FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Miller, SD Shevach, EM AF Miller, SD Shevach, EM TI Immunoregulation of experimental autoimmune encephalomyelitis: editorial overview SO RESEARCH IN IMMUNOLOGY LA English DT Review ID EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; MYELIN BASIC-PROTEIN; NEUROANTIGEN-SPECIFIC TOLERANCE; TUMOR-NECROSIS-FACTOR; T-CELLS; MONOCLONAL-ANTIBODY; IMMUNE DEVIATION; BYSTANDER SUPPRESSION; MULTIPLE-SCLEROSIS; ORAL TOLERANCE C1 Northwestern Univ, Sch Med, Dept Microbiol & Immunol, Chicago, IL 60611 USA. Northwestern Univ, Sch Med, Interdept Immunobiol Ctr, Chicago, IL 60611 USA. NIAID, Immunol Lab, Cellular Immunol Sect, NIH, Bethesda, MD 20892 USA. RP Miller, SD (reprint author), Northwestern Univ, Sch Med, Dept Microbiol & Immunol, 303 E Chicago Ave, Chicago, IL 60611 USA. NR 62 TC 18 Z9 18 U1 1 U2 1 PU EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS CEDEX 15 PA 23 RUE LINOIS, 75724 PARIS CEDEX 15, FRANCE SN 0923-2494 J9 RES IMMUNOL JI Res. Immunol. PD NOV-DEC PY 1998 VL 149 IS 9 BP 753 EP 759 DI 10.1016/S0923-2494(99)80002-9 PG 7 WC Immunology SC Immunology GA 162DX UT WOS:000078331100002 PM 9923630 ER PT J AU Segal, BM AF Segal, BM TI The comeback of the elusive "suppressor" cell: an update on the regulatory network in EAE SO RESEARCH IN IMMUNOLOGY LA English DT Article ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; EXPERIMENTAL-ALLERGIC-ENCEPHALOMYELITIS; MYELIN BASIC-PROTEIN; CD8+ T-CELLS; CENTRAL-NERVOUS-SYSTEM; MULTIPLE-SCLEROSIS; TH2 CELLS; IMMUNE DEVIATION; SELF-TOLERANCE; RECEPTOR C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Segal, BM (reprint author), NIAID, Immunol Lab, NIH, Rm 11N311,10 Ctr Dr MSC 1892, Bethesda, MD 20892 USA. OI Segal, Benjamin/0000-0002-0906-6319 NR 54 TC 1 Z9 1 U1 0 U2 0 PU EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS CEDEX 15 PA 23 RUE LINOIS, 75724 PARIS CEDEX 15, FRANCE SN 0923-2494 J9 RES IMMUNOL JI Res. Immunol. PD NOV-DEC PY 1998 VL 149 IS 9 BP 811 EP 820 DI 10.1016/S0923-2494(99)80009-1 PG 10 WC Immunology SC Immunology GA 162DX UT WOS:000078331100009 PM 9923637 ER PT J AU Ory, MG Zablotsky, DL Crystal, S AF Ory, MG Zablotsky, DL Crystal, S TI HIV/AIDS and aging: Identifying a prevention research and care agenda SO RESEARCH ON AGING LA English DT Editorial Material ID AIDS C1 NIA, Bethesda, MD 20892 USA. Univ N Carolina, Charlotte, NC 28223 USA. RP Ory, MG (reprint author), NIA, Bethesda, MD 20892 USA. NR 22 TC 23 Z9 23 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0164-0275 J9 RES AGING JI Res. Aging PD NOV PY 1998 VL 20 IS 6 BP 637 EP 652 DI 10.1177/0164027598206001 PG 16 WC Gerontology SC Geriatrics & Gerontology GA 133ZM UT WOS:000076717500001 ER PT J AU Ory, MG Mack, KA AF Ory, MG Mack, KA TI Middle-aged and older people with AIDS - Trends in national surveillance rates, transmission routes, and risk factors SO RESEARCH ON AGING LA English DT Article AB This article explores the stability and changes in national trends related to AIDS rates, transmission routes, and risk factors from the mid-1980s to 1997. The authors show that while the numbers of AIDS cases have grown dramatically for all age groups, the proportion of cases for persons age 50 and older (at diagnosis) has remained a fairly stable 10% of the total case load, resulting in more than 60,000 cases in 1997. Contrary to popular belief, the most prevalent transmission route for middle-aged and older people has always been through sexual contact. While middle-aged and older people may be at reduced risk compared to younger age groups, these data af so reveal a disturbing trend. People age 50 and older continue to be less knowledgeable about AIDS risks, perceive themselves to be at lower risk, and, for those with known AIDS-related risks, have made fewer behavioral accommodations to avoid such risks as compared to younger people. With recent data indicating a faster rise in new AIDS cases among the 50-plus population, middle-aged and older people can no longer be ignored in AIDS prevention or treatment efforts. C1 NIA, Bethesda, MD 20892 USA. Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. RP Ory, MG (reprint author), NIA, Bethesda, MD 20892 USA. RI Mack, Karin/A-3263-2012 OI Mack, Karin/0000-0001-9274-3001 NR 25 TC 38 Z9 39 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0164-0275 J9 RES AGING JI Res. Aging PD NOV PY 1998 VL 20 IS 6 BP 653 EP 664 DI 10.1177/0164027598206002 PG 12 WC Gerontology SC Geriatrics & Gerontology GA 133ZM UT WOS:000076717500002 ER PT J AU Moustafa, ME El-Saadani, MA Kandeel, KM Mansur, DB Lee, BJ Hatfield, DL Diamond, AM AF Moustafa, ME El-Saadani, MA Kandeel, KM Mansur, DB Lee, BJ Hatfield, DL Diamond, AM TI Overproduction of selenocysteine tRNA in Chinese hamster ovary cells following transfection of the mouse tRNA([Ser]Sec) gene SO RNA-A PUBLICATION OF THE RNA SOCIETY LA English DT Article DE glutathione peroxidase; methylation; selenium; selenoprotein ID TRANSFER-RNA GENE; GLUTATHIONE-PEROXIDASE ACTIVITY; PHOSPHOSERINE TRANSFER-RNA; SELENIUM-DEFICIENT RATS; MAMMALIAN-CELLS; TRANSFER RNASEC; ELEMENTS; TRANSCRIPTION; EXPRESSION; POPULATION AB Selenocysteine insertion during selenoprotein biosynthesis begins with the aminoacylation of selenocysteine tRNA([Ser]Sec) with serine, the conversion of the serine moiety to selenocysteine, and the recognition of specific UGA codons within the mRNA. Selenocysteine tRNA([Ser]Sec) exists as two major forms, differing by methylation of the ribose portion of the nucleotide at the wobble position of the anticodon. The levels and relative distribution of these two forms of the tRNA are influenced by selenium in mammalian cells and tissues. We have generated Chinese hamster ovary cells that exhibit increased levels of tRNA([Ser]Sec) following transfection of the mouse tRNA([Ser]Sec) gene. The levels of selenocysteine tRNA([Ser]Sec) in transfectants increased proportionally to the number of stably integrated copies of the tRNA([Ser]Sec) gene. Although we were able to generate transfectants overproducing tRNA([Ser]Sec) by as much as tenfold, the additional tRNA was principally retained in the unmethylated form. Selenium supplementation could not significantly affect the relative distributions of the two major selenocysteine tRNA([Ser]Sec) isoacceptors. In addition, increased levels of tRNA([Ser]Sec) did not result in measurable alterations in the levels of selenoproteins, including glutathione peroxidase. C1 Univ Illinois, Dept Human Nutr & Dietet, Chicago, IL 60612 USA. NCI, Sect Mol Biol Selenium, Basic Res Lab, NIH, Bethesda, MD 20892 USA. Univ Alexandria, Fac Sci, Dept Biochem, Alexandria, Egypt. Seoul Natl Univ, Inst Mol Biol & Genet, Genet Mol Lab, Seoul 151742, South Korea. RP Diamond, AM (reprint author), Univ Illinois, Dept Human Nutr & Dietet, 1919 W Taylor St,MC 517, Chicago, IL 60612 USA. NR 33 TC 18 Z9 18 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 USA SN 1355-8382 J9 RNA JI RNA-Publ. RNA Soc. PD NOV PY 1998 VL 4 IS 11 BP 1436 EP 1443 DI 10.1017/S1355838298981043 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 134XA UT WOS:000076768000010 PM 9814763 ER PT J AU Strober, W Fuss, IJ Ehrhardt, RO Neurath, M Boirivant, M Ludviksson, BR AF Strober, W Fuss, IJ Ehrhardt, RO Neurath, M Boirivant, M Ludviksson, BR TI Mucosal immunoregulation and inflammatory bowel disease: New insights from murine models of inflammation SO SCANDINAVIAN JOURNAL OF IMMUNOLOGY LA English DT Review ID CD4(+) T-CELLS; RESIDENT INTESTINAL FLORA; ULCERATIVE-COLITIS; CROHNS-DISEASE; ORAL TOLERANCE; COLONIC INFLAMMATION; IL-2-DEFICIENT MICE; MUTANT MICE; IFN-GAMMA; BETA C1 NIAID, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. Prot Design Labs Inc, Mt View, CA USA. Univ Mainz, Immunol Lab 1, D-6500 Mainz, Germany. Inst Super Sanita, Immunol Lab, Rome, Italy. RP Strober, W (reprint author), NIAID, Clin Invest Lab, NIH, Bldg 10,Room 11N238, Bethesda, MD 20892 USA. RI BOIRIVANT, MONICA/B-9977-2016; OI Ludviksson, Bjorn/0000-0002-6445-148X NR 60 TC 46 Z9 48 U1 1 U2 4 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0300-9475 J9 SCAND J IMMUNOL JI Scand. J. Immunol. PD NOV PY 1998 VL 48 IS 5 BP 453 EP 458 PG 6 WC Immunology SC Immunology GA 137XK UT WOS:000076942200001 PM 9822251 ER PT J AU Lenfant, C Kiley, J AF Lenfant, C Kiley, J TI Sleep research: Celebration and opportunity SO SLEEP LA English DT Editorial Material C1 NHLBI, NIH, Bethesda, MD 20892 USA. NIH, Natl Ctr Sleep Disorders Res, Bethesda, MD 20892 USA. RP Lenfant, C (reprint author), NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SLEEP DISORDERS ASSOC PI ROCHESTER PA 1610 14TH STREET NW SUITE 300, ROCHESTER, MN 55806 USA SN 0161-8105 J9 SLEEP JI Sleep PD NOV 1 PY 1998 VL 21 IS 7 BP 665 EP + PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 136XP UT WOS:000076884600001 PM 11286341 ER PT J AU Redline, S Sanders, MH Lind, BK Quan, SF Iber, C Gottlieb, DJ Bonekat, WH Rapoport, DM Smith, PL Kiley, JP AF Redline, S Sanders, MH Lind, BK Quan, SF Iber, C Gottlieb, DJ Bonekat, WH Rapoport, DM Smith, PL Kiley, JP TI Methods for obtaining and analyzing unattended polysomnography data for a multicenter study SO SLEEP LA English DT Article DE polysomnography; epidemiology; sleep apnea AB This paper reviews the data collection, processing, and analysis approaches developed to obtain comprehensive unattended polysomnographic data for the Sleep Heart Health Study, a multicenter study of the cardiovascular consequences of sleep-disordered breathing. Protocols were developed and implemented to standardize in-home data collection procedures and to perform centralized sleep scoring. Of 7027 studies performed on 6697 participants, 5534 studies were determined to be technically acceptable (failure rate 5.3%). Quality grades varied over time, reflecting the influences of variable technician experience, and equipment aging and modifications. Eighty-seven percent of studies were judged to be of "good" quality or better, and 75% were judged to be of sufficient quality to provide reliable sleep staging and arousal data. Poor submental EMG (electromyogram) accounted for the largest proportion of poor signal grades (9% of studies had <2 hours artifact free EMG signal). These data suggest that with rigorous training and clear protocols for data collection and processing, good-quality multichannel polysomnography data can be obtained for a majority of unattended studies performed in a research setting. Data most susceptible to poor signal quality are sleep staging and arousal data that require clear EEG (electroencephalograph) and EMG signals. C1 Case Western Reserve Univ, Dept Med, Cleveland, OH 44106 USA. Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. Univ Pittsburgh, Dept Anesthesiol, Pittsburgh, PA USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. Univ Arizona, Dept Med, Tucson, AZ USA. Univ Arizona, Resp Sci Ctr, Tucson, AZ USA. Univ Minnesota, Dept Med, Minneapolis, MN 55455 USA. Boston Univ, Dept Med, Boston, MA USA. Univ Calif Davis, Dept Med, Davis, CA USA. NYU, Dept Med, New York, NY 10016 USA. Johns Hopkins Univ, Dept Med, Baltimore, MD USA. NHLBI, NIH, Bethesda, MD 20892 USA. RP Redline, S (reprint author), Rainbow Babies & Childrens Hosp, Div Clin Epidemiol, 11100 Euclid Ave, Cleveland, OH 44106 USA. FU NHLBI NIH HHS [U01HL53940, U01 HL053938, U01HL53941, UO1HL53938] NR 4 TC 222 Z9 222 U1 2 U2 7 PU AMER SLEEP DISORDERS ASSOC PI ROCHESTER PA 1610 14TH STREET NW SUITE 300, ROCHESTER, MN 55806 USA SN 0161-8105 J9 SLEEP JI Sleep PD NOV 1 PY 1998 VL 21 IS 7 BP 759 EP 767 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 136XP UT WOS:000076884600012 PM 11300121 ER PT J AU Comi, RJ Gorden, P AF Comi, RJ Gorden, P TI Long-term medical treatment of ectopic ACTH syndrome SO SOUTHERN MEDICAL JOURNAL LA English DT Article ID ADRENOCORTICOTROPIC HORMONE SYNDROME; ACTING SOMATOSTATIN ANALOG; CUSHINGS-SYNDROME; CARCINOID-TUMOR; KETOCONAZOLE; OCTREOTIDE; SECRETION; METYRAPONE; SUPPRESSION; MANAGEMENT AB Background. The morbidity of hypercortisolemia due to ectopic production of ACTH by various tumors may be greater than the morbidity of the tumor itself. Methods. We report three cases of long-term treatment of ectopic ACTH syndrome due to metastatic bronchial carcinoid, islet cell carcinoma, and malignant thymoma tumors. Clinical and biochemical eucortisolemia was achieved in each case and was sustained from 24 to 55 months. We review the therapeutic options and their reported efficacy. Results. Cessation of therapy resulted in recurrence of hypercortisolemia in each case, showing the effectiveness of therapy Conclusion. Long-term treatment of ectopic ACTH-induced hypercortisolemia by blocking adrenal steroidogenesis is clinically effective and well tolerated. C1 NIDDKD, Diabet Branch, NIH, Bethesda, MD 20892 USA. Dartmouth Hitchcock Med Ctr, Dept Med, Lebanon, NH 03766 USA. RP Gorden, P (reprint author), NIDDKD, Diabet Branch, NIH, Bldg 31,Room 9A52,31 Ctr Dr,MSC 2560, Bethesda, MD 20892 USA. NR 25 TC 2 Z9 5 U1 0 U2 0 PU SOUTHERN MEDICAL ASSN PI BIRMINGHAM PA 35 LAKESHORE DR PO BOX 190088, BIRMINGHAM, AL 35219 USA SN 0038-4348 J9 SOUTHERN MED J JI South.Med.J. PD NOV PY 1998 VL 91 IS 11 BP 1014 EP 1018 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 137QE UT WOS:000076926100004 PM 9824181 ER PT J AU Chen, TT Tai, JJ AF Chen, TT Tai, JJ TI A conversation with C. C. Li SO STATISTICAL SCIENCE LA English DT Editorial Material ID PATERNITY AB Ching Chun Li was born on October 27, 1912, in Tianjin, China. He received his B.S. degree in agronomy from the University of Nanjing, China, in 1936 and a Ph.D. in plant breeding and genetics from Cornell University in 1940. He did postgraduate work in mathematics, mathematical statistics and experimental statistics at the University of Chicago, Columbia University and North Carolina State College, 1940-1941. He is a Fellow of the American Statistical Association (elected 1969), an elected member of the International Statistical Institute, a Fellow of the American Association for the Advancement of Science and an elected member of Academia Sinica (Chinese Academy). He served as President of the American Society of Human Genetics in 1960. His tenure at the University of Pittsburgh began in 1951. He was Professor and Department Chairman, Biostatistics, from 1969 to 1975, and he was promoted to University Professor in 1975. Although he retired in 1983, he has remained active in research. C1 Univ Maryland, Biostat Sect, Greenebaum Canc Ctr, Baltimore, MD 21201 USA. Natl Taiwan Univ, Coll Publ Hlth, Grad Inst Epidemiol, Taipei 100, Taiwan. NCI, Bethesda, MD 20892 USA. Acad Sinica, Inst Stat Sci, Taipei 11529, Taiwan. RP Chen, TT (reprint author), Univ Maryland, Biostat Sect, Greenebaum Canc Ctr, Baltimore, MD 21201 USA. NR 25 TC 1 Z9 2 U1 0 U2 0 PU INST MATHEMATICAL STATISTICS PI HAYWARD PA IMS BUSINESS OFFICE-SUITE 7, 3401 INVESTMENT BLVD, HAYWARD, CA 94545 USA SN 0883-4237 J9 STAT SCI JI Stat. Sci. PD NOV PY 1998 VL 13 IS 4 BP 378 EP 387 PG 10 WC Statistics & Probability SC Mathematics GA 177CH UT WOS:000079189500006 ER PT J AU Schwartz, SM Petitti, DB Siscovick, DS Longstreth, WT Sidney, S Raghunathan, TE Quesenberry, CP Kelaghan, J AF Schwartz, SM Petitti, DB Siscovick, DS Longstreth, WT Sidney, S Raghunathan, TE Quesenberry, CP Kelaghan, J TI Stroke and use of low-dose oral contraceptives in young women - A pooled analysis of two US studies SO STROKE LA English DT Article DE contraceptives, oral; stroke, hemorrhagic; stroke, ischemic; women ID OF-GENERAL-PRACTITIONERS; CARDIOVASCULAR-DISEASE; RISK; PROGESTOGENS AB Background and Purpose-The available data on low-dose oral contraceptive pill (OCP) use and stroke risk in US women are limited by small numbers. We sought more precise estimates by conducting a pooled analysis of data from 2 US population-based case-control studies. Methods-We analyzed interview data from 175 ischemic stroke cases, 198 hemorrhagic stroke cases, and 1191 control subjects 18 to 44 years of age. Results-For ischemic stroke, the pooled odds ratio (pOR) adjusted for stroke risk factors for current use of low-dose OCPs compared with women who had never used OCP (never users) was 0.66 (95% confidence interval [CI], 0.29 to 1.47) and compared with women not currently using OCPs (nonusers) the pOR was 1.09 (95% CI, 0.54 to 2.21). For hemorrhagic stroke, the pOR for current use of low-dose OCPs compared with never users was 0.95 (95% CI, 0.46 to 1.93) and compared with nonusers the pOR was 1.11 (95% CI, 0.61 to 2.01). The pORs for-current low-dose OCP use and either stroke type were not elevated among women who were greater than or equal to 35 years, cigarette smokers, obese, or not receiving medical therapy for hypertension. pORs for current low-dose OCP use were 2.08 (95% CI, 1.19 to 3.65) for ischemic stroke and 2.15 (95% CI, 0.85 to 5.45) for hemorrhagic stroke among women reporting a history of migraine but were not elevated among women without such a history. Past OCP use (irrespective of formulation) was inversely related to ischemic stroke but unrelated to hemorrhagic stroke. Conclusions-Women who use low-dose OCPs are, in the aggregate, not at increased risk of stroke. Studies are needed to clarify the risk of stroke among users who may be susceptible on the basis of age, smoking, obesity, hypertension, or migraine history. C1 Univ Washington, Sch Publ Hlth & Community Med, Cardiovasc Hlth Res Unit, Seattle, WA 98101 USA. Univ Washington, Sch Publ Hlth & Community Med, Dept Epidemiol, Seattle, WA 98101 USA. Univ Washington, Sch Med, Dept Med, Div Gen Internal Med, Seattle, WA 98101 USA. Univ Washington, Sch Publ Hlth & Community Med, Dept Biostat, Seattle, WA 98101 USA. Univ Washington, Sch Med, Dept Neurol, Seattle, WA 98101 USA. So Calif Permanente Med Grp, Pasadena, CA USA. KP Med Care Program No Calif, Div Res, Oakland, CA USA. NICHHD, Contracept & Reprod Hlth Branch, Bethesda, MD 20892 USA. RP Schwartz, SM (reprint author), Univ Washington, Sch Publ Hlth & Community Med, Cardiovasc Hlth Res Unit, 1730 Minor Ave,Suite 1360, Seattle, WA 98101 USA. EM stevesch@u.washington.edu NR 18 TC 117 Z9 120 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0039-2499 J9 STROKE JI Stroke PD NOV PY 1998 VL 29 IS 11 BP 2277 EP 2284 PG 8 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 134QM UT WOS:000076754100006 PM 9804634 ER PT J AU Bhardwaj, A Sawada, M London, ED Koehler, RC Traystman, RJ Kirsch, JR AF Bhardwaj, A Sawada, M London, ED Koehler, RC Traystman, RJ Kirsch, JR TI Potent sigma(1)-receptor ligand 4-phenyl-1-(4-phenylbutyl) piperidine modulates basal and N-methyl-D-aspartate evoked nitric oxide production in vivo SO STROKE LA English DT Article DE excitotoxicity; ligands; microdialysis; nitric oxide; receptors, sigma; rats ID SIGMA-RECEPTOR LIGAND; PRODUCTION IN-VIVO; TRANSIENT FOCAL ISCHEMIA; DECREASES BRAIN INJURY; CEREBRAL-ISCHEMIA; RAT-BRAIN; INTRAVENTRICULAR INFUSION; MEDIATED NEUROTOXICITY; GLUTAMATE; NMDA AB Background and Purpose-sigma-Receptor ligands ameliorate ischemic neuronal injury and modulate neuronal responses to N-methyl-D-aspartate (NMDA) receptor stimulation. Because NMDA-evoked synthesis of nitric oxide (NO) may play an important role in excitotoxic-mediated injury, we tested the hypothesis that sigma-receptor ligands attenuate basal and NMDA-evoked NO production in the striatum in vivo. Methods-Microdialysis probes were placed bilaterally into the striatum of halothane-anesthetized adult Wistar mts. Rats were divided into 7 treatment groups and perfused with artificial cerebrospinal fluid (aCSF) containing 3 mu mol/L [C-14]L-arginine for 2 to 3 hours followed by NMDA in various combinations with the following drugs: L-nitroarginine (L-NNA); the sigma(1)-receptor ligand 4-phenyl-1-(4-phenylbutyl) piperidine (PPBP); the selective sigma(1)-receptor antagonist 1-(cyclopropylmethyl)-4-(2'-oxoethyl) piperidine hydrobromide (DuP 734); and the noncompetitive NMDA receptor blocker MK-801 in aCSF. Right-left differences between [C-14]L-citrulline in the effluent from rats treated with different drug combinations were assumed to reflect differences in NO production. Results-After a 3-hour loading period with [C-14]L-arginine, addition of 1 mmol/L NMDA increased [C-14]L-citrulline recovery compared with aCSF alone. This NMDA-evoked increase was inhibited by 1 mmol/L of L-NNA and PPBP, Perfusion of 1 mmol/L of the sigma(1)-receptor antagonist DuP 734 with 1 mmol/L PPBP augmented NMDA-evoked [C-14]L-citrulline recovery compared with perfusion with PPBP and NMDA, MK-801 attenuated the basal as well as NMDA-evoked [C-14]L-citrulline recovery. PPBP did not cause any further attenuation in the basal and NMDA-evoked [C-14]L-citrulline recovery in the presence of MK-801. Conclusions-These data indicate that a sigma(1)-receptor ligand attenuates basal as well as NMDA-evoked NO production. Because the attenuated NO production was reversed by DuP 734, PPBP appears to act as an agonist at the sigma(1)-receptor. Attenuated NO production by sigma(1)-receptor agonists provides one possible mechanism for focal ischemic neuroprotection, C1 Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Anesthesiol & Crit Care Med, Baltimore, MD 21205 USA. NIDA, Baltimore, MD USA. RP Bhardwaj, A (reprint author), Johns Hopkins Hosp, Neurosci Crit Care Div, Meyer 8-140,600 N Wolfe St, Baltimore, MD 21287 USA. EM abhardwa@welchlink.welch.jhu.edu NR 46 TC 32 Z9 33 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0039-2499 J9 STROKE JI Stroke PD NOV PY 1998 VL 29 IS 11 BP 2404 EP 2410 PG 7 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 134QM UT WOS:000076754100029 PM 9804655 ER PT J AU McCann, UD Jie, Y Ricaurte, GA AF McCann, UD Jie, Y Ricaurte, GA TI Neurotoxic effects of (+/-)fenfluramine and phentermine, alone and in combination, on monoamine neurons in the mouse brain SO SYNAPSE LA English DT Article DE fenfluramine; phentermine; serotonin; neurotoxicity; dopamine; obesity ID RAT-BRAIN; SEROTONIN NEUROTOXICITY; REPEATED FENFLURAMINE; NONHUMAN-PRIMATES; DL-FENFLURAMINE; TIME-COURSE; DEXFENFLURAMINE; DEPLETION; DOPAMINE; TERM AB Until recently, (+/-)fenfluramine (FEN) was widely prescribed as an appetite suppressant. In animals, FEN is a potent and selective brain serotonin neurotoxin. The present studies assessed the effects of phentermine (PHEN), an appetite suppressant frequently used clinically in combination with FEN, on FEN-induced serotonin neurotoxicity. Groups (n = 6/group) of mice were treated with FEN (10 mg/kg), PHEN (20 mg/kg or 40 mg/kg), FEN (10 mg/kg) plus PHEN (20 mg/kg or 40 mg/kg), or vehicle twice daily for four days. Food intake and body weight were measured during and after drug treatment. Brains were evaluated for regional brain serotonin and dopamine axonal markers two weeks after drug treatment. PHEN enhanced the anorectic and weight-reducing effects of FEN. PHEN also significantly enhanced FEN's long-term toxic effects on 5-HT axons. This effect was evident in some (hypothalamus, striatum) but not all (hippocampus, cortex) brain regions examined. PHEN alone produced no long-term effects on 5-HT axonal markers. However, whether given alone or in combination with FEN, PHEN produced significant, dose-related decreases in striatal DA axonal markers. These results, coupled with those from previous studies, suggest that PHEN has the potential to exacerbate FEN-induced serotonin neurotoxicity, if utilized in certain doses. Further, the present results indicate that PHEN possesses dopamine (DA) neurotoxic potential. The relevance of these data to humans previously treated with FEN/PHEN is discussed. Synapse 30:239-248, 1998. (C) 1998 Wiley-Liss. Inc. C1 Johns Hopkins Med Inst, Dept Neurol, Baltimore, MD 21205 USA. NIMH, Unit Anxiety & Affect Disorders, Bethesda, MD 20892 USA. RP Ricaurte, GA (reprint author), Johns Hopkins Med Inst, Dept Neurol, 5501 Bayview Blvd, Baltimore, MD 21205 USA. FU NIDA NIH HHS [DA05707, R01 DA06275, DA05938] NR 36 TC 12 Z9 12 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0887-4476 J9 SYNAPSE JI Synapse PD NOV PY 1998 VL 30 IS 3 BP 239 EP 246 DI 10.1002/(SICI)1098-2396(199811)30:3<239::AID-SYN1>3.0.CO;2-C PG 8 WC Neurosciences SC Neurosciences & Neurology GA 123JM UT WOS:000076122100001 PM 9776127 ER PT J AU Heidbreder, CA Schenk, S Partridge, B Shippenberg, TS AF Heidbreder, CA Schenk, S Partridge, B Shippenberg, TS TI Increased responsiveness of mesolimbic and mesostriatal dopamine neurons to cocaine following repeated administration of a selective kappa-opioid receptor agonist SO SYNAPSE LA English DT Article DE cocaine; kappa-opioid receptors; nucleus accumbens; caudate-putamen ID FREELY MOVING RATS; NUCLEUS-ACCUMBENS; EXTRACELLULAR DOPAMINE; STEREOTYPED BEHAVIOR; MU; MODULATION; RELEASE; SYSTEMS; MICRODIALYSIS; SENSITIZATION AB Previous data have shown that the repeated administration of kappa-opioid receptor agonists attenuates the acute behavioral effects of cocaine. The site and mechanism by which kappa-agonists interact with this psychostimulant, however, are unknown. Accordingly, the present microdialysis study characterized the effects of prior, repeated administration of the selective kappa-opioid receptor agonist U69593 on basal and cocaine-evoked DA levels within the nucleus accumbens (NAC) and caudate putamen (CPU). The influence of U69593 treatment on the locomotor-activating effects of an acute cocaine challenge was also assessed. Rats received once daily injections of U69593 (0.16-0.32 mg/kg/day) or vehicle (1.0 ml/kg/day) for 3 days. The behavioral and neurochemical effects produced by an acute cocaine challenge (20 mg/kg i.p.) were assessed 2 days following treatment cessation. Administration of cocaine to control animals increased locomotor activity. This effect was attenuated in animals which had previously received U69593 (0.32 mg/kg/day x 3 days). Prior administration of U69593 failed to modify basal DA levels in either the NAC or CPU. Thus, 2 days following the cessation of U69593 treatment, dialysate DA levels did not differ from that of controls. Administration of cocaine to vehicle-treated animals increased dialysate levels of DA in both brain regions. However, in animals previously exposed to U69593 (0.32 mg/kg/day x 3 days), a significant enhancement in the response of DA neurons to cocaine was seen. These data demonstrate that prior, repeated administration of a selective kappa-opioid receptor agonist attenuates the locomotor-activating effects of cocaine and increases cocaine-evoked DA overflow in terminal projection areas of mesostriatal and mesolimbic DA neurons. These findings indicate that the behavioral interactions of kappa-agonists with cocaine observed in this and previous studies cannot be attributed to a presynaptic inhibition of DA release. Rather, they suggest that postsynaptic or non-DA mechanisms mediate the interaction of these agents with cocaine. Synapse 30:255-262, 1998. (C) 1998 Wiley-Liss, Inc.dagger C1 NIDA, Integrat Neurosci Unit, Behav Neurosci Branch, NIH, Baltimore, MD 21224 USA. Texas A&M Univ, Dept Psychol, College Stn, TX 77843 USA. RP Shippenberg, TS (reprint author), NIDA, Integrat Neurosci Unit, Behav Neurosci Branch, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. FU NIDA NIH HHS [DA 10084] NR 37 TC 35 Z9 35 U1 0 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0887-4476 J9 SYNAPSE JI Synapse PD NOV PY 1998 VL 30 IS 3 BP 255 EP 262 DI 10.1002/(SICI)1098-2396(199811)30:3<255::AID-SYN3>3.3.CO;2-M PG 8 WC Neurosciences SC Neurosciences & Neurology GA 123JM UT WOS:000076122100003 PM 9776129 ER PT J AU Izenwasser, S Acri, JB Kunko, PM Shippenberg, T AF Izenwasser, S Acri, JB Kunko, PM Shippenberg, T TI Repeated treatment with the selective kappa opioid agonist U-69593 produces a marked depletion of dopamine D-2 receptors SO SYNAPSE LA English DT Article DE cocaine; sensitization; tolerance ID FREELY MOVING RATS; NUCLEUS-ACCUMBENS; LIGAND-BINDING; H-3 DOPAMINE; IN-VIVO; COCAINE; STRIATUM; INHIBITION; RELEASE; MODULATE AB U-69593, the selective kappa-opioid agonist, was repeatedly administered in single daily injections (0.32 mg/kg) to male, Sprague-Dawley rats. Two or ten days later, the rats were euthanized and dopamine D-1 and D-2 receptors were measured using [H-3]SCH 23390 or [H-3]sulpiride, respectively, in caudate putamen and nucleus accumbens. Two days after the last of three injections, dopamine D-2 receptors in the caudate putamen were decreased by approximately 40%, with no change in D-1 receptors. Dopamine D-2 receptor number had returned to normal by 10 days posttreatment. In contrast, in the nucleus accumbens there was a small, nonsignificant decrease in dopamine D-2 receptors 2 days after treatment, but a large increase (65%) after 10 days. In agreement with the changes in D-2 receptors, there was a significant downward shift in the locomotor activity curve for the D-2 agonist quinpirole after a 2-day withdrawal. There were no differences in either the total amount of dopamine taken up or in the IC50 for cocaine to inhibit dopamine uptake following this treatment, suggesting that the dopamine transporter and presynaptic terminals were intact. The results of these studies demonstrate that repeated administration of a selective kappa-opioid agonist induces long-term alterations in dopamine D-2 receptors. Furthermore, the finding that these changes in receptor number require both repeated injections and a withdrawal time greater than 1 day suggests that these alterations are compensatory in nature. Synapse 30:275-283, 1998. (C) 1998 Wiley-Liss, Inc. C1 NIDA, Psychobiol Sect, Div Intramural Res, NIH, Baltimore, MD USA. NIDA, Integrat Neurosci Unit, Div Intramural Res, NIH, Baltimore, MD USA. RP Izenwasser, S (reprint author), Univ Miami, Sch Med, Dept Neurol, 1501 NW 9th Ave,Rm 4061, Miami, FL 33136 USA. EM sizenwas@newssun.med.miami.edu RI Izenwasser, Sari/G-9193-2012 NR 32 TC 31 Z9 31 U1 1 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0887-4476 J9 SYNAPSE JI Synapse PD NOV PY 1998 VL 30 IS 3 BP 275 EP 283 DI 10.1002/(SICI)1098-2396(199811)30:3<275::AID-SYN5>3.0.CO;2-8 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 123JM UT WOS:000076122100005 PM 9776131 ER PT J AU Kauffman, RD Schmidt, PM Rall, WF Hoeg, JM AF Kauffman, RD Schmidt, PM Rall, WF Hoeg, JM TI Superovulation of rabbits with FSH alters in vivo development of vitrified morulae SO THERIOGENOLOGY LA English DT Article DE superovulation; follicle-stimulating hormone; vitrification; embryo banking ID TRANSGENIC RABBITS; CHOLESTEROL ACYLTRANSFERASE; EMBRYO RECOVERY; ETHYLENE-GLYCOL; MOUSE EMBRYOS; SURVIVAL; VITRIFICATION; CRYOPRESERVATION; OVEREXPRESSION; BLASTOCYSTS AB Morulae were flushed from the oviducts and uteri of New Zealand White (NZW) rabbits superovulated with either 6 (3 d) or 8 (4 d) injections of FSH and from nonsuperovulated controls. The percentages of embryos recovered from 4 d (100%, n=8) donors was significantly higher (P<0.01) than that of 3 d (76%, n=16) and control (87%, n=22) donors. Overall, fertilization rates were significantly lower for the 3 d embryos (P<0.01). Most (86 to 90%) morulae were morphologically suitable for vitrification in an ethylene glycol-based solution. Following storage in liquid nitrogen, morulae were rapidly thawed and transferred to the uteri of pseudopregnant recipients. The total number of kits born for the 3 d, 4 d, and control groups was 40, 61 and 48, respectively. The percentage of live kits from morulae transferred was significantly lower for the 3 d (20%, n=201) than either the 4 d (36%, n=169; P<0.01) or the control (31%, n=157; P<0.05) group. The mean number of kits born/recipient for the 3 d (2.4+/-2.9), 4 d (4.7+/-3.5), and control (3.0+/-2.2) protocols did not differ (P>0.05). The estimated overall efficiency of producing kits based on normal morulae collected for control and 4 d groups, however, was nearly two-fold that for females given 6 FSH treatments. We conclude that the 4 d FSH superovulation regimen enhances the efficiency of rabbit reproductive biotechnology after embryo cryopreservation. These findings have important implications for rabbit colony management using embryo cryopreservation. Published by Elsevier Science Inc. C1 NHLBI, Mol Dis Branch, NIH, Bethesda, MD 20892 USA. NIH, Vet Resources Program, Off Res Serv, Bethesda, MD 20892 USA. RP Kauffman, RD (reprint author), NHLBI, Mol Dis Branch, NIH, 10-7N115,10 Ctr Dr, Bethesda, MD 20892 USA. EM Rick@mdb.nhlbi.nih.gov RI Rall, William/C-5104-2008 NR 41 TC 26 Z9 29 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0093-691X J9 THERIOGENOLOGY JI Theriogenology PD NOV PY 1998 VL 50 IS 7 BP 1081 EP 1092 DI 10.1016/S0093-691X(98)00209-X PG 12 WC Reproductive Biology; Veterinary Sciences SC Reproductive Biology; Veterinary Sciences GA 146ZK UT WOS:000077463600009 PM 10734425 ER PT J AU George, JD Price, CJ Marr, MC Myers, CB Schwetz, BA Heindel, JJ AF George, JD Price, CJ Marr, MC Myers, CB Schwetz, BA Heindel, JJ TI Evaluation of the developmental toxicity of methacrylamide and N,N '-methylenebisacrylamide in Swiss mice SO TOXICOLOGICAL SCIENCES LA English DT Article DE acrylamides; developmental toxicity; teratogenicity; mice; morphological development ID ZERO DOSE CONTROL; GAMMA-SCINTIGRAPHY; DNA FRAGMENTS; ELECTROPHORESIS; DOXORUBICIN; POLYMER; RAT; GALACTOSAMINE; COPOLYMERS; ACRYLAMIDE AB Timed-pregnant CD-1 outbred albino Swiss mice received either methacrylamide (MAC; 0, 60, 120, or 180 mg/kg/day) or N,N'-methylenebisacrylamide (BAC; 0, 3, 10, or 30 mg/kg/day) po in distilled water on gestational days (GD) 6 through 17. Maternal clinical status was monitored daily. At termination (GD 17), confirmed-pregnant females (27-30 per group, MAC; 24-25 per group, BAG) were evaluated for clinical status and gestational outcome; live fetuses were examined for external, visceral, and skeletal malformations. For MAC, no treatment-related maternal mortality was observed. Maternal body weight on GD 17, maternal weight gain during treatment and gestation, and corrected maternal weight gain were reduced at the high dose. Relative maternal food and water intake was not adversely affected; neurotoxicity was not observed. Relative maternal liver weight was increased at greater than or equal to 120 mg/kg/day; gravid uterine weight was decreased at 180 mg/kg/day. The maternal no-observed adverse effect level (NOAEL) was 60 mg/kg/day. The NOAEL for developmental toxicity was also 60 mg/kg/day. At greater than or equal to 120 mg/kg/day, mean fetal body weight was reduced. At 180 mg/kg/day, increased postimplantation death per litter was observed. Morphological development was not affected. The maternal NOAEL for BAC was 10 mg/kg/day. At 30 mg/kg/day, decreased maternal body weight on GD 17, maternal body weight change during treatment and gestation, corrected maternal body weight, and gravid uterine weight were observed. Relative maternal liver weight increased at 30 mg/kg/day. The developmental NOAEL was 3 mg/kg/day BAG. Mean fetal body weight was reduced at 30 mg/kg/day. At greater than or equal to 10 mg/kg/day, an increased incidence of fetal variations (extra rib) was observed, although fetal malformation rate was unaffected. MAC and BAC were not teratogenic to Swiss mice at the doses tested. BAC was more potent than MAC in causing adverse maternal and developmental effects. (C) 1998 Society of Toxicology. C1 Res Triangle Inst, Res Triangle Pk, NC 27709 USA. NIEHS, Natl Toxicol Program, Dev & Reprod Toxicol Grp, Res Triangle Pk, NC 27709 USA. RP George, JD (reprint author), Res Triangle Inst, POB 12194, Res Triangle Pk, NC 27709 USA. FU NIEHS NIH HHS [N01-ES-45061, N01-ES-95255] NR 44 TC 7 Z9 7 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD NOV PY 1998 VL 46 IS 1 BP 124 EP 133 DI 10.1006/toxs.1998.2506 PG 10 WC Toxicology SC Toxicology GA 151GB UT WOS:000077711400013 PM 9928675 ER PT J AU Melnick, RL Kohn, MC AF Melnick, RL Kohn, MC TI Untitled - Reply SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Letter ID REGENERATIVE CELL-PROLIFERATION; DRINKING-WATER; B6C3F(1) MICE; AD-LIBITUM; CORN-OIL; CHLOROFORM; GAVAGE; KIDNEYS; LIVERS; RATS C1 NIEHS, Environm Toxicol Program, Res Triangle Pk, NC 27709 USA. RP Melnick, RL (reprint author), NIEHS, Environm Toxicol Program, POB 12233, Res Triangle Pk, NC 27709 USA. NR 9 TC 3 Z9 3 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD NOV PY 1998 VL 153 IS 1 BP 135 EP 136 DI 10.1006/taap.1998.8497 PG 2 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 148ZU UT WOS:000077581900015 ER PT J AU Kohn, MC AF Kohn, MC TI Untitled - Reply SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Letter ID BUTADIENE; RATS; MICE C1 NIEHS, Lab Computat Biol & Risk Anal, Res Triangle Pk, NC 27709 USA. RP Kohn, MC (reprint author), NIEHS, Lab Computat Biol & Risk Anal, POB 12233, Res Triangle Pk, NC 27709 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD NOV PY 1998 VL 153 IS 1 BP 139 EP 140 DI 10.1006/taap.1998.8520 PG 2 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 148ZU UT WOS:000077581900019 ER PT J AU Altschul, SF Koonin, EV AF Altschul, SF Koonin, EV TI Iterated profile searches with PSI-BLAST - a tool for discovery in protein databases SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Article ID SEQUENCE DATABASES; STATISTICS; SEGMENTS; MOTIF; GENES C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Altschul, SF (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. EM altschul@ncbi.nlm.nih.gov NR 30 TC 410 Z9 422 U1 3 U2 14 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0968-0004 J9 TRENDS BIOCHEM SCI JI Trends Biochem.Sci. PD NOV PY 1998 VL 23 IS 11 BP 444 EP 447 DI 10.1016/S0968-0004(98)01298-5 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 144EV UT WOS:000077301800011 PM 9852764 ER PT J AU Schuler, GD AF Schuler, GD TI Electronic PCR: bridging the gap between genome mapping and genome sequencing SO TRENDS IN BIOTECHNOLOGY LA English DT Article ID YAC CONTIG MAP; PHYSICAL MAP AB A crucial event in the history of the Human Genome Project was the decision to use sequence-tagged sites (STSs) as common landmarks for genomic mapping. Following several years of constructing STS-based maps of ever-increasing detail, the emphasis has recently shifted towards large-scale genomic sequencing. A computational procedure called 'electronic PCR' allows STS landmarks to be revealed as data emerge from the sequencing pipeline, thereby bridging the gap between mapping and sequencing activities. C1 NIH, Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. RP Schuler, GD (reprint author), NIH, Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. NR 16 TC 49 Z9 51 U1 0 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0167-7799 J9 TRENDS BIOTECHNOL JI Trends Biotechnol. PD NOV PY 1998 VL 16 IS 11 BP 456 EP 459 DI 10.1016/S0167-7799(98)01232-3 PG 4 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 135NR UT WOS:000076809400003 PM 9830153 ER PT J AU Strunnikov, AV AF Strunnikov, AV TI SMC proteins and chromosome structure SO TRENDS IN CELL BIOLOGY LA English DT Article ID DOSAGE COMPENSATION COMPLEX; COMPLETE GENOME SEQUENCE; NEMATODE X-CHROMOSOME; SACCHAROMYCES-CEREVISIAE; SCHIZOSACCHAROMYCES-POMBE; SISTER CHROMATIDS; SCAFFOLD PROTEIN; ESCHERICHIA-COLI; CONDENSATION; GENE AB The structure of chromosomes is largely determined by chromosome-associated proteins. Members of the SMC (structural maintenance of chromosomes) family play an important role in both prokaryotic and eukaryotic chromosome structure and dynamics. SMC proteins are involved in chromosome condensation, sister-chromatin cohesion, sex-chromosome dosage compensation, genetic recombination and DNA repair. There have been major advances recently in understanding the function of SMC proteins - including the identification of biochemical activities of SMC-containing protein complexes and the realization that individual SMC proteins might link seemingly unrelated aspects of chromosomal metabolism. C1 NICHD, Mol Embryol Lab, Unit Chromosome Struct & Funct, NIH, Bethesda, MD 20892 USA. RP Strunnikov, AV (reprint author), NICHD, Mol Embryol Lab, Unit Chromosome Struct & Funct, NIH, 18T Lib Dr,Room 106, Bethesda, MD 20892 USA. OI Strunnikov, Alexander/0000-0002-9058-2256 NR 48 TC 65 Z9 69 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0962-8924 J9 TRENDS CELL BIOL JI Trends Cell Biol. PD NOV PY 1998 VL 8 IS 11 BP 454 EP 459 DI 10.1016/S0962-8924(98)01370-1 PG 6 WC Cell Biology SC Cell Biology GA 144EX UT WOS:000077302000007 PM 9854313 ER PT J AU De Weerd, P Desimone, R Ungerleider, LG AF De Weerd, P Desimone, R Ungerleider, LG TI Why does the brain fill in? Response SO TRENDS IN COGNITIVE SCIENCES LA English DT Editorial Material ID VISUAL-CORTEX; BRIGHTNESS C1 NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA. NIMH, Neuropsychol Lab, NIH, Bethesda, MD 20892 USA. RP De Weerd, P (reprint author), NIMH, Lab Brain & Cognit, 49 Convent Dr,MSC 4415, Bethesda, MD 20892 USA. EM pdw@ln.nimh.nih.gov NR 8 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1364-6613 J9 TRENDS COGN SCI JI TRENDS COGN. SCI. PD NOV PY 1998 VL 2 IS 11 BP 425 EP 426 DI 10.1016/S1364-6613(98)01243-1 PG 2 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA 171PQ UT WOS:000078872900005 PM 21227270 ER PT J AU Bagnato, A Catt, KJ AF Bagnato, A Catt, KJ TI Endothelins as autocrine regulators of tumor cell growth SO TRENDS IN ENDOCRINOLOGY AND METABOLISM LA English DT Review ID BREAST-CANCER CELLS; PROTEIN-COUPLED RECEPTORS; OVARIAN-CARCINOMA CELLS; FOCAL ADHESION KINASE; RAT MESANGIAL CELLS; STROMAL CELLS; IMMUNOREACTIVE ENDOTHELIN-1; HEPATOCELLULAR-CARCINOMA; GRANULOSA-CELLS; PROSTATE-CANCER AB Endothelin 1 (ET-1) is produced by several types of human cancer cells and has been proposed to participate in tumor development or progression by exerting autocrine or paracrine actions on neoplastic cells and their surrounding stromal cells. Recently, an ET-1-mediated autocrine loop has been implicated in the growth of ovarian tumor cells. The co-expression of ET-1 and ETA receptors, with consequent activation of growth signaling pathways in human ovarian carcinoma cells, constitutes a mechanism for the autocrine regulation of tumor cell growth. Such findings also provide a basis for further investigation of the role of tyrosine phosphorylation in ET-1-regulated growth responses in ovarian tumor cells. The overexpression of ET-1 and its receptor in cancer cells may serve as a tumor marker, and could provide potential targets for therapy. C1 NICHD, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA. RP Bagnato, A (reprint author), NICHD, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA. RI Bagnato, Anna/G-9747-2016 OI Bagnato, Anna/0000-0002-7269-9522 NR 45 TC 75 Z9 77 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 1043-2760 J9 TRENDS ENDOCRIN MET JI Trends Endocrinol. Metab. PD NOV PY 1998 VL 9 IS 9 BP 378 EP 383 DI 10.1016/S1043-2760(98)00094-0 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 134UK UT WOS:000076761800006 PM 18406309 ER PT J AU Aravind, L Tatusov, RL Wolf, YI Walker, DR Koonin, EV AF Aravind, L Tatusov, RL Wolf, YI Walker, DR Koonin, EV TI Evidence for massive gene exchange between archaeal and bacterial hyperthermophiles SO TRENDS IN GENETICS LA English DT Letter ID COMPLETE GENOME SEQUENCE C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Aravind, L (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. NR 11 TC 222 Z9 232 U1 2 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0168-9525 J9 TRENDS GENET JI Trends Genet. PD NOV PY 1998 VL 14 IS 11 BP 442 EP 444 DI 10.1016/S0168-9525(98)01553-4 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA 137ZC UT WOS:000076946100003 PM 9825671 ER PT J AU Segev, I Rall, W AF Segev, I Rall, W TI Excitable dendrites and spines: earlier theoretical insights elucidate recent direct observations SO TRENDS IN NEUROSCIENCES LA English DT Article ID NEOCORTICAL PYRAMIDAL NEURONS; ACTION-POTENTIAL INITIATION; CELL DENDRITES; SYNAPTIC TRANSMISSION; CALCIUM DYNAMICS; TIME COURSE; ONE BRANCH; IN-VIVO; MODEL; PROPAGATION AB Important advances in experimental methods have made it possible to measure the electrical events in dendrites directly and to record optically from dendritic spines,These new techniques allow us to focus on the input region of the neuron and highlight the excitable properties of the dendritic membrane. Interestingly, some of the recent experimental findings were anticipated by earlier theoretical research, for example, the observation that some spines possess excitable channels that might generate local all-or-none events. Computer models were used previously to explore the conditions for initiating an action potential at the dendritic tree, in particular, at the spine head, and for active propagation between excitable spines and excitable dendritic arbors. The consequences for synaptic amplification, for the extent of active spread in the tree and for non-linear discriminations between different patterns of synaptic inputs were also considered. Here we review the biophysical insights gained from the theory and demonstrate how these elucidate the recent experimental results. C1 Hebrew Univ Jerusalem, Inst Life Sci, Dept Neurobiol, IL-91904 Jerusalem, Israel. Hebrew Univ Jerusalem, Ctr Neural Computat, IL-91904 Jerusalem, Israel. NIDDK, Math Res Branch, NIH, Bethesda, MD 20892 USA. RP Segev, I (reprint author), Hebrew Univ Jerusalem, Inst Life Sci, Dept Neurobiol, IL-91904 Jerusalem, Israel. NR 93 TC 114 Z9 115 U1 0 U2 5 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0166-2236 J9 TRENDS NEUROSCI JI Trends Neurosci. PD NOV PY 1998 VL 21 IS 11 BP 453 EP 460 DI 10.1016/S0166-2236(98)01327-7 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 135XR UT WOS:000076828500002 PM 9829684 ER PT J AU Tirindelli, R Mucignat-Caretta, C Ryba, NJP AF Tirindelli, R Mucignat-Caretta, C Ryba, NJP TI Molecular aspects of pheromonal communication via the vomeronasal organ of mammals SO TRENDS IN NEUROSCIENCES LA English DT Review ID ACCESSORY OLFACTORY-BULB; MAJOR URINARY PROTEIN; MALE-MOUSE URINE; ADENYLYL-CYCLASE; MULTIGENE FAMILY; SIGNAL-TRANSDUCTION; GLUTAMATE RECEPTORS; BINDING-PROTEINS; GENE-EXPRESSION; MUS-MUSCULUS AB Recently, two large multigene families of putative G-protein-linked receptors that are expressed in distinct subpopulations of neurones in the vomeronasal organ have been identified. These receptors probably mediate pheromone detection. The most surprising aspects of these findings are that there are so many receptors of two very different classes and that the receptors are unrelated to their counterparts in the main olfactory epithelium. This suggests that many active ligands are likely to exert effects through the vomeronasal organ. Parallel experiments addressing the nature of these ligands indicate a role for some proteins, as well as small molecules, as functional mammalian pheromones. In combination, these results begin to suggest a molecular basis for mammalian pheromone signalling. C1 Univ Parma, Ist Fisiol Umana, I-43100 Parma, Italy. Univ Padua, Ist Fisiol Umana, Padua, Italy. NIDR, Taste & Smell Unit, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. RP Tirindelli, R (reprint author), Univ Parma, Ist Fisiol Umana, Via Volturno 39, I-43100 Parma, Italy. NR 58 TC 80 Z9 82 U1 2 U2 8 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0166-2236 J9 TRENDS NEUROSCI JI Trends Neurosci. PD NOV PY 1998 VL 21 IS 11 BP 482 EP 486 DI 10.1016/S0166-2236(98)01274-0 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 135XR UT WOS:000076828500009 PM 9829690 ER PT J AU Ornstein, DK Oh, J Herschman, JD Andriole, GL AF Ornstein, DK Oh, J Herschman, JD Andriole, GL TI Evaluation and management of the man who has failed primary curative therapy for prostate cancer SO UROLOGIC CLINICS OF NORTH AMERICA LA English DT Article ID RADICAL RETROPUBIC PROSTATECTOMY; EXTERNAL-BEAM RADIOTHERAPY; ULTRASOUND-GUIDED BIOPSY; TRANS-RECTAL ULTRASOUND; RADIATION-THERAPY; ANTIGEN LEVELS; LOCAL RECURRENCE; TRANSRECTAL ULTRASOUND; CRYOSURGICAL ABLATION; MONOCLONAL-ANTIBODY AB The rapid increase in the number of men undergoing potential curative local therapy for prostate cancer has made the evaluation and management of men failing local therapy a common urologic problem. Clinical factors such as tumor grade, pathologic stage, and rate of prostate-specific antigen (PSA) change are important in predicting the site of recurrence. New technologies such as monoclonal antibody scanning may provide helpful diagnostic information. Salvage radiation therapy for men failing radical prostatectomy is relatively well tolerated and reduces PSA to undetectable levels approximately half of the time although later relapse is uncommon. Salvage radical prostatectomy and cryotherapy for men failing external beam radiation are morbid procedures that less frequently result in undetectable PSA levels. The timing or hormonal therapy for men with presumed distant disease recurrence is controversial, as is the optimal form of therapy (such as potency sparing regimens, employing 5-alpha reductase inhibitors and/or anti-androgens, intermittent LHRH agonists, or conventional hormone therapy). C1 Washington Univ, Sch Med, Div Urol Surg, St Louis, MO 63110 USA. NCI, Urol Oncol Branch, Bethesda, MD 20892 USA. RP Andriole, GL (reprint author), Washington Univ, Sch Med, Div Urol Surg, 4960 Childrens Pl, St Louis, MO 63110 USA. NR 94 TC 36 Z9 36 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0094-0143 J9 UROL CLIN N AM JI Urol. Clin. N. Am. PD NOV PY 1998 VL 25 IS 4 BP 591 EP + DI 10.1016/S0094-0143(05)70050-1 PG 12 WC Urology & Nephrology SC Urology & Nephrology GA 136QV UT WOS:000076871400006 PM 10026768 ER PT J AU Coughlin, RT White, AC Anderson, CA Carlone, GM Klein, DL Treanor, J AF Coughlin, RT White, AC Anderson, CA Carlone, GM Klein, DL Treanor, J TI Characterization of pneumococcal specific antibodies in healthy unvaccinated adults SO VACCINE LA English DT Article DE pneumococcal capsular polysaccharides; Streptococcus pneumoniae; antibody; C-polysaccharide; enzyme-linked immunosorbent assay (ELISA) ID STREPTOCOCCUS-PNEUMONIAE; VACCINE; POLYSACCHARIDES AB Unlike the elderly healthy middle aged adults are at relatively low risk of acquiring serious pneumococcal disease, An explanation that has been proposed is that people in this age group have significant amounts of serum antibody (primarily IgG2) that react with many pneumococcal capsular polysaccharide serotypes, The level of antibody can be as high as several hundred micrograms per milliliter of blood for some serotypes, A significant component of this reactivity is directed coward the conserved C-polysaccharide depletion, Even after C-polysaccharide depletion, which is included as a routine part of the assay to determine antibody levels, resting antibody levels in a normal healthy adult population can vary widely. We have analyzed the reactivity of serum from 76 people to 16 pneumococcal capsular polysaccharide serotypes, The antibody, reactivities to 13 of 16 serotypes are highly correlated with one another Depletion of serum with C-polysaccharide and purified capsular polysaccharide inhibited antibody binding to type specific capsular polysaccharide, Cross-serotype inhibition of antibody binding was also observed. This indicates that there are materials contained within the pneumococcal polysaccharides that contribute to the cross-reactivity of serum antibodies in people that have not been vaccinated with the pneumococcal vaccine. (C) 1998 Elsevier Science Ltd, All rights reserved. C1 Aquila Biopharmaceut Inc, Framingham, MA 01702 USA. Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. NIH, Bacterial Resp Dis Branch, Bethesda, MD 20892 USA. Univ Rochester, Infect Dis Unit, Rochester, NY 14642 USA. RP Coughlin, RT (reprint author), Aquila Biopharmaceut Inc, 175 Crossing Blvd, Framingham, MA 01702 USA. FU NIAID NIH HHS [R01-AI33560, N01 AI45248] NR 13 TC 42 Z9 43 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD NOV PY 1998 VL 16 IS 18 SI SI BP 1761 EP 1767 DI 10.1016/S0264-410X(98)00139-X PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 122CJ UT WOS:000076052900012 PM 9778753 ER PT J AU Meldrum, M AF Meldrum, M TI "A calculated risk": the Salk polio vaccine field trials of 1954 SO BRITISH MEDICAL JOURNAL LA English DT Article C1 NIH, Bethesda, MD 20892 USA. RP Meldrum, M (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 12 TC 20 Z9 20 U1 0 U2 3 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0959-8138 J9 BRIT MED J JI Br. Med. J. PD OCT 31 PY 1998 VL 317 IS 7167 BP 1233 EP 1236 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 138GF UT WOS:000076963000034 PM 9794869 ER PT J AU McCann, UD Szabo, Z Scheffel, U Dannals, RF Ricaurte, GA AF McCann, UD Szabo, Z Scheffel, U Dannals, RF Ricaurte, GA TI Positron emission tomographic evidence of toxic effect of MDMA ("Ecstasy") on brain serotonin neurons in human beings SO LANCET LA English DT Article ID UPTAKE SITES; (+/-)3,4-METHYLENEDIOXYMETHAMPHETAMINE MDMA; METHYLENEDIOXYMETHAMPHETAMINE MDMA; NONHUMAN-PRIMATES; BABOON BRAIN; RAT-BRAIN; NEUROTOXICITY; TERMINALS; PET; 3,4-METHYLENEDIOXYMETHAMPHETAMINE AB Background. (+/-)3,4-methylenedioxymethamphetamine (MDMA; "Ecstasy") is, a popular recreational drug that selectively damages brain. serotonin (5-HT) neurons in animals at doses' that closely approach those used by humans. We investigated the status of brain 5-HT neurons in MDMA users. Methods We enrolled 14 previous users of MDMA who were currently abstaining from use and 15 controls who had never used MDMA. We used positron emission tomography (PET) with the radioligand carbon-11-labelled McN-5652, which selectively labels the 5-HT transporter. We analysed whether there were differences in 5-HT transporter binding between abstinent MDMA users and participants in the control group. Blood and urine samples were taken and tested to check for abstinence. Findings MDMA users showed decreased global and regional brain BHT transporter binding compared with controls. Decreases in 5-HT transporter binding positively correlated with the extent of previous MDMA use. Interpretation Quantitative PET studies with a ligand selective for 5-HT transporters can be used to assess the status of 5-HT neurons in the living human brain. We show direct evidence of a decrease in a structural component of brain 5-HT neurons in human MDMA users. C1 Johns Hopkins Med Inst, Dept Neurol, Baltimore, MD 21224 USA. NIMH, Biol Psychiat Branch, Bethesda, MD 20892 USA. Johns Hopkins Med Inst, Dept Radiol, Baltimore, MD 21224 USA. RP Ricaurte, GA (reprint author), Johns Hopkins Med Inst, Dept Neurol, Baltimore, MD 21224 USA. FU NIDA NIH HHS [DA05938, DA06275, DA10217] NR 34 TC 454 Z9 456 U1 4 U2 43 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON WC1B 3SL, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD OCT 31 PY 1998 VL 352 IS 9138 BP 1433 EP 1437 DI 10.1016/S0140-6736(98)04329-3 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 134AJ UT WOS:000076719500010 PM 9807990 ER PT J AU Kim, HY Pak, M Jakubowski, H AF Kim, HY Pak, M Jakubowski, H TI A site in the dinucleotide-fold domain contributes to the accuracy of tRNA selection by Escherichia coli methionyl tRNA synthetase SO MOLECULES AND CELLS LA English DT Article DE aminoacylation; anticodon; dinucleotide-fold domain; methionyl-tRNA synthetase ID TRANSFER-RNA-SYNTHETASE; ANTICODON BINDING-SITE; PROTEIN-SYNTHESIS; MICROHELIX AMINOACYLATION; AMINO-ACIDS; ACTIVE-SITE; INVIVO; IDENTITY; RECOGNITION; INITIATION AB Interactions of specific amino acid residues of the carboxyl-terminal domain of MetRS with the CAU anticodon of tRNA(Met) assure accurate and efficient aminoacylation, The substitution of one such residue, Trp461 by Phe, impairs the binding of cognate tRNA, but enhances the binding of noncognate tRNAs, particularly those containing G at the wobble position. However, the enhanced binding of noncognate tRNAs is not accompanied by the increased aminoacylation of these tRNAs, A genetic screening procedure was designed to isolate methionyl-tRNA synthetase mutants which were able to aminoacylate a GGU (threonine) anticodon derivative of tRNA(fMet). One such mutant, obtained from W461F MetRS, had an Ile29 to Thr substitution in helix A located in the amino-terminal dinucleotide-fold domain that forms the site for amino acid activation. Analysis of the catalytic properties of the I29T/W461F enzyme indicates that the mutation in helix A of the dinucleotide-fold domain affects k(cat) for aminoacylation of tRNAs having a GGU threonine anticodon, Interactions with cognate tRNA(fMet) (CAU), as well as,vith methionine and ATP were not affected by the Ile29 to Thr substitution. We conclude that the I29T substitution leads to a slight adjustment of the alignment of the CCA stem of noncognate tRNAs (CGU) in the catalytic domain of the enzyme, reflected in the increase in k(cat), which also allows mischarging in vivo. A function of Ile29 is therefore to minimize the mischarging of tRNA(Thr) (GGU) by methionyl-tRNA synthetase, The methods described here pro,ide useful tools for examining the mechanisms of tRNA selection by aminoacyl-tRNA synthetases. C1 Kyung Hee Univ, Dept Food Sci, Suwon 449701, South Korea. Kyung Hee Univ, Inst Genet Engn, Suwon 449701, South Korea. NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Microbiol & Mol Genet, Newark, NJ 07103 USA. RP Kim, HY (reprint author), Kyung Hee Univ, Dept Food Sci, Suwon 449701, South Korea. OI Jakubowski, Hieronim/0000-0001-5845-4409 NR 28 TC 1 Z9 1 U1 0 U2 1 PU SPRINGER-VERLAG SINGAPORE PTE LTD PI SINGAPORE PA #04-01 CENCON I, 1 TANNERY RD, SINGAPORE 347719, SINGAPORE SN 1016-8478 J9 MOL CELLS JI Mol. Cells PD OCT 31 PY 1998 VL 8 IS 5 BP 623 EP 628 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 134ML UT WOS:000076746800018 PM 9856352 ER PT J AU Lekstrom-Himes, J Xanthopoulos, KG AF Lekstrom-Himes, J Xanthopoulos, KG TI Biological role of the CCAAT enhancer-binding protein family of transcription factors SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Review ID ALPHA C/EBP-ALPHA; NEUTROPHIL ELASTASE PROMOTER; FACTOR-RECEPTOR PROMOTER; ACUTE-PHASE RESPONSE; DNA-BINDING; ADIPOCYTE DIFFERENTIATION; LEUCINE-ZIPPER; MOLECULAR-CLONING; 3T3-L1 ADIPOCYTES; GENE-EXPRESSION AB CCAAT/enhancer-binding proteins (C/EBPs) comprise a family of transcription factors that are critical for normal cellular differentiation and function in a variety of tissues. The prototypic C/EBP is a modular protein, consisting of an activation domain, a dimerization bZIP region, and a DNA binding domain. All family members share the highly conserved dimerization domain, required for DNA binding, by which they form homo- and heterodimers with other family members. C/EBPs are least conserved in their activation domains and vary from strong activators to dominant negative repressors. The pleiotropic effects of C/EBPs are in part because of tissue- and stage-specific expression. Dimerization of different C/EBP proteins precisely modulates transcriptional activity of target genes, Recent work with mice deficient in specific C/EBPs underscores the effects of these factors in tissue development, function, and response to injury. C1 Natl Human Genome Res Inst, Clin Gene Therapy Branch, NIH, Bethesda, MD 20892 USA. RP Xanthopoulos, KG (reprint author), Aurora Biosci Inc, 11010 Torreyana Rd, San Diego, CA 92121 USA. EM xanthopoulosk@aurorabio.com NR 86 TC 583 Z9 589 U1 1 U2 17 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 30 PY 1998 VL 273 IS 44 BP 28545 EP 28548 DI 10.1074/jbc.273.44.28545 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 133NC UT WOS:000076691800002 PM 9786841 ER PT J AU Hoffman, MP Nomizu, M Rogue, E Lee, S Jung, DW Yamada, Y Kleinman, HK AF Hoffman, MP Nomizu, M Rogue, E Lee, S Jung, DW Yamada, Y Kleinman, HK TI Laminin-1 and laminin-2 G-domain synthetic peptides bind syndecan-1 and are involved in acinar formation of a human submandibular gland cell line SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HEPARAN-SULFATE PROTEOGLYCANS; MOUSE SALIVARY EPITHELIUM; TERMINAL GLOBULAR DOMAIN; MEMBRANE-LIKE SUBSTRATUM; BRANCHING MORPHOGENESIS; NEURITE OUTGROWTH; ALPHA-CHAINS; SHORT ARM; IDENTIFICATION; ADHESION AB The culture of human submandibular gland (HSG) cells on laminin-l induces acinar differentiation. me identified a site on laminin involved in acinar differentiation using synthetic peptides derived from the C-terminal G-domain of the laminin alpha 1 and alpha 2 chains. The alpha 1 chain peptide AG73 (RKRLQVQLSIRT) decreases the size of acini formed on laminin-1, Cells cultured with either AG73 or the homologous alpha 2 chain peptide MG73 (KNRLTIELEVRT) form structures that appear acinar-like, but the cell nuclei are not polarized to the basal surface and no lumen formation occurs, indicating that additional sites on laminin are required for complete differentiation. The G-domain of laminin-l contains both integrin and heparin binding sites, and anti-beta(1)-integrin antibodies disrupt acinar formation. Cell adhesion to the peptides and to E3, an elastase digest fragment of laminin-1 containing AG73, is specific, since other laminin peptides or EDTA do not compete the binding. Heparin and heparan sulfate decrease cell adhesion to AG73 and MG73 but anti-beta(1)-integrin antibodies have no effect. Treating the cell surface with heparitinase inhibits adhesion to both AG73 and MG73, We isolated cell surface ligands using both peptide affinity chromatography and laminin-l affinity chromatography, Treating the material bound to the affinity columns with heparitinase and chondroitinase enriches for a core protein identified as syndecan-1 by Western blot analysis, thus identifying a syndecan-1 binding site in the globular domain of laminin-2 and laminin-2, In summary, multiple interactions between laminin and HSG cells contribute to acinar differentiation, involving both beta(1)-integrins and syndecan-1. C1 NIDR, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD 20892 USA. RP Kleinman, HK (reprint author), NIDR, Craniofacial Dev Biol & Regenerat Branch, NIH, 30-433,30 Convent Dr,MSC 4370, Bethesda, MD 20892 USA. EM kleinman@yoda.nidr.nih.gov NR 36 TC 146 Z9 146 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 30 PY 1998 VL 273 IS 44 BP 28633 EP 28641 DI 10.1074/jbc.273.44.28633 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 133NC UT WOS:000076691800017 PM 9786856 ER PT J AU Wolf, I Pevzner, V Kaiser, E Bernhardt, G Claudio, E Siebenlist, U Forster, R Lipp, M AF Wolf, I Pevzner, V Kaiser, E Bernhardt, G Claudio, E Siebenlist, U Forster, R Lipp, M TI Downstream activation of a TATA-less promoter by Oct-2, Bob1, and NF-kappa B directs expression of the homing receptor BLR1 to mature B cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-COUPLED RECEPTOR; TRANSCRIPTION FACTORS; FUNCTIONAL-CHARACTERIZATION; MURINE HOMOLOG; POU DOMAIN; COACTIVATOR; DIFFERENTIATION; CLONING; GENE; LYMPHOMA AB The chemokine receptor, BLR1, is a major regulator of the microenvironmental homing of B cells in lymphoid organs. In vitro studies identify three essential elements of the TATA-less blr1 core promoter that confer cell type- and differentiation-specific expression in the B cells of both humans and mice, a functional promoter region (-36 with respect to the transcription start site), a NF-kappa B motif (+44), and a noncanonical octamer motif (+157), The importance of these sites was confirmed by in vivo studies in gene-targeted mice deficient of either Oct-2, Bob1, or both NF-kappa B subunits p50 and p52, In all of these animals, the expression of BLR1 was reduced or absent. In mice deficient only of p52/NF-KB, BLR1 expression was unaffected. Thus our data demonstrate that BLR1 is a target gene for Oct-2, Bob1, and members of the NF-kappa B/Rel family and provides a link to the impaired B cell functions in mice deficient for these factors. C1 Max Delbruck Ctr Mol Med, Dept Tumorgenet & Immunogenet, D-13122 Berlin, Germany. Univ Munich, Inst Biochem, D-81377 Munich, Germany. NICHD, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. RP Lipp, M (reprint author), Max Delbruck Ctr Mol Med, Dept Tumorgenet & Immunogenet, Robert Rossle Str 10, D-13122 Berlin, Germany. RI Lipp, Martin/G-2235-2010; Forster, Reinhold/D-6770-2011; Bernhardt, Gunter/F-6946-2012 NR 35 TC 51 Z9 52 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 30 PY 1998 VL 273 IS 44 BP 28831 EP 28836 DI 10.1074/jbc.273.44.28831 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 133NC UT WOS:000076691800044 PM 9786883 ER PT J AU Edskes, HK Ohtake, Y Wickner, RB AF Edskes, HK Ohtake, Y Wickner, RB TI Mak21p of Saccharomyces cerevisiae, a homolog of human CAATT-binding protein, is essential for 60 S ribosomal subunit biogenesis SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DOUBLE-STRANDED-RNA; POL FUSION PROTEIN; MESSENGER-RNA; SUPERKILLER MUTATIONS; ANTIVIRAL SYSTEM; KILLER VIRUS; YEAST; EXPRESSION; TRANSLATION; POLY(A) AB Mak21-1 mutants are unable to propagate M-1 double-stranded RNA, a satellite of the L-A double-stranded RNA virus, encoding a secreted protein toxin lethal to yeast strains that do not carry M-1. We cloned MAK21 using its map location and found that Mak21p is homologous to a human and mouse CAATT-binding protein and open reading frames in Schizosaccharomyces pombe and Caenorhabditis elegans, Although the human protein regulates Hsp70 production, Mak21p is essential for growth and necessary for 60 S ribosomal subunit biogenesis. mak21-1 mutants have decreased levels of L-A coat protein and L-A double-stranded RNA. Electroporation with reporter mRNAs shows that mak21-1 cells cannot optimally express mRNAs which, like L-A viral mRNA, lack 3'-poly(A) or 5'-cap structures but can normally express mRNA with both cap and poly(A), The virus propagation phenotype of mak21-1 is suppressed by ski2 or ski6 mutations, each of which derepresses translation of non-poly(A) mRNA. C1 NIDDK, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. RP Wickner, RB (reprint author), NIDDK, Lab Biochem & Genet, NIH, Bldg 8,Rm 225,8 Ctr Dr,MSC0830, Bethesda, MD 20892 USA. NR 51 TC 25 Z9 27 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 30 PY 1998 VL 273 IS 44 BP 28912 EP 28920 DI 10.1074/jbc.273.44.28912 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 133NC UT WOS:000076691800055 PM 9786894 ER PT J AU Borowsky, B Hoffman, BJ AF Borowsky, B Hoffman, BJ TI Analysis of a gene encoding two glycine transporter variants reveals alternative promoter usage and a novel gene structure SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BETA-TROPOMYOSIN GENE; NEUROTRANSMITTER TRANSPORTERS; NMDA ANTAGONISTS; MOUSE-BRAIN; RAT-BRAIN; EXPRESSION; CLONING; LOCALIZATION; RECEPTOR; CNS AB The rat GLYT-1 gene encodes two glycine transporter variants, GLYT-1a and GLYT-1b, that differ in NH2 termini and 5'-noncoding regions as well as in tissue distribution. The GLYT-1 gene contains 15 exons, with the first two specific for GLYT-1a and the third specific for GLYT-1b. By combining RNase protection and rapid amplification of cDNA ends analysis, we have determined transcription start sites for GLYT-1a and GLYT-1b. By using a functional luciferase reporter assay, we demonstrate that distinct promoters regulate the expression of these transporters in several cell lines. Serially truncated GLYT-1b promoter constructs reveal a basal promoter within 304 base pairs of the transcription start site, possible negative regulatory elements between -304 and -1310, and additional positive regulatory elements between -1310 and -5264. The GLYT-1 gene contains three sets of dinucleotide repeats, two AC repeats, and one TG repeat which may form stem-loop structures to either facilitate or interfere with transcription of one of the transporter isoforms. The potential use of dinucleotide repeats in this manner would represent a novel mechanism for gene splicing. The use of distinct promoters for GLYT-1a and GLYT-1b suggests that these transporters have unique regulatory requirements that may reflect the differential tissue-specific expression patterns in white matter (GLYT-1b) and gray matter (GLYT-1a). C1 NIMH, Unit Mol Pharmacol, Lab Cellular & Mol Regulat, Bethesda, MD 20892 USA. RP Hoffman, BJ (reprint author), Eli Lilly & Co, Lilly Corp Ctr, Lilly Res Labs, Crop Code 8510, Indianapolis, IN 46285 USA. EM Hoffman_Beth@Lilly.com NR 33 TC 50 Z9 52 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 30 PY 1998 VL 273 IS 44 BP 29077 EP 29085 DI 10.1074/jbc.273.44.29077 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 133NC UT WOS:000076691800075 PM 9786914 ER PT J AU McKee, TC Galinis, DL Pannell, LK Cardellina, JH Laakso, J Ireland, CM Murray, L Capon, RJ Boyd, MR AF McKee, TC Galinis, DL Pannell, LK Cardellina, JH Laakso, J Ireland, CM Murray, L Capon, RJ Boyd, MR TI The lobatamides, novel cytotoxic macrolides from southwestern Pacific tunicates SO JOURNAL OF ORGANIC CHEMISTRY LA English DT Article ID BROMOTYROSINE-DERIVED METABOLITES; SPONGE PSAMMAPLYSILLA-PURPUREA; MARINE SPONGE; APLIDIUM SP; AUSTRALIAN TUNICATE; IANTHELLA-BASTA; ALKALOIDS; ELUCIDATION; ASCIDIANS; PUREA AB Novel macrolides, lobatamides A-F (1-6), have been isolated from shallow water Australian collections of Aplidium lobatum, from a deep water collection of Aplidium sp., and from an unidentified Philippine ascidian. Full details of the isolation and structure elucidation of 1-6 are provided herein, along with results and analyses of the testing of lobatamides A-D (1-4) in the NCI human tumor 60 cell-line screen. The lobatamides share a common core structure with the recently described salicylihalamides, which were isolated from a Haliclona sp. sponge. COMPARE analyses of the mean-graph differential cytotoxicity profiles of the lobatamides and the salicylihalamides showed high correlations with each other but not with members of the NCI's standard agents database. These compounds, therefore, appear to comprise a new mechanistic class, meriting further antitumor investigations. C1 NCI, Lab Drug Discovery Res & Dev, Dev Therapeut Program, Div Canc Treatment & Diag,FCRDC, Frederick, MD 21702 USA. NIDDK, Bioorgan Chem Lab, Bethesda, MD 20892 USA. Univ Melbourne, Sch Chem, Parkville, Vic 3052, Australia. Univ Utah, Dept Med Chem, Salt Lake City, UT 84112 USA. RP Boyd, MR (reprint author), NCI, Lab Drug Discovery Res & Dev, Dev Therapeut Program, Div Canc Treatment & Diag,FCRDC, Bldg 1052,Rm 121, Frederick, MD 21702 USA. RI Capon, Rob/G-9238-2012 OI Capon, Rob/0000-0002-8341-7754 NR 36 TC 77 Z9 78 U1 0 U2 9 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-3263 J9 J ORG CHEM JI J. Org. Chem. PD OCT 30 PY 1998 VL 63 IS 22 BP 7805 EP 7810 DI 10.1021/jo980939r PG 6 WC Chemistry, Organic SC Chemistry GA 135CB UT WOS:000076781600039 ER PT J AU Chong, NW Cassone, VM Bernard, M Klein, DC Iuvone, PM AF Chong, NW Cassone, VM Bernard, M Klein, DC Iuvone, PM TI Circadian expression of tryptophan hydroxylase mRNA in the chicken retina SO MOLECULAR BRAIN RESEARCH LA English DT Article DE tryptophan hydroxylase; retina; pineal gland; melatonin; circadian clock; photoreceptor cells ID SEROTONIN N-ACETYLTRANSFERASE; HYDROXYINDOLE-O-METHYLTRANSFERASE; XENOPUS-LAEVIS RETINA; MESSENGER-RNA LEVELS; PINEAL-GLAND; MELATONIN SYNTHESIS; KAINIC ACID; CLOCK; CELLS; PHOTORECEPTORS AB Many aspects of retinal physiology are controlled by a circadian clock located within the eye. This clock controls the rhythmic synthesis of melatonin, which results in elevated levels during the night and low levels during the day. The rate-limiting enzyme in melatonin biosynthesis in retina appears to be tryptophan hydroxylase (TPH)[G.M. Cahill and J.C. Besharse, Circadian regulation of melatonin in the retina of Xenopus laevis: Limitation by serotonin availability, J. Neurochem. 54 (1990) 716-719]. In this report, we found that TPH mRNA is strongly expressed in the photoreceptor layer and the vitread portion of the inner nuclear layer; the message is also expressed, but to a lesser extent, in the ganglion cell layer. The abundance of retinal TPH mRNA exhibits a circadian rhythm which persists in constant light or constant darkness. The phase of the rhythm can be reversed by reversing the light:dark cycle. In parallel experiments we found a similar pattern of expression in the chicken pineal gland. However, whereas a pulse of light at midnight suppressed retinal TPH mRNA by 25%, it did not alter pineal TPH mRNA, suggesting that there are tissue-specific differences in photic regulation of TPH mRNA. In retinas treated with kainic acid to destroy serotonin-containing amacrine and bipolar cells, a high amplitude rhythm of TPH mRNA was observed indicating that melatonin-synthesizing photoreceptors are the primary source of the rhythmic message. These observations provide the first evidence that chick retinal TPH mRNA is under control of a circadian clock. (C) 1998 Elsevier Science B.V. All rights reserved. C1 Emory Univ, Sch Med, Dept Pharmacol, Atlanta, GA 30332 USA. NICHHD, Dev Neurobiol Lab, Sect Neuroendocrinol, NIH, Bethesda, MD 20892 USA. Texas A&M Univ, Dept Biol, College Stn, TX 77843 USA. Neuroendocrinol Lab, URA CNRS 1869, Poitiers, France. RP Iuvone, PM (reprint author), Emory Univ, Sch Med, Dept Pharmacol, Atlanta, GA 30332 USA. NR 30 TC 37 Z9 37 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD OCT 30 PY 1998 VL 61 IS 1-2 BP 243 EP 250 DI 10.1016/S0169-328X(98)00219-8 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 133GY UT WOS:000076679900029 ER PT J AU Khasar, SG Gold, MS Levine, JD AF Khasar, SG Gold, MS Levine, JD TI A tetrodotoxin-resistant sodium current mediates inflammatory pain in the rat SO NEUROSCIENCE LETTERS LA English DT Article DE tetrodotoxin-resistant sodium current; pain; hyperalgesia; primary afferent nociceptor; sensitization ID DORSAL-ROOT GANGLION; ASPIRIN-LIKE DRUGS; SENSORY NEURONS; EXPRESSION; NERVE AB We report evidence for a contribution of tetrodotoxin-resistant sodium current (TTX-R I-Na) to prostaglandin E-2 (PGE(2))-induced hyperalgesia. Behavioral experiments were performed in rats chronically implanted with spinal cannulae. The study employed intrathecal administration of oligodeoxynucleotide (ODN) antisense to the recently cloned channel underlying TTX-R I-Na (PN3/SNS). The nociceptive flexion reflex was employed to determine changes in mechanical stimulus-induced paw-withdrawal threshold. Administration of antisense but not of sense or mismatch ODN, led to a decrease in PGE(2)-induced hyperalgesia. PGE(2)-induced hyperalgesia returned to normal 7 days after the last injection of antisense ODN. Antisense ODN selectively and significantly reduced TTX-R I-Na current density in cultured sensory neurons. Our observations support the hypothesis that modulation of TTX-R I-Na, present in peripheral terminals of primary afferent nociceptors, contributes, at least in part, to inflammatory hyperalgesia. Since TTX-R I-Na is found only in primary afferent nociceptors, our findings suggest TTX-R I-Na as a promising target for novel therapeutic interventions for the treatment of inflammatory pain. