, HNF3 gamma, and HNF4), and two of the genes (cu-fetoprotein [AFP] and albumin) regulated by these factors. A low dose of 2-AAF (and its analogs, 2-AF [2-aminofluorene] and N-OH-2-AAF) elicited a mitogenic response in ductal cells and nondescript periductular cells within 24 hours after administration. The compounds also induced the expression of HNF1 beta, HNF3 gamma, AFP, and albumin in ductal structures but had no detectable effect of HNF4 expression, In contrast, initiation of bile duct proliferation by ligation of the common bile duct had no effect on the expression of these genes in ductal cells. In addition to inducing a mitogenic response, 2-AAF resulted in increased numbers of apoptotic cells in the portal areas, a process that contributed to overall retention of liver morphology. Our results demonstrate that 2-AAF and some of its analogs can elicit a specific mitogenic response and induce expression of the ''establishment'' transcription factors, HNF1 beta and HNF3 gamma, in ductal cells, Our data provide further support of a precursor-product relationship between ''stem-like'' cells located in ductal structures, oval cells, and hepatocytes. C1 NCI,EXPTL CARCINOGENESIS LAB,BETHESDA,MD 20892. NR 31 TC 66 Z9 67 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD JAN PY 1996 VL 23 IS 1 BP 62 EP 70 DI 10.1002/hep.510230110 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA TN801 UT WOS:A1996TN80100010 PM 8550050 ER PT J AU Nagy, P Bisgaard, HC SantoniRugiu, E Thorgeirsson, SS AF Nagy, P Bisgaard, HC SantoniRugiu, E Thorgeirsson, SS TI In vivo infusion of growth factors enhances the mitogenic response of rat hepatic ductal (oval) cells after administration of 2-acetylaminofluorene SO HEPATOLOGY LA English DT Article ID LIVER-REGENERATION; FACTOR-ALPHA; C-MYC; PARTIAL-HEPATECTOMY; EXPRESSION; DIFFERENTIATION; PROLIFERATION; HEPATOCYTES; ACTIVATION; APOPTOSIS AB Expression of several growth factors is elevated in rat liver, after induction of oval cell proliferation by chemical carcinogens. However, the exact roles played by individual factors are not defined, We infused and examined the effects of epidermal growth factor (EGF) and hepatocyte growth factor (HGF) on the proliferation of ductal and periductal cells after their activation with 2-acetylaminofluorene (2-AAF). Furthermore, we included studies on urokinase-type plasminogen activator (uPA), because Northern blot analysis showed a strong coincidence of uPA expression with oval cell proliferation, Low doses of 2-AAF were used to activate ductal and periductal cells, whereafter growth factors were infused. Infusion of EGF, HGF, uPA, or any combination thereof for up to 7 days resulted in increased numbers of [H-3]thymidine-labeled ductal and periductal cells expanding into the liver acinus, Although the growth factors all increased the number of labeled cells, they preferentially acted on different cell populations. Although exposure to 2-AAF alone or combined with infusion of HGF resulted in proliferation of almost equal numbers of ductal and Ito cells, infusion of EGF and any combination hereof resulted in 75% to 80% of labeled cells having a ductal phenotype. Also, infusion of EGF and HGF resulted in decreased numbers of cells undergoing apoptosis in response to 2-AAF, Our results demonstrate that, although 2-AAF acts as a mitogenic stimulus for ductal and periductal cells, growth factors are necessary for survival, motility, and expansion of these cells into the liver acini. C1 NCI,EXPTL CARCINOGENESIS LAB,BETHESDA,MD 20892. NR 38 TC 68 Z9 71 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD JAN PY 1996 VL 23 IS 1 BP 71 EP 79 DI 10.1002/hep.510230111 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA TN801 UT WOS:A1996TN80100011 PM 8550051 ER PT J AU Mosley, JVV Nowicki, MJ Aach, RD Barbosa, LH Nemo, GF Yun, A Kim, JP AF Mosley, JVV Nowicki, MJ Aach, RD Barbosa, LH Nemo, GF Yun, A Kim, JP TI Pattern of RNA detectability during course of transfusion-transmitted HGV hepatitis SO HEPATOLOGY LA English DT Meeting Abstract C1 UNIV SO CALIF,LOS ANGELES,CA 90089. NHLBI,BETHESDA,MD 20892. GENELABS TECHNOL INC,REDWOOD CITY,CA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD JAN PY 1996 VL 23 IS 1 BP T46 EP T46 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA TN801 UT WOS:A1996TN80100078 ER PT J AU Williams, AO Knapton, AD Geiser, A Letterio, JJ Roberts, AB AF Williams, AO Knapton, AD Geiser, A Letterio, JJ Roberts, AB TI Ultrastructural analysis of hepatocytes in TGF-beta 1 gene knockout mice suggests novel roles in carbohydrate processing SO HEPATOLOGY LA English DT Meeting Abstract C1 NCI,LAB EXPTL PATHOL,BETHESDA,MD 20892. NCI,CHEMOPREVENT LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD JAN PY 1996 VL 23 IS 1 BP T75 EP T75 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA TN801 UT WOS:A1996TN80100105 ER PT J AU Pei, XF Yu, QS Lu, BY Greig, NH Brossi, A AF Pei, XF Yu, QS Lu, BY Greig, NH Brossi, A TI Practical total syntheses of physostigmines and of phenserines: A synopsis SO HETEROCYCLES LA English DT Article ID UNNATURAL (+)-PHYSOSTIGMINE; (-)-PHYSOSTIGMINE; ANALOGS; (-)-PHYSOVENOL; (-)-ESEROLINE; ENANTIOMERS; ALKALOIDS; OXINDOLES; ROUTE AB (+/-)-1,3-Dimethyl-3-cyanomethyl-5-methoxyoxindole (8), or (3S)-enriched 8 obtained by asymmetric alkylation, separated into the optically pure enantiomers (8a) and (8b) when chromatographed on a microcrystalline cellulose triacetate (MCTA) column. Asymmetric alkylation of (+/-)-1,3-dimethyl-5-tetrahydropyranyloxyoxindole (6) gave the nitrile (9) ((3S) 66 % ee) which could not be separated on the MCTA column. Optically pure eseroline (17a) was obtained by recrystallization of the fumarate salt (66 % ee) obtained from 9 after reduction with Vitride, reductive N-methylation, and treatment with 2N HCl. C1 NIA,NEUROSCI LAB,BETHESDA,MD 20892. ACAD SINICA,SHANGHAI INST ORGAN CHEM,SHANGHAI 200032,PEOPLES R CHINA. GEORGETOWN UNIV,DEPT CHEM,WASHINGTON,DC 20057. NR 30 TC 19 Z9 20 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0385-5414 J9 HETEROCYCLES JI Heterocycles PD JAN 1 PY 1996 VL 42 IS 1 BP 229 EP 236 PG 8 WC Chemistry, Organic SC Chemistry GA TQ113 UT WOS:A1996TQ11300037 ER PT B AU Sekely, LI AF Sekely, LI BE Li, JJ Li, SA Gustafsson, JA Nandi, S Sekely, LI TI Introductory remarks SO HORMONAL CARCINOGENESIS II LA English DT Proceedings Paper CT 2nd International Hormonal Carcinogenesis Symposium CY 1994 CL STOCKHOLM, SWEDEN SP NIEHS, NIH, NICHHD, Off Res Womens Hlth, Karolinska Inst, NOVUM Res Pk, Ctr Nutr & Toxicol, Med Res Council Sweden, Stockholm Canc Soc, Wyeth Ayerst Res, R W Johnson Pharm Res Inst, Schering AG, Int Life Sci Inst, Risk Sci Inst, Phytosyn Inc, Zenayako Kogyo Co Ltd, Bayer, Amer Tobacco Inst, NIDDKD, Upjohn Co, Nitta Gelatin Inc C1 NCI,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 BN 0-387-94469-9 PY 1996 BP 1 EP 1 PG 1 WC Oncology; Endocrinology & Metabolism SC Oncology; Endocrinology & Metabolism GA BF44F UT WOS:A1996BF44F00001 ER PT B AU Pinn, VW AF Pinn, VW BE Li, JJ Li, SA Gustafsson, JA Nandi, S Sekely, LI TI Important questions in women's health research: Determining the influence of hormones on health - Opening address SO HORMONAL CARCINOGENESIS II LA English DT Proceedings Paper CT 2nd International Hormonal Carcinogenesis Symposium CY 1994 CL STOCKHOLM, SWEDEN SP NIEHS, NIH, NICHHD, Off Res Womens Hlth, Karolinska Inst, NOVUM Res Pk, Ctr Nutr & Toxicol, Med Res Council Sweden, Stockholm Canc Soc, Wyeth Ayerst Res, R W Johnson Pharm Res Inst, Schering AG, Int Life Sci Inst, Risk Sci Inst, Phytosyn Inc, Zenayako Kogyo Co Ltd, Bayer, Amer Tobacco Inst, NIDDKD, Upjohn Co, Nitta Gelatin Inc C1 NIH,DEPT HLTH & HUMAN SERV,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 BN 0-387-94469-9 PY 1996 BP 2 EP 10 PG 9 WC Oncology; Endocrinology & Metabolism SC Oncology; Endocrinology & Metabolism GA BF44F UT WOS:A1996BF44F00002 ER PT B AU Perlman, JA Porter, J AF Perlman, JA Porter, J BE Li, JJ Li, SA Gustafsson, JA Nandi, S Sekely, LI TI Patterns of cancer mortality in women who had used sex steroid hormones under age 60 SO HORMONAL CARCINOGENESIS II LA English DT Proceedings Paper CT 2nd International Hormonal Carcinogenesis Symposium CY 1994 CL STOCKHOLM, SWEDEN SP NIEHS, NIH, NICHHD, Off Res Womens Hlth, Karolinska Inst, NOVUM Res Pk, Ctr Nutr & Toxicol, Med Res Council Sweden, Stockholm Canc Soc, Wyeth Ayerst Res, R W Johnson Pharm Res Inst, Schering AG, Int Life Sci Inst, Risk Sci Inst, Phytosyn Inc, Zenayako Kogyo Co Ltd, Bayer, Amer Tobacco Inst, NIDDKD, Upjohn Co, Nitta Gelatin Inc C1 NCI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 BN 0-387-94469-9 PY 1996 BP 350 EP 355 PG 6 WC Oncology; Endocrinology & Metabolism SC Oncology; Endocrinology & Metabolism GA BF44F UT WOS:A1996BF44F00042 ER PT J AU Hirschfeld, S AF Hirschfeld, S TI Use of human recombinant growth hormone and human recombinant insulin-like growth factor-I in patients with human immunodeficiency virus infection SO HORMONE RESEARCH LA English DT Article DE growth hormone; insulin-like growth factor-I; HIV; nutrition; thyroid; growth ID RESTING ENERGY-EXPENDITURE; TUMOR-NECROSIS-FACTOR; HIV-INFECTION; ENDOCRINE FUNCTION; IMMUNE FUNCTION; ADIPOSE-TISSUE; CALORIC-INTAKE; INFANTS BORN; IGF-I; CHILDREN AB Infection with the human immunodeficiency virus (HIV) can lead to global alterations in metabolism as well as immunodeficiency. There is dysregulation of endocrine function in adults and children, the extent and magnitude correlating with disease progression. Some of the more prominent abnormalities occur in the thyroid, gonadal, and somatomedin axes. Clinical manifestations of these abnormalities are growth failure in children, which is one of the most sensitive indicators of disease progression, and a wasting syndrome in adults and children. Although there are case reports of growth hormone (GH) deficiency in HIV-infected children, most patients with growth failure have normal serum levels of GH and normal to low levels of insulin-like growth factor-I (IGF-I). Antiretrovial therapy can improve the growth rate in children for a period of time if there is a drop in viral titer, but as the viral load increases, the growth rate decreases again. Administration of GH or IGF-I to these patients can improve the growth rate and lean body mass, and in some patients improve immune function. Although studies on resting energy expenditure in HIV-infected patients have shown increases, these are not proportional to disease progression, but may be dependent upon cytokine activation and other abnormalities. Adult patients with wasting have been shown to have relatively normal total energy expenditure, but decreased intake. Appetite stimulants have been shown to have some benefit, but do not increase lean body mass. The most significant clinical benefit has come from administration of GH in short-term trials. GH and IGF-I are both able to inhibit apoptosis and reconstitute the immune system in rodents treated with ablative therapy. In addition, GH can modulate the marrow suppressive effects of zidovudine and may enhance its ability to inhibit viral reverse transcriptase. Current clinical trials are ongoing in both adults and children. GH and IGF-I may have a role in regimens intended for immune reconstruction, and could be useful as adjuvant therapy in selected patients with HIV infection. RP Hirschfeld, S (reprint author), NCI, PEDIAT BRANCH, BLDG 10 ROOM 13N240, BETHESDA, MD 20892 USA. RI Hirschfeld, Steven/E-2987-2016 OI Hirschfeld, Steven/0000-0003-0627-7249 NR 106 TC 18 Z9 19 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-0163 EI 1663-2826 J9 HORM RES JI Horm. Res. PY 1996 VL 46 IS 4-5 BP 215 EP 221 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VT868 UT WOS:A1996VT86800013 PM 8950624 ER PT J AU McIntosh, AR Grady, CL Haxby, JV Maisog, JM Horwitz, B Clark, CM AF McIntosh, AR Grady, CL Haxby, JV Maisog, JM Horwitz, B Clark, CM TI Within-subject transformations of PET regional cerebral blood flow data: ANCOVA, ratio, and Z-score adjustments on empirical data SO HUMAN BRAIN MAPPING LA English DT Article DE cerebral blood flow; statistical analysis; image normalization; activation; positron emission tomography; image standardization ID HUMAN EXTRASTRIATE CORTEX; ACTIVATION; PATHWAYS; OBJECT; FACES AB In the statistical analysis of PET rCBF data, it has become routine to use a mathematical transformation to reduce individual differences in global metabolic rate and increase the power of statistical tests. Two methods of adjustment have been proposed: the ratio adjustment, dividing rCBF for a brain region by the whole-brain average CBF, and the ANCOVA adjustment based on a regression model. We compared these two transformations on the empirically derived PET data sets to assess which of these transforms worked best. Within-subject Z-scores were also considered as an additional transformation technique. Comparisons between the three transform techniques, and the untransformed raw data, were made on the detected significant differences, the size of the statistical effects, and the relative reduction in error variance. Two data sets were considered: 1) a visual perception study comparing object and spatial vision; 2) a data set from a parametric visual working memory study. There was no striking difference in the detected significant differences between any of the three transformed data sets and all transformed data sets defected more differences than the raw data set. There was little difference between the transformed data sets in terms of effect sizes, with the Z-score data set showing slightly lower total error variance that either the ratio-adjusted or ANCOVA-adjusted data sets. It was concluded that PET data sets should be closely examined for task-related changes in global CBF and subject heterogeneities (outliers) since these factors will influence the outcome of image-based statistical comparison more than the particular data transformation. (C) 1996 Wiley-Liss, Inc. C1 NIA, NEUROSCI LAB, NIH, BETHESDA, MD 20892 USA. NIMH, PSYCHOL & PSYCHOPATHOL LAB, NIH, BETHESDA, MD 20892 USA. UNIV BRITISH COLUMBIA, DEPT PSYCHIAT, VANCOUVER, BC V6T 2A1, CANADA. RI McIntosh, Anthony/G-4955-2011; OI McIntosh, Anthony/0000-0002-1784-5662 NR 26 TC 21 Z9 21 U1 1 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1065-9471 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PY 1996 VL 4 IS 2 BP 93 EP 102 PG 10 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA VK814 UT WOS:A1996VK81400001 PM 20408189 ER PT J AU Ramsey, NF Tallent, K vanGelderen, P Frank, JA Moonen, CTW Weinberger, DR AF Ramsey, NF Tallent, K vanGelderen, P Frank, JA Moonen, CTW Weinberger, DR TI Reproducibility of human 3D fMRI brain maps acquired during a motor task SO HUMAN BRAIN MAPPING LA English DT Article DE neuroimaging; magnetic resonance imaging; cognitive neuroscience; topography; activation ID SENSORY STIMULATION; MRI TECHNIQUE; CORTEX; ACTIVATION; MOVEMENTS AB This study is an investigation into the reproducibility of brain activation in the sensorimotor cortex obtained with 3D ''PRESTO'' fMRI on eleven normal subjects. During one session, two series of functional scans were acquired while the subjects performed a finger opposition task (2 Hz). Nine subjects were tested once more on a different day. Each individual motor trial was analyzed separately, with a conservative z(t)-based method. Using these results, the agreement between repeated series was examined in a number of ways, comparing the two series within one session, and the two series across sessions. In 28 of the 31 series (90%) significant signal change was found in the contralateral primary sensorimotor cortex (PSM). Overall, 0.20% of all voxels (total about 11,000) in the scanned volume reached significance, and approximately 60% of the significant positive signal changes were located in the PSM (P < 5 x 10(-7) for a chance occurrence). Comparisons within and across sessions yielded similar results: there was a 20-30% overlap of the clusters