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved. C1 Univ Calif San Francisco, NIH Pain Ctr, Grad Program Neurosci, Dept Anat Med & Oral & Maxillofacial Surg, San Francisco, CA 94143 USA. Univ Maryland, Baltimore Dent Sch, Dept Oral & Craniofacial Biol Sci, Baltimore, MD 21201 USA. RP Levine, JD (reprint author), Univ Calif San Francisco, NIH Pain Ctr, Grad Program Neurosci, Dept Anat Med & Oral & Maxillofacial Surg, C-522,Box 0440, San Francisco, CA 94143 USA. FU NINDS NIH HHS [NS21647] NR 19 TC 179 Z9 185 U1 2 U2 5 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD OCT 30 PY 1998 VL 256 IS 1 BP 17 EP 20 DI 10.1016/S0304-3940(98)00738-1 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 138UY UT WOS:000076992700005 PM 9832206 ER PT J AU Chen, TT Ng, TH AF Chen, TT Ng, TH TI Optimal flexible designs in phase II clinical trials SO STATISTICS IN MEDICINE LA English DT Article ID MULTIPLE TESTING PROCEDURE; TOXICITY AB In the conduct of a phase II cancer clinical trial, patients usually enter in two stages. If the response rate from the first stage is low, then the study terminates. Within various two-stage designs, Simon proposed the optimal and minimax criteria. In the co-operative group setting, practical considerations make it difficult to arrive at the planned sample size exactly. Green and Dahlberg proposed and compared several flexible designs. In this paper, we explicitly define a flexible design as a collection of two-stage designs where the first stage size is in a set of consecutive values (n(1), ..., n(k)) and the second stage size is also in another set of consecutive values (N-1, ..., N-k), and each of k(2) possible designs has the same probability of occurrence. We apply Simon's optimal and minimax criteria to flexible designs for phase II trials in order to minimize the number of patients tested on an ineffective drug. (C) 1998 John Wiley & Sons, Ltd. This paper was produced under the auspices of the US Government and is therefore not subject to copyright in the US. C1 NCI, Biometr Res Branch, Bethesda, MD 20892 USA. US FDA, Div Biostat & Epidemiol, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Chen, TT (reprint author), NCI, Biometr Res Branch, EPN-739, Bethesda, MD 20892 USA. EM tchen@helix.nih.gov NR 14 TC 91 Z9 92 U1 0 U2 3 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD OCT 30 PY 1998 VL 17 IS 20 BP 2301 EP 2312 DI 10.1002/(SICI)1097-0258(19981030)17:20<2301::AID-SIM927>3.0.CO;2-X PG 12 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 130YK UT WOS:000076548100002 PM 9819829 ER PT J AU Havlir, DV Marschner, IC Hirsch, MS Collier, AC Tebas, P Bassett, RL Ioannidis, JPA Holohan, MK Leavitt, R Boone, G Richman, DD AF Havlir, DV Marschner, IC Hirsch, MS Collier, AC Tebas, P Bassett, RL Ioannidis, JPA Holohan, MK Leavitt, R Boone, G Richman, DD CA AIDS Clin Trials Grp Study 343 Team TI Maintenance antiretroviral therapies in HIV-infected subjects with undetectable plasma HIV RNA after triple-drug therapy SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID IMMUNODEFICIENCY-VIRUS INFECTION; CUBIC MILLIMETER; ZIDOVUDINE; LAMIVUDINE; SUPPRESSION; REPLICATION; RESERVOIR; INDINAVIR; DYNAMICS AB Background Combination antiretroviral therapy with indinavir, zidovudine, and lamivudine can suppress the level of human immunodeficiency virus (HIV) RNA in plasma below the threshold of detection for two years or more. We investigated whether a less intensive maintenance regimen could sustain viral suppression after an initial response to combination therapy. Methods HIV-infected subjects who had CD4 cell counts greater than 200 per cubic millimeter, who had been treated with indinavir, lamivudine, and zidovudine, and who had less than 200 copies of HIV RNA per milliliter of plasma after 16, 20, and 24 weeks of induction therapy were randomly assigned to receive either continued triple-drug therapy (106 subjects), indinavir alone (103 subjects), or a combination of zidovudine and lamivudine (107 subjects). The primary end point was loss of viral suppression, which was defined as a plasma level of at least 200 copies of HIV RNA per milliliter on two consecutive measurements during maintenance therapy. Results During maintenance treatment, 23 percent of the subjects receiving indinavir and 23 percent of those receiving zidovudine and lamivudine, but only 4 percent of those receiving all three drugs, had loss of viral suppression (P<0.001 for the comparison between triple-drug therapy and the other two maintenance regimens). Subjects with greater increases in CD4 cell counts during induction therapy, higher viral loads at base line (i.e., at the beginning of induction therapy), and slower rates of viral clearance were at greater risk for loss of viral suppression. The presence of zidovudine-resistance mutations in HIV RNA at base line was strongly predictive of the loss of viral suppression in subjects treated with zidovudine and lamivudine. Conclusions The suppression of plasma HIV RNA after six months of treatment with indinavir, zidovudine, and lamivudine is better sustained by the continuation of these three drugs than by maintenance therapy with either indinavir alone or zidovudine and lamivudine. (N Engl J Med 1998;339:1261-8.) (C)1998, Massachusetts Medical Society. C1 Univ Calif San Diego, San Diego, CA 92103 USA. San Diego Vet Affairs Med Ctr, San Diego, CA USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Washington, Sch Med, Seattle, WA USA. Washington Univ, St Louis, MO USA. NIAID, Div Aids, Bethesda, MD 20892 USA. Aids Clin Trials Grp, Operat Ctr, Rockville, MD USA. Merck & Co Inc, W Point, PA USA. Glaxo Wellcome Inc, Res Triangle Pk, NC 27709 USA. RP Havlir, DV (reprint author), Univ Calif San Diego, 2760 5th Ave,Suite 300, San Diego, CA 92103 USA. RI Tebas, Pablo/A-7061-2008; Ioannidis, John/G-9836-2011 FU NIAID NIH HHS [AI36214, AI27670, AI38858] NR 33 TC 245 Z9 246 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD OCT 29 PY 1998 VL 339 IS 18 BP 1261 EP 1268 DI 10.1056/NEJM199810293391801 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 132XC UT WOS:000076655300001 PM 9791141 ER PT J AU Mills, JL AF Mills, JL TI Answer to the latest medical mystery SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 NIH, Bethesda, MD 20892 USA. RP Mills, JL (reprint author), NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD OCT 29 PY 1998 VL 339 IS 18 BP 1333 EP 1333 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 132XC UT WOS:000076655300033 ER PT J AU Amundson, SA Zhan, Q Penn, LZ Fornace, AJ AF Amundson, SA Zhan, Q Penn, LZ Fornace, AJ TI Myc suppresses induction of the growth arrest genes gadd34, gadd45, and gadd153 by DNA-damaging agents SO ONCOGENE LA English DT Article DE gadd45; myc; transcriptional repression ID C-MYC; REPRESSES TRANSCRIPTION; INDUCED APOPTOSIS; RAT FIBROBLASTS; CELL-GROWTH; P53; ACTIVATION; PROMOTER; RADIATION; PATHWAY AB The growth arrest and DNA damage inducible (gadd) genes are induced by various genotoxic and nongenotoxic stresses such as serum starvation, ultraviolet irradiation and treatment with alkylating agents. Their coordinate induction is a growth arrest signal which may play an important role in the response of cells to DNA damage. Conversely, c-myc is a strong proliferative signal, and overexpression of Myc is frequently observed in cancer cells, We have found that ectopic expression of v-myc in RAT-I cells results in an attenuated induction of the three major gadd transcripts by methyl methanesulfonate (MMS), and almost completely blocks the response to ultraviolet (UV) radiation. Myc acts in part by reducing the stress-responsiveness of the gadd45 promoter, as a c-myc expression vector strongly suppressed activation of gadd-reporter constructs. This activity of Myc localizes to a recently described CC-rich binding site within the gadd45 promoter. These results indicate that a coordinate down-regulation of the gadd gene response is one mechanism by which Myc can circumvent growth arrest and contribute to the neoplastic phenotype. C1 NCI, NIH, Bethesda, MD 20892 USA. Univ Toronto, Ontario Canc Inst, Dept Med Biophys, Toronto, ON M5G 2M9, Canada. RP Fornace, AJ (reprint author), NCI, NIH, 37 Convent Dr,Bldg,37 Room 5C09, Bethesda, MD 20892 USA. RI Fornace, Albert/A-7407-2008 OI Fornace, Albert/0000-0001-9695-085X NR 28 TC 72 Z9 75 U1 1 U2 5 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD OCT 29 PY 1998 VL 17 IS 17 BP 2149 EP 2154 DI 10.1038/sj.onc.1202136 PG 6 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 133QX UT WOS:000076698200001 PM 9811446 ER PT J AU Miller, FG Rosenstein, DL DeRenzo, EG AF Miller, FG Rosenstein, DL DeRenzo, EG TI Professional integrity in clinical research SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID TRIALS AB In response to public concern over abuses in human medical experimentation, the dominant approach to the ethics of clinical research during the past 30 years has been regulation, particularly via institutional review board review and approval of scientific protocols and written consent forms. However, the effectiveness of regulatory mechanisms in ensuring the ethical conduct of clinical research is limited. Little attention has been devoted to the nature and role of professional integrity of physician investigators, a conscientious framework for guiding investigators in the socially important but morally complex activity of clinical research. Professional integrity is vital in forging an ethically sound relationship between investigators and patient volunteers, a relationship that differs in important ways from the patient-physician relationship in standard clinical practice. We examine critically 2 models of the moral identity of physician investigators, the investigator as clinician and the investigator as scientist; in neither of these 2 models can the physician investigator eliminate completely the moral conflicts posed by clinical research. The professional integrity of physician investigators depends on a coherent moral identity that is proper to the enterprise of clinical research. The roles of clinician and scientist must be integrated to manage conscientiously the ethical complexity, ambiguity, and tensions between the potentially competing loyalties of science and care of volunteer patients. C1 Univ Virginia, Sch Med, Dept Med Educ, Charlottesville, VA 22908 USA. Consultat Liaison Serv, Dept Psychiat, Bethesda, MD USA. NIH, Dept Clin Bioeth, Bethesda, MD 20892 USA. RP Miller, FG (reprint author), 3910 Underwood St, Chevy Chase, MD 20815 USA. EM FGM3910@aol.com NR 28 TC 111 Z9 112 U1 2 U2 10 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD OCT 28 PY 1998 VL 280 IS 16 BP 1449 EP 1454 DI 10.1001/jama.280.16.1449 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 130YA UT WOS:000076546900044 PM 9801009 ER PT J AU Fushman, D Tjandra, N Cowburn, D AF Fushman, D Tjandra, N Cowburn, D TI Direct measurement of N-15 chemical shift anisotropy in solution SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID PROTEIN BACKBONE DYNAMICS; POWDER PATTERNS; NMR RELAXATION; PEPTIDE-BOND; SOLID-STATE; TENSORS; DIPOLAR; NUCLEI AB The magnitude and orientation of the N-15 chemical shift anisotropy (CSA) tensors are determined for human ubiquitin in solution from N-15 relaxation data at 600, 500, and 360 MHz. The analysis uses the model-independent approach [Fushman, D.; Cowburn, D. J. Am. Chem. Soc. 1998, 120, 7109-10] based on a ratio, eta/R-2, of the cross correlation (eta) between N-15 CSA and N-15-H-1 dipolar interaction and of the rate (R-2) of N-15 transverse relaxation. Since the eta/R-2 ratio does not contain any direct dependence on protein dynamics, the present approach is free from assumptions about overall and local motions. The N-15 CSA values fall in the range -125 to -216 ppm, with the average value of -157 +/- 19 ppm; the average angle between the NH bond and the unique principal axis of the N-15 CSA tensor was 15.7 +/- 5.0 degrees (range 6-26 degrees). The results indicate the importance of residue-specific N-15 CSA for accurate analysis of dynamics from relaxation data, and provide access to the CSA in solution, which may be structurally useful. C1 Rockefeller Univ, New York, NY 10021 USA. NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. RP Cowburn, D (reprint author), Rockefeller Univ, 1230 York Ave, New York, NY 10021 USA. RI Cowburn, David/A-8448-2008; OI Cowburn, David/0000-0001-6770-7172 NR 30 TC 151 Z9 153 U1 0 U2 8 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD OCT 28 PY 1998 VL 120 IS 42 BP 10947 EP 10952 DI 10.1021/ja981686m PG 6 WC Chemistry, Multidisciplinary SC Chemistry GA 133NR UT WOS:000076693100019 ER PT J AU Patel, SB Salen, G Hidaka, H Kwietrovich, PO Stalenhoef, AFH Miettinen, T Grundy, SM Lee, MH Rubenstein, JS Polymeropoulos, MH Brownstein, MJ AF Patel, SB Salen, G Hidaka, H Kwietrovich, PO Stalenhoef, AFH Miettinen, T Grundy, SM Lee, MH Rubenstein, JS Polymeropoulos, MH Brownstein, MJ TI Mapping a gene involved in regulating dietary cholesterol absorption; the sitosterolemia locus is found at chromosome 2p21 SO CIRCULATION LA English DT Meeting Abstract C1 Univ Texas, SW Med Ctr, Dallas, TX USA. Shiga Univ Med Sci, Shiga, Japan. Johns Hopkins Univ, Baltimore, MD USA. Univ Nijmegen Hosp, NL-6500 HB Nijmegen, Netherlands. Univ Helsinki Hosp, Helsinki, Finland. Univ Texas, SW Med Ctr, Dallas, TX USA. NIH, Bethesda, MD 20892 USA. RI Stalenhoef, A.F.H./H-8094-2014 NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 23 BP 5 EP 5 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594400073 ER PT J AU Vaitkeviclus, PV Lane, M Ebersold, C Ingram, D Roth, G Cerami, A Egan, J Vasan, S Ulrich, P Lakatta, EG AF Vaitkeviclus, PV Lane, M Ebersold, C Ingram, D Roth, G Cerami, A Egan, J Vasan, S Ulrich, P Lakatta, EG TI A novel collagen crosslink breaker effects a sustained reduction in arterial stiffness in old primates SO CIRCULATION LA English DT Meeting Abstract C1 NIA, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. Kenneth S Warren Labs, Tarrytown, NY USA. Alteon, Ramsey, NJ USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 40 BP 8 EP 9 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594400090 ER PT J AU Prasad, A Narayanan, S Padder, FA Waclawiw, M Epstein, N Quyyumi, AA AF Prasad, A Narayanan, S Padder, FA Waclawiw, M Epstein, N Quyyumi, AA TI The deletion allele of the angiotensin converting enzyme gene determines reversibility of endothelial dysfunction with converting enzyme inhibition SO CIRCULATION LA English DT Meeting Abstract C1 Natl Inst Hlth, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 133 BP 27 EP 27 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594400182 ER PT J AU van Vlijmen, BJ van Dijk, KW van't Hof, BH van der Zee, A Santamarina-Fojo, S van Berkel, TJ Havekes, LM Hofker, MH AF van Vlijmen, BJ van Dijk, KW van't Hof, BH van der Zee, A Santamarina-Fojo, S van Berkel, TJ Havekes, LM Hofker, MH TI In the absence of the LDL receptor, only a narrow range of hepatic APOE expression reduces hyperlipidemia in ApoE deficient mice SO CIRCULATION LA English DT Meeting Abstract C1 TNO, Gaubius Lab, Leiden, Netherlands. Leiden Univ, Med Ctr, Leiden, Netherlands. NHLBI, NIH, Bethesda, MD 20892 USA. Leiden Amsterdam Ctr Drug Res, Leiden, Netherlands. RI Willems van Dijk, Ko/A-1798-2008 OI Willems van Dijk, Ko/0000-0002-2172-7394 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 164 BP 34 EP 35 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594400213 ER PT J AU Amar, MJA Shamburek, RD Foger, B Hoyt, RF Wood, DO Santamarina-Fojo, S Brewer, HB AF Amar, MJA Shamburek, RD Foger, B Hoyt, RF Wood, DO Santamarina-Fojo, S Brewer, HB TI Adenovirus-mediated expression of LCAT in non-human primates leads to an antiatherogenic lipoprotein profile with increased HDL and decreased LDL SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI, NIH, Bethesda, MD 20892 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 8 Z9 8 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 166 BP 35 EP 35 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594400215 ER PT J AU Zhu, JH Quyyumi, AA Norman, JE Csako, GA Epstein, SE AF Zhu, JH Quyyumi, AA Norman, JE Csako, GA Epstein, SE TI Cytomegalovirus infection in women is associated with elevated levels of C-reactive protein and coronary artery disease, but susceptibility is modulated by the type of immune response mounted by the host SO CIRCULATION LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. Washington Hosp Ctr, Washington, DC 20010 USA. NR 0 TC 3 Z9 3 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 207 BP 42 EP 42 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594400255 ER PT J AU Zhu, JH Quyyumi, AA Norman, JE Csako, GA Shearer, GM Grayston, JT Epstein, SE AF Zhu, JH Quyyumi, AA Norman, JE Csako, GA Shearer, GM Grayston, JT Epstein, SE TI Total pathogen burden contributes incrementally to coronary artery disease risk and to C-reactive protein levels SO CIRCULATION LA English DT Meeting Abstract C1 Univ Washington, Seattle, WA 98195 USA. NIH, Bethesda, MD 20892 USA. Washington Hosp Ctr, Washington, DC 20010 USA. NR 0 TC 3 Z9 3 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 204 BP 42 EP 42 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594400252 ER PT J AU Lloyd-Jones, DM O'Donnell, CJ Silbershatz, H D'Agostino, RB Wilson, PWF AF Lloyd-Jones, DM O'Donnell, CJ Silbershatz, H D'Agostino, RB Wilson, PWF TI Applicability of cholesterol-lowering primary prevention studies to a general population SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI, Framingham Heart Study, Framingham, MA USA. Boston Univ, Boston, MA 02215 USA. RI Lloyd-Jones, Donald/C-5899-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 227 BP 46 EP 46 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594400275 ER PT J AU Chen, W Murphy, E Steenbergen, C AF Chen, W Murphy, E Steenbergen, C TI Inhibition of p38 MAPK, but not p42/44 MAPK, blocks enhanced glucose uptake and improved recovery of function in preconditioned hearts SO CIRCULATION LA English DT Meeting Abstract C1 Duke Univ, Med Ctr, Durham, NC USA. NIEHS, NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 362 BP 72 EP 72 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594400408 ER PT J AU Detre, KM Kip, KE Williams, DO Sopko, G Frye, RL Alderman, EL AF Detre, KM Kip, KE Williams, DO Sopko, G Frye, RL Alderman, EL TI Coronary angiography in diabetic patients: The bypass angioplasty revascularization investigation (BARI) SO CIRCULATION LA English DT Meeting Abstract C1 Univ Pittsburgh, Pittsburgh, PA USA. Brown Univ, Rhode Isl Hosp, Providence, RI 02903 USA. NHLBI, NIH, Bethesda, MD USA. Mayo Clin, Rochester, MN USA. Stanford Univ, Stanford, CA 94305 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 448 BP 89 EP 89 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594400493 ER PT J AU Chikada, M Shiota, T Sahn, DJ Jones, M AF Chikada, M Shiota, T Sahn, DJ Jones, M TI Gorlin formulas of aortic regurgitant and mitral regurgitant orifice area for evaluating the severity of regurgitation - An animal study SO CIRCULATION LA English DT Meeting Abstract C1 Natl Childrens Hosp, Tokyo 154, Japan. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Oregon Hlth Sci Univ, Portland, OR 97201 USA. NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 460 BP 91 EP 91 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594400505 ER PT J AU Lloyd-Jones, DM Larson, MG Beiser, A Levy, D AF Lloyd-Jones, DM Larson, MG Beiser, A Levy, D TI Lifetime risk of developing coronary heart disease by sex and age in the Framingham Heart Study SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI, Framingham Heart Study, Framingham, MA USA. Boston Univ, Boston, MA 02215 USA. RI Lloyd-Jones, Donald/C-5899-2009 NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 488 BP 96 EP 97 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594400533 ER PT J AU Sheps, DS Kaufmann, PG McMahon, RP Sheffield, D Bonsall, R Light, KC Cohen, JD Goldberg, D Ketterer, MW Raczynski, J Pepine, CJ AF Sheps, DS Kaufmann, PG McMahon, RP Sheffield, D Bonsall, R Light, KC Cohen, JD Goldberg, D Ketterer, MW Raczynski, J Pepine, CJ TI Gender differences in chest pain in patients with documented CAD and exercise-induced ischemia: Results from the psychophysiological investigation of myocardial ischemia (PIMI) study SO CIRCULATION LA English DT Meeting Abstract C1 E Tennessee State Univ, Johnson City, TN 37614 USA. NHLBI, Bethesda, MD 20892 USA. Maryland Med Res Inst, Baltimore, MD USA. Emory Univ, Sch Med, Atlanta, GA USA. Univ N Carolina, Chapel Hill, NC USA. St Louis Univ, Hlth Sci Ctr, St Louis, MO 63103 USA. Henry Ford Hosp, Detroit, MI 48202 USA. Univ Alabama, Birmingham, AL USA. Univ Florida, Gainesville, FL USA. RI McMahon, Robert/C-5462-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 493 BP 97 EP 97 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594400538 ER PT J AU Merz, CNB Bittner, V Kenkre, T Matthews, KA Kelsey, SF Lin, L Reichek, N Reis, SE Rogers, WJ Sharaf, BL Sopko, G AF Merz, CNB Bittner, V Kenkre, T Matthews, KA Kelsey, SF Lin, L Reichek, N Reis, SE Rogers, WJ Sharaf, BL Sopko, G TI New variable improves diagnostic accuracy of chest pain assessment in women: The NHLBI-sponsored WISE study SO CIRCULATION LA English DT Meeting Abstract C1 Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. Univ Alabama, Birmingham, AL USA. Univ Pittsburgh, Pittsburgh, PA USA. Univ Florida, Gainesville, FL USA. Allegheny Univ Hlth Sci, Pittsburgh, PA USA. Brown Univ, Providence, RI 02912 USA. NHLBI, NIH, Bethesda, MD 20892 USA. RI Reis, Steven/J-3957-2014 NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 494 BP 98 EP 98 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594400539 ER PT J AU Blum, A Kirby, M Schenke, WH Koh, KK Cannon, RO AF Blum, A Kirby, M Schenke, WH Koh, KK Cannon, RO TI Estrogen inhibits cell adhesion molecule expression in postmenopausal women SO CIRCULATION LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 538 BP 106 EP 106 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594400583 ER PT J AU Daniel, M Wang, J Brousseau, ME Demosky, SJ Hoeg, JM AF Daniel, M Wang, J Brousseau, ME Demosky, SJ Hoeg, JM TI Identification, characterization and expression of rabbit apolipoprotein J: Relation to LDL receptor expression, steroidegenesis, and atherosclerosis SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI, Mol Dis Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 556 BP 109 EP 109 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594400600 ER PT J AU Vodovotz, Y Chan, RC Cook, JA Mitchell, JB Wink, D Kim, WH Collins, S Seabron, R Waksman, R AF Vodovotz, Y Chan, RC Cook, JA Mitchell, JB Wink, D Kim, WH Collins, S Seabron, R Waksman, R TI S-nitrosoglutathione reduces thrombosis and enhances healing following balloon injury and endovascular radiation of porcine coronary arteries SO CIRCULATION LA English DT Meeting Abstract C1 Washington Hosp Ctr, Washington, DC 20010 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 579 BP 113 EP 113 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594400622 ER PT J AU Leiser, KJ Arai, AE Taylor, JL Vossoughi, J Hoeg, JM AF Leiser, KJ Arai, AE Taylor, JL Vossoughi, J Hoeg, JM TI Pulse wave transit time reflects compositional and compliance changes in early atherosclerosis SO CIRCULATION LA English DT Meeting Abstract C1 NIH, MDB, NHLB, Bethesda, MD 20892 USA. Univ Dist Columbia, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 707 BP 137 EP 137 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594400749 ER PT J AU Schmidt, MA Laurienzo, JM Brenneman, CL Freidlin, RZ Ohazamas, CJ Jones, M Panza, JA AF Schmidt, MA Laurienzo, JM Brenneman, CL Freidlin, RZ Ohazamas, CJ Jones, M Panza, JA TI Accuracy of left ventricular mass measurements using real-time three-dimensional echocardiography SO CIRCULATION LA English DT Meeting Abstract C1 Natl Inst Hlth, Bethesda, MD USA. Duke Univ, Durham, NC USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 792 BP 153 EP 153 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594400834 ER PT J AU Gonzalez, AA Segura, AM Horiba, K Luna, RE Stetler-Stevenson, WG Willerson, JT McAllister, HA Ferrans, VJ AF Gonzalez, AA Segura, AM Horiba, K Luna, RE Stetler-Stevenson, WG Willerson, JT McAllister, HA Ferrans, VJ TI Matrix metalloproteinases and their inhibitors in granulomatous lesions of pulmonary and cardiac sarcoidosis. SO CIRCULATION LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. Texas Heart Inst, Houston, TX 77025 USA. Univ Med Sch, Houston, TX USA. RI Stetler-Stevenson, William/H-6956-2012 OI Stetler-Stevenson, William/0000-0002-5500-5808 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 920 BP 178 EP 179 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594400962 ER PT J AU Domanski, MJ Saksena, S Hallstrom, A Lancaster, S AF Domanski, MJ Saksena, S Hallstrom, A Lancaster, S TI Benefit with implantable cardioverter-defibrillators in patients with malignant ventricular arrhythmias and varying degrees of left ventricular dysfunction SO CIRCULATION LA English DT Meeting Abstract C1 Eastern Heart Inst, Passaic, NJ USA. NIH, Bethesda, MD 20892 USA. Univ Washington, Seattle, WA 98195 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 989 BP 191 EP 191 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594401028 ER PT J AU Chase, MB Santamaiina-Fojo, S Shamburek, RD Amar, MJ Knapper, CL Meyn, SK Brewer, HB AF Chase, MB Santamaiina-Fojo, S Shamburek, RD Amar, MJ Knapper, CL Meyn, SK Brewer, HB TI CLA-1/SR-B1: In vivo evidence for selective uptake of cholesterol esters from ApoB remnant lipoproteins in ApoE deficient mice SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 1050 BP 202 EP 203 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594401087 ER PT J AU Lambert, GC Remaley, AT Chase, MB Peterson, KM Bensadoun, A Brewer, B Santamarina-Fojo, S AF Lambert, GC Remaley, AT Chase, MB Peterson, KM Bensadoun, A Brewer, B Santamarina-Fojo, S TI Role of hepatic lipase in the Cia-1 mediated selective uptake of HDL cholesterol esters SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI, NIH, Bethesda, MD 20892 USA. Cornell Univ, Ithaca, NY 14853 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 1048 BP 202 EP 202 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594401085 ER PT J AU Folsom, AR Rosamond, WD Shahar, E Cooper, LS Aleksic, N Nieto, FJ Rasmussen, ML Wu, KK AF Folsom, AR Rosamond, WD Shahar, E Cooper, LS Aleksic, N Nieto, FJ Rasmussen, ML Wu, KK TI Prospective study of markers of hemostatic function, inflammation, and endothelial function with risk of ischemic stroke SO CIRCULATION LA English DT Meeting Abstract C1 Univ Minnesota, Minneapolis, MN 55455 USA. Univ N Carolina, Chapel Hill, NC 27515 USA. NHLBI, Bethesda, MD 20892 USA. Univ Texas, Sch Med, Houston, TX USA. Johns Hopkins Univ, Baltimore, MD USA. RI Wu, Kenneth Kun-Yu/B-1070-2010 NR 0 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 1072 BP 207 EP 207 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594401109 ER PT J AU Haider, AW Roubenoff, R Silbershatz, H D'Agostino, R Levy, D O'Donnell, CJ AF Haider, AW Roubenoff, R Silbershatz, H D'Agostino, R Levy, D O'Donnell, CJ TI Inflammation, cytokine production and atherosclerotic cardiovascular disease in the elderly: The Framingham heart study SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI, Frmaingham Heart Study, Framingham, MA USA. Tufts Univ, USDA, Human Nutr Res Ctr Aging, Boston, MA 02111 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 1076 BP 207 EP 208 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594401113 ER PT J AU Wilson, PWF D'Agostino, RB Levy, D Silbershatz, H Kannel, WB Tofler, GH AF Wilson, PWF D'Agostino, RB Levy, D Silbershatz, H Kannel, WB Tofler, GH TI Fibrinogen and lipoprotein cholesterol levels in the prediction of coronary heart disease SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI, Framingham Heart Study, Framingham, MA USA. Boston Univ, Boston, MA 02215 USA. Harvard Univ, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 1071 BP 207 EP 207 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594401108 ER PT J AU Territo, PR French, SA Mootha, VK Balaban, RS AF Territo, PR French, SA Mootha, VK Balaban, RS TI Calcium activation of oxidative phosphorilation: Evidence for dehydrogenase independent mechanisms SO CIRCULATION LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 1101 BP 212 EP 213 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594401138 ER PT J AU Speir, E Yu, ZX Ferrans, VJ Cannon, RO AF Speir, E Yu, ZX Ferrans, VJ Cannon, RO TI Estrogen inhibits transcription factor and cell adhesion molecule activation in cytokine-stimulated human coronary smooth muscle cells via antioxidant effects SO CIRCULATION LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 1143 BP 220 EP 220 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594401180 ER PT J AU Domanski, MJ Mitchell, GF Norman, J Exner, D Pitt, B Pfeffer, MA AF Domanski, MJ Mitchell, GF Norman, J Exner, D Pitt, B Pfeffer, MA TI Independent prognostic information provided by sphygmomanometrically determined pulse pressure and mean arterial pressure in patients with left ventricular dysfunction SO CIRCULATION LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Off Biostat Res, Bethesda, MD USA. NHLBI, NIH, Bethesda, MD 20892 USA. Univ Michigan, Ann Arbor, MI 48109 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 1166 BP 225 EP 225 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594401203 ER PT J AU Sahn, DJ Zetts, AD Jones, M Irvine, T Stetten, G von Ramm, OT Ramsperger, C Castellucci, J AF Sahn, DJ Zetts, AD Jones, M Irvine, T Stetten, G von Ramm, OT Ramsperger, C Castellucci, J TI Calculation of aortic regurgitant stroke volume from real-time 3D ultrasound images as the difference between left and right ventricular 3D determined stroke volumes in a chronic animal model of aortic regurgitation: A new method with potentially wide application in cardiology SO CIRCULATION LA English DT Meeting Abstract C1 Oregon Hlth Sci Univ, Portland, OR 97201 USA. NHLBI, LAMS, Bethesda, MD 20892 USA. NIH, Bethesda, MD 20892 USA. Duke Univ, Durham, NC 27706 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 1170 BP 226 EP 226 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594401207 ER PT J AU Shiota, T Jones, M Zetts, A Cardon, LA Greenberg, N Thomas, JD AF Shiota, T Jones, M Zetts, A Cardon, LA Greenberg, N Thomas, JD TI Real-time 3-dimensional contrast echocardiography for visualizing and quantifying left ventricular inflow phenomena: Comparison with Doppler method SO CIRCULATION LA English DT Meeting Abstract C1 Cleveland Clin Fdn, Cleveland, OH 44195 USA. NIH, Bethesda, MD 20892 USA. NHLBI, LAMS, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 1172 BP 226 EP 226 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594401209 ER PT J AU Kuschel, M Lakatta, EG Xiao, RP AF Kuschel, M Lakatta, EG Xiao, RP TI Pertussis toxin restores the ability of beta(2)-adrenoceptor stimulation to induce phospholamban phosphorylation SO CIRCULATION LA English DT Meeting Abstract C1 NIA, NIH, GRC, Baltimore, MD 21224 USA. NR 0 TC 2 Z9 2 U1 2 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 1213 BP 234 EP 234 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594401250 ER PT J AU Xiao, RP Zhang, SJ Zhou, YY Cheng, HP Lakatta, EG AF Xiao, RP Zhang, SJ Zhou, YY Cheng, HP Lakatta, EG TI Ligand-directed differential coupling of beta 2-adrenergic receptor to G proteins in intact cardiomyocytes SO CIRCULATION LA English DT Meeting Abstract C1 NIA, NIH, Baltimore, MD 21224 USA. NR 0 TC 1 Z9 1 U1 2 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 1212 BP 234 EP 234 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594401249 ER PT J AU Zhou, YY Cheng, HP Song, LS Wang, DJ Lakatta, EG Xiao, RP AF Zhou, YY Cheng, HP Song, LS Wang, DJ Lakatta, EG Xiao, RP TI Spontaneously-activated beta(2)-adrenoceptors bypass l-type ca(2+) channel to modulate cardiac excitation-contraction coupling SO CIRCULATION LA English DT Meeting Abstract C1 NIA, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 2 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 1214 BP 234 EP 234 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594401251 ER PT J AU Uren, D Tullio, AN Hwang, HK Kawamoto, S Takeda, K Yu, ZXX Ferrans, VJ Preston, YA Adelstein, RS AF Uren, D Tullio, AN Hwang, HK Kawamoto, S Takeda, K Yu, ZXX Ferrans, VJ Preston, YA Adelstein, RS TI Downregulation of nonmuscle myosin II-B in mice increases the severity of cardiac defects SO CIRCULATION LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 1222 BP 236 EP 236 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594401259 ER PT J AU Shamburek, RD Dinger, ML Talley, GD Kindt, MR Brewer, HB AF Shamburek, RD Dinger, ML Talley, GD Kindt, MR Brewer, HB TI ApoA-I and ApoA-II metabolism in hyperalphalipoproteinemia induced by ETOH SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI, MDB, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 1240 BP 239 EP 239 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594401277 ER PT J AU Koh, KK Cardillo, G Bui, MN Hathaway, L Mincemoyer, R Panza, JA Cannon, RO AF Koh, KK Cardillo, G Bui, MN Hathaway, L Mincemoyer, R Panza, JA Cannon, RO TI Effects of estrogen and simvastatin on markers of inflammation in hypercholestrolemic postmenopausal women SO CIRCULATION LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 1247 BP 240 EP 241 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594401284 ER PT J AU Speir, E Yu, ZX Cannon, RO AF Speir, E Yu, ZX Cannon, RO TI Estrogen attenuates cytomegalovirus-induced inflammatory response in human coronary smooth muscle cells SO CIRCULATION LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 1246 BP 240 EP 240 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594401283 ER PT J AU Zhou, YF Shou, M Epstein, SE AF Zhou, YF Shou, M Epstein, SE TI Relative role of Chlamydia pneumonia versus cytomegalovirus on the risk of restenosis following directional coronary atherectomy SO CIRCULATION LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 1245 BP 240 EP 240 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594401282 ER PT J AU Prasad, A Zhu, JH Mincemoyer, R Schenke, WH Epstein, SE Quyyumi, AA AF Prasad, A Zhu, JH Mincemoyer, R Schenke, WH Epstein, SE Quyyumi, AA TI Cytomegalovirus infection is a determinant of endothelial dysfunction and coronary flow reserve SO CIRCULATION LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 1264 BP 244 EP 244 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594401300 ER PT J AU Wilson, PWF Abbott, RD D'Agostino, RB Silbershatz, H Rodriquez, BL Curb, JD AF Wilson, PWF Abbott, RD D'Agostino, RB Silbershatz, H Rodriquez, BL Curb, JD TI Prediction of coronary heart disease in Japanese-American men SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI, Framingham Heart Study, Framingham, MA USA. Hawaii Ctr Hlth Res, Honolulu, HI USA. Boston Univ, Boston, MA 02215 USA. Univ Hawaii, John A Burns Sch Med, Honolulu, HI 96822 USA. NR 0 TC 4 Z9 4 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 1690 BP 323 EP 323 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594401718 ER PT J AU Franklin, SS Khan, SA Wong, ND Larson, MG Levy, D AF Franklin, SS Khan, SA Wong, ND Larson, MG Levy, D TI Is pulse pressure more important than systolic blood pressure in predicting coronary heart disease events? The Framingham heart study SO CIRCULATION LA English DT Meeting Abstract C1 Univ Calif Irvine, Irvine, CA 92717 USA. NHLBI, Framingham Heart Study, Framingham, MA USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 1697 BP 324 EP 324 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594401725 ER PT J AU Arai, AE Ding, SJ Balaban, RS AF Arai, AE Ding, SJ Balaban, RS TI High resolution myocardial perfusion measurements using a magnetic resonance vascular contrast agent. SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 1742 BP 332 EP 332 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594401769 ER PT J AU Chikada, M Aida, S Yamada, I AF Chikada, M Aida, S Yamada, I TI Application of a digital Doppler color flow mapping method to LV outflow and MV inflow volumes calculated in orthogonal imaging planes with electromagnetic flow recordings: An animal model SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI, LAMS, Bethesda, MD 20892 USA. Oregon Hlth Sci Univ, Portland, OR 97201 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 1879 BP 357 EP 357 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594401905 ER PT J AU Qin, JX Jones, M Greenberg, N Shiota, T Cardon, LA Zetts, AD Thomas, JD AF Qin, JX Jones, M Greenberg, N Shiota, T Cardon, LA Zetts, AD Thomas, JD TI Estimation of left ventricular function by real-time 3-dimensional echocardiography and conductance catheterization: An animal study with chronic aortic regurgitation SO CIRCULATION LA English DT Meeting Abstract C1 Cleveland Clin Fdn, Cleveland, OH 44195 USA. NIH, Bethesda, MD 20892 USA. NHLBI, LAMS, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 1876 BP 357 EP 357 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594401902 ER PT J AU Daniel, M Brigger, P Hong, MK Burke, AP Virmani, R Mintz, GS Hoeg, JM AF Daniel, M Brigger, P Hong, MK Burke, AP Virmani, R Mintz, GS Hoeg, JM TI Automated quantitation of intravascular ultrasound measurements accurately reflects human coronary atherosclerosis SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI, MDB, NIH, Bethesda, MD 20892 USA. NIH, BEIP, Bethesda, MD 20892 USA. Washington Hosp Ctr, Washington, DC 20010 USA. Armed Forces Inst Pathol, Washington, DC 20306 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 1934 BP 368 EP 368 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594401959 ER PT J AU Shirani, J Lee, J Kitslou, AN Ohler, L Miller-Davis, C Dilsizian, V AF Shirani, J Lee, J Kitslou, AN Ohler, L Miller-Davis, C Dilsizian, V TI Histomorphologic correlates of reversible and mild-moderate irreversible thallium defects in chronic ischemic cardiomyopathy SO CIRCULATION LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 1945 BP 370 EP 370 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594401970 ER PT J AU Rosenberg, IH Bostom, AG Silbershatz, H Jacques, PF Selhub, J D'Agostino, RB Wilson, PWF Wolf, PA AF Rosenberg, IH Bostom, AG Silbershatz, H Jacques, PF Selhub, J D'Agostino, RB Wilson, PWF Wolf, PA TI Non-fasting plasma total homocysteine levels and stroke occurrence in elderly framingham women and men: A prospective study SO CIRCULATION LA English DT Meeting Abstract C1 Tufts Univ, Boston, MA 02111 USA. Brown Univ, Providence, RI 02912 USA. Boston Univ, University, MA USA. Boston Univ, Boston, MA 02215 USA. NHLBI, Framingham Heart Study, Framingham, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 1961 BP 374 EP 374 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594401986 ER PT J AU Cardillo, C Nambi, S Kilcoyne, CM Choucair, W Wuon, MJ Panza, JA AF Cardillo, C Nambi, S Kilcoyne, CM Choucair, W Wuon, MJ Panza, JA TI Insulin stimulates both endothelin and nitric oxide activity in the human forearm. SO CIRCULATION LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NHLBI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 1973 BP 376 EP 376 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594401998 ER PT J AU Fedorova, OV Lakatta, EG Bagrov, AY AF Fedorova, OV Lakatta, EG Bagrov, AY TI Endogenous ligands of the Na,K pump in NaCl induced hypertension SO CIRCULATION LA English DT Meeting Abstract C1 NIA, NIH, Baltimore, MD 21224 USA. NR 0 TC 2 Z9 2 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 1978 BP 377 EP 377 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594402003 ER PT J AU Hoogwerf, BJ Lindquist, R Terrin, M Dupuis, G Herd, JA Gray, RJ Czajkowski, S AF Hoogwerf, BJ Lindquist, R Terrin, M Dupuis, G Herd, JA Gray, RJ Czajkowski, S TI Pre- and perioperative characteristics and clinical outcomes through one year in patients undergoing coronary artery bypass graft (CABG) surgery SO CIRCULATION LA English DT Meeting Abstract C1 Cleveland Clin Fdn, Cleveland, OH 44195 USA. Univ Minnesota, Minneapolis, MN USA. Maryland Med Res Inst, Baltimore, MD USA. Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada. Baylor Coll Med, Houston, TX 77030 USA. Hlth Partners, St Paul, MN USA. NHLBI, Post CABG Biobehav Study, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 2006 BP 382 EP 382 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594402031 ER PT J AU Merante, F Tumiafi, LC Thatcher, BJ Li, RK Martin, BM Marshall, JG Mickle, DAG AF Merante, F Tumiafi, LC Thatcher, BJ Li, RK Martin, BM Marshall, JG Mickle, DAG TI The purification and characterization of a novel human oxygen responsive transcription factor which modulates myocardial glutathione peroxidase gene expression SO CIRCULATION LA English DT Meeting Abstract C1 Univ Toronto, Toronto Hosp, Toronto, ON, Canada. NIMH, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 2084 BP 396 EP 396 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594402109 ER PT J AU Stoll, HP Szabo, A March, KL AF Stoll, HP Szabo, A March, KL TI Sustained transmyocardial loading with bFGF following single intrapericardial delivery: Local kinetics and tissue penetration SO CIRCULATION LA English DT Meeting Abstract C1 Indiana Univ, Indianapolis, IN 46204 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 2100 BP 399 EP 399 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594402125 ER PT J AU Bittner, V Hardison, R Weiner, BH Jacobs, AK Sopko, G AF Bittner, V Hardison, R Weiner, BH Jacobs, AK Sopko, G TI Baseline lipid levels predict five year outcome in file bypass angioplasty revascularization investigation (BARI) SO CIRCULATION LA English DT Meeting Abstract C1 Univ Pittsburgh, Pittsburgh, PA USA. Univ Alabama, Birmingham, AL USA. Univ Massachusetts, Worcester, MA 01605 USA. Boston Univ, Boston, MA 02215 USA. NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 2170 BP 412 EP 412 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594402195 ER PT J AU Dougherty, C Schofield, P Jacobson, KA Liang, BT AF Dougherty, C Schofield, P Jacobson, KA Liang, BT TI Cardiac myocytes rendered ischemia-resistant by overexpressing the human adenosine A(3) receptor SO CIRCULATION LA English DT Meeting Abstract C1 Univ Penn, Philadelphia, PA 19104 USA. Garvan Inst Med Res, Sydney, NSW, Australia. NIH, Bethesda, MD 20892 USA. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 2196 BP 417 EP 417 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594402221 ER PT J AU Albanese, N Mancuso, A Talley, GD Yang, W Kruth, HS Santamarina-Fojo, S Brewer, HB AF Albanese, N Mancuso, A Talley, GD Yang, W Kruth, HS Santamarina-Fojo, S Brewer, HB TI Effects of dysfunctional HDL on cholesterol efflux in LCAT transgenic mice SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 2365 BP 450 EP 450 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594402390 ER PT J AU Foger, B Vaisman, BL Koch, CA Allen, DT Paiz, JA Paigen, B Brewer, HB Santamarina-Fojo, S AF Foger, B Vaisman, BL Koch, CA Allen, DT Paiz, JA Paigen, B Brewer, HB Santamarina-Fojo, S TI Expression of human ApoA-l abolishes aortic atherosclerosis in LCAT-transgenic mice SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI, NIH, Bethesda, MD 20892 USA. Jackson Lab, Bar Harbor, ME 04609 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 2364 BP 450 EP 450 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594402389 ER PT J AU Lazarous, DF Unger, EF Epstein, SE Stine, A Arevalo, JL Quyyumi, AA AF Lazarous, DF Unger, EF Epstein, SE Stine, A Arevalo, JL Quyyumi, AA TI Effect of basic fibroblast growth factor on lower extremity blood flow in patients with intermittent claudication: Preliminary results SO CIRCULATION LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 4 Z9 4 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 2398 BP 456 EP 456 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594402423 ER PT J AU Feng, DL Lindpaintner, K Larson, MG O'Donnell, C Silbershatz, H Lipinska, I Sutherland, PA Muller, JE D'Agostino, RB Myers, RH Tofler, GH AF Feng, DL Lindpaintner, K Larson, MG O'Donnell, C Silbershatz, H Lipinska, I Sutherland, PA Muller, JE D'Agostino, RB Myers, RH Tofler, GH TI Factor VII gene polymorphism and cardiovascular disease: The Framingham Heart Study SO CIRCULATION LA English DT Meeting Abstract C1 BI Deaconess Med Ctr, IPCD, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Boston Univ, Boston, MA 02215 USA. NHLBI, Framingham Heart Dis Epidemiol Study, Framingham, MA USA. Univ Kentucky, Lexington, KY 40506 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 2410 BP 458 EP 458 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594402435 ER PT J AU Hoeg, JM Kauffman, RD Herderick, E Demosky, SJ Evans, W Brousseau, ME AF Hoeg, JM Kauffman, RD Herderick, E Demosky, SJ Evans, W Brousseau, ME TI Lecithin : cholesterol acyl transferase requires functional LDL receptors to prevent atherosclerosis SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI, MDB, NIH, Bethesda, MD 20892 USA. Ohio State Univ, Columbus, OH 43210 USA. Tufts Univ, Boston, MA 02111 USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 2444 BP 464 EP 465 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594402468 ER PT J AU Yokoyama, Y Chaitman, BR Hardison, R Guo, P Krone, R Stocke, K Gussak, I Attubato, MJ Rautaharju, PM Sopko, G Detre, KM AF Yokoyama, Y Chaitman, BR Hardison, R Guo, P Krone, R Stocke, K Gussak, I Attubato, MJ Rautaharju, PM Sopko, G Detre, KM TI Prognostic impact of new post-procedure ECG abnormalities after coronary bypass surgery as compared to coronary angioplasty in BARI SO CIRCULATION LA English DT Meeting Abstract C1 St Louis Univ, Sch Med, St Louis, MO USA. Univ Pittsburgh, Pittsburgh, PA USA. Washington Univ, St Louis, MO USA. NYU, New York, NY USA. Wake Forest Univ, Winston Salem, NC 27109 USA. NHLBI, NIH, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 2503 BP 476 EP 476 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594402527 ER PT J AU Parsons, M Musikabhumma, A Jacobson, KA Liang, BT AF Parsons, M Musikabhumma, A Jacobson, KA Liang, BT TI Selective coupling of adenosine A(1) receptor to phospholipase C and of adenosine A(3) receptor to phospholipase D SO CIRCULATION LA English DT Meeting Abstract C1 Univ Penn, Philadelphia, PA 19104 USA. NIH, Bethesda, MD 20892 USA. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 2582 BP 490 EP 491 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594402606 ER PT J AU Exner, DV Epstein, AE Reiter, MJ Yao, Q Ledingham, R Reiffel, JA Brodsky, M Akiyama, T Schron, E Follmann, D Anderson, J AF Exner, DV Epstein, AE Reiter, MJ Yao, Q Ledingham, R Reiffel, JA Brodsky, M Akiyama, T Schron, E Follmann, D Anderson, J TI Beta-blocker use and mortality in the antiarrhythmics versus implantable defibrillators (AVID) cohort. SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI, NIH, Bethesda, MD 20892 USA. Univ Alabama, Birmingham, AL USA. Univ Colorado, Denver, CO 80202 USA. Univ Washington, Seattle, WA 98195 USA. Columbia Presbyterian Med Ctr, New York, NY 10032 USA. Univ Calif Irvine, Irvine, CA 92717 USA. Univ Rochester, Rochester, MN USA. Univ Utah, LDS Hosp, Salt Lake City, UT USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 2598 BP 494 EP 494 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594402622 ER PT J AU Pratt, CM Greene, L Anderson, JL Cobb, LA Epstein, AE Flynn, D Kim, S Richards, DW Schron, E Epstein, AE AF Pratt, CM Greene, L Anderson, JL Cobb, LA Epstein, AE Flynn, D Kim, S Richards, DW Schron, E Epstein, AE TI Causes of death in the antiarrhythmics versus implantable defibrillators (AVID) trial SO CIRCULATION LA English DT Meeting Abstract C1 Baylor Coll Med, Houston, TX 77030 USA. Univ Utah, Latter Day St Hosp, Salt Lake City, UT 84143 USA. St Lukes Roosevelt Hosp, New York, NY 10025 USA. Univ Alabama, Birmingham, AL USA. Univ Rochester, Rochester, NY USA. Montefiore Med Ctr, Bronx, NY USA. Virginia Commonwealth Univ, Med Coll Virginia, Richmond, VA 23298 USA. NHLBI, Bethesda, MD 20892 USA. Univ Washington, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 2602 BP 494 EP 495 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594402626 ER PT J AU Cook, JR Rizo-Patron, C Domanski, M Kim, SG Coromilas, J Curtis, AB Kutalek, S Gillis, AM Berns, E Powell, J Hallstrom, A AF Cook, JR Rizo-Patron, C Domanski, M Kim, SG Coromilas, J Curtis, AB Kutalek, S Gillis, AM Berns, E Powell, J Hallstrom, A TI The effect of myocardial revascularization in patients with VT/VF and coronary artery disease: Relationship to outcome in the antiarrhythmics versus implantable defibrillators (AVID) registry SO CIRCULATION LA English DT Meeting Abstract C1 Baystate Med Ctr, Springfield, MA USA. Baylor Coll Med, Houston, TX 77030 USA. NIH, Bethesda, MD 20892 USA. Montefiore Med Ctr, New York, NY USA. Columbia Univ, New York, NY USA. Univ Florida, Gainesville, FL USA. Allegheny Univ Hlth Sci, Philadelphia, PA 19102 USA. Univ Calgary, Calgary, AB, Canada. Univ Connecticut, Farmington, CT USA. Univ Washington, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 2608 BP 496 EP 496 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594402632 ER PT J AU Roman, MJ Fabsitz, RR Crawford, A Lee, ET Fishman, D Howard, BV AF Roman, MJ Fabsitz, RR Crawford, A Lee, ET Fishman, D Howard, BV TI Comparison of carotid atherosclerosis in American Indians and the general US population SO CIRCULATION LA English DT Meeting Abstract C1 Cornell Univ, Coll Med, New York, NV USA. NHLBI, NIH, Bethesda, MD 20892 USA. Aberdeen Area Tribal Chairmens Hlth Board, Rapid City, SD USA. Univ Oklahoma, Oklahoma City, OK USA. Cornell Univ, Med Ctr, New York, NY 10021 USA. Medlant Res Inst, Washington, DC USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 2711 BP 516 EP 516 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594402735 ER PT J AU Haider, AW Larson, MG Franklin, SS Levy, D AF Haider, AW Larson, MG Franklin, SS Levy, D TI Pulse pressure is associated with risk for overt heart failure SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI, Framingham Heart Study, Framingham, MA USA. Univ Calif Irvine, Irvine, CA 92717 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 2722 BP 518 EP 518 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594402745 ER PT J AU Lloyd-Jones, DM Evans, JC Larson, MG O'Donnell, CJ Levy, D AF Lloyd-Jones, DM Evans, JC Larson, MG O'Donnell, CJ Levy, D TI Systolic versus diastolic blood pressure level as the criterion for JNC-VI blood pressure stage classification: The Framingham Heart Study SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI, Framingham Heart Study, Framingham, MA USA. RI Lloyd-Jones, Donald/C-5899-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 2723 BP 518 EP 518 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594402746 ER PT J AU Dipla, K Xiao, RP Margulies, KB Lakatta, EG Houser, SR AF Dipla, K Xiao, RP Margulies, KB Lakatta, EG Houser, SR TI Reduced response to beta(2)-adrenergic stimulation in hypertrophied failing feline and failing human ventricular myocytes SO CIRCULATION LA English DT Meeting Abstract C1 Temple Univ, Sch Med, Philadelphia, PA 19122 USA. NIA, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 2 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 2917 BP 554 EP 554 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594402938 ER PT J AU Liu, JE Roman, MJ Palmieri, V Fabsitz, RR Welty, TK Lee, ET AF Liu, JE Roman, MJ Palmieri, V Fabsitz, RR Welty, TK Lee, ET TI Cardiac and biochemical correlates of diastolic dysfunction in diabetes: The Strong Heart Study. SO CIRCULATION LA English DT Meeting Abstract C1 NYU, Cornell Med Ctr, New York, NY USA. Cornell Univ, Coll Med, New York, NY USA. NHLBI, NIH, Bethesda, MD USA. Aberdeen Area Tribal Chairmens Hlth Board, Rapid City, SD USA. Univ Oklahoma, Oklahoma City, OK USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 3022 BP 574 EP 574 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594403042 ER PT J AU Arai, AE Plexico, GJ Bove, KE Tripodi, D Fananapazir, L AF Arai, AE Plexico, GJ Bove, KE Tripodi, D Fananapazir, L TI Myocardial ischemia in hypertrophic cardiomyopathy detected by exercise thallium is not related to severity of left ventricular hypertrophy SO CIRCULATION LA English DT Meeting Abstract C1 Natl Inst Hlth, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 3029 BP 575 EP 575 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594403049 ER PT J AU Burchfiel, CM Rodriguez, BL Abbott, RD Sharp, DS Curb, JD Burns, JA AF Burchfiel, CM Rodriguez, BL Abbott, RD Sharp, DS Curb, JD Burns, JA TI Predictors of hyperinsulinemia: The Honolulu heart program SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI, Bethesda, MD 20892 USA. Univ Hawaii, Honolulu, HI 96822 USA. Univ Virginia, Charlottesville, VA USA. Univ Hawaii, John A Burns Sch Med, Honolulu, HI 96822 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 3066 BP 582 EP 583 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594403086 ER PT J AU Ferrand, SK Smith, MF Carson, JM Brigger, P Bacharach, SL Dilsizian, V AF Ferrand, SK Smith, MF Carson, JM Brigger, P Bacharach, SL Dilsizian, V TI Variability in SPECT thallium ejection fraction estimates SO CIRCULATION LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 3092 BP 587 EP 587 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594403111 ER PT J AU Haudenschild, CC Knapper, CL Duarte, CJ Santamarina-Fojo, S AF Haudenschild, CC Knapper, CL Duarte, CJ Santamarina-Fojo, S TI Adenovirus-mediated expression of LPL: In vivo evidence for a nonlipolytic role of LPL in the metabolism of remnant-Lp and HDL. SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 3102 BP 591 EP 591 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594403121 ER PT J AU Basson, CT Casey, M Mah, C Stratakis, CA Carney, JA AF Basson, CT Casey, M Mah, C Stratakis, CA Carney, JA TI Identification of a novel genetic basis for familial cardiac myxomas SO CIRCULATION LA English DT Meeting Abstract C1 Cornell Univ, Coll Med, New York, NY USA. NICHHD, Bethesda, MD 20892 USA. Mayo Clin & Mayo Fdn, Rochester, MN 55905 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 3132 BP 596 EP 596 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594403150 ER PT J AU Koh, KK Bui, MN Hathaway, L Mincemoyer, R Panza, JA Cannon, RO AF Koh, KK Bui, MN Hathaway, L Mincemoyer, R Panza, JA Cannon, RO TI Vascular response to angiotensin converting enzyme inhibition is associated with reduced luminal release of nitric oxide in coronary artery disease SO CIRCULATION LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 3189 BP 607 EP 607 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594403207 ER PT J AU Prasad, A Narayanan, S Mincemoyer, R Tupas-Habib, T Ellahham, S Quyyumi, AA AF Prasad, A Narayanan, S Mincemoyer, R Tupas-Habib, T Ellahham, S Quyyumi, AA TI Acute and lang term effects of angiotensin type I receptor inhibition on endothelial dysfunction in atherosclerosis SO CIRCULATION LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. Washington Hosp Ctr, Washington, DC 20010 USA. NR 0 TC 5 Z9 5 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 3191 BP 607 EP 607 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594403209 ER PT J AU Bolling, SF Benedict, PE Benedict, ME Su, TP AF Bolling, SF Benedict, PE Benedict, ME Su, TP TI Delta opioid receptors and myocardial protection SO CIRCULATION LA English DT Meeting Abstract C1 Univ Michigan, Ann Arbor, MI 48109 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 3222 BP 613 EP 613 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594403240 ER PT J AU Starc, TJ Lipshultz, SE Easley, KA Colan, SD Lai, WW Gersony, WM Bricker, JT Moodie, DS Sopko, G Schluchter, MD Kaplan, S AF Starc, TJ Lipshultz, SE Easley, KA Colan, SD Lai, WW Gersony, WM Bricker, JT Moodie, DS Sopko, G Schluchter, MD Kaplan, S TI Cardiac complications in congenital HIV infection SO CIRCULATION LA English DT Meeting Abstract C1 Columbia Univ, New York, NY USA. Univ Rochester, Rochester, NY USA. Cleveland Clin, Cleveland, OH 44106 USA. Childrens Hosp, Boston, MA 02115 USA. CUNY Mt Sinai Sch Med, New York, NY 10029 USA. Baylor Coll Med, Houston, TX 77030 USA. NHLBI, NIH, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 3249 BP 618 EP 618 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594403267 ER PT J AU Cross, HR Steenbergen, C Koch, WJ Elizabeth, M AF Cross, HR Steenbergen, C Koch, WJ Elizabeth, M TI Overexpression of the cardiac beta(2)-adrenergic receptor increases ischemic energy demand and exacerbates injury in male, but not female, transgenic mice SO CIRCULATION LA English DT Meeting Abstract C1 NIEHS, Res Triangle Pk, NC 27709 USA. Duke Univ, Med Ctr, Durham, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 3298 BP 627 EP 627 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594403316 ER PT J AU Wyse, DG Love, JC Yao, Q Carlson, MD Cassidy, P Greene, HL Martins, JB Ocampo, C Raitt, MH Schron, EB Stamato, NJ AF Wyse, DG Love, JC Yao, Q Carlson, MD Cassidy, P Greene, HL Martins, JB Ocampo, C Raitt, MH Schron, EB Stamato, NJ CA Antiarrhythm Implant Defibrill Stud Invest TI Atrial fibrillation: A risk factor for increased mortality in patients with ventricular tachyarrhythmias - An AVID registry analysis SO CIRCULATION LA English DT Meeting Abstract C1 Univ Calgary, Calgary, AB, Canada. Maine Med Ctr, Portland, ME 04102 USA. Univ Washington, Seattle, WA 98195 USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. Univ Iowa, Iowa City, IA USA. Univ Rochester, Rochester, MN USA. Portland VA Med Ctr, Portland, OR USA. NHLBI, Bethesda, MD 20892 USA. Wilson Reg Med Ctr, Johnson City, NY USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 3329 BP 633 EP 633 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594403347 ER PT J AU Guidry, UA Evans, JC Wilson, PW Murabito, J Levy, D AF Guidry, UA Evans, JC Wilson, PW Murabito, J Levy, D TI Temporal trends in event rates after a Q wave myocardial infarction: The Framingham Heart Study 1950-1989 SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI, Framingham Heart Study, Framingham, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 3335 BP 634 EP 634 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594403353 ER PT J AU Rosenberg, YD Campeau, L Knatterud, G Hunninghake, D Domanski, MJ Forrester, JS Geller, NL Gobel, FI Herd, JA Hoogwerf, B AF Rosenberg, YD Campeau, L Knatterud, G Hunninghake, D Domanski, MJ Forrester, JS Geller, NL Gobel, FI Herd, JA Hoogwerf, B TI Angiographic and clinical characteristics influencing long-term prognosis in coronary artery bypass graft (CABG) patients. Results from the PostCABG clinical trial. SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI, NIH, Bethesda, MD 20892 USA. Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada. Maryland Med Res Inst, Baltimore, MD USA. Univ Minnesota, Minneapolis, MN USA. Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. Baylor Coll Med, Houston, TX 77030 USA. Cleveland Clin, Cleveland, OH 44106 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 3337 BP 635 EP 635 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594403355 ER PT J AU Singh, JP Larson, MG O'Donnell, CJ Tsuji, H Lloyd-Jones, DM Wilson, P Levy, D AF Singh, JP Larson, MG O'Donnell, CJ Tsuji, H Lloyd-Jones, DM Wilson, P Levy, D TI Hyperglycemia is associated with reduced heart rate variability SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI, Framingham Heart Study, Framingham, MA USA. Kansai Med Univ, Osaka, Japan. RI Lloyd-Jones, Donald/C-5899-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 3399 BP 647 EP 647 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594403416 ER PT J AU Bella, JN MacCluer, J Roman, MJ Almasy, L North, K Welty, TK Fabsitz, RR Howard, BV Lee, ET Devereux, RB AF Bella, JN MacCluer, J Roman, MJ Almasy, L North, K Welty, TK Fabsitz, RR Howard, BV Lee, ET Devereux, RB TI Heritability of left ventricular dimensions and mass: The Strong Heart Study SO CIRCULATION LA English DT Meeting Abstract C1 Cornell Univ, New York Hosp, Coll Med, New York, NY USA. SW Fdn Biomed Res, San Antonio, TX 78284 USA. Aberdeen Area Tribal Chairmans Hlth Board, Rapid City, SD USA. NHLBI, NIH, Bethesda, MD USA. Med Res Inst, Washington, DC USA. Univ Oklahoma, Oklahoma City, OK USA. New York Hosp, Cornell Med Ctr, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 3458 BP 658 EP 658 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594403475 ER PT J AU Chae, CU Glynn, RJ Manson, JE Guralnik, JM Taylor, JO Pfeffer, MA Hennekens, CH AF Chae, CU Glynn, RJ Manson, JE Guralnik, JM Taylor, JO Pfeffer, MA Hennekens, CH TI Diabetes predicts congestive heart failure risk in the elderly SO CIRCULATION LA English DT Meeting Abstract C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. NIA, Bethesda, MD 20892 USA. E Boston Neighborhood Hlth Ctr, E Boston, MA USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 3460 BP 658 EP 658 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594403477 ER PT J AU Reis, SE Holubkov, R Reichek, N Zell, KA Bairey-Merz, CN Sopko, G AF Reis, SE Holubkov, R Reichek, N Zell, KA Bairey-Merz, CN Sopko, G TI Coronary microvascular dysfunction is not associated with abnormal brachial artery flow-mediated dilatation in women with chest pain and normal coronaries: Results from the NHLBI-sponsored WISE study SO CIRCULATION LA English DT Meeting Abstract C1 Univ Pittsburgh, Pittsburgh, PA USA. Allegheny Univ Hlth Sci, Pittsburgh, PA USA. Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. NHLBI, NIH, Bethesda, MD 20892 USA. Univ Florida, Gainesville, FL USA. RI Reis, Steven/J-3957-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 3466 BP 659 EP 659 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594403483 ER PT J AU Koh, KK Blum, A Schenke, WH Hathaway, L Mincemoyer, R Panza, JA Cannon, RO AF Koh, KK Blum, A Schenke, WH Hathaway, L Mincemoyer, R Panza, JA Cannon, RO TI Vitamin E improves endothelium-dependent vasodilator responsiveness comparable to estrogen in postmenopausal women SO CIRCULATION LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 3468 BP 660 EP 660 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594403485 ER PT J AU Remaley, AT Shirali, AC Stonik, JA Sampson, ML Chako, G Hoeg, JM Brewer, HB AF Remaley, AT Shirali, AC Stonik, JA Sampson, ML Chako, G Hoeg, JM Brewer, HB TI Squalene synthase promoter coupled to a secretory reporter: A novel system for monitoring the regulatory pool of cholesterol in cells SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI, NIH, Bethesda, MD 20892 USA. NHLB, MDB, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 3492 BP 665 EP 665 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594403509 ER PT J AU Schmidt, MA Agyeman, KO Laurienzo, JM Brenneman, CL Freidlin, RZ Ohazama, CJ Arai, AE Panza, JA AF Schmidt, MA Agyeman, KO Laurienzo, JM Brenneman, CL Freidlin, RZ Ohazama, CJ Arai, AE Panza, JA TI Left ventricular volume measurements in humans using real-time three-dimensional echocardiography: Comparison with magnetic resonance imaging SO CIRCULATION LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. Duke Univ, Durham, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 3685 BP 701 EP 701 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594403701 ER PT J AU Mori, Y Jones, M Wanitkun, S Irvine, T Li, XK Delabays, A Sahn, DJ AF Mori, Y Jones, M Wanitkun, S Irvine, T Li, XK Delabays, A Sahn, DJ TI Color Doppler-imaged vena contracta derived by three-dimensional reconstruction of aortic regurgitant jet flows can be used for quantifying aortic regurgitation: A chronic animal study SO CIRCULATION LA English DT Meeting Abstract C1 Oregon Hlth Sci Univ, Portland, OR 97201 USA. NIH, Bethesda, MD 20892 USA. Tufts Univ, New England Med Ctr, Boston, MA 02111 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 3690 BP 702 EP 702 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594403706 ER PT J AU Domanski, MJ Exner, DV Borkowf, CB Geller, NL Rosenberg, Y Pfeffer, MA AF Domanski, MJ Exner, DV Borkowf, CB Geller, NL Rosenberg, Y Pfeffer, MA TI Effect of angiotensin converting enzyme inhibition on sudden cardiac death in patients following acute myocardial infarction: a meta-analysis of randomized clinical trials SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI, NIH, Bethesda, MD 20892 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 3775 BP 718 EP 718 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594403790 ER PT J AU Gottdiener, JS Arnold, AM Marshall, RJ Aurigemma, GP Gardin, JM Rutledge, JC Smith, VE Bolneau, RE AF Gottdiener, JS Arnold, AM Marshall, RJ Aurigemma, GP Gardin, JM Rutledge, JC Smith, VE Bolneau, RE TI LV function and congestive head failure in the elderly - Relevance of therapeutic trials. The cardiovascular health study. SO CIRCULATION LA English DT Meeting Abstract C1 Georgetown Univ, Med Ctr, Washington, DC 20007 USA. Univ Washington, Seattle, WA 98195 USA. Univ Calif Irvine, Orange, CA 92668 USA. Univ Calif Davis, Davis, CA USA. Albany Med Coll, Albany, NY 12208 USA. NHLBI, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 3774 BP 718 EP 718 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594403789 ER PT J AU Devereux, RB Liu, JE Fishman, D Lee, ET Fabsitz, RR Welty, TK AF Devereux, RB Liu, JE Fishman, D Lee, ET Fabsitz, RR Welty, TK TI Improvements in echocardiographic LV mass measurement yield and non-randomness of missing measurements: Strong heart and Framingham Heart Studies. SO CIRCULATION LA English DT Meeting Abstract C1 Cornell Univ, Med Ctr, New York Hosp, New York, NY 10021 USA. Cornell Univ, Med Ctr, New York, NY 10021 USA. Univ Oklahoma, Oklahoma City, OK USA. NHLBI, NIH, Bethesda, MD 20892 USA. Aberdeen Area Tribal Chairmens Hlth Board, Rapid City, SD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 3792 BP 721 EP 722 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594403807 ER PT J AU Glynn, RJ Chae, CU Guralnik, JM Taylor, JO Pfeffer, MA Hennekens, CH AF Glynn, RJ Chae, CU Guralnik, JM Taylor, JO Pfeffer, MA Hennekens, CH TI Change in blood pressure and risk of congestive heart failure in the elderly SO CIRCULATION LA English DT Meeting Abstract C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. NIA, Bethesda, MD 20892 USA. E Boston Neighborhood Hlth Ctr, E Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 3789 BP 721 EP 721 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594403804 ER PT J AU Liao, DP Simpson, R Arnett, D Manolio, T Szklo, M Evans, G Heiss, G AF Liao, DP Simpson, R Arnett, D Manolio, T Szklo, M Evans, G Heiss, G TI Association of arterial stiffness and left ventricular hypertrophy SO CIRCULATION LA English DT Meeting Abstract C1 Univ N Carolina, Chapel Hill, NC USA. Univ Minnesota, Minneapolis, MN USA. NHLBI, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Baltimore, MD USA. Wake Forest Univ, Winston Salem, NC 27109 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 3791 BP 721 EP 721 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594403806 ER PT J AU Zieman, SJ Gerstenblith, G Ricker, KM Sollott, SJ Vandegaer, KM Hare, JM AF Zieman, SJ Gerstenblith, G Ricker, KM Sollott, SJ Vandegaer, KM Hare, JM TI Enhanced nitric oxide synthase activity contributes to decreased beta-adrenergic inotropic responsiveness in aged myocardium SO CIRCULATION LA English DT Meeting Abstract C1 Johns Hopkins Univ, Baltimore, MD USA. NIA, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. Johns Hopkins Med Inst, Baltimore, MD 21205 USA. NR 0 TC 1 Z9 1 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 3835 BP 731 EP 731 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594403850 ER PT J AU Li, A Prasad, A Mincemoyer, R Satorius, C Epstein, N Finkel, T Quyyumi, AA AF Li, A Prasad, A Mincemoyer, R Satorius, C Epstein, N Finkel, T Quyyumi, AA TI The C242T polymorphism of the p22phox gene does not decrease the risk of coronary artery disease SO CIRCULATION LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 3855 BP 735 EP 735 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594403870 ER PT J AU Byrne, BJ Raben, N Plotz, PH Fraites, TJ Kessler, PD AF Byrne, BJ Raben, N Plotz, PH Fraites, TJ Kessler, PD TI Reconstitution of acid alpha-glucosidase activity in a mouse model of cardio-skeletal myopathy, Pompe's Disease SO CIRCULATION LA English DT Meeting Abstract C1 Univ Florida, Gainesville, FL USA. NIAMS, NIH, Bethesda, MD USA. Johns Hopkins Univ, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 3863 BP 737 EP 737 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594403878 ER PT J AU Ordovas, JM Otvos, JD Martinez, A Najera, G Wilson, PWF Cupples, AL McNamara, JR Schaefer, EJ AF Ordovas, JM Otvos, JD Martinez, A Najera, G Wilson, PWF Cupples, AL McNamara, JR Schaefer, EJ TI Association of a common variant of the CETP gene (TaqIB) with lipoprotein subfractions: The Framingham Offspring Study SO CIRCULATION LA English DT Meeting Abstract C1 Tufts Univ, USDA, Human Nutr Res Ctr Aging, JM, Boston, MA 02111 USA. N Carolina State Univ, Raleigh, NC 27695 USA. NHLBI, Framingham Heart Study, Framingham, MA USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Tufts Univ, USDA, Human Nutr Res Ctr, JM, Boston, MA 02111 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 3872 BP 738 EP 738 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594403887 ER PT J AU Cross, HR Steenbergen, C Korach, KS Murphy, E AF Cross, HR Steenbergen, C Korach, KS Murphy, E TI Estrogen receptor knock-out mice exhibit higher myocardial contractility than wild-type mice but are equally susceptible to ischemic injury SO CIRCULATION LA English DT Meeting Abstract C1 NIEHS, NIH, Res Triangle Pk, NC 27709 USA. Duke Univ, Durham, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 3979 BP 758 EP 758 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594403991 ER PT J AU Janczewski, AM Spurgeon, HA Lakatta, EG AF Janczewski, AM Spurgeon, HA Lakatta, EG TI Cellular mechanisms underlying beta(1)-adrenergic effects in cardiac myocytes. SO CIRCULATION LA English DT Meeting Abstract C1 Lab CV Sci, Baltimore, MD USA. NIA, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 4005 BP 763 EP 763 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594404016 ER PT J AU Song, LS Sham, JSK Stern, MD Lakatta, EG Cheng, HP AF Song, LS Sham, JSK Stern, MD Lakatta, EG Cheng, HP TI Temporal synchrony of SR Ca2+ release: Novel determinant or cardiac contractility SO CIRCULATION LA English DT Meeting Abstract C1 NIA, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. Johns Hopkins Med Inst, Baltimore, MD 21205 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 4003 BP 763 EP 763 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594404014 ER PT J AU Cheng, HP Song, LS Stern, MD Lakatta, EG Sham, JSK AF Cheng, HP Song, LS Stern, MD Lakatta, EG Sham, JSK TI Does "adaptation" of cardiac ryanodine receptors Ca2+ release channels occur in situ? SO CIRCULATION LA English DT Meeting Abstract C1 NIA, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. Johns Hopkins Med Inst, Baltimore, MD 21205 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 4007 BP 764 EP 764 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594404018 ER PT J AU Shirani, J Lee, J Ohler, L Miller-Davis, C Dilsizian, V AF Shirani, J Lee, J Ohler, L Miller-Davis, C Dilsizian, V TI Impact of the severity of coronary artery stenosis on pathologic remodeling of viable myocardium in chronic ischemic cardiomyopathy SO CIRCULATION LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 4035 BP 769 EP 769 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594404046 ER PT J AU Shiota, T Jones, M Agler, DA Cardon, LA Greenberg, N Zetts, AD Thomas, JD AF Shiota, T Jones, M Agler, DA Cardon, LA Greenberg, N Zetts, AD Thomas, JD TI A quantitative evaluation of aortic regurgitant volume using color Doppler flow convergence and vena contracta imaging from right parasternal window: A clinical and chronic animal study. SO CIRCULATION LA English DT Meeting Abstract C1 Cleveland Clin Fdn, Cleveland, OH 44195 USA. NIH, Bethesda, MD 20892 USA. Cleveland Clin, Cleveland, OH 44106 USA. NHLBI, LAMS, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 4118 BP 786 EP 786 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594404129 ER PT J AU Ordovas, JM McNamara, JR Otvos, JD Wilson, PWF Cupples, AL Lahoz, C Osgoo, D Schaefer, EJ AF Ordovas, JM McNamara, JR Otvos, JD Wilson, PWF Cupples, AL Lahoz, C Osgoo, D Schaefer, EJ TI Association between APOE alleles, remnant lipoproteins and VLDL subclass phenotypes in the Framingham Offspring Study SO CIRCULATION LA English DT Meeting Abstract C1 Tufts Univ, Jean Mayer HNRCA, USDA, Boston, MA 02111 USA. N Carolina State Univ, Raleigh, NC 27695 USA. NHLBI, Framingham Heart Study, Framingham, MA USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Tufts Univ, USDA, Human Nutr Res Ctr, JM, Boston, MA 02111 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 4140 BP 790 EP 790 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594404150 ER PT J AU Chen, WN Murphy, E London, R Steenbergen, C AF Chen, WN Murphy, E London, R Steenbergen, C TI Regulation of the Ca2+ gradient across sarcoplasmic reticulum in perfused rabbit heart: a F-19 NMR study SO CIRCULATION LA English DT Meeting Abstract C1 NIEHS, NIH, Res Triangle Pk, NC 27709 USA. Duke Univ, Med Ctr, Durham, NC 27706 USA. Duke Univ, Durham, NC 27706 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 4319 BP 823 EP 823 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594404328 ER PT J AU Sheps, DS McMahon, RP Becker, LC Cohen, JD Freedland, KE Kaufmann, PG Ketterer, MW Light, KC Pepine, CJ Raczynski, J Sheffield, D AF Sheps, DS McMahon, RP Becker, LC Cohen, JD Freedland, KE Kaufmann, PG Ketterer, MW Light, KC Pepine, CJ Raczynski, J Sheffield, D TI Factors associated with chest pain during mental stress in patients with documented coronary artery disease: Results from the psychophysiological investigation of myocardial ischemia (PIMI) study SO CIRCULATION LA English DT Meeting Abstract C1 E Tennessee State Univ, Johnson City, TN 37614 USA. Maryland Med Res Inst, Baltimore, MD USA. Johns Hopkins Univ, Baltimore, MD USA. St Louis Univ, Hlth Sci Ctr, St Louis, MO 63103 USA. Washington Univ, Sch Med, St Louis, MO USA. NHLBI, Bethesda, MD 20892 USA. Henry Ford Hosp, Detroit, MI 48202 USA. Univ N Carolina, Chapel Hill, NC USA. Univ Florida, Gainesville, FL USA. Univ Alabama, Birmingham, AL USA. RI McMahon, Robert/C-5462-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 4460 BP 850 EP 850 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594404468 ER PT J AU Arai, AE Epstein, FH Agyeman, KO Karen, BE AF Arai, AE Epstein, FH Agyeman, KO Karen, BE TI Accurate left ventricular volumes and ejection fraction by ungated multislice cine MRI in 16 seconds SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI, NIH, Bethesda, MD 20892 USA. Appl Sci Lab, Milwaukee, WI USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 4492 BP 856 EP 856 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594404500 ER PT J AU Bos, AJG Brant, LJ Fleg, JL AF Bos, AJG Brant, LJ Fleg, JL TI Do longitudinal changes in systolic blood pressure predict the development of coronary heart disease? SO CIRCULATION LA English DT Meeting Abstract C1 NIA, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 4510 BP 859 EP 860 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594404518 ER PT J AU Dries, DL Exner, DV Domanski, MJ Carson, PE Gersh, BJ AF Dries, DL Exner, DV Domanski, MJ Carson, PE Gersh, BJ TI Increased mortality in black compared to white patients with left ventricular systolic dysfunction in the SOLVD trials. SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI, NIH, Bethesda, MD 20892 USA. Washington VA Med Ctr, Washington, DC USA. Georgetown Univ, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S MA 4539 BP 865 EP 865 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594404547 ER PT J AU Collins, FS AF Collins, FS TI Lewis A. Conner Memorial Lecture - Medical and societal consequences of the human genome project SO CIRCULATION LA English DT Meeting Abstract C1 Natl Human Genome Res Inst, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S BP A EP A PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594400002 ER PT J AU Prasad, A Narayanan, S Padder, FA Waclawiw, M Epstein, N Quyyumi, AA AF Prasad, A Narayanan, S Padder, FA Waclawiw, M Epstein, N Quyyumi, AA TI The deletion allele of the angiotensin-converting enzyme gene determines reversibility of endothelial dysfunction with converting enzyme inhibition SO CIRCULATION LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 27 PY 1998 VL 98 IS 17 SU S BP N EP N PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131UV UT WOS:000076594400035 ER PT J AU Hill, TL Chamberlin, RV AF Hill, TL Chamberlin, RV TI Extension of the thermodynamics of small systems to open metastable states: An example SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE gas phase; spherical clusters; surface effects; open partition function; physical convergence ID SUPERCOOLED ORTHO-TERPHENYL; DYNAMIC HETEROGENEITY; RELAXATION; LIQUIDS; NMR AB By using a simplified model of small open liquid-like clusters with surface effects, in the gas phase, it is shown how the statistical thermodynamics of small systems can be extended to include metastable supersaturated gaseous states not too far from the gas-liquid equilibrium transition point. To accomplish this, one has to distinguish between mathematical divergence and physical convergence of the open-system partition function. C1 NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Arizona State Univ, Dept Phys & Astron, Tempe, AZ 85287 USA. RP Hill, TL (reprint author), 433 Logan St, Santa Cruz, CA 95062 USA. NR 22 TC 40 Z9 40 U1 0 U2 16 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 27 PY 1998 VL 95 IS 22 BP 12779 EP 12782 DI 10.1073/pnas.95.22.12779 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 134RT UT WOS:000076757300012 PM 9788990 ER PT J AU Liu, W Northup, JK AF Liu, W Northup, JK TI The helical domain of a G protein alpha subunit is a regulator of its effector SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ROD OUTER SEGMENTS; CYCLIC-GMP PHOSPHODIESTERASE; GTP-GAMMA-S; CGMP-PHOSPHODIESTERASE; ADENYLYL-CYCLASE; MOLECULAR-CLONING; CRYSTAL-STRUCTURE; BINDING PROTEINS; RETINAL RODS; BETA-GAMMA AB The alpha subunit (G alpha) of heterotrimeric G proteins is a major determinant of signaling selectivity. The G alpha structure essentially comprises a GTPase "Ras-like" domain (RasD) and a unique alpha-helical domain (HD). We used the vertebrate phototransduction model to test for potential functions of HD and found that the HD of the retinal transducin G alpha (G alpha(t)) and the closely related gustducin (G alpha(g)), but not G alpha(i1), G alpha(s), Or G alpha(q) synergistically enhance guanosine 5'-gamma[-thio]triphosphate bound G alpha(t) (G alpha(t)GTP gamma S) activation of bovine rod cGMP phosphodiesterase (PDE), In addition, both HDt and HDg, but not HDil, HDs, or HDq attenuate the trypsin-activated PDE, G alpha(t)GDP and HD, attenuation of trypsin-activated PDE saturate with similar affinities and to an identical 38% of initial activity. These data suggest that interaction of intact G alpha(t) with the PDE catalytic core may be caused by the HD moiety, and they indicate an independent site(s) for the HD moiety of G alpha(t) within the PDE catalytic core in addition to the sites for the inhibitory P gamma subunits, The HD moiety of G alpha(t)GDP is an attenuator of the activated catalytic core, whereas in the presence of activated G alpha(t)GTP gamma S the independently expressed HDt is a potent synergist, Rhodopsin catalysis of cat activation enhances the PDE activation produced by subsaturating levels of G alpha(t), suggesting a HD-moiety synergism from a transient conformation of G alpha(t), These results establish HD-selective regulations of vertebrate retinal PDE, and they provide evidence demonstrating that the HD is a modulatory domain. We suggest that the HD works in concert with the RasD, enhancing the efficiency of G protein signaling. C1 Natl Inst Deafness & Other Commun Disorders, Lab Cellular Biol, Rockville, MD 20850 USA. RP Northup, JK (reprint author), NIH, Dept Hlth & Human Serv, Publ Hlth Serv, 5 Res Court,Room 2A-11, Rockville, MD 20850 USA. EM drjohn@codon.nih.gov NR 48 TC 22 Z9 22 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 27 PY 1998 VL 95 IS 22 BP 12878 EP 12883 DI 10.1073/pnas.95.22.12878 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 134RT UT WOS:000076757300030 PM 9789008 ER PT J AU Albini, A Ferrini, S Benelli, R Sforzini, S Giunciuglio, D Aluigi, MG Proudfoot, AEI Alouani, S Wells, TNC Mariani, G Rabin, RL Farber, JM Noonan, DM AF Albini, A Ferrini, S Benelli, R Sforzini, S Giunciuglio, D Aluigi, MG Proudfoot, AEI Alouani, S Wells, TNC Mariani, G Rabin, RL Farber, JM Noonan, DM TI HIV-1 Tat protein mimicry of chemokines SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID FUNCTIONAL EXPRESSION; MOLECULAR-CLONING; HUMAN MONOCYTES; GROWTH-FACTOR; RECEPTOR; INFECTION; CCR5; TRANSDUCTION; CHEMOTAXIS; CYTOKINES AB The HIV-1 Tat protein is a potent chemoattractant for monocytes, We observed that Tat shows conserved amino acids corresponding to critical sequences of the chemokines, a family of molecules known for their potent ability to attract monocytes, Synthetic Tat and a peptide (CysL(24-51)) encompassing the "chemokine-like" region of Tat induced a rapid and transient Ca2+ influx in monocytes and macrophages, analogous to beta-chemokines, Both monocyte migration and Ca2+ mobilization were pertussis toxin sensitive and cholera toxin insensitive. Cross-desensitization studies indicated that Tat shares receptors with MCP-1, MCP-3, and eotaxin, Tat was able to displace binding of beta-chemokines from the beta-chemokine receptors CCR2 and CCR3, but not CCR1, CCR4, and CCR5, Direct receptor binding experiments with the CysL(24-51) peptide confirmed binding to cells transfected with CCR2 and CCR3. HIV-1 Tat appears to mimic beta-chemokine features, which may serve to locally recruit chemokine receptor-expressing monocytes/macrophages toward HIV producing cells and facilitate activation and infection. C1 Ist Nazl Ric Canc, Ctr Biotecnol Avanzate, I-16132 Genoa, Italy. Glaxo Wellcome Res & Dev Ltd, Geneva Biomed Res Inst, CH-1228 Geneva, Switzerland. Univ Genoa, Dipartimento Med Interna, I-16132 Genoa, Italy. NIAID, NIH, Bethesda, MD 20892 USA. RP Noonan, DM (reprint author), Ist Nazl Ric Canc, Ctr Biotecnol Avanzate, Largo Rosanna Benzi 10, I-16132 Genoa, Italy. RI Noonan, Douglas/A-8620-2010; OI Noonan, Douglas/0000-0001-8058-0719; Ferrini, Silvano/0000-0001-7254-2616 NR 37 TC 220 Z9 228 U1 0 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 27 PY 1998 VL 95 IS 22 BP 13153 EP 13158 DI 10.1073/pnas.95.22.13153 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 134RT UT WOS:000076757300079 PM 9789057 ER PT J AU Cervenakova, L Goldfarb, LG Garruto, R Lee, HS Gajdusek, DC Brown, P AF Cervenakova, L Goldfarb, LG Garruto, R Lee, HS Gajdusek, DC Brown, P TI Phenotype-genotype studies in kuru: Implications for new variant Creutzfeldt-Jakob disease SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID FATAL FAMILIAL INSOMNIA; FEATURES; GENE AB The PRNP polymorphic (methionine/valine) codon 129 genotype influences the phenotypic features of transmissible spongiform encephalopathy. All tested cases of new variant Creutzfeldt-Jakob disease (nvCJD) have been homozygous for methionine, and it is conjectural whether different genotypes, if they appear, might have distinctive phenotypes and implications for the future "epidemic curve" of nvCJD, Genotype-phenotype studies of kuru, the only other orally transmitted transmissible spongiform encephalopathy, might be instructive in predicting the answers to these questions. We therefore extracted DNA from blood clots or sera from 92 kuru patients, and analyzed their codon 129 PRNP genotypes with respect to the age at onset and duration of illness and, in nine cases, to detailed clinical and neuropathology data. Homozygosity at codon 129 (particularly for methionine) was associated with an earlier age at onset and a shorter duration of illness than was heterozygosity, but other clinical characteristics were similar for all genotypes. In the nine neuropathologically examined cases, the presence of histologically recognizable plaques was limited to cases carrying at least one methionine allele (three homozygotes and one heterozygote). If nvCJD behaves like kuru, future cases (with longer incubation periods) may begin to occur in older individuals with heterozygous codon 129 genotypes and signal a maturing evolution of the nvCJD "epidemic." The clinical phenotype of such cases should be similar to that of homozygous cases, but may have less (or at least less readily identified) amyloid plaque formation. C1 NINDS, Cent Nervous Syst Studies Lab, NIH, Bethesda, MD 20892 USA. NINDS, Med Neurol Branch, NIH, Bethesda, MD 20892 USA. Amer Red Cross, Jerome H Holland Lab, Rockville, MD 20855 USA. SUNY Binghamton, Dept Anthropol, Binghamton, NY 13902 USA. RP Brown, P (reprint author), NINDS, Cent Nervous Syst Studies Lab, NIH, Bldg 36,Room 5B20, Bethesda, MD 20892 USA. NR 15 TC 108 Z9 112 U1 1 U2 6 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 27 PY 1998 VL 95 IS 22 BP 13239 EP 13241 DI 10.1073/pnas.95.22.13239 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 134RT UT WOS:000076757300094 PM 9789072 ER PT J AU Lautens, LL Chiou, XG Sharp, JD Young, WS Sprague, DL Ross, LS Felder, CC AF Lautens, LL Chiou, XG Sharp, JD Young, WS Sprague, DL Ross, LS Felder, CC TI Cytosolic phospholipase A2 (cPLA2) distribution in murine brain and functional studies indicate that cPLA2 does not participate in muscarinic receptor-mediated signaling in neurons SO BRAIN RESEARCH LA English DT Article DE cPLA2; muscarinic receptor; signal transduction; arachidonic acid; oligodendrocyte; glia ID ARACHIDONIC-ACID RELEASE; HIPPOCAMPAL-NEURONS; A(2) ACTIVITY; STIMULATES PHOSPHOLIPASE-A2; MOLECULAR-CLONING; STRIATAL NEURONS; PRIMARY CULTURES; GENE-EXPRESSION; CELLS; ACTIVATION AB Cytosolic phospholipase A2 (cPLA2) catalyzes the selective release of arachidonic acid from the sn-2 position of membrane phospholipids and has been suggested as an effector in the receptor-mediated release of arachidonic acid in signal transduction. The potential role of cPLA2 as an effector in muscarinic acetylcholine receptor signaling was investigated through ectopic expression of either the mi or m5 receptor in combination with cPLA2 in COS-1, CHO and U-373 MG cell lines. U-373 MG and COS-1 cells express undetectable or very low levels of cPLA2. CHO cell extracts are characterized by a significant endogenous PLA2 activity that was increased over 20-fold following transient expression with cPLA2 cDNA. However, in none of the cells lines did the co-expression of muscarinic receptor and cPLA2 result in a significant increase in muscarinic receptor-mediated arachidonic acid release over cells expressing muscarinic receptor alone. The distribution of cPLA2 mRNA and cPLA2 immunoreactivity in murine brain were determined in order to investigate a potential role for cPLA2 in neurotransmission. cPLA2 mRNA was expressed in white matter, including cells contained within linear arrays characteristic of interfascicular oligodendrocytes. cPLA2 immunoreactivity in white matter was evident throughout the processes of fibrous astrocytes. cPLA2 expression in gray matter was confined to astrocytes at the pial surface of the brain. cPLA2 mRNA was detected in pia mater, both at the brain surface and inner core of the choroid plexus. cPLA2 may not be directly linked to neurotransmission since enzyme expression, mRNA, and cPLA2 immunoreactivity were undetectable in neurons of murine brain. Support or regulation of neurotransmission may be provided through the activity of cPLA2 in glial cells. (C) 1998 Elsevier Science B.V. All rights reserved. C1 Eli Lilly & Co, Lilly Corp Ctr, Eli Lilly Res Labs, Indianapolis, IN 46285 USA. Ohio Univ, Neurobiol Program, Dept Biol Sci, Athens, OH 45701 USA. NIMH, Lab Cellular & Mol Recognit, Bethesda, MD 20892 USA. RP Felder, CC (reprint author), Eli Lilly & Co, Lilly Corp Ctr, Eli Lilly Res Labs, Drop 0510, Indianapolis, IN 46285 USA. EM felder@lilly.com RI Young, W Scott/A-9333-2009 OI Young, W Scott/0000-0001-6614-5112 NR 52 TC 22 Z9 22 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD OCT 26 PY 1998 VL 809 IS 1 BP 18 EP 30 DI 10.1016/S0006-8993(98)00806-3 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 134BJ UT WOS:000076722700004 PM 9795110 ER PT J AU Clifford, JJ Tighe, O Croke, DT Drago, J Sibley, DR Waddington, JL AF Clifford, JJ Tighe, O Croke, DT Drago, J Sibley, DR Waddington, JL TI Behavioral topography to D-1-like and D-2-like agonists following D(1)A dopamine receptor knockout SO BRAIN RESEARCH LA English DT Meeting Abstract C1 Royal Coll Surg Ireland, Dept Clin Pharmacol, Dublin 2, Ireland. Royal Coll Surg Ireland, Dept Biochem, Dublin 2, Ireland. Monash Univ, Dept Anat, Clayton, Vic 3168, Australia. NINDS, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD OCT 26 PY 1998 VL 809 IS 1 MA P34 BP A24 EP A24 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 134BJ UT WOS:000076722700077 ER PT J AU Crawley, JN AF Crawley, JN TI Experimental design and evaluation of general health, sensory functions, motor abilities, and specific behavioral paradigms in transgenic and knockout mice SO BRAIN RESEARCH LA English DT Meeting Abstract C1 NIMH, Sect Behav Neuropharmacol, Expt Therapeut Branch, Bethesda, MD 20892 USA. NR 2 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD OCT 26 PY 1998 VL 809 IS 1 MA S31 BP A12 EP A13 PG 2 WC Neurosciences SC Neurosciences & Neurology GA 134BJ UT WOS:000076722700030 ER PT J AU Fletcher, CF Cleveland, LS Copeland, NG Jenkins, NA AF Fletcher, CF Cleveland, LS Copeland, NG Jenkins, NA TI Identification of the gene affected in the nervous mutant mouse SO BRAIN RESEARCH LA English DT Meeting Abstract C1 ABL Basic Res Program, NCIFCRDC, Ft Detrick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD OCT 26 PY 1998 VL 809 IS 1 MA P23 BP A22 EP A22 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 134BJ UT WOS:000076722700067 ER PT J AU McDonald, MP Wong, R Goldstein, G Weintraub, BD Cheng, SY Crawley, JN AF McDonald, MP Wong, R Goldstein, G Weintraub, BD Cheng, SY Crawley, JN TI Hyperactivity and learning deficits in mice bearing a mutant thyroid receptor gene SO BRAIN RESEARCH LA English DT Meeting Abstract C1 NIMH, Sect Behav Neuropharmacol, ETB, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD OCT 26 PY 1998 VL 809 IS 1 MA P314 BP A26 EP A27 PG 2 WC Neurosciences SC Neurosciences & Neurology GA 134BJ UT WOS:000076722700087 ER PT J AU Cohrs, S Tergau, F Riech, S Kastner, S Paulus, W Ziemann, U Ruther, E Hajak, G AF Cohrs, S Tergau, F Riech, S Kastner, S Paulus, W Ziemann, U Ruther, E Hajak, G TI High-frequency repetitive transcranial magnetic stimulation delays rapid eye movement sleep SO NEUROREPORT LA English DT Article DE depression; polysomnography; rapid eye movement sleep; REM sleep; repetitive transcranial ID PREFRONTAL CORTEX; MOTOR CORTEX; DEPRESSION; MOOD; DISORDERS AB REPETITIVE transcranial magnetic stimulation (rTMS) is a promising new treatment for patients with major depression. However, the mechanisms underlying the antidepressive action of rTMS are widely unclear. Rapid eye movement (REM) sleep has been shown to play an important role in the pathophysiology of depression. In the present study we demonstrate that rTMS delays the first REM sleep epoch on average by 17 min (102.6 +/- 22.5 min vs 85.7 +/- 18.8 min; p < 0.02) and prolongs the nonREM-REM cycle length (109.1 +/- 11.4 min vs 101.8 +/- 13.2 min, p < 0.012). These rTMS-induced changes in REM sleep variables correspond to findings observed after pharmacological and electroconvulsive treatment of depression. Therefore, it is likely that the capability of rTMS to affect circadian and ultradian biological rhythms contributes to its antidepressive action. (C) 1998 Lippincott Williams & Wilkins. C1 Univ Gottingen, Sleep Disorders Ctr, Dept Psychiat, D-37075 Gottingen, Germany. Univ Gottingen, Dept Clin Neurophysiol, Dept Psychiat, D-37075 Gottingen, Germany. NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA. NIMH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. NINDS, Human Cortex Physiol Unit, Bethesda, MD 20892 USA. RP Hajak, G (reprint author), Univ Gottingen, Sleep Disorders Ctr, Dept Psychiat, Von Siebold Str 5, D-37075 Gottingen, Germany. RI Paulus, Walter/A-3544-2009 OI Paulus, Walter/0000-0001-5549-8377 NR 32 TC 46 Z9 48 U1 5 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD OCT 26 PY 1998 VL 9 IS 15 BP 3439 EP 3443 DI 10.1097/00001756-199810260-00019 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 146MC UT WOS:000077432000019 PM 9855295 ER PT J AU Sherman, ME Schiffman, M Herrero, R Kelly, D Bratti, C Mango, LJ Alfaro, M Hutchinson, ML Mena, F Hildesheim, A Morales, J Greenberg, MD Balmaceda, I Lorincz, AT AF Sherman, ME Schiffman, M Herrero, R Kelly, D Bratti, C Mango, LJ Alfaro, M Hutchinson, ML Mena, F Hildesheim, A Morales, J Greenberg, MD Balmaceda, I Lorincz, AT TI Performance of a semiautomated Papanicolaou smear screening system - Results of a population-based study conducted in Guanacaste, Costa Rica SO CANCER CYTOPATHOLOGY LA English DT Article; Proceedings Paper CT 43rd Annual Meeting of the American-Society-of-Cytopathology CY NOV 07-12, 1995 CL NEW YORK, NEW YORK SP Amer Soc Cytopathol DE cervix; screening; human papillomavirus; automation; screening; PAPNET ID NEGATIVE CERVICAL SMEARS; PAPNET TESTING SYSTEM; QUALITY-CONTROL; CARCINOMA; EFFICACY; CYTOLOGY AB BACKGROUND, Automated cytology devices have utility in quality assurance applications, but the effectiveness of these devices in primary screening is unknown. METHODS. Enrollment smears obtained from 7323 women participating in a population-based study sponsored by the National Cancer Institute were screened manually in Costa Rica and then evaluated independently in the U.S. with the PAPNET system (Neuromedical Systems, Inc., Suffern, NY), a semiautomated, neural network-based device. Smears with abnormal PAPNET images were microscopically rescreened and then diagnosed by a U.S. cytopathologist. ThinPrep slides (Cytyc Corporation, Boxborough, MA), prepared from rinses of the cytologic sampler, and cervigrams (National Testing Laboratories, Fenton, MO) were also evaluated. Women with ally abnormal cytologic diagnosis or a positive cervigram were referred for colposcopy with biopsy and definitive therapy if indicated. RESULTS. Based on the U.S. cytotechnologist's review of the PAPNET images, 1017 (13.9%) of 7323 smears were selected for manual screening, resulting in the selection of 492 (6.7%) possibly abnormal slides for referral to the U.S. pathologist. Ultimately, 312 smears (4.3% of the total) were diagnosed as containing squamous cells of undetermined significance or a more severe abnormality (greater than or equal to ASCUS), resulting, hypothetically, in the referral of 66.5% of women with a final diagnosis of a squamous intraepithelial lesion or a more severe abnormality (greater than or equal to SIL) and 86.0% of patients with greater than or equal to high grade SIL. Conventional microscopic screening performed in Costa Rica resulted in the hypothetical :referral of 6.5% of patients with greater than or equal to ASCUS for colposcopy, including 69.5% of patients with greater than or equal to SIL and 79.8% of those with greater than or equal to high grade SIL. CONCLUSIONS. In this study, PAPNET-assisted cytologic screening accurately identified smears obtained from women with high grade SIL or carcinoma. Determination of the clinical cost-effectiveness of PAPNET-assisted screening in routine practice awaits future study. [See editorial on pages 269-72, this issue.] Cancer (Cancer Cytopathol) 1998;84:273-80. (C) 1998 American Cancer Society. C1 NCI, Div Canc Epidemiol & Genet, NIH, EEB, Bethesda, MD 20892 USA. Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21205 USA. Int Agcy Res Canc, F-69372 Lyon, France. Minist Salud, San Jose, Costa Rica. Neuromed Syst Inc, Suffern, NY USA. Caja Costarricense Seguro Social, San Jose, Costa Rica. Women & Infants Hosp Rhode Isl, Dept Pathol, Providence, RI 02908 USA. Omnia Corp, Philadelphia, PA USA. Digene Corp, Silver Spring, MD USA. RP Sherman, ME (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, EEB, Execut Plaza N,Room 443,6130 Execut Blvd, Bethesda, MD 20892 USA. FU NCI NIH HHS [N01-CP-31061, N01-CP-21081] NR 19 TC 34 Z9 34 U1 0 U2 1 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0008-543X J9 CANCER CYTOPATHOL JI Cancer Cytopathol. PD OCT 25 PY 1998 VL 84 IS 5 BP 273 EP 280 PG 8 WC Oncology; Pathology SC Oncology; Pathology GA 132FH UT WOS:000076619300002 PM 9801201 ER PT J AU De Bruijn, MLH Greenstone, HL Vermeulen, H Melief, CJM Lowy, DR Schiller, JT Kast, WM AF De Bruijn, MLH Greenstone, HL Vermeulen, H Melief, CJM Lowy, DR Schiller, JT Kast, WM TI L1-specific protection from tumor challenge elicited by HPV16 virus-like particles SO VIROLOGY LA English DT Article ID HUMAN PAPILLOMAVIRUS TYPE-16; MONOCLONAL-ANTIBODIES; L1; ANTIGEN; ERADICATION; IMMUNITY; HPV-16; REGION; CELLS; GENE AB A single injection of HPV16 L1 virus-like particles induced potent CD8-mediated protection from tumor challenge by C3 cells, a line derived from embryonic mouse cells transfected with the HPV16 genome. L1 RNA, but not protein, was detected biochemically in C3 cells. These results indicate that low-level expression of HPV16 L1 can occur in proliferating cells and serve as a tumor vaccine target. Although L1 expression is generally thought to be restricted to terminally differentiated epithelial cells, these results suggest that additional analysis for low-level L1 expression in proliferating cells of HPV-induced lesions is warranted and might help in predicting the clinical potential of HPV L1 virus-like particle-based vaccines. (C) 1998 Academic Press C1 NIH, Cellular Oncol Lab, Bethesda, MD 20892 USA. Leiden Univ Hosp, Dept Immunohaematol, NL-2300 RC Leiden, Netherlands. Leiden Univ Hosp, Blood Bank, NL-2300 RC Leiden, Netherlands. Loyola Univ, Cardinal Bernardin Canc Ctr, Maywood, IL 60153 USA. RP Kast, WM (reprint author), Loyola Univ, Cardinal Bernardin Canc Ctr, 2160 S First Ave, Maywood, IL 60153 USA. FU NCI NIH HHS [R01-CA74397, P01-CA74182] NR 23 TC 53 Z9 54 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD OCT 25 PY 1998 VL 250 IS 2 BP 371 EP 376 DI 10.1006/viro.1998.9372 PG 6 WC Virology SC Virology GA 132VV UT WOS:000076652100012 PM 9792847 ER PT J AU Senkevich, TG Moss, B AF Senkevich, TG Moss, B TI Domain structure, intracellular trafficking, and beta 2-microglobulin binding of a major histocompatibility complex class I homolog encoded by molluscum contagiosum virus SO VIROLOGY LA English DT Article ID NATURAL-KILLER-CELLS; BACTERIOPHAGE-T7 RNA-POLYMERASE; VACCINIA VIRUS; HUMAN CYTOMEGALOVIRUS; TRANSMEMBRANE DOMAIN; BREFELDIN-A; EXPRESSION; ANTIGENS; MOLECULES; SEQUENCE AB The MC80R gene of molluscum contagiosum virus (MCV) type 1 encodes a major histocompatibility complex (MHC) class I homolog that lacks several amino-acid residues critical for peptide binding by MHC molecules, contains an unusually long N-terminal hydrophobic domain possibly derived by triplication of a signal peptide, and has a C-terminal transmembrane domain with two glutamate residues. All of these features were present in the orthologous gene of MCV type 2. The MC80R gene was expressed as two glycosylated polypeptides of Mr 47,000 and 42,000. Pulse-chase experiments indicated that the larger polypeptide was a precursor of the shorter one and that the entire N-terminal domain was slowly removed, consistent with its function as a long signal peptide. The protein was largely sequestered in the endoplasmic reticulum and Golgi membranes, remained endoglycosidase-H sensitive, and was not detected on the cell surface. In addition, a genetically modified form of the MC80R protein lacking the transmembrane and cytoplasmic domains was not secreted. The roles of the MC80R protein domains were investigated by constructing chimera between the viral protein and the MHC class I protein HLA-A2. Expression studies confirmed that the N- and C-terminal hydrophobic regions of the MC80R protein served as signal and transmembrane domains, respectively. The central portion of the MC80R protein, corresponding to the alpha 1-alpha 3 extracellular domains of HLA-A2, was largely responsible for sequestering the protein in the endoplasmic reticulum or Golgi compartments. The MC80R protein, as well as HLA-A2 chimera with the central region of MG80R, formed stable intracellular complexes with beta 2-microglobulin. Complex formation, however, was detected only by overexpression of the MC80R protein or beta 2-microglobulin. C1 NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. RP Moss, B (reprint author), NIAID, Viral Dis Lab, NIH, 4 Ctr Dr,MSC 0445, Bethesda, MD 20892 USA. NR 42 TC 34 Z9 34 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD OCT 25 PY 1998 VL 250 IS 2 BP 397 EP 407 DI 10.1006/viro.1998.9390 PG 11 WC Virology SC Virology GA 132VV UT WOS:000076652100015 PM 9792850 ER PT J AU Thorlacius, S Struewing, JP Hartge, P Olafsdottir, GH Sigvaldason, H Tryggvadottir, L Wacholder, S Tulinius, H Eyfjord, JE AF Thorlacius, S Struewing, JP Hartge, P Olafsdottir, GH Sigvaldason, H Tryggvadottir, L Wacholder, S Tulinius, H Eyfjord, JE TI Population-based study of risk of breast cancer in carriers of BRCA2 mutation SO LANCET LA English DT Article ID ASHKENAZI-JEWISH INDIVIDUALS; OVARIAN-CANCER; GERMLINE MUTATIONS; GENE; FREQUENCY; FAMILIES; ICELAND; JEWS AB Background Estimates of an 80-90% risk of breast cancer for carriers of germline mutations in the BRCA1 and BRCA2 genes are based on studies of families at high risk of breast cancer. Risk estimates for a population are possible if the mutation status of a representative sample of that population can be assessed. In Iceland, one common founder BRCA2 mutation occurs in 0.6% of the population. Iceland has a population-based cancer registry and a large collection of pedigrees, and estimation of cancer risk in mutation carriers is therefore possible. Methods We studied 575 breast-cancer patients, 541 women and 34 men unselected for family history of breast cancer. Data on cancer in first-degree relatives were available from the cancer registry. Risk of cancer was estimated by comparing the history of cancer in first-degree relatives of carriers and non-carriers. Findings 56 (10.4%) of the 541 women and 13 (38%) of the 34 men carried the 999del5 mutation. The estimated risk of breast cancer at age 50 for all female carriers of the 999de15 mutation was 17.0% (95% CI 9.1-25.9) and 37.2%(22.4-53.9) at age 70. Interpretation The results of our population-based study show that the mean risk of breast cancer in carriers of mutation in BRCA2 is lower than previously suggested. Individual risk assessment will, however, have to take account of family history. C1 Iceland Canc Soc, Mol & Cell Biol Res Lab, Reykjavik, Iceland. Iceland Canc Soc, Iceland Canc Registry, Reykjavik, Iceland. NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. RP Eyfjord, JE (reprint author), Iceland Canc Soc, Mol & Cell Biol Res Lab, Reykjavik, Iceland. RI Struewing, Jeffery/C-3221-2008; Struewing, Jeffery/I-7502-2013 OI Struewing, Jeffery/0000-0002-4848-3334 NR 25 TC 248 Z9 251 U1 1 U2 8 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON WC1B 3SL, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD OCT 24 PY 1998 VL 352 IS 9137 BP 1337 EP 1339 DI 10.1016/S0140-6736(98)03300-5 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 133NB UT WOS:000076691700010 PM 9802270 ER PT J AU Ko, KWS McLeod, RS Avramoglu, RK Nimpf, J FitzGerald, DJ Vukmirica, J Yao, ZM AF Ko, KWS McLeod, RS Avramoglu, RK Nimpf, J FitzGerald, DJ Vukmirica, J Yao, ZM TI Mutation at the processing site of chicken low density lipoprotein receptor-related protein impairs efficient endoplasmic reticulum exit, but proteolytic cleavage is not essential for its endocytic functions SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ALPHA-2-MACROGLOBULIN RECEPTOR; PSEUDOMONAS EXOTOXIN; MOLECULAR CHAPERONE; 39-KDA PROTEIN; LRP; BINDING; IDENTIFICATION; CALCIUM; LIGANDS; SUGGEST AB The low density lipoprotein receptor-related protein (LRP) is synthesized as a proreceptor that undergoes post-translational proteolytic processing yielding a noncovalently associated alpha beta dimer as the mature LRP. We tested the role of processing by creating a mutant in which the P1 residue (Arg(3942)) of the consensus site for furin cleavage (Arg-Asn-Arg-Arg(3942)down arrow) was replaced with Ser in chicken LRP, Transfection of the mutant LRP (designated LRP-RS) into a Chinese hamster ovary cell line lacking endogenous LRP resulted in expression of the unprocessed full-length proreceptor. Comparison of cell lines stably expressing either the wild-type LRP (LRP-wt) or the unprocessed LRP-RS showed that at comparable expression levels, both receptors restored the sensitivity of cellular protein synthesis to Pseudomonas exotoxin A (IC50 = 25 ng/ml). Subcellular fractionation and neuraminidase treatment showed that both LRP forms were transported to the plasma membrane. In addition, LRP-RS exhibited kinetics of binding, endocytosis, and degradation of methylamine-activated alpha(2)-macroglobulin that were identical to those of LRP-wt, The internalization rate constant was similar for LRP-wt (K-e = 0.259 min(-1)) and mutant LRP-RS (K-e = 0.252 min(-1)), suggesting that it takes about 4 min for the entire surface LRP pool to be internalized. Sorting of LRP from the endosomal compartment to lysosomes or recycling to the plasma membrane were also unaltered in mutant LRP-RS, Pulse-chase analysis showed that the lack of processing of LRP had no effect on the stability of its post-endoplasmic reticulum form or on the rate of its intracellular transit from the endoplasmic reticulum to the Golgi apparatus. However, the exit of mutant LRP from the endoplasmic reticulum was retarded by the Arg(3942)-to-Ser substitution, as evidenced by prolonged retention within the endoplasmic reticulum (t(1/2) = 4 h for LRP-wt and t(1/2) > 13 h for LRP-RS). C1 Univ Ottawa, Inst Heart, Lipoprot & Atherosclerosis Grp, Ottawa, ON K1Y 4W7, Canada. Univ Vienna, A-1010 Vienna, Austria. Bioctr, Dept Mol Genet, Vienna, Austria. NCI, Mol Biol Lab, NIH, Div Canc Biol Diag & Ctr, Bethesda, MD 20892 USA. RP Yao, ZM (reprint author), Univ Ottawa, Inst Heart, Lipoprot & Atherosclerosis Grp, 40 Ruskin St, Ottawa, ON K1Y 4W7, Canada. EM zyao@heartinst.on.ca RI McLeod, Roger/F-8014-2015 OI McLeod, Roger/0000-0002-6740-5569 NR 32 TC 22 Z9 22 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 23 PY 1998 VL 273 IS 43 BP 27779 EP 27785 DI 10.1074/jbc.273.43.27779 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 130ZD UT WOS:000076549800006 PM 9774386 ER PT J AU Shields, MJ Kubota, R Hodgson, W Jacobson, S Biddison, WE Ribaudo, RK AF Shields, MJ Kubota, R Hodgson, W Jacobson, S Biddison, WE Ribaudo, RK TI The effect of human beta(2)-microglobulin on major histocompatibility complex I peptide loading and the engineering of a high affinity variant - Implications for peptide-based vaccines SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID T-LYMPHOCYTE EPITOPES; TRANSGENIC MICE; MHC MOLECULES; CELL-SURFACE; DNA VACCINES; HAPLOTYPE FREQUENCIES; ENDOGENOUS PEPTIDES; MATRIX PEPTIDE; VIABLE CELLS; HLA GENE AB The ability to directly load cell surface major histocompatibility complex (MHC) class I molecules with peptides provides a potentially powerful approach toward the development of vaccines to generate cell-mediated immunity. We demonstrate that exogenous beta(2)-microglobulin (beta(2)m) stabilizes human cell surface MHC I molecules and facilitates their loading with exogenous peptides, Additionally, using three-dimensional crystal structures and known interaction sites between MHC I heavy chains and beta(2)m, we engineered variants of human beta(2)m (h beta(2)m) with a single serine substitution at residue 55, This alteration was predicted to promote hydrophobic interactions at the MHC I heavy chain/beta(2)m interface and displace an ordered water molecule. Compared with h beta(2)m, the serine to valine substitution at residue 55 had improved ability to bind to cell surface HLA-A1, HLA-A2, and HLA-A3 molecules, facilitate exogenous peptide loading, and promote recognition by peptide-specific T cells. The inclusion of h beta(2)m or higher affinity variants when pulsing cells with MHC-restricted peptides increases the efficiency of peptide loading 50-80-fold. Therefore, the inclusion of h beta(2)m in peptide-based vaccines may increase cell surface antigen densities above thresholds that allow recognition of peptide antigens by the immune system, particularly for cryptic, subdominant, or marginally antigenic peptides. C1 NCI, Lab Immune Cell Biol, NIH, Bethesda, MD 20892 USA. NINDS, Neuroimmunol Branch, Bethesda, MD 20892 USA. RP Ribaudo, RK (reprint author), Mol Applicat Grp, 11800 Dewey Rd, Silver Spring, MD 20906 USA. RI Kubota, Ryuji/A-7139-2009 NR 74 TC 21 Z9 25 U1 1 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 23 PY 1998 VL 273 IS 43 BP 28010 EP 28018 DI 10.1074/jbc.273.43.28010 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 130ZD UT WOS:000076549800036 PM 9774416 ER PT J AU Eder, AM Dominguez, L Franke, TF Ashwell, JD AF Eder, AM Dominguez, L Franke, TF Ashwell, JD TI Phosphoinositide 3-kinase regulation of T cell receptor-mediated interleukin-2 gene expression in normal T cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-KINASE-B; GLYCOGEN-SYNTHASE KINASE-3; PHOSPHATIDYLINOSITOL 3-KINASE; IL-2 GENE; SIGNAL-TRANSDUCTION; BOVINE BRAIN; ACTIVATION; WORTMANNIN; AKT; INHIBITION AB Phosphoinositide (PI) 3-kinase has been implicated in T cell receptor (TCR) signaling, either as a positive or a negative regulatory molecule. Here, we show that for normal mouse lymph node T cells, PI 3-kinase activity is required for interleukin-2 (IL-2) production following TCR-mediated activation. Furthermore, in normal T cells, inhibition of PI 3-kinase prevented activation of enzymes in the extracellular signal-regulated protein kinase (ERK) signaling pathway (MEK-1 and ERK-2). Overexpression of a dominant-negative mutant of PI 3-kinase and pharmacological inhibitors of PI 3-kinase prevented transcriptional activation of AP-1 and NF-AT, transcription factors regulated by ERK-2 and pivotal for IL-2 gene expression. Although a constitutively active form of Akt kinase, a downstream mediator of PI 3-kinase function, enhanced TCR-induced IL-2 gene transcription, it could not bypass the requirement for PI 3-kinase activity. Therefore, PI 3-kinase is likely to be involved in signaling for IL-2 production in at least two steps in the TCR-initiated signaling pathway. C1 NCI, Lab Immune Cell Biol, NIH, Bethesda, MD 20892 USA. Univ Santiago de Compostela, Dept Biochem & Mol Biol, Santiago De Compostela 15706, Spain. Columbia Univ, Dept Pharmacol, New York, NY 10032 USA. RP Ashwell, JD (reprint author), NCI, Lab Immune Cell Biol, NIH, Bldg 10,Rm 1B40, Bethesda, MD 20892 USA. NR 50 TC 59 Z9 61 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 23 PY 1998 VL 273 IS 43 BP 28025 EP 28031 DI 10.1074/jbc.273.43.28025 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 130ZD UT WOS:000076549800038 PM 9774418 ER PT J AU Bowman, EP Campbell, JJ Druey, KM Scheschonka, A Kehrl, JH Butcher, EC AF Bowman, EP Campbell, JJ Druey, KM Scheschonka, A Kehrl, JH Butcher, EC TI Regulation of chemotactic and proadhesive responses to chemoattractant receptors by RGS (Regulator of G-protein Signaling) family members SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GTPASE-ACTIVATING PROTEINS; FORMYL PEPTIDE RECEPTOR; FUNCTIONAL EXPRESSION; CHEMOKINE RECEPTORS; LEUKOCYTE ADHESION; COUPLED RECEPTORS; TRANSITION-STATE; GENE-EXPRESSION; ALPHA-SUBUNITS; LYMPHOID-CELLS AB Serpentine G alpha(i)-linked receptors support rapid adhesion and directed migration of leukocytes and other cell types. The intracellular mechanisms mediating and regulating chemoattractant-directed adhesion and locomotion are only now beginning to be explored. RGS (for regulator of G-protein signaling) proteins are a recently described family that regulate G alpha(i)-stimulated pathways by acting as GTPase-activating proteins. Little is known about the GTPase activity of the G alpha(i) proteins involved in adhesion and chemotaxis, or the significance of their regulation to these responses. Using transiently transfected lymphoid cells as a model system, we show that expression of RGS1, RGS3, and RGS4 inhibits chemoattractant-induced migration. In contrast, RGS2, a regulator of G alpha(q) activity, had no effect on cell migration to any chemoattractant. RGS1, RGS3, and RGS4 also reduced rapid chemoattractant-triggered adhesion, although the proadhesive response appears quantitatively less sensitive to RGS action than chemotaxis, The results suggest that the duration of the G alpha(i) signal may be a particularly important parameter in the chemotactic responses of leukocytes, and demonstrate the potential for RGS family members to regulate cellular adhesive and migratory behaviors. C1 Stanford Univ, Sch Med, Dept Pathol, Lab Immunol & Vasc Biol, Stanford, CA 94305 USA. Stanford Univ, Sch Med, Ctr Digest Dis, Dept Med, Stanford, CA 94305 USA. Dept Vet Affairs, Palo Alto Hlth Care Syst, Foothill Res Ctr, Ctr Mol Biol & Med, Palo Alto, CA 94305 USA. NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. RP Butcher, EC (reprint author), Stanford Univ, Sch Med, Dept Pathol, Lab Immunol & Vasc Biol, Stanford, CA 94305 USA. OI Kehrl, John/0000-0002-6526-159X FU NCI NIH HHS [5T32CA090302]; NIDDK NIH HHS [DK38707]; NIGMS NIH HHS [GM56527] NR 63 TC 101 Z9 104 U1 1 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 23 PY 1998 VL 273 IS 43 BP 28040 EP 28048 DI 10.1074/jbc.273.43.28040 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 130ZD UT WOS:000076549800040 PM 9774420 ER PT J AU Sowka, S Hsieh, LS Krebitz, M Akasawa, A Martin, BM Starrett, D Peterbauer, CK Scheiner, O Breiteneder, H AF Sowka, S Hsieh, LS Krebitz, M Akasawa, A Martin, BM Starrett, D Peterbauer, CK Scheiner, O Breiteneder, H TI Identification and cloning of Prs a 1, a 32-kDa endochitinase and major allergen of avocado, and its expression in the yeast Pichia pastoris SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NATURAL-RUBBER LATEX; ANTIFUNGAL ACTIVITY; HEVEA-BRASILIENSIS; IGE-BINDING; CHITINASES; PLANT; HYPERSENSITIVITY; PATHOGENS; SEQUENCE; PROTEINS AB Avocado, the fruit of the tropical tree Persea americana, is a source of allergens that can elicit diverse IgE-mediated reactions including anaphylaxis in sensitized individuals. We characterized a 32-kDa major avocado allergen, Prs a 1, which is recognized by 15 out of 20 avocado- and/or latex-allergic patients. Natural Prs a 1 was purified, and its N-terminal and two tryptic peptide sequences were determined. We isolated the Prs al encoding cDNA by PCR using degenerate primers and 5'-rapid amplification of cDNA ends. The Prs a 1 cDNA coded for an endochitinase of 326 amino acids with a leader peptide of 25 amino acids. We expressed Prs a 1 in the yeast Pichia pastoris at 50 mg/liter of culture medium. The recombinant Prs a I showed endochitinase activity, inhibited growth and branching of Fusarium oxysporum hyphae, and possessed IgE binding capacity. IgE cross-reactivity with latex proteins including a 20-kDa allergen, most likely prohevein, was demonstrated, providing an explanation for the commonly observed cross-sensitization between avocado and latex proteins. Sequence comparison showed that Prs a 1 and prohevein had 70% similarity in their chitin-binding domains. Characterization of chitinases as allergens has implications for engineering transgenic crops with increased levels of chitinases. C1 Univ Vienna, Dept Gen & Expt Pathol, A-1090 Vienna, Austria. Div Oncol Drug Prod, Rockville, MD 20852 USA. Natl Childrens Hosp, Dept Allergy, Setagaya Ku, Tokyo 154, Japan. NIMH, Clin Neurosci Branch, Unit Mol Struct, Bethesda, MD 20892 USA. SE Missouri State Univ, Dept Biol, Cape Girardeau, MO 63701 USA. RP Breiteneder, H (reprint author), Univ Vienna, Dept Gen & Expt Pathol, AKH-EBO-3Q,Waehringer Guertel 18-20, A-1090 Vienna, Austria. EM Heimo.Breiteneder@akh-mien.ac.at RI Moussa, Luciana /M-2257-2013 NR 39 TC 67 Z9 70 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 23 PY 1998 VL 273 IS 43 BP 28091 EP 28097 DI 10.1074/jbc.273.43.28091 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 130ZD UT WOS:000076549800047 PM 9774427 ER PT J AU Negrusz, A Moore, CM McDonagh, NS Woods, EF Crowell, JA Levine, BS AF Negrusz, A Moore, CM McDonagh, NS Woods, EF Crowell, JA Levine, BS TI Determination of phenethylamine, a phenethyl isothiocyanate marker, in dog plasma using solid-phase extraction and gas chromatography mass spectrometry with chemical ionization SO JOURNAL OF CHROMATOGRAPHY B LA English DT Article DE phenethylamine; phenethyl isothiocyanate ID 4-(METHYLNITROSAMINO)-1-(3-PYRIDYL)-1-BUTANONE; MICE; RAT AB Phenethyl isothiocyanate is unstable in aqueous media and at low pH, and rapidly degrades to phenethylamine. Concentrations of phenethylamine, a phenethyl isothiocyanate marker, in dog plasma, were determined utilizing solid-phase extraction and gas chromatography-mass spectrometry with chemical ionization using acetone as the reagent gas. Deuterated d(5)-amphetamine was used as an internal standard. After extraction, phenethylamine and d(5)-amphetamine were derivatized using MBHFBA. Ions monitored for d(5)-amphetamine were mit 337 and 338; and for phenethylamine were m/z 318 and 319. Precision and accuracy were studied using control solutions prepared in naive dog plasma (80 and 300 ng/ml). Intra-day variability was determined using six replicates of each control solution analyzed on a single day. The relative standard deviation for the 80 ng/ml control was 12.9% and for the 300 ng/ml it was 12.1%. Relative accuracy was 10.9% for the low control and -4.1% for the high control. Inter-day variability was determined over a 6-day period. For the 80 and 300 ng/ml control solutions, the relative standard deviations were 15.8 and 9.1%, respectively, and relative accuracy values were 10.1 and -5.2%, respectively. Standard curves were prepared in naive dog plasma and were linear over the range of phenethylamine assayed (10-500 ng/ml). The results of this study indicate that the proposed method is simple, precise, accurate and sensitive enough for analysis of large numbers of plasma samples. (C) 1998 Elsevier Science B.V. All rights reserved. C1 Univ Illinois, Coll Pharm, Dept Pharmaceut & Pharmacodynam MC 865, Chicago, IL 60612 USA. US Drug Testing Labs Inc, Des Plaines, IL 60018 USA. NCI, Div Canc Prevent & Control, Bethesda, MD 20892 USA. Univ Illinois, Coll Med, Dept Pharmacol, Toxicol Res Lab, Chicago, IL 60612 USA. RP Negrusz, A (reprint author), Univ Illinois, Coll Pharm, Dept Pharmaceut & Pharmacodynam MC 865, 833 S Wood St, Chicago, IL 60612 USA. FU NCI NIH HHS [N01-CN-25508-01] NR 12 TC 5 Z9 7 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-4347 J9 J CHROMATOGR B JI J. Chromatogr. B PD OCT 23 PY 1998 VL 718 IS 1 BP 193 EP 198 DI 10.1016/S0378-4347(98)00354-5 PG 6 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 135CF UT WOS:000076782000023 PM 9832376 ER PT J AU Weinstein, JN AF Weinstein, JN TI Fishing expeditions SO SCIENCE LA English DT Letter C1 NCI, Bethesda, MD 20892 USA. RP Weinstein, JN (reprint author), NCI, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 3 TC 21 Z9 23 U1 0 U2 0 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD OCT 23 PY 1998 VL 282 IS 5389 BP 628 EP 629 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 132AM UT WOS:000076607500021 PM 9841413 ER PT J AU Collins, FS Patrinos, A Jordan, E Chakravarti, A Gesteland, R Walters, L Fearon, E Hartwelt, L Langley, CH Mathies, RA Olson, M Pawson, AJ Pollard, T Williamson, A Wold, B Buetow, K Branscomb, E Capecchi, M Church, G Garner, H Gibbs, RA Hawkins, T Hodgson, K Knotek, M Meisler, M Rubin, GM Smith, LM Smith, RF Westerfield, M Clayton, EW Fisher, NL Lerman, CE McInerney, JD Nebo, W Press, N Valle, D AF Collins, FS Patrinos, A Jordan, E Chakravarti, A Gesteland, R Walters, L Fearon, E Hartwelt, L Langley, CH Mathies, RA Olson, M Pawson, AJ Pollard, T Williamson, A Wold, B Buetow, K Branscomb, E Capecchi, M Church, G Garner, H Gibbs, RA Hawkins, T Hodgson, K Knotek, M Meisler, M Rubin, GM Smith, LM Smith, RF Westerfield, M Clayton, EW Fisher, NL Lerman, CE McInerney, JD Nebo, W Press, N Valle, D CA DOE Grp NIH Grp TI New goals for the US Human Genome Project: 1998-2003 SO SCIENCE LA English DT Review AB The Human Genome Project has successfully completed all the major goals in its current 5-year plan, covering the period 1993-98. A new plan, for 1998-2003, is presented, in which human DNA sequencing will be the major emphasis. An ambitious schedule has been set to complete the full sequence by the end of 2003, 2 years ahead of previous projections. In the course of completing the sequence, a "working draft" of the human sequence will be produced by the end of 2001. The plan also includes goals for sequencing technology development; for studying human genome sequence variation; for developing technology for functional genomics; for completing the sequence of Caenorhabditis elegans and Drosophila melanogaster and starting the mouse genome; for studying the ethical, Legal, and social implications of genome research; for bioinformatics and computational studies; and for training of genome scientists. C1 Natl Human Genome Res Inst, NIH, Bethesda, MD 20892 USA. US DOE, Off Biol & Environm Res, Washington, DC 20585 USA. Case Western Reserve Univ, Dept Genet, Cleveland, OH 44106 USA. Case Western Reserve Univ, Ctr Human Genet, Cleveland, OH 44106 USA. Univ Hosp Cleveland, Cleveland, OH 44106 USA. Univ Utah, Howard Hughes Med Inst, Salt Lake City, UT 84112 USA. Georgetown Univ, Kennedy Inst Eth, Washington, DC 20057 USA. RP Collins, FS (reprint author), Natl Human Genome Res Inst, NIH, Bethesda, MD 20892 USA. EM fc23a@nih.gov NR 8 TC 569 Z9 614 U1 3 U2 34 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD OCT 23 PY 1998 VL 282 IS 5389 BP 682 EP 689 DI 10.1126/science.282.5389.682 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 132AM UT WOS:000076607500040 PM 9784121 ER PT J AU Deloukas, P Schuler, GD Gyapay, G Beasley, EM Soderlund, C Rodriguez-Tome, P Hui, L Matise, TC McKusick, KB Beckmann, JS Bentolila, S Bihoreau, MT Birren, BB Browne, J Butler, A Castle, AB Chiannilkulchai, N Clee, C Day, PJR Dehejia, A Dibling, T Drouot, N Duprat, S Fizames, C Fox, S Gelling, S Green, L Harrison, P Hocking, R Holloway, E Hunt, S Keil, S Lijnzaad, P Louis-Dit-Sully, C Ma, J Mendis, A Miller, J Morissette, J Muselet, D Nusbaum, HC Peck, A Rozen, S Simon, D Slonim, DK Staples, R Stein, LD Stewart, EA Suchard, MA Thangarajah, T Vega-Czarny, N Webber, C Wu, X Hudson, J Auffray, C Nomura, N Sikela, JM Polymeropoulos, MH James, MR Lander, ES Hudson, TJ Myers, RM Cox, DR Weissenbach, J Boguski, MS Bentley, DR AF Deloukas, P Schuler, GD Gyapay, G Beasley, EM Soderlund, C Rodriguez-Tome, P Hui, L Matise, TC McKusick, KB Beckmann, JS Bentolila, S Bihoreau, MT Birren, BB Browne, J Butler, A Castle, AB Chiannilkulchai, N Clee, C Day, PJR Dehejia, A Dibling, T Drouot, N Duprat, S Fizames, C Fox, S Gelling, S Green, L Harrison, P Hocking, R Holloway, E Hunt, S Keil, S Lijnzaad, P Louis-Dit-Sully, C Ma, J Mendis, A Miller, J Morissette, J Muselet, D Nusbaum, HC Peck, A Rozen, S Simon, D Slonim, DK Staples, R Stein, LD Stewart, EA Suchard, MA Thangarajah, T Vega-Czarny, N Webber, C Wu, X Hudson, J Auffray, C Nomura, N Sikela, JM Polymeropoulos, MH James, MR Lander, ES Hudson, TJ Myers, RM Cox, DR Weissenbach, J Boguski, MS Bentley, DR TI A physical map of 30,000 human genes SO SCIENCE LA English DT Article ID EXPRESSED SEQUENCE TAGS; RADIATION HYBRID MAP; OPEN-ANGLE GLAUCOMA; HOLT-ORAM SYNDROME; HUMAN GENOME; POSITIONAL CLONING; MUTATIONS; HOMOLOGY; IDENTIFICATION; PROTEIN AB A map of 30,181 human gene-based markers was assembled and integrated with the current genetic map by radiation hybrid mapping. The new gene map contains nearly twice as many genes as the previous release, includes most genes that encode proteins of known function, and is twofold to threefold more accurate than the previous version. A redesigned, more informative and functional World Wide Web site (www.ncbi.nlm.nih.gov/genemap) provides the mapping information and associated data and annotations. This resource constitutes an important infrastructure and tool for the study of complex genetic traits, the positional cloning of disease genes, the cross-referencing of mammalian genomes, and validated human transcribed sequences for Large-scale studies of gene expression. C1 Sanger Ctr, Cambridge CB10 1SA, England. Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. CNRS, URA 1922, F-91000 Evry, France. Stanford Univ, Sch Med, Stanford Human Genome Ctr, Dept Genet, Stanford, CA 94305 USA. European Bioinformat Inst, European Mol Biol Lab Outstn, Cambridge CB10 1SD, England. MIT, Whitehead Inst Biomed Res, Ctr Genome Res, Cambridge Ctr 9, Cambridge, MA 02142 USA. Rockefeller Univ, Lab Stat Genet, New York, NY 10021 USA. Genethon, CNRS, URA 1922, F-91000 Evry, France. Univ Oxford, Nuffield Dept Clin Med, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England. NIH, Lab Genet Dis Res, Natl Ctr Human Genome Res, Bethesda, MD 20892 USA. CHU Laval, Ctr Rech, Quebec City, PQ G1V 4G2, Canada. Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA. Univ Calif Los Angeles, Sch Med, Dept Biomath, Los Angeles, CA 90095 USA. Res Genet, Huntsville, AL 35801 USA. CNRS, UPR 420, F-94801 Villejuif, France. Kazusa DNA Res Inst, Chiba 292, Japan. Univ Colorado, Hlth Sci Ctr, Dept Pharmacol, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Program Mol Biol, Denver, CO 80262 USA. MIT, Dept Biol, Cambridge, MA 02142 USA. McGill Univ, Montreal Gen Hosp, Res Inst, Montreal, PQ H3G 1A4, Canada. RP Deloukas, P (reprint author), Sanger Ctr, Hixton Hall, Cambridge CB10 1SA, England. RI Beckmann, Jacques S /A-9772-2008; Deloukas, Panos/B-2922-2013; OI Beckmann, Jacques S /0000-0002-9741-1900; Deloukas, Panos/0000-0001-9251-070X; Hudson, Thomas/0000-0002-1376-4849; Rozen, Steven G./0000-0002-4288-0056 FU Wellcome Trust NR 45 TC 544 Z9 557 U1 1 U2 15 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD OCT 23 PY 1998 VL 282 IS 5389 BP 744 EP 746 DI 10.1126/science.282.5389.744 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 132AM UT WOS:000076607500051 PM 9784132 ER PT J AU Stephens, RS Kalman, S Lammel, C Fan, J Marathe, R Aravind, L Mitchell, W Olinger, L Tatusov, RL Zhao, QX Koonin, EV Davis, RW AF Stephens, RS Kalman, S Lammel, C Fan, J Marathe, R Aravind, L Mitchell, W Olinger, L Tatusov, RL Zhao, QX Koonin, EV Davis, RW TI Genome sequence of an obligate intracellular pathogen of humans: Chlamydia trachomatis SO SCIENCE LA English DT Article ID ESCHERICHIA-COLI; OUTER-MEMBRANE; HAEMOPHILUS-INFLUENZAE; PHOSPHOLIPID SYNTHASES; PROTEIN SEQUENCES; PSITTACI; GENE; CELLS; IDENTIFICATION; SYNTHETASE AB Analysis of the 1,042,519-base pair Chlamydia trachomatis genome revealed unexpected features related to the complex biology of chlamydiae. Although chlamydiae lack many biosynthetic capabilities, they retain functions for performing key steps and interconversions of metabolites obtained from their mammalian host cells. Numerous potential virulence-associated proteins also were characterized. Several eukaryotic chromatin-associated domain proteins were identified, suggesting a eukaryotic-like mechanism for chlamydial nucleoid condensation and decondensation. The phylogenetic mosaic of chlamydial genes, including a Large number of genes with phylogenetic origins from eukaryotes, implies a complex evolution for adaptation to obligate intracellular parasitism. C1 Univ Calif Berkeley, Program Infect Dis, Berkeley, CA 94720 USA. Univ Calif San Francisco, Francis I Proctor Fdn, San Francisco, CA 94143 USA. Stanford Univ, DNA Sequencing & Technol Ctr, Stanford, CA 94305 USA. NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP Stephens, RS (reprint author), Univ Calif Berkeley, Program Infect Dis, Berkeley, CA 94720 USA. RI Mitchell, Wayne/C-5219-2008 FU NIAID NIH HHS [AI 39258] NR 53 TC 1037 Z9 1479 U1 9 U2 54 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD OCT 23 PY 1998 VL 282 IS 5389 BP 754 EP 759 DI 10.1126/science.282.5389.754 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 132AM UT WOS:000076607500055 PM 9784136 ER PT J AU Carpenter, MA Appel, MJG Roelke-Parker, ME Munson, L Hofer, H East, M O'Brien, SJ AF Carpenter, MA Appel, MJG Roelke-Parker, ME Munson, L Hofer, H East, M O'Brien, SJ TI Genetic characterization of canine distemper virus in Serengeti carnivores SO VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY LA English DT Article; Proceedings Paper CT 2nd International Feline Immunology Workshop CY AUG 01-03, 1997 CL UNIV CALIFORNIA, DAVIS CAMPUS, DAVIS, CALIFORNIA SP Univ California Davis, Sch Vet Med, Ctr Compan Anim Hlth HO UNIV CALIFORNIA, DAVIS CAMPUS ID LIONS; SEQUENCE AB The lion (Panthera leo) population in the Serengeti ecosystem was recently afflicted by a fatal epidemic involving neurological disease, encephalitis and pneumonia. The cause was identified as canine distemper virus (CDV). Several other species in the Serengeti were also affected. This report presents CDV H and P gene sequences isolated from Serengeti lions (Panthera lee), spotted hyenas (Crocuta crocuta), bat-eared fox (Otocyon megalotis) and domestic dog (Canis familiaris). Sequence analyses demonstrated that the four Serengeti species carry closely related CDV isolates which are genetically distinct from other CDV isolates from various species and locations. The results are consistent with the conclusions that: (1) a particularly virulent strain of CDV emerged among Serengeti carnivores within the last few years; (2) that strain has recognizable shared-derived (synapomorphic) genetic differences in both H and P genes when compared to CDV from other parts of the world; and (3) that the CDV strain has frequently crossed host species among Serengeti carnivores. (C) 1998 Published by Elsevier Science B.V. All rights reserved. C1 NCI, SAIC Frederick, Frederick, MD 21702 USA. Cornell Univ, Dept Pathol, Ithaca, NY 14853 USA. Cornell Univ, James A Baker Inst Anim Hlth, Coll Vet Med, Ithaca, NY 14853 USA. Serengeti Wildlife Res Inst, Tanzania Natl Pk, Arusha, Tanzania. Univ Tennessee, Coll Vet Med, Dept Pathol, Knoxville, TN 37901 USA. Max Planck Inst Verhaltensphysiol, Abt Wickler, D-82319 Seeweisen Past Starnberg, Germany. NCI, Lab Genom Divers, Frederick, MD 21702 USA. NCI, Lab Genom Divers, FCRDC, Frederick, MD 21702 USA. RP Carpenter, MA (reprint author), NCI, SAIC Frederick, Frederick, MD 21702 USA. OI Carpenter, Margaret/0000-0003-1606-1986; Hofer, Heribert/0000-0002-2813-7442 NR 15 TC 68 Z9 76 U1 0 U2 15 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-2427 J9 VET IMMUNOL IMMUNOP JI Vet. Immunol. Immunopathol. PD OCT 23 PY 1998 VL 65 IS 2-4 BP 259 EP 266 DI 10.1016/S0165-2427(98)00159-7 PG 8 WC Immunology; Veterinary Sciences SC Immunology; Veterinary Sciences GA 140TN UT WOS:000077104600014 PM 9839878 ER PT J AU Mueller, BU Zeichner, SL Kuznetsov, VA Heath-Chiozzi, M Pizzo, PA Dimitrov, DS AF Mueller, BU Zeichner, SL Kuznetsov, VA Heath-Chiozzi, M Pizzo, PA Dimitrov, DS TI Individual prognoses of long-term responses to antiretroviral treatment based on virological, immunological and pharmacological parameters measured during the first week under therapy SO AIDS LA English DT Article DE antiretroviral therapy; HIV-1; pediatrics; prognosis ID PLASMA HIV-1 RNA; LYMPHOCYTE COUNTS; INFECTION; MARKERS AB Objective: To predict long-term (12 weeks or longer) virological responses to antiretroviral treatment from measurements made during the first few days on therapy. Methods: Forty-one HIV-l-infected children were treated with ritonavir for 12 weeks followed by triple drug combination treatment, and the kinetics of virus decay in plasma, ritonavir concentration and CD4 cell counts were measured. A robust multivariate pattern recognition method was used for prediction of the longterm virological responses. Results: The virus decay rate constants calculated from measurements of plasma viral RNA concentrations on the first, second, third, fourth and seventh day on therapy, the drug concentrations in the plasma on day seven, and the pretreatment levels of viral RNA and CD4 cell counts, correlated with long-term levels of plasma HIV-1 RNA. The combination of these parameters contained sufficient information for correct and robust prediction of the long-term response in 88% of the treated children. The predictions of individual responses were stable as demonstrated by a cross-validation analysis, which was highly statistically significant (r = 0.87) and specific. Conclusion: These results demonstrate that multiple parameters determine the response to antiretroviral therapy and offer a very early measure of individual long-term responses, suggesting that treatment could be optimized after few days of therapy. (C) 1998 Lippincott Williams & Wilkins. C1 NCI, Lab Expt & Computat Biol, Div Basic Sci, Frederick Canc Res & Dev Ctr,NIH, Frederick, MD 21702 USA. NCI, HIV & AIDS Malignancy Branch, NIH, Bethesda, MD 20892 USA. Abbott Labs, Div Pharmaceut Prod, Dept 48U, Abbott Pk, IL 60064 USA. RP Dimitrov, DS (reprint author), NCI, Lab Expt & Computat Biol, Div Basic Sci, Frederick Canc Res & Dev Ctr,NIH, Bldg 469,Room 216,Miller Dr,POB B, Frederick, MD 21702 USA. NR 12 TC 31 Z9 31 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0269-9370 J9 AIDS JI Aids PD OCT 22 PY 1998 VL 12 IS 15 BP F191 EP F196 DI 10.1097/00002030-199815000-00004 PG 6 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 132WF UT WOS:000076653100006 PM 9814861 ER PT J AU Horti, AG Scheffel, U Kimes, AS Musachio, JL Ravert, HT Mathews, WB Zhan, YG Finley, PA London, ED Dannals, RF AF Horti, AG Scheffel, U Kimes, AS Musachio, JL Ravert, HT Mathews, WB Zhan, YG Finley, PA London, ED Dannals, RF TI Synthesis and evaluation of N-[C-11]methylated analogues of epibatidine as tracers for positron emission tomographic studies of nicotinic acetylcholine receptors SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID BINDING-SITES; IN-VIVO; CEREBRAL-CORTEX; POISON FROG; HUMAN-BRAIN; RAT-BRAIN; FLUORINE-18-FPH; DIVERSITY; AGONIST; MEMORY AB Four halogen-substituted analogues of N-methylepibatidine, a nicotinic acetylcholine receptor (nAChR) ligand, were synthesized. They were (+)-exo-N-methyl-2-(2-halogeno-5-pyridyl)-7- azabicyclo[2.2.1]heptanes, where halogeno = F (1a), Cl (2a), Br (3a), I (4a). (+/-)-N-Ethylepibatidine (2b) also was synthesized. The compounds 1a, 2a, 3a, and 4a and their corresponding normethyl analogues 1, 2, 3, and 4 inhibited the in vitro binding of [H-3]epibatidine to nAChRs to a similar degree, with affinities in the 27-50 pM range. The binding affinity of N-ethylepibatidine (2b), however, was substantially lower. The N-[C-11]methyl derivatives of 1, 2, and 3 were synthesized from high-specific radioactivity [C-11]methyl iodide using a high-temperature/high-pressure technique. The corresponding radiolabeled compounds [C-11]1a, [C-11]2a, and [C-11]3a were administrated to mice intravenously. The pattern of regional distribution of the three tracers in the mouse brain following intravenous administration matched those of [H-3]epibatidine, [H-3]norchloroepibatidine, and (+/-)-exo-2-(2-[F-18]fluoro-5-pyridyl)-7-azabicyclo[2.2.1]heptane ([F-18]FPH), which are highly specific nAChR probes. The initial brain uptake of the C-11 analogues and the acute toxicity of the corresponding authentic nonlabeled compounds appeared to be related to their lipophilicity. C1 NIDA, Brain Imaging Ctr, Intramural Res Program, Baltimore, MD 21224 USA. Johns Hopkins Med Inst, Div Nucl Med, Dept Radiol, Baltimore, MD 21287 USA. RP Horti, AG (reprint author), NIDA, Brain Imaging Ctr, Intramural Res Program, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 41 TC 55 Z9 55 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD OCT 22 PY 1998 VL 41 IS 22 BP 4199 EP 4206 DI 10.1021/jm980233p PG 8 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 133FL UT WOS:000076676100005 PM 9784094 ER PT J AU Overpeck, MD Brenner, RA Trumble, AC Trifiletti, LB Berendes, HW AF Overpeck, MD Brenner, RA Trumble, AC Trifiletti, LB Berendes, HW TI Risk factors for infant homicide in the United States SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID CHILD-ABUSE; NEGLECT; INJURY; MORTALITY; DEATH; ADOLESCENTS; PREVALENCE; PATTERNS; WOMEN AB Background Homicide is the leading cause of infant deaths due to injury. More than 80 percent of infant homicides are considered to be fatal child abuse. This study assessed the timing of deaths and risk factors for infant homicide. Methods Using linked birth and death certificates for all births in the U.S, between 1983 and 1991, we identified 2776 homicides occurring during the first year of life. Birth-certificate variables were reviewed in both bivariate and multivariate stratified analyses. Variables potentially predictive of homicide were selected on the basis of increased relative risks among subcategories with adequate numbers for stable estimates, Results Half the homicides occurred by the fourth month of life, The most important risk factors were a second or subsequent infant born to a mother less than 17 years old (relative risk, 10.9) or 17 to 19 years old (relative risk, 9.3), as compared with a first infant born to a mother 25 years old or older; a maternal age of less than 15 years, as compared with an age of at least 25 years (relative risk, 6.8); no prenatal care as compared with early prenatal care (relative risk, 10.4); and less than 12 years of education among mothers who were at least 17 years old (relative risk, 8.0), as compared with 16 or more years of education. Conclusions Childbearing at an early age was strongly associated with infant homicide, particularly if the mother had given birth previously. Our findings may have implications for prevention. (N Engl J Med 1998;339:1211-6.) (C) 1998. Massachusetts Medical Society. C1 NICHHD, Div Epidemiol Stat & Prevent Res, Bethesda, MD 20892 USA. RP Overpeck, MD (reprint author), NICHHD, Div Epidemiol Stat & Prevent Res, Bldg 6100,Rm 7B03,9000 Rockville Pike,MSC 7510, Bethesda, MD 20892 USA. RI McKenzie, Lara/C-5122-2012 NR 39 TC 174 Z9 177 U1 0 U2 4 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD OCT 22 PY 1998 VL 339 IS 17 BP 1211 EP 1216 DI 10.1056/NEJM199810223391706 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 130QW UT WOS:000076532400006 PM 9780342 ER PT J AU Webb, CP Taylor, GA Jeffers, M Fiscella, M Oskarsson, M Resau, JH Woude, GFV AF Webb, CP Taylor, GA Jeffers, M Fiscella, M Oskarsson, M Resau, JH Woude, GFV TI Evidence for a role of Met-HGF/SF during Ras-mediated tumorigenesis/metastasis SO ONCOGENE LA English DT Article DE Ras; Met; HGF/SF; tumorigenesis; metastasis ID HEPATOCYTE GROWTH-FACTOR; FACTOR SCATTER FACTOR; PROTOONCOGENE PRODUCT; ONCOGENE ACTIVATION; FACTOR RECEPTOR; NIH/3T3 CELLS; HUMAN CANCER; EXPRESSION; TRANSFORMATION; TUMORIGENICITY AB Aberrations in Met-hepatocyte growth factor/scatter factor (HGF/SF) signaling have been implicated in the acquisition of tumorigenic and metastatic phenotypes, Here we show that murine NIH3T3 and C127 cells transformed by the Ras oncogene overexpress the Met receptor, resulting in enhanced HGF/SF-mediated responses in vitro including invasion through basement membrane. Accompanying the increase in Met in ras-transformed NIH3T3 cells, there is a decrease in endogenous HGF/SF expression as previously observed in cells exogenously overexpressing Met. However, subcutaneously grown tumors and experimental lung metastases derived from these cells express significantly higher levels of endogenous HGF/SF together with high levels of Met, These results suggest Met-HGF/SF signaling enhances tumor growth and metastasis of Ras-transformed NIH3T3 cells. C1 NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Frederick, MD 21702 USA. RP Woude, GFV (reprint author), NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, POB B, Frederick, MD 21702 USA. RI Webb, Craig/I-8123-2012; Tang, Amy/L-3226-2016 OI Tang, Amy/0000-0002-5772-2878 FU NCI NIH HHS [N01-CO-46000] NR 31 TC 52 Z9 55 U1 0 U2 2 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD OCT 22 PY 1998 VL 17 IS 16 BP 2019 EP 2025 DI 10.1038/sj.onc.1202135 PG 7 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 130VK UT WOS:000076540900001 PM 9798673 ER PT J AU von Brevern, M Hollstein, MC Risk, JM Garde, J Bennett, WP Harris, CC Muehlbauer, KR Field, JK AF von Brevern, M Hollstein, MC Risk, JM Garde, J Bennett, WP Harris, CC Muehlbauer, KR Field, JK TI Loss of heterozygosity in sporadic oesophageal tumors in the tylosis oesophageal cancer (TOC) gene region of chromosome 17q SO ONCOGENE LA English DT Article DE tylosis; loss of heterozygosity; oesophageal cancer ID ESOPHAGEAL CANCER; PALMOPLANTAR KERATODERMA; P53 GENE; CARCINOMA; ALLELOTYPE; MUTATIONS AB From the genotyping of UK and US tylotic families with a high risk of oesophageal cancer we have previously localized the tylosis-associated cancer susceptibility gene (TOC gene, tylosis oesophageal cancer gene) to a 1 cM region on the long arm of chromosome 17 (Kelsell et al,, 1996), In the present study we investigated loss of heterozygosity (LOH) patterns of 35 sporadic squamous cell carcinomas of the oesophagus using six polymorphic microsatellite markers encompassing this locus. Twenty-four of the 35 cases (69%) revealed LOH at one or more loci. Deletion was most frequently observed with the marker D17S801 (64% LOH, informative cases), which shows significant linkage to the TOC locus. The LOH analysis in sporadic oesophageal cancer we report here is thus consistent with the hypothesis that the tylosis oesophageal cancer susceptibility gene is also involved in the pathogenesis of a proportion of sporadic squamous cell carcinomas of the oesophagus. C1 Univ Liverpool, Dept Clin Dent Sci, Mol Genet & Oncol Grp, Liverpool L69 3BX, Merseyside, England. Deutsch Krebsforschungszentrum, German Canc Res Ctr, D-69120 Heidelberg, Germany. NCI, Human Carcinogenesis Lab, Bethesda, MD 20892 USA. Roy Castle Int Ctr Lung Canc Res, Liverpool L3 4TA, Merseyside, England. RP Field, JK (reprint author), Univ Liverpool, Dept Clin Dent Sci, Mol Genet & Oncol Grp, Liverpool L69 3BX, Merseyside, England. OI Field, John/0000-0003-3951-6365 NR 17 TC 32 Z9 32 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD OCT 22 PY 1998 VL 17 IS 16 BP 2101 EP 2105 DI 10.1038/sj.onc.1202139 PG 5 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 130VK UT WOS:000076540900009 PM 9798681 ER PT J AU Hilbert, DM Theisen, PW Rudikoff, EK Bauer, SR AF Hilbert, DM Theisen, PW Rudikoff, EK Bauer, SR TI Interaction of abl and raf with IL-7 signaling pathway and transformation of pre-B cells from resistant mice SO ONCOGENE LA English DT Article DE pre-B lymphomagenesis; JAK-STAT signaling; raf/myc retrovirus; abl/myc retrovirus; IL-7 signal transduction ID T-CELLS; MURINE PLASMACYTOMAGENESIS; LEUKEMIA-VIRUS; MYC ONCOGENES; V-ABL; EXPRESSION; ABROGATION; MOUSE; DEPENDENCE; RETROVIRUS AB After in vivo inoculation with abl/myc- and raf/myc-containing retroviruses, BALB/c mice predominantly develop late stage B cell tumors (plasmacytomas) and less frequently develop earlier B-lineage tumors while DBA/2 mice do not develop B-lineage tumors. We have investigated the in vitro tumorigenic potential of these viruses using cultured normal pre-B cell lymphocytes from both BALB/c and DBA/2 mice. Interestingly, both viruses infect cultured pre-B lymphocytes from both mouse strains. Following infection, IL-7 dependent pre-B cells become independent of normal in vitro growth requirements within 24 h and can rapidly form in vivo pre-B lymphomas in both mouse strains, Mechanisms mediating loss of IL-7 dependence are different depending on whether the I nf or abl gene is present in myc-containing viruses. IL-7 JAK-STAT signaling is constitutively active in abl/myc induced pre-B cell tumors, In contrast, IL-7 JAK-STAT signaling is not constitutive in raf/myc induced pre-B cell tumors, demonstrating that subversion of this component of IL-7 signal transduction is not obligatory for pre-B cell transformation or loss of IL-7 dependence. C1 US FDA, Mol Immunol Lab, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Rockville, MD 20852 USA. NCI, Genet Lab, NIH, Bethesda, MD 20892 USA. RP Bauer, SR (reprint author), US FDA, Mol Immunol Lab, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Bldg 29B,2E16 HFM-521,1401 Rockville Pike, Rockville, MD 20852 USA. RI Bauer, Steven/G-5559-2012; OI Bauer, Steven/0000-0003-2831-846X NR 38 TC 5 Z9 5 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD OCT 22 PY 1998 VL 17 IS 16 BP 2125 EP 2135 DI 10.1038/sj.onc.1202134 PG 11 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 130VK UT WOS:000076540900012 PM 9798684 ER PT J AU Lindberg, DAB Humphreys, BL AF Lindberg, DAB Humphreys, BL TI Medicine and health on the Internet - The good, the bad, and the ugly SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID INFORMATION C1 Natl Lib Med, Bethesda, MD 20894 USA. RP Lindberg, DAB (reprint author), Natl Lib Med, 8600 Rockville Pike, Bethesda, MD 20894 USA. NR 16 TC 61 Z9 61 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD OCT 21 PY 1998 VL 280 IS 15 BP 1303 EP 1304 DI 10.1001/jama.280.15.1303 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 129PQ UT WOS:000076472500012 PM 9794299 ER PT J AU Gladyshev, VN Factor, VM Housseau, F Hatfield, DL AF Gladyshev, VN Factor, VM Housseau, F Hatfield, DL TI Contrasting patterns of regulation of the antioxidant selenoproteins, thioredoxin reductase, and glutathione peroxidase, in cancer cells SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID SELENIUM SUPPLEMENTATION; P53-INDUCED APOPTOSIS; GENE-EXPRESSION; TRANSGENIC MICE; FACTOR-ALPHA; C-MYC; SELENOCYSTEINE; EUKARYOTES; LINES; LIVER AB There is strong evidence that selenium protects against certain human cancers, but the underlying mechanism is unknown. Glutathione peroxidase (GPX1) and thioredoxin reductase (TR), the most abundant antioxidant selenium-containing proteins in mammals, have been implicated in this protection. me analyzed the expression of TR and GPX1 in the following model cancer systems: (1) liver tumors in TGF alpha/c-myc transgenic mice; (2) human prostate cell lines from normal and cancer tissues; and (3) p53-induced apoptosis in a human colon cancer cell line. TR was induced while GPX1 was repressed in malignancies relative to controls in transgenic mice and prostate cell Lines. In the colon cell line, p53 expression resulted in elevated GPX1, but repressed TR. The data indicate that TR and GPX1 are regulated in a contrasting manner in the cancer systems tested and reveal the p53-dependent regulation of selenoprotein expression. The data suggest that additional studies on selenoprotein regulation in different cancers are required to evaluate future implementation of selenium as a dietary supplement in individuals at risk for developing certain cancers. (C) 1998 Academic Press. C1 Univ Nebraska, Dept Biochem, Lincoln, NE 68588 USA. NCI, Basic Res Labs, NIH, Bethesda, MD 20892 USA. NCI, Expt Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. RP Gladyshev, VN (reprint author), Univ Nebraska, Dept Biochem, Lincoln, NE 68588 USA. EM vng@unlinfo2.unl.edu RI Gladyshev, Vadim/A-9894-2013 NR 31 TC 96 Z9 100 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD OCT 20 PY 1998 VL 251 IS 2 BP 488 EP 493 DI 10.1006/bbrc.1998.9495 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 132PN UT WOS:000076638900016 PM 9792801 ER PT J AU Ledakis, P Tanimura, H Fojo, T AF Ledakis, P Tanimura, H Fojo, T TI Limitations of differential display SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE DD-PCR; differential display PCR; RT-PCR; drug resistance; multidrug resistance ID POLYMERASE CHAIN-REACTION; GENE-EXPRESSION; MESSENGER-RNA; CELL-LINES AB Since its original description, differential display PCR (DD-PCR) has been extensively used in attempts to identify novel genes under a variety of circumstances. Despite its widespread use, however, few novel genes of interest have been identified. In the present study we describe a set of experiments examining reasons for failure of differential display. Evidence is presented that aberrant priming at both the 5' and 3' ends results in competition in the PCR, precluding detection of messages other than those which are abundantly expressed. Appropriate calculations are discussed which indicate this was predictable and unlikely to be overcome. While DD may be successfully applied in some settings, the evidence indicates that only abundantly expressed messages can be detected. This limitation is emphasized. (C) 1998 Academic Press. C1 NCI, Med Branch, Bethesda, MD 20892 USA. RP Fojo, T (reprint author), NCI, Med Branch, Bldg 10,Rm 12N226,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 11 TC 21 Z9 22 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD OCT 20 PY 1998 VL 251 IS 2 BP 653 EP 656 DI 10.1006/bbrc.1998.9517 PG 4 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 132PN UT WOS:000076638900044 PM 9792829 ER PT J AU Yau, WM Wimley, WC Gawrisch, K White, SH AF Yau, WM Wimley, WC Gawrisch, K White, SH TI The preference of tryptophan for membrane interfaces SO BIOCHEMISTRY LA English DT Article ID MAGNETIC-RESONANCE SPECTROSCOPY; BILAYER STRUCTURE DETERMINATION; ALPHA-HELICAL PEPTIDES; CATION-PI INTERACTIONS; NEUTRON-DIFFRACTION; LIPID BILAYERS; X-RAY; GRAMICIDIN CHANNEL; PROTEINS; MODEL AB One of the ubiquitous features of membrane proteins is the preference of tryptophan and tyrosine residues for membrane surfaces that presumably arises from enhanced stability due to distinct interfacial interactions. The physical basis for this preference is widely believed to arise from amphipathic interactions related to imino group hydrogen bonding and/or dipole interactions. We have examined these and other possibilities for tryptophan's interfacial preference by using H-1 magic angle spinning (MAS) chemical shift measurements, two-dimensional (2D) nuclear Overhauser effect spectroscopy (2D-NOESY) H-1 MAS NMR, and solid state H-2 NMR to study the-interactions of four tryptophan analogues with phosphatidylcholine membranes. We find that the analogues reside in the vicinity of the glycerol group where they all cause similar modest changes in acyl chain organization and that hydrocarbon penetration was not increased by reduction of hydrogen bonding or electric dipole interaction ability. These observations rule out simple amphipathic or dipolar interactions as the physical basis for the interfacial preference. More likely, the preference is dominated by tryptophan's flat rigid shape that limits access to the hydrocarbon core and its pi electronic structure and associated quadrupolar moment (aromaticity) that favor residing in the electrostatically complex interface environment. C1 Univ Calif Irvine, Dept Physiol & Biophys, Irvine, CA 92697 USA. NIAAA, NIH, Rockville, MD 20852 USA. RP White, SH (reprint author), Univ Calif Irvine, Dept Physiol & Biophys, Irvine, CA 92697 USA. RI White, Stephen/B-1053-2009 OI White, Stephen/0000-0001-8540-7907 FU NIGMS NIH HHS [GM46823] NR 33 TC 655 Z9 660 U1 6 U2 74 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD OCT 20 PY 1998 VL 37 IS 42 BP 14713 EP 14718 DI 10.1021/bi980809c PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 134DP UT WOS:000076727900008 PM 9778346 ER PT J AU Wu, P Nossal, N Benkovic, SJ AF Wu, P Nossal, N Benkovic, SJ TI Kinetic characterization of a bacteriophage T4 antimutator DNA polymerase SO BIOCHEMISTRY LA English DT Article ID DEOXYRIBONUCLEIC-ACID POLYMERASE; EXONUCLEASE ACTIVITY; ESCHERICHIA-COLI; SPONTANEOUS MUTATION; CB120 ANTIMUTATOR; BIOCHEMICAL BASIS; FRAGMENT; REPLICATION; FREQUENCY; SELECTION AB Fidelity of DNA replication by bacteriophage T4 DNA polymerase is achieved in a multiplicative process: base selection by its polymerase activity and removal of misincorporated nucleotides by its exonuclease activity. The wild-type polymerase is capable of maintaining a balance between the two activities so that DNA replication fidelity is maximized without excessive waste of nucleotidos. Antimutator enzymes exhibit a higher DNA replication fidelity than the wild-type enzyme, at the cost of increased nucleotide turnover. The antimutator A737V polymerase has been characterized kinetically using pre-steady-state and steady-state methods to provide a kinetic sequence which defines the effect of the mutation on the discrete steps controlling DNA replication fidelity, Comparison of this sequence to that of the wild type [Capson, L. T., Peliska, J, A., Kaboord, B. F., Frey, M. W., Lively, C., Dahiberg, M., and Benkovic, S, J. (1992) Biochemistry 31, 10984-10994] revealed that A737V polymerase differs in two ways. The rates at which DNA is transferred between the exonuclease and polymerase sites are reduced approximately 7-fold for a duplex DNA containing a mismatched 3'-terminus, and the partitioning of the mismatched duplex between the polymerase and exonuclease sites is 1:2 versus 4:1 for the wildtype enzyme. The exonuclease activity of A737V relative to the wild-type enzyme is unchanged on single-stranded DNA. However, the difference in partitioning the duplex DNA between the exonuclease and polymerase active sites results in an enhanced exonuclease activity for the antimutator enzyme. C1 Penn State Univ, Dept Chem, University Pk, PA 16802 USA. NIDDKD, Bethesda, MD 20892 USA. RP Benkovic, SJ (reprint author), Penn State Univ, Dept Chem, 414 Wartik Lab, University Pk, PA 16802 USA. FU NIGMS NIH HHS [GM13306] NR 36 TC 19 Z9 19 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD OCT 20 PY 1998 VL 37 IS 42 BP 14748 EP 14755 DI 10.1021/bi980835a PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 134DP UT WOS:000076727900011 PM 9778349 ER PT J AU Varnai, P Balla, T AF Varnai, P Balla, T TI Visualization of phosphoinositides that bind pleckstrin homology domains: Calcium- and agonist-induced dynamic changes and relationship to myo-[H-3]inositol-labeled phosphoinositide pools SO JOURNAL OF CELL BIOLOGY LA English DT Article DE phosphoinositides; calcium; green fluorescent protein; pleckstrin-homology domain; phospholipase C ID PHOSPHATIDYLINOSITOL 4-KINASE; INOSITOL 1,4,5-TRISPHOSPHATE; KINASE; CELL; SPECIFICITY; ACTIVATION; RECEPTORS; MEMBRANE AB Phosphatidylinositol 4,5-bisphosphate (PtdIns[4,5]P-2) pools that bind pleckstrin homology (PH) domains were visualized by cellular expression of a phospholipase C (PLC)delta PH domain-green fluorescent protein fusion construct and analysis of confocal images in living cells. Plasma membrane localization of the fluorescent probe required the presence of three basic residues within the PLC delta PH domain known to form critical contacts with PtdIns(4,5)P-2. Activation of endogenous PLCs by ionophores or by receptor stimulation produced rapid redistribution of the fluorescent signal from the membrane to cytosol, which was reversed after Ca2+ chelation. In both ionomycin- and agonist-stimulated cells, fluorescent probe distribution closely correlated with changes in absolute mass of PtdIns(4,5)P-2. Inhibition of PtdIns(4,5)P-2 synthesis by quercetin or phenylarsine oxide prevented the relocalization of the fluorescent probe to the membranes after Ca2+ chelation in ionomycin-treated cells or during agonist stimulation. In contrast, the synthesis of the PtdIns(4,5)P-2 imaged by the PH domain was not sensitive to concentrations of wortmannin that had been found inhibitory of the synthesis of myo-[H-3]inositol-labeled PtdIns(4,5)P-2. Identification and dynamic imaging of phosphoinositides that interact with PH domains will further our understanding of the regulation of such proteins by inositol phospholipids. C1 NICHHD, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA. RP Balla, T (reprint author), NICHHD, Endocrinol & Reprod Res Branch, NIH, Bldg 49,Rm 6A35,49 Convent Dr, Bethesda, MD 20892 USA. EM tambal@box-t.nih.gov OI Balla, Tamas/0000-0002-9077-3335 NR 35 TC 483 Z9 487 U1 3 U2 12 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD OCT 19 PY 1998 VL 143 IS 2 BP 501 EP 510 DI 10.1083/jcb.143.2.501 PG 10 WC Cell Biology SC Cell Biology GA 132EW UT WOS:000076618200018 PM 9786958 ER PT J AU Herkenham, M Lee, HY Baker, RA AF Herkenham, M Lee, HY Baker, RA TI Temporal and spatial patterns of c-fos mRNA induced by intravenous interleukin-1: A cascade of non-neuronal cellular activation at the blood-brain barrier SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE cytokine; endothelia; glia; choroid plexus; circumventricular organ; inflammation ID CENTRAL-NERVOUS-SYSTEM; RECEPTOR MESSENGER-RNA; IMMUNE-CHALLENGED RATS; PROSTAGLANDIN FORMATION; RAMIFIED MICROGLIA; ENDOTHELIAL-CELLS; FEBRILE RESPONSE; LIPOPOLYSACCHARIDE; ENDOTOXIN; INDUCTION AB Brain cells responsive to a peripheral immune challenge, identified by in situ hybridization of c-fos mRNA following intravenous administration of the proinflammatory cytokine interleukin-1 beta (IL-1) or sterile saline, were investigated at 0.5, 1, and 3 hours postinjection in rats. Doses of IL-1 ranged from 0.05 to 10 mu g/kg; induction of c-fos mRNA occurred at greater than or equal to 0.5 mu g/kg. The majority of IL-1-induced c-fos mRNA-positive cells were non-neuronal cells located in barrier regions of the brain. The cells became radiolabeled in two separate but related spatiotemporal patterns. The first pattern, occurring at 0.5 hour, was characterized by c-fos mRNA labeling of cells of the outer meninges (mainly arachnoid), blood vessels (arteries, veins, and capillaries), and choroid plexus. This activation pattern disappeared at 1 hour. At 3 hours, a second activation pattern appeared in cells located just inside the now quiescent barrier cells. In addition, the circumventricular organs each showed characteristic spatiotemporal labeling patterns resulting from successive activation of specific cell types, with a general spread of activation directed away from the circumventricular organs over time. At 3 hours post IL-1, c-fas and glial fibrillary acidic protein (GFAP) mRNAs showed colocalization in the arcuate nucleus/median eminence/glia limitans region. We propose that the first wave of activation is elicited by blood-borne immune signals, but the second wave is caused by molecules generated within the first set of activated cells. The transduced signal appears to propagate to neighboring receptive cells by extracellular diffusion. In this manner, blood-brain barrier cells can transduce peripheral IL-1 signals in widespread areas of the brain, although the circumventricular organs may be the most effective loci for signal transduction. (C) 1998 Wiley-Liss, Inc. C1 NIMH, Funct Neuroanat Sect, Bethesda, MD 20892 USA. RP Herkenham, M (reprint author), NIMH, Funct Neuroanat Sect, Bldg 36,Rm 2D-15, Bethesda, MD 20892 USA. OI Herkenham, Miles/0000-0003-2228-4238 NR 59 TC 58 Z9 58 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD OCT 19 PY 1998 VL 400 IS 2 BP 175 EP 196 DI 10.1002/(SICI)1096-9861(19981019)400:2<175::AID-CNE2>3.0.CO;2-6 PG 22 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA 123BN UT WOS:000076106100002 PM 9766398 ER PT J AU Alexander-Miller, MA Derby, MA Sarin, A Henkart, PA Berzofsky, JA AF Alexander-Miller, MA Derby, MA Sarin, A Henkart, PA Berzofsky, JA TI Supraoptimal peptide major histocompatibility complex causes a decrease in Bcl-2 levels and allows tumor necrosis factor alpha receptor II-mediated apoptosis of cytotoxic T lymphocytes SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE T lymphocytes, cytotoxic; apoptosis; protooncogene; proteins c-bel-2; tumor necrosis factor ID NF-KAPPA-B; TNF RECEPTOR; CELL-DEATH; ANTIGEN; VIRUS; ACTIVATION; MOLECULES; SUPPRESSION; EXPRESSION; INDUCTION AB Cytotoxic T lymphocytes (CTLs) are primary mediators of viral clearance, but high viral burden can result in deletion of antigen-specific CTLs. We previously reported a potential mechanism for this deletion: tumor necrosis factor (TNF)-alpha-mediated apoptosis resulting from stimulation with supraoptimal peptide-major histocompatibility complex. Here, we show that although death is mediated by TNF-alpha and its receptor (TNF-RII), surprisingly neither the antigen dose dependence of TNF-alpha. production nor that of TNF-RII expression can account for the dose dependence of apoptosis. Rather, a previously unrecognized effect of supraoptimal antigen in markedly decreasing levels of the antiapoptotic protein Bcl-2 was discovered and is likely to account for the gain in susceptibility or competence to sustain the death signal through TNF-RII. This decrease requires a signal through the TCR, not just through TNF-RII. Although death mediated by TNF-RII is not as widely studied as that mediated by TNF-RI, we show here that it is also dependent on proteolytic cleavage by caspases and triggered by a brief initial encounter with antigen. These results suggest that determinant density can regulate the immune response by altering the sensitivity of CTLs to the apoptotic effects of TNF-alpha by decreasing Bcl-2 levels. C1 NCI, Metab Branch, Mol Immunogenet & Vaccine Res Sect, NIH, Bethesda, MD 20892 USA. NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. RP Berzofsky, JA (reprint author), NCI, Metab Branch, Mol Immunogenet & Vaccine Res Sect, NIH, Bldg 10,Rm 6B12, Bethesda, MD 20892 USA. EM berzofsk@helix.nih.gov NR 39 TC 79 Z9 81 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD OCT 19 PY 1998 VL 188 IS 8 BP 1391 EP 1399 DI 10.1084/jem.188.8.1391 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 132FR UT WOS:000076620100001 PM 9782116 ER PT J AU von Stebut, E Belkaid, Y Jakob, T Sacks, DL Udey, MC AF von Stebut, E Belkaid, Y Jakob, T Sacks, DL Udey, MC TI Uptake of Leishmania major amastigotes results in activation and interleukin 12 release from murine skin-derived dendritic cells: Implications for the initiation of anti-Leishmania immunity SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE Langerhans cell; dendritic cell; Leishmania major; T helper cell type 1 T helper cell type 2 immune response; interleukin 12 ID EPIDERMAL LANGERHANS CELLS; CUTANEOUS LEISHMANIASIS; INTERFERON-GAMMA; IL-12 PRODUCTION; CLASS-II; PROMASTIGOTES; MICE; MACROPHAGES; RESISTANCE; EXPRESSION AB Epidermal Langerhans cells (LC) are immature dendritic cells (DC) located in close proximity to the site of inoculation of infectious Leishmania major metacyclic promastigotes by sand flies. Using LC-like DC expanded from C57BL/6 fetal skin, we characterized interactions involving several developmental stages of Leishmania and DC. We confirmed that L. major amastigotes, but not promastigotes, efficiently entered LC-like DC. Parasite internalization was associated with activation manifested by upregulation of major histocompatibility complex (MHC) class I and II surface antigens, increased expression of costimulatory molecules (CD40, CD54, CD80, and CD86), and interleukin (IL)-12 p40 release within 18 h. L. major-induced IL-12 p70 release by DC required interferon gamma and prolonged (72 h) incubation. In contrast, infection of inflammatory macrophages (M phi) with amastigotes or promastigotes did not lead to significant changes in surface antigen expression or cytokine production. These results suggest that skin M phi and DC are infected sequentially in cutaneous