of activated voxels in the PSM (chance overlap within the PSM: P < 0.01). The mean distance between z(t)-weighted centers of mass was 4.0-4.4 mm (chance distance within the PSM: P = 0.033 and 0.058, respectively). No significant difference was found between series in the magnitude of significant signal change. Whereas the number of activated voxels in the PSM was not consistently correlated between series, the ratio of this number over the total number of activated voxels in the scanned volume was significantly correlated (rho = 0.75-0.79, P < 0.05). These results indicate that activation in sensorimotor cortex associated with oppositional finger movement is reliably mapped with 3D PRESTO fMRI. (C) 1996 Wiley-Liss, Inc. C1 NIMH,CLIN BRAIN DISORDERS BRANCH,NEUROSCI CTR ST ELIZABETHS,NIH,WASHINGTON,DC 20032. NCRR,BEIP,IN VIVO NMR RES CTR,BETHESDA,MD 20892. NIH,LAB DIAGNOST RADIOL RES,OIR,BETHESDA,MD 20892. RI Moonen, Chrit/K-4434-2016 OI Moonen, Chrit/0000-0001-5593-3121 NR 22 TC 47 Z9 50 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 1065-9471 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PY 1996 VL 4 IS 2 BP 113 EP 121 DI 10.1002/(SICI)1097-0193(1996)4:2<113::AID-HBM3>3.0.CO;2-6 PG 9 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA VK814 UT WOS:A1996VK81400003 PM 20408191 ER PT J AU Grady, CL Horwitz, B Pietrini, P Mentis, MJ Ungerleider, LG Rapoport, SI Haxby, JV AF Grady, CL Horwitz, B Pietrini, P Mentis, MJ Ungerleider, LG Rapoport, SI Haxby, JV TI Effect of task difficulty on cerebral blood flow during perceptual matching of faces SO HUMAN BRAIN MAPPING LA English DT Article DE vision; PET; human; brain mapping; form perception ID POSITRON EMISSION TOMOGRAPHY; HUMAN EXTRASTRIATE CORTEX; SUPERIOR TEMPORAL SULCUS; WORKING-MEMORY TASKS; FUNCTIONAL NEUROANATOMY; SELECTIVE ATTENTION; PREFRONTAL CORTEX; RHESUS-MONKEY; BRAIN-REGIONS; PET IMAGES AB To aid our understanding of age-related changes in brain activation during visuoperceptual we designed an experiment to test the effect of task difficulty on regional cerebral blood flow (rCBF) as measured by positron emission tomography (PET). We report here the results from 10 young subjects engaged in match-to-sample tasks of progressively degraded faces. ?he tasks consisted of a control task, a face matching task with no stimulus degradation, and five levels of degradation: 20%, 40%, 50%, 60%, and 70%. Both performance accuracy and reaction times deteriorated significantly with increasing lace degradation. There was a significant increase of rCBF in bilateral fusiform gyri during all face-matching conditions compared to the control task, and bilateral prefrontal activation during the 70% degradation condition. Linear regression analyses revealed a significant increase of rCBF in the right prefrontal cortex, and linear decreases of rCBF in the striate and fusiform cortex as face degradation increased. Performance on the 70% task was correlated positively with rCBF in right prefrontal and bilateral fusiform gyri, and negatively with left prefrontal and striate rCBF. These results show that the right prefrontal, striate, and ventral extrastriate cortex are the principal brain regions that modulate their activity as this visual discrimination task becomes more difficult. The right prefrontal increase probably represents an increasing demand on working memory or attention, whereas decreased rCBF in the striate cortex may be due to changes in the characteristics of the stimuli, or to suppression of low-level processing by one of a number of mechanisms. This experiment has implications both for the design of neuroimaging experiments, and for interpreting differences in rCBF activation between groups. (C) 1997 Wiley-Liss, Inc. C1 NIA, NEUROSCI LAB, BETHESDA, MD 20892 USA. NIMH, PSYCHOL & PSYCHOPATHOL LAB, BETHESDA, MD 20892 USA. NR 47 TC 91 Z9 91 U1 0 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1065-9471 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PY 1996 VL 4 IS 4 BP 227 EP 239 PG 13 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA WK786 UT WOS:A1996WK78600001 PM 20408201 ER PT J AU Azari, NP Binkofski, F Pettigrew, KD Freund, HJ Seitz, RJ AF Azari, NP Binkofski, F Pettigrew, KD Freund, HJ Seitz, RJ TI Enhanced regional cerebral metabolic interactions in thalamic circuitry predicts motor recovery in hemiparetic stroke SO HUMAN BRAIN MAPPING LA English DT Article DE thalamic circuitry; brain infarction; glucose metabolism; motor recovery; supplementary motor area ID POSITRON EMISSION TOMOGRAPHY; OBSESSIVE-COMPULSIVE DISORDER; LINKING BASAL GANGLIA; ALZHEIMERS-DISEASE; MACACA-FASCICULARIS; VOLUNTARY MOVEMENTS; GLUCOSE-UTILIZATION; FUNCTIONAL-ANATOMY; CORTICAL AREAS; RHESUS-MONKEY AB We applied a multiple regression/discriminant analysis to resting metabolic data from patients with first hemiparetic suprathalamic infarctions to determine if metabolic interdependencies, which may separate recovered (N = 12) from nonrecovered (N = 9) patients, suggest important motor-recovery pathways. Recovered, vs. nonrecovered, patients showed an enhanced ipsileisonal thalamic-contralesional cerebellar metabolic interdependency. This pattern correctly classified 91% of recovered and 88% of nonrecovered patients. Metabolic interactions involving bilateral supplementary motor area, ipsilesional thalamus, and contralesional cerebellum distinguished all recovered patients from age/sex-matched controls (N = 12). These results suggest that altered functional interactions in thalamic circuitry may reflect plastic reorganization associated with motor recovery from hemiparesis. (C) 1997 Wiley-Liss, Inc., Inc. C1 UNIV DUSSELDORF,DEPT NEUROL,D-40225 DUSSELDORF,GERMANY. NIMH,DIV EPIDEMIOL APPL & SERV RES,NIH,BETHESDA,MD 20892. NR 66 TC 22 Z9 23 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 1065-9471 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PY 1996 VL 4 IS 4 BP 240 EP 253 PG 14 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA WK786 UT WOS:A1996WK78600002 PM 20408202 ER PT J AU Kraul, H Pasanen, M Sigusch, H Stenback, F Park, SS Gelboin, HV Pelkonen, O AF Kraul, H Pasanen, M Sigusch, H Stenback, F Park, SS Gelboin, HV Pelkonen, O TI Immunohistochemical properties of dipyrone-induced cytochromes P450 in rats SO HUMAN & EXPERIMENTAL TOXICOLOGY LA English DT Article DE dipyrone; aminopyrine; CYP2B1/2; drug metabolism; immunohistochemistry ID DRUG-METABOLIZING ENZYMES; GAMMA-GLUTAMYL-TRANSPEPTIDASE; MONOCLONAL-ANTIBODIES; LIVER CYTOCHROME-P-450; CIGARETTE-SMOKING; SENSITIVE ASSAY; O-DEETHYLASE; AMINOPYRINE; INDUCTION; INVIVO AB 1 Rat hepatic cytochrome P450s induced by dipyrone were studied enzymatically, immunochemically and immunohistochemically. 2 Dipyrone administered to male Wistar rats increased pentoxyresorufin O-depentylation (PROD), ethoxyresorufin O-deethylation (EROD) and 7-ethoxycoumarin O-deethylation (ECOD) activities up to 44-, 1.9-, and 2.6-fold, respectively. Aryl hydrocarbon hydroxylase (AHH) activity was not affected. 3 Immunoinhibition with the monoclonal antibody (Mab) 2-66-3 (to CYP2B1/2) markedly decreased PROD and EROD activities, but not AHH activity. The Mab 1-7-1 (to CYP1A1/2) was without effect. 4 Histochemically, the Mab 2-66-3 gave a strong and uniform staining in livers from dipyrone-treated rats, whereas the Mab 1-7-1 gave a positive reaction in a narrow perivenous strip. 5 The induction pattern as well as inhibition by the Mabs convincingly demonstrate the predominant production of CYP2B1/2 in the induction spectrum of dipyrone. The increase in enzyme activities other than PROD may be due to the overlapping substrate specificity of CYP2B1/2 enzymes. The immunohistochemical analysis also indicated the participation of CYP1A1/2. C1 UNIV OULU,DEPT PHARMACOL & TOXICOL,SF-90220 OULU,FINLAND. UNIV OULU,DEPT PATHOL,SF-90220 OULU,FINLAND. NCI,LAB MOLEC CARCINOGENESIS,BETHESDA,MD 20892. NR 45 TC 9 Z9 9 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0144-5952 J9 HUM EXP TOXICOL JI Hum. Exp. Toxicol. PD JAN PY 1996 VL 15 IS 1 BP 45 EP 50 PG 6 WC Toxicology SC Toxicology GA TQ720 UT WOS:A1996TQ72000008 PM 8845208 ER PT J AU Sekhar, M Kotani, H Doren, S Agarwal, R McGarrity, G Dunbar, CE AF Sekhar, M Kotani, H Doren, S Agarwal, R McGarrity, G Dunbar, CE TI Retroviral transduction of CD34-enriched hematopoietic progenitor cells under serum-free conditions SO HUMAN GENE THERAPY LA English DT Article ID MEDIATED GENE-TRANSFER; BONE-MARROW CELLS; HUMAN ADENOSINE-DEAMINASE; STEM-CELLS; EXPRESSION; TRANSPLANTATION; INFUSION; THERAPY; CANCER AB The use of defined or serum-free culture conditions during retroviral transduction of hematopoietic cells would be desirable for standardization and safety reasons, as well as potentially allowing greater expansion of progenitor cells. Retroviral vector supernatants were concentrated and purified via tangential now filtration polyethylene glycol (PEG)-precipitation, and ultracentrifugation, allowing serum-free transductions at standard multiplicities of infection (moil. Protein content of transductions using these concentrated vectors was 5-6 logs lower than in standard transductions. Transduction efficiencies of these concentrated vector preparations added back to serum-free or serum-containing media were equivalent to standard retroviral supernatant transductions of CD34-enriched progenitors. Absolute progenitor (CFU-C) numbers at the end of transduction were higher in serum-free + concentrated virus transductions, as opposed to transductions in standard vector supernatants containing fetal calf serum. C1 NHLBI,HEMATOL BRANCH,NATL INST HLTH,BETHESDA,MD 20892. CHILDRENS HOSP,CINCINNATI,OH. GENET THERAPY INC,GAITHERSBURG,MD. NR 25 TC 18 Z9 18 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD JAN PY 1996 VL 7 IS 1 BP 33 EP 38 DI 10.1089/hum.1996.7.1-33 PG 6 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA UA845 UT WOS:A1996UA84500004 PM 8825866 ER PT J AU Kehn, PJ Deulofeut, H LaRocque, R Robinson, MA AF Kehn, PJ Deulofeut, H LaRocque, R Robinson, MA TI T cell response and TCRBV CDR3 length restriction in humans to HBsAg and peptides. SO HUMAN IMMUNOLOGY LA English DT Meeting Abstract C1 NIAID,IMMUNOGENET LAB,NIH,ROCKVILLE,MD 20852. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PY 1996 VL 49 SU 1 BP 9 EP 9 DI 10.1016/S0198-8859(96)89920-4 PG 1 WC Immunology SC Immunology GA VD912 UT WOS:A1996VD91200012 ER PT J AU Moonsamy, PV Zimmerman, PA Suraj, VC Jaspan, JB Hill, AVS Begovich, AB AF Moonsamy, PV Zimmerman, PA Suraj, VC Jaspan, JB Hill, AVS Begovich, AB TI The HLA-DPA1 locus: Polymorphism and population genetics. SO HUMAN IMMUNOLOGY LA English DT Meeting Abstract C1 ROCHE MOL SYST,DEPT HUMAN GENET,ALAMEDA,CA. TULANE UNIV,DEPT INTERNAL MED,NEW ORLEANS,LA 70118. NIAID,PARASIT DIS LAB,NIH,BETHESDA,MD 20892. UNIV OXFORD,MOL IMMUNOL GRP,OXFORD OX1 2JD,ENGLAND. RI HILL, Adrian/C-1306-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PY 1996 VL 49 SU 1 BP 13 EP 13 PG 1 WC Immunology SC Immunology GA VD912 UT WOS:A1996VD91200091 ER PT J AU Barcellos, LF Hollenbach, JA Carrington, M Thomson, G Klitz, W AF Barcellos, LF Hollenbach, JA Carrington, M Thomson, G Klitz, W TI HLA neighbors: Extracting information from the DQCAR microsatellite. SO HUMAN IMMUNOLOGY LA English DT Meeting Abstract C1 UNIV CALIF BERKELEY,BERKELEY,CA 94720. NCI,FREDERICK,MD 21701. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PY 1996 VL 49 SU 1 BP 18 EP 18 PG 1 WC Immunology SC Immunology GA VD912 UT WOS:A1996VD91200096 ER PT J AU Zimmerman, P Hunter, J Bailey, E Nielsen, J Nutman, T AF Zimmerman, P Hunter, J Bailey, E Nielsen, J Nutman, T TI Tumor necrosis factor alpha promoter mutation frequencies among four North American racial groups. SO HUMAN IMMUNOLOGY LA English DT Meeting Abstract C1 NIAID,PARASIT DIS LAB,NIH,BETHESDA,MD 20892. GEORGETOWN UNIV,WASHINGTON,DC 20057. AMER RED CROSS,NATL HLA REFERENCE LAB,ROCKVILLE,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PY 1996 VL 49 SU 1 BP 20 EP 20 PG 1 WC Immunology SC Immunology GA VD912 UT WOS:A1996VD91200098 ER PT J AU Carrington, M Marti, D Malasky, M Barcellos, L Wade, J Awdeh, Z Truedsson, L AF Carrington, M Marti, D Malasky, M Barcellos, L Wade, J Awdeh, Z Truedsson, L TI Mapping disease loci within the MHC by typing microsatellite loci. SO HUMAN IMMUNOLOGY LA English DT Meeting Abstract C1 NCI,SAIC,FCRDC,FREDERICK,MD 21701. UNIV CALIF BERKELEY,SCH PUBL HLTH,BERKELEY,CA 94720. UNIV TORONTO,TTH REG HISTO LAB,TORONTO,ON M5S 1A1,CANADA. CTR BLOOD RES,BOSTON,MA 02115. LUND UNIV,DEPT MED MICROBIOL,S-22100 LUND,SWEDEN. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PY 1996 VL 49 SU 1 BP 24 EP 24 DI 10.1016/S0198-8859(96)89951-4 PG 1 WC Immunology SC Immunology GA VD912 UT WOS:A1996VD91200043 ER PT J AU Mann, D Nelson, G AF Mann, D Nelson, G TI Disease progression rates correlate with frequency of HLA class I peptide binding motifs in HIV-1 protein. SO HUMAN IMMUNOLOGY LA English DT Meeting Abstract C1 NCI,IMMUNOGENET SECT,VIRAL CARCINOGENESIS LAB,FCRDC,FREDERICK,MD 21702. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PY 1996 VL 49 SU 1 BP 25 EP 25 DI 10.1016/S0198-8859(96)89953-8 PG 1 WC Immunology SC Immunology GA VD912 UT WOS:A1996VD91200045 ER PT J AU Hollenbach, JA Grote, M Winkler, C Thomson, G Klitz, W AF Hollenbach, JA Grote, M Winkler, C Thomson, G Klitz, W TI Evolution of complete HLA haplotypes in mesoamerican natives. SO HUMAN IMMUNOLOGY LA English DT Meeting Abstract C1 UNIV CALIF BERKELEY,BERKELEY,CA 94720. NCI,FREDERICK,MD 21701. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PY 1996 VL 49 SU 1 BP 28 EP 28 PG 1 WC Immunology SC Immunology GA VD912 UT WOS:A1996VD91200106 ER PT J AU Harding, A Wade, J Chadwick, R Kronick, M Carrington, M AF Harding, A Wade, J Chadwick, R Kronick, M Carrington, M TI Typing microsatellite loci located in the MHC using fluorescence-based methodology. SO HUMAN IMMUNOLOGY LA English DT Meeting Abstract C1 NCI,FREDERICK CANC RES & DEV CTR,SAIC,FREDERICK,MD 21701. UNIV TORONTO,TTH REG HISTOCOMPATIBIL LAB,TORONTO,ON,CANADA. PE APPL BIOSYST,FOSTER CITY,CA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PY 1996 VL 49 SU 1 BP 157 EP 157 PG 1 WC Immunology SC Immunology GA VD912 UT WOS:A1996VD91200235 ER PT J AU Couch, FJ Weber, BL Borresen, AL Brody, L Casey, G Devilee, P Fitzgerald, M Friend, S Gayther, S Goldgar, D Murphy, P Szabo, C Weber, B Wiseman, R Anderson, T Durocher, F Ganguly, A King, MC Lenoir, G Narod, S Olopade, O Plummer, S Ponder, B Serova, O Simard, J Stratton, M Warren, B AF Couch, FJ Weber, BL Borresen, AL Brody, L Casey, G Devilee, P Fitzgerald, M Friend, S Gayther, S Goldgar, D Murphy, P Szabo, C Weber, B Wiseman, R Anderson, T Durocher, F Ganguly, A King, MC Lenoir, G Narod, S Olopade, O Plummer, S Ponder, B Serova, O Simard, J Stratton, M Warren, B TI Mutations and polymorphisms in the familial early-onset breast cancer (BRCA1) gene SO HUMAN MUTATION LA English DT Article DE BRCA1; BIC; polymorphisms AB Mutations in the familial early-onset breast cancer gene (BRCA1) account for approximately 2-5% of all breast cancer cases (Easton et al., 1993). Since the isolation of the BRCA1 gene in 1994, many mutations have been identified. We report here a total of 254 BRCA1 mutations, 132 (52%) of which are unique. These represent mutations entered into a database established by the Breast Cancer Information Core (BIC), which have appeared in the literature or have been submitted by BIC members and other contributors prior to publication. A total of 221 (87%) of all mutations or 107 (81%) of the unique mutations are small deletions, insertions, nonsense point mutations, splice variants, and regulatory mutations that result in truncation or absence of the BRCA1 protein. A total of 11 disease-associated missense mutations (5 unique), and 21 variants (19 unique) as yet unclassified as either missense mutations or polymorphisms have been detected. Thirty-five independent benign polymorphisms are also described. The most common mutations are 185delAG and 5382insC, which account for 