leishmaniasis and that they play distinct roles in the inflammatory and immune response initiated by L. major M phi capture organisms near the site of inoculation early in the course of infection after establishment of cellular immunity, and kill amastigotes but probably do not actively participate in T cell priming. In contrast, skin DC are induced to express increased amounts of MHC antigens and costimulatory molecules and to release cytokines (including IL-12 p70) by exposure to L. major amastigotes that ultimately accumulate in lesional tissue, and thus very likely initiate protective T helper cell type 1 immunity. C1 NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Udey, MC (reprint author), NCI, Dermatol Branch, NIH, Bldg 10,Rm 12N238,9000 Rockville Rd, Bethesda, MD 20892 USA. RI Jakob, Thilo/J-1621-2012 NR 30 TC 199 Z9 205 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD OCT 19 PY 1998 VL 188 IS 8 BP 1547 EP 1552 DI 10.1084/jem.188.8.1547 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 132FR UT WOS:000076620100018 PM 9782133 ER PT J AU Kannel, WB Wolf, PA Benjamin, EJ Levy, D AF Kannel, WB Wolf, PA Benjamin, EJ Levy, D TI Prevalence, incidence, prognosis, and predisposing conditions for atrial fibrillation: Population-based estimates SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article; Proceedings Paper CT Symposium on Atrial Fibrillation: Mechanism and Management CY MAY 05, 1998 CL SAN DIEGO, CALIFORNIA ID ACUTE MYOCARDIAL-INFARCTION; RISK-FACTORS; HEART-DISEASE; ACUTE STROKE; EPIDEMIOLOGIC FEATURES; FOLLOW-UP; FRAMINGHAM; COMPLICATIONS; PREVENTION; MORTALITY AB Atrial fibrillation (AF) is the most common of the serious cardiac rhythm disturbances and is responsible for substantial morbidity and mortality in the general population. Its prevalence doubles with each advancing decade of age, from 0.5% at age 50-59 years to almost 9% at age 80-89 years. It is also becoming more prevalent, increasing in men aged 65-84 years From 3.2% in 1968-1970 to 9.1% in 1987-1989. This statistically significant increase in men was not explained by an increase in age, valve disease, or myocardial infarctions in the cohort. The incidence of new onset of AF also doubled with each decade of age, independent of the increasing prevalence of known predisposing conditions. Based on 38-year follow-up data from the Framingham Study, men had a 1.5-fold greater risk of developing AF than women after adjustment for age and predisposing conditions. Of the cardiovascular risk factors, only hypertension and diabetes were significant independent predictors of AF, adjusting for age and other predisposing conditions. Cigarette smoking was a significant risk factor in women adjusting only for age (OR = 1.4), but was just short of significance on adjustment for of her risk factors. Neither obesity nor alcohol intake was associated with AF incidence in either sex. For men and women, respectively, diabetes conferred a 1.4- and 1.6-fold risk, and hypertension a 1.5- and 1.4-fold risk, after adjusting For other associated conditions. Because of ifs high prevalence in the population, hypertension was responsible for more AF in the population (14%) than any other risk factor. Intrinsic overt cardiac conditions imposed a substantially higher risk. Adjusting for other relevant conditions, heart failure was associated with a 4.5- and 5.9-fold risk, and valvular heart disease a 1.8- and 3.4-fold risk for AF in men and women, respectively. Myocardial infarction significantly increased the risk factor-adjusted likelihood of AF by 40% in men only. Echocardiographic predictors of nonrheumatic AF include left atrial enlargement (39% increase in risk per 5-mm increment), left ventricular fractional shortening (34% per 5% decrement), and left ventricular wall thickness (28% per 4-mm increment). These echocardiographic features offer prognostic information for AF beyond the traditional clinical risk factors. Electrocardiographic left ventricular hypertrophy increased risk of AF 3-4-fold after adjusting only for age, but this risk ratio is decreased to 1.4 after adjustment for the of her associated conditions. The chief hazard of AF is stroke, the risk of which is increased 4-5-fold. Because of its high prevalence in advanced age, AF assumes great importance as a risk factor for stroke and by the ninth decade becomes a dominant factor. The attributable risk far stroke associated with AF increases steeply from 1.5% at age 50-59 years to 23.5% at age 80-89 years. AF is associated with a doubling of mortality in both sexes, which is decreased to 1.5-1.9-fold after adjusting for associated cardiovascular conditions. Decreased survival associated with AF occurs across a wide range of ages. (C) 1998 by Excerpta Medica, Inc. C1 Boston Univ, Sch Med, Evans Dept Clin Res, Dept Epidemiol & Prevent Med, Boston, MA 02118 USA. NHLBI, Framingham Heart Study, Framingham, MA USA. RP Kannel, WB (reprint author), Boston Univ, Sch Med, Evans Dept Clin Res, Dept Epidemiol & Prevent Med, Boston, MA 02118 USA. FU NHLBI NIH HHS [N01-HC-38038] NR 45 TC 478 Z9 528 U1 1 U2 19 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD OCT 16 PY 1998 VL 82 IS 8A SI SI BP 2N EP 8N DI 10.1016/S0002-9149(98)00583-9 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 135PU UT WOS:000076812400002 PM 9809895 ER PT J AU Zhu, XG Hanover, JA Hager, GL Cheng, SY AF Zhu, XG Hanover, JA Hager, GL Cheng, SY TI Hormone-induced translocation of thyroid hormone receptors in living cells visualized using a receptor green fluorescent protein chimera SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NUCLEAR RECEPTOR; L-TRIIODOTHYRONINE; GLUCOCORTICOID RECEPTOR; BINDING; LOCALIZATION; DOMAIN; GROWTH; DNA; MODULATION; MUTANTS AB Thyroid hormone nuclear receptors (TRs) are ligand-dependent transcription factors that regulate growth, differentiation, and development. To understand the role of the hormone, 3,3',5-triiodo-L-thyronine (T-3), in the nuclear translocation and targeting of TRs to the regulatory sites in chromatin, we appended green fluorescent protein (GFP) to the human TR subtype beta 1 (TR beta 1). The fusion of GFP to the amino terminus of TR beta 1 protein did not alter T-3 binding or transcriptional activities of the receptor. The subcellular localization of GFP-TR beta 1 in living cells was visualized by laser-scanning confocal microscopy. In the presence of T-3, the expressed GFP-TR beta 1 was predominately localized in the nucleus, exhibiting a nuclear/cytoplasmic ratio of similar to 5.5. No GFP-TR beta 1 was detected in the nucleolus. In the absence of T-3, more GFP-TR beta 1 was present in the cytoplasm, exhibiting a nuclear/cytoplasmic ratio of similar to 1.5. In these cells, cytoplasmic GFP-TR beta 1 could be induced to enter the nucleus by T-3. The T-3-induced translocation was blocked when Lys(184)-Arg(185) in domain D of TR beta 1 was mutated to Ala(184)-Ala(185). Furthermore, the inability of the mutant TR to translocate to the nucleus correlated with the loss of most of its transcriptional activity. These results suggest that TR functions may, in part, be regulated by T-3-induced nuclear entry. C1 NCI, Mol Biol Lab, Bethesda, MD 20892 USA. NCI, Lab Receptor Biol & Gene Express, Bethesda, MD 20892 USA. NIDDK, Lab Cellular Biochem & Biol, NIH, Bethesda, MD 20892 USA. RP Cheng, SY (reprint author), Bldg 37,Rm 2D24,37 Convent Dr,MSC 4255, Bethesda, MD 20892 USA. NR 32 TC 84 Z9 87 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 16 PY 1998 VL 273 IS 42 BP 27058 EP 27063 DI 10.1074/jbc.273.42.27058 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 129DM UT WOS:000076448000007 PM 9765220 ER PT J AU Pourquier, P Bjornsti, MA Pommier, Y AF Pourquier, P Bjornsti, MA Pommier, Y TI Induction of topoisomerase I cleavage complexes by the vinyl chloride adduct 1,N-6-ethenoadenine SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ACTIVE-SITE TYROSINE; METABOLITE CHLOROACETALDEHYDE; DNA CLEAVAGE; CAMPTOTHECIN; CELLS; 1,N-6-ETHENODEOXYADENOSINE; MUTAGENESIS; OXIDATION; INVITRO; GENOME AB We used purified mammalian topoisomerases I (top1) and oligonucleotides to study top1-mediated cleavage and religation in the presence of a potent carcinogenic adduct, 1,N-6-ethenoadenosine (EA) incorporated immediately downstream of a unique top1 cleavage site. We found tha epsilon A markedly enhanced top1 cleavage complexes when it was incorporated at the +1 position of the top1 cleavage. This enhancement was due to a reduction of the religation step of the top1 reaction. In addition, epsilon A reduced the top1-mediated cleavage and decreased binding of the enzyme to DNA. We also studied the effects of the epsilon A adduct on top1 trapping by camptothecin (CPT), a web known top1 inhibitor. CPT was inactive when epsilon A was present at the +1 position. Alkylation of the top1 cleavage complex by 7-chloromethyl-10,11-methylenedioxycamptothecin (7-ClMe-MDO-CPT) was also blocked by the epsilon A adduct. Altogether, these results demonstrate that the epsilon A carcinogenic ad duct can efficiently trap human top1 and mimic CPT effects. Normal hydrogen bonding of the base pairs immediately downstream from the top1 cleavage site is probably essential for efficient DNA religation and binding of camptothecins in the top1 cleavage complex. C1 NCI, Mol Pharmacol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. Thomas Jefferson Univ, Dept Biochem & Mol Pharmacol, Philadelphia, PA 19107 USA. RP Pommier, Y (reprint author), NCI, Mol Pharmacol Lab, Div Basic Sci, NIH, Bldg 37,Rm 5D02, Bethesda, MD 20892 USA. EM pommier@nih.gov NR 39 TC 32 Z9 33 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 16 PY 1998 VL 273 IS 42 BP 27245 EP 27249 DI 10.1074/jbc.273.42.27245 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 129DM UT WOS:000076448000034 PM 9765247 ER PT J AU Kakuta, Y Petrotchenko, EV Pedersen, LC Negishi, M AF Kakuta, Y Petrotchenko, EV Pedersen, LC Negishi, M TI The sulfuryl transfer mechanism - Crystal structure of a vanadate complex of estrogen sulfotransferase and mutational analysis SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TRANSITION-STATE; FLAVONOL 3-SULFOTRANSFERASE; SULFATION; PHOSPHATASE; ENZYMOLOGY; ACTIVATION; ANALOGS; BINDING; BIOLOGY; DOMAIN AB Estrogen sulfotransferase (EST) catalyzes transfer of the 5'-sulfuryl group of adenosine 3'-phosphate 5'-phosphosulfate (PAPS) to the 3 alpha-phenol group of estrogenic steroids such as estradiol (E-2), The recent crystal structure of EST adenosine 3',5'-diphosphate (PAP)- E-2 complex has revealed that residues Lys(48), Thr(45) Thr(51), Thr(52), Lys(106), His(108), and Try(240) are in position to play a catalytic role in the sulfuryl transfer reaction of EST (Kakuta Y., Pedersen, L. G., Carter, C. W., Negishi, M., and Pedersen, L. C. (1997) Nat. Struct. BioL. 4, 904-908). Mutation of Lys(48), Lys(106), or His(108) nearly abolishes EST activity, indicating that they play a critical role in catalysis, A present 2.2-A resolution structure of EST-PAP-vanadate complex indicates that the vanadate molecule adopts a trigonal bipyramidal geometry with its equatorial oxygens coordinated to these three residues. The apical positions of the vanadate molecule are occupied by a terminal oxygen of the 5'-phosphate of PAP (2.1 ) and a possible water molecule (2.3 Angstrom), This water molecule superimposes well to the 3 alpha-phenol group of E-2 in the crystal structure of the EST . PAP . E-2 complex. These structures are characteristic of the transition state for an in-line sulfuryl transfer reaction from PAPS to E-2. Moreover, residues Lys(48), Lys(106), His(108) are found to be coordinated with the vanadate molecule at the transition state of EST. C1 NIEHS, Reprod & Dev Toxicol Lab, Pharmacogenet Sect, NIH, Res Triangle Pk, NC 27709 USA. RP Negishi, M (reprint author), NIEHS, Reprod & Dev Toxicol Lab, Pharmacogenet Sect, NIH, Res Triangle Pk, NC 27709 USA. EM negishi@niehs.nih.gov NR 35 TC 91 Z9 96 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 16 PY 1998 VL 273 IS 42 BP 27325 EP 27330 DI 10.1074/jbc.273.42.27325 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 129DM UT WOS:000076448000046 PM 9765259 ER PT J AU Thompson, J Pikis, A Ruvinov, SB Henrissat, B Yamamoto, H Sekiguchi, J AF Thompson, J Pikis, A Ruvinov, SB Henrissat, B Yamamoto, H Sekiguchi, J TI The gene glvA of Bacillus subtilis 168 encodes a metal-requiring, NAD (H)-dependent 6-phospho-alpha-glucosidase - Assignment to family 4 of the glycosylhydrolase superfamily SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GRAM-POSITIVE BACTERIA; D-PHOSPHOGALACTOSIDE GALACTOHYDROLASE; FUSOBACTERIUM-MORTIFERUM ATCC-25557; SUGAR PHOSPHOTRANSFERASE SYSTEM; AGROBACTERIUM BETA-GLUCOSIDASE; ACID-SEQUENCE SIMILARITIES; ACTIVE-SITE NUCLEOPHILE; ESCHERICHIA-COLI K-12; NUCLEOTIDE-SEQUENCE; AMINO-ACID AB The gene gluA (formerly glu-1) from Bacillus subtilis has been cloned and expressed in Escherichia coli. The purified protein GlvA (449 residues, M-r = 50,513) is a unique 6-phosphoryl-O-alpha-D-glucopyranosyl:phosphoglucohydrolase (6-phospho-alpha-glucosidase) that requires both NAD(H) and divalent metal (Mn2+, Fe2+, Co2+, or Ni2+) for activity. 6-Phospho-alpha-glucosidase (EC 3.2.1.122) from B. subtilis cross-reacts with polyclonal antibody to maltose 6-phosphate hydrolase from Fusobacterium mortiferum, and the two proteins exhibit amino acid sequence identity of 73%. Estimates for the M-r of GlvA determined by SDS-polyacrylamide gel electrophoresis (51,000) and electrospray-mass spectroscopy (50,510) were in excellent agreement with the molecular weight of 50,513 deduced from the amino acid sequence. The sequence of the first 37 residues from the N terminus determined by automated analysis agreed precisely with that predicted by translation of gluA. The chromogenic and fluorogenic substrates, p-nitrophenyl-alpha-D-glucopyranoside 6-phosphate and 4-methylumbelliferyl-alpha-D-glucopyranoside 6-phosphate were used for the discontinuous assay and in situ detection of enzyme activity, respectively. Site directed mutagenesis shows that three acidic residues, Asp(41), Glu(111), and Glu(359), are required for GlvA activity. Asp(41) is located at the C terminus of a beta alpha beta fold that may constitute the dinucleotide binding domain of the protein. Glu(111) and GlU(359) may function as the catalytic acid (proton donor) and nucleophile (base), respectively, during hydrolysis of 6-phospho-alpha-glucoside substrates including maltose 6-phosphate and trehalose 6-phosphate, In metal-free buffer, GlvA exists as an inactive dimer, but in the presence of Mn2+ ion, these species associate to form the NAD(H)-dependent catalytically active tetramer, By comparative sequence alignment with its homologs, the novel 6-phospho-alpha-glucosidase from B. subtilis can be assigned to the nine-member family 4 of the glycosylhydrolase superfamily. C1 NIDR, Oral Infect & Immun Branch, Microbial Biochem & Genet Unit, NIH, Bethesda, MD 20892 USA. NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. Childrens Natl Med Ctr, Dept Infect Dis, Washington, DC 20010 USA. CNRS, Struct Enzymol & Glycobiol Grp, F-13402 Marseille, France. Shinshu Univ, Fac Text Sci & Technol, Dept Appl Biol, Ueda, Nagano 386, Japan. RP Thompson, J (reprint author), NIDR, Oral Infect & Immun Branch, Microbial Biochem & Genet Unit, NIH, Bldg 30,Rm 528,Convent Dr,MSC-4350, Bethesda, MD 20892 USA. EM jthompson@yoda.nidr.nih.gov RI Sekiguchi, Junichi/F-9963-2010; Henrissat, Bernard/J-2475-2012 NR 71 TC 62 Z9 65 U1 0 U2 7 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 16 PY 1998 VL 273 IS 42 BP 27347 EP 27356 DI 10.1074/jbc.273.42.27347 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 129DM UT WOS:000076448000049 PM 9765262 ER PT J AU Li, HM Natarajan, K Malchiodi, EL Margulies, DH Mariuzza, RA AF Li, HM Natarajan, K Malchiodi, EL Margulies, DH Mariuzza, RA TI Three-dimensional structure of H-2D(d) complexed with an immunodominant peptide from human immunodeficiency virus envelope glycoprotein 120 SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE MHC class I; HIV glycoprotein 120; peptide; natural killer receptor; crystal structure ID MAJOR HISTOCOMPATIBILITY COMPLEX; MHC CLASS-I; T-CELL RECEPTOR; MEDIATED GENE-TRANSFER; CRYSTAL-STRUCTURE; 3-DIMENSIONAL STRUCTURE; ANGSTROM RESOLUTION; ANTIGEN RECEPTOR; VIRAL PEPTIDES; LYMPHOCYTES-T AB The crystal structure of the mouse major histocompatibility complex (MHC) class I molecule H-2D(d) with an immunodominant peptide, designated P18-I10 (RGPGRAFVTI), from human immunodeficiency virus envelope glycoprotein 120 was determined at 3.2 Angstrom resolution. A novel orientation of the alpha 3 domain of Dd relative to the alpha 1/alpha 2 domains results in significantly fewer contacts between alpha 3 and beta(2)-microglobulin compared with other MHC class I proteins. Four out of ten peptide residues (P2 Gly, P3 Pro, P5 Arg and P10 Ile) are nearly completely buried in the D-d binding groove. This is consistent with previous findings that D-d exploits a four-residue binding motif comprising a glycine at P2, a proline at P3, a positively charged residue at P5, and a C-terminal hydrophobic residue at P9 or P10. The side-chain of P5 Arg is directed toward the floor of the predominantly hydrophobic binding groove where it forms two salt bridges and one hydrogen bond with D-d residue Asp77. The selection of glycine at P2 appears to be due to a narrowing of the B pocket, relative to that of other class I molecules, caused by Arg66 whose side-chain folds down into the binding cleft. Residue P3 Pro of P18-I10 occupies part of pocket D, which in D-d is partially split by a prominent hydrophobic ridge in the floor of the binding groove formed by Trp97 and Trp114. Residues P6 through P9 form a solvent-exposed bulge, with P7 Phe protruding the most from the binding groove and thereby probably constituting a major site of interaction with T cell receptors. A comparison of H-2D(d)/P18-I10 with other MHC class I/peptide complexes of known structure provides insights into the possible basis for the specificity of the natural killer cell receptor Ly-49A for several related class I molecules. (C) 1998 Academic Press. C1 Univ Maryland, Maryland Biotechnol Inst, Ctr Adv Res Biotechnol, Rockville, MD 20850 USA. NIAID, Immunol Lab, Mol Biol Sect, NIH, Bethesda, MD 20892 USA. Univ Buenos Aires, CONICET, Catedra Inmunol, Inst Estudios Inmunidad,FFyB, RA-1113 Buenos Aires, DF, Argentina. RP Mariuzza, RA (reprint author), Univ Maryland, Maryland Biotechnol Inst, Ctr Adv Res Biotechnol, 9600 Gudelsky Dr, Rockville, MD 20850 USA. EM mariuzza@indigo2.carb.nist.gov RI Margulies, David/H-7089-2013; OI Li, Hongmin/0000-0002-8684-5308; Margulies, David/0000-0001-8530-7375; Malchiodi, Emilio/0000-0001-7501-3330 FU NIAID NIH HHS [AI36900] NR 68 TC 54 Z9 55 U1 0 U2 3 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD OCT 16 PY 1998 VL 283 IS 1 BP 179 EP 191 DI 10.1006/jmbi.1998.2091 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 129EN UT WOS:000076450900015 PM 9761682 ER PT J AU Chuluyan, HE Lang, BJ Yoshimura, T Kenney, JS Issekutz, AC AF Chuluyan, HE Lang, BJ Yoshimura, T Kenney, JS Issekutz, AC TI Chemokine production and adhesion molecule expression by neural cells exposed to IL-1, TNF alpha and interferon gamma SO LIFE SCIENCES LA English DT Article DE neuroblastoma; cytokine; monocyte chemotactic protein-1; interleukin-8; adhesion molecule ID MONOCYTE CHEMOATTRACTANT PROTEIN-1; NECROSIS-FACTOR-ALPHA; MONOCLONAL-ANTIBODIES; TRANSENDOTHELIAL MIGRATION; NERVOUS-SYSTEM; RETINOIC ACID; HUMAN BRAIN; INDUCTION; CYTOKINES; DIFFERENTIATION AB We investigated the effect of TNF alpha, IL-1 alpha and IFN gamma on two neuroblastoma (NB) cell lines (SK-N-SH and SK-N-MC). These lines responded differentially to IL-1 alpha, TNF alpha and IFN gamma for MCP-1 and IL-8 production and expression of the ICAM-1 and VCAM-1 adhesion molecules. None of the cytokines induced MCP-1 or IL-8 on SK-N-MC cells. Both chemokines were produced in response to IL-1 alpha by SK-N-SH cells, while TNF alpha induced mainly MCP-1 production. Addition of IFN gamma decreased IL-8, but not MCP-1 production. These responses correlated with monocyte and neutrophil chemotactic activity in NE culture supernatants. This activity was neutralized by antibodies to IL-8 and MCP-1. The expression of ICAM-1 on SK-N-MC was up-regulated by TNF alpha or IFN gamma, while IL-1 alpha also upregulated ICAM-1 on SK-N-SH cells. VCAM-1 expression on SK-N-SH was induced by IL-1 alpha and TNF alpha and IFN gamma synergized with TNF alpha in this respect on both NE cell lines. These results suggest that mechanisms for chemokine production and VCAM-1 and ICAM-1 upregulation by inflammatory cytokines differ and IFN gamma, in conjunction with TNF alpha, stimulate neural cell responses (high MCP-1 and VCAM-1 and decreased IL-8) favouring mononuclear cell recruitment. C1 Dalhousie Univ, IWK Grace Hlth Ctr, Dept Pediat Microbiol & Immunol, Halifax, NS B3J 3G9, Canada. NCI, Frederick, MD 21701 USA. Antibody Solut, Palo Alto, CA USA. RP Issekutz, AC (reprint author), Dalhousie Univ, IWK Grace Hlth Ctr, Dept Pediat Microbiol & Immunol, 5850 Univ Ave, Halifax, NS B3J 3G9, Canada. EM aissekutz@iwkgrace.ns.ca NR 46 TC 16 Z9 16 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0024-3205 J9 LIFE SCI JI Life Sci. PD OCT 16 PY 1998 VL 63 IS 21 BP 1939 EP 1952 DI 10.1016/S0024-3205(98)00470-6 PG 14 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 133DV UT WOS:000076671900011 PM 9825772 ER PT J AU Etzioni, R Cha, R Feuer, EJ Davidov, O AF Etzioni, R Cha, R Feuer, EJ Davidov, O TI Asymptomatic incidence and duration of prostate cancer SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE disease progression; natural history; prevalence; prostatic neoplasms; SEER program ID AGE-SPECIFIC PREVALENCE; NATURAL-HISTORY; CARCINOMA; PREDICTOR; MODEL; MEN AB Prostate cancer is known as a disease with an extremely high prevalence relative to its clinical incidence in the population. The combination of preclinical incidence and duration that could yield this phenomenon is of tremendous interest to researchers trying to understand the natural history of the disease and to develop efficient screening strategies. In this article, the authors present estimates of the age-specific asymptomatic incidence and average preclinical duration of prostate cancer. The methodological approach is to first estimate the age-specific incidence of new (stage Al) prostate cancers using preclinical prevalence data from autopsy studies performed between 1941 and 1964 and clinical incidence data for the years 1960-1986 from the Surveillance, Epidemiology, and End Results (SEER) program of the National Cancer Institute. Then, the preclinical prevalence estimates are divided by the derived preclinical incidence estimates to yield estimates of the average duration of asymptomatic disease. The estimated mean duration among white men is between 11 and 12 years and appears to be approximately 1 year shorter for blacks than for whites. Comparison of the lifetime risks of preclinical and clinical disease suggests that approximately 75% of prostate cancers will never become diagnosed if clinical incidence remains at levels observed in 1984-1986, prior to the introduction of prostate-specific antigen (PSA) screening in the population. C1 Fred Hutchinson Canc Res Ctr, Program Biostat, Seattle, WA 98109 USA. NCI, Bethesda, MD 20892 USA. RP Etzioni, R (reprint author), Fred Hutchinson Canc Res Ctr, Program Biostat, 1100 Fairview Ave N,MPE-665,POB 19024, Seattle, WA 98109 USA. FU NCI NIH HHS [5 F32 CA 71133-02, R29 CA70227, N01CN-05230] NR 19 TC 79 Z9 80 U1 0 U2 1 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD OCT 15 PY 1998 VL 148 IS 8 BP 775 EP 785 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 128VW UT WOS:000076429900008 PM 9786232 ER PT J AU Konig, S Fales, HM AF Konig, S Fales, HM TI Comment on the cylindrical capacitor electrospray interface SO ANALYTICAL CHEMISTRY LA English DT Article ID MASS-SPECTROMETRY AB Wang and Hackett have recently proposed (Anal. Chem. 1998, 70, 205-212) a new electrospray interface described as a "concentric cylindrical capacitor". Excellent spectra were obtained, especially in the negative ion mode, with lipid A, a 15-mer oligonucleotide, and a series of proteins. We find that similar results can be obtained merely by ensuring a direct electrical contact between the analyte inside a fused-silica capillary and the high-voltage supply. No capacitor effect need be invoked. C1 NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. Hoechst Marion Roussell, Res Ctr, Bridgewater, NJ 08807 USA. RP Fales, HM (reprint author), NHLBI, Biophys Chem Lab, NIH, Bldg 10,Room 7N318,10 Ctr Dr,MSC 1676, Bethesda, MD 20892 USA. RI Konig, Simone/B-6504-2008 OI Konig, Simone/0000-0003-0672-7246 NR 10 TC 24 Z9 24 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0003-2700 J9 ANAL CHEM JI Anal. Chem. PD OCT 15 PY 1998 VL 70 IS 20 BP 4453 EP 4455 DI 10.1021/ac980169j PG 3 WC Chemistry, Analytical SC Chemistry GA 129WV UT WOS:000076487800034 PM 9796428 ER PT J AU Taylor, T Specker, B Robbins, J Sperling, M Ho, M Ain, K Bigos, ST Brierley, J Cooper, D Haugen, B Hay, I Hertzberg, V Klein, I Klein, H Ladenson, P Nishiyama, R Ross, D Sherman, S Maxon, HR AF Taylor, T Specker, B Robbins, J Sperling, M Ho, M Ain, K Bigos, ST Brierley, J Cooper, D Haugen, B Hay, I Hertzberg, V Klein, I Klein, H Ladenson, P Nishiyama, R Ross, D Sherman, S Maxon, HR TI Outcome after treatment of high-risk papillary and non-Hurthle-cell follicular thyroid carcinoma SO ANNALS OF INTERNAL MEDICINE LA English DT Article DE thyroid neoplasms; carcinoma, papillary, follicular; outcome and process assessment (health care); thyroidectomy; radiotherapy ID EXTERNAL RADIOTHERAPY; NERVE PALSY; CANCER; IMPACT; OPERATIONS; THERAPY; SURGERY AB Background: Treatment of differentiated thyroid cancer has been studied for many years, but the benefits of extensive initial thyroid surgery and the addition of radioiodine therapy or external radiation therapy remain controversial. Objective: To determine the relations among extent of surgery, radioiodine therapy, and external radiation therapy in the treatment of high-risk papillary and non-Hurthle-cell follicular thyroid carcinoma. Design: Analysis of data from a multicenter study. Setting: 14 institutions in the United States and Canada participating in the National Thyroid Cancer Treatment Cooperative Study Registry. Patients: 385 patients with high-risk thyroid cancer (303 with papillary carcinoma and 82 with follicular carcinoma). Measurements: Death, disease progression, and disease-free survival. Results: Total or near-total thyroidectomy was done in 85.3% of patients with papillary carcinoma and 71.3% of patients with follicular cancer. Overall surgical complication rate was 14.3%. Total or near-total thyroidectomy improved overall survival (risk ratio [RR], 0.37 [95% CI, 0.18 to 0.75]) but not cancer-specific mortality, progression, or disease-free survival in patients with papillary cancer. No effect of extent of surgery was seen in patients with follicular thyroid cancer. Postoperative iodine-131 was given to 85.4% of patients with papillary cancer and 79.3% of patients with follicular cancer. In patients with papillary cancer, radioiodine therapy was associated with improvement in cancer-specific mortality (RR, 0.30 [CI, 0.09 to 0.93 by multivariate analysis only]) and progression (RR, 0.30 [CI, 0.13 to 0.72]). When tall-cell variants were excluded, the effect on outcome was not significant. After radioiodine therapy, patients with follicular thyroid cancer had improvement in overall mortality (RR, 0.17 [CI, 0.06 to 0.47]), cancer-specific mortality (RR, 0.12 [CI, 0.04 to 0.42]), progression (RR, 0.21 [CI, 0.08 to 0.56]), and disease-free survival (RR, 0.29 [CI, 0.08 to 1.01]). External radiation therapy to the neck was given to 18.5% of patients and was not associated with improved survival, lack of progression, or disease-free survival. Conclusions: This study supports improvement in overall and cancer-specific mortality among patients with papillary and follicular thyroid cancer after postoperative iodine-131 therapy. Radioiodine therapy was also associated with improvement in progression in patients with papillary cancer and improvement in progression and disease-free survival in patients with follicular carcinoma. C1 Univ Cincinnati, Med Ctr, Cincinnati, OH 45267 USA. Georgetown Univ, Med Ctr, Washington, DC 20007 USA. NIH, Bethesda, MD 20892 USA. Univ Kentucky, Med Ctr, Dept Med, Lexington, KY USA. Maine Med Ctr, Dept Pathol, Scarborough, ME 04074 USA. Princess Margaret Hosp, Ontario Canc Inst, Toronto, ON M4X 1K9, Canada. Sinai Hosp, Div Endocrine, Baltimore, MD 21215 USA. Univ Colorado, Hlth Sci Ctr, Div Endocrinol, Denver, CO 80262 USA. Mayo Clin & Mayo Fdn, Div Endocrinol W18, Rochester, MN 55905 USA. N Shore Univ Hosp, Manhasset, NY USA. Johns Hopkins Hosp, Baltimore, MD 21287 USA. Massachusetts Gen Hosp, Thyroid Unit ACC730, Boston, MA 02114 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Pittsburgh, Med Ctr, Pittsburgh, PA 15260 USA. Maine Med Ctr, Dept Pathol, Scarborough, ME 04074 USA. RP Taylor, T (reprint author), Bayer Pharmaceut, Metab Dept, 400 Morgan Lane, W Haven, CT 06516 USA. OI Sherman, Steven/0000-0002-3079-5153 NR 25 TC 101 Z9 105 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 J9 ANN INTERN MED JI Ann. Intern. Med. PD OCT 15 PY 1998 VL 129 IS 8 BP 622 EP + PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 128WR UT WOS:000076431800004 PM 9786809 ER PT J AU Jacobs, S Schurmann, A Becker, W Bockers, TM Copeland, NG Jenkins, NA Joost, HG AF Jacobs, S Schurmann, A Becker, W Bockers, TM Copeland, NG Jenkins, NA Joost, HG TI The mouse ADP-ribosylation factor-like 4 gene: two separate promoters direct specific transcription in tissues and testicular germ cell SO BIOCHEMICAL JOURNAL LA English DT Article ID ANGIOTENSIN-CONVERTING ENZYME; GTP-BINDING PROTEINS; ARF-FAMILY; PHOSPHOLIPASE-D; NUCLEOTIDE-SEQUENCE; MESSENGER-RNAS; CHOLERA-TOXIN; EXPRESSION; ORGANIZATION; ACTIVATOR AB ADP-ribosylation factor-like protein 4 (ARL4) is a Ras-related GTPase that has been cloned from the 3T3-L1 preadipocyte cell line as an adipocyte-specific cDNA [Schurmann, Breiner, Becker, Huppertz, Kainulainen, Kentrup and Joost (1994) J. Biol. Chem. 269, 15683-15688]. The Ar14 gene maps to the proximal region of mouse chromosome 12 linked to Lamb1-1, Hfhbf1 and Sos2. Compared with all other known genes of Ras-related GTPases, the genomic organization of Ar14 is unusual in that its entire coding region, the 3' untranslated region (UTR) and most of the 5' UTR are located on a single exon, This structure suggests that Arl4 has evolved by retroposition of an Arf (ADP-ribosylation factor) or Arf-like gene. Isolation of the 5' UTR by rapid amplification of cDNA ends (RACE)-PCR revealed heterogeneous transcription initiation sites in alternative exons 1. Both 5'-flanking regions exhibited promoter activity when expressed in COS-7 cells, indicating that the expression of Arl4 is directed by two separate promoters. mRNA transcribed under the control of the downstream promoter was isolated by RACE-PCR from all investigated tissues. In contrast, the upstream promoter seems to drive specifically the expression of Arl4 in adult testis. Hybridization of rat testis in situ indicated that Arl4 is expressed in germ cells of puberal and adult testis, but not in prepuberal testis, suggesting that Arl4 is involved in sperm production. C1 Rhein Westfal TH Aachen, Fak Med, Inst Pharmakol & Toxikol, D-52057 Aachen, Germany. Univ Munster, Inst Anat, D-48149 Munster, Germany. Leibniz Inst Neurobiol, D-39118 Magdeburg, Germany. NCI, Mammalian Genet Lab, ABL Basic Res Program, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Joost, HG (reprint author), Rhein Westfal TH Aachen, Fak Med, Inst Pharmakol & Toxikol, Wendlingweg 2, D-52057 Aachen, Germany. EM joost@rwth-aachen.de RI Becker, Walter/B-8889-2008; Joost, Hans-Georg/J-4462-2013 OI Becker, Walter/0000-0002-0347-4768; Joost, Hans-Georg/0000-0002-5860-606X NR 38 TC 11 Z9 14 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 OCT 15 PY 1998 VL 335 BP 259 EP 265 PN 2 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 134TP UT WOS:000076759700009 PM 9761722 ER PT J AU Purdon, AD Rapoport, SI AF Purdon, AD Rapoport, SI TI Energy requirements for two aspects of phospholipid metabolism in mammalian brain SO BIOCHEMICAL JOURNAL LA English DT Article ID DEPENDENT AMINOPHOSPHOLIPID TRANSLOCATION; VANADATE-SENSITIVE ATPASE; ERYTHROCYTE-MEMBRANE; BOVINE BRAIN; RAT-BRAIN; ENDOPLASMIC-RETICULUM; ACID INCORPORATION; FATTY-ACIDS; TURNOVER; MICROSOMES AB Previous estimates have placed the energy requirements of total phospholipid metabolism in mammalian brain at 2% or less of total ATP consumption. This low estimate was consistent with the very long half-lives (up to days) reported for fatty acids esterified within phospholipids. However, using an approach featuring analysis of brain acyl-CoA, which takes into account dilution of the precursor acyl-CoA pool by recycling of fatty acids, we reported that half-lives of fatty acids in phospholipids are some 100 times shorter (min-h) than previously thought. Based on these new estimates of short half-lives, palmitic acid and arachidonic acid were used as prototype fatty acids to calculate energy consumption by fatty acid recycling at the sn-1 and sn-2 positions of brain phospholipids. We calculated that the energy requirements for reacylation of fatty acids into lysophospholipids are 5% of net brain ATP consumption. We also calculated ATP requirements for maintaining asymmetry of the aminophospholipids, phosphatidylserine and phosphatidylethanolamine across brain membrane bilayers. This asymmetry is maintained by a translocase at a stoichiometry of 1 mol of ATP per mol of phospholipid transferred in either direction across the membrane. The energy cost of maintaining membrane bilayer asymmetry of aminophospholipids at steady-state was calculated to be 8% of total ATP consumed. Taken together, deacylation-reacylation and maintenance of membrane asymmetry of phosphatidylserine and phosphatidylethanolamine require about 13% of ATP consumed by brain as a whole. This is a lower limit for energy consumption by processes involving phospholipids, as other processes, including phosphorylation of polyphosphoinositides and de novo phospholipid biosynthesis, were not considered. C1 NIA, Neurosci Lab, NIH, Bethesda, MD 20892 USA. RP Rapoport, SI (reprint author), NIA, Neurosci Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. EM SIR@Helix.nih.gov NR 46 TC 44 Z9 45 U1 0 U2 1 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON, ENGLAND W1N 3AJ SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD OCT 15 PY 1998 VL 335 BP 313 EP 318 PN 2 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 134TP UT WOS:000076759700016 PM 9761729 ER PT J AU Lang, DH Yeung, CK Peter, RM Ibarra, C Gasser, R Itagaki, K Philpot, RM Rettie, AE AF Lang, DH Yeung, CK Peter, RM Ibarra, C Gasser, R Itagaki, K Philpot, RM Rettie, AE TI Isoform specificity of trimethylamine N-oxygenation by human flavin containing monooxygenase (FMO) and P450 enzymes - Selective catalysis by FMO3 SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE flavin containing monooxygenase; trimethylamine; benzydamine; N-oxidation; trimethylaminuria; cytochrome P450 ID PERFORMANCE LIQUID-CHROMATOGRAPHY; FISH-ODOR SYNDROME; LIVER-MICROSOMES; EXPRESSION; OXIDE; IDENTIFICATION; METABOLISM; MECHANISM; FAMILY; AMINES AB In the present study, we expressed human flavin-containing monooxygenase 1 (FMO1), FMO3, FMO4t (truncated), and FMO5 in the baculovirus expression vector system at levels of 0.6 to 2.4 nmol FMO/mg of membrane protein. These four isoforms, as well as purified rabbit FMO2, and eleven heterologously expressed human P450 isoforms were examined for their capacity to metabolize trimethylamine (TMA) to its N-oxide (TMAO), using a new, specific HPLC method with radiochemical detection. Human FMO3 was by far the most active isoform, exhibiting a turnover number of 30 nmol TMAO/nmol FMO3/min at pH 7.4 and 0.5 mM TMA. None of the other monooxygenases formed TMAO at rates greater than 1 nmol/nmol FMO/min under these conditions. Human fetal liver, adult liver, kidney and intestine microsomes were screened for TMA oxidation, and only human adult liver microsomes provided substantial TMAO formation (range 2.9 to 9.1 nmol TMAO/mg protein/min, N = 5). Kinetic studies of TMAO formation by recombinant human FMO3, employing three different analytical methods, resulted in a K-m of 28 +/- 1 mu M and a V-max of 36.3 +/- 5.7 nmol TMAO/nmol FMO3/min. The K-m determined in human liver microsomes ranged from 13.0 to 54.8 mu M. Therefore, at physiological pH, human FMO3 is a very specific and efficient TMA N-oxygenase, and is likely responsible for the metabolic clearance of TMA in vivo in humans. In addition, this specificity provides a good in vitro probe for the determination of FMO3-mediated activity in human tissues, by analyzing TMAO formation at pH 7.4 with TMA concentrations not higher than 0.5 mM. (C) 1998 Elsevier Science Inc. C1 Univ Washington, Dept Med Chem, Seattle, WA 98195 USA. F Hoffmann La Roche, Basel, Switzerland. NIEHS, Cellular & Mol Pharmacol Lab, Res Triangle Pk, NC 27709 USA. RP Rettie, AE (reprint author), Univ Washington, Dept Med Chem, Box 357610, Seattle, WA 98195 USA. FU NIGMS NIH HHS [GM43511] NR 33 TC 114 Z9 118 U1 4 U2 33 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD OCT 15 PY 1998 VL 56 IS 8 BP 1005 EP 1012 DI 10.1016/S0006-2952(98)00218-4 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 125DV UT WOS:000076222900011 PM 9776311 ER PT J AU Tisdale, JF Stewart, AK Dickstein, B Little, RF Dube, L Cappe, D Dunbar, CE Brown, KE AF Tisdale, JF Stewart, AK Dickstein, B Little, RF Dube, L Cappe, D Dunbar, CE Brown, KE TI Molecular and serological examination of the relationship of human herpesvirus 8 to multiple myeloma: orf 26 sequences in bone marrow stroma are not restricted to myeloma patients and other regions of the genome are not detected SO BLOOD LA English DT Article ID SARCOMA-ASSOCIATED HERPESVIRUS; HUMAN-HERPESVIRUS-8 DNA-SEQUENCES; KAPOSIS-SARCOMA; NEGATIVE INDIVIDUALS; INFECTION; CELLS; KSHV; ANTIBODIES; PREVALENCE; LYMPHOMA AB Human herpesvirus 8 (HHV-8) genomic sequences were recently detected by polymerase chain reaction (BCR) and in situ hybridization in bone marrow stromal cells grown from multiple myeloma (MM) patients, but not in cells from control subjects (Rettig et al, Science 276:1851, 1997). We sought to confirm these observations in our own group of MM patients In = 30). DNA was extracted from adherent stromal cells grown under varying conditions and assayed for HHV-8 sequence using PCR to amplify the orf 26 (KS330) sequence (Chang et al, Science 266:1865, 1997), as initially reported. Samples from human control subjects (n = 25) were concurrently extracted and analyzed. After 30 cycles of amplification, we did not detect any positive samples. In a more sensitive nested PCR, samples from 18 of 30 (60%) MM patients were positive, at about the limit of detection, but orf 26 sequence was also amplified from 11 of 25 (44%) human control samples. However, PCR amplification from other regions of the viral genome (orf 72 and orf 75) was uniformly negative for all MM and control samples, despite equivalent sensitivity, Additionally, all sera from MM patients were negative for HHV-8 IgG by immunofluorescence. Our data do not support a role of HHV-8 in the etiology of MM but may suggest the presence of a related (KS330-containing) virus in MM patients and in some control subjects, This is a US government work, There are no restrictions on its use. C1 NHLBI, Hematol Branch, Bethesda, MD 20892 USA. Toronto Hosp, Toronto, ON M5T 2S8, Canada. NCI, HIV & AIDS Malignancy Branch, Bethesda, MD 20892 USA. Sunnybrook Reg Hlth Sci Ctr, Dept Lab Med, Toronto, ON, Canada. RP Brown, KE (reprint author), NIH, Bldg 10,Room 7C218,9000 Rockville Pike, Bethesda, MD 20892 USA. EM brownk@gwgate.nhlbi.nih.gov NR 38 TC 43 Z9 43 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD OCT 15 PY 1998 VL 92 IS 8 BP 2681 EP 2687 PG 7 WC Hematology SC Hematology GA 128AZ UT WOS:000076384200009 PM 9763550 ER PT J AU Krausner, RD AF Krausner, RD TI Cancer, minorities & the medically underserved - The role of the National Cancer Institute SO CANCER LA English DT Editorial Material CT 6th Biennial Symposium on Minorities, the Medically Underserved and Cancer CY APR 23-27, 1997 CL WASHINGTON, D.C. SP Intercultural Canc Council C1 NCI, Bethesda, MD 20892 USA. RP Krausner, RD (reprint author), NCI, Bldg 31,Room 11A-48, Bethesda, MD 20892 USA. 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 USA SN 0008-543X J9 CANCER JI Cancer PD OCT 15 PY 1998 VL 83 IS 8 SU S BP 1703 EP 1706 PG 4 WC Oncology SC Oncology GA 128VG UT WOS:000076428600007 ER PT J AU Liu, ET AF Liu, ET TI The uncoupling of race and cancer genetics SO CANCER LA English DT Article; Proceedings Paper CT 6th Biennial Symposium on Minorities, the Medically Underserved and Cancer CY APR 23-27, 1997 CL WASHINGTON, D.C. SP Intercultural Canc Council ID BREAST-CANCER; JEWISH WOMEN; SURVIVAL; MUTATIONS; WHITE; BLACK AB The incidence of breast cancer is higher among white Americans than black Americans, but the mortality is significantly greater in blacks. One of the most common explanations for this discrepancy is that the biology or the genetics of African Americans and their tumors are different for whites. However, the argument that these differences are determined by genes is fundamentally flawed both on genetic and on social criteria. By using rough estimates of economic status and cancer stage, there is an approximate 12-30% residual difference in breast cancer mortality between the races that is not accounted for by measurable social factors. As Asians move to the United States, there is a dramatic increase in breast and prostate cancer and a reduction in nasopharyngeal carcinomas, all approaching those of the host society. This is strong evidence that the effects of race on cancer incidence and mortality are attributable mainly to social, environmental, and cultural/behavioral factors and that genetics are secondary. What is needed is a new mind set for dealing with race and cancer research. Race should be viewed as a surrogate to identify social and cultural subgroups whose genetic pools and environmental exposures may differ from the general population. Therefore, we may use race 1) as a tool to identify high risk individuals, 2) for targeted intervention to prevent disease, and 3) to uncover the important economic, cultural, and behavioral contributions to cancer outcome. In conclusion, biology and genetics are the basis for understanding the cancer cell, but socioeconomic issues, such as access to health care, are vitally important in the outcome of cancer patients. Cancer 1998;83:1765-9. (C) 1998 American Cancer Society. C1 NCI, Div Clin Sci, NIH, Bethesda, MD 20892 USA. RP Liu, ET (reprint author), NCI, Div Clin Sci, NIH, Bldg 31,Room 3A11,31 Ctr Dr,MSC 2440, Bethesda, MD 20892 USA. RI Liu, Edison/C-4141-2008 NR 12 TC 10 Z9 10 U1 1 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0008-543X J9 CANCER JI Cancer PD OCT 15 PY 1998 VL 83 IS 8 SU S BP 1765 EP 1769 PG 5 WC Oncology SC Oncology GA 128VG UT WOS:000076428600019 ER PT J AU Rimer, BK AF Rimer, BK TI Interventions to enhance cancer screening - A brief review of what works and what is on the horizon SO CANCER LA English DT Article; Proceedings Paper CT 6th Biennial Symposium on Minorities, the Medically Underserved and Cancer CY APR 23-27, 1997 CL WASHINGTON, D.C. SP Intercultural Canc Council DE interventions; breast and cervical cancer screening; tailored; community directed; provider directed ID INCOME MINORITY WOMEN; MAMMOGRAPHY UTILIZATION; PROMOTE MAMMOGRAPHY; BLACK-WOMEN; ADHERENCE; STRATEGY; PROGRAM; BREAST AB Although major advances have been made in the proportion of women who have been screened for breast and cervical cancer, there are still large numbers of women who are not being screened on schedule. This article includes a very selective review of types of interventions that have been used to increase cancer screening. These include the following kinds of interventions: mass media, patient-directed, provider- and system-directed access-enhancing, community-directed, policy level, and multilevel interventions. Several different kinds of interventions have been used to increase cancer screening. The most extensive research has been conducted in the areas of breast and cervical cancer screening. Some relatively simple and inexpensive interventions have been shown to double or triple the odds that women will get screened; these include simple reminder letters or cards and telephone counseling. Tailored interventions are a new area and hold promise. Some studies have shown the value of access-enhancing strategies, such as the use of mobile vans. Policy changes are necessary but are not sufficient to increase the use of screening. One of the challenges for the future is to reach the groups in the population that have remained resistant to screening despite numerous messages in the mass media. The interventions of the future should reflect what has been learned in the past, such as the importance of reminders and cues to screening and overcoming women's barriers through strategies, such as counseling. However, tomorrow's interventions also should take advantage of digital technology and other advances in communications, and interventions should be tailored to the special needs of individuals in ways that are responsive to their learning preferences, situational constraints, and life styles. Far more research is needed to address the heterogeneity of minority populations in the United States and elsewhere. At present, it is not known to what extent interventions tested among black populations will extend to other minorities. Cancer 1998;83:1770-4. (C) 1998 American Cancer Society. C1 Duke Univ, Med Ctr, Durham, NC USA. RP Rimer, BK (reprint author), NCI, Div Canc Control & Populat Sci, Execut Plaza N,Room 242,6130 Execut Blvd, Bethesda, MD 20892 USA. NR 35 TC 10 Z9 10 U1 2 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0008-543X J9 CANCER JI Cancer PD OCT 15 PY 1998 VL 83 IS 8 SU S BP 1770 EP 1774 DI 10.1002/(SICI)1097-0142(19981015)83:8+<1770::AID-CNCR20>3.0.CO;2-7 PG 5 WC Oncology SC Oncology GA 128VG UT WOS:000076428600020 ER PT J AU Tyson, FL Cook, K Gavin, J Gaylord, CE Lee, C Setlow, VP Wilson, S AF Tyson, FL Cook, K Gavin, J Gaylord, CE Lee, C Setlow, VP Wilson, S TI Cancer, the environment, and environmental justice SO CANCER LA English DT Article; Proceedings Paper CT 6th Biennial Symposium on Minorities, the Medically Underserved and Cancer CY APR 23-27, 1997 CL WASHINGTON, D.C. SP Intercultural Canc Council C1 NIEHS, Div Intramural Res, Res Triangle Pk, NC 27713 USA. SUNY Albany, Albany, NY 12222 USA. Howard Hughes Med Inst, Coconut Grove, FL 33133 USA. US EPA, Environm Justice Off, Washington, DC 20460 USA. Natl Acad Sci, Inst Med, Dept Hlth Sci Policy, Washington, DC 20418 USA. NIEHS, NIH, Bethesda, MD USA. RP Tyson, FL (reprint author), NIEHS, Div Intramural Res, 104 Alexander Dr, Res Triangle Pk, NC 27713 USA. NR 0 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 USA SN 0008-543X J9 CANCER JI Cancer PD OCT 15 PY 1998 VL 83 IS 8 SU S BP 1784 EP 1792 DI 10.1002/(SICI)1097-0142(19981015)83:8+<1784::AID-CNCR22>3.0.CO;2-P PG 9 WC Oncology SC Oncology GA 128VG UT WOS:000076428600022 ER PT J AU Epps, RP AF Epps, RP TI A comprehensive national minority intervention in tobacco control SO CANCER LA English DT Article; Proceedings Paper CT 6th Biennial Symposium on Minorities, the Medically Underserved and Cancer CY APR 23-27, 1997 CL WASHINGTON, D.C. SP Intercultural Canc Council DE tobacco control; American Stop Smoking Intervention Study; multicultural populations AB Tobacco use is a major cancer risk among minorities, as evidenced by their high cancer mortality rates compared with white populations. Prior public health prevention efforts have concentrated on affecting individual behavior change through education and smoking-cessation techniques. The American Stop Smoking Intervention Study (ASSIST) project, which is sponsored by the National Cancer Institute and the American Cancer Society, is a 7-year research and applications project designed to demonstrate the effectiveness of coalition-based policy interventions on smoking prevention and cessation. ASSIST places major emphasis on the involvement of minority populations in this project as well as all women and youth. Minority involvement is evident through 1) representation and leadership on all levels of ASSIST policy development and administration; 2) inclusion of minority components in all national ASSIST conferences, including minority recruitment, coalition development, and sustainability design; 3) provision of specialized technical assistance and training to the 17 states by the ASSIST Coordinating Center; and 4) incorporation of minority specific activities in the various ASSIST states. Outcome evaluation of the effectiveness of the ASSIST approach will be conducted after the project's completion in 1998. However, early indicators show a marked increase in minority participation. Between 1994 and 1996, there has been an almost four-fold increase in proposed activities to reach underserved and minority communities. Most ASSIST states have formed multicultural coalitions. These results show that 1) intervention models emphasizing community-based policy activities in cancer prevention can address multicultural concerns successfully, 2) linkages with groups with similar multicultural interests increase the likelihood and success of joint cancer control efforts, and 3) policy-based interventions are more likely to have a pronounced effect on decreasing smoking and cancer prevalence than education programs or individual smoking-cessation efforts alone. Cancer 1998;83:1793-5. (C) 1998 American Cancer Society. C1 NCI, Publ Hlth Applicat Branch, Canc Control Res Program, Div Canc Prevent & Control,NIH, Bethesda, MD 20892 USA. RP Epps, RP (reprint author), NCI, Publ Hlth Applicat Branch, Canc Control Res Program, Div Canc Prevent & Control,NIH, Execut Plaza N,Room 241,6130 Execut Blvd,MSC-7337, Bethesda, MD 20892 USA. NR 2 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 USA SN 0008-543X J9 CANCER JI Cancer PD OCT 15 PY 1998 VL 83 IS 8 SU S BP 1793 EP 1795 DI 10.1002/(SICI)1097-0142(19981015)83:8+<1793::AID-CNCR23>3.0.CO;2-O PG 3 WC Oncology SC Oncology GA 128VG UT WOS:000076428600023 ER PT J AU Huerta, EE Weed, DL AF Huerta, EE Weed, DL TI Cuidando su Salud - Spanish-language radio in preventive medicine and public health SO CANCER LA English DT Article; Proceedings Paper CT 6th Biennial Symposium on Minorities, the Medically Underserved and Cancer CY APR 23-27, 1997 CL WASHINGTON, D.C. SP Intercultural Canc Council DE Hispanic Americans; radio; media; health promotion; disease prevention; health protection; preventive services; Healthy People 2000 ID UNITED-STATES; HISPANICS; BLACKS AB In large urban areas, Hispanics are often dependent upon local Spanish-language broadcast and print media for news and entertainment. Since 1989, a radio show has provided daily disease prevention and health promotion messages to Hispanics on a Washington, DC area Spanish-language station. "Cuidando su Salud" (Taking Care of Your Health) lasts 2 minutes and is heard three times a day during news segments. By November 1997, 1543 different individual programs had been produced. Categorized according to Healthy People 2000 guidelines, these programs included 603 on health promotion (including programs on tobacco, alcohol, violence, and mental health), 162 on health protection (including programs on unintentional injuries, food and drug safety, and environmental health), and 733 on preventive services (acquired immune defeciency syndrome, cancer, infectious diseases, maternal and infant health, and policy issues affecting Hispanics). The show has been used successfully to recruit women for preventive health services and cancer clinical trials. Radio should be considered a tool for reaching special populations with health promotion and disease prevention messages. Cancer 1998;83:1805-8, (C) 1998 American Cancer Society. C1 Washington Hosp Ctr, Washington Canc Inst, Washington, DC 20010 USA. NCI, Bethesda, MD 20892 USA. RP Huerta, EE (reprint author), Washington Hosp Ctr, Washington Canc Inst, 110 Irving St NW,Room C1219, Washington, DC 20010 USA. NR 21 TC 3 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 USA SN 0008-543X J9 CANCER JI Cancer PD OCT 15 PY 1998 VL 83 IS 8 SU S BP 1805 EP 1808 DI 10.1002/(SICI)1097-0142(19981015)83:8+<1805::AID-CNCR26>3.0.CO;2-F PG 4 WC Oncology SC Oncology GA 128VG UT WOS:000076428600026 ER PT J AU Stevenson-Perez, H AF Stevenson-Perez, H TI America's cancer prevention, treatment, research, and education programs must include Hispanic Americans SO CANCER LA English DT Article; Proceedings Paper CT 6th Biennial Symposium on Minorities, the Medically Underserved and Cancer CY APR 23-27, 1997 CL WASHINGTON, D.C. SP Intercultural Canc Council DE war on cancer; Hispanic-Americans; cancer treatment; cancer prevention; bilingual/bicultural services; Latino education Executive Order 12900; retraining of Latin-American-educated health professionals; cancer research; community-based Latino health infrastructure development; Historically Black Colleges and Universities AB During the Sixth Biennial Symposium on Minorities, the Underserved and Cancer, several presentations highlighted the unresolved barriers that preclude appropriate levels of Latino participation in the nation's cancer programs. This report summarizes the key demographic data regarding the fastest growing population of eligible U.S. cancer services consumers, Hispanic Americans, as presented in recent federal reports. The barriers that preclude appropriate levels of Latino inclusion in our nation's cancer treatment, prevention, research, and educational programs, likewise, are abstracted from federal sources and from other reports that reflect the national dialogue that has taken place on this topic over the past 5 years. In the nation, as it enters the second millenium, there will be over 39 million Latinos who expect their fair share of the cancer treatment, research, prevention, and education service that they pay for each year in taxes. However, to date, the representation of Latinos in our nation's cancer clinical research is less than 2% of all participants, with very little bilingual services provided, thus raising serious questions about the true safety of the novel cancer treatments that are approved each year by the Food and Drug Administration. Similarly, the Hispanic community faces a staggering 30% overall drop-out rate from our educational system, much higher in the oncology professional series, raising serious concerns about the ability of our nation's cancer infrastructure ever to be able to serve adequately this very large consumer base, many of whom prefer to conduct their cancer health care family decisions in Spanish. This lack of Hispanic customer service capability is clearly highlighted by the recent declaration of Latinos as the only globally underrepresented employment group in the federal government, as in most private health care delivery organizations. In the public health agencies of the federal government, Hispanic employment hovers at around 2.5% and is even lower in the policy-making professional series that deal with cancer. Numerous federal reports have highlighted the specific steps that must be taken to break this vicious cycle of Latino exclusion from the nation's health infrastructure, including, with regard to cancer, 1) recognize that Latino health consumers, as taxpayers, must be served appropriately, including in our cancer clinical trials programs; 2) recognize that appropriate Latino customer service, including service provision in Spanish, is everyone's responsibility; 3) develop special incentive packages to adequately hire and promote Latinos and others with bilingual/bicultural skills in the nation's cancer infrastructure; 4) immediately amend Executive Order 12900, "Educational Excellence for Hispanic-Americans," to provide the level of funding required to reverse the enormous Latino educational drop-out rate-our nation requires more Hispanic-American cancer professionals, as well as a better educated Latino cancer consumer base; and 5) insist that all cancer clinical trials include adequate numbers of Latinos, including those with limited English proficiency, to scientifically prove treatment safety in this at-risk population-before any new drug approvals are granted. Cancel 1998;83:1872-6. (C) 1998 American Cancer Society. C1 NCI, NIH, Bethesda, MD 20892 USA. RP Stevenson-Perez, H (reprint author), ZIB Sci Power Syst Inc, 11223 Valley View Ave, Kensington, MD 20895 USA. RI Johnson, Marilyn/E-7209-2011 NR 9 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 USA SN 0008-543X J9 CANCER JI Cancer PD OCT 15 PY 1998 VL 83 IS 8 SU S BP 1872 EP 1876 DI 10.1002/(SICI)1097-0142(19981015)83:8+<1872::AID-CNCR41>3.0.CO;2-U PG 5 WC Oncology SC Oncology GA 128VG UT WOS:000076428600041 ER PT J AU Vandier, D Rixe, O Brenner, M Gouyette, A Besnard, F AF Vandier, D Rixe, O Brenner, M Gouyette, A Besnard, F TI Selective killing of glioma cell lines using an astrocyte-specific expression of the herpes simplex virus thymidine kinase gene SO CANCER RESEARCH LA English DT Article ID FIBRILLARY ACIDIC PROTEIN; TRANSGENIC MICE; BRAIN-TUMORS; PROMOTER; GANCICLOVIR; THERAPY; GFAP; DNA AB Gene therapy using the herpes simplex virus thymidine kinase gene (HSV-TK) is a promising new approach for the treatment of gliomas, a tumor type with a poor prognosis. To limit the toxic effects of this procedure, it is desirable to restrict expression of the HSV-TK gene to the target cells. This can be accomplished by use of the promoter of the glial fibrillary acidic protein gene, an intermediate filament protein expressed primarily in astrocytes. A plasmid containing the HSV-TK gene, driven by the human glial fibrillary acidic protein promoter gfa2, was lipofected into glioma cell lines and into an ovarian cancer fell line. Treatment with ganciclovir showed efficient killing of glioma cells, with no effect on the ovarian cells. Thus, the gfa2 promoter is a promising candidate for directing expression of toxic genes to gliomas. C1 Synthelabo Rech, F-92500 Rueil Malmaison, France. Inst Gustave Roussy, Dept Med, F-94805 Villejuif, France. Inst Gustave Roussy, Dept Pharmacotoxicol & Pharmacogenet, CNRS, UMR 1772, F-94805 Villejuif, France. NINDS, Bethesda, MD 20892 USA. RP Besnard, F (reprint author), Synthelabo Rech, 10 Rue Carrieres, F-92500 Rueil Malmaison, France. NR 24 TC 35 Z9 36 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD OCT 15 PY 1998 VL 58 IS 20 BP 4577 EP 4580 PG 4 WC Oncology SC Oncology GA 129GR UT WOS:000076455900017 PM 9788604 ER PT J AU Pizer, ES Chrest, FJ DiGiuseppe, JA Han, WF AF Pizer, ES Chrest, FJ DiGiuseppe, JA Han, WF TI Pharmacological inhibitors of mammalian fatty acid synthase suppress DNA replication and induce apoptosis in tumor cell lines SO CANCER RESEARCH LA English DT Article ID ANTIBIOTIC CERULENIN; CANCER; TARGET; CYCLE; P53 AB Pharmacological inhibitors of the anabolic enzyme, fatty acid synthase (FAS), including the natural product cerulenin and the novel compound c75, are selectively cytotoxic to cancer cells via induction of apoptosis, apparently related to the tumor cell phenotype of abnormally elevated fatty acid synthetic metabolism. As part of a larger effort to understand the immediate downstream effect of FAS inhibition that leads to apoptosis, the effects of these inhibitors on cell cycle progression were examined. Both FAS inhibitors produce rapid, profound inhibition of DNA replication and S phase progression in human cancer cells. The dose responses for fatty acid synthesis inhibition and DNA synthesis inhibition are similar. The kinetics of both effects are rapid, with fatty acid synthesis inhibition occurring within 30 min and DNA synthesis inhibition occurring within 90 min of drug exposure. Meanwhile, apoptotic changes are not detected until 6 h or later after inhibitor exposure. Fatty acid synthetic pathway activity and the magnitude of DNA synthesis inhibition by FAS inhibitors are increased in parallel by withdrawal of lipid-containing serum from the cultures. The mechanism of DNA synthesis inhibition by cerulenin is indirect, because expression of certain viral oncogenes rescues DNA synthesis/S phase progression in cerulenin-exposed cells. The data suggest a direct linkage at a regulatory level, between fatty acid synthesis and DNA synthesis in proliferating tumor cells. C1 Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21224 USA. NIA, Clin Immunol Sect, Gerontol Res Ctr, Baltimore, MD 21224 USA. RP Pizer, ES (reprint author), Johns Hopkins Bayview Med Ctr, Dept Pathol, AA154C,4940 Eastern Ave, Baltimore, MD 21224 USA. FU NCI NIH HHS [R29CA75219] NR 18 TC 190 Z9 202 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD OCT 15 PY 1998 VL 58 IS 20 BP 4611 EP 4615 PG 5 WC Oncology SC Oncology GA 129GR UT WOS:000076455900025 PM 9788612 ER PT J AU Krystal, GW DeBerry, CS Linnekin, D Litz, J AF Krystal, GW DeBerry, CS Linnekin, D Litz, J TI Lck associates with and is activated by Kit in a small cell lung cancer cell line: Inhibition of SCF-mediated growth by the Src family kinase inhibitor PP1 SO CANCER RESEARCH LA English DT Article ID C-KIT; SIGNAL-TRANSDUCTION; TYROSINE KINASES; FACTOR-I; RECEPTOR; IDENTIFICATION; EXPRESSION; MYC; PROTOONCOGENE; COEXPRESSION AB At least 70% of small cell lung cancers (SCLCs) express the Kit receptor tyrosine kinase and its ligand, stem cell factor (SCF), In an effort to define the signal transduction pathways activated by Kit in SCLC,,ce focused on Src family kinases and, in particular, Lck, a Src-related tyrosine kinase that is expressed in hemopoietic cells and certain tumors, including SCLC. SCF treatment of the H526 cell Line induced a physical association between Kit and Lck that, in vitro, was dependent on phosphorylation of the juxtamembrane domain of Kit. Stimulation of Kit with recombinant SCF resulted in a rapid 3-6-fold increase in the specific activity of Lck, which was similar in magnitude to the activation of Lck resulting from the cross-linking of the T-cell receptor complex of Jurkat cells. Lck activity peaked by 5 min after SCF addition, and the elevated activity persisted for at least 30 min in the presence of SCF, with kinetics similar to the activation of mitogen-activated protein kinase, PP1 an inhibitor of Src family kinases with selectivity for Lck, completely inhibited SCP-mediated growth but had little effect on insulin-like growth factor-I-mediated growth, PP1 antagonized both SCF-mediated proliferation and inhibition of apoptosis, PP1 had no effect on Kit kinase activity but was shown to block total Lck activity by at least 90% by immune complex kinase assay, Low levels of Src, Hck, and Yes mere also expressed in the H526 cell line; only Yes showed a consistent increase in specific activity, which was also inhibited by PP1 following SCF treatment. These data demonstrate that, in the H526 SCLC cell line, Lck and, possibly, Yes are downstream of Kit in a signal transduction pathway; the inhibition by PP1 of SCF-mediated proliferation and inhibition of apoptosis suggests that Src family kinases are intermediates in the signaling pathways that regulate these processes. C1 Virginia Commonwealth Univ, Med Coll Virginia, McGuire Vet Affairs Med Ctr, Dept Med,Div Hematol Oncol, Richmond, VA 23249 USA. NCI, Lab Leukocyte Biol, Div Basic Sci, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Krystal, GW (reprint author), Richmond Vet Affairs Med Ctr, 111K,1201 Broad Rock Blvd, Richmond, VA 23249 USA. NR 33 TC 62 Z9 62 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD OCT 15 PY 1998 VL 58 IS 20 BP 4660 EP 4666 PG 7 WC Oncology SC Oncology GA 129GR UT WOS:000076455900032 PM 9788619 ER PT J AU Russ, G Ramachandra, M Hrycyna, CA Gottesman, MM Pastan, I Bennink, JR Yewdell, JW AF Russ, G Ramachandra, M Hrycyna, CA Gottesman, MM Pastan, I Bennink, JR Yewdell, JW TI P-glycoprotein plays an insignificant role in the presentation of antigenic peptides to CD8+ T cells SO CANCER RESEARCH LA English DT Article ID CLASS-I MOLECULES; TRANSIENT-EXPRESSION SYSTEM; MULTIDRUG-RESISTANT CELLS; HYDROPHOBIC PEPTIDES; TRANSPORTER; VIRUS; TAP; LOCALIZATION; DOXORUBICIN; GENERATION AB Most antigenic peptides presented to CD8(+) T cells are generated from cytosolic precursors and are translocated by TAP into the endoplasmic reticulum, where they associate with MHC class I molecules. TAP-deficient cells exhibit a limited capacity to deliver peptides from cytosolic proteins to class I molecules. One candidate for an alternative peptide transporter is P-glycoprotein, which transports numerous substances, including peptides, across membranes. Elevation of P-glycoprotein expression is partially responsible for the resistance developed by neoplasias to chemotherapeutic drugs. Overexpression of P-glycoprotein has been reported to enhance the expression of class I molecules, Here, we investigated the role of P-glycoprotein in the generation of peptide-MHC complexes. We were unable to detect P-glycoprotein-mediated transport of synthetic peptides into the endoplasmic reticulum of either T2 cells (TAP-deficient) infected with a recombinant vaccinia virus (rVV) expressing P-glycoprotein or drug-resistant cells in which TAP is inactivated by a peptide from the herpes simplex virus ICP47 protein. Expression of rVV-encoded P-glycoprotein in T2 cells was unable to enhance cell surface expression of any of three MHC class I allomorphs tested, rVV-mediated expression of P-glycoprotein enabled T2 cells to produce limited amounts of class I-peptide complexes from cytosolic antigens, but this was not blocked by a drug that inhibits its transporter function, and a similar degree of presentation was mediated by functionally inactive mutated forms of P-glycoprotein, Thus, this was a nonspecific effect that we attributed to diminished membrane integrity resulting from P-glycoprotein overexpression, Taken together, our findings cast serious doubts that P-glycoprotein is a biologically significant transporter of cytosolic peptides. C1 NIAID, Viral Dis Lab, Bethesda, MD 20892 USA. NCI, Mol Biol Lab, Div Basic Sci, Bethesda, MD 20892 USA. NCI, Cell Biol Lab, Div Basic Sci, Bethesda, MD 20892 USA. RP Yewdell, JW (reprint author), NIH, Room 213,Bldg 4, Bethesda, MD 20892 USA. EM jyewdell@nih.gov RI yewdell, jyewdell@nih.gov/A-1702-2012 NR 37 TC 7 Z9 7 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD OCT 15 PY 1998 VL 58 IS 20 BP 4688 EP 4693 PG 6 WC Oncology SC Oncology GA 129GR UT WOS:000076455900036 PM 9788623 ER PT J AU Weil, RJ Huang, S Pack, S Vortmeyer, AO Tsokos, M Lubensky, IA Oldfield, EH Zhuang, ZP AF Weil, RJ Huang, S Pack, S Vortmeyer, AO Tsokos, M Lubensky, IA Oldfield, EH Zhuang, ZP TI Pluripotent tumor cells in benign pituitary adenomas associated with multiple endocrine neoplasia type 1 SO CANCER RESEARCH LA English DT Article ID MEN1 REGION; GENE; DIFFERENTIATION; MUTATION; LINEAGE; CANCER; 11Q13 AB Analysis of human tumor cells in vitro enhances the study of numerous neoplastic conditions. However, it has been difficult to establish long-term cultures of adenoma cells, especially those of neuroendocrine origin, because the endocrine cells survive only briefly in culture, and fibroblasts overgrow the culture dish in 1 or 2 weeks. We describe cells isolated from pituitary adenomas in two patients with multiple endocrine neoplasia type 1 in which cells with a mesenchymal phenotype evolved from pituitary tumor cells. It appears that these poorly differentiated cells arose from multipotent adenoma cells. This represents a path of cell differentiation not observed previously in humans and may help explain the diverse nature of the benign tumors in multiple endocrine neoplasia type 1. C1 NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Zhuang, ZP (reprint author), NCI, Pathol Lab, NIH, Bldg 10,Room 2A 33, Bethesda, MD 20892 USA. EM zpzhuang@helix.nih.gov RI Pack, Svetlana/C-2020-2014 NR 30 TC 8 Z9 8 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD OCT 15 PY 1998 VL 58 IS 20 BP 4715 EP 4720 PG 6 WC Oncology SC Oncology GA 129GR UT WOS:000076455900040 PM 9788627 ER PT J AU Tzahar, E Moyer, JD Waterman, H Barbacci, EG Bao, J Levkowitz, G Shelly, M Strano, S Pinkas-Kramarski, R Pierce, JH Andrews, GC Yarden, Y AF Tzahar, E Moyer, JD Waterman, H Barbacci, EG Bao, J Levkowitz, G Shelly, M Strano, S Pinkas-Kramarski, R Pierce, JH Andrews, GC Yarden, Y TI Pathogenic poxviruses reveal viral strategies to exploit the ErbB signaling network SO EMBO JOURNAL LA English DT Article DE DNA virus; growth factor; oncogene; signal transduction; tyrosine kinase ID EPIDERMAL GROWTH-FACTOR; NEU DIFFERENTIATION FACTOR; FACTOR-RELATED PEPTIDES; VACCINIA VIRUS ENCODES; SHOPE FIBROMA VIRUS; FACTOR-RECEPTOR; FACTOR-ALPHA; EGF RECEPTOR; PROTO-ONCOGENE; MYXOMA VIRUS AB Virulence of poxviruses, the causative agents of smallpox, depends on virus-encoded growth factors related to the mammalian epidermal growth factor (EGF), Here we report that the growth factors of Shope fibroma virus, Myxoma virus and vaccinia virus (SFGF, MGF and VGF) display unique patterns of specificity to ErbB receptor tyrosine kinases; whereas SFGF is a broad-specificity ligand, VGF binds primarily to ErbB-1 homodimers, and the exclusive receptor for MGF is a heterodimer comprised of ErbB-2 and ErbB3. In spite of 10- to 1000-fold lower binding affinity to their respective receptors, the viral ligands are mitogenically equivalent or even more potent than their mammalian counterparts. This remarkable enhancement of cell growth is due to attenuation of receptor degradation and ubiquitination, which leads to sustained signal transduction, Our results imply that signal potentiation and precise targeting to specific receptor combinations contribute to cell transformation at sites of poxvirus infection, and they underscore the importance of the often ignored low-affinity ligand-receptor interactions. C1 Weizmann Inst Sci, Dept Regulat Biol, IL-76100 Rehovot, Israel. NCI, Bethesda, MD 20892 USA. Pfizer Inc, Cent Res, Groton, CT 06340 USA. RP Yarden, Y (reprint author), Weizmann Inst Sci, Dept Regulat Biol, IL-76100 Rehovot, Israel. EM liyarden@weizmann.weizmann.ac.il RI strano, sabrina/B-6743-2013; YARDEN, YOSEF/K-1467-2012; OI strano, sabrina/0000-0002-6341-4230; Levkowitz, Gil/0000-0002-3896-1881 FU Fondazione Telethon NR 69 TC 81 Z9 84 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD OCT 15 PY 1998 VL 17 IS 20 BP 5948 EP 5963 DI 10.1093/emboj/17.20.5948 PG 16 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 133EN UT WOS:000076673600010 PM 9774339 ER PT J AU Zhang, AX Altuvia, S Tiwari, A Argaman, L Hengge-Aronis, R Storz, G AF Zhang, AX Altuvia, S Tiwari, A Argaman, L Hengge-Aronis, R Storz, G TI The OxyS regulatory RNA represses rpoS translation and binds the Hfq (HF-I) protein SO EMBO JOURNAL LA English DT Article DE hfq protein; oxidative stress; OxyS RNA; RNA-binding protein; rpoS ID SIGMA-FACTOR SIGMA(S); PHAGE Q-BETA; ESCHERICHIA-COLI; HOST FACTOR; SALMONELLA-TYPHIMURIUM; EXPRESSION; GENE; POLYMERASE; STABILITY; SUBUNIT AB The OxyS regulatory RNA integrates the adaptive response to hydrogen peroxide with other cellular stress responses and protects against DNA damage. Among the OxyS targets is the rpoS-encoded sigma(S) subunit of RNA polymerase. sigma(S) is a central regulator of genes induced by osmotic stress, starvation and entry into stationary phase. We examined the mechanism whereby OxyS represses rpoS expression and found that the OxyS RNA inhibits translation of the rpoS message. This repression is dependent on the hfq-encoded RNA-binding protein (also denoted host factor I, HF-I). Co-immunoprecipitation and gel mobility shift experiments revealed that the OxyS RNA binds Hfq, suggesting that OxyS represses rpoS translation by altering Hfq activity. C1 NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. Hebrew Univ Jerusalem, Hadassah Med Sch, Dept Mol Genet & Biotechnol, IL-91120 Jerusalem, Israel. Univ Konstanz, Dept Biol, D-78434 Constance, Germany. RP Storz, G (reprint author), NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. OI Storz, Gisela/0000-0001-6698-1241 NR 26 TC 238 Z9 244 U1 4 U2 15 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD OCT 15 PY 1998 VL 17 IS 20 BP 6061 EP 6068 DI 10.1093/emboj/17.20.6061 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 133EN UT WOS:000076673600020 PM 9774349 ER PT J AU Altuvia, S Zhang, AX Argaman, L Tiwari, A Storz, G AF Altuvia, S Zhang, AX Argaman, L Tiwari, A Storz, G TI The Escherichia coli OxyS regulatory RNA represses fhlA translation by blocking ribosome binding SO EMBO JOURNAL LA English DT Article DE antisense regulation; oxidative stress; OxyS RNA; ribosome binding; translation ID MESSENGER-RNA; TRANSCRIPTIONAL ACTIVATOR; FORMATE HYDROGENLYASE; PLASMID REPLICATION; CIII-GENE; MICF RNA; ANTISENSE; INITIATION; PROTEIN; INHIBITION AB OxyS is a small untranslated RNA which is induced in response to oxidative stress in Escherichia coli. This novel RNA acts as a global regulator to activate or repress the expression of as many as 40 genes, including the fhlA-encoded transcriptional activator and the rpoS-encoded sigma(S) subunit of RNA polymerase. Deletion analysis of OxyS showed that different domains of the small RNA are required for the regulation of fhlA and rpoS, We examined the mechanism of OxyS repression of fhlA and found that the OxyS RNA inhibits fhlA translation by pairing with a short sequence overlapping the Shine-Dalgarno sequence, thereby blocking ribosome binding/translation. C1 NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. Hebrew Univ Jerusalem, Hadassah Med Sch, Dept Mol Genet & Biotechnol, IL-91120 Jerusalem, Israel. RP Storz, G (reprint author), NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. OI Storz, Gisela/0000-0001-6698-1241 NR 27 TC 147 Z9 151 U1 2 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD OCT 15 PY 1998 VL 17 IS 20 BP 6069 EP 6075 DI 10.1093/emboj/17.20.6069 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 133EN UT WOS:000076673600021 PM 9774350 ER PT J AU Radnedge, L Youngren, B Davis, M Austin, S AF Radnedge, L Youngren, B Davis, M Austin, S TI Probing the structure of complex macromolecular interactions by homolog specificity scanning: the P1 and P7 plasmid partition systems SO EMBO JOURNAL LA English DT Article DE homolog specificity scanning; macromolecular interactions; plasmid partition systems; protein-DNA; protein-protein interactions ID BIPOLAR LOCALIZATION; BACILLUS-SUBTILIS; DAUGHTER CELLS; PARB PROTEIN; DNA-BINDING; HOST FACTOR; SITE; SEQUENCE AB The P1 plasmid partition locus, pi par, actively distributes plasmid copies to Escherichia coli daughter cells. It encodes two DNA sites and two proteins, ParA and ParB, Plasmid P7 uses a similar system, but the key macromolecular interactions are species specific, Homolog specificity scanning (HSS) exploits such specificities to map critical contact points between component macromolecules. The ParA protein contacts the par operon operator for operon autoregulation, and the ParB contacts the parS partition site during partition. Here, we refine the mapping of these contacts and extend the use of HSS to map protein-protein contacts. We found that ParB participates in autoregulation at the operator site by making a specific contact with ParA, Similarly, ParA acts in partition by making a specific contact with ParB bound at parS, Both these interactions involve contacts between a C-terminal region of ParA and the extreme N-terminus of ParB, As a single type of ParA-ParB complex appears to be involved in recognizing both DNA sites, the operator and the parS sites may both be occupied by a single protein complex during partition. The general HSS strategy may aid in solving the three-dimensional structures of large complexes of macromolecules. C1 NCI, Lab Gene Regulat & Chromosome Biol, ABL Basic Res Program, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Austin, S (reprint author), NCI, Lab Gene Regulat & Chromosome Biol, ABL Basic Res Program, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. EM austin@ncifcrf.gov NR 22 TC 47 Z9 48 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD OCT 15 PY 1998 VL 17 IS 20 BP 6076 EP 6085 DI 10.1093/emboj/17.20.6076 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 133EN UT WOS:000076673600022 PM 9774351 ER PT J AU Moitra, J Mason, MM Olive, M Krylov, D Gavrilova, O Marcus-Samuels, B Feigenbaum, L Lee, E Aoyama, T Eckhaus, M Reitman, ML Vinson, C AF Moitra, J Mason, MM Olive, M Krylov, D Gavrilova, O Marcus-Samuels, B Feigenbaum, L Lee, E Aoyama, T Eckhaus, M Reitman, ML Vinson, C TI Life without white fat: a transgenic mouse SO GENES & DEVELOPMENT LA English DT Article DE AP-1; C/EBP; dominant negative proteins; adipocytes; lipodystrophy; diabetes ID MITOCHONDRIAL UNCOUPLING PROTEIN; CCAAT/ENHANCER-BINDING-PROTEIN; DIFFERENTIATION-INDUCED GENE; BROWN ADIPOSE-TISSUE; MESSENGER-RNA; DNA-BINDING; ADIPOCYTE DIFFERENTIATION; MOLECULAR-CLONING; LEPTIN RECEPTOR; FACTOR-ALPHA AB We have generated a transgenic mouse with no white fat tissue throughout life. These mice express a dominant-negative protein, termed A-ZIP/F, under the control of the adipose-specific aP2 enhancer/promoter. This protein prevents the DNA binding of B-ZIP transcription factors of both the C/EBP and Tun families. The transgenic mice (named A-ZIP/F-1) have no white adipose tissue and dramatically reduced amounts of brown adipose tissue, which is inactive. They are initially growth delayed, but by week 12, surpass their littermates in weight. The mice eat, drink, and urinate copiously, have decreased fecundity, premature death, and frequently die after anesthesia. The physiological consequences of having no white fat tissue are profound. The liver is engorged with lipid, and the internal organs are enlarged. The mice are diabetic, with reduced leptin (20-fold) and elevated serum glucose (3-fold), insulin (50- to 400-fold), free fatty acids (2-fold), and triglycerides (3- to 5-fold). The A-ZIP/F-1 phenotype suggests a mouse model for the human disease lipoatrophic diabetes (Seip-Berardinelli syndrome), indicating that the lack of fat can cause diabetes. The myriad of consequences of having no fat throughout development can be addressed with this model. C1 NIDDKD, Diabet Branch, Bethesda, MD 20892 USA. NCI, Biochem Lab, Bethesda, MD 20892 USA. NICHHD, Lab Mammalian Genes & Dev, Bethesda, MD 20892 USA. NIH, Vet Resources Program, Off Res Serv, Bethesda, MD 20892 USA. NCI, Frederick Canc Res & Dev Ctr, Sci Applicat Int Corp, Frederick, MD 21702 USA. Shinshu Univ, Sch Med, Dept Biochem, Matsumoto, Nagano 390, Japan. RP Reitman, ML (reprint author), NIDDKD, Diabet Branch, Bethesda, MD 20892 USA. EM mlr@helix.nih.gov; vinsonc@dc37a.nci.nih.gov RI Reitman, Marc/B-4448-2013 OI Reitman, Marc/0000-0002-0426-9475 NR 77 TC 518 Z9 526 U1 1 U2 17 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD OCT 15 PY 1998 VL 12 IS 20 BP 3168 EP 3181 DI 10.1101/gad.12.20.3168 PG 14 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 134ZG UT WOS:000076773600005 PM 9784492 ER PT J AU Gdula, DA Sandaltzopoulos, R Tsukiyama, T Ossipow, V Wu, C AF Gdula, DA Sandaltzopoulos, R Tsukiyama, T