30 (11.7%) and 26 (10.1%), respectively, of all mutations shown. The biological and clinical relevance of these BRCA1 mutations is discussed. (C) 1996 Wiley-Liss, Inc. C1 UNIV PENN,DEPT MED,PHILADELPHIA,PA 19104. UNIV PENN,DEPT GENET,PHILADELPHIA,PA 19104. NORWEGIAN RADIUM HOSP,OSLO,NORWAY. NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. CLEVELAND CLIN,RES INST,CLEVELAND,OH. LEIDEN UNIV,LEIDEN,NETHERLANDS. HARVARD UNIV,CAMBRIDGE,MA 02138. FRED HUTCHINSON CANC RES CTR,SEATTLE,WA 98104. CRC,HUMAN CANC GENET RES GRP,CAMBRIDGE,ENGLAND. IARC,LYON,FRANCE. ONCORMED,GAITHERSBURG,MD. UNIV WASHINGTON,SEATTLE,WA 98195. NIEHS,RES TRIANGLE PK,NC 27709. UNIV LAVAL,QUEBEC CITY,PQ,CANADA. UNIV TORONTO,TORONTO,ON M5S 1A1,CANADA. UNIV CHICAGO,CHICAGO,IL 60637. CRC,CANC RES INST,SUTTON,SURREY,ENGLAND. NR 35 TC 231 Z9 234 U1 1 U2 15 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 1059-7794 J9 HUM MUTAT JI Hum. Mutat. PY 1996 VL 8 IS 1 BP 8 EP 18 DI 10.1002/humu.1380080102 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA UU743 UT WOS:A1996UU74300002 PM 8807330 ER PT J AU Seto, D Weintraub, BD AF Seto, D Weintraub, BD TI Rapid molecular diagnosis of mutations associated with generalized thyroid hormone resistance by PCR-coupled automated direct sequencing of Genomic DNA: Detection of two novel mutations SO HUMAN MUTATION LA English DT Article DE GTHR; ADHD; PCR; DNA; fluorescence; sequencing; diagnostics; mutations ID DEFICIT HYPERACTIVITY DISORDER; LIGAND-BINDING DOMAIN; RECEPTOR-BETA-GENE; KINDREDS; IDENTIFICATION; CELLS AB Generalized thyroid hormone resistance (GTHR) is a syndrome characterized by tissue nonrespon siveness to thyroid hormones and by variable clinical phenotype manifestations. This syndrome has also been implicated as a predisposing factor in some cases of attention deficit-hyperactivity disorder (ADHD). GTHR results from single mutations in the gene encoding the thyroid hormone receptor. These mutations are clustered in two major sites surrounding the ligand-binding domain. Mutations in 10 previously described patients as well as in five new THR cases have been identified using PCR amplification of genomic DNA coupled with automated direct sequencing with commercially available ''universal'' fluorescent dye labeled primers. This strategy allows for the accurate and automated base-calling of normal and mutated nucleotides at the same position in a heterozygote. The rapid molecular diagnostic protocol, from whole blood to DNA sequence data, takes approximately 15 hr, allowing for rapid, efficient, and unambiguous direct detection of the mutant alleles. (C) 1996 Wiley-Liss, Inc. C1 NIDDKD,MOL & CELLULAR ENDOCRINOL BRANCH,NIH,BETHESDA,MD 20892. NR 31 TC 4 Z9 5 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 1059-7794 J9 HUM MUTAT JI Hum. Mutat. PY 1996 VL 8 IS 3 BP 247 EP 257 DI 10.1002/(SICI)1098-1004(1996)8:3<247::AID-HUMU8>3.0.CO;2-6 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA VK177 UT WOS:A1996VK17700010 PM 8889584 ER PT J AU Zbar, B Kishida, T Chen, F Schmidt, L Maher, ER Richards, FM Crossey, PA Webster, AR Affara, NA FergusonSmith, MA Brauch, H Glavac, D Neumann, HPH Tisherman, S Mulvihill, JJ Gross, DJ Shuin, T Whaley, J Seizinger, B Kley, N Olschwang, S Boisson, C Richard, S Lips, CHM Linehan, WM Lerman, M AF Zbar, B Kishida, T Chen, F Schmidt, L Maher, ER Richards, FM Crossey, PA Webster, AR Affara, NA FergusonSmith, MA Brauch, H Glavac, D Neumann, HPH Tisherman, S Mulvihill, JJ Gross, DJ Shuin, T Whaley, J Seizinger, B Kley, N Olschwang, S Boisson, C Richard, S Lips, CHM Linehan, WM Lerman, M TI Germline mutations in the Von Hippel-Lindau disease (VHL) gene in families from North America, Europe, and Japan SO HUMAN MUTATION LA English DT Article DE Von Hippel-Lindau disease; germline mutations; renal cell carcinoma; pheochromocytoma ID TUMOR-SUPPRESSOR GENE; MULTIPLE ENDOCRINE NEOPLASIA; SOMATIC MUTATIONS; RET PROTOONCOGENE; RENAL-CARCINOMA; POINT MUTATIONS; PHEOCHROMOCYTOMA; IDENTIFICATION; FEATURES; BINDING AB Germline mutation analysis was performed in 469 VHL families from North America, Europe, and Japan. Germline mutations were identified in 300/469 (63%) of the families tested; 137 distinct intragenic germline mutations were detected. Most of the germline VHL mutations (124/137) occurred in 1-2 families; a few occured in four or more families, The common germline VHL mutations were: delPhe76, Asn78Ser, Arg161Stop, Arg167Gln, Arg167Trp, and Leu178Pro. In this large series, it was possible to compare the effects of identical germline mutations in different populations. Germline VHL mutations produced similar cancer phenotypes in Caucasian and Japanese VHL families. Germline VHL mutations were identified that produced three distinct cancer phenotypes: (1) renal carcinoma without pheochromocytoma, (2) renal carcinoma with pheochromocytoma, and (3) pheochromocytoma alone. The catalog of VHL germline mutations with phenotype information should be useful for diagnostic and prognostic studies of VHL and for studies of genotype phenotype correlations in VHL. (C) 1996 Wiley-Liss, Inc.(dagger) C1 SAIC FREDERICK,BIOL CARCINOGENESIS & DEV PROGRAM,IMMUNOBIOL LAB,FREDERICK,MD. NCI,SURG BRANCH,BETHESDA,MD 20892. UNIV CAMBRIDGE,SCH MED,DEPT PATHOL,CAMBRIDGE CB2 1TN,ENGLAND. BRISTOL MYERS SQUIBB CO,PRINCETON,NJ. YOKOHAMA UNIV,SCH MED,DEPT UROL,YOKOHAMA,KANAGAWA,JAPAN. EPHE,ST ANNE HOSP,INST CURIE,LAB TUMOR GENET,F-75006 PARIS,FRANCE. EPHE,ST ANNE HOSP,LAB NEUROONCOL,F-75006 PARIS,FRANCE. UNIV UTRECHT HOSP,DEPT INTERNAL MED,UTRECHT,NETHERLANDS. UNIV FREIBURG,DEPT HYPERTENS & NEPHROL,D-7800 FREIBURG,GERMANY. TECH UNIV MUNICH,INST PATHOL,LAB MOL PATHOL,D-8000 MUNICH,GERMANY. HADASSAH UNIV HOSP,DEPT ENDOCRINOL,IL-91120 JERUSALEM,ISRAEL. UNIV LJUBLJANA,FAC MED,LJUBLJANA,SLOVENIA. UNIV PITTSBURGH,DEPT HUMAN GENET,PITTSBURGH,PA 15260. UNIV PITTSBURGH,DEPT MED,PITTSBURGH,PA 15260. RP Zbar, B (reprint author), NCI,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21701, USA. RI MAHER, EAMONN/A-9507-2008; Olschwang, Sylviane/G-2716-2013 OI MAHER, EAMONN/0000-0002-6226-6918; NR 43 TC 341 Z9 354 U1 1 U2 6 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 1059-7794 J9 HUM MUTAT JI Hum. Mutat. PY 1996 VL 8 IS 4 BP 348 EP 357 DI 10.1002/(SICI)1098-1004(1996)8:4<348::AID-HUMU8>3.0.CO;2-3 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA VV880 UT WOS:A1996VV88000008 PM 8956040 ER PT J AU Bergen, A Wang, CY Nakhai, B Goldman, D AF Bergen, A Wang, CY Nakhai, B Goldman, D TI Mass allele detection (MAD) of rare 5-HT1A structural variants with allele-specific amplification and electrochemiluminescent detection SO HUMAN MUTATION LA English DT Article DE ASA-PCR; ECL; allele detection; diagnostic screening method ID POOLING STRATEGY; PCR; POLYMERASE; DNA AB A strategy is described that exploits allele-specific amplification (ASA-PCR) and electrochemiluminescence (ECL) detection technology to rapidly and cheaply screen large numbers of DNAs arranged in pooled matrices in order to identify individual nucleotide sequence variants, To demonstrate this strategy, a large genomic DNA collection was screened for two nucleotide variants in the 5-HT1A serotonin receptor gene and individual heterozygotes were identified. Conversion of two SSCP variants to allele specific PCR polymorphisms was accomplished, and PCR product capture and ECL detection were enabled by the covalent addition of biotin to allele-specific PCR primers and ruthenium to the nonspecific PCR primer. A two-level DNA pooling strategy was used to reduce the number of individual PCR reactions required. Pooling experiments established that ASA-PCR with ECL detection is sufficiently sensitive to reproducibly detect a single specific allele in the presence of a 40 fold excess of gnomic DNA from individuals negative for the specific allele. The detection sensitivity of the ECL device and the design of the pooled DNA arrays reduced the number of PCRs required to detect the rare individuals with the variant sequences by approximately 90%. This