Ossipow, V Wu, C TI Inorganic pyrophosphatase is a component of the Drosophila nucleosome remodeling factor complex SO GENES & DEVELOPMENT LA English DT Article DE chromatin; ISWI; NURF; pyrophosphatase; remodeling ID CELL-FREE SYSTEM; SACCHAROMYCES-CEREVISIAE; CHROMATIN STRUCTURE; TRANSCRIPTIONAL ACTIVATION; SWI/SNF COMPLEX; YEAST; FAMILY; REGULATOR; BINDING; PROTEIN AB The Drosophila nucleosome remodeling factor (NURF) is a protein complex consisting of four polypeptides that facilitates the perturbation of chromatin structure in vitro in an ATP-dependent manner. The 140-kD NURF subunit, imitation switch (ISWI), is related to the SWI2/SNF2 ATPase. Another subunit, NURF-55, is a 55-kD WD repeat protein homologous to the human retinoblastoma-associated protein RbAp48. Here, we report the cloning and characterization of the smallest (38 kD) component of NURF. NURF-38 is strikingly homologous to known inorganic pyrophosphatases. Both recombinant NURF 38 alone and the purified NURF complex are shown to have inorganic pyrophosphatase activity. Inhibition of the pyrophosphatase activity of NURF with sodium fluoride has no significant effect on chromatin remodeling, indicating that these two activities may be biochemically uncoupled. Our results suggest that NURF-38 may serve a structural or regulatory role in the complex. Alternatively, because accumulation of unhydrolyzed pyrophosphate during nucleotide incorporation inhibits polymerization, NURF may also have been adapted to deliver pyrophosphatase to chromatin to assist in replication or transcription by efficient removal of the inhibitory metabolite. C1 NCI, Mol Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Wu, C (reprint author), NCI, Mol Cell Biol Lab, NIH, Bethesda, MD 20892 USA. EM carlwu@helix.nih.gov NR 57 TC 61 Z9 64 U1 0 U2 1 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD OCT 15 PY 1998 VL 12 IS 20 BP 3206 EP 3216 DI 10.1101/gad.12.20.3206 PG 11 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 134ZG UT WOS:000076773600008 PM 9784495 ER PT J AU Festing, MFW Lin, L Devereux, TR Gao, F Yang, A Anna, CH White, CM Malkinson, AM You, M AF Festing, MFW Lin, L Devereux, TR Gao, F Yang, A Anna, CH White, CM Malkinson, AM You, M TI At least four loci and gender are associated with susceptibility to the chemical induction of lung adenomas in A/J x BALB/c mice SO GENOMICS LA English DT Article ID INDUCED PULMONARY ADENOMAS; TUMOR-SUPPRESSOR GENE; K-RAS ACTIVATION; MOUSE LUNG; ALLELOTYPE ANALYSIS; RESISTANCE LOCUS; URETHANE; CHROMOSOME-4; P15(INK4B); DELETION AB Four putative quantitative trait loci (QTLs) that influence susceptibility to the induction of lung adenomas by urethane in an F-2 cross between A/J and BALB/cOlaHsd have been mapped. Following microsatellite typing of mice with resistant and susceptible phenotypes at 97 microsatellite marker loci, a major locus was identified on chromosome 18 with a lod score of 15. This was responsible for an 8- to 10-fold increase in tumor multiplicity in males and females, respectively, having the AA and CC genotypes at the D18Mit188 marker locus. It mapped close to Dcc (deleted in colorectal cancer). A locus on chromosome 4 (lod score 6.5) had the resistant allele in strain A/J and the susceptible allele in BALB/c, with a 14-fold difference in tumor multiplicity between mice of the AA and CC: genotypes. This mapped close to the Cdkn2a (cyclin-dependent kinase inhibitor 2A) locus, which is commonly deleted in mouse lung tumors. Two loci with smaller effects (lod scores 3.03 and 3.25) were identified on chromosomes 1 and 11. There was also significant sexual dimorphism in tumor multiplicity both among 151 F-2 hybrids and among 52 mice resulting from a backcross to strain A/J, with males having higher tumor counts than females. (C) 1998 Academic Press. C1 Univ Leicester, MRC, Toxicol Unit, Leicester LE1 9HN, Leics, England. Med Coll Ohio, Dept Pathol, Toledo, OH 43699 USA. NIEHS, Mol Toxicol Grp, Res Triangle Pk, NC 27709 USA. Univ Colorado, Hlth Sci Ctr, Sch Pharm, Dept Pharmaceut Sci, Denver, CO 80262 USA. RP Festing, MFW (reprint author), Univ Leicester, MRC, Toxicol Unit, Hodgkin Bldg,POB 138,Lancaster Rd, Leicester LE1 9HN, Leics, England. FU NCI NIH HHS [CA/ES 78797]; NIEHS NIH HHS [ES02370] NR 39 TC 56 Z9 56 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD OCT 15 PY 1998 VL 53 IS 2 BP 129 EP 136 DI 10.1006/geno.1998.5450 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 132RN UT WOS:000076643700002 PM 9790761 ER PT J AU Downes, GB Copeland, NG Jenkins, NA Gautam, N AF Downes, GB Copeland, NG Jenkins, NA Gautam, N TI Structure and mapping of the G protein gamma 3 subunit gene and a divergently transcribed novel gene, Gng3lg SO GENOMICS LA English DT Article ID HEAD-TO-HEAD; BIDIRECTIONAL PROMOTER; SIGNAL TRANSDUCTION; MOLECULAR-CLONING; COLLAGEN GENES; IV COLLAGEN; MOUSE; CDNA; LOCALIZATION; ORGANIZATION AB The mammalian nervous system is rich in signaling mediated by heterotrimeric (alpha beta gamma) G proteins. As an initial step to define the roles that particular gamma subunit types play in signaling, we have begun to clone and characterize those genes that encode gamma subunits enriched within neural tissue. In the present study, we have isolated and characterized the mouse gamma 3 subunit gene (Gng3). The gamma 3 subunit is expressed abundantly in the brain and at low levels in testes. Gng3 is composed of three exons spanning similar to 1.4 kb. A comparison of Gng3 with the gene structure for five other gamma subtypes indicates that although these proteins are diverse at the amino acid level, their exon-intron boundaries are conserved. Sequence analysis of the 5' flanking region of Gng3 revealed the presence of a novel gene, the gamma 3 linked gene (Gng3lg). Gng3 and Gng3lg are organized in a head-to-head fashion with major transcription initiation sites separated by approximately 133 bp. Sequence analysis of a Gng3lg cDNA clone revealed an open reading frame encoding a 410-amino-acid protein of unknown function. Gng3lg transcripts are expressed in a variety of tissues including both brain and testes. Using an interspecific backcross panel, we localized both Gng3 and Gng3lg to the same locus on chromosome 19. The orientation, close proximity, and expression pattern of these two genes raise the distinct possibility that shared regulatory elements are used to control their expression. (C) 1998 Academie Press. C1 Washington Univ, Sch Med, Dept Anesthesiol, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA. NCI, Frederick Canc Res Ctr, Mammalian Genet Lab, Frederick, MD 21702 USA. RP Gautam, N (reprint author), Washington Univ, Sch Med, Dept Anesthesiol, St Louis, MO 63110 USA. FU NIGMS NIH HHS [GM 46963, GM 17289-04] NR 34 TC 24 Z9 26 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD OCT 15 PY 1998 VL 53 IS 2 BP 220 EP 230 DI 10.1006/geno.1998.5508 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 132RN UT WOS:000076643700012 PM 9790771 ER PT J AU Wang, K Yin, XM Copeland, NG Gilbert, DJ Jenkins, NA Keck, CL Zimonjic, DB Popescu, NC Korsmeyer, SJ AF Wang, K Yin, XM Copeland, NG Gilbert, DJ Jenkins, NA Keck, CL Zimonjic, DB Popescu, NC Korsmeyer, SJ TI BID, a proapoptotic BCL-2 family member, is localized to mouse chromosome 6 and human chromosome 22q11 SO GENOMICS LA English DT Article ID DNA-SEQUENCES; FLUORESCENCE; LEUKEMIA; HYBRIDIZATION; BREAKPOINTS; REGION; INSITU; DEATH; BCR AB BID is a proapoptotic member of the BCL-2 family of cell death regulators. BID shares sequence homology with other members of the family within a single alpha-helical domain, BH3. BH3 is required for BID to interact with BCL-2 and BAX, as well as for its function as a death agonist. We have isolated and characterized mouse Bid and human BID genomic clones. The sequence for BID is encoded within five exons. We used interspecific backcross analysis to localize Bid to the distal region of mouse chromosome 6 near the Atp6e locus. Fluorescence in situ hybridization analysis localized human BID to a syntenic human region, chromosome 22q11, close to the BCR-1 gene. (C) 1998 Academic Press. C1 Washington Univ, Sch Med, Dept Med, Howard Hughes Med Inst,Div Mol Oncol, St Louis, MO 63110 USA. Washington Univ, Sch Med, Howard Hughes Med Inst, Dept Pathol,Div Mol Oncol, St Louis, MO 63110 USA. NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Mammalian Genet Lab, Frederick, MD 21702 USA. NCI, Expt Carcinogenesis Lab, Bethesda, MD 20892 USA. RP Korsmeyer, SJ (reprint author), Dana Farber Canc Inst, Dept Immunol & AIDS, Smith Bldg,Room 758,44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [R01 CA50239] NR 15 TC 13 Z9 14 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD OCT 15 PY 1998 VL 53 IS 2 BP 235 EP 238 DI 10.1006/geno.1998.5489 PG 4 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 132RN UT WOS:000076643700014 PM 9790773 ER PT J AU Nelms, K Snow, AJ Noben-Trauth, K AF Nelms, K Snow, AJ Noben-Trauth, K TI Dok1 encoding p62(dok) maps to mouse chromosome 6 and human chromosome 2 in a region of translocation in chronic lymphocytic leukemia SO GENOMICS LA English DT Article ID PROTEIN; IDENTIFICATION; RAS; GAP C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. Natl Inst Deafness & Other Commun Disorders, Sect Murine Genet, NIH, Rockville, MD 20850 USA. RP Nelms, K (reprint author), NIAID, Immunol Lab, NIH, Bldg 10,Room 11N311,10 Ctr Dr,MSC 1892, Bethesda, MD 20892 USA. FU ODCDC CDC HHS [ZO1 CD00036-01] NR 14 TC 10 Z9 10 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD OCT 15 PY 1998 VL 53 IS 2 BP 243 EP 245 DI 10.1006/geno.1998.5514 PG 3 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 132RN UT WOS:000076643700017 PM 9790776 ER PT J AU Howard, OMZ Farrar, WL AF Howard, OMZ Farrar, WL TI The chemokine kidnapping receptor of HHV8 SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Editorial Material ID KAPOSIS-SARCOMA; HERPESVIRUS; KSHV C1 NCI, SAIC Frederick, IRSP, Lab Mol Immunoregulat,FCRDC, Bethesda, MD 20892 USA. NCI, Cytokine Mol Mechanisms Sect, Mol Immunoregulat Lab, FCRDC, Bethesda, MD 20892 USA. RP Howard, OMZ (reprint author), NCI, SAIC Frederick, IRSP, Lab Mol Immunoregulat,FCRDC, Bethesda, MD 20892 USA. RI Howard, O M Zack/B-6117-2012 OI Howard, O M Zack/0000-0002-0505-7052 NR 9 TC 4 Z9 4 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD OCT 15 PY 1998 VL 102 IS 8 BP 1467 EP 1468 DI 10.1172/JCI5355 PG 2 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 132KV UT WOS:000076629800001 PM 9788957 ER PT J AU Moriuchi, M Moriuchi, H Turner, W Fauci, AS AF Moriuchi, M Moriuchi, H Turner, W Fauci, AS TI Exposure to bacterial products renders macrophages highly susceptible to T-tropic HIV-1 SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE lipopolysaccharide; lipoteichoic acid; lipoarabinomannan; chemokines; chemokine receptors ID HUMAN-IMMUNODEFICIENCY-VIRUS; NECROSIS-FACTOR-ALPHA; INFECTIOUS MOLECULAR CLONE; LONG TERMINAL REPEAT; PROTEIN-KINASE-C; CHEMOKINE RECEPTORS; HUMAN MONOCYTES; MYCOBACTERIUM-TUBERCULOSIS; LIPOPOLYSACCHARIDE LPS; TYPE-1 EXPRESSION AB Microbial coinfections variably influence HIV-1 infection through immune activation or direct interaction of microorganisms with HIV-1 or its target cells. In this study, we investigated whether exposure of macrophages to bacterial products impacts the susceptibility of these cells to HIV-1 of different cellular tropisms. We demonstrate that (1) macrophages exposed to bacterial cell wall components such as lipopolysaccharide (LPS) (Gram-negative rods), lipoteichoic acid (Gram-positive cocci), and lipoarabinomannan (Mycobacteria) become highly susceptible to T cell (T)-tropic HIV-1 (which otherwise poorly replicate in macrophages) and variably susceptible to macrophage (M)-tropic HIV-1; (2) LPS-stimulated macrophages secrete a number of soluble factors (i.e., chemokines, interferon, and proinflammatory cytokines) that variably affect HIV infection of macrophages, depending on the virus phenotype in question; and (3) LPS-stimulated macrophages express CCR5 (a major coreceptor for M-tropic HIV-1) at lower levels and CXCR4 (a major coreceptor for T-tropic HIV-1) at higher levels compared with unstimulated macrophages. We hypothesize that a more favorable environment for T-tropic HIV-1 and a less favorable or even unfavorable environment for M-tropic HIV-1 secondary to exposure of macrophages to those bacterial products may accerelate a transition from M- to T-tropic viral phenotype, which is indicative of disease progression. C1 NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. Howard Univ, Coll Med, Dept Microbiol, Washington, DC 20059 USA. RP Moriuchi, M (reprint author), NIAID, Immunoregulat Lab, NIH, Bldg 10,Room 6A11, Bethesda, MD 20892 USA. NR 82 TC 74 Z9 75 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD OCT 15 PY 1998 VL 102 IS 8 BP 1540 EP 1550 DI 10.1172/JCI4151 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 132KV UT WOS:000076629800011 PM 9788967 ER PT J AU Sayers, TJ Brooks, AD Lee, JK Fenton, RG Komschlies, KL Wigginton, JM Winkler-Pickett, R Wiltrout, RH AF Sayers, TJ Brooks, AD Lee, JK Fenton, RG Komschlies, KL Wigginton, JM Winkler-Pickett, R Wiltrout, RH TI Molecular mechanisms of immune-mediated lysis of murine renal cancer: Differential contributions of perforin-dependent versus Fas-mediated pathways in lysis by NK and T cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NATURAL-KILLER-CELLS; TUMOR-NECROSIS-FACTOR; SERINE ESTERASE GENE; DEFICIENT MICE; GRANZYME-B; IN-VIVO; CHROMOSOMAL ASSIGNMENT; INITIATES APOPTOSIS; DEATH DOMAIN; ANTI-FAS AB Mice bearing the experimental murine renal cancer Renca can be successfully treated with some forms of immunotherapy, In the present study, we have investigated the molecular pathways used by NK and T cells to lyse Renca cells, Renca cells normally express low levels of Fas that can be substantially enhanced by either IFN-gamma or TNF-alpha, and the combination of IFN-gamma + TNF-alpha synergistically enhances cell-surface Fas expression. In addition, cells pretreated with IFN-gamma and TNF-alpha are sensitive to lysis mediated by Fas ligand (FasL)-expressing hybridomas (dllS), cross-linking of anti-Fas Abs or soluble Fas (FasL), Lysis via Fas occurs by apoptosis, since Renca shows all the typical characteristics of apoptosis, No changes in levels of bcl-2 were observed after cytokine treatments. We also examined cell-mediated cytotoxic effects using activated NK cells and T cells from gld FasL-deficient mice, and perforin-deficient mice, as well as wild-type C57BL/6 and BALB/c mice. Interestingly, the granule-mediated pathway predominated in killing of Renca by activated NK cells, while the Fas/FasL pathway contributed significantly to cell-mediated killing of Renca by activated T cells. These results suggest that killing of Renca tumor cells by immune effector cells can occur by both granule and Fas-mediated cytotoxicity. However, for the Fas-mediated pathway to function, cell surface levels of Fas need to be increased beyond a critical threshold level by proinflammatory cytokines such as IFN-gamma and TNF-alpha. C1 NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick, Intramural Res Support Program, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Expt Immunol Lab, Div Basic Sci, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Dept Expt Transplantat & Immunol, Div Clin Sci, Frederick, MD 21702 USA. NCI, Pediat Oncol Branch, DCS, Bethesda, MD 20892 USA. RP Sayers, TJ (reprint author), NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick, Intramural Res Support Program, Bldg 560,Room 31-30, Frederick, MD 21702 USA. EM Sayers@mail.ncifcrf.gov RI Sayers, Thomas/G-4859-2015 FU PHS HHS [N01-C0-56000] NR 71 TC 76 Z9 83 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD OCT 15 PY 1998 VL 161 IS 8 BP 3957 EP 3965 PG 9 WC Immunology SC Immunology GA 127GV UT WOS:000076343300024 PM 9780164 ER PT J AU Castellino, F Zappacosta, F Coligan, JE Germain, RN AF Castellino, F Zappacosta, F Coligan, JE Germain, RN TI Large protein fragments as substrates for endocytic antigen capture by MHC class II molecules SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; T-CELL RECOGNITION; INVARIANT CHAIN COMPLEXES; HLA-DR; IMMUNOGENIC PEPTIDES; 3-DIMENSIONAL STRUCTURE; ENDOPLASMIC-RETICULUM; SURFACE EXPRESSION; INTACT PROTEINS; BINDING AB Although the binding sites of MRC class II molecules can accommodate longer ligands, peptides of 15 to 20 residues are the primary form of processed Bg recovered from class II dimers isolated from living cells. These peptides are derived from intact Ags by proteolysis in endocytic organelles, where binding to class II dimers also occurs. Whether generation of these short peptides typically precedes association with class II molecules, or whether class Il molecules initially hind to unfolded proteins or large protein fragments, followed by degradation of the unprotected regions, remains unknown. Here we report the identification of an SDS-stable, long-lived, 120-kDa complex composed of two class IT dimers bound to a common large Ag fragment, This complex is produced within the endocytic pathway from newly synthesized MHC class II molecules following exposure of the cells to exogenous hers egg lysozyme. These data suggest that a major pathway of Ag processing involves the initial binding of class LT heterodimers to large protein substrates upon exposure of regions with suitable motifs, followed by cleavage and/or trimming of the exposed protein around this bound region. This sequence of events during Ag processing mag provide a partial molecular explanation for the immunodominance of certain determinants in protein Ags. C1 NIAID, Lymphocyte Biol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. NIAID, Mol Struct Lab, NIH, Bethesda, MD 20892 USA. RP Germain, RN (reprint author), NIAID, Lymphocyte Biol Sect, Immunol Lab, NIH, Bldg 10,Room 11N311,10 Ctr Dr,MSC 1892, Bethesda, MD 20892 USA. EM ronald_germain@nih.gov NR 68 TC 62 Z9 63 U1 2 U2 5 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD OCT 15 PY 1998 VL 161 IS 8 BP 4048 EP 4057 PG 10 WC Immunology SC Immunology GA 127GV UT WOS:000076343300035 PM 9780175 ER PT J AU Ruiz, ME Cicala, C Arthos, J Kinter, A Catanzaro, AT Adelsberger, J Holmes, KL Cohen, OJ Fauci, AS AF Ruiz, ME Cicala, C Arthos, J Kinter, A Catanzaro, AT Adelsberger, J Holmes, KL Cohen, OJ Fauci, AS TI Peripheral blood-derived CD34(+) progenitor cells: CXC chemokine receptor 4 and CC chemokine receptor 5 expression and infection by HIV SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; HUMAN-BONE-MARROW; HEMATOPOIETIC STEM-CELLS; T-CELL; ENVELOPE GLYCOPROTEIN; MAJOR RESERVOIR; AIDS PATIENTS; TYPE-1; ENTRY; CD4 AB The present study demonstrates cell surface expression of both CXC chemokine receptor 4 (CXCR4) and CC chemokine receptor 5 (CCR5), major coreceptors for T cell-tropic and macrophage-tropic strains of HIV, respectively, on CD34(+) progenitor cells derived from the peripheral blood. CD34+ progenitor cells were susceptible to infection by diverse strains of HIV, and infection could be sustained for prolonged periods in vitro. HIV entry into CD34(+) progenitor cells could be modulated by soluble CD4, HIV gp120 third variable loop neutralizing mAb and the cognate ligands for the CXCR4 and CCR5 HIV coreceptors, This study suggests that a significant proportion of the circulating progenitor cell pool may serve as a reservoir for HIV that is capable of trafficking the virus to diverse anatomic compartments. Furthermore, the infection and ultimate destruction of these progenitor cells may explain in part the defective lymphopoiesis in certain HIV-infected individuals despite effective control of virus replication during highly active antiretroviral therapy. C1 NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. NIAID, Immunopathol Lab, NIH, Bethesda, MD 20892 USA. NCI, Frederick Canc Res & Dev Ctr, Sci Applicat Int Corp, NIH, Frederick, MD 21702 USA. RP Ruiz, ME (reprint author), NIAID, Immunoregulat Lab, NIH, Bldg 10,Room 6A23,10 Ctr Dr,MSC 1576, Bethesda, MD 20892 USA. EM mruiz@nih.gov NR 70 TC 52 Z9 53 U1 1 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD OCT 15 PY 1998 VL 161 IS 8 BP 4169 EP 4176 PG 8 WC Immunology SC Immunology GA 127GV UT WOS:000076343300050 PM 9780190 ER PT J AU Lee, KH Panelli, MC Kim, CJ Riker, AI Bettinotti, MP Roden, MM Fetsch, P Abati, A Rosenberg, SA Marincola, FM AF Lee, KH Panelli, MC Kim, CJ Riker, AI Bettinotti, MP Roden, MM Fetsch, P Abati, A Rosenberg, SA Marincola, FM TI Functional dissociation between local and systemic immune response during anti-melanoma peptide vaccination SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CYTOLYTIC T-LYMPHOCYTES; TUMOR-INFILTRATING LYMPHOCYTES; MONOCLONAL-ANTIBODIES; PERIPHERAL-BLOOD; CELL-LINES; IN-VITRO; SYNTHETIC PEPTIDES; MULTIPLE EPITOPES; HLA-A2 MELANOMAS; REACTIVE CTL AB Peptide vaccination against tumor Ags can induce powerful systemic CTL responses. However, in the majority of patients, no tumor regression is noted, To study this discrepancy, we analyzed CTL reactivity in a melanoma patient (F001) vaccinated with g209-2M peptide, a single residue variant of gp100(209-217). G209/g209-2M-reactive CTL were identified in post- but not prevaccination PBL, Limiting dilution analysis identified one predominant CTL clone (C1-35), with TCR V beta 6s2, recognizing g209/HLA-A*0201-expressing targets. Additionally, two autologous melanoma lines (:F001TU-3 and -4) and 20 separate tumor-infiltrating lymphocyte cultures were generated from a fine needle aspirate of a metastatic lesion progressing after initial response to vaccination. Both F001TU did not express gp100 and were not recognized by C1-35, Loss of gp100 by F001TU correlated with a marked reduction of gp100 expression in the same metastatic lesion compared with prevaccination, Thus, ineffectiveness of C1-35 and tumor progression could be best explained by loss of target Ag expression. Interestingly, 12 of 20 tumor-infiltrating lymphocyte cultures recognized F001TU, but none demonstrated g209/g209-2M reactivity, suggesting a functional dissociation between systemic and local immune response. This study suggests that vaccination effects must be analyzed in the target tissue, rather than in the systemic circulation alone. C1 NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. NCI, Dept Transfus Med, Ctr Clin, NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, Div Clin Sci, NIH, Bethesda, MD 20892 USA. RP Marincola, FM (reprint author), NCI, Surg Branch, NIH, Bldg 10,Room 2B42,10 Ctr Dr MSC 1502, Bethesda, MD 20892 USA. RI Riker, Adam/A-6065-2011 NR 35 TC 102 Z9 104 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD OCT 15 PY 1998 VL 161 IS 8 BP 4183 EP 4194 PG 12 WC Immunology SC Immunology GA 127GV UT WOS:000076343300052 PM 9780192 ER PT J AU Hoffmann, KF Caspar, P Cheever, AW Wynn, TA AF Hoffmann, KF Caspar, P Cheever, AW Wynn, TA TI IFN-gamma, IL-12, and TNF-alpha are required to maintain reduced liver pathology in mice vaccinated with Schistosoma mansoni eggs and IL-12 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NECROSIS-FACTOR-ALPHA; INTERFERON-GAMMA; CUTANEOUS LEISHMANIASIS; TH2 CYTOKINES; MESSENGER-RNA; INTERLEUKIN-12; INFECTION; RESPONSES; INFLAMMATION; EXPRESSION AB The development of hepatic fibrosis and portal hypertension is the principal cause of morbidity and mortality in schistosomiasis mansoni, Nevertheless, relatively little is known about the mechanisms that lead to excessive collagen deposition during infection with Schistosoma mansoni. In the murine model, infection leads to significant egg-induced granuloma formation, tissue eosinophilia, and hepatic fibrosis, The pathology has been linked to dominant type 2 cytokine expression, and our recent studies showed that sensitizing animals to egg Ags in combination with IL-12, before infection, led to a highly significant reduction in egg-induced immunopathology, In this study, we demonstrate that in contrast with egg/IL-12-sensitized animals that showed marked decreases in pathology, mice similarly sensitized but depleted of IFN-gamma, IL-12, or TNF-alpha at the time of egg laying developed granulomas that were similar to the non-IL-12-treated control group. Although all three anticytokine-treated groups exhibited a dominant type 1 response in lymph node cells restimulated ex vivo, the expression of type 2 cytokine mRNA was markedly restored at the site of granuloma formation, which suggests that all three cytokines are required to maintain the suppressed type 2 pattern. Moreover, egg/IL-12-sensitized mice depleted of IFN-gamma or IL-12 displayed a partial reduction in IFN-gamma production, suggesting that multiple type 1 cytokines were required to maintain polarized type 1 responses to chronic type 2-inducing stimuli. Together, these data reveal key roles for IFN-gamma, IL-12, and TNF-alpha in the protective effects mediated by this IL-12-based vaccine to prevent pathology. C1 NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. Biomed Res Inst, Rockville, MD 20852 USA. RP Wynn, TA (reprint author), NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, Bldg 4,Room 126,9000 Rockville Pike, Bethesda, MD 20892 USA. EM twynn@atlas.niaid.nih.gov RI Wynn, Thomas/C-2797-2011 NR 43 TC 45 Z9 46 U1 0 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD OCT 15 PY 1998 VL 161 IS 8 BP 4201 EP 4210 PG 10 WC Immunology SC Immunology GA 127GV UT WOS:000076343300054 PM 9780194 ER PT J AU Wang, JM Ueda, H Howard, OMZ Grimm, MC Chertov, O Gong, XQ Gong, WH Resau, JH Broder, CC Evans, G Arthur, LO Ruscetti, FW Oppenheim, JJ AF Wang, JM Ueda, H Howard, OMZ Grimm, MC Chertov, O Gong, XQ Gong, WH Resau, JH Broder, CC Evans, G Arthur, LO Ruscetti, FW Oppenheim, JJ TI HIV-1 envelope gp120 inhibits the monocyte response to chemokines through CD4 signal-dependent chemokine receptor down-regulation SO JOURNAL OF IMMUNOLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; MULTIPLE LEUKOCYTE RECEPTORS; PROTEIN-3 MCP3 INTERACTS; FUNCTIONAL EXPRESSION; FUSION COFACTOR; TROPIC HIV-1; GLYCOPROTEIN; INFECTION; RANTES; LIGAND AB Since HIV-1 infection results in severe immunosuppression, and the envelope protein gp120 has been reported to interact with some of the chemokine receptors on human T lymphocytes, we postulated that gp120 may also affect monocyte activation by a variety of chemokines. This study shows that human peripheral blood monocytes when preincubated with gp120 either purified from laboratory-adapted strains or as recombinant proteins exhibited markedly reduced binding, calcium mobilization, and chemotactic response to chemokines. The gp-120-pretreated monocytes also showed a decreased response to FMLP, This broad inhibition of monocyte activation by chemoattractants required interaction of gp120 with CD4, since the effect of gp120 was only observed in CD4(+) monocytes and in HEK 293 cells only if cotransfected with both chemokine receptors and an intact CD4, but not a CD4 lacking its cytoplasmic domain. Anti-CD4 mAbs mimicked the effect of gp120, and both anti-CD4 Ab and gp120 caused internalization of CXCR4 in HEK 293 cells provided they also expressed CH4. Staurosporine blocked the inhibitory effect of gp120 on monocytes, suggesting that cellular signaling was required for gp120 to inhibit the response of CD4(+) cells to chemoattractants. Our study demonstrates a broad suppressive effect of gp120 on monocyte activation by chemoattractants through the downregulation of cell surface receptors, Thus, gp120 may be used by HIV-1 to disarm the monocyte response to inflammatory stimulation. C1 NCI, Frederick Canc Res & Dev Ctr, Mol Immunoregulat Lab, Div Basic Sci, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Lab Leukocyte Biol, Div Basic Sci, Frederick, MD 21702 USA. SAIC Frederick, Intramural Res Support Program, Frederick, MD USA. SAIC Frederick, AIDS Vaccine Program, Frederick, MD USA. NCI, Frederick Canc Res & Dev Ctr, Adv BioSci Labs, Basic Res Program, Frederick, MD 21702 USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. RP Wang, JM (reprint author), NCI, Frederick Canc Res & Dev Ctr, Mol Immunoregulat Lab, Div Basic Sci, Bldg 560,Room 31-19, Frederick, MD 21702 USA. EM wangji@fcrfv1.ncifcrf.gov RI Howard, O M Zack/B-6117-2012 OI Howard, O M Zack/0000-0002-0505-7052 NR 45 TC 38 Z9 39 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD OCT 15 PY 1998 VL 161 IS 8 BP 4309 EP 4317 PG 9 WC Immunology SC Immunology GA 127GV UT WOS:000076343300067 PM 9780207 ER PT J AU Kuhns, D Young, HA Gallin, EK Gallin, JI AF Kuhns, D Young, HA Gallin, EK Gallin, JI TI Ca2+-dependent production and release of IL-8 in human neutrophils SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INTRACELLULAR CA-2+; PROTEIN-KINASE; CA2+ INFLUX; THAPSIGARGIN; INHIBITION; CELLS; LYMPHOCYTES; PATHWAY; ENTRY; EXPRESSION AB IL-8, a potent neutrophil chemoattractant that is elevated about 200-find in exudative neutrophils isolated from localized inflammatory sites in vivo, is thought to play a major role in recruitment of neutrophils to inflammatory sites. Incubation of peripheral blood neutrophils with thapsigargin, an inhibitor of the endoplasmic reticulum Ca2+-sequestering-ATPase, causes a dose-dependent induction of IL-8 synthesis that continues for up to 8 h, Cycloheximide inhibits the thapsigargin-induced IL-8 production, suggesting the induction of protein synthesis de novo. In addition, Northern blot analysis of mRNA isolated from neutrophils indicates that thapsigargin treatment increases IL-8 mRNA in a time- and dose-dependent manner. Thapsigargin also induces a biphasic rise in the intracellular Ca2+ concentration, [Ca2+](i), which is composed of an initial (within 15 s) EGTA-insensitive elevation in [Ca2+](i), followed by a delayed (2-min) EGTA-sensitive component. Addition of EGTA before thapsigargin inhibited the induction of IL-8 production. Experiments in which EGTA was added at various times after thapsigargin treatment indicated that a sustained Ca2+ influx was required for maximum IL-8 production. Ascomycin and cyclosporin A, inhibitors of the Ca2+-dependent phosphatase, calcineurin, also inhibited thapsigargin-induced IL-8 production, Thus, in neutrophils, a prolonged Increase in [Ca2+](i) stimulates IL-8 transcription and synthesis, possibly through a calcineurin-dependent pathway. C1 NIAID, Host Def Lab, Bethesda, MD 20892 USA. Frederick Canc Res & Dev Ctr, Sci Applicat Int Corp, Clin Serv Program, Ft Detrick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Expt Immunol Lab, Frederick, MD 21702 USA. SUNY Hlth Sci Ctr, Brooklyn, NY 11203 USA. RP Gallin, JI (reprint author), NIAID, Host Def Lab, Bldg 10,Room 11N107, Bethesda, MD 20892 USA. NR 25 TC 73 Z9 78 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD OCT 15 PY 1998 VL 161 IS 8 BP 4332 EP 4339 PG 8 WC Immunology SC Immunology GA 127GV UT WOS:000076343300070 PM 9780210 ER PT J AU Zhang, J Kimura, T Siraganian, RP AF Zhang, J Kimura, T Siraganian, RP TI Mutations in the activation loop tyrosines of protein tyrosine kinase Syk abrogate intracellular signaling but not kinase activity SO JOURNAL OF IMMUNOLOGY LA English DT Article ID AFFINITY IGE RECEPTOR; FC-EPSILON-RI; INSULIN-RECEPTOR; SH2 DOMAINS; MONOCLONAL-ANTIBODIES; CRYSTAL-STRUCTURE; MAST-CELLS; PHOSPHORYLATION; ZAP-70; P72(SYK) AB The protein tyrosine kinase Syk plays a pivotal role in mediating the high-affinity IgE receptor (Fc epsilon RI)-induced degranulation of mast cells, To examine the mechanism of Syk regulation, the two tyrosine residues at 519 and 520 in the putative activation loop of rat Syk were mutated to phenylalanine either singly or in combination, The various mutants were expressed in a Syk-negative variant of the RBL-2H3 (rat basophilic leukemia 2H3) mast cell line. in these transfected cell lines, mutant Syk did show increased tyrosine phosphorylation in vivo and increased enzymatic activity in vitro after FceRI aggregation. There were conformational changes detected by an Ab when the wild-type and mutant Syk were either tyrosine phosphorylated or bound to tyrosine-phosphorylated immunoreceptor tyrosine-based activation moth peptides, However, these mutant Syk were incapable of transducing Fc epsilon RI signaling. In cells in which the expression level of mutant Syk was similar to that of the wild-type Syk, Fc epsilon RI cross-linking induced no increase in cellular protein tyrosine phosphorylation, no increase in tyrosine phosphorylation of phospholipase C-gamma 2 and mitogen-activated protein kinase, and no histamine release. Overexpression of Y519F or Y520F Syk mutants partially reconstituted the signaling pathways, These results indicate that these tyrosines in the putative activation loop are not essential for thr enzymatic activity of Syk or for the conformational changes induced by binding of tyrosine-phosphorylated immunoreceptor tyrosine-based activation motif peptides, However, these tyrosines are necessary for Syk-mediated propagation of Fc epsilon RI signaling. C1 NIDR, RAST Sect, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. RP Zhang, J (reprint author), NIDR, RAST Sect, Oral Infect & Immun Branch, NIH, Bldg 10,Room 1N106, Bethesda, MD 20892 USA. NR 51 TC 48 Z9 49 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD OCT 15 PY 1998 VL 161 IS 8 BP 4366 EP 4374 PG 9 WC Immunology SC Immunology GA 127GV UT WOS:000076343300074 PM 9780214 ER PT J AU Kawahito, Y Cannon, GW Gulko, PS Remmers, EF Longman, RE Reese, VR Wang, JP Griffiths, MM Wilder, RL AF Kawahito, Y Cannon, GW Gulko, PS Remmers, EF Longman, RE Reese, VR Wang, JP Griffiths, MM Wilder, RL TI Localization of quantitative trait loci regulating adjuvant-induced arthritis in rats: Evidence for genetic factors common to multiple autoimmune diseases SO JOURNAL OF IMMUNOLOGY LA English DT Article ID COLLAGEN-INDUCED ARTHRITIS; MAJOR HISTOCOMPATIBILITY COMPLEX; GENOME-WIDE SEARCH; RHEUMATOID-ARTHRITIS; SUSCEPTIBILITY LOCI; IMMUNE-RESPONSE; II COLLAGEN; BB RAT; ASSOCIATION; MICE AB Adjuvant-induced arthritis (AIA) in rats is a widely used autoimmune experimental model with many features similar to rheumatoid arthritis (RA), To identify potential genetic regulatory mechanisms in IM, we conducted genome-wide linkage analysis in F-2 progeny of arthritis-susceptible Dark Agouti (DA) and relatively resistant Fischer 344 (F344) inbred rats. We compared the data with our previously reported investigation of collagen-induced arthritis (CIA), which was expanded in the follow-up study reported in this work. We found two quantitative trait loci (QTLs) in common, i.e., Aia1/Cia1 on chromosome 20, which includes the MHC, and Aia3/Cia3 on chromosome 4, We also identified a second unique QTL in AIA, Aia2, on chromosome 4, Interestingly, the QTL region on chromosome 4 (Aia3/Cia3), like the MHC, appears to he involved in several other autoimmune diseases in rats, including insulin-dependent diabetes, thyroiditis, and experimental autoimmune uveitis, Moreover, an analysis of conserved synteny among rats, mice, and humans suggested that Aia2 and Aia3/Cia3, like Aia1/Cia1, contain candidate genes for several autoimmune/inflammatory diseases in mice and humans, including diabetes, systemic lupus erythematosus, inflammatory bowel disease, asthma/atopy, multiple sclerosis, and RA, The rat models appear to provide a powerful complementary approach to identify and characterize candidate genes that may contribute to autoimmune diseases in several species. C1 NIAMSD, Arthritis & Rheumatism Branch, Inflammatory Joint Dis Sect, Bethesda, MD 20892 USA. Univ Utah, Dept Med Rheumatol, Salt Lake City, UT 84132 USA. Univ Utah, Res Serv Vet Affairs Med Ctr, Salt Lake City, UT 84132 USA. RP Wilder, RL (reprint author), NIH, Bldg 10,Room 9N240 10 Ctr Dr MSC 1820, Bethesda, MD 20892 USA. NR 61 TC 91 Z9 97 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD OCT 15 PY 1998 VL 161 IS 8 BP 4411 EP 4419 PG 9 WC Immunology SC Immunology GA 127GV UT WOS:000076343300080 PM 9780220 ER PT J AU Bertoni, R Sette, A Sidney, J Guidotti, LG Shapiro, M Purcell, R Chisari, FV AF Bertoni, R Sette, A Sidney, J Guidotti, LG Shapiro, M Purcell, R Chisari, FV TI Human class I supertypes and CTL repertoires extend to chimpanzees SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HEPATITIS-B VIRUS; CYTOTOXIC T-LYMPHOCYTES; ACUTE VIRAL-HEPATITIS; A-LOCUS ALLELES; TRANSGENIC MICE; PEPTIDE-BINDING; HLA-A; TARGET-CELLS; HIGH-LEVEL; C VIRUS AB Using an in vitro peptide stimulation strategy, two chimpanzees that were acutely infected by the hepatitis B virus (HBV) produced peripheral blood CTL responses to several HBV-encoded epitopes that are known to be recognized by class I-restricted CTL in acutely infected humans. One animal responded to three HBV peptides that, in humans, are restricted by HLA-A2; the other animal responded to three peptides that are restricted by HLA-B35 and HLA-BSI, members of the HLA-B7 supertype in man. The peptides recognized by each chimp corresponded with the ability of its class I molecules to bind peptides containing the HLA-A2 and HLA-B7 supermotifs. Similar, apparently class I-restricted CTL responses to some of these peptides were also detected in occasional HBV-uninfected chimps. These results demonstrate that the CTL repertoire overlaps in humans and chimps and that the HLA-A2 and HLA-B7 supertypes extend to the chimpanzee. Based on these results, the immunogenicity and efficacy of vaccines designed to induce CTL responses to human HLA-restricted viral epitopes may be testable in chimpanzees. C1 Scripps Res Inst, Dept Mol & Expt Med, La Jolla, CA 92037 USA. Epimmune Corp, San Diego, CA 92037 USA. Bioqual, Rockville, MD 20850 USA. NIAID, Bethesda, MD 20892 USA. RP Chisari, FV (reprint author), Scripps Res Inst, Dept Mol & Expt Med, 10550 N Torrey Pines Rd, La Jolla, CA 92037 USA. EM fchisari@scripps.edu RI Chisari, Francis/A-3086-2008; OI Guidotti, Luca G./0000-0002-0205-2678; Chisari, Francis/0000-0002-4832-1044 FU NCI NIH HHS [R37-CA40489]; NIAID NIH HHS [R01-AI20001, R01-AI40696] NR 46 TC 52 Z9 52 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD OCT 15 PY 1998 VL 161 IS 8 BP 4447 EP 4455 PG 9 WC Immunology SC Immunology GA 127GV UT WOS:000076343300084 PM 9780224 ER PT J AU Bowie, D Lange, GD Mayer, ML AF Bowie, D Lange, GD Mayer, ML TI Activity-dependent modulation of glutamate receptors by polyamines SO JOURNAL OF NEUROSCIENCE LA English DT Article DE polyamines; glutamate receptors; plasticity; channel block; kinetic analysis; AMPA; kainate; ion channel block; ionic mechanism ID CA2+-PERMEABLE AMPA RECEPTORS; SINGLE-CHANNEL PROPERTIES; KAINATE RECEPTORS; INWARD RECTIFICATION; RECOMBINANT AMPA; RAT HIPPOCAMPUS; ION; NEURONS; BLOCK; GLUR6 AB The mechanisms by which polyamines block AM PA and kainate receptors are not well understood, but it has been generally assumed that they act as open-channel blockers. Consistent with this, voltage-jump relaxation analysis of GluR6 equilibrium responses to domoate could be well fit, assuming that spermine, spermidine, and philanthotoxin are weakly permeable open-channel blockers. Analysis of rate constants for binding and dissociation of polyamines indicated that the voltage dependence of block arose primarily from changes in k(off) rather than k(on). Experiments with changes in Na concentration further indicate that the voltage dependence of polyamine block was governed by ion flux via open channels. However, responses to 1 msec applications of L-Glu revealed slow voltage-dependent rise-times, suggesting that polyamines additionally bind to closed states. A kinetic model, which included closed-channel block, reproduced these observations but required that polyamines accelerate channel closure either through an allosteric mechanism or by emptying the pore of permeant ions. Simulations with this model reveal that polyamine block confers novel activity-dependent regulation on calcium-permeable AMPA and kainate receptor responses. C1 NICHHD, Lab Cellular & Mol Neurophysiol, NIH, Bethesda, MD 20892 USA. NINDS, Instrumentat & Comp Sect, NIH, Bethesda, MD 20892 USA. RP Mayer, ML (reprint author), Bldg 49,Room 5A78,49 Convent Dr, Bethesda, MD 20892 USA. RI Mayer, Mark/H-5500-2013 NR 47 TC 81 Z9 83 U1 0 U2 2 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD OCT 15 PY 1998 VL 18 IS 20 BP 8175 EP 8185 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 126WL UT WOS:000076317600008 PM 9763464 ER PT J AU McCann, UD Wong, DF Yokoi, F Villemagne, V Dannals, RF Ricaurte, GA AF McCann, UD Wong, DF Yokoi, F Villemagne, V Dannals, RF Ricaurte, GA TI Reduced striatal dopamine transporter density in abstinent methamphetamine and methcathinone users: Evidence from positron emission tomography studies with [C-11]WIN-35,428 SO JOURNAL OF NEUROSCIENCE LA English DT Article DE amphetamines; methamphetamine; dopamine; neurotoxicity; dopamine transporter; parkinsonism ID IDIOPATHIC PARKINSONS-DISEASE; COCAINE RECOGNITION SITES; OLIVOPONTOCEREBELLAR ATROPHY; C-11 WIN-35,428; MONKEY BRAIN; RAT-BRAIN; H-3 CFT; TERMINALS; BINDING; AGE AB Methamphetamine and methcathinone are psychostimulant drugs with high potential for abuse. In animals, methamphetamine and related drugs are known to damage brain dopamine (DA) neurons, and this damage has recently been shown to be detectable in living nonhuman primates by means of positron emission tomography (PET) with [C-11]WIN-35,428, a DA transporter (DAT) ligand. The present studies determined whether living humans with a history of methamphetamine or methcathinone abuse showed evidence of lasting decrements in brain DAT density. PET studies were performed in 10 control subjects, six abstinent methamphetamine users, four abstinent methcathinone users, and three patients with Parkinson's disease (PD). On average, subjects had abstained from amphetamine use for similar to 3 years. Before PET studies, all subjects underwent urine and blood toxicology screens to rule out recent drug use. Compared with controls, abstinent methamphetamine and methcathinone users had significant decreases in DAT density in the caudate nucleus (-23 and -24%, respectively) and putamen (-25 and -16%, respectively). Larger decreases in DAT density were evident in patients with PD (47 and 68% in caudate and putamen, respectively). Neither methamphetamine nor methcathinone users showed clinical signs of parkinsonism. Persistent reductions of DAT density in methamphetamine and methcathinone users are suggestive of loss of DAT or loss of DA terminals and raise the possibility that as these individuals age, they may be at increased risk for the development of parkinsonism or neuropsychiatric conditions in which brain DA neurons have been implicated. C1 Johns Hopkins Med Inst, Dept Neurol, Baltimore, MD 21224 USA. Johns Hopkins Med Inst, Dept Radiol, Div Nucl Med, Baltimore, MD 21224 USA. NIMH, Unit Anxiety Disorders, Biol Psychiat Branch, Intramural Res Program, Bethesda, MD 20892 USA. RP Ricaurte, GA (reprint author), Johns Hopkins Med Inst, Dept Neurol, 5501 Bayview Dr,Room 5B71E, Baltimore, MD 21224 USA. FU NIDA NIH HHS [DA05707, DA06275, DA09482] NR 57 TC 392 Z9 399 U1 2 U2 15 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD OCT 15 PY 1998 VL 18 IS 20 BP 8417 EP 8422 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 126WL UT WOS:000076317600028 PM 9763484 ER PT J AU Powell, SK Williams, CC Nomizu, M Yamada, Y Kleinman, HK AF Powell, SK Williams, CC Nomizu, M Yamada, Y Kleinman, HK TI Laminin-like proteins are differentially regulated during cerebellar development and stimulate granule cell neurite outgrowth in vitro SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE laminin-1; laminin-2; cerebellum; granule neuron; neurite outgrowth; laminin peptides ID CONGENITAL MUSCULAR-DYSTROPHY; TERMINAL GLOBULAR DOMAIN; RAT SYMPATHETIC NEURONS; CENTRAL-NERVOUS-SYSTEM; S-LAMININ; SYNTHETIC PEPTIDES; STOP SIGNAL; IN-VITRO; POSTNATAL-DEVELOPMENT; MOLECULAR LAYER AB The basement membrane glycoprotein laminin-1 is a potent stimulator of neurite outgrowth, Although a variety of laminin isoforms have been described in recent years, the role of alternative laminin isoforms in neural development remains largely uncharacterized, We found that a polyclonal antibody raised against the alpha 1, beta 1, and gamma 1 chains of laminin-1 and a monoclonal antibody raised against the alpha 2 chain of laminin-2 detect immunoreactive material in neuronal cell bodies in the developing mouse cerebellum, In addition, laminin-1-like immunoreactivity was found in cell types throughout the cerebellum, but laminin-alpha 2-like immunoreactivity was restricted to the Purkinje cells, Purified laminin-1 and laminin-2 stimulated neurite outgrowth in primary cultures of mouse cerebellar granule neurons to a similar extent, whereas the synthetic peptides tested appeared to he active only for cell adhesion and not for stimulation of neurite outgrowth, The E8 proteolytic fragment of laminin-1 contained full neurite outgrowth activity, The identity of laminins expressed in granule neurons was also examined by Western blotting; lanainin-like complexes were associated with the cell and appeared to have novel compositions, These results suggest that laminin-like complexes play important roles in cerebellar development. (C) 1998 Wiley-Liss, Inc.dagger C1 NIDR, Dev Biol Lab, NIH, Bethesda, MD 20892 USA. RP Kleinman, HK (reprint author), NIDR, Dev Biol Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 77 TC 42 Z9 42 U1 1 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD OCT 15 PY 1998 VL 54 IS 2 BP 233 EP 247 DI 10.1002/(SICI)1097-4547(19981015)54:2<233::AID-JNR11>3.0.CO;2-5 PG 15 WC Neurosciences SC Neurosciences & Neurology GA 126PW UT WOS:000076303200011 PM 9788282 ER PT J AU Ding, JX Yang, L Yan, YT Chen, A Desai, N Wynshaw-Boris, A Shen, MM AF Ding, JX Yang, L Yan, YT Chen, A Desai, N Wynshaw-Boris, A Shen, MM TI Cripto is required for correct orientation of the anterior-posterior axis in the mouse embryo SO NATURE LA English DT Article ID NEURAL PLATE; PRIMITIVE ENDODERM; GENE; EXPRESSION; MESODERM; GASTRULATION; FAMILY; GROWTH; BRAIN; CELLS AB The anterior-posterior axis of the mouse embryo is established by two distinct organizing centres in the anterior visceral endoderm and the distal primitive streak(1-7). These organizers induce and pattern the head and trunk respectively, and have been proposed to be localized through coordinate cell movements that rotate a pre-existing pre-existing proximal-distal axis(6,8). Here we show that correct localization of both head- and trunk-organizing centres requires Cripto(9,10), a putative signalling molecule that is a member of the EGF-CFC gene family(11,12), Before gastrulation, Cripto is asymmetrically expressed in a proximal-distal gradient in the epiblast, and subsequently is expressed in the primitive streak and newly formed embryonic mesoderm. A Cripto null mutation generated by targeted gene disruption results in homozygous Cripto(-/-) embryos that mostly consist of anterior neuroectoderm and lack posterior structures, thus resembling a head without a trunk, Notably, markers of the head organizer are located at the distal end of the embryo, whereas markers of the primitive streak are absent or localized to the proximal side. Our results indicate that Cripto signalling is essential for the conversion of a pro;proximal-distal asymmetry into an orthogonal anterior-posterior axis. C1 Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Ctr Adv Biotechnol & Med, Piscataway, NJ 08854 USA. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Pediat, Piscataway, NJ 08854 USA. Natl Human Genome Res Inst, Lab Genet Dis Res, Bethesda, MD 20892 USA. RP Shen, MM (reprint author), Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Ctr Adv Biotechnol & Med, 679 Hoes Lane, Piscataway, NJ 08854 USA. EM mshen@cabm.rutgers.edu RI Shen, Michael/C-7546-2009 OI Shen, Michael/0000-0002-4042-1657 NR 30 TC 325 Z9 330 U1 1 U2 4 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD OCT 15 PY 1998 VL 395 IS 6703 BP 702 EP 707 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 129PR UT WOS:000076472600053 PM 9790191 ER PT J AU Baker, SG Connor, RJ Kessler, LG AF Baker, SG Connor, RJ Kessler, LG TI The partial testing design: A less costly way to test equivalence for sensitivity and specificity SO STATISTICS IN MEDICINE LA English DT Article ID LOG-LINEAR MODELS; CATEGORICAL-DATA; SAMPLE-SIZE; MISCLASSIFICATION ERRORS; EM ALGORITHM; INSPECTION AB We propose a new, less costly, design to test the equivalence of digital versus analogue mammography in terms of sensitivity and specificity, Because breast cancer is a rare event among asymptomatic women, the sample size for testing equivalence of sensitivity is larger than that for testing equivalence of specificity. Hence calculations of sample size are based on sensitivity. With the proposed design it is possible to achieve the same power as a completely paired design by increasing the number of less costly analogue mammograms and not giving the more expensive digital mammograms to some randomly selected subjects who are negative on the analogue mammogram. The key idea is that subjects who are negative on the analogue mammogram are unlikely to have cancer and hence contribute less information for estimating sensitivity than subjects who are positive on the analogue mammogram. To ascertain disease state among subjects not biopsied, we propose another analogue mammogram at a later time determined by a natural history model. The design differs from a double sampling design because it compares two imperfect tests instead of combining information from a perfect and imperfect test. (C0 1998 John Wiley & Sons, Ltd. C1 NCI, Biometry Branch, EPN 344, Bethesda, MD 20892 USA. NCI, Appl Res Branch, EPN 3444, Bethesda, MD 20892 USA. RP Baker, SG (reprint author), NCI, Biometry Branch, EPN 344, 6130 Execut Blvd,MSC 7354, Bethesda, MD 20892 USA. EM xpv@helix.nih.gov NR 31 TC 11 Z9 11 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD OCT 15 PY 1998 VL 17 IS 19 BP 2219 EP 2232 PG 14 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 126ML UT WOS:000076297200005 PM 9802180 ER PT J AU Dress, KR Goossen, LJ Liu, H Jerina, DM Sharpless, KB AF Dress, KR Goossen, LJ Liu, H Jerina, DM Sharpless, KB TI Catalytic aminohydroxylation using adenine-derivatives as the nitrogen source SO TETRAHEDRON LETTERS LA English DT Article ID ASYMMETRIC AMINOHYDROXYLATION; OLEFINS AB The N-chloro-N-sodio salts of adenine derivatives are suitable nitrogen sources for the osmium catalyzed aminohydroxylation of olefins, achieving suprafacial, vicinal addition of adenine and a hydroxyl group. The scope of this transformation was examined using adenine and adenosine-derivatives in conjunction with three different olefins. (C) 1998 Elsevier Science Ltd. All rights reserved. C1 NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. Skaggs Inst Chem Biol, La Jolla, CA 92037 USA. Scripps Res Inst, Dept Chem, La Jolla, CA 92037 USA. RP Jerina, DM (reprint author), NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RI Goossen, Lukas/L-9764-2015 OI Goossen, Lukas/0000-0002-2547-3037 NR 13 TC 11 Z9 11 U1 1 U2 7 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0040-4039 J9 TETRAHEDRON LETT JI Tetrahedron Lett. PD OCT 15 PY 1998 VL 39 IS 42 BP 7669 EP 7672 DI 10.1016/S0040-4039(98)01716-X PG 4 WC Chemistry, Organic SC Chemistry GA 125CX UT WOS:000076220800014 ER PT J AU Caterina, NCM Windsor, LJ Bodden, MK Yermovsky, AE Taylor, KB Birkedal-Hansen, H Engler, JA AF Caterina, NCM Windsor, LJ Bodden, MK Yermovsky, AE Taylor, KB Birkedal-Hansen, H Engler, JA TI Glycosylation and NH2-terminal domain mutants of the tissue inhibitor of metalloproteinases-1 (TIMP-1) SO BIOCHIMICA ET BIOPHYSICA ACTA-PROTEIN STRUCTURE AND MOLECULAR ENZYMOLOGY LA English DT Article DE collagenase; M-r 72 000 gelatinase; extracellular matrix ID FIBROBLAST COLLAGENASE INHIBITOR; N-LINKED OLIGOSACCHARIDE; MATRIX METALLOPROTEINASES; PLASMID DNA; MONOCLONAL-ANTIBODIES; DIRECTED MUTAGENESIS; TERMINAL DOMAIN; RNA-POLYMERASE; AMNIOTIC-FLUID; PURIFICATION AB Mutants in the tissue inhibitor of metalloproteinases-(1) (TIMP-1) protein have been created by site-directed mutagenesis and expressed in HeLa cells, using a recombinant vaccinia virus system. Removal of either or both glycosylation sites yielded proteins which retained wild-type inhibitory activity against both human fibroblast-type collagenase (FIB-CL) and M-r 72 000 gelatinase (GL). However, the double glycosylation mutant protein was expressed at a level that was 2-4-fold lower than that of the wild-type or the single site glycosylation mutants. The 'tiny-TIMP' COOH-terminal deletion mutant that lacks the last 57 residues was also inhibitory, but the dose-response curve suggested that the interaction with the M-r 72 000 gelatinase had been altered. A number of replacement mutants in the highly conserved NH2-terminal domain, including replacement of P5A and P8A or a double mutation in the VIRAK sequence which is absolutely conserved in all TIMPs in all species (VIRAK to VIAAA), also yielded functional proteins capable of inhibiting FIB-CL and M-r 72 000 GL and of forming SDS-resistant complexes with FIB-CL. None of the above manipulations abolished inhibitory function suggesting that binding of the inhibitor by the enzyme involves multiple interactions. (C) 1998 Elsevier Science B.V. All rights reserved. C1 Univ Alabama, Sch Med, Dept Biochem & Mol Genet, Birmingham, AL 35294 USA. NIDR, NIH, Bethesda, MD 20892 USA. Univ Alabama, Sch Med, Oral Biol Res Ctr, Birmingham, AL 35294 USA. Univ Alabama, Sch Dent, Birmingham, AL 35294 USA. Univ Alabama, Sch Med, Oral Canc Res Ctr, Birmingham, AL 35294 USA. RP Engler, JA (reprint author), Univ Alabama, Sch Med, Dept Biochem & Mol Genet, Birmingham, AL 35294 USA. EM jengler@bmg.bhs.uab.edu FU NIDCR NIH HHS [DE/CA 11910, DE08228, DE10631] NR 58 TC 13 Z9 13 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4838 J9 BBA-PROTEIN STRUCT M JI Biochim. Biophys. Acta-Protein Struct. Molec. Enzym. PD OCT 14 PY 1998 VL 1388 IS 1 BP 21 EP 34 DI 10.1016/S0167-4838(98)00158-7 PG 14 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 132YP UT WOS:000076659800003 PM 9774703 ER PT J AU Blom, AM Covell, DG Wallqvist, A Dahlback, B Villoutreix, BO AF Blom, AM Covell, DG Wallqvist, A Dahlback, B Villoutreix, BO TI The C4b-binding protein protein S interaction is hydrophobic in nature SO BIOCHIMICA ET BIOPHYSICA ACTA-PROTEIN STRUCTURE AND MOLECULAR ENZYMOLOGY LA English DT Article DE complement control protein; protein modeling; vitamin K dependence; blood coagulation; c4b-binding protein ID BETA-CHAIN; MOLECULAR-CLONING; BINDING-SITE; MODULE; REGION; C4BP; PURIFICATION; PEPTIDE AB C4b-binding protein (C4BP) is a major regulatory molecule of the complement system. By forming a non covalent complex with the anticoagulant cofactor protein S (PS), it also plays an important role in blood coagulation. C4BP is composed of one beta-chain and seven alpha-chains that are essentially built from complement control protein (CCP)-modules. Our group has previously reported that the first (N-terminal) CCP module of the beta-chain (beta CCP1) contains the entire binding site for protein S, We now investigate further the binding of protein S to C4BP and show that the complex formation is essentially dependent on hydrophobic forces with minor contribution from electrostatic interactions. This result is in agreement with homology modeling experiments carried out in conjunction with inter-species sequence comparison and theoretical enumeration of potential binding sites. These methods pinpoint a solvent exposed hydrophobic cluster at the surface of the beta CCP1 module that is of crucial importance for the binding process. (C) 1998 Elsevier Science B.V. All rights reserved. C1 Univ Lund, Malmo Univ Hosp, Dept Clin Chem, Wallenberg Lab, S-20502 Malmo, Sweden. NCI, Frederick Canc Res & Dev Ctr, Sci Applicat Int Corp, Frederick, MD 21702 USA. Rutgers State Univ, Dept Chem, Piscataway, NJ 08855 USA. RP Villoutreix, BO (reprint author), Univ Lund, Malmo Univ Hosp, Dept Clin Chem, Wallenberg Lab, S-20502 Malmo, Sweden. RI Blom, Anna/B-9607-2009; OI Blom, Anna/0000-0002-1348-1734; wallqvist, anders/0000-0002-9775-7469 NR 30 TC 21 Z9 21 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4838 J9 BBA-PROTEIN STRUCT M JI Biochim. Biophys. Acta-Protein Struct. Molec. Enzym. PD OCT 14 PY 1998 VL 1388 IS 1 BP 181 EP 189 DI 10.1016/S0167-4838(98)00178-2 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 132YP UT WOS:000076659800019 PM 9774728 ER PT J AU Wechselberger, C AF Wechselberger, C TI Cloning of cDNAs encoding new peptides of the dermaseptin-family SO BIOCHIMICA ET BIOPHYSICA ACTA-PROTEIN STRUCTURE AND MOLECULAR ENZYMOLOGY LA English DT Article DE phyllomedusinae; skin secretion; cDNA cloning; antibiotic peptide; dermaseptin ID FROG-SKIN; AMPHIBIAN SKIN; ANTIMICROBIAL PEPTIDES; DEFENSIVE PEPTIDES; OPIOID-PEPTIDES; XENOPUS-LAEVIS; SEQUENCE; PRECURSOR; DERMORPHIN; ADENOREGULIN AB Dermaseptins are a group of basic (lysine-rich) peptides, 27-34 amino acids in length and involved in the defense of frog skin against microbial invasion. By using a degenerated oligonucleotide primer binding to the 5'-untranslated region of previously characterized cDNAs of these peptides, it was possible ro identify new members of the dermaseptin family in the South American frogs Agalychnis annae and Pachymedusa dacnicolor. Amino acid alignment and secondary structure prediction reveals, that only five of the deduced peptides can be supposed to be also functional homologs to the known dermaseptins from Phyllomedusa bicolor and Phyllomedusa sauvagei. The remaining six peptides described in this paper have not been isolated and characterized yet. (C) 1998 Elsevier Science B.V. All rights reserved. C1 Austrian Acad Sci, Inst Mol Biol, Dept Biochem, A-5020 Salzburg, Austria. RP Wechselberger, C (reprint author), NCI, Tumor Growth Factor Sect, NIH, 10 Ctr Dr,10-5B43, Bethesda, MD 20892 USA. NR 40 TC 41 Z9 52 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4838 J9 BBA-PROTEIN STRUCT M JI Biochim. Biophys. Acta-Protein Struct. Molec. Enzym. PD OCT 14 PY 1998 VL 1388 IS 1 BP 279 EP 283 DI 10.1016/S0167-4838(98)00202-7 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 132YP UT WOS:000076659800031 PM 9774745 ER PT J AU Paone, D Des Jarlais, DC Singh, MP Grove, D Shi, Q Krim, M Purchase, D Needle, RH Hartsock, P AF Paone, D Des Jarlais, DC Singh, MP Grove, D Shi, Q Krim, M Purchase, D Needle, RH Hartsock, P TI Update: Syringe exchange programs - United States, 1997 (Reprinted from MMWR, vol 47, pg 652-653, 1998) SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Reprint C1 Beth Israel Med Ctr, New York, NY 10003 USA. Amer Fdn AIDS Res, New York, NY 10001 USA. N Amer Syringe Exchange Network, Tacoma, WA 98402 USA. NIDA, Commun Res Br, Div Epidemiol & Prevent, NIH, Bethesda, MD 20892 USA. CDC, Div HIV AIDS Prevent Intervent Res & Support, Natl Ctr HIV STD & TB Prevent, Atlanta, GA 30333 USA. RP Paone, D (reprint author), Beth Israel Med Ctr, New York, NY 10003 USA. NR 12 TC 2 Z9 2 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD OCT 14 PY 1998 VL 280 IS 14 BP 1217 EP 1218 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 127NR UT WOS:000076357900010 ER PT J AU Ishima, R Wingfield, PT Stahl, SJ Kaufman, JD Torchia, DA AF Ishima, R Wingfield, PT Stahl, SJ Kaufman, JD Torchia, DA TI Using amide H-1 and N-15 transverse relaxation to detect millisecond time-scale motions in perdeuterated proteins: Application to HIV-1 protease SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID CHEMICAL-SHIFT ANISOTROPY; MAGNETIC-RESONANCE RELAXATION; MODEL-FREE APPROACH; NMR-SPECTROSCOPY; BACKBONE DYNAMICS; STAPHYLOCOCCAL NUCLEASE; CROSS-CORRELATION; SPIN RELAXATION; WATER-MOLECULES; MACROMOLECULES AB Measurements of proton transverse relaxation rates, R-2 and R-1 rho, have not been commonly performed for proteins because cross correlations among the numerous H-1-H-1 dipolar interactions complicate analysis of the data. In addition, these interactions make large contributions to the relaxation of the amide protons, making it difficult to detect if an exchange of chemical shifts also makes a contribution, R-ex, to relaxation. To overcome these problems, we have investigated proton relaxation of a perdeuterated protein, HIV-1 protease, bound to a small protonated inhibitor DMP323. Perdeuteration significantly reduces the contributions of H-1-H-1 dipolar interactions to the relaxation of the amide protons. The ROESY R-1 rho experiment further reduces the overall relaxation rate as compared with the usual R-1 rho experiment because the protons relax as unlike spins, with rate R-1 rho.unlike. in the former experiment but as like spins, with rate R-1 rho, in the latter. These reductions of the proton transverse-relaxation rate facilitated the detection of R-ex contributions at several sites in the protein (1) from the B-1-field dependence of R-1 rho,R-unlike and (2) by comparing R-1 rho,R-unlike values with relaxation rates, R-2, obtained from Carr-Purcell-Meiboom-Gill (CPMG) and Hahn-echo experiments. The significant reduction of the proton spin-flip rate in the perdeuterated protein enabled measurement of N-15 R-2 values using the CPMG method and the same large duration between 180 degrees pulses as used in the H-1 CPMG experiments. Hence, relaxation data of both nuclei were utilized to obtain complementary information about sites experiencing exchange of chemical shifts in the protein. C1 NIDR, Struct Mol Biol Unit, Bethesda, MD 20892 USA. NIAMSD, Prot Express Lab, NIH, Bethesda, MD 20892 USA. RP Torchia, DA (reprint author), NIDR, Struct Mol Biol Unit, Bethesda, MD 20892 USA. NR 59 TC 92 Z9 92 U1 0 U2 8 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD OCT 14 PY 1998 VL 120 IS 40 BP 10534 EP 10542 DI 10.1021/ja981546c PG 9 WC Chemistry, Multidisciplinary SC Chemistry GA 129UK UT WOS:000076481900034 ER PT J AU Clore, GM Starich, MR Gronenborn, AM AF Clore, GM Starich, MR Gronenborn, AM TI Measurement of residual dipolar couplings of macromolecules aligned in the nematic phase of a colloidal suspension of rod-shaped viruses SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID NMR C1 NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Clore, GM (reprint author), NIDDKD, Chem Phys Lab, NIH, Bldg 5, Bethesda, MD 20892 USA. RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 NR 15 TC 294 Z9 295 U1 2 U2 14 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD OCT 14 PY 1998 VL 120 IS 40 BP 10571 EP 10572 DI 10.1021/ja982592f PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 129UK UT WOS:000076481900049 ER PT J AU Joshi, MK Dracheva, S Mukhopadhyay, AK Bose, S Hendler, RW AF Joshi, MK Dracheva, S Mukhopadhyay, AK Bose, S Hendler, RW TI Importance of specific native lipids in controlling the photocycle of Bacteriorhodopsin SO BIOCHEMISTRY LA English DT Article ID PURPLE MEMBRANE-LIPIDS; TO-BLUE TRANSITION; HALOBACTERIUM-HALOBIUM; POLAR LIPIDS; PROTON PUMP; RECONSTITUTION; BEHAVIOR; BACTERIA; PROTEIN; LIGHT AB Brief treatment of purple membrane (PM) with dilute detergent can cause major disruption of the BR photocycle without disrupting the trimer structure of BR [Mukhopadhyay et al. (1996) Biochemistry 35, 9245-9252]. Normal photocyle behavior can be recovered by incubating the damaged membranes with a total extract of the five types of native lipids present in PM. It is shown here that full restoration can also be obtained with combinations of squalene (SQ) and phosphatidyl glycerophosphate (PGP) which act synergistically. The addition of SQ to suboptimal levels of PGP induces complete reconstitution, principally by restoring the characteristics of the fast M intermediate, M-f (as defined in Mukhopadhyay et al. (1996) Biochemistry, 35, 9245-9252). The addition of small amounts of PGP to SQ, which alone is ineffective, also induces full reconstituion. At very high levels, full reconstitution can be obtained with PGP alone. These results, in combination with earlier studies which implicate an acidic amino acid residue [Bose et al. (1997) J. Phys. Chem. B 101, 10584-10587], suggest that a crucial interaction between a particular amino acid residue and a SQ-PGP Lipid complex may be essential for normal BR photocycle activity. C1 NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Joshi, MK (reprint author), NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. NR 36 TC 40 Z9 40 U1 1 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD OCT 13 PY 1998 VL 37 IS 41 BP 14463 EP 14470 DI 10.1021/bi980965j PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 129VP UT WOS:000076485000015 PM 9772173 ER PT J AU Jhee, KH McPhie, P Ro, HS Miles, EW AF Jhee, KH McPhie, P Ro, HS Miles, EW TI Tryptophan synthase mutations that alter cofactor chemistry lead to mechanism-based inactivation SO BIOCHEMISTRY LA English DT Article ID INDUCED CONFORMATIONAL-CHANGES; AMINO-ACID AMINOTRANSFERASE; CYSTATHIONINE BETA-LYASE; SERINE O-SULFATE; ESCHERICHIA-COLI; SALMONELLA-TYPHIMURIUM; CRYSTAL-STRUCTURE; ALPHA-SUBUNIT; ALPHA(2)BETA(2) COMPLEX; 3-DIMENSIONAL STRUCTURE AB Mutations in the pyridoxal phosphate binding site of the tryptophan synthase beta subunit (S377D and S377E) alter cofactor chemistry [Jhee, K.-H., et al. (1998) J. Biol. Chem. 273, 11417-11422]. We now report that the S377D, S377E, and S377A beta(2) subunits form alpha(2)beta(2) complexes with the of subunit and activate the alpha subunit-catalyzed cleavage of indole 3-glycerol phosphate. The apparent K-d for dissociation of the alpha and beta subunits is unaffected by the S377A mutation but is increased up to 500-fold by the S377D and S377E mutations. Although the three mutant alpha(2)beta(2) complexes exhibit very low activities in beta elimination and beta replacement reactions catalyzed at the beta site in the presence of Na+, the activities and spectroscopic properties of the S377A alpha(2)beta(2) complex are partially repaired by addition of Cs+. The S377D and S377E alpha(2)beta(2) complexes, unlike the wild-type and S377A alpha(2)beta(2) complexes and the mutant beta(2) subunits, undergo irreversible substrate-induced inactivation by L-serine or by beta-chloro-L-alanine. The rates of inactivation (k(inact)) are similar to the rates of catalysis (k(cat)). The partition ratios are very low (k(cat)/k(inact) = 0.25-3) and are affected by alpha subunit ligands and monovalent cations. The inactivation product released by alkali was shown by HPLC and by fluorescence, absorption, and mass spectroscopy to be identical to a compound previously synthesized from pyridoxal phosphate and pyruvate. We suggest that alterations in the cofactor chemistry that result from the engineered Asp377 in the active site of the beta subunit may promote the mechanism-based inactivation. C1 NIDDKD, Lab Biochem & Genet, Bethesda, MD 20892 USA. RP Miles, EW (reprint author), NIDDKD, Lab Biochem & Genet, Room 225,Bldg 8,8 Ctr Dr,MSC 0830, Bethesda, MD 20892 USA. NR 72 TC 15 Z9 15 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD OCT 13 PY 1998 VL 37 IS 41 BP 14591 EP 14604 DI 10.1021/bi981325j PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 129VP UT WOS:000076485000030 PM 9772188 ER PT J AU Nagai, Y Matter, EJ Earley, CJ Kemper, MK Becker, LC Lakatta, EG Fleg, JL AF Nagai, Y Matter, EJ Earley, CJ Kemper, MK Becker, LC Lakatta, EG Fleg, JL TI Increased carotid artery intimal-medial thickness in asymptomatic older subjects with exercise-induced myocardial ischemia SO CIRCULATION LA English DT Article DE coronary disease; carotid arteries; ultrasonics; exercise; risk factors ID ATHEROSCLEROSIS RISK; WALL THICKNESS; HEART-DISEASE; COMMUNITIES; POPULATION; MEN; ENLARGEMENT; PREVALENCE; SMOKING AB Background - Previous studies have shown an association between symptomatic coronary artery disease (CAD) and increased intimal-medial thickness of the common carotid artery (CCA IMT), a purported index of atherosclerosis. This study determines whether CCA IMT is increased in asymptomatic older subjects with an ischemic ST-segment response to treadmill exercise. Methods and Results - CCA IMT was measured by B-mode ultrasound in community-dwelling volunteers from the Baltimore Longitudinal Study of Aging, including 397 healthy subjects (age, 58.5 +/- 15.8 years) with normal ECG responses to maximum treadmill exercise, 72 asymptomatic subjects (age, 66.1 +/- 13.4 years) with exercise-induced horizontal or downsloping ST-segment depression greater than or equal to 1 mm, and 38 subjects (age, 77.4 +/- 7.8 years) with clinically manifest CAD as diagnosed by medical history and resting EGG. Forty-three subjects with abnormal exercise ECGs also underwent exercise thallium scintigraphy. Exercise-induced ST-segment depression was associated with increased IMT (P < 0.0001) independent of age and manifest CAD. After adjustment for age, IMT values progressively increased from healthy subjects to asymptomatic subjects with positive exercise ECG alone to those with concordant positive ECG and thallium scintigraphic findings who had virtually identical IMT to subjects with manifest CAD, Each 0.1-mm increase in IMT was associated with a 1.91-fold (95% CI, 1.46 to 2.50; P < 0.0001) increased risk for concordant positive exercise tests or manifest CAD, independent of other significant predictors of CAD. Conclusions - CCA IMT is increased in older subjects with asymptomatic myocardial ischemia as evidenced by exercise ECG alone or in combination with thallium scan. Carotid ultrasound may help to identify asymptomatic individuals with CAD. C1 NIA, Clin Invest Lab, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. Johns Hopkins Bayview Med Ctr, Dept Neurol, Baltimore, MD USA. Johns Hopkins Univ, Sch Med, Div Cardiol, Baltimore, MD USA. RP Matter, EJ (reprint author), NIA, Clin Invest Lab, Gerontol Res Ctr, NIH, Box 06,5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 29 TC 141 Z9 149 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 13 PY 1998 VL 98 IS 15 BP 1504 EP 1509 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 127GN UT WOS:000076342700006 PM 9769303 ER PT J AU Blum, A AF Blum, A TI Role of lymphocytes in heart disease SO CIRCULATION LA English DT Letter ID INJURY C1 NHLBI, Cardiol Branch, Bethesda, MD 20892 USA. RP Blum, A (reprint author), NHLBI, Cardiol Branch, Bldg 10, Bethesda, MD 20892 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 13 PY 1998 VL 98 IS 15 BP 1590 EP 1590 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 127GN UT WOS:000076342700024 PM 9769318 ER PT J AU Caughey, WS Raymond, LD Horiuchi, M Caughey, B AF Caughey, WS Raymond, LD Horiuchi, M Caughey, B TI Inhibition of protease-resistant prion protein formation by porphyrins and phthalocyanines SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CONGO RED; APOCYTOCHROME B(5); AGENT REPLICATION; INCUBATION PERIOD; PRP ACCUMULATION; DEXTRAN SULFATE; SCRAPIE; HEME; AGGREGATION; PROTOPORPHYRIN AB A central aspect of pathogenesis in the transmissible spongiform encephalopathies or prion diseases is the conversion of normal protease-sensitive prion protein (PrP-sen) to the abnormal protease-resistant form, PrP-res. Here we identify porphyrins and phthalocyanines as inhibitors of PrP-res accumulation. The most potent of these tetrapyrroles had IC(50) values of 0.5-1 mu M in scrapie-infected mouse neuroblastoma (ScNB) cell cultures. Inhibition was observed without effects on protein biosynthesis in general or PrP-sen biosynthesis in particular. Tetrapyrroles also inhibited PrP-res formation in a cell-free reaction composed predominantly of hamster PrP-res and PrP-sen, Inhibitors were found among phthalocyanines, deuteroporphyrins IX, and meso-substituted porphines; examples included compounds containing anionic, neutral protic, and cationic peripheral substituents and various metals. We conclude that certain tetrapyrroles specifically inhibit the conversion of PrP-sen to PrP-res without apparent cytotoxic effects, The inhibition observed in the cell-free conversion reaction suggests that the mechanism involved direct interactions of the tetrapyrrole with PrP-res and/or PrP-sen. These findings introduce a new class of inhibitors of PrP-res formation that represents a potential source of therapeutic agents for transmissible spongiform encephalopathies. C1 NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, NIH, Hamilton, MT 59840 USA. RP Caughey, B (reprint author), NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, NIH, 903 S 4th St, Hamilton, MT 59840 USA. EM byron_caughey@nih.gov NR 50 TC 191 Z9 204 U1 2 U2 10 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 13 PY 1998 VL 95 IS 21 BP 12117 EP 12122 DI 10.1073/pnas.95.21.12117 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 129DL UT WOS:000076447900011 PM 9770449 ER PT J AU Hoskins, JR Pak, M Maurizi, MR Wickner, S AF Hoskins, JR Pak, M Maurizi, MR Wickner, S TI The role of the ClpA chaperone in proteolysis by ClpAP SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE ATP-dependent proteolysis; molecular chaperones ID ATP-DEPENDENT PROTEASE; HEAT-SHOCK PROTEINS; ESCHERICHIA-COLI; MU-TRANSPOSASE; SPECIFICITY COMPONENT; MOLECULAR CHAPERONE; 20S PROTEASOME; HSP104; RESOLUTION; COMPLEX AB ClpA, a member of the Clp/Hsp100 family of ATPases, is a molecular chaperone and, in combination with a proteolytic component ClpP, participates in ATP-dependent proteolysis. We investigated the role of ClpA in protein degradation by ClpAP by dissociating the reaction into several discrete steps. In the assembly step, ClpA-ClpP-substrate complexes assemble either by ClpA-substrate complexes interacting with ClpP or by ClpA-ClpP complexes interacting with substrate; ClpP in the absence of ClpA is unable to bind substrates. Assembly requires ATP binding but not hydrolysis. We discovered that ClpA translocates substrates from their binding sites on ClpA to ClpP. The translocation step specifically requires ATP; nonhydrolyzable ATP analogs are ineffective. Only proteins that are degraded by ClpAP are translocated. Characterization of the degradation step showed that substrates can be degraded in a single round of ClpA-ClpP-substrate binding followed by ATP hydrolysis. The products generated are indistinguishable from steady-state products. Taken together, our results suggest that ClpA, through its interaction with both the substrate and ClpP, acts as a gatekeeper, actively translocating specific substrates into the proteolytic chamber of ClpP where degradation occurs. As multicomponent ATP-dependent proteases are widespread in nature and share structural similarities, these findings may provide a general mechanism for regulation of substrate import into the proteolytic chamber. C1 NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Wickner, S (reprint author), NCI, Mol Biol Lab, NIH, Bldg 37,Room 2D19,37 Convent Dr MSC37-4255, Bethesda, MD 20892 USA. NR 39 TC 116 Z9 118 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 13 PY 1998 VL 95 IS 21 BP 12135 EP 12140 DI 10.1073/pnas.95.21.12135 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 129DL UT WOS:000076447900014 PM 9770452 ER PT J AU Longley, MJ Prasad, R Srivastava, DK Wilson, SH Copeland, WC AF Longley, MJ Prasad, R Srivastava, DK Wilson, SH Copeland, WC TI Identification of 5 '-deoxyribose phosphate lyase activity in human DNA polymerase gamma and its role in mitochondrial base excision repair in vitro SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID APURINIC APYRIMIDINIC SITES; OXIDATIVE DAMAGE; DEOXYRIBOSE PHOSPHATE; MAMMALIAN-CELLS; RAT-LIVER; BETA; ENDONUCLEASE; REPLICATION; MECHANISM; NUCLEAR AB Mitochondria have been proposed to possess base excision repair processes to correct oxidative damage to the mitochondrial genome. As the only. DNA polymerase (pol) present in mitochondria, pol gamma is necessarily implicated in such processes. Therefore, we tested the ability of the catalytic subunit of human pol gamma to participate in uracil-provoked base excision repair reconstituted in vitro with purified components. Subsequent to actions of uracil-DNA glycosylase and apurinic/apyrimidinic endonuclease, human pol gamma was able to fill a single nucleotide gap in the presence of a 5' terminal deoxyribose phosphate (dRP) flap. We report here that the catalytic subunit of human pol gamma catalyzes release of the dRP residue from incised apurinic/apyrimidinic sites to produce a substrate for DNA ligase. The heat sensitivity of this activity suggests the dRP lyase function requires a three-dimensional protein structure. The dRP lyase activity does not require divalent metal ions, and the ability to trap covalent enzyme-DNA complexes with NaBH4 strongly implicates a Schiff base intermediate in a beta-elimination reaction mechanism. C1 NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. NIEHS, Struct Biol Lab, Res Triangle Pk, NC 27709 USA. RP Copeland, WC (reprint author), NIEHS, Mol Genet Lab, POB 12233, Res Triangle Pk, NC 27709 USA. NR 39 TC 140 Z9 142 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 13 PY 1998 VL 95 IS 21 BP 12244 EP 12248 DI 10.1073/pnas.95.21.12244 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 129DL UT WOS:000076447900033 PM 9770471 ER PT J AU Majdalani, N Cunning, C Sledjeski, D Elliott, T Gottesman, S AF Majdalani, N Cunning, C Sledjeski, D Elliott, T Gottesman, S TI DsrA RNA regulates translation of RpoS message by an anti-antisense mechanism, independent of its action as an antisilencer of transcription SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID SITE-SPECIFIC MUTAGENESIS; ESCHERICHIA-COLI; SALMONELLA-TYPHIMURIUM; PHENOTYPIC SELECTION; EXPRESSION; GENE AB DsrA RNA regulates both transcription, by overcoming transcriptional silencing by the nucleoid-associated H-NS protein, and translation, by promoting efficient translation of the stress a factor, RpoS. These two activities of DsrA can be separated by mutation: the first of three stem-loops of the 85 nucleotide RNA is necessary for RpoS translation but not for anti-H-NS action, while the second stem-loop is essential for antisilencing and less critical for RpoS translation. The third stem-loop, which behaves as a transcription terminator, can be substituted by the trp transcription terminator without loss of either DsrA function. The sequence of the first stem-loop of DsrA is complementary with the upstream leader portion of rpoS messenger RNA, suggesting that pairing of DsrA with the rpoS message might be important for translational regulation. Mutations in the Rpos leader and compensating mutations in DsrA confirm that this predicted pairing is necessary for DsrA stimulation of RpoS translation. We propose that DsrA pairing stimulates RpoS translation by acting as an anti-antisense RNA, freeing the translation initiation region from the cis-acting antisense RNA and allowing increased translation. C1 NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Med Coll Ohio, Dept Immunol & Microbiol, Toledo, OH 43614 USA. W Virginia Univ, Hlth Sci Ctr, Dept Immunol & Microbiol, Morgantown, WV 26506 USA. RP Gottesman, S (reprint author), NCI, Mol Biol Lab, NIH, Bldg 37,Room 2E18, Bethesda, MD 20892 USA. OI Sledjeski, Darren/0000-0001-9882-6625 FU NIGMS NIH HHS [GM40403, GM56448] NR 20 TC 331 Z9 339 U1 1 U2 13 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 13 PY 1998 VL 95 IS 21 BP 12462 EP 12467 DI 10.1073/pnas.95.21.12462 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 129DL UT WOS:000076447900070 PM 9770508 ER PT J AU Markham, RB Wang, WC Weisstein, AE Wang, Z Munoz, A Templeton, A Margolick, J Vlahov, D Quinn, T Farzadegan, H Yu, XF AF Markham, RB Wang, WC Weisstein, AE Wang, Z Munoz, A Templeton, A Margolick, J Vlahov, D Quinn, T Farzadegan, H Yu, XF TI Patterns of HIV-1 evolution in individuals with differing rates of CD4 T cell decline SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; DISEASE PROGRESSION; MACROPHAGE TROPISM; SEQUENCE VARIATION; GENETIC-VARIATION; PRIMARY INFECTION; AIDS; CCR5; VARIANTS; REGION AB Evolution of HIV-1 env sequences was studied in 15 seroconverting injection drug users selected for differences in the extent of CD4 T cell decline. The rates of increase of either sequence diversity at a given visit or divergence from the first seropositive visit were both higher in progressors than in nonprogressors. Viral evolution in individuals with rapid or moderate disease progression showed selection favoring nonsynonymous mutations, while nonprogressors with low viral loads selected against the nonsynonymous mutations that might have resulted in viruses with higher levels of replication. For 10 of the 15 subjects no single variant predominated over time. Evolution away from a dominant variant was followed frequently at a later time point by return to dominance of strains closely related to that variant. The observed evolutionary pattern is consistent with either selection against only the predominant virus or independent evolution occurring in different environments within the host. Differences in the level to which CD4 T cells fall in a given time period reflect not only quantitative differences in accumulation of mutations, but differences in the types of mutations that pro,ide the best adaptation to the host environment. C1 Johns Hopkins Sch Hyg & Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD 21205 USA. Johns Hopkins Sch Hyg & Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA. Washington Univ, Dept Biol, St Louis, MO 63130 USA. NIAID, NIH, Bethesda, MD 20892 USA. Johns Hopkins Sch Med, Dept Med, Baltimore, MD 21205 USA. RP Markham, RB (reprint author), Johns Hopkins Sch Hyg & Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD 21205 USA. EM rmarkham@jhsph.edu RI Templeton, Alan/F-5963-2011 FU NIDA NIH HHS [DA 09973]; PHS HHS [04334, 09541] NR 51 TC 75 Z9 77 U1 1 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 13 PY 1998 VL 95 IS 21 BP 12568 EP 12573 DI 10.1073/pnas.95.21.12568 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 129DL UT WOS:000076447900088 PM 9770526 ER PT J AU Wahl, SM Greenwell-Wild, T Peng, G Hale-Donze, P Doherty, TM Mizel, D Orenstein, JM AF Wahl, SM Greenwell-Wild, T Peng, G Hale-Donze, P Doherty, TM Mizel, D Orenstein, JM TI Mycobacterium avium complex augments macrophage HIV-1 production and increases CCR5 expression SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; LEUKOCYTE PROTEASE INHIBITOR; TUMOR-NECROSIS-FACTOR; DENDRITIC CELLS; CHEMOKINE RECEPTORS; GENE-EXPRESSION; VIRAL LOAD; KAPPA-B; IN-VIVO; INFECTION AB Infection with HIV-1 results in pronounced immune suppression and susceptibility to opportunistic infections (OI). Reciprocally, OI augment HIV-1 replication. As we have shown for Mycobacterium avium complex (MAC) and Pneumocystis carinii, macrophages infected with opportunistic pathogens and within lymphoid tissues containing OI, exhibit striking levels of viral replication. To explore potential underlying mechanisms for increased HIV-1 replication associated with coinfection, blood monocytes were exposed to MAC antigens (MAg) or viable MAC and their levels of tumor necrosis factor alpha (TNF alpha) and HIV-1 coreceptors monitored. MAC enhanced TNF alpha production in vitro, consistent with its expression in coinfected lymph nodes. Using a polyclonal antibody to the CCR5 coreceptor that mediates viral entry of macrophage tropic HIV-1, a subset of unstimulated monocytes was shown to be CCR5-positive by fluorescence-activated cell sorter analysis. After stimulation with MAg or infection with MAC, CCR5 expression was increased at both the mRNA level and on the cell surface. Up-regulation of CCR5 by MAC was not paralleled by an increase in the T cell tropic coreceptor, CXCR4. Increases in NF-kappa B, TNF alpha, and CCR5 were consistent with the enhanced production of HIV-1 in MAg-treated adherent macrophage cultures as measured by HIV-1 p24 levels. Increased CCR5 was also detected in coinfected lymph nodes as compared with tissues with only HIV-1. The increased production of TNF alpha, together with elevated expression of CCR5, provide potential mechanisms for enhanced infection and replication of HIV-1 by macrophages in OI infected cells and tissues. Consequently, treating OI may inhibit not only the OI-induced pathology, but also limit the viral burden. C1 NIDR, Oral Infect & Immun Branch, Bethesda, MD 20892 USA. NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. George Washington Univ, Dept Pathol, Washington, DC 20037 USA. RP Wahl, SM (reprint author), NIDR, Oral Infect & Immun Branch, 30 Convent Dr,MSC 4352, Bethesda, MD 20892 USA. EM smwahl@yoda.nidr.nih.gov FU NIDCR NIH HHS [R01 DE012585, DE 12585] NR 54 TC 70 Z9 70 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 13 PY 1998 VL 95 IS 21 BP 12574 EP 12579 DI 10.1073/pnas.95.21.12574 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 129DL UT WOS:000076447900089 PM 9770527 ER PT J AU Ivanov, SV Kuzmin, I Wei, MH Pack, S Geil, L Johnson, BE Stanbridge, EJ Lerman, MI AF Ivanov, SV Kuzmin, I Wei, MH Pack, S Geil, L Johnson, BE Stanbridge, EJ Lerman, MI TI Down-regulation of transmembrane carbonic anhydrases in renal cell carcinoma cell lines by wild-type von Hippel-Lindau transgenes SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE gene targets; differential display; carcinogenesis ID TUMOR-SUPPRESSOR GENE; DIAGNOSTIC BIOMARKER; TRANSCRIPTION ELONGATION; MN ANTIGEN; PROTEIN; MUTATIONS; IDENTIFICATION; PRODUCT; BINDING; FAMILIES AB To discover genes involved in von Hippel-Lindau (VHL)-mediated carcinogenesis, we used renal cell carcinoma cell lines stably transfected with wild-type VHL-expressing transgenes, Large-scale RNA differential display technology applied to these cell lines identified several differentially expressed genes, including an alpha carbonic anhydrase gene, termed CA12. The deduced protein sequence was classified as a one-pass transmembrane CA possessing an apparently intact catalytic domain in the extracellular CA module. Reintroduced wild-type VHL strongly inhibited the overexpression of the CA12 gene in the parental renal cell carcinoma cell lines. Similar results were obtained with CA9, encoding another transmembrane CA with an intact catalytic domain. Although both domains of the VHL protein contribute to regulation of CA12 expression, the elongin binding domain alone could effectively regulate CA9 expression. We mapped CA12 and CA9 loci to chromosome bands 15q22 and 17q21,2 respectively, regions prone to amplification in some human cancers. Additional experiments are needed to define the role of CA IX and CA XII enzymes in the regulation of pH in the extracellular microenvironment and its potential impact on cancer cell growth. C1 Sci Applicat Int Corp Frederick, Immunol Lab, Intramural Res Support Program, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Immunobiol Lab, Frederick, MD 21702 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20889 USA. NCI, Med Branch, NIH, Bethesda, MD 20892 USA. Univ Calif Irvine, Coll Med, Dept Microbiol & Mol Genet, Irvine, CA 92717 USA. RP Ivanov, SV (reprint author), Sci Applicat Int Corp Frederick, Immunol Lab, Intramural Res Support Program, Frederick, MD 21702 USA. EM ivanov@ncifcrf.gov RI Pack, Svetlana/C-2020-2014 FU NCI NIH HHS [CA19401, N01-CO-56000] NR 40 TC 271 Z9 281 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 13 PY 1998 VL 95 IS 21 BP 12596 EP 12601 DI 10.1073/pnas.95.21.12596 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 129DL UT WOS:000076447900093 PM 9770531 ER PT J AU Halvorson, MJ Magner, W Coligan, JE AF Halvorson, MJ Magner, W Coligan, JE TI alpha 4 and alpha 5 integrins costimulate the CD3-dependent proliferation of fetal thymocytes SO CELLULAR IMMUNOLOGY LA English DT Article ID T-CELL-DEVELOPMENT; RECEPTOR-DEFICIENT MICE; NATURAL-KILLER-CELLS; THYMIC STROMAL CELLS; LYMPHOCYTES-T; INTERLEUKIN-2 DEFICIENT; SIGNAL TRANSDUCTION; MATURATION STAGE; BETA-CHAIN; CD2 GENE AB Although integrin receptors have been shown to function as costimulatory molecules on mature thymocytes and T cells, it is not known. whether these receptors tors can function as costimulatory molecules on immature thymocytes, Previous studies have shown that the expression of alpha 3. and alpha 5 integrins were significantly higher on immature, adult CD4(-)CD8(-) thymocytes than on either mature thymocytes or T cells, suggesting that these receptors are involved in early thymocyte development, In this study, we show that day 16 fetal thymocytes express levels of alpha 4 and alpha 5 equivalent to those of adult CD4(-)CD8(-) thymocytes. Immobilized fibronectin, a ligand for alpha 4 and a5 integrins, was found to enhance the CD3-dependent proliferation of these fetal thymocytes, In the presence of IL-7, the magnitude of the proliferative response increased with time of incubation, resulting in a dramatic increase in the percentage of gamma delta thymocytes, The enhancement of proliferation by fibronectin was abrogated by soluble antibodies against alpha 4 and alpha 5, whereas immobilized mAb to alpha 4 and alpha 5 substituted for fibronectin in enhancing CD3-dependent proliferation, demonstrating that alpha 4 and alpha 5 integrins were responsible for the enhanced proliferation by fibronectin. Anti-alpha 4 mAb enhanced proliferation of fetal thymocytes by 100%, whereas anti-alpha 5 mAb and anti-CD28 mAb enhanced proliferation by 25%. Other costimulatory molecules, such as CD2, FcR gamma, and Thy-1, had no effect on the CD3-dependent proliferation of day 16 fetal thymocytes. This study demonstrates that alpha 4 and alpha 5 integrins are capable of costimulating fetal thymocytes, (C) 1998 Academic Press. C1 NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. Uniformed Serv Univ Hlth Sci, Dept Microbiol & Immunol, Bethesda, MD 20814 USA. NIAID, Struct Biol Sect, NIH, Rockville, MD 20852 USA. RP Coligan, JE (reprint author), NIAID, Immunogenet Lab, NIH, Twinbrook II,Rm 205,12441 Parklawn Dr, Rockville, MD 20852 USA. NR 46 TC 4 Z9 4 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD OCT 10 PY 1998 VL 189 IS 1 BP 1 EP 9 DI 10.1006/cimm.1998.1368 PG 9 WC Cell Biology; Immunology SC Cell Biology; Immunology GA 129ZU UT WOS:000076494700001 PM 9758688 ER PT J AU Carman, TA Afshar, CA Barrett, JC AF Carman, TA Afshar, CA Barrett, JC TI Cellular senescence in telomerase-expressing Syrian hamster embryo cells SO EXPERIMENTAL CELL RESEARCH LA English DT Article DE telomeres; telomerase; senescence; Syrian hamster embryo cells; rodent telomerase ID ONE COMPLEMENTATION GROUP; NORMAL HUMAN FIBROBLASTS; IMMORTAL CELLS; DNA-DAMAGE; LENGTH; IDENTIFICATION; ASSIGNMENT; ELONGATION; INDUCTION; REPEATS AB We have observed that normal, diploid Syrian hamster embryo cells (SHE) express the enzyme telomerase but undergo senescence at the end of their replicative lifespan. After 20-30 population doublings (pd) these cells cease proliferating, enlarge in size, exhibit a pH 6.0 senescence-associated beta-galactosidase activity, and fail to phosphorylate the RE protein or enter into S-phase after serum stimulation. We have observed that SHE cells express telomerase throughout their replicative lifespan and that the average telomere length does not appear to decrease, remaining at about 23 kb in senescent cells. In addition, individual clones of SHE cells also have telomerase activity and telomeres that do not decrease in length, ruling out the possibility that there is a rare, immortal subpopulation of telomerase-expressing cells that is lost during passaging. Together, these data suggest that SHE cells are likely to senesce by a mechanism that does not involve telomere loss. (C) 1998 Academic Press. C1 NIEHS, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. Univ N Carolina, Dept Pathol, Chapel Hill, NC 27599 USA. RP Barrett, JC (reprint author), NIEHS, Mol Carcinogenesis Lab, POB 12233,MD C2-15, Res Triangle Pk, NC 27709 USA. NR 46 TC 38 Z9 38 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD OCT 10 PY 1998 VL 244 IS 1 BP 33 EP 42 DI 10.1006/excr.1998.4207 PG 10 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 130BL UT WOS:000076499300004 PM 9770346 ER PT J AU An, WG Chuman, Y Fojo, T Blagosklonny, MV AF An, WG Chuman, Y Fojo, T Blagosklonny, MV TI Inhibitors of transcription, proteasome inhibitors, and DNA-damaging drugs differentially affect feedback of p53 degradation SO EXPERIMENTAL CELL RESEARCH LA English DT Article DE p53; mdm-2; protein stabilization; proteasome; DNA damage ID HUMAN PAPILLOMAVIRUS TYPE-16; TUMOR-SUPPRESSOR PROTEIN; WILD-TYPE P53; IN-VIVO; MUTATED P53; APOPTOSIS; CELLS; MDM2; E6; CONFORMATION AB Mutations of the p53 gene are the most common abnormalities in human cancer. In contrast to mutant p53, wild-type (wt) p53 protein is present at low levels due to rapid degradation by proteasome. We demonstrated that wt p53 protein stabilization following DNA damage or proteasome inhibition did not abolish the wild-type conformation. DNA damage did not cause accumulation of ubiquitinated forms of wt p53, suggesting abrogation of ubiquitination, Consistent with this, the E6 oncoprotein which targets p53 for ubiquitination abolished stabilization of p53 protein by DNA-damaging drugs but not by proteasome inhibitors. In contrast to the effects on wt p53, inhibitors of proteolysis downregulated mutant p53. Regulation of p53 levels can be explained by a feedback mechanism where wt p53 transcriptionally induces "sensor" proteins (Mdm-2, as an example) and these, in turn, target p53 for degradation. Like p53, Mdm-2 is degraded by proteasome. Therefore, inhibition of proteasome caused accumulation of Mdm-2, leading to degradation of mutant p53 by the remaining proteolytic activity of the cell. We propose that inhibition of transcription should increase wt p53 protein due to inhibition of Mdm-2 synthesis. An inhibitor of transcription, alpha-amanitin, dramatically induced wt p53 protein, whereas Mdm-2 protein was downregulated. Moreover, alpha-amanitin increased p53 protein levels in E6-transfected cells. Although inhibitors of transcription, such as actinomycin D, also damage DNA, reduction of Mdm-2 or other putative "sensor" proteins may contribute to their p53-stabilizing activity, Similarly, antimetabolites augment accumulation of wt p53 due to interference with RNA synthesis. (C) 1998 Academic Press. C1 NCI, Med Branch, NIH, Bethesda, MD 20892 USA. RP Blagosklonny, MV (reprint author), NCI, Med Branch, NIH, Bldg 10,Room 12N226, Bethesda, MD 20892 USA. EM mikhailb@box-m.nih.gov NR 43 TC 44 Z9 45 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD OCT 10 PY 1998 VL 244 IS 1 BP 54 EP 60 DI 10.1006/excr.1998.4193 PG 7 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 130BL UT WOS:000076499300006 PM 9770348 ER PT J AU Potterf, SB Furumura, M Sviderskaya, EV Santis, C Bennett, DC Hearing, VJ AF Potterf, SB Furumura, M Sviderskaya, EV Santis, C Bennett, DC Hearing, VJ TI Normal tyrosine transport and abnormal tyrosinase routing in pink-eyed dilution melanocytes SO EXPERIMENTAL CELL RESEARCH LA English DT Article DE melanin; pinkeyed-dilution; transport; tyrosinase ID COAT-COLOR MUTANTS; II OCULOCUTANEOUS ALBINISM; MURINE MELANOCYTES; MEMBRANE-PROTEINS; MELANOMA-CELLS; MELANOSOMES; GENE; IDENTIFICATION; LYSOSOMES; MUTATION AB The pink-eyed dilution phenotype in mice arises from mutations in the p gene; in humans, analogous mutations in the P gene result in oculocutaneous albinism type 2, Although the molecular mechanisms which underlie this phenotype remain obscure, it has been postulated that mutations in p result in defective tyrosine transport into murine melanosomes, resulting in hypopigmentation and diminished coat color. However, we previously reported no difference in melanosomal tyrosine transport in unpigmented, melanoblast-like pink-eyed dilution (p(cp)/p(cp)), and in pigmented (melan-a) murine melanocytes. In this study, we utilized melan-p1 cells, more differentiated pink-eyed dilution (p(cp)/p(25H)) melanocytes which can be induced to produce melanin, to characterize the melanogenic lesion(s) more definitively. Uptake of [H-3]tyrosine into melan-a melanosomes did not differ significantly from uptake into melanosomes derived from melan-p1 melanocytes, further arguing against its critical role as a tyrosine transporter. Pink-eyed dilution melanocytes incubated in high tyrosine concentrations became extremely pigmented as they became confluent and secreted large amounts of black material into the medium. Total cellular tyrosinase activity in melan-p1 melanocytes was significantly higher than that in melan-a melanocytes (which are wild-type at the p locus), but the localization of tyrosinase to melanosomes was impaired in melan-p1 melanocytes compared to melan-a melanocytes. These results indicate that mechanisms other than deficient tyrosine transport are involved in the pink-eyed dilution phenotype and that this protein may serve a chaperone-like or stabilizing function in melanocytes. (C) 1998 Academic Press. C1 NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. St George Hosp, Sch Med, London SW17 0RE, England. RP Hearing, VJ (reprint author), NCI, Cell Biol Lab, NIH, Bldg 37,Room 1B25, Bethesda, MD 20892 USA. EM hearingv@nih.gov RI Bennett, Dorothy/C-2418-2008; Sviderskaya, Elena/D-2419-2009 OI Bennett, Dorothy/0000-0002-3639-7527; NR 28 TC 43 Z9 44 U1 0 U2 4 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD OCT 10 PY 1998 VL 244 IS 1 BP 319 EP 326 DI 10.1006/excr.1998.4173 PG 8 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 130BL UT WOS:000076499300033 PM 9770375 ER PT J AU Weichert, WS Parker, JSL Wahid, ATM Chang, SF Meier, E Parrish, CR AF Weichert, WS Parker, JSL Wahid, ATM Chang, SF Meier, E Parrish, CR TI Assaying for structural variation in the parvovirus capsid and its role in infection SO VIROLOGY LA English DT Article ID AMINO-ACID SUBSTITUTIONS; FOREST VIRUS SPIKE; CANINE HOST-RANGE; MINUTE VIRUS; LOW-PH; NEUTRALIZING ANTIBODIES; ENDOSOMAL PROTEOLYSIS; ENVELOPE GLYCOPROTEIN; LYMPHOTROPIC STRAIN; ADENOVIRUS PROTEASE AB The capsid of canine parvovirus (CPV) was assayed for susceptibility to proteases and for structural variation. The natural cleavage of VP2 to VP3 in CPV full (DNA containing) particles recovered from tissue culture occurred within the sequence Arg-Asn-Glu-Arg down arrow Ala-Thr. Trypsin, chymotrypsin, bromelain, and cathepsin a all cleaved >90% of the VP2 to VP3 in full but not in empty capsids and did not digest the capsid further. Digestion with proteinase K, Pronase, papain, or subtilisin cleaved the VP2 to VP3 and also cleaved at additional internal sites, causing particle disintegration and protein degradation. Several partial digestion products produced by proteinase K or subtilisin were similar to 31-32.5 kDa, indicating cleavage within loop 3 of the capsid protein as well as other sites. Protease treatment of capsids at pH 5.5 or 7.5 did not significantly alter their susceptibility to digestion. The isoelectric point of CPV empty capsids was pH 5.3, and full capsids were 0.3 pH more acidic, but after proteolysis of VP2 to VP3, the pi of the full capsids became the same as that of the empty capsids. Antibodies against Various capsid protein sequences showed the amino termini of most VP2 molecules were on the outside of full but not empty particles, that the VP1-unique sequence was internal, and that the capsid could be disintegrated by heat or urea treatment to expose the internal sequences. Capsids added to cells were localized within the cell cytoplasm in vesicles that appeared to be lysosomes. Microinjected capsids remained primarily in the cytoplasm, although a small proportion was observed to be in the nucleus after 2 h. After CPV capsids labeled with [S-35]methionine were bound to cells at 0 degrees C and the cells warmed, little cleavage of VPI or VP2 was observed even after prolonged incubation. Inoculation of cells with virus in the presence of proteinase inhibitors did not significantly reduce the infection. (C) 1998 Academic Press. C1 Cornell Univ, Coll Vet Med, James A Baker Inst, Ithaca, NY 14853 USA. NINDS, Lab Dev Neurogenet, NIH, Bethesda, MD 20892 USA. RP Parrish, CR (reprint author), Cornell Univ, Coll Vet Med, James A Baker Inst, Ithaca, NY 14853 USA. OI Parker, John/0000-0003-4487-4175 FU NIAID NIH HHS [AI28385, AI33468] NR 72 TC 65 Z9 67 U1 0 U2 8 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD OCT 10 PY 1998 VL 250 IS 1 BP 106 EP 117 DI 10.1006/viro.1998.9352 PG 12 WC Virology SC Virology GA 132ZP UT WOS:000076662200012 PM 9770425 ER PT J AU Cox, E Reddy, S Iofin, I Cohen, JI AF Cox, E Reddy, S Iofin, I Cohen, JI TI Varicella-zoster virus ORF57, unlike its pseudorabies virus UL3.5 homolog, is dispensable for viral replication in cell culture SO VIROLOGY LA English DT Article ID DNA-SEQUENCE; GENE-CLUSTER; TRANSCRIPTIONAL ANALYSIS; BOVINE HERPESVIRUS-1; IN-VITRO; UL1; IDENTIFICATION; PROTEIN; VZV AB Varicella tester virus (VZV) encodes five genes that do not have homologs in herpes simplex virus. One of these genes, VN ORF57, is predicted to encode a protein containing 71 amino acids. Antibody to ORF57 protein immunoprecipitated a 6-kDa protein in the cytosol of VZV-infected cells. Although the homolog of VZV ORF57 in pseudorabies virus, UL3.5, is critical for viral egress and growth in cell culture, VN unable to express ORF57 replicated to titers similar to those seen with parental virus. Thus VZV ORF57 has a different role in Viral replication than its pseudorabies virus homolog. C1 NIAID, Med Virol Sect, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. RP Cohen, JI (reprint author), NIAID, Med Virol Sect, Clin Invest Lab, NIH, Bldg 10,Room 11N214, Bethesda, MD 20892 USA. NR 13 TC 21 Z9 21 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD OCT 10 PY 1998 VL 250 IS 1 BP 205 EP 209 DI 10.1006/viro.1998.9349 PG 5 WC Virology SC Virology GA 132ZP UT WOS:000076662200021 PM 9770434 ER PT J AU Teramoto, T Kiss, A Thorgeirsson, SS AF Teramoto, T Kiss, A Thorgeirsson, SS TI Induction of p53 and Bax during TGF-beta 1 initiated apoptosis in rat liver epithelial cells SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID GROWTH-FACTOR-BETA; JUN; DIFFERENTIATION; TRANSFORMATION; EXPRESSION; RECEPTOR; CULTURE; DEATH; AP-1; FOS AB The relationship between transforming growth factor-beta 1 (TGF-beta 1) induced growth arrest and apoptosis in rat liver derived epithelial (RLE) cells was analyzed. TGF-beta 1 treatment of RLE cells induced both cell cycle arrest and apoptosis. However, pretreatment of the cells with either dexamethasone or cyclohexamide suppressed TGF-beta 1 induced apoptosis, without preventing the cell cycle arrest. Both p53 and Bax were subsequently shown to be overexpressed during the TGF-beta 1 induced apoptosis. Furthermore, it was revealed that cycloheximide suppressed expression of both p53 and Bax. In contrast, dexamethasone treatment prevented Bax expression alone. Treatment of RLE cells with several growth factors either alone or in combination was ineffective in counteracting TGF-beta 1 induced apoptosis. In additon, we show that TGF-alpha also induced both p53 and Bax expressions and augmented TGF-beta-induced apoptosis. Thus, p53 and Bax are likely to be key factors in TGF-beta 1 induced apoptosis in RLE cells. (C) 1998 Academic Press. C1 NCI, Expt Carcinogenesis Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Thorgeirsson, SS (reprint author), NCI, Expt Carcinogenesis Lab, Div Basic Sci, NIH, Bldg 37,Room 3C28,37 Convent Dr MSC-4255, Bethesda, MD 20892 USA. NR 20 TC 56 Z9 59 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD OCT 9 PY 1998 VL 251 IS 1 BP 56 EP 60 DI 10.1006/bbrc.1998.9411 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 132PM UT WOS:000076638800010 PM 9790906 ER PT J AU Sanchez-Roa, PM Wagner, HN Villemagne, VL London, ED Lever, JR AF Sanchez-Roa, PM Wagner, HN Villemagne, VL London, ED Lever, JR TI Effects of extracellular acetylcholine on muscarinic receptor binding assessed by [I-125]dexetimide and a simple probe SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE acetylcholine; muscarinic receptor; dexetimide; physostigmine; brain; radiation detection system ID ALZHEIMERS-DISEASE; CHOLINERGIC RECEPTORS; LIVING MICE; IN-VIVO; RAT; PHYSOSTIGMINE; MEMORY; INVIVO; PHARMACOKINETICS; 4-IODODEXETIMIDE AB New pharmacologic approaches to enhance brain cholinergic function focus on increasing intrasynaptic acetylcholine. We examined the usefulness of a simple probe and [I-125]dexetimide to evaluate in vivo the effects of extracellular acetylcholine on muscarinic receptor binding in the mouse brain. After radiotracer injection continuous time/activity curves were generated over 330 min. [I-125]Dexetimide reached a plateau at 90 min post-injection. To increase extracellular acetylcholine, the anticholinesterase physostigmine was administered at 120 min, producing a reversible decrease in [I-125]dexetimide specific binding (23%) for 30 min. These findings demonstrate that dynamic changes in extracellular acetylcholine can be evaluated by displacement of [I-125]dexetimide binding in vivo using a simple probe system. (C) 1998 Elsevier Science B.V. All rights reserved. C1 Johns Hopkins Univ, Dept Environm Hlth Sci, Div Nucl Med, Baltimore, MD 21205 USA. Johns Hopkins Univ, Dept Environm Hlth Sci, Div Radiat Hlth Sci, Baltimore, MD 21205 USA. NIDA, Brain Imaging Ctr, NIH, Baltimore, MD 21224 USA. RP Wagner, HN (reprint author), Johns Hopkins Univ, Dept Environm Hlth Sci, Div Nucl Med, 615 N Wolfe St,Room 2001, Baltimore, MD 21205 USA. FU NCI NIH HHS [CA 32845] NR 32 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD OCT 9 PY 1998 VL 358 IS 3 BP 207 EP 211 DI 10.1016/S0014-2999(98)00633-5 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 131ZA UT WOS:000076604100004 PM 9822886 ER PT J AU Fan, GF Ray, K Zhao, XM Goldsmith, PK Spiegel, AM AF Fan, GF Ray, K Zhao, XM Goldsmith, PK Spiegel, AM TI Mutational analysis of the cysteines in the extracellular domain of the human Ca2+ receptor: effects on cell surface expression, dimerization and signal transduction SO FEBS LETTERS LA English DT Article DE G protein-coupled receptor; disulfide; human calcium receptor ID CALCIUM-SENSING RECEPTOR; PUTATIVE PHEROMONE RECEPTORS; FUNCTIONAL EXPRESSION; GLUTAMATE RECEPTORS; MOLECULAR-CLONING; MULTIGENE FAMILY; MAMMALS; BINDING; RAT AB Mammalian calcium receptors (CaRs) share with the metabotropic glutamate receptors (mGluRs) the relative positions of 16 cysteine residues in the amino-terminal extracellular domain. To investigate the role of these cysteines, a series of mutants in the extracellular domain of the human CaR was prepared in which each of these 16 cysteine residues and three others not conserved in the mGluRs were replaced by serines, Wild-type and mutant CaR cDNAs were expressed in HEK-293 cells, and evaluated for expression and response to extracellular calcium, Mutation of three non-conserved cysteines and of two conserved cysteines produced proteins with near wild-type phenotype, In contrast, mutation of the other conserved cysteines gave proteins that showed drastic reduction in cell surface expression and/or failed to respond to calcium, We identified 14 cysteines essential for proper trafficking and function of the receptor, two of which may be involved in formation of a disulfide-linked dimer, (C) 1998 Federation of European Biochemical Societies. C1 NIDDKD, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. RP Spiegel, AM (reprint author), NIDDKD, Metab Dis Branch, NIH, Bldg 10,Rm 9N-222, Bethesda, MD 20892 USA. NR 23 TC 72 Z9 72 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD OCT 9 PY 1998 VL 436 IS 3 BP 353 EP 356 DI 10.1016/S0014-5793(98)01165-X PG 4 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 130VE UT WOS:000076540400012 PM 9801147 ER PT J AU DaSilva, L Kirken, RA Taub, DD Evans, GA Duhe, RJ Bailey, MA Farrar, WL AF DaSilva, L Kirken, RA Taub, DD Evans, GA Duhe, RJ Bailey, MA Farrar, WL TI Molecular cloning of FKHRL1P2, a member of the developmentally regulated fork head domain transcription factor family SO GENE LA English DT Article DE fork head domain protein; T helper differentiation; differential display; cDNA cloning ID BINDING-FACTOR; TH2 CELLS; EXPRESSION; PATTERN; GENE; INTERLEUKIN-4; RESPONSES; MICE; RECEPTORS AB Here we report the expression of a fork head domain protein in human T helper cells. We cloned and characterized a fork head cDNA from human T helper cell mRNA using differential display RT-PCR. The cDNA contains a 546-nucleotide (nt) open reading frame (ORF) that codes for the carboxyl-terminal 180 amino acids (aa) of the recently identified fkhrl1 gene. This ORF does not contain the characteristic DNA-binding domain found in members of the forkhead protein family. In-vitro transcription/translation of this cDNA expressed a protein of approximately 20 kDa. We have generated antibodies that specifically immunoprecipitated the in-vitro-translated 20-kDa protein. This antibody also recognizes in human T lymphocytes a 70-kDa protein corresponding in size to that predicted for the fkhrl1 gene product. The mRNA levels for fkhrl1 is elevated in T helper-induced lymphocytes in comparison to PHA-stimulated T lymphocytes. Further characterization of FKHRL1 and its related family members should shed light on the transcriptional mechanisms of this fork head gene subfamily and their role in T helper cell differentiation and regulation of cell growth. (C) 1998 Elsevier Science B.V. All rights reserved. C1 SAIC Frederick, IRSP, Div Basic Sci, Frederick, MD 21702 USA. NIA, Immunol Lab, GRC, NIH, Baltimore, MD 21224 USA. NCI, Frederick Canc Res & Dev Ctr, Mol Immunoregulat Lab, Cytokine Mol Mech Sect, Frederick, MD 21702 USA. RP DaSilva, L (reprint author), SAIC Frederick, IRSP, Div Basic Sci, Frederick, MD 21702 USA. EM dasilva@mail.ncifcrf.gov FU NCI NIH HHS [N01-CO-56000] NR 26 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 EI 1879-0038 J9 GENE JI Gene PD OCT 9 PY 1998 VL 221 IS 1 BP 135 EP 142 DI 10.1016/S0378-1119(98)00441-7 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 139KE UT WOS:000077027200016 PM 9852958 ER PT J AU Pacheco-Rodriguez, G Meacci, E Vitale, N Moss, J Vaughan, M AF Pacheco-Rodriguez, G Meacci, E Vitale, N Moss, J Vaughan, M TI Guanine nucleotide exchange on ADP-ribosylation factors catalyzed by cytohesin-1 and its Sec7 domain SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GTPASE-ACTIVATING PROTEIN; PHOSPHOLIPASE-D; BREFELDIN-A; BINDING PROTEIN; CHOLERA-TOXIN; PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE; SACCHAROMYCES-CEREVISIAE; HOMOLOGY DOMAINS; BOVINE BRAIN; FACTOR ARF AB ADP-ribosylation factors (ARFs) are 20-kDa guanine nucleotide-binding proteins that require specific guanine nucleotide-exchange proteins (GEPs) to accelerate the conversion of inactive ARF-GDP to active ARF-GTP, Cytohesin-1, a 46-kDa ARF GEP, contains a central Sec7 domain of 188 amino acids similar in sequence to a region of the yeast Sec7 protein. Cytohesin-1 and its 22-kDa Sec7 domain (C-1 Sec7), synthesized in Escherichia coli, were assayed with recombinant non-myristoylated ARFs and related proteins to compare their GEP activities. Both were effective with native mammalian ARFs 1 and 3. Cytohesin-1 accelerated GTP gamma S (guanosine 5'-3-O-(thio)triphosphate) binding to recombinant human ARF1 (rARF1), yeast ARF3, and ARD1 (a 64-kDa guanine nucleotide-binding protein containing a C-terminal ARF domain). In contrast, C-1 Sec7 enhanced GTP gamma S binding to recombinant human ARFs 1, 5, and 6; yeast ARFs 1, 2, and 3; ARD1; two ARD1 mutants that contain the ARF domain; and Delta 13ARF1, which lacks the N-terminal alpha-helix. Neither C-1 Sec7 nor cytohesin-1 increased GTP gamma S binding to human ARF-like ARL proteins 1, 2, and 3. Thus, ARLs, initially differentiated from ARFs because of their inability to activate cholera toxin, differ also in their failure to interact functionally with C-1 Sec7 or cytohesin-1. As C-1 Sec7 was much less substrate-specific than cytohesin-1, it appears that structure outside of the Sec7 domain is important for ARF specificity. Data obtained with mutant ARF constructs are all consistent with the conclusion that the ARF N terminus is an important determinant of cytohesin-1 specificity. C1 NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. RP Pacheco-Rodriguez, G (reprint author), NHLBI, Pulm Crit Care Med Branch, NIH, Rm 5N-307,Bldg 10,10 Ctr Dr,MSC 1434, Bethesda, MD 20892 USA. RI Vitale, nicolas/G-5967-2014 OI Vitale, nicolas/0000-0002-4752-4907 NR 47 TC 38 Z9 39 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 9 PY 1998 VL 273 IS 41 BP 26543 EP 26548 DI 10.1074/jbc.273.41.26543 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 127WJ UT WOS:000076373300045 PM 9756891 ER PT J AU Erlenbach, I Wess, J AF Erlenbach, I Wess, J TI Molecular basis of V2 vasopressin receptor/G(s) coupling selectivity SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NEPHROGENIC DIABETES-INSIPIDUS; RANDOM SATURATION MUTAGENESIS; G-PROTEIN ACTIVATION; FUNCTIONAL EXPRESSION; CLONING; BINDING; DOMAINS; PALMITOYLATION; RHODOPSIN; RAT AB The molecular mechanisms governing the coupling selectivity of G protein-coupled receptors activated by peptide ligands are not well understood. To shed light on this issue, we have used the G(q/11)-linked V1a and the G(s)-coupled V2 vasopressin peptide receptors as model systems. To explore the structural basis underlying the ability of the V2 receptor to selectively recognize G(s), we systematically substituted distinct V2 receptor segments (or single amino acids) into the V1a receptor and studied whether the resulting hybrid receptors gained the ability to mediate hormone-dependent cAMP production. This strategy appeared particularly attractive since hormone stimulation of the Via receptor has virtually no effect on intracellular cAMP levels. Functional analysis of a large number of mutant receptors transiently expressed in COS-7 cells indicated that the presence of V2 receptor sequence at the N terminus of the third intracellular loop is critical for efficient activation of G(s). More detailed mutational analysis of this receptor region showed that two polar V2 receptor residues, Gln(225) and Glu(231), play key roles in G(s) recognition. In addition, a short sequence at the N terminus of the cytoplasmic tail was found to make an important contribution to V2 receptor/G(s) coupling selectivity. We also made the novel observation that the efficiency of V2 receptor/G(s) coupling can be modulated by the length of the central portion of the third intracellular loop (rather than the specific amino acid sequence within this domain). These findings provide novel insights into the molecular mechanisms regulating peptide receptor/G protein coupling selectivity. C1 NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Wess, J (reprint author), NIDDK, Bioorgan Chem Lab, NIH, Bldg 8A,Rm B1A-05, Bethesda, MD 20892 USA. EM jwess@helix.nih.gov NR 42 TC 36 Z9 37 U1 1 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 9 PY 1998 VL 273 IS 41 BP 26549 EP 26558 DI 10.1074/jbc.273.41.26549 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 127WJ UT WOS:000076373300046 PM 9756892 ER PT J AU Glaab, WE Risinger, JI Umar, A Kunkel, TA Barrett, JC Tindall, KR AF Glaab, WE Risinger, JI Umar, A Kunkel, TA Barrett, JC Tindall, KR TI Characterization of distinct human endometrial carcinoma cell lines deficient in mismatch repair that originated from a single tumor SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DNA; CANCER; HETERODIMER; MSH3; MUTATIONS; GENE; HOMOLOGS; PROTEINS; BINDING; DEFECTS AB The role of specific mismatch repair (MMR) gene products was examined by observing several phenotypic end points in two MMR-deficient human endometrial carcinoma cell lines that were originally isolated from the same tumor. The first cell Line, HEC-1-A, contains a nonsense mutation ire the hPMS2 gene, which results in premature termination and a truncated hPMS2 protein. In addition, REC-1-A cells carry a splice mutation in the hMSH6 gene and lack wild-type hMSH6 protein, The second cell line, HEC-1-B, possesses thee same defective hMSH6 locus, However, HEC-1-B cells are heterozygous at the hPMS2 locus; that is, along with carrying the same nonsense mutation in hPMS2 as in HEC-1-A, HEC-1-B cells also contain a wild-type hPMS2 gene. initial recognition of mismatches in DNA requires either the hMSH2/hMSH6 or hMSH2/hMSH3 heterodimer, with hPMS2 functioning downstream of damage recognition. Therefore, cells defective in hPMS2 should completely lack MMR (HEC-1-A), whereas cells mutant in hMSH6 only (HEC-1-B) can potentially repair damage via the hMSH2/hMSH3 heterodimer. The data presented here in HEC-1-B cells illustrate (i) the reduction of instability at microsatellite sequences, (ii) a significant decrease in frameshift mutation rate at HPRT, and (iii) the in vitro repair of looped substrates, relative to HEC-1-A cells, illustrating the repair of frameshift intermediates by hMSH2/hMSH3 heterodimer. Furthermore, the role of hMSH2/hMSH3 heterodimer in the repair of base:base mismatches is supported by observing the reduction in base substitution mutation rate at HPRT in HEC-1-B cells (hMSH6-defective but possessing wild-type hPMS2), as compared with HEC-1-A (hMSH6/hPMS2-defective) cells, These data support a critical role for hPMS2 in human MMR, while further defining the role of the hMSH2/hMSH3 heterodimer in maintaining genomic stability in the absence of a wild-type hMSH2/hMSH6 heterodimer. C1 NIEHS, Lab Environm Carcinogenesis & Mutagenesis, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Genet Mol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Glaab, WE (reprint author), Merck Res Labs, WP45-320, W Point, PA 19486 USA. EM warren_glaab@merck.com NR 34 TC 25 Z9 25 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 9 PY 1998 VL 273 IS 41 BP 26662 EP 26669 DI 10.1074/jbc.273.41.26662 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 127WJ UT WOS:000076373300061 PM 9756907 ER PT J AU Myers, MG Mendez, R Shi, P Pierce, JH Rhoads, R White, MF AF Myers, MG Mendez, R Shi, P Pierce, JH Rhoads, R White, MF TI The COOH-terminal tyrosine phosphorylation sites on IRS-1 bind SHP-2 and negatively regulate insulin signaling SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SRC HOMOLOGY-2 DOMAINS; RECEPTOR SUBSTRATE FAMILY; GROWTH-FACTOR-I; PHOSPHATIDYLINOSITOL 3-KINASE; HEMATOPOIETIC-CELLS; PHOSPHOTYROSINE PROTEIN; PHOSPHATASE SHP-2; SH2 DOMAINS; YMXM MOTIFS; SH-PTP2 AB Activation of tyrosine kinases by numerous growth factor and cytokine receptors leads to tyrosine phosphorylation of the insulin receptor substrate (IRS)-proteins. Tyrosine-phosphorylated motifs on the IRS proteins bind to the SH2 domains in proteins that mediate down-stream signals, including phosphatidylinositol 3'-kinase, GRB-2, and SHP-2. We investigated the function of the two SHP-2 binding COOH-terminal tyrosines of IRS-l by replacing them with phenylalanine (IRS-1(FCT)). IRS-1(FCT) failed to bind SHP-2 or mediate its tyrosine phosphorylation during insulin stimulation. Although several reports suggest a critical role for SHP-2 in insulin stimulated mitogen-activated protein kinase activation and cell proliferation, IRS-1(FCT) mediated these effects normally in 32D cells. indeed, IRS-1(FCT) exhibited increased tyrosine phosphorylation, phosphatidylinositol 3'-kinase binding and activation of protein synthesis in response to insulin. These results suggest that SHP-2 attentuates the phosphorylation and downstream signal transmission of IRS-1 and that the interaction of IRS-1 and SHP-2 is an important regulatory event which attenuates insulin metabolic responses. C1 Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. Louisiana State Univ, Med Ctr, Dept Biochem & Mol Biol, Shreveport, LA 71130 USA. NIH, Lab Cell & Mol Biol, Bethesda, MD 20892 USA. RP Myers, MG (reprint author), Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. EM myersmg@joslab.harvard.edu OI Mendez, Raul/0000-0002-1952-6905 FU NIDDK NIH HHS [DK 43808] NR 55 TC 107 Z9 109 U1 1 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 9 PY 1998 VL 273 IS 41 BP 26908 EP 26914 DI 10.1074/jbc.273.41.26908 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 127WJ UT WOS:000076373300092 PM 9756938 ER PT J AU Chang, MCJ Connolly, C Hill, D Purdon, AD Hayakawa, T Grimes, G Shetty, HU AF Chang, MCJ Connolly, C Hill, D Purdon, AD Hayakawa, T Grimes, G Shetty, HU TI Pharmacokinetics of methyl palmoxirate, an inhibitor of beta-oxidation, in rats and humans SO LIFE SCIENCES LA English DT Article DE methyl palmoxirate; beta-oxidation; half-life; human; rat; palmitate; fatty acids; phospholipids; in vivo imaging; positron tomography ID BRAIN AB Recent studies from our laboratory have shown that methyl palmoxirate (MEP), an inhibitor of mitochondrial beta-oxidation of long chain fatty acids, can be used to increase incorporation of radiolabeled palmitic acid into brain lipids and reduce beta-oxidation of the fatty acid. Thus, MEP allows the use of carbon labeled palmitate for studying brain lipid metabolism in animals and humans by quantitative autoradiography or positron emission tomography (PET). As it is essential to pretreat human subjects with an acute dose of MEP prior to intravenous injection of [1-C-11]palmitate for PET scanning, this study was undertaken to determine the plasma elimination half-life of MEP in rats and human subjects and to provide insight about the drug's absorption and metabolism. A gas chromatographic method was developed to measure MEP in body fluids. Following oral administration of MEP to rats (2.5 and 10 mg/kg) and to humans, the unmetabolized drug could not be detected in plasma or urine (sensitivity of detection was 1 ng). However, when MEP was injected intravenously (10 mg/kg) in rats, a peak initial concentration could be measured in plasma (7.7 mu g/mL), the clearance of the drug from plasma was rapid (t(1/2) = 0.6 min), which indicates that MEP readily enters tissue lipid pools or is metabolized like long-chain fatty acids. As no adverse experience occured in the 11 human subjects studied, oral administration of a single dose of MEP was safe under the conditions of this study and may be used to increase the incorporation of positron labeled palmitic acid for studying brain lipid metabolism in vivo by PET. Published by Elsevier Science Inc. C1 NIA, Neurosci Lab, NIH, Bethesda, MD 20892 USA. NIH, Dept Pharm, Bethesda, MD 20892 USA. RP Chang, MCJ (reprint author), NIA, Neurosci Lab, NIH, Bldg 10,Rm 6C10,10 Ctr Dr,MSC 1582, Bethesda, MD 20892 USA. NR 11 TC 2 Z9 2 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0024-3205 J9 LIFE SCI JI Life Sci. PD OCT 9 PY 1998 VL 63 IS 20 BP PL297 EP PL302 PG 6 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 130UV UT WOS:000076539500010 PM 9820128 ER PT J AU Kusama, T Hatama, K Sakurai, M Kizawa, Y Uhl, GR Murakami, H AF Kusama, T Hatama, K Sakurai, M Kizawa, Y Uhl, GR Murakami, H TI Consensus phosphorylation sites of human GABA(C)/GABA(rho) receptors are not critical for inhibition by protein kinase C activation SO NEUROSCIENCE LETTERS LA English DT Article DE GABA(C) receptor; p1 subunit; p2 subunit; Xenopus oocyte; protein kinase C; mutagenesis; phosphorylation; voltage clamp ID RETINAL BIPOLAR CELLS; XENOPUS-OOCYTES; GABA(C) RECEPTORS; A-RECEPTOR; RHO-1; PHARMACOLOGY; SEQUENCES; CLONING; CDNA; RNA AB The mechanism of inhibition of human GABA(C)/GABA rho receptors by protein kinase C (PKC) activation was investigated in Xenopus oocytes, Phorbol 12-myristate 13 acetate (PMA), a potent PKC activator, at 25 nM inhibited the currents through GABA rho 2 receptors, which have one consensus phosphorylation site by PKC in the predicted intracellular loops. The time-courses and amplitudes of inhibition were not significantly different from those occurring through GABA rho 1 receptors, which have six such sites. The inhibitory effect of PMA was also observed after removing each consensus phosphorylation site in both GABA rho 1 and rho 2 receptors by site-directed mutagenesis. These results suggest that phosphorylation of consensus sites in the intracellular loops is not involved in the inhibition of human GABA(C)/GABA rho receptors by PKC activation. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved. C1 Nihon Univ, Coll Pharm, Dept Physiol & Anat, Funabashi, Chiba 274, Japan. Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21224 USA. NIDA, Mol Neurobiol Branch, Intramural Res Program, Baltimore, MD 21224 USA. RP Murakami, H (reprint author), Nihon Univ, Coll Pharm, Dept Physiol & Anat, Funabashi, Chiba 274, Japan. RI Kizawa, Yasuo/E-3031-2010 OI Kizawa, Yasuo/0000-0001-9884-7186 NR 20 TC 8 Z9 8 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3940 EI 1872-7972 J9 NEUROSCI LETT JI Neurosci. Lett. PD OCT 9 PY 1998 VL 255 IS 1 BP 17 EP 20 DI 10.1016/S0304-3940(98)00696-X PG 4 WC Neurosciences SC Neurosciences & Neurology GA 135KR UT WOS:000076801300005 PM 9839716 ER PT J AU Bernstein, HD AF Bernstein, HD TI Protein targeting: Getting into the groove SO CURRENT BIOLOGY LA English DT Article ID SIGNAL-RECOGNITION PARTICLE; ENDOPLASMIC-RETICULUM; ESCHERICHIA-COLI; SEQUENCE BINDING; PEPTIDE COMPLEX; GTPASE DOMAIN; SUBUNIT; TRANSLOCATION; RNA; CALMODULIN AB The 54 kDa subunit of the signal recognition particle has to identify a diverse family of substrates and deliver them in a controlled manner to the translocation machinery of the endoplasmic reticulum. Important new insights into the function of this sorting protein have emerged from recent biochemical and structural studies. (C) Current Biology Ltd ISSN 0960-9822. C1 NIDDKD, Genet & Biochem Branch, NIH, Bethesda, MD 20892 USA. RP Bernstein, HD (reprint author), NIDDKD, Genet & Biochem Branch, NIH, Bldg 10,Room 9D-20,10 Ctr Dr, Bethesda, MD 20892 USA. NR 23 TC 8 Z9 8 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON W1P 6LE, ENGLAND SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD OCT 8 PY 1998 VL 8 IS 20 BP R715 EP R718 DI 10.1016/S0960-9822(98)70456-7 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 128EN UT WOS:000076392900008 PM 9778518 ER PT J AU Thomas, JB Zheng, XL Mascarella, SW Rothman, RB Dersch, CM Partilla, JS Flippen-Anderson, JL George, CF Cantrell, BE Zimmerman, DM Carroll, FI AF Thomas, JB Zheng, XL Mascarella, SW Rothman, RB Dersch, CM Partilla, JS Flippen-Anderson, JL George, CF Cantrell, BE Zimmerman, DM Carroll, FI TI N-substituted 9 beta-methyl-5-(3-hydroxyphenyl)morphans are opioid receptor pure antagonists SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID LIGAND AB The inhibition of radioligand binding and [S-35]GTP gamma S functional assay data for N-methyl- and N-phenethyl-9 beta-methyl-5-(3-hydroxyphenyl (5b and 5c) show that these compounds are pure antagonists at the mu, delta, and kappa opioid receptors. Since 5b and 5c have the 5-(3-hydroxyphenyl) group locked in a conformation comparable to an equatorial group of a piperidine chair conformation, this information provides very strong evidence that opioid antagonists can interact with opioid receptors in this conformation. In addition, it suggests that the trans-3,4-dimethyl-4-(3-hydroxyphenyl)piperidine class of antagonist operates via a phenyl equatorial piperidine chair conformation. Importantly, the close relationship between the 4-(3-hydroxyphenyl)piperidines and 5-(3-hydroxyphenyl)morph an antagonists shows that the latter class of compound provides a rigid platform on which to build a novel series of opioid antagonists. C1 Res Triangle Inst, Res Triangle Pk, NC 27709 USA. NIDA, Addict Res Sect, Clin Psychopharmacol Sect, Baltimore, MD 21224 USA. USN, Res Lab, Struct Matter Lab, Washington, DC 20375 USA. Eli Lilly & Co, Lilly Corp Ctr, Lilly Res Labs, Indianapolis, IN 46285 USA. RP Carroll, FI (reprint author), Res Triangle Inst, POB 12194, Res Triangle Pk, NC 27709 USA. OI Mascarella, Wayne/0000-0003-0092-8178 FU NIDA NIH HHS [DA09045] NR 23 TC 22 Z9 23 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD OCT 8 PY 1998 VL 41 IS 21 BP 4143 EP 4149 DI 10.1021/jm980290i PG 7 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 127WV UT WOS:000076374300022 PM 9767649 ER PT J AU Esteve, P Embade, N Perona, R Jimenez, B del Peso, L Leon, J Arends, M Miki, T Lacal, JC AF Esteve, P Embade, N Perona, R Jimenez, B del Peso, L Leon, J Arends, M Miki, T Lacal, JC TI Rho-regulated signals induce apoptosis in vitro and in vivo by a p53-independent, but Bcl2 dependent pathway SO ONCOGENE LA English DT Article DE apoptosis; Rho proteins; p53; Bcl2; ceramides; TNF alpha ID GTP-BINDING PROTEIN; NF-KAPPA-B; FAS-INDUCED APOPTOSIS; MYC-INDUCED APOPTOSIS; ACTIN STRESS FIBERS; CELL-DEATH; C-MYC; RAS TRANSFORMATION; GROWTH-FACTOR; ADP-RIBOSYLTRANSFERASE AB Rho proteins are a branch of GTPases that belongs to the Ras superfamily which are critical elements of signal transduction pathways leading to a variety of cellular responses. This family of small GTPases has been involved in diverse biological functions such as cytoskeleton organization, cell growth and transformation, cell motility, migration, metastasis, and responses to stress. We report that several human Rho proteins including Rho A, Rho C and Rac I, are capable of inducing apoptosis in different cell systems like murine NIH3T3 fibroblasts and the human erythroleukemia K562 cell line, Since K562 cells are devoid of p53, apoptosis induced by Rho in this system is independent of p53, Rho-dependent apoptosis is mediated by the generation of ceramides, and it is drastically inhibited by ectopic expression of Bcl2, both under in vitro and in vivo conditions. Furthermore, the human oncogenes vav and ost that have been shown to function as guanine exchange factors for Rho proteins, were also able to induce apoptosis under similar conditions. Finally, we also report that the levels of endogenous Rho proteins are increased when U937 myeloid leukemia cells are exposed to apoptosis-inducing conditions such as TNF alpha treatment. Furthermore, TNF alpha-induced apoptosis in these cells is inhibited by expression of a dominant negative mutant of Rac 1 but it is not affected by a similar mutant of Rho A. These results suggest that Rho proteins play an important role in the physiological regulation of the apoptotic response to stress-inducing agents. C1 Univ Autonoma Madrid, Fac Med, CSIC, Inst Invest Biomed, Madrid, Spain. Univ Autonoma Madrid, Fac Med, Dept Bioquim, Madrid, Spain. Univ Cantabria, Dept Biol Mol, E-39005 Santander, Spain. Univ Edinburgh, Dept Pathol, Edinburgh, Midlothian, Scotland. NCI, LCMB, Bethesda, MD 20892 USA. RP Lacal, JC (reprint author), Univ Autonoma Madrid, Fac Med, CSIC, Inst Invest Biomed, Madrid, Spain. RI embade, Nieves/K-5190-2014; del Peso, Luis/K-9391-2014; Jimenez Cuenca, Benilde/K-9959-2014; Lacal, Juan Carlos/N-9064-2015 OI embade, Nieves/0000-0001-9878-3290; del Peso, Luis/0000-0003-4014-5688; Lacal, Juan Carlos/0000-0002-1908-2777 NR 78 TC 89 Z9 89 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD OCT 8 PY 1998 VL 17 IS 14 BP 1855 EP 1869 DI 10.1038/sj.onc.1202082 PG 15 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 126PX UT WOS:000076303300012 PM 9778052 ER PT J AU Kaye, FJ AF Kaye, FJ TI The retinoblastoma-like protein family: Still in the shadow of the RB gene? SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID LARGE T-ANTIGEN; GROWTH SUPPRESSION; P107; PRODUCT; SIMIAN-VIRUS-40; P130; MEMBERS; CLONING; TUMORS; DOMAIN C1 Natl Naval Med Ctr, Bethesda, MD USA. NCI, Metab Branch, Div Clin Sci, Bethesda, MD 20892 USA. RP Kaye, FJ (reprint author), USN Hosp, Bldg 8,Rm 5101, Bethesda, MD 20889 USA. RI kaye, frederic/E-2437-2011 NR 25 TC 1 Z9 1 U1 0 U2 1 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD OCT 7 PY 1998 VL 90 IS 19 BP 1418 EP 1419 DI 10.1093/jnci/90.19.1418 PG 2 WC Oncology SC Oncology GA 127QV UT WOS:000076362800002 PM 9776402 ER PT J AU Cecconi, I Moroni, M Vilardo, PG Dal Monte, M Borella, P Rastelli, G Costantino, L Garland, D Carper, D Petrash, JM Del Corso, A Mura, U AF Cecconi, I Moroni, M Vilardo, PG Dal Monte, M Borella, P Rastelli, G Costantino, L Garland, D Carper, D Petrash, JM Del Corso, A Mura, U TI Oxidative modification of aldose reductase induced by copper ion. Factors and conditions affecting the process SO BIOCHEMISTRY LA English DT Article ID METAL-CATALYZED OXIDATION; BOVINE LENS; HYDROXYL RADICALS; WILSONS-DISEASE; Z-DNA; PROTEINS; DAMAGE; THIOL; COMPLEXES; BINDING AB Bovine lens aldose reductase (ALR2) is inactivated by copper ion [Cu(II)] through an oxygen-independent oxidative modification process. A stoichiometry of 2 equiv of Cu(II)/enzyme mol is required to induce inactivation. While metal chelators such as EDTA or o-phenantroline prevent but do not reverse the ALR2 inactivation, DTT allows the enzyme activity to be rescued by inducing the recovery of the native enzyme form. The inactive enzyme form is characterized by the presence of 2 equiv of bound copper, at least one of which present as Cu(I), and by the presence of two lesser equivalents, with respect to the native enzyme, of reduced thiol residues. Data are presented which indicate that the Cu-induced protein modification responsible for the inactivation of ALR2 is the generation on the enzyme of an intramolecular disulfide bond. GSH significantly interferes with the Cu-dependent inactivation of ALR2 and induces, through its oxidation to GSSG, the generation of an enzyme form linked to a glutathionyl residue by a disulfide bond. C1 Univ Pisa, Dipartimento Fisiol & Biochim, I-56100 Pisa, Italy. Univ Modena, Dipartimento Sci Biomed, I-41100 Modena, Italy. Univ Modena, Dipartimento Sci Farmaceut, I-41100 Modena, Italy. NEI, NIH, Bethesda, MD 20892 USA. Washington Univ, Sch Med, Dept Ophthalmol & Visual Sci, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA. RP Mura, U (reprint author), Univ Pisa, Dipartimento Fisiol & Biochim, Via S Maria 55, I-56100 Pisa, Italy. EM cmario@dfb.unipi.it RI Rastelli, Giulio/D-2224-2015; Costantino, Luca/D-7608-2015; Borella, Paola/A-6040-2016 OI Rastelli, Giulio/0000-0002-2474-0607; Costantino, Luca/0000-0001-5334-8084; Borella, Paola/0000-0001-9474-3566 NR 50 TC 12 Z9 12 U1 1 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD OCT 6 PY 1998 VL 37 IS 40 BP 14167 EP 14174 DI 10.1021/bi981159f PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 128AW UT WOS:000076383900029 PM 9760253 ER PT J AU Sakai, N Ni, CY Bezrukov, SM Matile, S AF Sakai, N Ni, CY Bezrukov, SM Matile, S TI Voltage-dependent ion channel formation by rigid rod-shaped polyols in planar lipid bilayers SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article ID GRAMICIDIN CHANNEL; CONDUCTANCE; MECHANISMS; MEMBRANES; TRANSPORT; PEPTIDES; LENGTH AB In this Letter, we describe the appearance of large, voltage-dependent currents in BLM induced by rigid rod-shaped polyols that function without charge and permanent dipole moment. The capacity of these symmetrical, nonpeptide models to form either short-living nanopores or small ion channels is shown to depend critically on the length of rigid-rod scaffold as well as the nature of the lateral side chains. (C) 1998 Elsevier Science Ltd. All rights reserved. C1 Georgetown Univ, Dept Chem, Washington, DC 20057 USA. NICHHD, Lab Phys & Struct Biol, NIH, Bethesda, MD 20892 USA. Russian Acad Sci, St Petersburg Nucl Phys Inst, St Petersburg 188350, Russia. RP Matile, S (reprint author), Georgetown Univ, Dept Chem, Washington, DC 20057 USA. OI Sakai, Naomi/0000-0002-9460-1944 FU NIGMS NIH HHS [GM56147-01] NR 20 TC 21 Z9 21 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD OCT 6 PY 1998 VL 8 IS 19 BP 2743 EP 2746 DI 10.1016/S0960-894X(98)00481-8 PG 4 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 132DH UT WOS:000076614700023 PM 9873614 ER PT J AU Li, WX Schoenberg, M AF Li, WX Schoenberg, M TI Behavior of N-phenylmaleimide- and p-phenylenedimaleimide-reacted muscle crossbridge heads SO BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS LA English DT Article DE essential sulfhydryl; muscle regulation; relaxation; rigor ID WEAKLY-BINDING CROSSBRIDGES; RABBIT PSOAS FIBERS; MYOSIN SUBFRAGMENT-1; RIGOR; SITE AB The finding of Barnett et al. (Biophys. J. 61 (1992) 358) that NPM-reacted crossbridge heads do not bind strongly to actin in rigor solution is not easily interpreted in terms of the solution studies of Xie and Schoenberg (Biochemistry 37 (1998) 8048) who found strong binding of NPM-reacted myosin subfragment-l to actin in solutions devoid of MgATP. For this reason, the current work uses stiffness measurement to re-investigate the binding of rabbit skeletal muscle crossbridges to actin in rigor solution. It is found that NPM-reacted crossbridge heads bind strongly to actin in rigor solution providing one is extremely careful to reduce MgATP contamination to levels well below those that would have a detectable effect on unmodified fibers. The reason for this is that NPM-reacted crossbridge heads, which hydrolyze MgATP extremely slowly, are especially susceptible to contaminant MgATP. The new fiber results show a strong correlation with the solution results. A further manifestation of this correlation is that pPDM-reacted crossbridge heads are different from NPM-reacted ones in that, like in solution, they remain weakly binding to actin even at extremely low MgATP levels. The findings suggest that the covalent crosslinking of SH1 and SH2 by pPDM is likely playing a significant role in locking pPDM-reacted crossbridge heads in a weakly binding conformation. (C) 1998 Published by Elsevier Science B.V. All rights reserved. C1 NIAMSD, Phys Biol Lab, NIH, Bethesda, MD 20892 USA. RP Schoenberg, M (reprint author), NIAMSD, Phys Biol Lab, NIH, Bethesda, MD 20892 USA. EM mark@lpb.niams.nih.gov NR 20 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0005-2728 J9 BBA-BIOENERGETICS JI Biochim. Biophys. Acta-Bioenerg. PD OCT 5 PY 1998 VL 1367 IS 1-3 BP 127 EP 133 DI 10.1016/S0005-2728(98)00138-8 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 129WB UT WOS:000076486100006 PM 9784622 ER PT J AU Hayakawa, T Chang, MCJ Bell, JM Seeman, R Rapoport, SI Appel, NM AF Hayakawa, T Chang, MCJ Bell, JM Seeman, R Rapoport, SI Appel, NM TI Fatty acid incorporation depicts brain activity in a rat model of Parkinson's disease SO BRAIN RESEARCH LA English DT Article DE arachidonic acid; autoradiography; basal ganglia; brain metabolism; fatty acid; functional brain imaging; 6-hydroxydopamine; Parkinson's disease; phospholipase A(2) ID CHOLINERGIC STIMULATION; UNANESTHETIZED RATS; GLUCOSE-UTILIZATION; ARACHIDONIC-ACID; SUBSTANTIA NIGRA; DOPAMINE; 6-HYDROXYDOPAMINE; RELEASE AB Following pulse labeling with [H-3]arachidonic acid ([H-3]AA), its incorporation pattern in brain reflects regional changes in neurotransmitter signal transduction using phospholipase A(2). that is, functional activity. In a rat model of Parkinson's disease, unilateral 6-hydroxydopamine lesion in the substantia nigra, [H-3]AA acid incorporation from blood was increased in cerebral cortex, caudate putamen, globus pallidus, entopeduncular nucleus, subthalamic nucleus and substantia nigra pars reticulata ipsilateral to the lesion. This increased [H-3]AA incorporation likely reflects disinhibition of basal ganglia and cortical circuits secondary to absent inhibitory nigrostriatal dopaminergic input. (C) 1998 Elsevier Science B.V. All rights reserved. C1 US FDA, Ctr Drug Evaluat & Res, Off Testing & Res, Div Appl Pharmacol Res, Laurel, MD 20708 USA. NIA, Neurosci Lab, NIH, Bethesda, MD 20892 USA. Tokyo Med & Dent Univ, Dept Neurosurg, Bunkyo Ku, Tokyo 113, Japan. RP Appel, NM (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Testing & Res, Div Appl Pharmacol Res, 8301 Muirkirk Rd,Room 2013, Laurel, MD 20708 USA. EM appeln@cder.fda.gov NR 25 TC 18 Z9 18 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD OCT 5 PY 1998 VL 807 IS 1-2 BP 177 EP 181 DI 10.1016/S0006-8993(98)00751-3 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 127TZ UT WOS:000076367800021 PM 9757030 ER PT J AU Bryant, W Janik, J Baumann, M Callahan, P AF Bryant, W Janik, J Baumann, M Callahan, P TI Orphanin FQ stimulates prolactin and growth hormone release in male and female rats SO BRAIN RESEARCH LA English DT Article DE Orphanin FQ; nociceptin; prolactin; growth hormone; opiates ID ANTI-OPIOID PEPTIDE; TISSUE DISTRIBUTION; INDUCED ANALGESIA; MORPHINE; NOCICEPTIN; RECEPTOR; ANTINOCICEPTION; ENDOCRINOLOGY; NEUROPEPTIDE; ANTAGONISM AB Intracerebroventricular administration of Orphanin FQ (5.5, 55 or 550 pmol) caused a dose-related increase in prolactin secretion in both male and female rats and stimulated GK secretion in males. The magnitude of the prolactin secretory response was greater in females than in males. These effects of OFQ on prolactin and growth hormone release are the same as the stimulatory effects of the endogenous opioid peptides. (C) 1998 Elsevier Science B.V. All rights reserved. C1 Miami Univ, Dept Zool, Ctr Neurosci, Oxford, OH 45056 USA. NIDA, Clin Psychopharmacol Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Callahan, P (reprint author), Miami Univ, Dept Zool, Ctr Neurosci, 290 Pearson Hall, Oxford, OH 45056 USA. EM callahp@muohio.edu NR 26 TC 40 Z9 41 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD OCT 5 PY 1998 VL 807 IS 1-2 BP 228 EP 233 DI 10.1016/S0006-8993(98)00802-6 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 127TZ UT WOS:000076367800031 PM 9757048 ER PT J AU Kono, K Yang, RC Charo, J Ichihara, F Celis, E Sette, A Appella, E Sekikawa, T Matsumoto, Y Kiessling, R AF Kono, K Yang, RC Charo, J Ichihara, F Celis, E Sette, A Appella, E Sekikawa, T Matsumoto, Y Kiessling, R TI Identification of HER2/neu-derived peptide epitopes recognized by gastric cancer-specific cytotoxic T lymphocytes SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID TUMOR-INFILTRATING LYMPHOCYTES; DENDRITIC CELLS; OVARIAN-CANCER; MELANOMA; RECEPTOR; GENE; CARCINOMAS; ONCOGENE; ANTIGEN; BREAST AB We have derived HLA-A2.1-restricted, gastric cancer-specific cytotoxic T lymphocyte (CTL) lines by repetitive in vitro stimulation of tumor-associated lymphocytes (TAL) with autologous tumor cells. The HER2/neu specificity of these gastric cancer-specific CTLs was demonstrated using HER2/neu-transfected cell lines and HER2/neu-expressing tumors, and with a set of HER2/neu-derived peptide epitopes, Gastric cancer-specific CTLs specifically lysed autologous and allogeneic HLA-A2.1(+), HER2/neu(+) gastric cancer cells, HER2/neu-transfected CIR/A2 cell lines (HLA-A2.1(+), HER2(+)) and HLA-A2.1-transfected SW626 tumor cell lines (HLA-A2.1(+), HER2(+)), This recognition could be inhibited by anti-HLA-AZ antibody or by cold target HER2/neo-transfected CIR/A2 cells. Our results demonstrate that the HER2/neu-encoded HLA-A2.1-associated epitopes recognized by CTLs are presented as naturally processed peptides on gastric cancer lines, Furthermore, 3 of 19 tested HER2/neu-derived peptide epitopes [HER2(9(106)), HER2(9(369)), HER2(9(689))], which all bound HLA-A2.1 with high (IC50 < 50 nM) affinity, were able to sensitize HLA-A2(+) CIR/A2 cells to be recognized by the gastric cancer-specific CTLs, demonstrating the immunodominance of these epitopes, In conclusion, our findings implicate HER2/neu-derived epitopes as potential candidates for novel immunotherapy and vaccine strategies against gastric (C) 1998 Wiley-Liss, Inc. C1 Yamanashi Med Univ, Dept Surg 1, Yamanashi 40938, Japan. Karolinska Inst, Ctr Microbiol & Tumor Biol, Stockholm, Sweden. Karolinska Hosp, Radiumhemmet, Dept Pathol & Oncol, S-10401 Stockholm, Sweden. Mayo Clin, Dept Immunol, Rochester, MN USA. Cytel Corp, Dept Cell Immunol, Epimmune Inc, San Diego, CA 92121 USA. NCI, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. RP Kono, K (reprint author), Yamanashi Med Univ, Dept Surg 1, Yamanashi 40938, Japan. RI Kono, Koji/A-4822-2012; Charo, Jehad/K-4433-2013 OI Charo, Jehad/0000-0002-5409-9160 NR 21 TC 71 Z9 77 U1 2 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD OCT 5 PY 1998 VL 78 IS 2 BP 202 EP 208 DI 10.1002/(SICI)1097-0215(19981005)78:2<202::AID-IJC14>3.0.CO;2-C PG 7 WC Oncology SC Oncology GA 122EC UT WOS:000076058100014 PM 9754653 ER PT J AU Canger, AK Passini, MA Asch, WS Leake, D Zafonte, BT Glasgow, E Schechter, N AF Canger, AK Passini, MA Asch, WS Leake, D Zafonte, BT Glasgow, E Schechter, N TI Restricted expression of the neuronal intermediate filament protein plasticin during zebrafish development SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article ID PERIPHERAL NERVOUS-SYSTEM; MESSENGER-RNA EXPRESSION; EMBRYONIC ZEBRAFISH; XENOPUS-LAEVIS; NEUROFILAMENT PROTEIN; DIFFERENTIAL EXPRESSION; BRACHYDANIO-RERIO; ALPHA-INTERNEXIN; SPINAL-CORD; NF-L AB In the adult goldfish visual pathway, expression of the neuronal intermediate filament (nIF) protein plasticin is restricted to differentiating retinal ganglion cells (RGCs) at the margin of the retina. Following optic nerve injury, plasticin expression is elevated transiently in all RGCs coincident with the early stages of axon regeneration. These results suggest that plasticin may be expressed throughout the nervous system during the early stages of axonogenesis. To test this hypothesis, we analyzed plasticin expression during zebrafish (Danio rerio) neuronal development. By using immunocytochemistry and in situ hybridization, we found that plasticin is expressed in restricted subsets of early zebrafish neurons. Expression coincides with axon outgrowth in projection neurons that pioneer distinct axon tracts in the embryo. Plasticin is expressed first in trigeminal, Rohon-Beard, and posterior lateral line ganglia neurons, which are among the earliest neurons to initiate axonogenesis in zebrafish. Plasticin is expressed also in reticulospinal neurons and in caudal primary motoneurons. Together these neurons establish the first behavioral responses in the embryo. Plasticin expression also coincides with initial RGC axonogenesis and progressively decreases after RGC axons reach the tectum. At later developmental stages, plasticin is expressed in a subset of the cranial nerves. The majority of plasticin-positive neurons are within or project axons to the peripheral nervous system. Our results suggest that plasticin subserves the changing requirements for plasticity and stability during axonal outgrowth in neurons that project long axons. (C) 1998 Wiley-Liss, Inc. C1 SUNY Stony Brook, Hlth Sci Ctr, Dept Psychiat & Behav Sci, Stony Brook, NY 11794 USA. SUNY Stony Brook, Dept Biochem & Cell Biol, Stony Brook, NY 11794 USA. SUNY Stony Brook, Inst Cell & Dev Biol, Stony Brook, NY 11794 USA. National Institute Neurological Diseases & Stroke, Neurochem Lab, Bethesda, MD 20892 USA. RP Schechter, N (reprint author), SUNY Stony Brook, Hlth Sci Ctr, Dept Psychiat & Behav Sci, Stony Brook, NY 11794 USA. OI Glasgow, Eric/0000-0001-7729-3954 FU NEI NIH HHS [EY05212] NR 70 TC 17 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 USA SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD OCT 5 PY 1998 VL 399 IS 4 BP 561 EP 572 DI 10.1002/(SICI)1096-9861(19981005)399:4<561::AID-CNE8>3.0.CO;2-# PG 12 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA 115DJ UT WOS:000075648000008 PM 9741483 ER PT J AU Chen, HJC Applewhite, T Jayachandran, B Kirk, KL AF Chen, HJC Applewhite, T Jayachandran, B Kirk, KL TI Synthesis of 4,6-difluoro-5-hydroxy-(alpha-methyl)tryptamine and 4,6-difluoro-5-hydroxy-(beta-methyl)tryptamine as potential selective monoamine oxidase B inhibitors SO JOURNAL OF FLUORINE CHEMISTRY LA English DT Article DE monoamine oxidase; serotonin (5HT); enzyme selectivity; fischer indole synthesis AB Condensation of 4-nitro-1-pentanal and 4-nitropentanal 3-methylbutanal with 3,5-difluoro-4-methoxyphenylhydrazine afforded 4,6-difluoro-5-methoxy-3-(2'-nitro)propylindole 4a and 4,6-difluoro-5-methoxy-3-(1'-methyl-2'-nitro)ethylindole 4b, respectively, in one step. Reduction of the nitro,group with lithium aluminum hydride followed by removal of the methyl ether with boron tribromide produced the title compounds. They were inactive as MAO B inhibitors. (C) 1998 Elsevier Science S.A. All rights reserved. C1 NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Kirk, KL (reprint author), NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. NR 8 TC 3 Z9 3 U1 1 U2 2 PU ELSEVIER SCIENCE SA PI LAUSANNE PA PO BOX 564, 1001 LAUSANNE, SWITZERLAND SN 0022-1139 J9 J FLUORINE CHEM JI J. Fluor. Chem. PD OCT 5 PY 1998 VL 92 IS 1 BP 41 EP 44 DI 10.1016/S0022-1139(98)00248-6 PG 4 WC Chemistry, Inorganic & Nuclear; Chemistry, Organic SC Chemistry GA 144RM UT WOS:000077328900008 ER PT J AU Lippa, CF Nee, LE Mori, H St George-Hyslop, P AF Lippa, CF Nee, LE Mori, H St George-Hyslop, P TI A beta-42 deposition precedes other changes in PS-1 Alzheimer's disease SO LANCET LA English DT Article C1 Allegheny Univ Hlth Sci Hahnemann, Dept Neurol, Philadelphia, PA 19129 USA. NINDS, NIH, Bethesda, MD 20892 USA. Tokyo Inst Psychiat, Dept Mol Biol, Tokyo, Japan. Univ Toronto, Dept Med, Ctr Res Neurodegenerat Dis, Toronto, ON, Canada. RP Lippa, CF (reprint author), Allegheny Univ Hlth Sci Hahnemann, Dept Neurol, Philadelphia, PA 19129 USA. FU NIA NIH HHS [AG13623] NR 5 TC 60 Z9 62 U1 0 U2 4 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON WC1B 3SL, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD OCT 3 PY 1998 VL 352 IS 9134 BP 1117 EP 1118 DI 10.1016/S0140-6736(05)79757-9 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 125PP UT WOS:000076246400016 PM 9798591 ER PT J AU Biesecker, LG Peters, KF Darling, TN Choyke, P Hill, S Schimke, N Cunningham, M Meltzer, P Cohen, MM AF Biesecker, LG Peters, KF Darling, TN Choyke, P Hill, S Schimke, N Cunningham, M Meltzer, P Cohen, MM TI Clinical differentiation between Proteus syndrome and hemihyperplasia: Description of a distinct form of hemihyperplasia SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article; Proceedings Paper CT 7th Robert J Gorlin Conference on Dysmorphology CY OCT 25-26, 1997 CL MINNEAPOLIS, MINNESOTA SP Guilan Norouzi, Hassan Norouzi DE overgrowth; hamartoma; lipoma; hemihypertrophy; hyperostosis AB Proteus syndrome is a rare and highly variable hamartomatous syndrome that can affect multiple organ systems. It is characterized by hyperplastic lesions of connective tissue, vascular malformations, linear verrucous epidermal nevi, and hyperostoses. The cause of the disorder is unknown, but the current working hypothesis is that it is caused by a mosaic alteration that leads to a highly variable phenotype, equal sex ratio, sporadic occurrence, and discordant mono zygotic twins. Herein we describe our experience with 18 patients with a referring diagnosis of Proteus syndrome. It was found that imaging studies are very useful for the characterization of the syndrome. One finding was that splenic hyperplasia can be a manifestation of Proteus syndrome. Analysis of the clinical data shows that Proteus syndrome is frequently confused with "hemihyperplasia." A distinct subtype of hemihyperplasia is defined that includes static or mildly progressive hemihyperplasia and multiple lipomata, (C) 1998 Wiley-Liss, Inc.(dagger) C1 NIH, Genet Dis Res Branch, Natl Human Genome Res Inst, Bethesda, MD 20892 USA. NIH, Med Genet Branch, Natl Human Genome Res Inst, Bethesda, MD 20892 USA. NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. NIH, Dept Radiol, Ctr Clin, Bethesda, MD 20892 USA. Univ Kansas, Med Ctr, Dept Pediat, Kansas City, KS 66103 USA. Univ Washington, Dept Pediat, Seattle, WA 98195 USA. NIH, Canc Genet Lab, Natl Human Genome Res Inst, Bethesda, MD 20892 USA. Dalhousie Univ, Dept Dent, Halifax, NS, Canada. Dalhousie Univ, Dept Med, Halifax, NS, Canada. RP Biesecker, LG (reprint author), NIH, Genet Dis Res Branch, Natl Human Genome Res Inst, Bldg 49,Room 4A80, Bethesda, MD 20892 USA. OI Darling, Thomas/0000-0002-5161-1974 NR 10 TC 58 Z9 59 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD OCT 2 PY 1998 VL 79 IS 4 BP 311 EP 318 DI 10.1002/(SICI)1096-8628(19981002)79:4<311::AID-AJMG14>3.0.CO;2-U PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 123KL UT WOS:000076124300014 PM 9781913 ER PT J AU Kassessinoff, TA Gabet, A Beaven, MA Sagi-Eisenberg, R AF Kassessinoff, TA Gabet, A Beaven, MA Sagi-Eisenberg, R TI Inositol polyphosphates regulate the membrane interactions of the endosomal p100, G-protein-related protein SO BIOCHIMICA ET BIOPHYSICA ACTA-LIPIDS AND LIPID METABOLISM LA English DT Article DE p100; purification; binding; microsomal membrane; inositol polyphosphate; permeabilized cell ID PLANAR LIPID BILAYERS; BINDING PROTEINS; RECEPTOR; IDENTIFICATION; TRISPHOSPHATE; INHIBITION; CHANNELS; CALCIUM; SYNAPSE; BRAIN AB The protein, p100, was previously identified as a G-protein related protein that cycles on and off the cytoplasmic face of the endosome membrane (Traub et al., Biochem. J. 280 (1991) 171-178). Here we present evidence that the inositol polyphosphates, inositol 1,4,5-trisphosphate (IP(3)) and inositol hexakisphosphate (IP(6)), release p100 from light-density microsomal membranes and inhibit rebinding of p100 through receptors, which are specific for IP(3) or for IP(6). These receptors can be co-extracted with p100 from the microsomes by 0.5 M Tris-HCl and, in the soluble state, they exhibit similar binding activity towards the inositol polyphosphates as do untreated microsomes. Soluble p100 self-aggregates and this aggregation is blocked by both IP(3) and IP(6). Stimulation of permeabilized rat basophilic leukemia (RBL-2H3) cells with carbachol, via transfected muscarinic mi receptors, results in increased levels of inositol polyphosphates and the quantitative release of p100 into the cytosol. This effect is reversible and cytosolic p100 rebinds to the membrane as the levels of inositol polyphosphates decline. These findings suggest that p100 may belong to a family of IF-binding proteins whose intracellular localization is determined by extracellular signals. (C) 1998 Published by Elsevier Science B.V. All rights reserved. C1 Tel Aviv Univ, Sackler Sch Med, Dept Cell Biol & Histol, IL-69978 Tel Aviv, Israel. NHLBI, Mol Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Sagi-Eisenberg, R (reprint author), Tel Aviv Univ, Sackler Sch Med, Dept Cell Biol & Histol, IL-69978 Tel Aviv, Israel. EM histol3@ccsg.tau.ac.il NR 34 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0005-2760 J9 BBA-LIPID LIPID MET JI Biochim. Biophys. Acta-Lipids Lipid Metab. PD OCT 2 PY 1998 VL 1394 IS 1 BP 111 EP 120 DI 10.1016/S0005-2760(98)00099-X PG 10 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 130ZZ UT WOS:000076552100012 PM 9767143 ER PT J AU Watanabe, D Inokawa, H Hashimoto, K Suzuki, N Kano, M Shigemoto, R Hirano, T Toyama, K Kaneko, S Yokoi, M Moriyoshi, K Suzuki, M Kobayashi, K Nagatsu, T Kreitman, RJ Pastan, I Nakanishi, S AF Watanabe, D Inokawa, H Hashimoto, K Suzuki, N Kano, M Shigemoto, R Hirano, T Toyama, K Kaneko, S Yokoi, M Moriyoshi, K Suzuki, M Kobayashi, K Nagatsu, T Kreitman, RJ Pastan, I Nakanishi, S TI Ablation of cerebellar Golgi cells disrupts synaptic integration involving GABA inhibition and NMDA receptor activation in motor coordination SO CELL LA English DT Article ID METABOTROPIC GLUTAMATE RECEPTORS; GRANULE CELLS; TRANSGENIC MICE; NERVOUS-SYSTEM; MUTANT MICE; TOXIN GENE; RAT; MGLUR2; EXPRESSION; CURRENTS AB The role of inhibitory Golgi cells in cerebellar function was investigated by selectively ablating Golgi cells expressing human interleukin-2 receptor alpha subunit in transgenic mice, using the immunotoxin-mediated cell targeting technique. Golgi cell disruption caused severe acute motor disorders. These mice showed gradual recovery but retained a continuing inability to perform compound movements. Optical and electrical recordings combined with immunocytological analysis indicated that elimination of Golgi cells not only reduces GABA-mediated inhibition but also attenuates functional NMDA receptors in granule cells. These results demonstrate that synaptic integration involving both GABA inhibition and NMDA receptor activation is essential for compound motor coordination. Furthermore, this integration can adapt after Golgi cell elimination so as not to evoke overexcitation by the reduction of NMDA receptors. C1 Kyoto Univ, Fac Med, Dept Sci Biol, Kyoto 6068501, Japan. Kyoto Prefectural Univ Med, Dept Physiol, Kyoto 6020841, Japan. Kanazawa Univ, Sch Med, Dept Physiol, Kanazawa, Ishikawa 9208640, Japan. Kyoto Univ, Grad Sch Sci, Dept Biophys, Kyoto 6068502, Japan. Kumamoto Univ, Sch Med, Lab Transgen Technol, Inst Mol Embryol & Genet, Kumamoto 8600976, Japan. Nara Inst Sci & Technol, Res & Educ Ctr Genet Informat, Ikoma 6300101, Japan. Fujita Hlth Univ, Sch Med, Inst Comprehens Med Sci, Toyoake, Aichi 4701192, Japan. NCI, Mol Biol Lab, Div Basic Sci, Bethesda, MD 20892 USA. RP Nakanishi, S (reprint author), Kyoto Univ, Fac Med, Dept Sci Biol, Kyoto 6068501, Japan. NR 44 TC 139 Z9 142 U1 0 U2 4 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD OCT 2 PY 1998 VL 95 IS 1 BP 17 EP 27 DI 10.1016/S0092-8674(00)81779-1 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 125MX UT WOS:000076242300007 PM 9778244 ER PT J AU Ariumi, Y Ueda, K Masutani, M Copeland, TD Noda, M Hatanaka, M Shimotohno, K AF Ariumi, Y Ueda, K Masutani, M Copeland, TD Noda, M Hatanaka, M Shimotohno, K TI In vivo phosphorylation of poly(ADP-ribose) polymerase is independent of its activation SO FEBS LETTERS LA English DT Article DE poly(ADP-ribose) polymerase; poly(ADP-ribosyl)ation; auto-modification; phosphorylation; serine kinase; apoptosis ID PROTEIN-KINASE-C; DNA-DAMAGE; SYNTHETASE; CLEAVAGE; REPAIR AB Poly(ADP-ribose) polymerase (PARP) is a nuclear enzyme, which is activated by DNA strand breaks. Although PARP is known to be cleaved by the cysteine protease, caspase-3/CPP32, during apoptosis, signal cascade which regulates the PARP activity has not been fully understood. In this study, we investigated post-translational modification of PARP, We found that PARP was phosphorylated by a serine kinase in vivo, PARP was activated temporarily and extensive auto-modification occurred on PARP, possibly by the fragmented DNA during apoptosis induced by etoposide in Jurkat cells. However, the phosphorylation level was not changed for up to 6 h, after PARP cleavage began in apoptosis by the treatment with etoposide, Furthermore, we showed the presence of a PARP-associated kinase in nuclear extracts of the HTLV-I infected T-cell lines but not in uninfected T-cell Lines, whereas this kinase did not inhibit the PARP activity even in the presence of ATP, Taken together, in vivo phosphorylation of PARP might be independent of the activation or cleavage of PARP. (C) 1998 Federation of European Biochemical Societies. C1 Kyoto Univ, Inst Virus Res, Sakyo Ku, Kyoto 6068507, Japan. Kyoto Univ, Chem Res Inst, Kyoto 6110011, Japan. Natl Canc Ctr Res Inst, Div Biochem, Tokyo 1040045, Japan. NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Frederick, MD 21702 USA. Kyoto Univ, Grad Sch Med, Dept Mol Oncol, Kyoto 6068501, Japan. RP Ariumi, Y (reprint author), Kyoto Univ, Inst Virus Res, Sakyo Ku, Kyoto 6068507, Japan. RI Ariumi, Yasuo/F-5804-2013 NR 18 TC 7 Z9 7 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD OCT 2 PY 1998 VL 436 IS 2 BP 288 EP 292 DI 10.1016/S0014-5793(98)01144-2 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 128YR UT WOS:000076436400032 PM 9781697 ER PT J AU Cremers, CWRJ Admiraal, RJC Huygen, PLM Bolder, C Everett, LA Joosten, FBM Green, ED van Camp, G Otten, BJ AF Cremers, CWRJ Admiraal, RJC Huygen, PLM Bolder, C Everett, LA Joosten, FBM Green, ED van Camp, G Otten, BJ TI Progressive hearing loss, hypoplasia of the cochlea and widened vestibular aqueducts are very common features in Pendred's syndrome SO INTERNATIONAL JOURNAL OF PEDIATRIC OTORHINOLARYNGOLOGY LA English DT Article DE Pendred's syndrome; PDS gene; widened vestibular aqueduct; enlarged vestibular aqueduct; childhood deafness; sensorineural hearing loss; autosomal recessive; genetic deafness; Mondini's dysplasia ID GENE AB Long-term hearing threshold-on-age follow-up data, including non-linear regression analysis, are given for 12 consecutive Pendred patients. The clinical diagnosis of Pendred's syndrome was confirmed by a mutation analysis of the PDS gene in 11 out of the 11 cases tested. Recent imaging of the temporal bones in seven out of these 12 patients showed widened vestibular aqueducts in each case. The diagnostic perchlorate test was negative in one patient, but this test was positive in her affected sister. Mutation analysis of the PDS gene in these patients confirmed that Pendred's syndrome is a monogenetic disorder. Progressive sensorineural hearing loss and widened vestibular aqueducts are characteristic features of Pendred's syndrome, which provides the opportunity to diagnose Pendred's syndrome clinically in the first few years of life, as has recently been suggested in a case report (Cremers et al., Progressive sensorineural hearing loss and a widend vestibular aqueduct in Pendred syndrome, Arch. Otolaryngol. 