strategy is called mass allele detection (MAD). (C) 1996 Wiley-Liss, Inc. RP Bergen, A (reprint author), NIAAA,NEUROGENET LAB,NIH,ROCKVILLE,MD 20852, USA. RI Goldman, David/F-9772-2010; OI Goldman, David/0000-0002-1724-5405; Bergen, Andrew/0000-0002-1237-7644 NR 13 TC 17 Z9 17 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 1059-7794 J9 HUM MUTAT JI Hum. Mutat. PY 1996 VL 7 IS 2 BP 135 EP 143 DI 10.1002/(SICI)1098-1004(1996)7:2<135::AID-HUMU7>3.0.CO;2-B PG 9 WC Genetics & Heredity SC Genetics & Heredity GA TX967 UT WOS:A1996TX96700007 PM 8829630 ER PT J AU Nasr, SZ Strong, TV Mansoura, MK Dawson, DC Collins, FS AF Nasr, SZ Strong, TV Mansoura, MK Dawson, DC Collins, FS TI Novel missense mutation (G314R) in a cystic fibrosis patient with hepatic failure SO HUMAN MUTATION LA English DT Article ID TRANSMEMBRANE CONDUCTANCE REGULATOR; GENETIC-ANALYSIS; MILD-DISEASE; CFTR; IDENTIFICATION; CHANNELS; DNA C1 UNIV MICHIGAN,DEPT HUMAN GENET,ANN ARBOR,MI 48109. UNIV MICHIGAN,DEPT BIOENGN,ANN ARBOR,MI 48109. UNIV MICHIGAN,DEPT PHYSIOL,ANN ARBOR,MI 48109. UNIV MICHIGAN,DEPT INTERNAL MED,ANN ARBOR,MI 48109. NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. RP Nasr, SZ (reprint author), UNIV MICHIGAN,DEPT PEDIAT,ANN ARBOR,MI 48109, USA. FU NIDDK NIH HHS [DK29786, DK45880] NR 20 TC 2 Z9 3 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 1059-7794 J9 HUM MUTAT JI Hum. Mutat. PY 1996 VL 7 IS 2 BP 151 EP 154 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA TX967 UT WOS:A1996TX96700010 PM 8829633 ER PT J AU Gentleman, S KaiserKupfer, MI Sherins, RJ Caruso, R Robison, WG LloydMuhammad, RA Crawford, MA Pikus, A Chader, GJ AF Gentleman, S KaiserKupfer, MI Sherins, RJ Caruso, R Robison, WG LloydMuhammad, RA Crawford, MA Pikus, A Chader, GJ TI Ultrastructural and biochemical analysis of sperm flagella from an infertile man with a rod-dominant retinal degeneration SO HUMAN PATHOLOGY LA English DT Article DE male infertility; retinal degeneration; microtubule; acetylation ID MICROTUBULE-ASSOCIATED PROTEINS; RETINITIS-PIGMENTOSA; ALPHA-TUBULIN; RDS GENE; CILIA; MUTATION; HETEROGENEITY; PATHOLOGY; STABILITY; RHODOPSIN AB This study examined the ultrastructural morphology and post-translationally modified alpha-tubulin isoforms in the sperm flagella of a patient presenting with infertility and retinal degeneration. Clinical evaluation showed impaired motility and gross morphological abnormalities of the sperm and a rod-dominant retinal degeneration with midperipheral pigment clumping and scattered bone spicules. Other neurological indications included delayed neuroelectric transmission in the auditory brainstem and a temporal lobe seizure disorder. Ultra-structural analysis showed that 46% of sperm axonemes had missing and/or misplaced doublets compared with 10% to 12% in control subjects. ELISA analysis showed hypoacetylation of cu-tubulin (30% of control) but normal levels of cu-tubulin tyrosination. Tubulin acetyltransferase specific activity was also 30% of control activity. These characteristics may be indicative of microtubule instability leading to the pathological consequences described. HUM PATHOL 27:80-84. This is a US government work. There are no restrictions on its use. C1 NEI,LAB MECHANISM OCULAR DIS,OPHTHALM GENET & CLIN SERV BRANCH,RETINAL CELL & MOLEC BIOL LAB,BETHESDA,MD 20892. GENET & IVF INST,FAIRFAX,VA 22039. NATL INST DEAFNESS & OTHER COMMUN DIS,AUDIOL UNIT,BETHESDA,MD. NR 37 TC 6 Z9 6 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD JAN PY 1996 VL 27 IS 1 BP 80 EP 84 DI 10.1016/S0046-8177(96)90142-2 PG 5 WC Pathology SC Pathology GA TP794 UT WOS:A1996TP79400014 PM 8543316 ER PT J AU Hampel, H Berger, C Moller, HJ MullerSpahn, F AF Hampel, H Berger, C Moller, HJ MullerSpahn, F TI Oral anticoagulation under the influence of reversible and irreversible MAO inhibitors SO HUMAN PSYCHOPHARMACOLOGY-CLINICAL AND EXPERIMENTAL LA English DT Letter C1 NIA,NATL INST HLTH,BETHESDA,MD 20892. UNIV MUNICH,DEPT PSYCHIAT,D-80336 MUNICH,GERMANY. UNIV BASEL,DEPT PSYCHIAT,CH-4025 BASEL,SWITZERLAND. NR 5 TC 0 Z9 0 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0885-6222 J9 HUM PSYCHOPHARM CLIN JI Hum. Psychopharmacol.-Clin. Exp. PD JAN-FEB PY 1996 VL 11 IS 1 BP 69 EP 70 PG 2 WC Clinical Neurology; Pharmacology & Pharmacy; Psychiatry; Psychology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry; Psychology GA TY276 UT WOS:A1996TY27600010 ER PT S AU Antonucci, JM Skrtic, D Eanes, ED AF Antonucci, JM Skrtic, D Eanes, ED BE Ottenbrite, RM Huang, SJ Park, K TI Bioactive polymeric dental materials based on amorphous calcium phosphate SO HYDROGELS AND BIODEGRADABLE POLYMERS FOR BIOAPPLICATIONS SE ACS SYMPOSIUM SERIES LA English DT Article; Proceedings Paper CT Symposium on Hydrogels and Biodegradable Polymers for Bioapplications, at the 208th National Meeting of the American-Chemical-Society CY AUG 21-26, 1994 CL WASHINGTON, DC SP Amer Chem Soc, Div Polym Chem Inc ID CEMENTS AB The effectiveness of acrylic-based visible light curable composites with amorphous calcium phosphate (ACP) as the filler phase to release Ca2+ and phosphate (PO4) ions in aqueous media was enhanced with the incorporation of zirconyl dimethacrylate (ZrM) or 3-methacryloxypropyltrimethoxysilane (MPTMS) as coupling agents. Relatively hydrophobic resin-based composites formulated with these coupling agents were found to more rapidly release these ions over a longer period to establish solution Ca2+ and PO4 concentrations much higher than those obtained from similar composites without these coupling agents. The increased effectiveness of the former composites was comparable to that observed with more hydrophilic composites formulated with 2-hydroxyethyl methacrylate. In addition, composite strength was not compromised by the incorporation of MPTMS or ZrM. These results suggest that coupling agents make ACP-filled composites even more effective as bioactive dental materials for use in clinical applications where preventing demineralization or promoting remineralization of tooth structures is desirable. C1 NIDR,BONE RES BRANCH,NIH,BETHESDA,MD 20892. RUDJER BOSKOVIC INST,DEPT CHEM,ZAGREB 41000,CROATIA. RP Antonucci, JM (reprint author), NIST,DIV POLYMERS,GAITHERSBURG,MD 20899, USA. NR 18 TC 9 Z9 9 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 SIXTEENTH ST NW, WASHINGTON, DC 20036 SN 0097-6156 BN 0-8412-3400-0 J9 ACS SYM SER PY 1996 VL 627 BP 243 EP 254 PG 12 WC Chemistry, Multidisciplinary; Mechanics SC Chemistry; Mechanics GA BF19C UT WOS:A1996BF19C00020 ER PT S AU Wehr, TA AF Wehr, TA BE Buijs, RM Kalsbeek, A Romijn, HJ Pennartz, CMA Mirmiran, M TI A 'clock for all seasons' in the human brain SO HYPOTHALAMIC INTEGRATION OF CIRCADIAN RHYTHMS SE Progress in Brain Research LA English DT Review CT 19th International Summer School of Brain Research - Hypothalamic Integration of Circadian Rhythms CY AUG 28-31, 1995 CL ROYAL NETHERLANDS ACAD SCI, AMSTERDAM, NETHERLANDS SP Royal Netherlands Acad Sci, Grad Sch Neurosci Amsterdam, Harlan CPB, Harry Fein World Precis Instruments, NedLow Sci, Netherlands Soc Adv Nat Sci Med & Surg, Organon Int B V, Oxford Univ Pr, Remmert Adriaan Laanfonds, Sage Publ Inc, SmithKline Beecham, Van den Houten Fdn, Fa Versluis, Zeiss Nederland B V HO ROYAL NETHERLANDS ACAD SCI ID RAT SUPRACHIASMATIC NUCLEUS; HUMAN MELATONIN SECRETION; CIRCADIAN PACEMAKERS; FUNCTIONAL-ANALYSIS; HUMAN-REPRODUCTION; NOCTURNAL RODENTS; SLEEP PROPENSITY; ANNUAL RHYTHM; PHOTOPERIOD; SHEEP RP Wehr, TA (reprint author), NIMH, CLIN PSYCHOBIOL BRANCH,INTRAMURAL RES PROGRAM,NIH, BLDG 10, ROOM 45239, BETHESDA, MD 20892 USA. NR 38 TC 24 Z9 25 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0079-6123 BN 0-444-82443-X J9 PROG BRAIN RES JI Prog. Brain Res. PY 1996 VL 111 BP 321 EP 342 DI 10.1016/S0079-6123(08)60416-1 PG 22 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA BJ08N UT WOS:A1996BJ08N00022 PM 8990923 ER PT B AU Nelson, MB AF Nelson, MB BE Alexander, NJ Wentz, AC TI Identifying funding opportunities at the NIH: A grants perspective SO IDEA TO PRODUCT: THE PROCESS SE SERONO SYMPOSIA, USA LA English DT Proceedings Paper CT Symposium on Idea to Product - The Process CY NOV 17-20, 1994 CL WASHINGTON, DC SP Serono Symp USA Inc, NICHHD, Amer Soc Reproduct Med RP Nelson, MB (reprint author), NICHHD,POPULAT RES GRANTS MANAGEMENTS SECT,NIH,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 BN 0-387-94742-6 J9 SERONO SYMP PY 1996 BP 21 EP 23 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BG72Z UT WOS:A1996BG72Z00005 ER PT B AU Wagner, RA AF Wagner, RA BE Alexander, NJ Wentz, AC TI Identifying funding opportunities at the NIH: A contract perspective SO IDEA TO PRODUCT: THE PROCESS SE SERONO SYMPOSIA, USA LA English DT Proceedings Paper CT Symposium on Idea to Product - The Process CY NOV 17-20, 1994 CL WASHINGTON, DC SP Serono Symp USA Inc, NICHHD, Amer Soc Reproduct Med RP Wagner, RA (reprint author), NICHHD,CONTRACTS MANAGEMENT BRANCH,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 BN 0-387-94742-6 J9 SERONO SYMP PY 1996 BP 25 EP 31 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BG72Z UT WOS:A1996BG72Z00006 ER PT B AU Ellis, GB AF Ellis, GB BE Alexander, NJ Wentz, AC TI Institutional review boards and informed consent SO IDEA TO PRODUCT: THE PROCESS SE SERONO SYMPOSIA, USA LA English DT Proceedings Paper CT Symposium on Idea to Product - The Process CY NOV 17-20, 1994 CL WASHINGTON, DC SP Serono Symp USA Inc, NICHHD, Amer Soc Reproduct Med RP Ellis, GB (reprint author), NIH,OFF PROTECT RES RISKS,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 BN 0-387-94742-6 J9 SERONO SYMP PY 1996 BP 141 EP 146 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BG72Z UT WOS:A1996BG72Z00021 ER PT J AU Ostuni, J Dunn, S AF Ostuni, J Dunn, S TI Motion from three weak perspective images using image rotation SO IEEE TRANSACTIONS ON PATTERN ANALYSIS AND MACHINE INTELLIGENCE LA English DT Article DE weak perspective; correspondence; object pose; rigid object motion; image rotation AB In this paper, it is shown that by using image rotation, one can develop a linear algorithm to find motion using three weak perspective images, By using the correspondence of four points over a pair of these images, a function can be developed which allows one to perform the necessary rotation. With the correct image rotation, one need only add a third image to have an overdetermined linear system with which to solve for the unknown elements of the rotation matrices relating these three images. C1 RUTGERS STATE UNIV,DEPT BIOMED ENGN,PISCATAWAY,NJ 08855. RP Ostuni, J (reprint author), NIH,DIV COMP RES & TECHNOL,BLDG 13,ROOM 3W13,BETHESDA,MD 20892, USA. NR 5 TC 9 Z9 9 U1 0 U2 0 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1264 SN 0162-8828 J9 IEEE T PATTERN ANAL JI IEEE Trans. Pattern Anal. Mach. Intell. PD JAN PY 1996 VL 18 IS 1 BP 64 EP 69 DI 10.1109/34.476013 PG 6 WC Computer Science, Artificial Intelligence; Engineering, Electrical & Electronic SC Computer Science; Engineering GA TP315 UT WOS:A1996TP31500008 ER PT B AU Roper, RL Phipps, RP AF Roper, RL Phipps, RP BE Faist, E Baue, AE Schildberg, FW TI Prostaglandin E and immunity: Intracellular cAMP and PGE-inducible regulatory proteins SO IMMUNE CONSEQUENCES OF TRAUMA, SHOCK AND SEPSIS - MECHANISMS AND THERAPEUTIC APPROACHES, VOL I: MOF, MODS AND SIRS - BASIC MECHANISMS IN INFLAMMATION AND TISSUE INJURY LA English DT Proceedings Paper CT 3rd International Congress on the Immune Consequences of Trauma, Shock and Sepsis - Mechanisms and Therapeutic Approaches CY MAR 02-05, 1994 CL MUNICH, GERMANY RP Roper, RL (reprint author), NIH,INST ALLERGY & INFECT DIS,BLDG 10,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PABST SCIENCE PUBLISHERS PI D-49525 LENGERICH PA EICHENGRUND 28, D-49525 LENGERICH, GERMANY BN 3-928057-75-8 PY 1996 BP 106 EP 116 PG 11 WC Immunology SC Immunology GA BH12N UT WOS:A1996BH12N00011 ER PT B AU Suffredini, AF AF Suffredini, AF BE Faist, E Baue, AE Schildberg, FW TI Therapeutic role of soluble tumor necrosis factor receptors in acute inflammation SO IMMUNE CONSEQUENCES OF TRAUMA, SHOCK AND SEPSIS - MECHANISMS AND THERAPEUTIC APPROACHES, VOL II, PTS 1 AND 2 LA English DT Proceedings Paper CT 3rd International Congress on the Immune Consequences of Trauma, Shock and Sepsis - Mechanisms and Therapeutic Approaches CY MAR 02-05, 1994 CL MUNICH, GERMANY RP Suffredini, AF (reprint author), NIH,DEPT CRIT CARE MED,WARREN G MAGNUSON CLIN CTR,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PABST SCIENCE PUBLISHERS PI D-49525 LENGERICH PA EICHENGRUND 28, D-49525 LENGERICH, GERMANY BN 3-928057-76-6 PY 1996 BP 1190 EP 1195 PG 6 WC Immunology SC Immunology GA BH12P UT WOS:A1996BH12P00151 ER PT B AU Vito, P Lacana, E DAdamio, L AF Vito, P Lacana, E DAdamio, L BE Banchereau, J Dodet, B Schwartz, R Trannoy, E TI Functional cloning of genes involved in T-cell death: Ca2+-binding protein ALG-2 and Alzheimer's disease gene ALG-3 SO IMMUNE TOLERANCE: INTERNATIONAL SYMPOSIUM ON IMMUNE TOLERANCE LA English DT Proceedings Paper CT International Symposium on Immune Tolerance CY MAY 09-11, 1996 CL ANNECY, FRANCE SP Marcel Merieux Fdn DE apoptosis; apoptosis-linked genes; T cells C1 NIAID,T CELL MOL BIOL UNIT,CELLULAR & MOL IMMUNOL LAB,NIH,BETHESDA,MD 20892. RP DAdamio, L (reprint author), NIAID,T CELL MOL BIOL UNIT,CELLULAR & MOL IMMUNOL LAB,NIH,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU EDITIONS SCIENTIFIQUE & MEDICALES ELSEVIER PI PARIS PA 141, RUE DE JAVEL, PARIS, FRANCE BN 2-906077-92-5 PY 1996 BP 159 EP 172 PG 14 WC Immunology SC Immunology GA BH33J UT WOS:A1996BH33J00016 ER PT J AU Gonzalo, JA Jia, GQ Aguirre, V Friend, D Coyle, AJ Jenkins, NA Lin, GS Katz, H Lichtman, A Copeland, N Kopf, M GutierrezRamos, JC AF Gonzalo, JA Jia, GQ Aguirre, V Friend, D Coyle, AJ Jenkins, NA Lin, GS Katz, H Lichtman, A Copeland, N Kopf, M GutierrezRamos, JC TI Mouse eotaxin expression parallels eosinophil accumulation during lung allergic inflammation but it is not restricted to a Th2-type response SO IMMUNITY LA English DT Article ID COLONY-STIMULATING FACTOR; CELL-ADHESION MOLECULE-1; TUMOR-NECROSIS-FACTOR; GROWTH-FACTOR; DIFFERENTIATION FACTOR; GENE JE; CYTOKINE; IL-4; CLONING; INTERLEUKIN-5 AB A model of lung eosinophilia based on the repeated exposure of mice to aerosolized OVA has been used to identify C-C chemokine genes expressed at stages of massive eosinophil infiltration. We describe the identification and cloning of a cDNA that encodes a mouse C-C chemokine with 68% amino acid identity to guinea pig Eotaxin. The recombinant protein encoded by this gene displays potent and specific chemotactic activity for eosinophils, both in vivo and in vitro. Its mRNA levels parallel the kinetics of eosinophil accumulation in the lung during the experimentally induced eosinophilia and it is mainly produced by type I alveolar epithelial cells. The mRNA expression of mouse Eotaxin is not restricted to Th2 T cells in vitro and is independent of the development of a Th2-type response during N. brasiliensis infection, in vivo. C1 HARVARD UNIV,SCH MED,DEPT GENET,CAMBRIDGE,MA 02138. BRIGHAM & WOMENS HOSP,DIV RHEUMATOL,BOSTON,MA 02115. NCI,FREDERICK CANC RES & DEV CTR,MAMMALIAN GENET LAB,FREDERICK,MD 21702. BASEL INST IMMUNOL,BASEL,SWITZERLAND. RP Gonzalo, JA (reprint author), HARVARD UNIV,SCH MED,CTR BLOOD RES INC,CAMBRIDGE,MA 02138, USA. NR 62 TC 154 Z9 156 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 1074-7613 J9 IMMUNITY JI Immunity PD JAN PY 1996 VL 4 IS 1 BP 1 EP 14 DI 10.1016/S1074-7613(00)80293-9 PG 14 WC Immunology SC Immunology GA TT319 UT WOS:A1996TT31900001 ER PT J AU Burshtyn, DN Scharenberg, AM Wagtmann, N Rajagopalan, S Berrada, K Yi, TL Kinet, JP Long, EO AF Burshtyn, DN Scharenberg, AM Wagtmann, N Rajagopalan, S Berrada, K Yi, TL Kinet, JP Long, EO TI Recruitment of tyrosine phosphatase HCP by the killer cell inhibitory receptor SO IMMUNITY LA English DT Article ID LYMPHOCYTE-ACTIVATION; SIGNAL-TRANSDUCTION; FC-RECEPTORS; SH2 DOMAINS; PROTEIN; EXPRESSION; PHOSPHORYLATION; LOCALIZATION; ASSOCIATION; RECOGNITION AB Cytolysis of target cells by natural killer (NK) cells and by some cytotoxic T cells occurs unless prevented by inhibitory receptors that recognize MHC class I on target cells. Human NK cells express a p58 inhibitory receptor specific for HLA-C. We report association of the tyrosine phosphatase HCP with the p58 receptor in NK cells. HCP association was dependent on tyrosine phosphorylation of p58. Phosphotyrosyl peptides corresponding to the p58 tail bound and activated HCP in vitro. Furthermore, introduction of an inactive mutant HCP into an NK cell line prevented the p58-mediated inhibition of target cell lysis. These data imply that the inhibitory function of p58 is dependent on its tyrosine phosphorylation and on recruitment and activation of HCP. C1 NIAID,MOLEC ALLERGY & IMMUNOL SECT,ROCKVILLE,MD 20852. CLEVELAND CLIN FDN,RES INST,DEPT CANC BIOL,CLEVELAND,OH 44195. RP Burshtyn, DN (reprint author), NIAID,IMMUNOGENET LAB,12441 PARKLAWN DR,ROCKVILLE,MD 20852, USA. RI Long, Eric/G-5475-2011 OI Long, Eric/0000-0002-7793-3728 FU Intramural NIH HHS [Z01 AI000525-20] NR 56 TC 532 Z9 535 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 1074-7613 J9 IMMUNITY JI Immunity PD JAN PY 1996 VL 4 IS 1 BP 77 EP 85 DI 10.1016/S1074-7613(00)80300-3 PG 9 WC Immunology SC Immunology GA TT319 UT WOS:A1996TT31900008 PM 8574854 ER PT J AU Kovalchuk, AL Potter, M Janz, S AF Kovalchuk, AL Potter, M Janz, S TI DNA sequence analysis of the genetic recombination between Igh6 and Myc in an uncommon BALB/c plasmacytoma, TEPC 1194 SO IMMUNOGENETICS LA English DT Article ID VISIBLE CHROMOSOMAL TRANSLOCATIONS; HEAVY-CHAIN GENE; MURINE PLASMACYTOMA; C-MYC; ABERRANT REARRANGEMENT; NEOPLASTIC DEVELOPMENT; ENHANCER; ONCOGENE C1 NCI,GENET LAB,NIH,BETHESDA,MD 20892. NR 11 TC 6 Z9 6 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0093-7711 J9 IMMUNOGENETICS JI Immunogenetics PY 1996 VL 44 IS 2 BP 151 EP 156 DI 10.1007/BF02660065 PG 6 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA UP881 UT WOS:A1996UP88100011 PM 8662079 ER PT J AU Howcroft, TK Weissman, JD Rudikoff, S Frels, WI Singer, DS AF Howcroft, TK Weissman, JD Rudikoff, S Frels, WI Singer, DS TI Repression of the nonclassical MHC class I gene H2-M1 by cis-acting silencer DNA elements SO IMMUNOGENETICS LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; TISSUE-SPECIFIC EXPRESSION; TRANSGENIC MICE; MOUSE; ANTIGEN; MOLECULES; CELLS; IDENTIFICATION; ORGANIZATION; EVOLUTION AB H2-M1 is a non-classical major histocompatibility complex (MHC) class I gene that is highly divergent from classical class I genes; M1 was the first gene in the recently classified M region of the mouse MHC to be cloned. Although the M1 DNA sequence contains normal splice sites, open reading frames within its exons, and a recognizable promoter, no M1 transcripts were detected in various healthy mouse tissues. However, M1 transcripts were detected in transfected L cells and in vivo in brains of M1 transgenic mice, albeit at very low levels, and the level of expression is correlated with transgene copy number. Analysis of the M1 promoter region identified a competent promoter capable of directing transcription, but whose expression is repressed by two strong upstream silencer elements, one mapping between -184 base pairs (bp) and -266 bp and the other between -1149 bp and 1702 bp. These studies suggest that M1 expression is highly regulated and restricted either temporally or to a very limited number of cell types. C1 NCI,EXPT IMMUNOL BRANCH,NIH,BETHESDA,MD 20892. NCI,GENET LAB,NIH,BETHESDA,MD 20892. BIOQUAL INC,ROCKVILLE,MD 20850. NR 34 TC 7 Z9 7 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0093-7711 J9 IMMUNOGENETICS JI Immunogenetics PY 1996 VL 44 IS 4 BP 268 EP 274 PG 7 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA VC969 UT WOS:A1996VC96900006 PM 8753857 ER PT J AU Zimmerman, PA Guderian, RH Nutman, TB AF Zimmerman, PA Guderian, RH Nutman, TB TI A new TNFA promoter allele identified in South American Blacks SO IMMUNOGENETICS LA English DT Article ID ALPHA PROMOTER; REGION; POLYMORPHISM C1 HOSP VOZANDES,INVEST CLIN,QUITO,ECUADOR. RP Zimmerman, PA (reprint author), NIAID,PARASIT DIS LAB,NIH,BLDG 4,ROOM 126,BETHESDA,MD 20892, USA. NR 9 TC 30 Z9 30 U1 0 U2 2 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0093-7711 J9 IMMUNOGENETICS JI Immunogenetics PY 1996 VL 44 IS 6 BP 485 EP 486 DI 10.1007/s002510050158 PG 2 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA VM455 UT WOS:A1996VM45500012 PM 8824163 ER PT J AU Janz, S Roschke, VV AF Janz, S Roschke, VV TI Completion of the DNA sequence determination of the lgh2 locus of the mouse: The 5'-I-A region SO IMMUNOGENETICS LA English DT Note ID IMMUNOGLOBULIN HEAVY-CHAIN; CHROMOSOMAL TRANSLOCATIONS; RECOMBINATION BREAKPOINTS; BINDING PROTEIN; SWITCH REGIONS; C-MYC; ONCOGENE; ALPHA; ORGANIZATION; HOTSPOTS RP Janz, S (reprint author), NCI,GENET LAB,BLDG 37,ROOM 2B09,BETHESDA,MD 20892, USA. NR 24 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0093-7711 J9 IMMUNOGENETICS JI Immunogenetics PY 1996 VL 43 IS 1-2 BP 101 EP 104 PG 4 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA TH216 UT WOS:A1996TH21600018 PM 8537111 ER PT J AU Verreck, FAW vandePoel, A Drijfhout, JW Amons, R Coligan, JE Koning, F AF Verreck, FAW vandePoel, A Drijfhout, JW Amons, R Coligan, JE Koning, F TI Natural peptides isolated from Gly(86)Val(86)-containing variants of HLA-DR1, -DR11, -DR13, and -DR52 SO IMMUNOGENETICS LA English DT Article ID HLA-DR MOLECULES; BINDING PEPTIDES; BETA-CHAIN; SPECIFICITY; MOTIF; POLYMORPHISM; RESIDUE-86; EPITOPES; ALLELES; SHARE C1 LEIDEN UNIV,BLOOD BANK,2300 RC LEIDEN,NETHERLANDS. SYLVIUS LABS,DEPT BIOCHEM MED,LEIDEN,NETHERLANDS. NIAID,MOLEC STRUCT LAB,NIH,ROCKVILLE,MD. RP Verreck, FAW (reprint author), LEIDEN UNIV,DEPT IMMUNOHAEMATOL,POB 9600,2300 RC LEIDEN,NETHERLANDS. NR 28 TC 35 Z9 35 U1 0 U2 4 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0093-7711 J9 IMMUNOGENETICS JI Immunogenetics PY 1996 VL 43 IS 6 BP 392 EP 397 DI 10.1007/BF02199809 PG 6 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA UD863 UT WOS:A1996UD86300009 PM 8606061 ER PT J AU Kinter, A Fauci, AS AF Kinter, A Fauci, AS TI Interleukin-2 and human immunodeficiency virus infection: Pathogenic mechanisms and potential for immunologic enhancement SO IMMUNOLOGIC RESEARCH LA English DT Review DE HIV; interleukin-2; pathogenesis ID IMMUNE-DEFICIENCY SYNDROME; AIDS-RELATED COMPLEX; CD4+ T-CELLS; HIV-1 SEROPOSITIVE INDIVIDUALS; PERIPHERAL-BLOOD LYMPHOCYTES; SOLUBLE IL-2 RECEPTOR; TUMOR-NECROSIS-FACTOR; MONONUCLEAR-CELLS; NATURAL-KILLER; MESSENGER-RNA AB A hallmark of human immunodeficiency virus (HIV) infection is the progressive loss of CD4+ T lymphocytes; however, qualitative defects in immune responses occur prior to the precipitous drop CD4+ T cell numbers. One of the first immunologic defects to be described in HIV-infected individuals is a deficiency in interleukin (IL)-2 production. The addition of IL-2 in vitro to cultures of mononuclear cells from HIV-infected individuals partially or completely restored certain defective cellular immune responses, However, production of or addition of IL-2 has also been associated with increased viral replication in infected T cells. These observations underscore the pernicious correlation between immune activation and HIV replication. However, recent in vitro and in vivo studies have provided promising preliminary results suggesting that, at least at certain stages of disease, the benefits of IL-2-mediated immune enhancement may outweigh or override the inductive effects of this cytokine on HIV production. RP Kinter, A (reprint author), NIAID,IMMUNOREGULAT LAB,NIH,BLDG 10,ROOM 6A33,10 CTR DR,MSC-1576,BETHESDA,MD 20892, USA. NR 136 TC 36 Z9 36 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0257-277X J9 IMMUNOL RES JI Immunol. Res. PY 1996 VL 15 IS 1 BP 1 EP 15 DI 10.1007/BF02918280 PG 15 WC Immunology SC Immunology GA UJ790 UT WOS:A1996UJ79000001 PM 8739561 ER EF