124 (1998) 501-505). Mutation analysis of the involved gene can be used to confirm the clinical diagnosis. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved. C1 Univ Nijmegen Hosp, Dept Otorhinolaryngol, NL-6500 HB Nijmegen, Netherlands. Univ Nijmegen Hosp, Dept Radiol, NL-6500 HB Nijmegen, Netherlands. Univ Nijmegen Hosp, Dept Paediat, NL-6500 HB Nijmegen, Netherlands. Natl Human Genome Res Inst, NIH, Bethesda, MD USA. Univ Antwerp, Dept Human Genet, B-2020 Antwerp, Belgium. RP Cremers, CWRJ (reprint author), Univ Nijmegen Hosp, Dept Otorhinolaryngol, POB 9101, NL-6500 HB Nijmegen, Netherlands. RI Van Camp, Guy/F-3386-2013; Admiraal, R.J.C./L-4171-2015; Cremers, C.W.R.J./L-4254-2015; Huygen, P.L.M./L-4401-2015; Otten, B.J./L-4562-2015 OI Van Camp, Guy/0000-0001-5105-9000; NR 15 TC 56 Z9 59 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0165-5876 J9 INT J PEDIATR OTORHI JI Int. J. Pediatr. Otorhinolaryngol. PD OCT 2 PY 1998 VL 45 IS 2 BP 113 EP 123 DI 10.1016/S0165-5876(98)00123-2 PG 11 WC Otorhinolaryngology; Pediatrics SC Otorhinolaryngology; Pediatrics GA 140WU UT WOS:000077113300001 PM 9849679 ER PT J AU Arora, KK Krsmanovic, LZ Mores, N O'Farrell, H Catt, KJ AF Arora, KK Krsmanovic, LZ Mores, N O'Farrell, H Catt, KJ TI Mediation of cyclic AMP signaling by the first intracellular loop of the gonadotropin-releasing hormone receptor SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-COUPLED RECEPTORS; SITE-DIRECTED MUTAGENESIS; THYROTROPIN RECEPTOR; CYTOPLASMIC DOMAINS; ADENYLYL-CYCLASE; PHOSPHOLIPASE-C; TRANSDUCTION; ACTIVATION; EXPRESSION; MUTATIONS AB The gonadotropin-releasing hormone (GnRH) receptor, which is a unique G protein-coupled receptor without a C-terminal cytoplasmic domain, activates both inositol phosphate (InsP) and cAMP signaling responses. The function of the highly basic first intracellular (1i) loop of the GnRH receptor in signal transduction was evaluated by mutating selected residues located in its N and C termini, Replacements of Leu(58), Lys(59), Gln(61), and Lys(62) at the N terminus, and Leu(73), Ser(74), and Leu(80) at the C terminus, caused no change in binding affinity. The agonist-induced InsP and cAMP responses of the Q61E and K59Q,K62Q receptors were also unaffected, but the L58A receptor showed a normal InsP response and an 80% decrease in cAMP production. At the C terminus, the InsP response of the L73R receptor was normal, but cAMP production was reduced by 80%, The EC50 for GnRH-induced InsP responses of the S74E and L80A receptors was increased by about one order of magnitude, and the cAMP responses were essentially abolished. These findings indicate that cAMP signaling from the GnRH receptor is dependent on specific residues in the 1i loop that are not essential for activation of the phosphoinositide signaling pathway. C1 NICHD, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA. RP Catt, KJ (reprint author), NICHD, Endocrinol & Reprod Res Branch, NIH, Bldg 49,Rm 6A36, Bethesda, MD 20892 USA. EM catt@helix.nih.gov OI MORES, Nadia/0000-0002-4197-0914 NR 35 TC 74 Z9 75 U1 1 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 2 PY 1998 VL 273 IS 40 BP 25581 EP 25586 DI 10.1074/jbc.273.40.25581 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 125XU UT WOS:000076263100013 PM 9748222 ER PT J AU Kim, YH Choi, CY Lee, SJ Conti, MA Kim, Y AF Kim, YH Choi, CY Lee, SJ Conti, MA Kim, Y TI Homeodomain-interacting protein kinases, a novel family of co-repressors for homeodomain transcription factors SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DNA-BINDING SPECIFICITY; HOMEOBOX GENES; EXTRADENTICLE; FTZ; EXPRESSION; SYSTEM; NK-2 AB A novel family of cofactors that differentially interact with homeoproteins have been identified via a yeast two-hybrid screen. The proteins contain a conserved protein kinase domain that is separated from a domain that interacts with homeoproteins and hence are termed homeodomain-interacting protein kinases (HIPKs): HIPK1, HIPK2, and HIPK3, We show that HIPKs are nuclear kinases using GFP-HIPK fusion constructs. The DNA binding activity of the NK-3 homeoprotein is greatly enhanced by HIPK2, but this effect is independent of its phosphorylation by HIPK2. In cultured cells, HIPKs localize to nuclear speckles and potentiate the repressor activities of NK homeoproteins. The co-repressor activity of HIPKs depends on both its homeodomain interaction domain and a co-repressor domain that maps to the N terminus. Thus, HIPKs represent a heretofore undescribed family of co-repressors for homeodomain transcription factors. C1 NHLBI, LMC, NIH, Bethesda, MD 20892 USA. RP Kim, Y (reprint author), NHLBI, LMC, NIH, Bldg 10,Rm 8N228,10 Ctr Dr MSC1762, Bethesda, MD 20892 USA. OI Lee, Seung-Jae/0000-0002-5155-5335 NR 24 TC 179 Z9 191 U1 0 U2 7 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 2 PY 1998 VL 273 IS 40 BP 25875 EP 25879 DI 10.1074/jbc.273.40.25875 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 125XU UT WOS:000076263100053 PM 9748262 ER PT J AU Ohno, H Aguilar, RC Yeh, D Taura, D Saito, T Bonifacino, JS AF Ohno, H Aguilar, RC Yeh, D Taura, D Saito, T Bonifacino, JS TI The medium subunits of adaptor complexes recognize distinct but overlapping sets of tyrosine-based sorting signals SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TRANS-GOLGI NETWORK; FACTOR-II RECEPTOR; MEMBRANE-PROTEIN; INTERNALIZATION SIGNALS; RAPID INTERNALIZATION; TRANSFERRIN RECEPTOR; CYTOPLASMIC TAIL; PLASMA-MEMBRANE; AP-2 COMPLEXES; MEDIUM CHAINS AB Tyrosine-based sorting signals conforming to the motif YXXO (Y is tyrosine, X is any amino acid, and O is an amino acid with a bulky hydrophobic side chain (leucine, isoleucine, phenylalanine, methionine, valine)) interact with the medium (mu) subunits of clathrin adaptor (AP) complexes. We have analyzed the selectivity of interaction between YXXO signals and the mu 1, mu 2, and mu 3 (A or B) subunits of the AP-1, AP-2, and AP-3 complexes, respectively, by screening a combinatorial XYXYXXO library using the yeast two-hybrid system. All the medium subunits were found to prefer proline at position Y+2, suggesting that YXXO signals are stabilized by a bend in the polypeptide backbone. Other than for this common preference, each medium subunit favored specific sets of residues at the X and O positions; these preferences were consistent with the proposed roles of the different adaptor complexes in rapid endocytosis and lysosomal targeting. A considerable specificity overlap was also revealed by these analyses, suggesting that additional factors, such as the context of the signals, must be important determinants of recognition. C1 NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. Chiba Univ, Grad Sch Med, Div Mol Genet, Chuo Ku, Chiba 2608670, Japan. RP Bonifacino, JS (reprint author), NICHHD, Cell Biol & Metab Branch, NIH, Bldg 18T Rm 101,18 Lib Dr,MSC 5430, Bethesda, MD 20892 USA. EM juan@helix.nih.gov RI Saito, Takashi/C-9684-2009; Ohno, Hiroshi/L-7899-2014; OI Saito, Takashi/0000-0001-9495-3547; Ohno, Hiroshi/0000-0001-8776-9661; Bonifacino, Juan S./0000-0002-5673-6370 NR 36 TC 183 Z9 185 U1 1 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 2 PY 1998 VL 273 IS 40 BP 25915 EP 25921 DI 10.1074/jbc.273.40.25915 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 125XU UT WOS:000076263100058 PM 9748267 ER PT J AU Tanaka, K Pracyk, JB Takeda, K Yu, ZX Ferrans, VJ Deshpande, SS Ozaki, M Hwang, PM Lowenstein, CJ Irani, K Finkel, T AF Tanaka, K Pracyk, JB Takeda, K Yu, ZX Ferrans, VJ Deshpande, SS Ozaki, M Hwang, PM Lowenstein, CJ Irani, K Finkel, T TI Expression of Id1 results in apoptosis of cardiac myocytes through a redox-dependent mechanism SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LOOP-HELIX PROTEINS; SENESCENT HUMAN FIBROBLASTS; MEDIATED GENE-TRANSFER; PROGRAMMED CELL-DEATH; DNA-BINDING PROTEINS; RETINOBLASTOMA PROTEIN; HYDROGEN-PEROXIDE; ADENOVIRUS TYPE-5; HEART-FAILURE; MUSCLE AB We have constructed a recombinant adenovirus (Ad.Id1) that allows for efficient expression of the helix-loop-helix protein Idl, After infection with Ad.Id1, neonatal cardiac myocytes display a significant reduction in viability, which was proportional to the level of Idl expression, A similar effect was observed in adult myocytes, Morphological and biochemical assays demonstrated that Id1 expression resulted in myocyte apoptosis. In contrast, expression of Idl in endothelial cells, vascular smooth muscle cells, or fibroblasts did not affect the viability of these cells, Along with the induction of apoptosis, the expression of Idl in neonatal cardiac myocytes resulted in an increase in the level of intracellular reactive oxygen species. The source of these reactive oxygen species appears to be the mitochondria, Reducing the ambient oxygen concentration or treatment with a cell-permeant H2O2 scavenger prevented Id1-stimulated apoptosis in cardiac myocytes, These results suggest that the expression of Idl leads to the induction of apoptosis in cardiac myocytes through a redox-dependent mechanism. C1 NHLBI, Cardiol Branch, NIH, Bethesda, MD 20892 USA. NHLBI, Pathol Sect, NIH, Bethesda, MD 20892 USA. Johns Hopkins Sch Med, Div Cardiol, Baltimore, MD 21205 USA. RP Finkel, T (reprint author), NHLBI, Cardiol Branch, NIH, 10 Ctr Dr,Bldg 10,Rm 7B15, Bethesda, MD 20892 USA. NR 46 TC 54 Z9 55 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 2 PY 1998 VL 273 IS 40 BP 25922 EP 25928 DI 10.1074/jbc.273.40.25922 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 125XU UT WOS:000076263100059 PM 9748268 ER PT J AU Okubo, Y Blakesley, VA Stannard, B Gutkind, S Le Roith, D AF Okubo, Y Blakesley, VA Stannard, B Gutkind, S Le Roith, D TI Insulin-like growth factor-I inhibits the stress-activated protein kinase/c-jun N-terminal kinase SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PHOSPHATIDYLINOSITOL 3-KINASE; SIGNALING PATHWAY; INDUCED APOPTOSIS; MEDIATED APOPTOSIS; NEURONAL SURVIVAL; CELL-DEATH; RECEPTOR; RAS; JNK; PHOSPHORYLATION AB The pathways involved in the cellular responses to the insulin-like growth factors (IGFs) are numerous and vary according to cell type. Following activation of the IGF-I receptor, the mitogen-activated protein kinase and phosphatidylinositide 3'-kinase (PI3'K) pathways are activated and result in cellular proliferation and inhibition of apoptosis. In this study, we analyzed the IGF-I effect on the stress-activated protein kinase/c-Jun N-terminal kinase (JNK) activity using human embryonic kidney 293 cells, 293 cells transiently expressing hemagglutinin-JNK, and 293 cells stably expressing a hemagglutinin-JNK transgene, In all cell types, endogenous or transfected JNK activity was strongly stimulated by anisomycin or tumor necrosis factor-alpha, and 10 nM IGF-I pretreatment suppressed the induced JNK activity. To determine whether the effect of IGF-I on JNK activity involves the mitogen-activated protein kinase or PI3'K pathway, we used the specific MEK1 inhibitor PD098059 and the PI3'K inhibitor LY 294002. PD098059 did not alter the IGF-I suppressive effect on stressor-induced JNK activity, but LY 294002 suppressed the IGF-I effect. Moreover, in transiently transfected parental 293 cells expressing dominant-negative Akt, anisomycin-increased JNK activity was not suppressed by pretreatment with IGF-I, Our results demonstrate that the action of IGF-I on JNK in these cells is via PI3'K and Akt. C1 NIDDK, Diabet Branch, NIH, Bethesda, MD 20892 USA. NIDR, Lab Cellular Dev & Oncol, NIH, Bethesda, MD 20892 USA. RP Le Roith, D (reprint author), NIDDK, Diabet Branch, NIH, Rm 8S235A,Bldg 10, Bethesda, MD 20892 USA. RI Gutkind, J. Silvio/A-1053-2009 NR 49 TC 72 Z9 73 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 2 PY 1998 VL 273 IS 40 BP 25961 EP 25966 DI 10.1074/jbc.273.40.25961 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 125XU UT WOS:000076263100064 PM 9748273 ER PT J AU Tlapak-Simmons, VL Kempner, ES Baggenstoss, BA Weigel, PH AF Tlapak-Simmons, VL Kempner, ES Baggenstoss, BA Weigel, PH TI The active streptococcal hyaluronan synthases (HASs) contain a single HAS monomer and multiple cardiolipin molecules SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RADIATION TARGET ANALYSIS; GROUP-A STREPTOCOCCI; ACID SYNTHASE; PROTEIN-KINASE; INACTIVATION; MEMBRANE; CLONING; SUBUNIT; BINDING; WEIGHT AB The functional sizes of the two streptococcal hyaluronan synthases (HASs) were determined by radiation inactivation analysis of isolated membranes. The native enzymes in membranes from Group A Streptococcus pyogenes HAS and Group C Streptococcus equisimilis HAS were compared with the recombinant proteins expressed in Escherichia coli membranes. Based on their amino acid sequences, the masses of these four proteins as monomers are similar to 48 kDa. In all cases, loss of enzyme activity was a simple single exponential function with increasing radiation dose. The functional sizes calculated from these data were identical for the four HASs at similar to 64 kDa. In contrast, the sizes of the proteins estimated by the loss of antibody reactivity on Western blots were essentially identical at 41 kDa for the four RAS species, consistently lower than the functional size by similar to 23 kDa. Matrix-assisted laser desorption time of flight mass spectrometry analysis of purified S. pyogenes HAS-H-6 and S. equisimilis HAS-H-6 gave masses that differed by <0.07% from the predicted monomer sizes, which confirms that neither protein is posttranslationally modified or covalently attached to another protein. Ongoing studies indicate that the purified HAS enzymes require cardiolipin (CL) for maximal activity and stability. When irradiated membranes were detergent solubilized and the extracts were incubated with exogenous CL, the residual level of HAS activity increased. Consequently, the calculated functional size decreased by similar to 23 kDa to the expected size of the RAS monomer. The similar to 23-kDa larger size of the functional HAS enzyme, compared with the HAS monomer, is due, therefore, to CL molecules. We propose that the active streptococcal IIA syntheses are monomers in complex with similar to 16 CL molecules. C1 Univ Oklahoma, Hlth Sci Ctr, Dept Biochem & Mol Biol, Oklahoma City, OK 73190 USA. NIAMS, Phys Biol Lab, NIH, Bethesda, MD 20892 USA. RP Weigel, PH (reprint author), Univ Oklahoma, Hlth Sci Ctr, Dept Biochem & Mol Biol, Oklahoma City, OK 73190 USA. FU NIGMS NIH HHS [GM35978] NR 61 TC 57 Z9 59 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 2 PY 1998 VL 273 IS 40 BP 26100 EP 26109 DI 10.1074/jbc.273.40.26100 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 125XU UT WOS:000076263100081 PM 9748290 ER PT J AU Goodier, JL Maraia, RJ AF Goodier, JL Maraia, RJ TI Terminator-specific recycling of a B1-Alu transcription complex by RNA polymerase III is mediated by the RNA terminus-binding protein La SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ALPHA-FETOPROTEIN GENE; INITIATION-FACTOR; EXPRESSION; SEQUENCES; ELEMENTS; PROMOTER; REGION; DOWNSTREAM; PRECURSOR; INCREASE AB Efficient synthesis of many small abundant RNAs is achieved by the proficient recycling of RNA polymerase (pol) III and stable transcription complexes. Cellular Alu and related retroposons represent unusual pol III genes that are normally repressed but are activated by viral infection and other conditions. The core sequences of these elements contain pol III promoters but must rely on fortuitous downstream oligo(dT) tracts for terminator function, me show that a B1-Alu gene differs markedly from a classical pol III gene (tRNA(i)(Met)) in terminator sequence requirements. B1-Alu genes that differ only in terminator sequence context direct differential RNA 3' end formation. These genes are assembled into stable transcription complexes but differ in their ability to be recycled in the presence of the La transcription termination factor. La binds to the nascent RNA 3' UUUOH end motif that is generated by transcriptional termination within the pol III termination signal, oligo(dT). We found that the recycling efficiency of the B1-Alu genes is correlated with the ability of La to access the 3' end of the nascent transcript and protect it from 3'-5' exonucleolytic processing. These results illuminate a relationship between RNA 3' end formation and transcription termination, and La-mediated reinitiation by pol III. C1 NICHD, Lab Mol Growth Regulat, NIH, Bethesda, MD 20892 USA. RP Maraia, RJ (reprint author), NICHD, Lab Mol Growth Regulat, NIH, 6-416,MSC-2753,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 39 TC 22 Z9 22 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 2 PY 1998 VL 273 IS 40 BP 26110 EP 26116 DI 10.1074/jbc.273.40.26110 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 125XU UT WOS:000076263100082 PM 9748291 ER PT J AU Krainc, D Bai, G Okamoto, S Carles, M Kusiak, JW Brent, RN Lipton, SA AF Krainc, D Bai, G Okamoto, S Carles, M Kusiak, JW Brent, RN Lipton, SA TI Synergistic activation of the N-methyl-D-aspartate receptor subunit 1 promoter by myocyte enhancer factor 2C and Sp1 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID UPSTREAM REGULATORY ELEMENTS; NEURON-SPECIFIC EXPRESSION; TRANSCRIPTION FACTOR SP1; SODIUM-CHANNEL GENE; NMDA RECEPTOR; DNA-BINDING; RAT-BRAIN; EMBRYONIC-DEVELOPMENT; CORTICAL-NEURONS; NERVOUS-SYSTEM AB The N-methyl-D-aspartate (NMDA) subtype of glutamate receptor plays important roles in neuronal development, plasticity, and cell death. NMDA receptor subunit 1 (NR1) is an essential subunit of the NMDA receptor and is developmentally expressed in postnatal neurons of the central nervous system. Here we identify on the NR1 promoter a binding site for myocyte enhancer factor 2C (MEF2C), a developmentally expressed neuron/muscle transcription factor found in cerebrocortical neurons, and study its regulation of the NR1 gene. Co-expression of MEF2C and Sp1 cDNAs in primary neurons or cell lines synergistically activates the NR1 promoter. Disruption of the MEF2 site or the MEF2C DNA binding domain moderately reduces this synergism. Mutation of the Sp1 sites or the activation domains of Sp1 protein strongly reduces the synergism. Results of yeast two-hybrid and co-immunoprecipitation experiments reveal a physical interaction between MEF2C and Sp1 proteins. The MEF2C DNA binding domain is sufficient for this interaction. Dominant-negative MEF2C interferes with expression of NR1 mRNA in neuronally differentiated P19 cells. Growth factors, including epidermal growth factor and basic fibroblast growth factor, can up-regulate NR1 promoter activity in stably transfected PC12 cells, even in the absence of the MEF2 site, but the Sp1 sites are necessary for this growth factor regulation, suggesting that Spl sites may mediate these effects. C1 Brigham & Womens Hosp, CNS Res Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. NIA, Mol Neurobiol Unit, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. RP Lipton, SA (reprint author), Brigham & Womens Hosp, CNS Res Inst, 221 Longwood Ave,LMRC 1st Floor, Boston, MA 02115 USA. FU NEI NIH HHS [R01 EY05477, R01 EY06087]; NICHD NIH HHS [P01 HD29587] NR 71 TC 71 Z9 73 U1 2 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 2 PY 1998 VL 273 IS 40 BP 26218 EP 26224 DI 10.1074/jbc.273.40.26218 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 125XU UT WOS:000076263100096 PM 9748305 ER PT J AU Hu, ZZ Zhuang, L Meng, JP Dufau, ML AF Hu, ZZ Zhuang, L Meng, JP Dufau, ML TI Transcriptional regulation of the generic promoter III of the rat prolactin receptor gene by C/EBP beta and Sp1 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-KINASE; BINDING PROTEINS; FACTOR-I; EXPRESSION; MULTIPLE; ACTIVATION; ELEMENT; CLONING; DOMAIN; SITES AB Three promoters are operative in the rat prolactin receptor gene as follows: promoter I (PI) and II (PII) are specific for the gonads and liver, respectively, and promoter III (PILI) is common to several tissues. To investigate the mechanisms controlling the activity of promoter III, its regulatory elements and transcription factors were characterized in gonadal and non-gonadal cells. The TATA-less PIII domain was localized to the region -437 to -179 (ATG + 1) containing the 5'-flanking region and part of the non-coding first exon, Within the promoter domain, a functional CAAT-box/enhancer binding protein (C/EBP) (-398) and an Sp1 element (-386), which bind C/EBP beta and Sp1/Sp3, respectively, contribute individually to promoter activation in gonadal and non-gonadal cells. However, significant redundancy was demonstrated between these elements in non-gonadal cells. Additionally, an element within the non-coding exon 1 (-338) is also required for promoter activity. Activation of PIII by the widely expressed Spl and C/EBP beta factors explains its common utilization in multiple tissues. Moreover, whereas the rat and mouse PIII share similar structure and function, the mouse PI lacks the functional SF-1 element and hence is inactive. These findings indicate that promoter III is of central importance in prolactin receptor gene transcription across species. C1 NICHD, Sect Mol Endocrinol, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA. RP Dufau, ML (reprint author), NICHD, Sect Mol Endocrinol, Endocrinol & Reprod Res Branch, NIH, Bldg 49,Rm 6A36,49 Convent Dr,MSC 4510, Bethesda, MD 20892 USA. EM dufau@helix.nih.gov NR 44 TC 47 Z9 47 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 2 PY 1998 VL 273 IS 40 BP 26225 EP 26235 DI 10.1074/jbc.273.40.26225 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 125XU UT WOS:000076263100097 PM 9748306 ER PT J AU Yang, FQ Quan, J Zhang, TY Ito, Y AF Yang, FQ Quan, J Zhang, TY Ito, Y TI Preparative separation of alkaloids from the root of Sophora flavescens Ait by pH-zone-refining counter-current chromatography SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article DE Sophora flavescens; counter-current chromatography; alkaloids; matrine; sophocarpine ID PURIFICATION; COMPONENTS; ACIDS AB pH-Zone-refming counter-current chromatography was applied to the separation of alkaloids from a crude extract of the root of Sophora flavescens Ait using a multilayer coil planet centrifuge. After methyl tert.-butyl ether and water were equilibrated, triethylamine (10 mM) was added to the organic phase as a retainer and hydrochloric acid (5-10 mM) to the aqueous phase as an eluter. The separation was performed by eluting the aqueous phase while the organic phase was used as the stationary phase. From. 1.0 g of the crude extract, sophocarpine (170 mg) and matrine (600 mg) were separated within 4.5 h at high purity of over 98%. (C) 1998 Published by Elsevier Science B.V. All rights reserved. C1 NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. Beijing Inst New Technol Applicat, Beijing 100035, Peoples R China. RP Ito, Y (reprint author), NHLBI, Biophys Chem Lab, NIH, Bldg 10,Room 7N322, Bethesda, MD 20892 USA. NR 16 TC 36 Z9 42 U1 2 U2 15 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR A JI J. Chromatogr. A PD OCT 2 PY 1998 VL 822 IS 2 BP 316 EP 320 DI 10.1016/S0021-9673(98)00624-4 PG 5 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 131ZD UT WOS:000076604400014 PM 9809449 ER PT J AU McDonald, JP Maury, EE Levine, AS Woodgate, R AF McDonald, JP Maury, EE Levine, AS Woodgate, R TI Regulation of UmuD cleavage: Role of the amino-terminal tail SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE E-coli; S-typhimurium; self-processing reactions; protein-protein interactions; SOS mutagenesis ID RECA-MEDIATED CLEAVAGE; MUTANT LEXA PROTEINS; ESCHERICHIA-COLI; SOS MUTAGENESIS; LAMBDA-REPRESSOR; DEPENDENT CLEAVAGE; DNA; OPERON; AUTODIGESTION; PURIFICATION AB An essential step in SOS mutagenesis is the RecA-mediated posttranslational processing of UmuD-like proteins to the shorter, but mutagenically active, UmuD'-like proteins. Interestingly, the UmuD-like proteins undergo posttranslational processing at different rates. For example, although the Escherichia coli UmuD (UmuD(Ec)) and the Salmonella typhimurium UmuD (UmuD(St)) proteins are 73% identical, UmuD(St) is processed in vivo at a significantly faster rate than the UmuD(Ec) protein. Here, we report experiments aimed at investigating the molecular basis of these phenotypic differences. The faster rate of UmuD(St) cleavage probably does not result solely from a better interaction with RecA, since we observed that, in vitro, UmuD(St) undergoes RecA-independent autocatalytic processing about four-times faster than UmuD(Ec). By constructing chimeric UmuD proteins, we determined that the amino-terminal tail of the UmuD proteins proximal to the Cys24-Gly25 cleavage site is mainly responsible for the difference in UmuD(St) and UmuD(Ec) cleavage rates. Site-directed mutagenesis of the UmuD(Ec) protein suggests that most of the enhanced cleavage observed with the UmuD(St) protein can be attributed to the presence of a Pro23 residue, juxtaposed to the cleavage site in UmuD(St). Furthermore, this proline residue appears to result in a UmuD protein that is a much better substrate for intermolecular cleavage. These findings clearly implicate the N-terminal tail of the UmuD-like proteins as playing an important and unexpected regulatory function in the maturation of the mutagenically active UmuD'-like mutagenesis proteins. (C) 1998 Academic Press. C1 NICHHD, Sect DNA Replicat Repair & Mutagenesis, NIH, Bethesda, MD 20892 USA. RP Woodgate, R (reprint author), NICHHD, Sect DNA Replicat Repair & Mutagenesis, NIH, Bethesda, MD 20892 USA. EM woodgate@helix.nih.gov NR 44 TC 12 Z9 12 U1 0 U2 2 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD OCT 2 PY 1998 VL 282 IS 4 BP 721 EP 730 DI 10.1006/jmbi.1998.2044 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 124QB UT WOS:000076192300003 PM 9743621 ER PT J AU Ohuoha, DC Schindler, CW Rothman, RB AF Ohuoha, DC Schindler, CW Rothman, RB TI Serotonin-4 receptor antagonists reverse cocaine-induced cardiac arrhythmia SO LIFE SCIENCES LA English DT Article DE cocaine; 5-HT4 receptors; cardiotoxicity; serotonin ID ATRIAL 5-HT4 RECEPTORS; HIGH-AFFINITY; 5-HYDROXYTRYPTAMINE; BLOCKADE; HEART; RATS; GR113808; PIG AB The effect of the 5-HT4 antagonists GR113808A and GR125487D on cocaine-induced cardiac arrhythmia was examined in the rat. Cocaine alone, given TV at a rate of 2 mg/kg every 5 min, produced an initial increase in blood pressure followed by a severe drop in pressure and bradycardia. Sustained ventricular fibrillation was noted after 6-12 mg/kg cocaine and quickly progressed to asystole. Pretreatment with both GR113808A and GR125487D antagonized these effects in a dose-dependent manner. When given after the onset of arrhythmia, both drugs reversed the cocaine-induced arrhythmia's. Thus, the 5-HT4 antagonists may be useful in the treatment of cocaine toxicity. C1 NIDA, Clin Psychopharm Sect, NIH, IRP, Baltimore, MD 21224 USA. NIDA, Behav Pharmacol Sect, NIH, IRP, Baltimore, MD 21224 USA. RP Rothman, RB (reprint author), NIDA, Clin Psychopharm Sect, NIH, IRP, POB 5180, Baltimore, MD 21224 USA. NR 30 TC 4 Z9 4 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0024-3205 J9 LIFE SCI JI Life Sci. PD OCT 2 PY 1998 VL 63 IS 19 BP 1673 EP 1678 DI 10.1016/S0024-3205(98)00438-X PG 6 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 126ZA UT WOS:000076324200001 PM 9806222 ER PT J AU Vamecq, J Van derpoorten, K Poupaert, JH Balzarini, J De Clercq, E Stables, JP AF Vamecq, J Van derpoorten, K Poupaert, JH Balzarini, J De Clercq, E Stables, JP TI Anticonvulsant phenytoinergic pharmacophores and anti-HIV activity - Preliminary evidence for the dual requirement of the 4-aminophthalimide platform and the N-(1-adamantyl) substitution for antiviral properties SO LIFE SCIENCES LA English DT Article DE anticonvulsant drugs; anti-HIV drugs; 4-amino-N-(1-adamantyl)phthalimide; AIDS; phenytoin; phthalimide; benzamide; adamantine ID NECROSIS-FACTOR-ALPHA; ANTIEPILEPTIC DRUG DEVELOPMENT; THALIDOMIDE; PROTEIN; VPR; INHIBITION; CHANNELS; MICE; RATS; PHENYLPHTHALIMIDES AB This work is aimed at further exploring the concept that phenytoin-related compounds' might present with an anti-HIV potential. We screened for anti-HIV activity, selected compounds whose structural design rests on pharmacophores successfully shown to convey phenytoinergic anticonvulsant activity. We determined the corresponding anticonvulsant protective doses in mice via the ip route of administration using the maximal electroshock seizure test (a test in which the anticonvulsant activity of phenytoin is well expressed). Firstly, 4-aminophthalimide pharmacophores were utilized with either N-(2,6-dimethyl)phenyl or N-(1-adamantyl) substitutions. While the former was found to be highly potent, the latter was devoid of significant activity. Secondly, the pharmacophores N-(2,6-dimethylphenyl)phthalimide and N-(l-adamantyl)phthalimide were compared for antiviral (antiHIV-1 and antiHIV-2) properties in CEM (human T-lymphocyte) cells infected with HIV-1 or HIV-2 strains. Various phthalimide C-4-substitutions (H, NO2, NH2, Cl, CH3, OCH3, COOH) of these pharmacophores were studied. From this set of experiments, 4-amino-N-(1-adamantyl)phthalimide emerged with EC50 (effective concentration-50) values of 16 and 27 mu M against HIV-1 and HIV-2, respectively. The CC50 (cytostatic concentration-50) of this compound was 30 mu M. Thirdly, the N-(2,6-dimethylphenyl) and N-(l-adamantyl) substitutions of the 4-aminobenzamide pharmacophore (another known phenytoinergic anticonvulsant platform) were shown to be devoid of anti-HIV activities. A similar negative result was obtained for amantadine. Taken as a whole, the present data indicate that both the 4-aminophthalimide pharmacophore and N-(l-adamantyl) substitutions are required for anti-HIV properties. Molecular modeling studies further provide clues for this dual requirement. (C) 1998 Elsevier Science Inc. C1 CHRU Lille, INSERM, F-59651 Villeneuve Dascq, France. Catholic Univ Louvain, Sch Pharm, Brussels, Belgium. Katholieke Univ Leuven, Rega Inst, B-3001 Louvain, Belgium. NINDS, Epilepsy Branch, DCDND, NIH, Bethesda, MD 20892 USA. RP Vamecq, J (reprint author), CHRU Lille, INSERM, Domaine Certia,369 Rue Jules Guesde,BP39, F-59651 Villeneuve Dascq, France. NR 34 TC 2 Z9 2 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0024-3205 J9 LIFE SCI JI Life Sci. PD OCT 2 PY 1998 VL 63 IS 19 BP PL267 EP PL274 DI 10.1016/S0024-3205(98)00445-7 PG 8 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 126ZA UT WOS:000076324200008 PM 9806229 ER PT J AU Kastner, S De Weerd, P Desimone, R Ungerleider, LC AF Kastner, S De Weerd, P Desimone, R Ungerleider, LC TI Mechanisms of directed attention in the human extrastriate cortex as revealed by functional MRI SO SCIENCE LA English DT Article ID VISUAL SELECTIVE ATTENTION; NEURAL MECHANISMS; AREAS; MACAQUE; V4; PERCEPTION; STIMULUS; V3; V2; MT AB A typical scene contains many different objects, but the capacity of the visual system to process multiple stimuli at a given time is limited, Thus, attentional mechanisms are required to select relevant objects from among the many objects competing for visual processing. Evidence from functional magnetic resonance imaging (MRI) in humans showed that when multiple stimuli are present simultaneously in the visual field, their cortical representations within the object recognition pathway interact in a competitive, suppressive fashion. Directing attention to one of the stimuli counteracts the suppressive influence of nearby stimuli. This mechanism may serve to filter out irrelevant information in cluttered visual scenes. C1 NIMH, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA. NIMH, Neuropsychol Lab, NIH, Bethesda, MD 20892 USA. RP Kastner, S (reprint author), NIMH, Lab Brain & Cognit, NIH, Bldg 49,Room 1B80, Bethesda, MD 20892 USA. EM sabine@ln.nimh.nih.gov NR 30 TC 584 Z9 595 U1 10 U2 30 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD OCT 2 PY 1998 VL 282 IS 5386 BP 108 EP 111 DI 10.1126/science.282.5386.108 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 126LM UT WOS:000076294900049 PM 9756472 ER PT J AU Zhuang, P Dang, N Waziri, A Gerloff, C Cohen, LG Hallett, M AF Zhuang, P Dang, N Waziri, A Gerloff, C Cohen, LG Hallett, M TI Implicit and explicit learning in an auditory serial reaction time task (vol 97, pg 131, 1998) SO ACTA NEUROLOGICA SCANDINAVICA LA English DT Correction DE auditory stimulus modality; EEG; alpha frequency; event-related desynchronization; implicit learning; explicit learning AB Objective - To explore the role of the motor cortex during implicit and explicit learning. Materials and methods - EEG signals were recorded from 30 channels by measuring task-related desynchronization (TRD) when 10 right-handed naive volunteers performed a variation of the serial reaction task. Stimuli, consisting of 4 pure tones of 500, 1000, 1500, and 2000 HZ, lasting 200 ms, were presented binaurally through a pair of tubephones at 60 dB with a 2-s constant interstimulus interval. A series of 10 repetitive tones represented the test sequence; the random sequence was the control. Results - All subjects developed implicit and explicit knowledge reflected by decreased response time, increased accuracy, and the ability to generate the sequence. Six of 10 subjects demonstrated implicit learning without explicit learning during the first 3 blocks. When subjects acquired full explicit learning, 10 Hz TRD at C3 reached a peak amplitude, declining thereafter. Conclusions - Properties of the sensorimotor cortex change during learning and these changes are independent of stimulus modality. C1 NINDS, Human Motor Control Sect, Med Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Hallett, M (reprint author), NINDS, Human Motor Control Sect, Med Neurol Branch, NIH, Bldg 10,Rm 5N226,10 Ctr Dr,MSC 1428, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 U1 0 U2 2 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0001-6314 J9 ACTA NEUROL SCAND JI Acta Neurol. Scand. PD OCT PY 1998 VL 98 IS 4 BP 295 EP 295 DI 10.1111/j.1600-0404.1998.tb07314.x PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 127WA UT WOS:000076372500015 ER PT J AU Liberski, PP Barcikowska, M Cervenakova, L Bratosiewicz, J Marczewska, M Brown, P Gajdusek, DC AF Liberski, PP Barcikowska, M Cervenakova, L Bratosiewicz, J Marczewska, M Brown, P Gajdusek, DC TI A case of sporadic Creutzfeldt-Jakob disease with a Gerstmann-Staussler-Scheinker phenotype but no alterations in the PRNP gene SO ACTA NEUROPATHOLOGICA LA English DT Article; Proceedings Paper CT Xth Conference of the Association-of-Polish-Neuropathologists CY MAY 15-17, 1996 CL WARSAW, POLAND SP Assoc Polish Neuropathologists DE prions; Creutzfeldt-Jakob disease; Gerstmann-Straussler-Scheinker disease ID PRION PROTEIN GENE; STRAUSSLER SYNDROME; SPONGIFORM ENCEPHALOPATHIES; AMYLOID PLAQUES; POINT MUTATION; VARIANT; FAMILY; PRP; BRAIN; MICROGLIA AB We report here an unusual sporadic case of Creutzfeldt-Jakob disease (CJD) characterized by an abundance of prion protein (PrP)-immunopositive kuru and multicentric but not florid plaques. Molecular genetic analysis of the PRNP open reading frame region spanning codons 8-221 was performed. Neither deletion nor insertion mutations were detected in the repeat area of the PRNP. No pathogenic mutation was found in the sequenced region between codon 108-221. Restriction analysis of the amplified fragment using restriction endonucleases DdeI, PvuII and AluI did not show any of the previously described pathogenic mutations at codon 102, 105, and 117 associated with Gerstmann-Straussler-Scheinker (GSS). The patient was heterozygous for the methionine/valine coding triplet at polymorphic codon 129 of the PRNP gene by sequence, restriction endonuclease analysis and hybridization with allele-specific nucleotides. Furthermore, hybridization with P-32-labeled allele-specific oligonucleotides confirmed the absence of pathogenic mutations at codons 102, 200 and 178. Such a case may present a missing "link" between sporadic CJD and familial GSS. C1 Med Acad Lodz, Dept Oncol, PL-93509 Lodz, Poland. Polish Acad Sci, Med Res Ctr, Dept Neuropathol, Warsaw, Poland. NINDS, Cent Nervous Syst Studies Lab, NIH, Bethesda, MD 20892 USA. Med Acad, Dept Anat Pathol, Warsaw, Poland. RP Liberski, PP (reprint author), Med Acad Lodz, Dept Oncol, Paderewskiego 4, PL-93509 Lodz, Poland. NR 38 TC 9 Z9 10 U1 1 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0001-6322 J9 ACTA NEUROPATHOL JI Acta Neuropathol. PD OCT PY 1998 VL 96 IS 4 BP 425 EP 430 PG 6 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 123KG UT WOS:000076123900016 PM 9797009 ER PT J AU Sperling, RS Shapiro, DE McSherry, GD Britto, P Cunningham, BE Culnane, M Coombs, RW Scott, G Van Dyke, RB Shearer, WT Jimenez, E Diaz, C Harrison, DD Delfraissy, JF AF Sperling, RS Shapiro, DE McSherry, GD Britto, P Cunningham, BE Culnane, M Coombs, RW Scott, G Van Dyke, RB Shearer, WT Jimenez, E Diaz, C Harrison, DD Delfraissy, JF CA Ped AIDS Clin Trials Grp Protocol 076 TI Safety of the maternal-infant zidovudine regimen utilized in the Pediatric AIDS Clinical Trial Group 076 Study SO AIDS LA English DT Article DE zidovudine safety; perinatal HIV-1 transmission ID HUMAN-IMMUNODEFICIENCY-VIRUS; INFECTED WOMEN; TRANSMISSION; REDUCTION; GROWTH; TYPE-1; COHORT AB Objective: To determine the safety of the zidovudine (ZDV) regimen utilized in the Pediatric AIDS Clinical Trial Group (ACTG) 076 study. Design: ACTG 076 was a randomized, double-blind, placebo-controlled trial which demonstrated that a ZDV regimen could prevent mother-to-child HIV-1 transmission. Infants were followed through 18 months of age and women were followed through 6 months postpartum. Methods: Maternal complications, pregnancy outcomes, growth and development of the uninfected infants, and HIV-1 disease progression in the women were monitored prospectively. Results: Maternal therapy was well tolerated. There was no serious pattern of adverse pregnancy outcomes associated with ZDV use. Amongst the ZDV-exposed infants, the only recognized toxicity was anemia within the first 6 weeks of life; the risk for anemia was not associated with premature delivery, duration of maternal treatment, degree of maternal immunosuppression, or maternal anemia. ZDV treatment was not associated with an increased incidence of newborn structural abnormalities. At 18 months of age, uninfected infants did not differ in growth parameters or immune function. No childhood neoplasias were reported in either group. In the women, at 6 months postpartum, there were no differences in clinical, immunologic, or virologic disease progression. Conclusion: There were no identified problems that would alter current recommendations for the routine use of ZDV for the prevention of mother-child HIV-1 transmission. (C) 1998 Lippincott Williams & Wilkins. C1 Mt Sinai Med Ctr, Dept Obstet Gynecol & Reprod Sci, New York, NY 10029 USA. Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA 02115 USA. Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Pediat, Newark, NJ 07103 USA. Frontier Sci & Technol Res Fdn Inc, Amherst, NY USA. NIAID, Div AIDS, Bethesda, MD 20892 USA. Univ Washington, Sch Med, Seattle, WA USA. Univ Miami, Sch Med, Dept Pediat, Miami, FL USA. Tulane Univ, Dept Pediat, New Orleans, LA 70118 USA. Texas Childrens Hosp, Baylor Coll Med, Houston, TX 77030 USA. San Juan City Hosp, San Juan, PR USA. Univ Puerto Rico, San Juan, PR 00936 USA. Wayne State Univ, Detroit, MI USA. Agence Natl Rech SIDA, INSERM, Serv Commun 10, Paris, France. RP Sperling, RS (reprint author), Mt Sinai Med Ctr, Dept Obstet Gynecol & Reprod Sci, Box 1173,1 Gustave Levy Pl, New York, NY 10029 USA. FU NIAID NIH HHS [U01 AI41110, N01 AI95030] NR 18 TC 97 Z9 99 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0269-9370 J9 AIDS JI Aids PD OCT 1 PY 1998 VL 12 IS 14 BP 1805 EP 1813 DI 10.1097/00002030-199814000-00012 PG 9 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 128RJ UT WOS:000076419900012 PM 9792381 ER PT J AU Olsen, SJ Chang, Y Moore, PS Biggar, RJ Melbye, M AF Olsen, SJ Chang, Y Moore, PS Biggar, RJ Melbye, M TI Increasing Kaposi's sarcoma-associated herpesvirus seroprevalence with age in a highly Kaposi's sarcoma endemic region, Zambia in 1985 SO AIDS LA English DT Article DE Kaposi's sarcoma-associated herpesvirus; Kaposi's sarcoma; Zambia; seroprevalence; epidemiology; HIV ID INFECTION; ANTIBODIES; HUMAN-HERPESVIRUS-8; POPULATION; PATTERN; PROTEIN; ANTIGEN; AFRICA AB Background: Kaposi's sarcoma (KS)-associated herpesvirus (KSHV) is a newly discovered virus found in all forms of KS. In the United States, KSHV infection appears to be most common amongst individuals at high-risk for KS. Preliminary data from Africa suggest that KSHV infection may be much more common in the general population. Objective: To examine the KSHV seroprevalence and age-specific patterns of infection in an African country with high rates of KS. Design: Cross-sectional seroprevalence study. Methods: Sera were taken for a hospital-based HIV seroprevalence study conducted in August 1985 in Lusaka, Zambia at a time when HIV was just becoming epidemic in this area. A total of 251 sera were randomly sampled and examined for antibodies against latent and lytic antigens to KSHV. KSHV seroprevalence was compared with demographic and clinical variables using chi(2) test for linear trend and odds ratios and 95% confidence intervals. Results: Overall, 58% of persons aged 14-84 years were KSHV-seropositive. KSHV seroprevalence increased linearly with age (P = 0.04) and was inversely related to years of education (P = 0.015). In contrast, HIV infection peaked in those aged 20-29 years and was positively related to years of education (P = 0.015). No association between KSHV and gender, marital status, or HIV serostatus was seen. Conclusions: KSHV infection was significantly more common in this region of Zambia in 1985 than it currently is in the United States. Our data are consistent with KSHV being well-established in this region prior to 1985 and that continued adult transmission of the virus was occurring. The high seroprevalence in the adolescent age-group and the relatively linear increase in prevalence with age suggest that nonsexual modes of transmission may be important for KSHV transmission in Africa. (C) 1998 Lippincott Williams & Wilkins. C1 Columbia Univ, Dept Pathol, New York, NY 10032 USA. Columbia Univ, Div Epidemiol, New York, NY 10032 USA. NCI, Bethesda, MD 20892 USA. Danish Epidemiol Sci Ctr, Statens Serum Inst, Copenhagen, Denmark. RP Moore, PS (reprint author), Columbia Univ, Dept Pathol, 630 W 168th St,P&S 14-442, New York, NY 10032 USA. RI Chang, Yuan/F-4146-2011; Moore, Patrick/F-3960-2011 OI Moore, Patrick/0000-0002-8132-858X FU NCI NIH HHS [CA73564-01A1]; PHS HHS [CCU210852] NR 21 TC 101 Z9 106 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0269-9370 J9 AIDS JI Aids PD OCT 1 PY 1998 VL 12 IS 14 BP 1921 EP 1925 DI 10.1097/00002030-199814000-00024 PG 5 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 128RJ UT WOS:000076419900024 PM 9792393 ER PT J AU Arthur, LO Bess, JW Chertova, EN Rossio, JL Esser, MT Benveniste, RE Henderson, LE Lifson, JD AF Arthur, LO Bess, JW Chertova, EN Rossio, JL Esser, MT Benveniste, RE Henderson, LE Lifson, JD TI Chemical inactivation of retroviral infectivity by targeting nucleocapsid protein zinc fingers: A candidate SIV vaccine SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; MURINE LEUKEMIA-VIRUS; ENVELOPE GLYCOPROTEIN; STRUCTURAL PROTEINS; CHALLENGE; MACAQUES; GP41; HIV; IMMUNIZATION; SEPARATION AB Although most viral vaccines used in humans have been composed of live attenuated viruses or whole killed viral particles, the latter approach has received little attention in research on experimental primate immunodeficiency virus vaccines. Inactivation procedures involving heat or formalin appear to adversely affect the viral envelope proteins. Recently we have inactivated human immunodeficiency virus type 1 (HIV-1) with the compound 2,2'-dithiodipyridine (Aldrithiol-2, Aldrich, Milwaukee, WI), which inactivates infectivity of retroviruses by covalently modifying the nucleocapsid zinc finger motifs, HIV-1 inactivated with Aldrithiol-2 retained the conformational and functional integrity of the viral and virion-associated cellular proteins on the viral membrane. We have extended our studies of zinc finger targeted inactivation to simian immunodeficiency virus (SIV) and evaluated the feasibility of applying the procedures to large scale (>30 1) production and purification of the primate immunodeficiency viruses. There was no detectable residual infectivity of SIV after treatment with 1 mM Aldrithiol-2 (>5 logs inactivation). Treatment with Aldrithiol-2 resulted in extensive reaction with the nucleocapsid protein of treated virus, as shown by immunoblot and high-performance liquid chromatography (HPLC) analysis. As expected, the virion gp120(SU) appeared to be completely unreactive with Aldrithiol-2, Sucrose gradient purification and concentration procedures resulted in little loss of viral infectivity or virion-associated gp120(SU), When tested in a gp120-CD4 dependent cell binding assay, the inactivated virus bound to cells comparably to the untreated virus. Analysis of gp120-CD4 mediated postbinding fusion events showed that the inactivated virus could induce CD4-dependent fusion with efficiencies similar to the untreated virus. Inactivation and processing of primate immunodeficiency viruses by methods described here results in highly concentrated virus preparations that retain their envelope proteins in a native configuration. These inactivated virus preparations should be useful in whole killed-particle vaccine experiments as well as laboratory reagents to prepare antisera, including monoclonal antibodies, and to study noninfective virion-cell interactions. C1 NCI, AIDS Vaccine Program, SAIC Frederick, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. NCI, Lab Genom Divers, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Arthur, LO (reprint author), NCI, AIDS Vaccine Program, SAIC Frederick, Frederick Canc Res & Dev Ctr, POB B, Frederick, MD 21702 USA. RI Bess, Jr., Julian/B-5343-2012 FU NCI NIH HHS [N01-CO-56000] NR 29 TC 88 Z9 89 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 1998 VL 14 SU 3 BP S311 EP S319 PG 9 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 133CV UT WOS:000076669600019 PM 9814959 ER PT J AU Schultz, A AF Schultz, A TI Encouraging vaccine results from primate models of HIV type 1 infection SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID SIMIAN IMMUNODEFICIENCY VIRUS; NEUTRALIZING ANTIBODY-RESPONSES; CYTOTOXIC T-CELLS; RHESUS MACAQUES; PERSISTENT INFECTION; SIV; CHALLENGE; AIDS; PATHOGENICITY; IMMUNIZATION AB Challenge studies in primates have established that vaccine-induced protection against immunodeficiency viruses, even against mucosal routes of challenge, is attainable, and that "sterile" immunity is not required for protection. Intelligent use of such studies in primate models, coupled with in vitro measurements of immunity, is the best tool for establishing which vaccine concepts have promise. C1 NIAID, Vaccine & Prevent Res Program, Div AIDS, NIH, Rockville, MD 20892 USA. RP Schultz, A (reprint author), NIAID, Vaccine & Prevent Res Program, Div AIDS, NIH, 6003 Execut Blvd, Rockville, MD 20892 USA. NR 33 TC 4 Z9 4 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 1998 VL 14 SU 3 BP S261 EP S263 PG 3 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 133CV UT WOS:000076669600013 PM 9814953 ER PT J AU Johnson, EO van den Bree, MBM Gupman, AE Pickens, RW AF Johnson, EO van den Bree, MBM Gupman, AE Pickens, RW TI Extension of a typology of alcohol dependence based on relative genetic and environmental loading SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE typology; alcoholism; genetics; subtypes ID SUBGROUPING ALCOHOLICS; II ALCOHOLISM; USE DISORDERS; CRITERIA; MEN; COMORBIDITY; INDICATORS; MECHANISMS; POPULATION; ADOPTION AB Mild, severe, and dyssocial subtypes of alcohol dependence, previously identified among Caucasian men from the Epidemiologic Catchment Area study, were also identified among Caucasian men and women with DSM-IV alcohol dependence from the National Longitudinal Alcohol Epidemiologic Survey (n = 2,703; 1,746 respectively). These subtypes were not identified among African American and Hispanic American men or women with DSM-IV alcohol dependence. Among Caucasians with alcohol dependence, the subtypes were characterized by differential loading on three dimensions: genetic, general environmental, and dyssocial environmental symptom scales developed in a prior twin study. The mild subtype (60% of men and 66% of women) was distinguished by low mean scores on all three scales; the dyssocial subtype (24% of men and 20% of women) by low mean genetic and general environmental scores but high mean dyssocial environmental scores; and the severe subtype (16% of men and 14% of women) by high scores on the genetic and general environmental scales. These subtypes also showed the expected distinctions in clinical characteristics. The severe subtype showed greater comorbid drug dependence and major depression, more treatment seeking, and a higher prevalence of parental alcoholism. The severe subtype also showed significantly greater genetic influence adjusted for overall severity of alcohol dependence (genetic ratio). Only the severe subtype showed a pattern of scale scores and clinical characteristics suggestive of substantial genetic influence. The present study indicates a robustness of the typology originally developed among DSM-III alcohol-dependent Caucasian men by empirical extension of the subtypes to a different sample of Caucasian men and, separately, Caucasian women. The use of this typology may aid in distinguishing between Caucasian alcohol-dependent individuals on the basis of relative genetic influence, enabling genetic, behavioral, and epidemiological investigations to reduce genetic or environmental "noise" and better focus on specific aspects of alcohol dependence. C1 Henry Ford Hlth Sci Ctr, Dept Psychiat, Detroit, MI 48202 USA. NIDA, Intramural Res Program, Baltimore, MD USA. RP Johnson, EO (reprint author), Henry Ford Hlth Sci Ctr, Dept Psychiat, 1 Ford Pl,Room 3A, Detroit, MI 48202 USA. RI turton, miranda/F-4682-2011 NR 43 TC 18 Z9 19 U1 2 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD OCT PY 1998 VL 22 IS 7 BP 1421 EP 1429 DI 10.1111/j.1530-0277.1998.tb03930.x PG 9 WC Substance Abuse SC Substance Abuse GA 130JA UT WOS:000076515600008 PM 9802523 ER PT J AU Chou, SP Grant, BF Dawson, DA AF Chou, SP Grant, BF Dawson, DA TI Alcoholic beverage preference and risks of alcohol-related medical consequences: A preliminary report from the National Longitudinal Alcohol Epidemiologic Survey SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE beer; wine; liquor; alcohol-related morbidity; prevalence ID CORONARY-ARTERY DISEASE; RED WINE; FRENCH PARADOX; CONSUMPTION; CANCER; MORTALITY; PANCREAS; DRINKERS; HISTORY; DIET AB In studying the alcohol-morbidity association, a substantial amount of attention and efforts has been focused on volume of alcohol intake. Considerably less is known about the differential health effects of beverage types. The present: study used a most recent national household survey of the U.S. general population on drinking practices, alcohol use disorders, and their associated disabilities. The prevalence of a broad range of alcohol-related diseases was examined with respect to preferred beverage type, as well as consumption level. Our findings showed a reduced health risk associated with beer and wine drinking for a number of physical disorders, and a somewhat favorable cardiovascular effect of these two beverage types in relation to abstention. Among preferrers of beer, wine, and liquor, the results indicate that liquor preference is associated with elevated morbidity for several medical consequences. However, interpretation of results and the public health implications of these findings need to be taken cautiously, because sociodemographic and other behavioral characteristics were not considered In this preliminary report. C1 NIAAA, Div Biometry & Epidemiol, Bethesda, MD 20892 USA. RP Chou, SP (reprint author), NIAAA, Div Biometry & Epidemiol, Suite 514,6000 Execut Blvd, Bethesda, MD 20892 USA. NR 31 TC 12 Z9 14 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD OCT PY 1998 VL 22 IS 7 BP 1450 EP 1455 DI 10.1111/j.1530-0277.1998.tb03934.x PG 6 WC Substance Abuse SC Substance Abuse GA 130JA UT WOS:000076515600012 PM 9802527 ER PT J AU Anton, RF Stout, RL Roberts, JS Allen, JP AF Anton, RF Stout, RL Roberts, JS Allen, JP TI The effect of drinking intensity and frequency on serum carbohydrate-deficient transferrin and gamma-glutamyl transferase levels in outpatient alcoholics SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article; Proceedings Paper CT Annual Meeting of the Research-Society-on-Alcoholism CY JUL 19-24, 1997 CL SAN FRANCISCO, CALIFORNIA SP Res Soc Alcoholism DE alcohol; carbohydrate-deficient transferrin; markers; gamma-glutamyltransferase; alcoholism ID CHRONIC ETHANOL; HEAVY DRINKING; CONSUMPTION; MARKER; INDICATOR AB Whereas heavy alcohol consumption is known to elevate serum carbohydrate-deficient transferrin (CDT) and gamma-glutamyl transferase (GGT) levels, the contribution of drinking pattern to these effects is not completely understood. We present data on 423 men and 146 women evaluated 1 year after treatment in a large-scale alcoholism treatment study (Project MATCH). Relationships between drinking frequency (number of days drinking), intensity (drinks per drinking day), and blood levels of CDT and GGT were analyzed by using response surface regression models and thin-plate spline-smoothing techniques. Both models indicated differences between CDT- and GGT-drinking pattern relationships in men and, also, a difference between men and women in CDT drinking-pattern relationships. For men, CDT levels appeared to respond primarily to frequency of drinking, whereas GGT was influenced primarily by drinking intensify, For women, both CDT and GGT were influenced more by drinks per drinking day (intensity) than by number of days drinking (frequency). The data confirm both the Independent nature of these biological markers of alcohol consumption and gender differences in alcohol-induced CDT response reported previously. C1 Med Univ S Carolina, Inst Psychiat, Ctr Drug & Alcohol Programs, Charleston, SC 29425 USA. Brown Univ, Ctr Alcohol & Addict Studies, Providence, RI 02912 USA. NIAAA, Rockville, MD 20852 USA. RP Anton, RF (reprint author), Med Univ S Carolina, Inst Psychiat, Ctr Drug & Alcohol Programs, 171 Ashley Ave, Charleston, SC 29425 USA. FU NIAAA NIH HHS [2U10AA08428] NR 22 TC 34 Z9 35 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD OCT PY 1998 VL 22 IS 7 BP 1456 EP 1462 DI 10.1111/j.1530-0277.1998.tb03935.x PG 7 WC Substance Abuse SC Substance Abuse GA 130JA UT WOS:000076515600013 PM 9802528 ER PT J AU Soderstrom, CA Dischinger, PC Kerns, TJ Kufera, JA McDuff, DR Gorelick, DA Smith, GS AF Soderstrom, CA Dischinger, PC Kerns, TJ Kufera, JA McDuff, DR Gorelick, DA Smith, GS TI Screening trauma patients for alcoholism according to NIAAA guidelines with alcohol use disorders identification test questions SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article; Proceedings Paper CT 41st Annual Meeting of the Association-for-the-Advancement-of-Automotive-Medicine CY NOV 10-11, 1997 CL ORLANDO, FLORIDA SP Assoc Advancement Automot Med DE alcohol screening; Alcohol Use Disorders Identification Test; alcoholism; trauma; trauma centers ID UNITED-STATES; GENERAL-POPULATION; INJURY; CONSUMPTION; EMERGENCY; ADULTS AB Drinking pattern criteria (drinking frequency and number of drinks per occasion) issued by the National Institute on Alcohol and Abuse and Alcoholism (NIAAA) to screen primary practice patients for alcohol problems were evaluated in 1216 injured patients treated in a regional trauma center. Vehicular crash Victims predominated (50.2%, of whom 64.5% were drivers), followed by victims of violence (31.2%) and nonviolent-injury victims (18.5%). Alcohol Use Disorders Identification Test (AUDIT) questions #1 (drinking frequency) and #2 (drinks/day) were used to assess the patients for current alcohol dependence (CAD). AUDIT responses roughly approximating NIAAA guidelines (high threshold: drinks greater than or equal to 4 times/week, greater than or equal to 5 drinks/day) and those indicating less drinking (low threshold: drinks greater than or equal to 2-8 times/week, greater than or equal to 3 drinks/day) were chosen. Comparisons were made relative to sensitivity and specificity of responses in detecting CAD. When low threshold responses were used for either question, sensitivity to detect CAD increased overall (#1 from 0.53 to 0.80, #2 from 0.62 to 0.88) as well as among the subgroups of patients, whereas specificity remained high or at acceptable levels overall (#1 from 0.95 to 0.82, #2 from 0.92 to 0.71) and among the subgroups of patients. Study findings suggest that, among injured drivers and other groups of trauma center patients, lesser amounts of drinking should be used as screening criteria for CAD than are used for the general population. C1 Univ Maryland, R Adams Cowley Shock Trauma Ctr, Baltimore, MD 21201 USA. Univ Maryland, Sch Med, Charles McC Mathias Natl Study Ctr Trauma & Emerg, Baltimore, MD 21201 USA. Univ Maryland, Sch Med, Dept Psychiat, Baltimore, MD 21201 USA. NIDA, Div Intramural Res, Baltimore, MD USA. Johns Hopkins Injury Prevent Ctr, Baltimore, MD USA. RP Soderstrom, CA (reprint author), Univ Maryland, R Adams Cowley Shock Trauma Ctr, 22 S Greene St, Baltimore, MD 21201 USA. OI Smith, Gordon/0000-0002-2911-3071 FU NIAAA NIH HHS [R01 AA09050] NR 29 TC 28 Z9 28 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD OCT PY 1998 VL 22 IS 7 BP 1470 EP 1475 DI 10.1097/00000374-199810000-00015 PG 6 WC Substance Abuse SC Substance Abuse GA 130JA UT WOS:000076515600015 PM 9802530 ER PT J AU Schooler, C Diakite, C Vogel, J Mounkoro, P Caplan, L AF Schooler, C Diakite, C Vogel, J Mounkoro, P Caplan, L TI Conducting a complex sociological survey in rural Mali - Three points of view SO AMERICAN BEHAVIORAL SCIENTIST LA English DT Article ID JAPAN; POLAND AB The authors describe a cross-cultural collaborative attempt between American and Malian investigators to apply standard sociological survey techniques to three generally preliterate, nonindustrial ethnic groups in rural Mali-the Dogon, Peulh, and Bozo. The study examines how socioenvironmental factors (e.g., occupational conditions, migration, exposure to Western culture) affect values, orientations to self and others, psychological distress, coping mechanisms, and AIDS-related attitudes and behaviors. Other medical dependent variables include HIV other sexually transmitted diseases, clinical depression, and psychosis. The authors depict this cross-cultural collaboration from the points of view of ifs three types of investigators: American behavioral scientist, Malian medical researcher American Africanist. Preliminary statistical analyses strongly suggest that the quality of both the data and the coding are more than satisfactory The authors have nor, however; analyzed the data to the point of publishable substantive findings. The article remains a promissory report on an ambitious work in progress. C1 NIMH, Sect Socioenvironm Studies US, Bethesda, MD 20892 USA. Reg Ctr Tradit Med, Bandiagara, Mali. Drew Univ, Program W Africa, Philadelphia, PA USA. RP Schooler, C (reprint author), NIMH, Sect Socioenvironm Studies US, Bethesda, MD 20892 USA. NR 9 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0002-7642 J9 AM BEHAV SCI JI Am. Behav. Sci. PD OCT PY 1998 VL 42 IS 2 BP 276 EP 284 DI 10.1177/0002764298042002010 PG 9 WC Psychology, Clinical; Social Sciences, Interdisciplinary SC Psychology; Social Sciences - Other Topics GA 118QH UT WOS:000075851100009 ER PT J AU Traber, MG Rader, D Acuff, RV Ramakrishnan, R Brewer, HB Kayden, HJ AF Traber, MG Rader, D Acuff, RV Ramakrishnan, R Brewer, HB Kayden, HJ TI Vitamin E dose-response studies in humans with use of deuterated RRR-alpha-tocopherol SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE vitamin E supplements; lipoproteins; chylomicrons; stable isotopes; absorption; alpha-tocopherol transfer protein; adults; humans ID LOW-DENSITY LIPOPROTEINS; TRANSFER PROTEIN; E-DEFICIENCY; RAT-LIVER; PLASMA-LIPOPROTEINS; CORONARY-DISEASE; BINDING-PROTEIN; E CONSUMPTION; DISCRIMINATION; ABSORPTION AB Background: Supplemental vitamin E does not raise plasma alpha-tocopherol concentrations more than approximate to 3-fold. Objective: To elucidate the mechanism for the limitation in plasma alpha-tocopherol, we undertook human supplementation trials using incrementally increased doses of deuterated vitamin E. Design: Plasma was obtained from 6 healthy, young adults (4 men and 2 women) during 3 sequential supplementation trials with doses of 15, 75, and 150 mg RRR-alpha-tocopheryl acetate labeled with deuterium (d(3)-RRR-alpha-tocopheryl acetate). A defined diet was provided on the day of deuterated vitamin E administration, but otherwise subjects ate ad libitum. Results: The areas under the curves calculated from the plasma d(3)-RRR-alpha-tocopherol concentrations increased linearly with dose-a 10-fold increase in dose resulted in a 10-fold increase in area under the curve. d(3)-RRR-alpha-Tocopherol absorption and incorporation into plasma did not decrease with increasing dose. At 11 h, the 15-, 75-, and 150-mg doses resulted in 8 +/- 4%, 21 +/- 10%, and 37 +/- 20% labeling, respectively, of plasma vitamin E. Plasma total (labeled plus unlabeled) alpha-tocopherol concentrations before supplementation were 12 +/- 3 mu mol/L and over the 96 h after the dose averaged 13.3 +/- 2.6, 15.4 +/- 3.0, and 16.7 +/- 4.9 mu mol/L for the 15-, 75-, and 150-mg doses, respectively. Conclusions: d(3)-RRR-alpha-Tocopherol was incorporated into the plasma in preference to circulating plasma RRR-alpha-tocopherol. This could occur if the newly absorbed d(3)-RRR-alpha-tocopherol was preferentially used to replenish circulating vitamin E. C1 NYU, Med Ctr, Dept Med, New York, NY 10016 USA. Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA. NHLBI, Mol Dis Branch, NIH, Bethesda, MD 20892 USA. Univ Penn, Med Ctr, Inst Human Gene Therapy, Dept Med,Div Med Genet, Philadelphia, PA 19104 USA. E Tennessee State Univ, Coll Med, Eastman Ctr Nutr Res, Johnson City, TN 37614 USA. Columbia Univ, New York, NY 10027 USA. RP Traber, MG (reprint author), Oregon State Univ, Linus Pauling Inst Sci & Med, Dept Nutr & Food Management, 571 Weniger Hall, Corvallis, OR 97331 USA. EM Maret.Traber@orst.edu OI Traber, Maret/0000-0002-2892-4024 NR 52 TC 68 Z9 71 U1 0 U2 2 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD OCT PY 1998 VL 68 IS 4 BP 847 EP 853 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 124QE UT WOS:000076192600013 PM 9771861 ER PT J AU Wacholder, S Hartge, P Struewing, JP Pee, D McAdams, M Brody, L Tucker, M AF Wacholder, S Hartge, P Struewing, JP Pee, D McAdams, M Brody, L Tucker, M TI The kin-cohort study for estimating penetrance SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE biometry; breast neoplasms; colon neoplasms; epidemiologic methods; genetics; Jews; ovarian neoplasms ID ASHKENAZI-JEWISH INDIVIDUALS; OVARIAN-CANCER; BREAST-CANCER; CARRIER FREQUENCY; FAMILY HISTORY; BRCA1; MUTATIONS; RISK; DISEASE; JEWS AB A cross-sectional study may be more feasible than a cohort or case-control study for examining the effect of a genetic mutation on cancer penetrance outside of cancer families. The kin-cohort design uses Volunteer probands selected from a population with a relatively high frequency of the mutations of interest. By considering the cancer risk in first-degree relatives of mutation-positive and -negative probands as a weighted average of the risk in carriers and noncarriers, with weights calculated assuming a known mode of inheritance, one can infer the penetrance of the mutations. The estimates of penetrance by age 70 years for three specific mutations in the BRCA1 and BRCA2 genes common among Ashkenazi Jews for the first occurrence of breast or ovary cancer is 63%. The kin-cohort design can be a useful tool for quickly estimating penetrance from volunteers in a setting in which the mutation prevalence is relatively high. C1 NCI, Biostat Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Informat Management Syst, Rockville, MD USA. Informat Management Syst, Silver Spring, MD USA. Natl Human Genome Res Inst, Bethesda, MD USA. RP Wacholder, S (reprint author), NCI, Biostat Branch, Div Canc Epidemiol & Genet, 6130 Execut Blvd,EPN 403, Bethesda, MD 20892 USA. RI Struewing, Jeffery/C-3221-2008; Tucker, Margaret/B-4297-2015; Struewing, Jeffery/I-7502-2013 OI Struewing, Jeffery/0000-0002-4848-3334 NR 16 TC 83 Z9 83 U1 0 U2 0 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD OCT 1 PY 1998 VL 148 IS 7 BP 623 EP 630 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 128PU UT WOS:000076415700001 PM 9778168 ER PT J AU Nelson, RG Morgenstern, H Bennett, PH AF Nelson, RG Morgenstern, H Bennett, PH TI Birth weight and renal disease in Pima Indians with type 2 diabetes mellitus SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE albuminuria; birth weight; diabetic nephropathies; Indians; North American; diabetes mellitus; type 2 ID IMPAIRED GLUCOSE-TOLERANCE; HYPERTENSION; NEPHROPATHY; GLOMERULI; GROWTH; DEATH; FETAL; NIDDM; RISK AB Congenital retardation of renal development may increase the risk of renal disease, and this risk may be enhanced by diseases, such as diabetes, that damage the kidney. In this study, the prevalence of urinary albumin excretion, determined in 308 Pima Indians with type 2 diabetes, was 63% in subjects with low birth weight (<2,500 g), 41% in those with normal birth weight (2,500-4,499 g), and 64% in those with high birth weight (greater than or equal to 4,500 g). When examined as a continuous variable by generalized additive logistic regression, birth weight had a U-shaped association with the prevalence of elevated urinary albuminuria (p = 0.04) after adjustment for age, sex, duration of diabetes, glycosylated hemoglobin, and blood pressure, The odds of elevated albuminuria in subjects of low birth weight was 2.3 times (95% confidence interval 0.72-7.2) that in subjects of normal birth weight, and the odds in subjects of high birth weight was 3.2 times (95% confidence interval 0.75-13.4) as high. Sixty-four percent of the subjects with high birth weight and none of those with low birth weight were offspring of diabetic mothers. After maternal diabetes during pregnancy was controlled for, the odds of elevated albuminuria in subjects of high birth weight was no longer higher (odds ratio = 1.0, 95% confidence interval 0.22-4.9). The higher prevalence of elevated albuminuria in diabetic Pima Indians with high birth weight may be due to intrauterine diabetes exposure, whereas the higher prevalence in those with low birth weight may be due to the effects of intrauterine growth retardation. C1 NIDDKD, Phoenix Epidemiol & Clin Res Branch, NIH, Phoenix, AZ 85014 USA. Univ Calif Los Angeles, Sch Publ Hlth, Dept Epidemiol, Los Angeles, CA 90024 USA. RP Nelson, RG (reprint author), NIDDKD, Phoenix Epidemiol & Clin Res Branch, NIH, 1550 E Indian Sch Rd, Phoenix, AZ 85014 USA. RI Nelson, Robert/B-1470-2012 NR 28 TC 89 Z9 91 U1 1 U2 1 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD OCT 1 PY 1998 VL 148 IS 7 BP 650 EP 656 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 128PU UT WOS:000076415700004 PM 9778171 ER PT J AU Leveille, SG Guralnik, JM Ferrucci, L Hirsch, R Simonsick, E Hochberg, MC AF Leveille, SG Guralnik, JM Ferrucci, L Hirsch, R Simonsick, E Hochberg, MC TI Foot pain and disability in order women SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE aged; disabled; foot; foot deformities; pain; walking ID KNEE OSTEOARTHRITIS; OLDER PERSONS; AGE AB In a study of the relation between foot pain and disability, a cross-sectional analysis was performed using baseline data (1992-1995) from the Women's Health and Aging Study, a population-based study of 1,002 disabled women aged 65 years and older living in Baltimore, Maryland. Chronic and severe foot pain, defined as pain lasting 1 month or longer in the previous year, plus pain in the previous month rated severe (7-10 on a scale of 0 to 10), was reported by 14% of the women. Severe foot pain was more common in women who were younger (aged 65-74 years), obese, or had hand or knee osteoarthritis. Walking speed and five repeated chair stands were slower in women with foot pain. After adjustment for age, body mass index, race, education, self-rated health, smoking status, comorbidities, and number of other pain sites, severe foot pain was independently associated with increased risk for walking difficulty (adjusted odds ratio = 1.69, 95% confidence interval 1.10-2.59) and disability in activities of daily living (adjusted odds ratio = 1.91, 95% confidence interval 1.21-3.01). These findings suggest that severe foot pain may play a key role in disability in older women. Further studies are warranted to confirm these results longitudinally and to determine whether interventions to alleviate foot pain could reduce or prevent disability in older women. C1 NIA, Epidemiol Demog & Biometry Program, Bethesda, MD 20892 USA. Natl Res Inst, Dept Geriatr, I Fraticini, Florence, Italy. Univ Maryland, Dept Med, Baltimore, MD 21201 USA. Univ Maryland, Dept Epidemiol & Prevent Med, Baltimore, MD 21201 USA. RP Leveille, SG (reprint author), NIA, Epidemiol Demog & Biometry Program, Gateway Bldg,Suite 3C-309,7201 Wisconsin Ave, Bethesda, MD 20892 USA. NR 25 TC 95 Z9 98 U1 1 U2 3 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD OCT 1 PY 1998 VL 148 IS 7 BP 657 EP 665 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 128PU UT WOS:000076415700005 PM 9778172 ER PT J AU McKeown, LP Hansmann, KE Wilson, O Gahl, W Gralnick, HR Rosenfeld, KE Rosenfeld, SJ Horne, MK Rick, ME AF McKeown, LP Hansmann, KE Wilson, O Gahl, W Gralnick, HR Rosenfeld, KE Rosenfeld, SJ Horne, MK Rick, ME TI Platelet von Willebrand factor in Hermansky-Pudlak syndrome SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article DE Hermansky-Pudlak syndrome; von Willebrand factor; bleeding diathesis ID VONWILLEBRAND-FACTOR; RELEASE REACTION; BLEEDING-TIME; POPULATION AB Hermansky-Pudlak Syndrome (HPS) is an autosomal recessive inherited disorder characterized by oculocutaneous albinism, tissue accumulation of ceroid pigment, and a mild to moderate bleeding diathesis attributed to storage-pool deficient (SPD) platlets. Patients have platelet aggregation and release abnormalities. In addition, low levels of plasma von Willebrand factor (vWF) antigen in some HPS patients have been associated with a greater bleeding tendency than would be predicted from either condition alone, Other HPS patients have severe bleeding despite normal levels of plasma vWF, suggesting that at least one additional factor is responsible for their bleeding diathesis. Because platelet vWF levels have been well correlated with clinical bleeding times in patients with von Willebrand's disease, we have measured the platelet vWF activity and antigen levels in 30 HPS patients and have attempted to correlate their clinical bleeding with these values. The platelet vWF activity levels in patients was significantly lower than that of normal subjects (P < 0.0001). The patients as a group also had slightly lower values of plasma vWF activity when compared with normals (P similar to 0.03). In 11 of the HPS patients, the multimeric structure of plasma vWF showed a decrease in the high molecular weight multimers and an increase in the low molecular weight multimers. In correlating the platelet and plasma vWF values with the bleeding histories, we were not able to show a predictable relationship in the majority of the patients. Am. J. Hematol. 59:115-120, 1998. (C) 1998 Wiley-Liss, Inc. C1 NICHHD, NIH, Bethesda, MD 20892 USA. NIH, Warren Grant Magnuson Clin Ctr, Hematol Serv, Bethesda, MD 20892 USA. RP Rick, ME (reprint author), NICHHD, NIH, 10 Ctr Dr,Bldg 10,Room 2C-390, Bethesda, MD 20892 USA. NR 20 TC 8 Z9 8 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD OCT PY 1998 VL 59 IS 2 BP 115 EP 120 DI 10.1002/(SICI)1096-8652(199810)59:2<115::AID-AJH3>3.0.CO;2-0 PG 6 WC Hematology SC Hematology GA 122QM UT WOS:000076083000003 PM 9766795 ER PT J AU Rioux, JD Stone, VA Daly, MJ Cargill, M Green, T Nguyen, H Nutman, T Zimmerman, PA Tucker, MA Hudson, T Goldstein, AM Lander, E Lin, AY AF Rioux, JD Stone, VA Daly, MJ Cargill, M Green, T Nguyen, H Nutman, T Zimmerman, PA Tucker, MA Hudson, T Goldstein, AM Lander, E Lin, AY TI Familial eosinophilia maps to the cytokine gene cluster on human chromosomal region 5q31-q33 SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID COLONY-STIMULATING FACTOR; HUMAN INTERLEUKIN-5 GENE; IDIOPATHIC HYPEREOSINOPHILIC SYNDROME; MULTILOCUS LINKAGE ANALYSIS; CORE-BINDING-FACTOR; MESSENGER-RNA; 3T3 FIBROBLASTS; HUMAN GENOME; EXPRESSION; PROMOTER AB Familial eosinophilia (FE) is an autosomal dominant disorder characterized by peripheral hypereosinophilia of unidentifiable cause with or without other organ involvement. To localize the gene for FE, we performed a genomewide search in a large U.S. kindred, using 312 different polymorphic markers. Seventeen affected subjects, 28 unaffected bloodline relatives, and 8 spouses were genotyped. The initial linkage results from the genome scan provided evidence for linkage on chromosome 5q31-q33. Additional genotyping of genetic markers located in this specific region demonstrated significant evidence that the FE locus is situated between the chromosome 5q markers D5S642 and D5S816 (multipoint LOD score of 6.49). Notably, this region contains the cytokine gene cluster, which includes three genes-namely, those for interleukin (IL)-3, IL-5, and granulocyte/macrophage colony-stimulating factor (GM-CSF)-whose products play important roles in the development and proliferation of eosinophils. These three cytokine genes were screened for potential disease-specific mutations by resequencing of a subgroup of individuals from the present kindred. No functional sequence polymorphisms were found within the promoter, the exons, or the introns of any of these genes or within the IL-3/CM-CSF enhancer, suggesting that the primary defect in FE is not caused by a mutation in any one of these genes but, rather, is caused by another gene in the area. C1 MIT, Whitehead Inst, Ctr Genome Res, Cambridge, MA 02139 USA. NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. NCI, Genet Epidemiol Branch, Bethesda, MD 20892 USA. RP Rioux, JD (reprint author), MIT, Whitehead Inst, Ctr Genome Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA. RI Tucker, Margaret/B-4297-2015; Rioux, John/A-9599-2015 OI Rioux, John/0000-0001-7560-8326 NR 55 TC 85 Z9 87 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1998 VL 63 IS 4 BP 1086 EP 1094 DI 10.1086/302053 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 131LP UT WOS:000076577800022 PM 9758611 ER PT J AU Hanson, RL Ehm, MG Pettitt, DJ Prochazka, M Thompson, DB Timberlake, D Foroud, T Kobes, S Baler, L Burns, DK Almasy, L Blangero, J Garvey, WT Bennett, PH Knowler, WC AF Hanson, RL Ehm, MG Pettitt, DJ Prochazka, M Thompson, DB Timberlake, D Foroud, T Kobes, S Baler, L Burns, DK Almasy, L Blangero, J Garvey, WT Bennett, PH Knowler, WC TI An autosomal genomic scan for loci linked to type II diabetes mellitus and body-mass index in Pima Indians SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID ASSESSING GENETIC-LINKAGE; QUANTITATIVE TRAIT LOCI; SIB-PAIR ANALYSIS; COMPONENTS MODELS; PEDIGREE ANALYSIS; WIDE SEARCH; SUSCEPTIBILITY; OBESITY; NIDDM; EXTENSIONS AB Genetic factors influence the development of type II diabetes mellitus, but genetic loci for the most common forms of diabetes have not been identified. A genomic scan was conducted to identify loci linked to diabetes and body-mass index (BMI) in Pima Indians, a Native American population with a high prevalence of type II diabetes. Among 264 nuclear families containing 966 siblings, 516 autosomal markers with a median distance between adjacent markers of 6.4 cM were genotyped. Variance-components methods were used to test for linkage with an age-adjusted diabetes score and with BMI. In multipoint analyses, the strongest evidence for linkage with age-adjusted diabetes (LOD = 1.7) was on chromosome 11q, in the region that was also linked most strongly with BMI (LOD = 3.6). Bivariate linkage analyses strongly rejected both the null hypothesis of no linkage with either trait and the null hypothesis of no contribution of the locus to the covariation among the two traits. Sib-pair analyses suggest additional potential diabetes-susceptibility loci on chromosomes Iq and 7q. C1 NIDDKD, Diabet & Arthritis Epidemiol Sect, NIH, Phoenix Epidemiol & Clin Res Branch, Phoenix, AZ 85014 USA. Glaxo Wellcome Inc, Res Triangle Pk, NC 27709 USA. Sequana Therapeut Inc, Dept Stat Genet, La Jolla, CA USA. Indiana Univ, Sch Med, Dept Med Genet, Indianapolis, IN USA. SW Fdn Biomed Res, Dept Genet, San Antonio, TX USA. Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP Hanson, RL (reprint author), NIDDKD, Diabet & Arthritis Epidemiol Sect, NIH, Phoenix Epidemiol & Clin Res Branch, 1550 E Indian Sch Rd, Phoenix, AZ 85014 USA. RI Baier, Leslie/F-9008-2013; Hanson, Robert/O-3238-2015 OI Hanson, Robert/0000-0002-4252-7068 FU NCRR NIH HHS [1P41 RR03655]; NIDDK NIH HHS [DK-47461]; NIGMS NIH HHS [GM-18897] NR 55 TC 357 Z9 368 U1 0 U2 10 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1998 VL 63 IS 4 BP 1130 EP 1138 DI 10.1086/302061 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 131LP UT WOS:000076577800027 PM 9758619 ER PT J AU Loeben, GL Marteau, TM Wilfond, BS AF Loeben, GL Marteau, TM Wilfond, BS TI Mixed messages: Presentation of information in cystic fibrosis screening pamphlets SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID PRIMARY-CARE; POPULATION; PRACTITIONERS; PREFERENCES; CARRIERS; STEPWISE; IMPACT AB Written pamphlets are an important source of information for individuals deciding whether to undergo carrier testing for cystic fibrosis (CF). Adequate understanding of the condition and reproductive options following the diagnosis of a fetus with CF are critical to informed decision making. The information given about CF and reproductive options in 28 pamphlets about carrier testing, from commercial and noncommercial organizations in the United States and the United Kingdom, aimed at prenatal and other populations, was assessed. The amount of information provided about CF showed a range of 1-37 sentences (median 6.5), with most being relatively neutral and with a minority conveying a positive or a negative image. Positive sentences were less common in British, U.S. commercial, and prenatal pamphlets. Statements about life expectancy also varied considerably, both in the ages provided and in the degree of optimism conveyed. In addition, the pamphlets varied in the amount of information they provided about reproductive options following the diagnosis of a fetus with CE Abortion was mentioned in just 15 pamphlets, more often in the United Kingdom than in the United States and more frequently in pamphlets from noncommercial than in those from commercial organizations. Wide variation in the descriptions of CF and the reproductive options presented raises concerns about the extent to which any one pamphlet may present balanced information. The choices about what information to include in educational materials need to be explicitly considered on the basis of the message intended to be sent. C1 Univ Penn, Ctr Bioeth, Philadelphia, PA 19104 USA. Univ London, United Med & Dent Sch Guys & St Thomas Hosp, Psychol & Genet Res Grp, London, England. Univ Arizona, Dept Pediat, Tucson, AZ USA. RP Wilfond, BS (reprint author), NHGRI, 9000 Rockville Pike,Bldg 10,Room 1C123, Bethesda, MD 20892 USA. EM Wilfond@nhgri.nih.gov OI Marteau, Theresa/0000-0003-3025-1129 FU AHRQ HHS [R29 HS08570]; Wellcome Trust NR 34 TC 27 Z9 27 U1 1 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1998 VL 63 IS 4 BP 1181 EP 1189 DI 10.1086/302036 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 131LP UT WOS:000076577800032 PM 9758594 ER PT J AU Bryan, RN Barker, P AF Bryan, RN Barker, P TI A new clinical application of MR spectroscopy in hepatic encephalopathy SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Editorial Material ID RESONANCE C1 NIH, Ctr Clin, Bethesda, MD 20892 USA. Johns Hopkins Univ, Baltimore, MD USA. RP Bryan, RN (reprint author), NIH, Ctr Clin, Bethesda, MD 20892 USA. RI Bryan, R. Nick/P-1661-2014 NR 2 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD OCT PY 1998 VL 19 IS 9 BP 1593 EP 1594 PG 2 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 129FF UT WOS:000076452600003 PM 9802476 ER PT J AU Richert, ND Ostuni, JL Bash, CN Duyn, JH McFarland, HF Frank, JA AF Richert, ND Ostuni, JL Bash, CN Duyn, JH McFarland, HF Frank, JA TI Serial whole-brain magnetization transfer imaging in patients with relapsing-remitting multiple sclerosis at baseline and during treatment with interferon beta-1b SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article; Proceedings Paper CT 35th Annual Meeting of the American-Society-of-Neuroradiology CY MAY, 1997 CL TORONTO, CANADA SP Amer Soc Neuroradiol ID APPEARING WHITE-MATTER; PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; TRANSFER RATIO; HISTOPATHOLOGIC CORRELATION; MICROSCOPIC DISEASE; ENHANCING LESIONS; TRANSFER CONTRAST; DOSE GADOLINIUM; MR-IMAGES; SPECTROSCOPY AB BACKGROUND AND PURPOSE: To determine whether occult disease fluctuates with macroscopic lesions during the natural history of multiple sclerosis (MS) and whether therapeutic interventions affect occult disease, we performed serial monthly magnetization transfer (MT) imaging in patients with relapsing-remitting MS in a crossover trial with interferon beta-1b. METHODS: Serial whole-brain magnetization transfer ratios (MTRs) in eight patients with relapsing-remitting MS and in four control subjects were plotted as normalized histograms, and MTR parameters were compared with contrast-enhancing lesions and bulk white matter lesion load. RESULTS: In patients with relapsing-remitting MS, the histographic peak of 0.25 +/- 0.01 and the histographic mean of 0.21 +/- 0.01 were statistically lower than corresponding values in control subjects, in whom the histographic peak was 0.27 +/- 0.01 and the histographic mean was 0.23 +/- 0.01. When histograms (with MTRs ranging from 0.0 to 0.5) were analyzed by quartiles (quartile 1 to quartile 4) based on histographic area, voxels with low MTRs in quartile 1 (0 to 0.12) increased during the baseline period and corresponded to bulk white matter lesion load. Interferon beta-1b reduced enhancing lesions by 91% and mean bulk white matter lesion load by 15%, but had no effect on MTR in this patient cohort. CONCLUSION: Occult disease in normal-appearing white matter of patients with relapsing-remitting MS measured by MTR parallels the waxing and waning pattern of enhancing lesions and bulk white matter lesion load during the baseline period. MTR is not altered by interferon beta-1b, which raises the possibility of ongoing disease in normal-appearing white matter (not detected by conventional MR sequences). C1 NINDS, Ctr Clin, Lab Diagnost Radiol Res, NIH, Bethesda, MD 20892 USA. NINDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. Childrens Natl Med Ctr, Dept Diagnost Imaging & Radiol, Washington, DC 20010 USA. RP Frank, JA (reprint author), NINDS, Ctr Clin, Lab Diagnost Radiol Res, NIH, Bldg 10,Room B1N256,10 Ctr Dr, Bethesda, MD 20892 USA. RI Duyn, Jozef/F-2483-2010 NR 35 TC 60 Z9 60 U1 0 U2 0 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD OCT PY 1998 VL 19 IS 9 BP 1705 EP 1713 PG 9 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 129FF UT WOS:000076452600021 PM 9802494 ER PT J AU Caritis, S Sibai, B Hauth, J Lindheimer, M VanDorsten, P Klebanoff, M Thom, E Landon, M Paul, R Miodovnik, M Meis, P Thurnau, G Dombrowski, M McNellis, D Roberts, J AF Caritis, S Sibai, B Hauth, J Lindheimer, M VanDorsten, P Klebanoff, M Thom, E Landon, M Paul, R Miodovnik, M Meis, P Thurnau, G Dombrowski, M McNellis, D Roberts, J CA Natl Inst Child Hlth Human Dev Network Maternal TI Predictors of pre-eclampsia in women at high risk SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 18th Annual Meeting of the Society-of-Perinatal-Obstetricians CY FEB 02-07, 1998 CL MIAMI, FLORIDA SP Soc Perinatal Obstetricians DE pre-eclampsia; hypertensive disorders; risk factors; mean arterial pressure; pregnancy ID LOW-DOSE ASPIRIN; PREGNANT-WOMEN; PREECLAMPSIA; PREVENTION; HYPERTENSION; PRESSURE; HEALTHY; GROWTH AB OBJECTIVE: We assessed several variables as predictors for pre-eclampsia risk in a group of women at high risk. STUDY DESIGN: We studied 2503 women with either diabetes mellitus, chronic hypertension, multifetal gestation, or pre-eclampsia in a previous pregnancy who participated in a multicenter study comparing aspirin and placebo in preventing pre-eclampsia. We evaluated multiple variables for predicting pre-eclampsia risk with use of univariate and multivariable analysis. RESULTS: Parity and mean arterial pressure at randomization were most predictive of pre-eclampsia risk. The risk was 8% with a mean arterial pressure at enrollment of <75 mm Hg versus 27% with a mean arterial pressure >85 mm Hg (relative risk and 95% confidence interval 3.3 [2.4 to 4.4]). The risk of pre-eclampsia was 26% in nulliparous patients versus 17% in parous subjects (relative risk and 95% confidence interval 1.5 [1.3-1.8]). CONCLUSIONS: The finding that second-trimester mean arterial pressure affects pre-eclampsia risk suggests that the pathophysiologic process of preeclampsia is initiated before that time. C1 NICHHD, Network Maternal Fetal Med Unit, Bethesda, MD 20892 USA. RP Caritis, S (reprint author), Univ Pittsburgh, Magee Womens Hosp, Sch Med, Dept Obstet & Gynecol, 300 Halket St, Pittsburgh, PA 15213 USA. OI caritis, steve/0000-0002-2169-0712 FU NICHD NIH HHS [HD19897, HD21410, HD21434] NR 19 TC 74 Z9 75 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD OCT PY 1998 VL 179 IS 4 BP 946 EP 951 DI 10.1016/S0002-9378(98)70194-2 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 129RC UT WOS:000076475900021 PM 9790376 ER PT J AU Joffe, GM Esterlitz, JR Levine, RJ Clemens, JD Ewell, MG Sibai, BM Catalano, PM AF Joffe, GM Esterlitz, JR Levine, RJ Clemens, JD Ewell, MG Sibai, BM Catalano, PM CA Calcium Preeclampsia Prevention CPEP Study TI The relationship between abnormal glucose tolerance and hypertensive disorders of pregnancy in healthy nulliparous women SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE gestational diabetes; glucose intolerance; glucose tolerance; hypertension; insulin resistance; preeclampsia; pregnancy; syndrome X ID INSULIN-RESISTANCE; PREECLAMPSIA; HYPERINSULINEMIA; INTOLERANCE; CALCIUM; TRIAL AB OBJECTIVE: The study's aim was to determine whether healthy nulliparous women with abnormal glucose tolerance during pregnancy are at increased risk for development of pregnancy-associated hypertension or preeclampsia. STUDY DESIGN: A series of 4589 healthy nulliparous women from 5 university centers were evaluated prospectively to determine whether calcium supplementation would prevent preeclampsia. Pregnancy-associated hypertension was a diastolic blood pressure greater than or equal to 90 mm Hg on 2 occasions 4 hours to 1 week apart. Pregnancy-associated proteinuria was proteinuria greater than or equal to 1+ by dipstick testing on 2 occasions 4 hours to 1 week apart, proteinuria;greater than or equal to 300 mg/24 h, a protein to creatinine ratio of greater than or equal to 0.35, or a single dipstick measurement of greater than or equal to 2+. Preeclampsia was defined as pregnancy-associated hypertension and pregnancy-associated proteinuria documented within 7 days of each other. Normal glucose tolerance was a plasma glucose level <140 mg/dL 1 hour after a 50-g oral glucose challenge. Abnormal glucose tolerance was a plasma glucose level greater than or equal to 140 mg/dL 1 hour after a 50-g oral glucose challenge followed by a 9-hour 100-g oral glucose tolerance test yielding <2 abnormal values. Gestational diabetes mellitus was a plasma glucose level greater than or equal to 200 mg/dL 1 hour after a 50-g oral glucose challenge in the absence of an oral glucose tolerance test or greater than or equal to 2 abnormal plasma glucose values in a 3-hour 100-g oral glucose tolerance test (greater than or equal to 105 mg/dL fasting, greater than or equal to 190 mg/dL at 1 hour, greater than or equal to 165 mg/dL at 2 hours, or greater than or equal to 145 mg/dL at 3 hours). For purposes of this study women with preeclampsia were excluded from the category of pregnancy-associated hypertension. RESULTS: Calcium supplementation did not prevent pregnancy-associated hypertension or preeclampsia. Of 3689 women with complete glucose testing data, 227 (6%) had abnormal glucose tolerance and 81 (2%) had gestational diabetes mellitus. Compared with women with normal glucose tolerance, women with abnormal glucose tolerance were significantly older, had greater body mass index,and were more likely to be white non-Hispanic, to smoke, and to have private medical insurance. Among women with gestational diabetes mellitus, after adjustment for clinical center the relative risks of preeclampsia and of all hypertensive disorders were increased (relative risk 1.67, 95% confidence interval 0.92-3.05, and relative risk 1.54, 95% confidence interval 1.28-2.11, respectively). Risk ratios were not substantially reduced after further adjustment for race and body mass index (odds ratios 1.41 and 1.48, respectively). Even within the normal range, multivariate analysis demonstrated that the level of plasma glucose 1 hour after a 50-g oral glucose challenge was an important predictor of preeclampsia. CONCLUSION: Even within the normal range, the level of plasma glucose 1 hour after a 50-g oral glucose challenge was positively correlated with the likelihood of preeclampsia. Women with gestational diabetes mellitus were at increased risk for hypertensive disorders during pregnancy after adjustment for clinical center, race, and body mass index, although the increase was not statistically significant. These findings suggest that insulin resistance may play a role in the pathogenesis of the hypertensive disorders of pregnancy. C1 Univ New Mexico, Hlth Sci Ctr, Dept Obstet & Gynecol, Albuquerque, NM 87131 USA. Emmes Corp, Potomac, MD USA. NICHHD, Div Epidemiol Stat & Prevent Res, NIH, Bethesda, MD 20892 USA. Univ Tennessee, Coll Med, Dept Obstet & Gynecol, Knoxville, TN 37996 USA. Case Western Reserve Univ, Metrohlth Med Ctr, Dept Obstet & Gynecol, Cleveland, OH 44106 USA. RP Joffe, GM (reprint author), Lovelace Med Ctr, Dept Obstet & Gynecol, 5400 Gibson SE, Albuquerque, NM 87108 USA. NR 14 TC 125 Z9 128 U1 1 U2 6 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD OCT PY 1998 VL 179 IS 4 BP 1032 EP 1037 DI 10.1016/S0002-9378(98)70210-8 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 129RC UT WOS:000076475900038 PM 9790393 ER PT J AU Zhao, JL Jia, LJ Sui, RF Ellwein, LB AF Zhao, JL Jia, LJ Sui, RF Ellwein, LB TI Prevalence of blindness and cataract surgery in Shunyi County, China SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article AB PURPOSE: To estimate the prevalence of blindness and cataract surgery among older adults in rural China. METHODS: Cluster sampling was used in randomly selecting men and women aged 50 years or older for visual acuity testing and an eye examination in 28 villages in Shunyi County. The survey, which was carried out in the fall of 1996, was preceded by a pilot study in which operational methods were refined and quality assurance evaluations carried out. RESULTS: Of 5,555 enumerated subjects greater than or equal to 50 years of age, 91.5% (5,084 /5,555) were examined and 90.9% (5,052/5,555) were tested for visual acuity. In this population, 2.8% (139/5,052) were blind, defined as presenting visual acuity less than 6/60 in both eyes. Blindness was associated with older age and female sex. Cataract was the principal cause of blindness in at least one eye in 48.2% (67/139) of blind people. The ratio of those blind from cataract who were operated on to the those who could have been operated on, cataract surgical coverage, was estimated to be 47.8% (54/113), Cataract surgery was associated with younger age but not sex or education. CONCLUSIONS: Blindness, particularly blindness related to cataract, continues to be a significant problem among the elderly, especially women, in this population-based sample of rural Chinese. Despite an active eye-care program in Shunyi County, only half of those who might benefit from cataract surgery are receiving it. (Am J Ophthalmol 1998; 126:506-514. (C) 1998 by Elsevier Science Inc. All rights reserved.). C1 NEI, NIH, Bethesda, MD 20892 USA. Peking Union Med Coll Hosp, Dept Ophthalmol, Beijing, Peoples R China. RP Ellwein, LB (reprint author), NEI, NIH, 31 Ctr Dr, Bethesda, MD 20892 USA. FU NEI NIH HHS [N01-EY-2103] NR 10 TC 71 Z9 96 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD OCT PY 1998 VL 126 IS 4 BP 506 EP 514 DI 10.1016/S0002-9394(98)00275-X PG 9 WC Ophthalmology SC Ophthalmology GA 126WA UT WOS:000076316500003 PM 9780095 ER PT J AU Zhao, JL Sui, RF Jia, LJ Fletcher, AE Ellwein, LB AF Zhao, JL Sui, RF Jia, LJ Fletcher, AE Ellwein, LB TI Visual acuity and quality of life outcomes in patients with cataract in Shunyi County, China SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article AB PURPOSE: To measure visual acuity and vision-related quality of life in individuals in rural China operated on for cataract. METHODS: Five thousand fifty-two persons age 50 years and older, 90.9% (5,052/5,555) of a randomly selected population in Shunyi County, were examined in the fall of 1996, Visual functioning and quality of life questionnaires were administered to those with presenting visual acuity less than 6/60 in either eye and to those who were aphakic or pseudophakic. RESULTS: Of the 87 individuals operated on for cataract, 12% (10/87) had presenting visual acuity of 6/18 or more in both eyes, and 24.1% (21/87) had less than 6/60, Twenty-five percent (29/116) of the 116 eyes operated on for cataract had presenting visual acuity of 6/18 or more, and 44.8% (52/116) had less than 6/60, Aphakic cases without glasses and uncorrectable aphakia attributable to surgical complications were common, In a multivariate regression model, including time period of surgery, hospital type, and surgical procedure, only pseudophakia was associated with better outcomes (P = .05), On a scale from O (maximum problems) to 100 (no problems), the mean visual functioning score (+/-SD) for the operated-on population was 61.9 +/- 30.0, and 71.0 +/- 31.8 for the quality of life questionnaire, These scores were comparable to those of the unoperated-on population with moderate bilateral blindness (<6/60 to 13/60 in the better eye). Visual functioning and quality of life scores were closely correlated with visual acuity in operated on (r = 0.64 and r = 0.61, respectively) and unoperated-on populations (r = 0.68 and r = 0.59, respectively). CONCLUSIONS: Both clinical and patient-reported cataract surgery outcomes are below what should be achievable. Improvement in outcomes must be given greater emphasis if the potential of cataract surgery in restoring sight is to be realized. (Am J Ophthalmol 1998;126:515-523, (C) 1998 by Elsevier Science Inc. All rights reserved.). C1 NEI, NIH, Bethesda, MD 20892 USA. Peking Union Med Coll Hosp, Dept Ophthalmol, Beijing, Peoples R China. London Sch Hyg & Trop Med, Dept Epidemiol & Populat Hlth, London, England. RP Ellwein, LB (reprint author), NEI, NIH, 31 Ctr Dr, Bethesda, MD 20892 USA. FU NEI NIH HHS [N01-EY-2103] NR 9 TC 95 Z9 123 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD OCT PY 1998 VL 126 IS 4 BP 515 EP 523 DI 10.1016/S0002-9394(98)00274-8 PG 9 WC Ophthalmology SC Ophthalmology GA 126WA UT WOS:000076316500004 PM 9780096 ER PT J AU Sasaki, N Fukatsu, R Tsuzuki, K Hayashi, Y Yoshida, T Fujii, N Koike, T Wakayama, I Yanagihara, R Garruto, R Amano, N Makita, Z AF Sasaki, N Fukatsu, R Tsuzuki, K Hayashi, Y Yoshida, T Fujii, N Koike, T Wakayama, I Yanagihara, R Garruto, R Amano, N Makita, Z TI Advanced glycation end products in Alzheimer's disease and other neurodegenerative diseases SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID AMYLOID PRECURSOR PROTEIN; ADVANCED GLYCOSYLATION; MAILLARD REACTION; TAU; LESIONS; BRAINS; STRESS; INVIVO; CELLS; AGE AB Advanced glycation end products (AGEs) have been implicated in the chronic complications of diabetes mellitus and have been reported to play an important role in the pathogenesis of Alzheimer's disease. In this study, we examined the immunohistochemical localization of AGEs, amyloid beta protein (A beta), apolipoprotein E (ApoE), and tau protein in senile plaques, neurofibrillary tangles (NFTs), and cerebral amyloid angiopathy (CAA) in Alzheimer's disease and other neurodegenerative diseases (progressive supranuclear palsy, Pick's disease, and Guamanian amyotrophic lateral sclerosis/Parkinsonism-dementia complex). In most senile plaques (including diffuse plaques) and CAA from Alzheimer's brains, AGE and ApoE were observed together. However, approximately 5% of plaques were AGE positive but AP negative, and the vessels without CAA often showed AGE immunoreactivity, In Alzheimer's disease, AGEs were mainly present in intracellular NFTs, whereas ApoE was mainly present in extracellular NFTs, Pick's bodies in Pick's disease and granulovacuolar degeneration in various neurodegenerative diseases were also AGE positive. In non-Alzheimer neurodegenerative diseases, senile plaques and NFTs showed similar findings to those in Alzheimer's disease. These results suggest that AGE may contribute to eventual neuronal dysfunction and death as an important factor in the progression of various neurodegenerative diseases, including Alzheimer's disease. C1 Sapporo Med Univ, Dept Neuropsychiat, Chuo Ku, Sapporo, Hokkaido 0608543, Japan. Sapporo Med Univ, Dept Microbiol, Sapporo, Hokkaido, Japan. Hokkaido Univ, Dept Med 2, Sapporo, Hokkaido 060, Japan. Kansai Coll Oriental Med, Osaka, Japan. Univ Tokyo, Dept Neuropsychiat, Tokyo, Japan. NINDS, Cent Nervous Syst Studies Lab, NIH, Bethesda, MD 20892 USA. RP Sasaki, N (reprint author), Sapporo Med Univ, Dept Neuropsychiat, Chuo Ku, South 1,West 16, Sapporo, Hokkaido 0608543, Japan. NR 32 TC 217 Z9 222 U1 0 U2 18 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD OCT PY 1998 VL 153 IS 4 BP 1149 EP 1155 DI 10.1016/S0002-9440(10)65659-3 PG 7 WC Pathology SC Pathology GA 127RT UT WOS:000076364900016 PM 9777946 ER PT J AU Giaretti, W Rapallo, A Geido, E Sciutto, A Merlo, F Risio, M Rossini, FP AF Giaretti, W Rapallo, A Geido, E Sciutto, A Merlo, F Risio, M Rossini, FP TI Specific K-ras2 mutations in human sporadic colorectal adenomas are associated with DNA near-diploid aneuploidy and inhibition of proliferation SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID ABERRANT CRYPT FOCI; K-RAS ONCOGENE; FLOW-CYTOMETRY; GENE-MUTATIONS; HA-RAS; NEOPLASTIC PROGRESSION; BARRETTS-ESOPHAGUS; TUMOR PROGRESSION; T TRANSVERSIONS; NIH3T3 CELLS AB Recent studies indicate that p21ras proteins mediate their multiple cell functions through interactions with multiple effecters and that the number of new effecters is growing. We recently reported that K-ras2 mutations in human colorectal adenomas were associated with chromosome instability and proliferation changes. In the present study, we extend these previous observations. Hereditary and multiple (n greater than or equal to 5) adenomas and adenomas with early cancer were excluded. Dysplasia was moderate in 91 cases and high in 25, and the median adenoma size was 1.5 cm, K-ras2 spectrum analysis was done by sequence-specific oligonucleotide hybridization using nuclear suspensions provided by analysis and sorting of multiparameter now cytometry. In particular, tissue inflammatory cells were separated for DNA diploid tumors, whereas DNA aneuploid epithelial subclones were analyzed separately. K-ras2 mutations and DNA aneuploidy were both detected in 29 of 116 (25%) cases. DNA aneuploid index was in the near-diploid region in the majority of cases. DNA aneuploidy was strongly associated with G-->C/T transversions, An association was also found between low S-phase values and G-->A transitions. These findings were confirmed using multivariate logistic regression analysis to account for the effects of size, dysplasia, site, type, age, and sex. These data suggest that specific K-ras2 mutations in a subgroup of human sporadic colorectal adenomas play a role in chromosome instability and, contrary to expectations, are associated with inhibition of proliferation. C1 Natl Inst Canc Res & Treatment, Lab Biophys Cytometry, Genoa, Italy. Natl Inst Canc Res & Treatment, Dept Environm Epidemiol & Biostat, Genoa, Italy. S Giovanni Vecchio Hosp, Dept Pathol, Turin, Italy. S Giovanni Vecchio Hosp, Dept Gastroenterol, Turin, Italy. RP Giaretti, W (reprint author), Natl Canc Inst, Lab Biophys Cytometry, Viale R Benzi 10, I-16132 Genoa, Italy. EM giaretti@hp380.ist.unige.it NR 74 TC 32 Z9 32 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD OCT PY 1998 VL 153 IS 4 BP 1201 EP 1209 DI 10.1016/S0002-9440(10)65664-7 PG 9 WC Pathology SC Pathology GA 127RT UT WOS:000076364900021 PM 9777951 ER PT J AU Makino, S Nishiyama, M Asaba, K Gold, PW Hashimoto, K AF Makino, S Nishiyama, M Asaba, K Gold, PW Hashimoto, K TI Altered expression of type 2 CRH receptor mRNA in the VMH by glucocorticoids and starvation SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Article DE corticotropin-releasing hormone; ventromedial hypothalamus; insulin; leptin ID CORTICOTROPIN-RELEASING FACTOR; MESSENGER-RIBONUCLEIC-ACID; HYPOTHALAMIC PARAVENTRICULAR NUCLEUS; RAT-BRAIN; WEIGHT-LOSS; FOOD-INTAKE; HORMONE; STRESS; RNA; LEPTIN AB In the rat, high-dose corticosterone (Cort) administration, the hypercortisolism of starvation, and adrenalectomy are all associated with decreased food intake and weight loss. We report here a study of the effects of high-dose Cort administration, starvation, and adrenalectomy on two peripheral hormones known to influence food intake and energy use, insulin and leptin. We also studied the impact of these interventions on the levels of type 2 corticotropin-releasing hormone receptor (CRHR-2) mRNA in the hypothalamic paraventricular nucleus (PVN) and ventromedial hypothalamus (VMH). The VMH is classically referred to as the satiety center because electrical stimulation of the VMH leads to inhibition of food intake, whereas CRHR-8 are thought to transduce the profound anorexogenic effects of CRH or its related peptide urocortin. Starvation and adrenalectomy each lowered plasma insulin and leptin levels and were associated with decrements in CRHR-8 mRNA levels in the VMH. Cort administration increased plasma leptin levels profoundly, as well as plasma insulin levels and the levels of VMH CRHR-8 mRNA. Under all experimental conditions, a positive correlation was seen between plasma leptin levels and VMH CRHR-2 mRNA. These data suggest that decreased food intake and weight loss after high-dose Cort administration at least partially depend on the profound impact of Cort on plasma leptin secretion in the rat; they suggest, moreover, an additional mechanism for the satiety-inducing effects of leptin, namely increasing CRHR-8 in the VMH. The concordance of a fall in plasma insulin and leptin levels with the fall in VMH CRHR-8 mRNA levels further supports the idea that compensatory responses during starvation and adrenalectomy include not only the disinhibiting effects of reduced insulin and leptin levels on appetite through already-described mechanisms but also via an effect of leptin on VMH CRHR-2. Neither Cort administration, starvation, nor adrenalectomy influenced the levels of CRHR-2 mRNA in the PVN, suggesting that these receptors are differentially regulated in different hypothalamic regions. C1 Kochi Med Sch, Dept Internal Med 2, Nanko Ku, Kochi 783, Japan. NIMH, Clin Neuroendocrinol Branch, Bethesda, MD 20892 USA. RP Makino, S (reprint author), Kochi Med Sch, Dept Internal Med 2, Nanko Ku, Okoh Cho, Kochi 783, Japan. NR 38 TC 62 Z9 62 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6119 J9 AM J PHYSIOL-REG I JI Am. J. Physiol.-Regul. Integr. Comp. Physiol. PD OCT PY 1998 VL 275 IS 4 BP R1138 EP R1145 PG 8 WC Physiology SC Physiology GA 125KB UT WOS:000076235800025 PM 9756544 ER PT J AU Pacak, K Palkovits, M Yadid, G Kvetnansky, R Kopin, IJ Goldstein, DS AF Pacak, K Palkovits, M Yadid, G Kvetnansky, R Kopin, IJ Goldstein, DS TI Heterogeneous neurochemical responses to different stressors: a test of Selye's doctrine of nonspecificity SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Article DE ACTH; norepinephrine; epinephrine ID SYMPATHETIC-NERVE ACTIVITY; IMMOBILIZATION STRESS; ELECTROCHEMICAL DETECTION; BEHAVIORAL HOMEOSTASIS; LIQUID-CHROMATOGRAPHY; PLASMA-LEVELS; CATECHOLAMINES; RATS; ACTIVATION; RELEASE AB Selye defined stress as the nonspecific response of the body to any demand. Stressors elicit both pituitary-adrenocortical and sympathoadrenomedullary responses. One can test Selye's concept by comparing magnitudes of responses at different stress intensities and assuming that the magnitudes vary with stress intensity, with the prediction that, at different stress intensities, ratios of increments neuroendocrine responses should be the same. We measured arterial plasma ACTH, norepinephrine, and epinephrine in conscious rats after hemorrhage, intravenous insulin, subctaneous formaldehyde solution, cold, or immobilization. Relative to ACTH increments, cold evoked large norepinephrine responses, insulin large epinephrine responses, and hemorrhage small norepinephrine and epinephrine responses, whereas immobilization elicited large increases in levels of all three compounds. The ACTH response to 25% hemorrhage exceeded five times that to 10%, and the epinephrine response to 25% hemorrhage was two times that to 10%. The ACTH response to 4% formaldehyde solution was two times that to 1%, and the epinephrine response to 4% formaldehyde solution exceeded four times that to 1%. These results are inconsistent with Selye's doctrine of nonspecificity and the existence of a unitary "stress syndrome," and they are more consistent with the concept that each stressor has its own central neurochemical and peripheral neuroendocrine "signature." C1 NINDS, Clin Neurosci Branch, NIH, Bethesda, MD 20892 USA. NIMH, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. Washington Hosp Ctr, Dept Med, Washington, DC 20010 USA. Bar Ilan Univ, Dept Life Sci, IL-52100 Ramat Gan, Israel. Slovak Acad Sci, Inst Expt Endocrinol, Bratislava 81000, Slovakia. RP Goldstein, DS (reprint author), NINDS, Clin Neurosci Branch, NIH, 9000 Rockville Pike,Bldg 10,Rm 6N252, Bethesda, MD 20892 USA. RI Palkovits, Miklos/F-2707-2013 NR 37 TC 121 Z9 122 U1 0 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6119 J9 AM J PHYSIOL-REG I JI Am. J. Physiol.-Regul. Integr. Comp. Physiol. PD OCT PY 1998 VL 275 IS 4 BP R1247 EP R1255 PG 9 WC Physiology SC Physiology GA 125KB UT WOS:000076235800038 PM 9756557 ER PT J AU Zhong, Z Arteel, GE Connor, HD Yin, M Frankenberg, MV Stachlewitz, RF Raleigh, JA Mason, RP Thurman, RG AF Zhong, Z Arteel, GE Connor, HD Yin, M Frankenberg, MV Stachlewitz, RF Raleigh, JA Mason, RP Thurman, RG TI Cyclosporin A increases hypoxia and free radical production in rat kidneys: prevention by dietary glycine SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE reperfusion; hypoxia marker ID DEPLETED PROXIMAL TUBULES; CELL INJURY; INDUCED NEPHROTOXICITY; LIPID-PEROXIDATION; CALCIUM; BINDING; POLYPHOSPHOINOSITIDES; VASOCONSTRICTION; HEMODYNAMICS; MISONIDAZOLE AB The major side effect of cyclosporin A is severe nephrotoxicity. It is likely that cyclosporin A causes vasoconstriction leading to hypoxia-reperfusion injury; therefore, these experiments were designed to attempt to obtain physical evidence for hypoxia and free radical production in kidney following cyclosporin A. Rats were treated daily with cyclosporin A (25 mg/kg ig) for 5 days, and pimonidazole, a hypoxia marker, was injected 2 h after the last dose of cyclosporin A. A dose of alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone (4-POBN) was injected 3 h after cyclosporin A to trap free radicals. Cyclosporin A doubled serum creatinine and decreased glomerular filtration rates by 65% as expected. Pimonidazole adduct binding in the kidney was increased nearly threefold by cyclosporin A, providing physical evidence for tissue hypoxia. Moreover, cyclosporin A increased 4-POBN/radical adducts nearly sixfold in the urine but did not alter levels in the serum. Glycine, which causes vasodilatation and prevents cyclosporin A toxicity, minimized hypoxia and blocked free radical production; however, it did not alter cyclosporin A blood levels. These results demonstrate for the first time that cyclosporin A causes hypoxia and increases production of a new free radical species exclusively in the kidney. Therefore, it is concluded that cyclosporin A causes renal injury by mechanisms involving hypoxiareoxygenation, effects which can be prevented effectively by dietary glycine. C1 Univ N Carolina, Dept Pharmacol, Hepatobiol & Toxicol Lab, Chapel Hill, NC 27599 USA. Univ N Carolina, Dept Radiat Oncol, Chapel Hill, NC 27599 USA. Univ N Carolina, Curriculum Toxicol, Chapel Hill, NC 27599 USA. NIEHS, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA. RP Thurman, RG (reprint author), Univ N Carolina, Dept Pharmacol, Hepatobiol & Toxicol Lab, CB 7365,Mary Ellen Jones Bldg, Chapel Hill, NC 27599 USA. NR 41 TC 137 Z9 141 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD OCT PY 1998 VL 275 IS 4 BP F595 EP F604 PG 10 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 127RR UT WOS:000076364800014 PM 9755131 ER PT J AU Richards, C Klabunde, C O'Malley, M AF Richards, C Klabunde, C O'Malley, M TI Physicians' recommendations for colon cancer screening in women - Too much of a good thing? SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article DE colorectal neoplasms; screening; cancer; primary care physicians; prevention ID PRIMARY-CARE PHYSICIANS; COLORECTAL-CANCER; PATIENT AB Background: Expert groups support periodic colorectal cancer (CRC) screening for persons aged 50 and older but not for persons younger than 50. We were interested in community primary care physicians' recommendations to women for fecal occult blood tests (FOBT), flexible sigmoidoscopy (SIG), and colonoscopy (COL). Methods: In a mailed survey of 1,292 community primary care physicians in North Carolina, we queried physicians regarding their recommendations to women for CRC screening. Results: Analysis was performed on 508 respondents (39%). Recommendation for FOBT (96%) and SIG (69%) for women >50 years old was high among all subgroups of physicians. Recommendation for women < 50 years old was high for FOBT (82%) but lower for SIG (28%). Overall, 19% of physicians recommended COL. Recommendation for FOBT, SIG, and COL varied by physician specialty, physician age, perceived patient demand, physician need for additional CRC screening information, practice size, and location. Conclusions: Although increasing physician recommendation for CRC screening is important, primary care physicians report recommending earlier and more aggressive screening than that supported by national guidelines. C1 Univ N Carolina, Lineberger Comprehens Canc Ctr, Sch Med, Chapel Hill, NC 27599 USA. Univ N Carolina, Lineberger Comprehens Canc Ctr, Canc Control Educ Program, Chapel Hill, NC 27599 USA. NCI, Canc Control Surveillance Program, Bethesda, MD 20892 USA. Univ N Carolina, Dept Hlth Policy & Adm, Sch Publ Hlth, Chapel Hill, NC 27599 USA. RP O'Malley, M (reprint author), Univ N Carolina, Lineberger Comprehens Canc Ctr, Sch Med, CB 7295, Chapel Hill, NC 27599 USA. FU AHRQ HHS [HS00032]; NCI NIH HHS [CA57726] NR 11 TC 27 Z9 27 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD OCT PY 1998 VL 15 IS 3 BP 246 EP 249 DI 10.1016/S0749-3797(98)00075-0 PG 4 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 122ZR UT WOS:000076101800012 PM 9791644 ER PT J AU Bertolino, A Kumra, S Callicott, JH Mattay, VS Lestz, RM Jacobsen, L Barnett, IS Duyn, JH Frank, JA Rapoport, JL Weinberger, DR AF Bertolino, A Kumra, S Callicott, JH Mattay, VS Lestz, RM Jacobsen, L Barnett, IS Duyn, JH Frank, JA Rapoport, JL Weinberger, DR TI Common pattern of cortical pathology in childhood-onset and adult-onset schizophrenia as identified by proton magnetic resonance spectroscopic imaging SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID TEMPORAL-LOBE STRUCTURES; IN-VIVO; PREFRONTAL CORTEX; N-ACETYLASPARTATE; FRONTAL LOBES; HUMAN BRAIN; ABNORMALITIES; INJURY; PSYCHOPATHOLOGY; HIPPOCAMPUS AB Objective: Multislice proton magnetic resonance spectroscopic imaging ((1)H-MRSI) permits simultaneous acquisition and mapping of signal intensities of N-acetyl-containing compounds (mainly N-acetylaspartate, NAA), choline-containing compounds (CHO), and creatine plus phosphocreatine (CRE) from multiple whole-brain slices consisting of small single-volume elements. Previous (1)H-MRSI studies of adult patients with schizophrenia showed small NAA relative signals in the hippocampal area and in the dorsolateral prefrontal cortex in comparison with healthy subjects. As part of a program to address the pathophysiological continuity between childhood-onset and adult-onset schizophrenia, the authors performed (1)H-MRSI of patients with childhood-onset schizophrenia to specifically test whether the hippocampal area and dorsolateral prefrontal cortex show the same abnormalities as seen in adult-onset schizophrenia. Method: A 1.5-T nuclear magnetic resonance machine was used to test 14 patients (mean age, 16.4 years) and 14 comparison subjects. Ratios of areas under the metabolite peaks of the proton spectra were determined (i,e., NAA/CRE, NAA/CHO, CHO/CRE) for multiple cortical and subcortical regions. Results: The patients showed significantly lower NAA/CRE ratios bilaterally in the hippocampal area and the dorsolateral prefrontal cortex than the comparison subjects. There were no significant differences in CHO/CRE or in NAA ratios in any other area sampled. Conclusions: The present study shows that patients with childhood-onset schizophrenia have smaller than normal regional NAA relative signals, suggesting neuronal damage or malfunction in the hippocampal area and dorsolateral prefrontal cortex. These differences were similar in magnitude to those found in patients with adult-onset schizophrenia. The present data extend other evidence of a biological continuum between childhood- and adult-onset schizophrenia. C1 NIH, Lab Diagnost Radiol Res, Off Director, Bethesda, MD 20892 USA. NIMH, Clin Brain Disorders Branch, Intramural Res Program, Bethesda, MD 20892 USA. NIMH, Child Psychiat Branch, Intramural Res Program, Bethesda, MD 20892 USA. NINDS, Neuroimaging Branch, Rockville, MD USA. RP Weinberger, DR (reprint author), NIMH, Clin Brain Disorders Branch, Intramural Res Program, Neurosci Ctr,St Elizabeths Hosp, 2700 Martin Luther King Jr Ave SE, Washington, DC 20032 USA. EM weinberd@dirpc.nimh.nih.gov RI Duyn, Jozef/F-2483-2010; Callicott, Joseph/C-9102-2009; Bertolino, Alessandro/O-6352-2016 OI Callicott, Joseph/0000-0003-1298-3334; Bertolino, Alessandro/0000-0002-1251-1380 NR 65 TC 84 Z9 87 U1 4 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 OCT PY 1998 VL 155 IS 10 BP 1376 EP 1383 PG 8 WC Psychiatry SC Psychiatry GA 125HY UT WOS:000076233200012 PM 9766769 ER PT J AU Breier, A Kestler, L Adler, C Elman, I Wiesenfeld, N Malhotra, A Pickar, D AF Breier, A Kestler, L Adler, C Elman, I Wiesenfeld, N Malhotra, A Pickar, D TI Dopamine D-2 receptor density and personal detachment in healthy subjects SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID SCHIZOPHRENIA; TRAITS AB Objective: The purpose of this study was to examine the relationship between the personality trait involving personal detachment and dopamine D-2 receptor specific binding in healthy subjects. Method: Eighteen adult subjects completed the Karolinska Scales of Personality and the Tridimensional Personality Questionnaire and participated in a study that used [C-11]raclopride positron emission tomography (PET) to quantify striatal D-2 receptor binding. Results: A significant relationship was found between D-2 receptor specific binding and detachment scores on the Karolinska Scales of Personality but not between D-2 receptor specific binding and attachment scores on the Tridimensional Personality Questionnaire. in an exploratory analysis, the authors found a significant relationship between binding and the sentimentality cluster on the Tridimensional Personality Questionnaire but on no other personality clusters scores on the Tridimensional Personality Questionnaire or Karolinska Scales of Personality. Conclusions: These findings replicate those of a recent report that personal detachment scores on the Karolinska Scales of Personality are related to dopamine D-2 receptor density and extends this finding by suggesting that the relationship is relatively specific to the trait defined by the Karolinska Scales of Personality and does not generalize to other forms of detachment. C1 NIMH, Expt Therapeut Branch, Bethesda, MD 20892 USA. RP Breier, A (reprint author), Eli Lilly & Co, Lilly Corp Ctr, Drop Code 0538, Indianapolis, IN 46285 USA. NR 8 TC 98 Z9 99 U1 1 U2 1 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD OCT PY 1998 VL 155 IS 10 BP 1440 EP 1442 PG 3 WC Psychiatry SC Psychiatry GA 125HY UT WOS:000076233200022 PM 9766779 ER PT J AU Reed, DM Foley, DJ White, LR Heimovitz, H Burchfiel, CM Masaki, K AF Reed, DM Foley, DJ White, LR Heimovitz, H Burchfiel, CM Masaki, K TI Predictors of healthy aging in men with high life expectancies SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID CORONARY HEART-DISEASE; JAPANESE-AMERICAN MEN; PHYSICAL PERFORMANCE; DISABILITY; PREVENTION; STRATEGIES; PREVALENCE; MORTALITY; MACARTHUR; SMOKING AB Objective. The purpose of this study was to identify risk factors that consistently predict staying healthy in contrast to developing clinical illness and/or physical and mental impairments. Methods. More than 8000 men of Japanese ancestry were followed for 28 years with repeat examinations and surveillance for deaths and incident clinical illness. Physical and cognitive functions were measured in 1993. Measures of healthy aging included surviving and remaining free of major chronic illnesses and physical and cognitive impairments. Results. Of 6505 healthy men at baseline, 2524 (39%) died prior to the final exam. Of the 3263 available survivors, 41% remained free of major clinical illnesses, 40% remained free of both physical and cognitive impairment, and 19% remained free of both illness and impairment. The most consistent predictors of healthy aging were low blood pressure, low serum glucose, not smoking cigarettes, and not being obese. Conclusions. Beyond the biological effects of aging, much of the illness and disability in the elderly is related to risk factors present at midlife. C1 NIA, Bethesda, MD 20892 USA. Buck Ctr Res Aging, Novato, CA USA. Sytel Inc, Bethesda, MD USA. NHLBI, Bethesda, MD 20892 USA. Univ Hawaii, John A Burns Sch Med, Honolulu, HI 96822 USA. RP Foley, DJ (reprint author), NIA, Room 3-C-309,Gateway Bldg,7201 Wisconsin Ave, Bethesda, MD 20892 USA. FU NHLBI NIH HHS [N01-HC-05102]; NIA NIH HHS [N01-AG-4-2149] NR 39 TC 63 Z9 68 U1 0 U2 3 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD OCT PY 1998 VL 88 IS 10 BP 1463 EP 1468 DI 10.2105/AJPH.88.10.1463 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 124PV UT WOS:000076191600005 PM 9772845 ER PT J AU Montuenga, LM Zhou, J Avis, I Vos, M Martinez, A Cuttitta, F Treston, AM Sunday, M Mulshine, JL AF Montuenga, LM Zhou, J Avis, I Vos, M Martinez, A Cuttitta, F Treston, AM Sunday, M Mulshine, JL TI Expression of heterogeneous nuclear ribonucleoprotein A2/B1 changes with critical stages of mammalian lung development SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article ID TERMINAL DIFFERENTIATION; CANCER DETECTION; HNRNP PROTEINS; MESSENGER-RNA; BINDING; CELLS; MARKERS; ANTIGEN; PHOSPHORYLATION; EPITHELIUM AB Recent reports have demostrated a link between expression of members of the family of heterogeneous nuclear ribonucleoproteins (hnRNPs) and cancer. Overexpression of hnRNP A2/B1 correlated with the eventual development of lung cancer in three different clinical cohorts. We have studied the expression of hnRNP A2/B1 messenger RNA (mRNA) and protein during mammalian development. The expression of hnRNP A2/B1 mRNA and protein are parallel but change dynamically during critical periods in mouse pulmonary development. hnRNP A2/B1 is first detected in the lung in the early pseudoglandular period, peaks at the beginning of the canalicular period, and remains high during the saccular (alveolar) period. In mouse and rat, hnRNP A2/B1 expression is first evident in the earliest lung buds. As lung development progresses, the cuboidal epithelial cells of the distal primitive alveoli show high levels of the ribonucleoprotein, which is almost undetectable in the proximal conducting airways. The expression of hnRNP A2/B1 is restricted in mature lung. Similar dynamic pattern of expression through lung development was also found in rat and human lung. Upregulated expression of hnRNP A2/B1 at critical periods of lung development was comparable to the level of expression found in lung cancers and preneoplastic lesions and is consistent with hnRNP A2/B1 overexpression playing an oncodevelopmental role. C1 NCI, Intervent Sect, CCBD, NIH,Med Branch, Bethesda, MD 20892 USA. Univ Navarra, Dept Histol & Pathol, E-31080 Pamplona, Spain. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Mulshine, JL (reprint author), NCI, Intervent Sect, CCBD, NIH,Med Branch, Bldg 10,Room 12N-226,9000 Rockville Pike, Bethesda, MD 20892 USA. EM jmulshine@bprb.nci.nih.gov RI Martinez, Alfredo/A-3077-2013 OI Martinez, Alfredo/0000-0003-4882-4044 NR 34 TC 42 Z9 49 U1 0 U2 1 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 USA SN 1044-1549 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD OCT PY 1998 VL 19 IS 4 BP 554 EP 562 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA 130RY UT WOS:000076535200004 PM 9761751 ER PT J AU Yao, XL Levine, SJ Cowan, MJ Logun, C Shelhamer, JH AF Yao, XL Levine, SJ Cowan, MJ Logun, C Shelhamer, JH TI Tumor necrosis factor-alpha stimulates human Clara cell secretory protein production by human airway epithelial cells SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article ID TISSUE-SPECIFIC EXPRESSION; GENE-EXPRESSION; PHOSPHOLIPASE A(2); RABBIT UTEROGLOBIN; BINDING-PROTEIN; POLYCHLORINATED-BIPHENYLS; PROGESTERONE-BINDING; NUCLEOTIDE-SEQUENCE; HORMONAL-REGULATION; ENDOTHELIAL-CELLS AB Clara cell secretory protein (CCSP), or CC10, is an inhibitor of secretory phospholipase A(2) which may be produced by phagocytic cells and by a variety of other cells in the airway. Tumor necrosis factor-alpha (TNF-alpha) is capable of activating phospholipases and inducing the expression of a variety of genes in the airway epithelium which may modulate the airway inflammatory response. Therefore, it was of interest to determine whether this proinflammatory cytokine could induce the production of a counterregulatory protein such as CCSP which might modulate the production of eicosanoid mediators in the airway. Using a human bronchial epithelial cell line (BEAS-2B), CCSP messenger RNA (mRNA) levels were detected by ribonuclease protection assay. TNF treatment of these cells increased CCSP mRNA levels in a time- and dose-dependent manner. The CCSP mRNA level increased in response to TNF-alpha (20 ng/ml) stimulation after 8 to 36 h with the peak increase at 18 h. Immunoblotting of CCSP protein released into the culture media demonstrated that TNF-alpha induced the synthesis and secretion of CCSP protein in a time-dependent manner over 8 to 18 h. The results of a CCSP reporter gene activity assay, nuclear run-on assay, and CCSP mRNA half-life assay indicated that the TNF-alpha-induced increases in CCSP gene expression are regulated at the post-transcriptional level. We conclude that TNF-alpha induces airway epithelial cell expression of human CCSP protein and may modulate airway inflammatory responses in this manner. C1 NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. RP Shelhamer, JH (reprint author), NIH, Dept Crit Care Med, Ctr Clin, Bldg 10,Rm 7-F-43, Bethesda, MD 20892 USA. NR 53 TC 32 Z9 33 U1 0 U2 2 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 USA SN 1044-1549 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD OCT PY 1998 VL 19 IS 4 BP 629 EP 635 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA 130RY UT WOS:000076535200013 PM 9761760 ER PT J AU Bonner, JC Rice, AB Lindroos, PM O'Brien, PO Dreher, KL Rosas, I Alfaro-Moreno, E Osornio-Vargas, AR AF Bonner, JC Rice, AB Lindroos, PM O'Brien, PO Dreher, KL Rosas, I Alfaro-Moreno, E Osornio-Vargas, AR TI Induction of the lung myofibroblast PDGF receptor system by urban ambient particles from Mexico City SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article ID RAT ALVEOLAR MACROPHAGES; OIL FLY-ASH; GROWTH-FACTOR; AIR-POLLUTION; ASTHMA; CHILDREN; STIMULATION; FIBROBLASTS; ADMISSIONS; EXPRESSION AB Platelet-derived growth factor (PDGF) and its receptor system regulate mesenchymal cell proliferation. We recently reported that emission-source fly-ash particles and asbestos fibers induce the PDGF alpha-receptor through a macrophage-dependent pathway, and upregulation of this receptor greatly enhances the mitogenic response of lung myofibroblasts to PDGF (Lindroos and colleagues, Plm. J. Respir. Cell Mel. Biol. 1997;16:283-292). In the present study we investigated the effect of particulate matter less than or equal to 10 mu m in size (PM(10)) from the southern, central, and northern regions of Mexico City on PDGF receptor induction and compared these urban, ambient particles with Mt. St. Helen's volcanic ash particles as a negative control. All Mexico City PM(10) samples, but not volcanic ash, stimulated rat alveolar macrophages to secrete a soluble, upregulatory factor(s) for the PDGF alpha-receptor on early passage rat lung myofibroblasts. The macrophage-derived upregulatory activity was blocked by the interleukin (IL)-1 receptor antagonist. The ability of PM(10) to stimulate IL-1 beta release was blocked in part by a recombinant endotoxin neutralizing protein (rENP). Lipopolysaccharide/endotoxin (LPS) and vanadium, both constituents that were present within these PM(10) samples, also stimulated macrophages to secrete factor(s) that upregulated PDGF-R alpha on lung myofibroblasts. Direct exposure of myofibroblasts to PM(10) also elicited upregulation of the PDGF alpha-receptor, and this effect was blocked by rENP and mimicked by LPS, but not vanadium. These findings suggest that PM(10) particles induce expression of the PDGF receptor system through macrophage-dependent and -independent mechanisms involving endotoxin and metals. C1 NIEHS, Airway Inflammat Sect, Pulm Pathobiol Lab, Res Triangle Pk, NC 27709 USA. US EPA, Natl Hlth & Environm Effects Res Lab, Res Triangle Pk, NC 27711 USA. Natl Canc Inst, Div Basic Invest, Mexico City, DF, Mexico. Univ Nacl Autonoma Mexico, Ctr Study Atmosphere, Mexico City, DF, Mexico. RP Bonner, JC (reprint author), NIEHS, Airway Inflammat Sect, Pulm Pathobiol Lab, POB 12233, Res Triangle Pk, NC 27709 USA. EM bonnerj@niehs.nih.gov RI Osornio Vargas, Alvaro/D-4012-2009; Osornio Vargas, Alvaro/B-4645-2010 OI Osornio Vargas, Alvaro/0000-0001-8287-7102 NR 36 TC 79 Z9 80 U1 1 U2 2 PU AMER THORACIC SOC PI NEW YORK PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA SN 1044-1549 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD OCT PY 1998 VL 19 IS 4 BP 672 EP 680 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA 130RY UT WOS:000076535200018 PM 9761765 ER PT J AU Nagao, E Dvorak, JA AF Nagao, E Dvorak, JA TI Developing the atomic force microscope for studies of living cells SO AMERICAN LABORATORY LA English DT Article AB The atomic force microscope with its powerful magnification and resolution would seem to have great potential for the investigation of cells and other biological assemblies. Having overcome some of the difficult technical problems, the authors present some early results on this exciting new technology. C1 NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Nagao, E (reprint author), NIAID, Parasit Dis Lab, NIH, 4 Ctr Dr, Bethesda, MD 20892 USA. EM jdvorak@atlas.niaid.nih.gov NR 9 TC 1 Z9 1 U1 0 U2 0 PU INT SCIENTIFIC COMMUN INC PI SHELTON PA PO BOX 870, 30 CONTROLS DRIVE, SHELTON, CT 06484-0870 USA SN 0044-7749 J9 AM LAB JI Am. Lab. PD OCT PY 1998 VL 30 IS 21 BP 36 EP + PG 5 WC Chemistry, Analytical; Instruments & Instrumentation SC Chemistry; Instruments & Instrumentation GA 138JZ UT WOS:000076969900007 ER PT J AU Kelloff, G Boone, C AF Kelloff, G Boone, C TI Quantitative methods in prostate pathology - Recent findings and future directions - Foreword SO ANALYTICAL AND QUANTITATIVE CYTOLOGY AND HISTOLOGY LA English DT Editorial Material DE prostatic neoplasms; prostate cancer; prostatic intraepithelial neoplasia C1 NCI, Chemoprevent Branch, Rockville, MD 20852 USA. RP Kelloff, G (reprint author), NCI, Chemoprevent Branch, EPN 201,6130 Execut Blvd, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SCI PRINTERS & PUBL INC PI ST LOUIS PA P.O. DRAWER 12425 8342 OLIVE BLVD, ST LOUIS, MO 63132 USA SN 0884-6812 J9 ANAL QUANT CYTOL JI Anal. Quant. Cytol. Histol. PD OCT PY 1998 VL 20 IS 5 BP 322 EP 322 PG 1 WC Cell Biology SC Cell Biology GA 130JD UT WOS:000076516000002 ER PT J AU Grace, MB Buzard, GS Hughes, MR Gore-Langton, RE AF Grace, MB Buzard, GS Hughes, MR Gore-Langton, RE TI Degradable dUMP outer primers in merged tandem (M/T)-nested PCR: Low- and single-copy DNA target amplification SO ANALYTICAL BIOCHEMISTRY LA English DT Article; Proceedings Paper CT 46th Annual Meeting of the American-Society-of-Human-Genetics / National-Neurofibromatosis-Foundation Symposium CY OCT 28-NOV 01, 1996 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Human Genet, Natl Neurofibromatosis Fdn DE nested PCR; PCR artifacts; uracil N-glycosylase; single-cell genetic diagnosis; Tay-Sachs disease; mutation analysis ID POLYMERASE CHAIN-REACTION; TUBE NESTED PCR; C VIRUS-RNA; CARRY-OVER; GLYCOSYLASE; CLONING; CONTAMINATION; PREVENTION; SEQUENCES; PRODUCTS AB PCR amplification of DNA from a single initiating genomic molecule or low-copy template often requires two sequential amplification reactions with nested primer pairs to achieve the necessary specificity and sensitivity. Residual outer primers can result in undesired primer activity during the inner nested cycles. To circumvent this problem, me have used dU-containing primers for first round amplification and then uracil N-glycosylase (UNG) to degrade them and the ends of their dU-primer-containing amplified DNA products. We have applied this method to the detection of an exon 11 mutation in the HEXA gene. We have merged the step of a single-tube PCR amplification with outer dU primers with a tandem amplification using non-dU-nested primers (hence, the term merged tandem-nested or M/T-nested PCR). Serial dilutions of genomic DNA showed that this method could amplify a specific target from as few as three haploid genome equivalents of template DNA. Specific products were obtained from the DNA of single cells in 19 of 20 replicates, using 12 outer and 28 inner nested PCR cycles, with an intervening UNG digestion step, When coupled with heteroduplex mutational analysis, this method reliably distinguished mutant versus wildtype HEXA gene fragments amplified from single cells without primer artifact. (C) 1998 Academic Press. C1 Natl Human Genome Res Inst, NIH, Bethesda, MD 20892 USA. NCI, Intramural Res Support Program, SAIC Frederick, FCRDC, Frederick, MD 21701 USA. Georgetown Univ, Med Ctr, Dept Obstet & Gynecol, Washington, DC 20007 USA. Georgetown Univ, Med Ctr, Dept Pediat, Washington, DC 20007 USA. RP Grace, MB (reprint author), NIMH, Lab Biochem Genet, NIH, 10 Ctr Dr MSC 1513,2D56, Bethesda, MD 20892 USA. EM marcy@codon.nih.gov NR 21 TC 6 Z9 8 U1 1 U2 7 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD OCT 1 PY 1998 VL 263 IS 1 BP 85 EP 92 DI 10.1006/abio.1998.2771 PG 8 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 127RC UT WOS:000076363500014 PM 9750148 ER PT J AU Archer, SL Liu, K Dyer, AR Ruth, KJ Jacobs, DR Van Horn, L Hilner, JE Savage, PJ AF Archer, SL Liu, K Dyer, AR Ruth, KJ Jacobs, DR Van Horn, L Hilner, JE Savage, PJ TI Relationship between changes in dietary sucrose and high density lipoprotein cholesterol: The CARDIA study SO ANNALS OF EPIDEMIOLOGY LA English DT Article ID CORONARY HEART-DISEASE; YOUNG-ADULTS; BLOOD-LIPIDS; ZUCKER RATS; GLUCOSE; OBESE; RISK; MEN AB PURPOSE: Cross-sectional data from several observational studies have suggested that dietary sucrose may be inversely associated with high density lipoprotein cholesterol (HDL-C). This study examined associations between energy from dietary sucrose and HDL-C at baseline, year 7 and longitudinally (year 7 minus baseline) in a cohort of young black and white men and women from the Coronary Artery Risk Development in Young Adults (CARDIA) study. METHODS: The sample included 4734 black men, black women, white men and white women, ages 18-30 years, in 1985-86 (baseline); 3513 at year 7; and 3335 for longitudinal analyses. Multivariate analyses was used with adjustment for age, BMI, cigarettes smoked per day, physical activity score, and alcohol intake. RESULTS: Multivariate analyses indicated chat energy intake from sucrose was inversely associated with HDL-C for each race-gender group at baseline, year 7, and longitudinally from baseline to year 7. This association was significant at baseline for black men, and white men and women (p < 0.01); at year 7 for white men and black women (p < 0.01), and longitudinally for white men, white women, and black women (p < 0.05). CONCLUSIONS: The consistent inverse associations between energy from dietary sucrose and HDL-C observed in both cross-sectional and longitudinal analyses, and in different race and gender groups in CARDIA suggest that lowering dietary sucrose intake may be beneficial for those who may have low HDL-C. Ann Epidemiol 1998;8:433-438. Published by Elsevier Science Inc. C1 Northwestern Univ, Sch Med, Dept Prevent Med, Chicago, IL 60611 USA. Univ Minnesota, Sch Publ Hlth, Div Epidemiol, Minneapolis, MN 55455 USA. Univ Alabama, CARDIA Coordinating Ctr, Birmingham, AL USA. NHLBI, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD 20892 USA. RP Archer, SL (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-48049, N01-HC-48047] NR 29 TC 17 Z9 19 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 1047-2797 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD OCT PY 1998 VL 8 IS 7 BP 433 EP 438 DI 10.1016/S1047-2797(98)00007-6 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 116KC UT WOS:000075722600004 PM 9738689 ER PT J AU Eisenberg, S Aksentijevich, I Deng, ZM Kastner, DL Matzner, Y AF Eisenberg, S Aksentijevich, I Deng, ZM Kastner, DL Matzner, Y TI Diagnosis of familial Mediterranean fever by a molecular genetics method SO ANNALS OF INTERNAL MEDICINE LA English DT Article DE periodic disease; mutation; molecular sequence data; polymerase chain reaction; diagnosis ID COLCHICINE; FREQUENCY; ATTACKS; FLUIDS; TRIAL; ARMS AB Background: Familial Mediterranean fever is a recessively inherited disorder characterized by episodes of fever with abdominal pain, pleurisy, or arthritis. The familial Mediterranean fever gene, designated MEFV, was recently cloned, and at least three missense mutations (M680I, M694V, and V726A) that account for a large percentage of patients with this disease were identified. Objective: To establish a diagnostic test for familial Mediterranean fever. Design: Cross-sectional study of a convenience sample of patients attending familial Mediterranean fever clinics. Setting: Tertiary referral hospitals. Patients: 107 patients with familiar Mediterranean fever, their family members, and controls. Measurements: Mutations in the 107 samples were assessed by amplifying genomic DNA with use of primers that selectively amplify the normal or altered DNA sequence of the 3 MEFV mutations (amplification refractory mutation system [ARMS]). Mutations were independently assessed by automated sequencing of genomic DNA amplified by polymerase chain reaction to evaluate the sensitivity and specificity of the ARMS assay. Results: The ARMS assay correctly identified M680I, M694V, and V726A mutations in 82 persons with mutations documented by DNA sequencing (21 homozygotes, 2 compound heterozygotes, and 59 simple heterozygotes). Of 7 persons known from family studies to be noncarriers and 18 unrelated persons who were negative for these mutations by sequencing, none had MEFV mutations according to ARMS. Conclusion: The ARMS assay is a rapid, cost-effective, and accurate method for detecting three common mutations in familial Mediterranean fever. C1 Hadassah Univ Hosp, Hematol Unit, IL-91240 Jerusalem, Israel. NIAMSD, Arthrit & Rheumatism Branch, Bethesda, MD 20892 USA. RP Matzner, Y (reprint author), Hadassah Univ Hosp, Hematol Unit, Mt Scopus, IL-91240 Jerusalem, Israel. EM matzner@cc.huji.ac.il NR 21 TC 72 Z9 74 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 J9 ANN INTERN MED JI Ann. Intern. Med. PD OCT 1 PY 1998 VL 129 IS 7 BP 539 EP + PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 123KN UT WOS:000076124500004 PM 9758573 ER PT J AU Nelson, KB Dambrosia, JM Grether, JK Phillips, TM AF Nelson, KB Dambrosia, JM Grether, JK Phillips, TM TI Neonatal cytokines and coagulation factors in children with cerebral palsy SO ANNALS OF NEUROLOGY LA English DT Article ID FACTOR-V-LEIDEN; PERFORMANCE IMMUNOAFFINITY CHROMATOGRAPHY; ANTIPHOSPHOLIPID ANTIBODY SYNDROME; ACTIVATED PROTEIN-C; DRIED BLOOD SPOTS; LOW-BIRTH-WEIGHT; FILTER-PAPER; ANTICARDIOLIPIN ANTIBODIES; INFLAMMATORY CYTOKINES; PLACENTAL INFARCTION AB We explored the association of inflammatory mediators and markers of autoimmune and coagulation disorders with cerebral palsy (CP), examining 53 analytes in dried neonatal blood of 31 children with spastic CP, most born at term, and 65 control children. Ultramicroanalysis was performed by recycling immunoaffinity chromatography coupled with laser-enhanced fluorescence and chemiluminescence detection. Reactive antibodies to lupus anticoagulant, anticardiolipin, antithrombin III, and the translational product of the factor V Leiden mutation were isolated by recycling immunoaffinity chromatography and measured by capillary electrophoresis with chemiluminescence-enhanced immunoassay. Higher concentrations of interleukins (ILs) 1, 8, 9, tumor necrosis factor-alpha, and RANTES were observed in these children with CP than in any control child. There were also substantial elevations of IL-6, 11, 13, and other chemokines and colony-stimulating factors in children with CP. Antiphospholipid antibody was present in a titer of 1:100 or greater in 4 children with CP and no control child. Using cuts empirically chosen by recursive partitioning, we found higher concentrations of antibody to antithrombin III, to a translational product of factor V Leiden mutation, and to proteins C and S in children with CP than in controls. We conclude that inflammation and these coagulation abnormalities, which have interacting pathways, are important in the etiology of CP. C1 NINDS, Neuroepidemiol Branch, Bethesda, MD 20892 USA. NINDS, Biometry & Field Studies Branch, Bethesda, MD 20892 USA. Calif Birth Defects Monitoring Program, Calif Dept Hlth Serv, Emeryville, CA USA. George Washington Univ, Ctr Med, Immunochem Lab, Washington, DC USA. RP Nelson, KB (reprint author), 7550 Wisconsin Ave,Room 714, Bethesda, MD 20892 USA. NR 79 TC 340 Z9 345 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD OCT PY 1998 VL 44 IS 4 BP 665 EP 675 DI 10.1002/ana.410440413 PG 11 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 126VZ UT WOS:000076316300012 PM 9778266 ER PT J AU DeAngelis, LM Burger, PC Green, SB Cairncross, JG AF DeAngelis, LM Burger, PC Green, SB Cairncross, JG TI Malignant glioma: Who benefits from adjuvant chemotherapy? SO ANNALS OF NEUROLOGY LA English DT Article; Proceedings Paper CT 121st Annual Meeting of the American-Neurological-Association CY OCT 13-16, 1996 CL MIAMI, FLORIDA SP Amer Neurol Assoc ID THERAPY-ONCOLOGY-GROUP; RADIATION-THERAPY; RADIOTHERAPY; OLIGODENDROGLIOMA; SURGERY; 19Q; 1P AB We combined two randomized prospective Brain Tumor Study Group data sets to analyze the effects of prognostic factors on survival by treatment group. Adjuvant chemotherapy increased longterm survival regardless of prognostic factors. Pathological review revealed that oligodendrogliomas were overrepresented among longterm survivors independent of therapy. Prognostic factors do not predict benefit from adjuvant nitrosourea in malignant gliomas, and long-term survival with chemotherapy is not explained by oligodendroglial tumors. C1 Mem Sloan Kettering Canc Ctr, Dept Neurol, New York, NY 10021 USA. Johns Hopkins Med Ctr, Dept Pathol, Baltimore, MD USA. NCI, Clin & Diagnost Trials Sect, Bethesda, MD 20892 USA. London Reg Canc Ctr, Dept Med Oncol, London, ON, Canada. RP DeAngelis, LM (reprint author), Mem Sloan Kettering Canc Ctr, Dept Neurol, 1275 York Ave, New York, NY 10021 USA. NR 12 TC 108 Z9 109 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD OCT PY 1998 VL 44 IS 4 BP 691 EP 695 DI 10.1002/ana.410440418 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 126VZ UT WOS:000076316300017 PM 9778271 ER PT J AU Naunton, RF AF Naunton, RF TI Recent advances in otitis media - Report of the Sixth Research Conference - Special remarks SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Editorial Material C1 Natl Inst Deafness & Other Commun Disorders, Div Human Commun, Bethesda, MD 20892 USA. RP Naunton, RF (reprint author), Natl Inst Deafness & Other Commun Disorders, Div Human Commun, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ANNALS PUBL CO PI ST LOUIS PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 USA SN 0003-4894 J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD OCT PY 1998 VL 107 IS 10 SU 174 BP 8 EP 8 PN 2 PG 1 WC Otorhinolaryngology SC Otorhinolaryngology GA 130QF UT WOS:000076531000002 ER PT J AU Klein, JO Tos, M Casselbrant, ML Daly, KA Hoffman, HJ Ingvarsson, L Karma, P van Cauwenberge, PB AF Klein, JO Tos, M Casselbrant, ML Daly, KA Hoffman, HJ Ingvarsson, L Karma, P van Cauwenberge, PB TI Epidemiology and natural history SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article; Proceedings Paper CT 6th International Symposium on Recent Advances in Otitis Media CY JUN 04-08, 1995 CL FT LAUDERDALE, FLORIDA SP Childrens Hosp Pittsburgh, Dept Pediat Otolaryngol, Univ Pittsburgh Med Ctr, Ctr Continuing Educ Hlth Sci, Int Symp Otitis Media Inc, Deafness Res Fdn, NIH, Natl Inst Deafness & Other Commun Disorders ID ACUTE OTITIS-MEDIA; CIGARETTE-SMOKE EXPOSURE; DAY-CARE; RISK-FACTORS; HAEMOPHILUS-INFLUENZAE; YOUNG-CHILDREN; PRONE CHILDREN; LIFE; INFECTIONS; INFANTS C1 Boston City Hosp, Maxwell Finland Lab Infect Dis, Boston, MA 02118 USA. Gentofte Univ Hosp, Dept ENT, Copenhagen, Denmark. Univ Pittsburgh, Sch Med, Dept Pediat Otolaryngol, Pittsburgh, PA USA. Univ Minnesota, Dept Epidemiol, Minneapolis, MN USA. NIDCD, Epidemiol Stat & Data Syst Branch, NIH, Bethesda, MD USA. Malmo Gen Hosp, Dept Otorhinolaryngol, S-21401 Malmo, Sweden. Univ Helsinki, Cent Hosp, Dept Otolaryngol, Helsinki, Finland. Univ Hosp, ENT Dept, Ghent, Belgium. RP Klein, JO (reprint author), Boston City Hosp, Maxwell Finland Lab Infect Dis, Boston, MA 02118 USA. NR 45 TC 2 Z9 2 U1 0 U2 0 PU ANNALS PUBL CO PI ST LOUIS PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 USA SN 0003-4894 J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD OCT PY 1998 VL 107 IS 10 SU 174 BP 9 EP 13 PN 2 PG 5 WC Otorhinolaryngology SC Otorhinolaryngology GA 130QF UT WOS:000076531000003 ER PT J AU Ogra, PL Barenkamp, SJ Mogi, G Murphy, TF Bakaletz, LO Bernstein, JM DeMaria, TF Faden, H Forsgren, J Garofalo, R Giebink, GS Gu, XX Karma, P Patel, J Prellner, K Ryan, AF AF Ogra, PL Barenkamp, SJ Mogi, G Murphy, TF Bakaletz, LO Bernstein, JM DeMaria, TF Faden, H Forsgren, J Garofalo, R Giebink, GS Gu, XX Karma, P Patel, J Prellner, K Ryan, AF TI Microbiology, immunology, and vaccination SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article; Proceedings Paper CT 6th International Symposium on Recent Advances in Otitis Media CY JUN 04-08, 1995 CL FT LAUDERDALE, FLORIDA SP Childrens Hosp Pittsburgh, Dept Pediat Otolaryngol, Univ Pittsburgh Med Ctr, Ctr Continuing Educ Hlth Sci, Int Symp Otitis Media Inc, Deafness Res Fdn, NIH, Natl Inst Deafness & Other Commun Disorders ID NONTYPABLE HAEMOPHILUS-INFLUENZAE; ACUTE OTITIS-MEDIA; OUTER-MEMBRANE PROTEIN; RESPIRATORY SYNCYTIAL VIRUS; MIDDLE-EAR FLUIDS; MORAXELLA BRANHAMELLA CATARRHALIS; OROPHARYNGEAL EPITHELIAL-CELLS; MOLECULAR-WEIGHT PROTEINS; TUMOR-NECROSIS-FACTOR; 1ST 3 YEARS C1 Childrens Hosp, Dept Pediat, Galveston, TX USA. St Louis Childrens Hosp, Div Infect Dis, St Louis, MO 63178 USA. Med Coll Oita, Dept Otolaryngol, Oita 87956, Japan. SUNY Buffalo, Vet Hosp Buffalo, Dept Med, Buffalo, NY USA. Ohio State Univ, Coll Med, Dept Otolaryngol, Columbus, OH 43210 USA. Amherst Otolaryngol Ctr, Williamsville, NY USA. SUNY Buffalo, Childrens Hosp, Dept Pediat, Buffalo, NY 14260 USA. Huddinge Univ Hosp, Dept ENT, S-14186 Huddinge, Sweden. Univ Texas, Med Branch, Childrens Hosp, Dept Allergy Immunol, Galveston, TX 77550 USA. Univ Texas, Med Branch, Childrens Hosp, Dept Pediat, Galveston, TX 77550 USA. Univ Minnesota, Dept Pediat, Minneapolis, MN 55455 USA. NIDCD, Immunol Lab, DIR, NIH, Rockville, MD USA. Univ Helsinki, Cent Hosp, Dept Otolaryngol, Helsinki, Finland. Univ Texas, Med Branch, Dept Pediat, Galveston, TX 77550 USA. Univ Lund Hosp, Dept Pediat Otolaryngol, S-22185 Lund, Sweden. Univ Calif San Diego, Vet Adm Med Ctr, Div Otolaryngol, San Diego, CA USA. RP Ogra, PL (reprint author), Childrens Hosp, Dept Pediat, Galveston, TX USA. NR 174 TC 3 Z9 3 U1 0 U2 0 PU ANNALS PUBL CO PI ST LOUIS PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 USA SN 0003-4894 J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD OCT PY 1998 VL 107 IS 10 SU 174 BP 29 EP 49 PN 2 PG 21 WC Otorhinolaryngology SC Otorhinolaryngology GA 130QF UT WOS:000076531000006 ER PT J AU Czajkowski, SM AF Czajkowski, SM TI Health-related quality of life outcomes in clinical research: NHLBI policy and perspectives SO ANNALS OF THORACIC SURGERY LA English DT Article; Proceedings Paper CT Outcomes 98 - the Key West Meeting CY MAY 27-31, 1998 CL KEY WEST, FLORIDA SP Bayer Pharmaceut, Medtron Bio Medicus, Sangtec Med AB, Somanet Corp C1 NHLBI, NIH, Bethesda, MD 20892 USA. RP Czajkowski, SM (reprint author), NHLBI, NIH, Suite 8130-B,6701 Rockledge,Bldg 2, Bethesda, MD 20892 USA. NR 4 TC 9 Z9 9 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD OCT PY 1998 VL 66 IS 4 BP 1486 EP 1487 DI 10.1016/S0003-4975(98)00837-6 PG 2 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 133NP UT WOS:000076692900112 PM 9800876 ER PT J AU Groll, AH Sein, T Petraitis, V Petraitiene, R Callender, D Gonzalez, CE Giri, N Bacher, J Piscitelli, S Walsh, TJ AF Groll, AH Sein, T Petraitis, V Petraitiene, R Callender, D Gonzalez, CE Giri, N Bacher, J Piscitelli, S Walsh, TJ TI Compartmental pharmacokinetics and tissue drug distribution of the pradimicin derivative BMS 181184 in rabbits SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID INVIVO ANTIFUNGAL ACTIVITIES; FUNGAL-INFECTIONS; INVITRO; EPIDEMIOLOGY; ANTIBIOTICS; BMS-181184; TRENDS AB The pharmacokinetics of the antifungal pradimicin derivative EMS 181184 in plasma of normal, catheterized rabbits were characterized after single and multiple daily intravenous administrations of dosages of 10, 25, 50, or 150 mg/kg of body weight, and drug levels in tissues were assessed after multiple dosing. Concentrations of BMS 181184 were determined by a validated high-performance liquid chromatography method, and plasma data were modeled into a two-compartment open model. Across the investigated dosage range, EMS 181184 demonstrated nonlinear, dose-dependent kinetics with enhanced clearance, reciprocal shortening of elimination half-life, and an apparently expanding volume of distribution with increasing dosage, After single-dose administration, the mean peak plasma BMS 181184 concentration (C-max) ranged from 120 mu g/ml at PO mg/kg to 648 mu g/ml at 150 mg/kg; the area under the concentration-time curve from 0 to 24 h (AUC(0-24)) ranged from 726 to 2.130 mu g . h/ml, the volume of distribution ranged from 0.397 to 0.799 liter/kg, and the terminal half-life ranged from 4.99 to 2.31 h, respectively (P < 0.005 to P < 0.001), No drug accumulation in plasma occurred after multiple daily dosing at 10, 25, or 50 mg/kg over 15 days, although mean elimination half-lives were slightly longer. Multiple daily dosing at 150 mg/kg was associated with enhanced total clearance and a significant decrease in AUC(0-24) below the values obtained at 50 mg/kg (r < 0.01) and after single-dose administration of the same dosage (P < 0.05), Assessment of tissue BMS 181184 concentrations after multiple dosing over 16 days revealed substantial uptake in the lungs, liver, and spleen and, most notably, dose-dependent accumulation of the drug within the kidneys. These findings are indicative of dose- and time-dependent elimination of EMS 181184 from plasma and renal accumulation of the compound after multiple dosing. C1 NCI, Immunocompromised Host Sect, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. NCI, Surg Branch, Vet Resources Serv, Natl Ctr Res Resources,NIH, Bethesda, MD 20892 USA. NCI, Pharmacokinet Res Lab, Dept Pharm, Warren Grant Magnuson Clin Ctr,NIH, Bethesda, MD 20892 USA. RP Walsh, TJ (reprint author), NCI, Immunocompromised Host Sect, Pediat Oncol Branch, NIH, Bldg 10,Rm 13N240,10 Ctr Dr, Bethesda, MD 20892 USA. NR 23 TC 6 Z9 6 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD OCT PY 1998 VL 42 IS 10 BP 2700 EP 2705 PG 6 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 126MH UT WOS:000076296900038 PM 9756780 ER PT J AU de Jong, MD Galasso, GJ Gazzard, B Griffiths, PD Jabs, DA Kern, ER Spector, SA AF de Jong, MD Galasso, GJ Gazzard, B Griffiths, PD Jabs, DA Kern, ER Spector, SA TI Summary of the II International Symposium on Cytomegalovirus SO ANTIVIRAL RESEARCH LA English DT Review DE human cytomegalovirus; diagnosis; treatment; prophylaxis ID POLYMERASE CHAIN-REACTION; BONE-MARROW TRANSPLANTATION; IMMUNE-DEFICIENCY-SYNDROME; ANTISENSE OLIGONUCLEOTIDE COMPLEMENTARY; PREEMPTIVE GANCICLOVIR THERAPY; PERIPHERAL-BLOOD LEUKOCYTES; PLACEBO-CONTROLLED TRIAL; HIGH-DOSE ACYCLOVIR; T-CELL CLONES; LIVER-TRANSPLANTATION AB Human cytomegalovirus (HCMV) is a highly species-specific DNA virus belonging to the Betaherpesvirinae subfamily of the herpesviridae family. Like other herpesviruses, primary infection with HCMV is followed by persistence of the virus in a latent form. The sites of latency are still largely undefined, but they probably include bone marrow progenitor cells and peripheral blood monocytes. From these sites, the virus can reactivate, resulting in renewed shedding of the virus, or, in immunocompromized persons, development of disease. Humans are the only reservoir of HCMV and transmission occurs by person-to-person contact. Infection with HCMV is common. In most developed countries, HCMV seroprevalence steadily increases after infancy and 10-20% of children are infected before puberty. In adults, the prevalence of antibodies ranges from 40 to 100%. Although HCMV has a world-wide distribution, infection with HCMV is more common in the developing countries and in areas of low socioeconomic conditions, which is predominantly related to the closeness of contacts within these populations. Except for a mononucleosis-like illness in some persons, infection with HCMV rarely causes disease in immunocompetent individuals. However, HCMV can cause severe morbidity and mortality in congenitally infected newborns and immunocompromized patients, most notably transplant-recipients and HIV-infected persons. This article provides a review of the information presented at the Second International Symposium on Cytomegalovirus organized and convened by The Macrae Group (New York City, NY) in Acapulco, Mexico on 24-28 April 1998. During this symposium, the stale-of-the-art knowledge on diagnosis, treatment and prophylaxis of HCMV infections were discussed, and, based on this information, attempts to highlight the future directions in basic and clinical research areas that need to be stimulated to facilitate advancement in prevention and treatment of CMV disease. (C) 1998 Elsevier Science B.V. All rights reserved. C1 Univ Amsterdam, Acad Med Ctr, Dept Clin Virol, NL-1105 AZ Amsterdam, Netherlands. NIH, Bethesda, MD 20892 USA. Chelsea & Westminster Hosp, Dept HIV GUM, London, England. Royal Free Hosp, Sch Med, Communicable Dis Div, London, England. Univ Alabama, Dept Pediat, Birmingham, AL USA. Univ Calif San Diego, Dept Pediat, Div Infect Dis, La Jolla, CA 92093 USA. Johns Hopkins Univ, Sch Med, Dept Ophthalmol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. RP de Jong, MD (reprint author), Univ Amsterdam, Acad Med Ctr, Dept Clin Virol, L1-104,Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands. EM m.d.dejong@amc.uva.nl NR 127 TC 100 Z9 107 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-3542 J9 ANTIVIR RES JI Antiviral Res. PD OCT PY 1998 VL 39 IS 3 BP 141 EP 162 DI 10.1016/S0166-3542(98)00044-8 PG 22 WC Pharmacology & Pharmacy; Virology SC Pharmacology & Pharmacy; Virology GA 137UD UT WOS:000076934000001 PM 9833956 ER PT J AU Waterman, SR Small, PLC AF Waterman, SR Small, PLC TI Acid-sensitive enteric pathogens are protected from killing under extremely acidic conditions of pH 2.5 when they are inoculated onto certain solid food sources SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID ESCHERICHIA-COLI O157-H7; SALMONELLA-TYPHIMURIUM; SHIGELLA-FLEXNERI; YERSINIA-ENTEROCOLITICA; RESISTANCE PHENOTYPE; CHEDDAR CHEESE; TOLERANCE; RPOS; SURVIVAL; MECHANISMS AB Gastric acidity is recognized as the first line of defense against food-borne pathogens, and the ability of pathogens to resist this pH corresponds to their oral infective dose (ID). Naturally occurring and genetically engineered acid-sensitive enteric pathogens were examined for their ability to survive under acidic conditions of pH 2.5 for 2 h at 37 degrees C when inoculated onto ground beef. Each of the strains displayed significantly high survival rates under these normally lethal conditions. The acid-sensitive pathogens Campylobacter jejuni and Vibrio cholerae, which were protected at lower levels from acid-induced killing by ground beef under these conditions, were sensitive to killing in acidified media at pH 5.0 but survived at pH 6.0. Salmonella inoculated onto the surface of preacidified ground beef could not survive if the pH on the surface of the beef was 2.61 or lower but was viable if the surface pH was 3.27. This implies that the pH of the microenvironment occupied by the bacteria on the surface of the food source is critical for their survival. Salmonella was also shown to be protected from killing when inoculated onto boiled egg,white, a food source high in protein and low in fat. These results may explain why Salmonella species have a higher oral ID of approximately 10(5) cells when administered under defined conditions but have been observed to cause disease at doses as low as 50 to 100 organisms when consumed as part of a contaminated food source. They. may also help explain why some pathogens are associated primarily with food-borne modes of transmission rather than fecal-oral transmission. C1 NIAID, Rocky Mt Lab, Microscopy Branch, Hamilton, MT 59840 USA. Hammersmith Hosp, Imperial Coll, Dept Infect Dis, London W12 0NN, England. RP Small, PLC (reprint author), NIAID, Rocky Mt Lab, Microscopy Branch, 903 S 4th St, Hamilton, MT 59840 USA. NR 36 TC 126 Z9 128 U1 0 U2 8 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0099-2240 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD OCT PY 1998 VL 64 IS 10 BP 3882 EP 3886 PG 5 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 126LP UT WOS:000076295100049 PM 9758814 ER PT J AU Roberts, KP Blades, M AF Roberts, KP Blades, M TI The effects of interacting in repeated events on children's eyewitness memory and source monitoring SO APPLIED COGNITIVE PSYCHOLOGY LA English DT Article ID IMAGINED ACTIONS; DEVELOPMENTAL-CHANGES; PARTICIPATION; PRESCHOOLERS; PERSPECTIVE; ABILITY; CUES AB Accurate eyewitness memory of an event may be affected by exposure to and degree of involvement with other related events. In this study, we investigated whether interacting in a related video event affected children's accounts of a real-life target event, and whether interacting in the target event affected memory for different details within the target event. Four-, 6-, and 9-year-old children interacted with an adult who made a puppet. Half of the children in each age group also interacted with a video of a similar event (interactive condition) and half sat and watched the video without interacting (watch condition). When asked nonmisleading questions a week later, children in the interactive condition confused the two events more than those in the watch condition. The 4-year-olds in the interactive condition reported a higher rate of confusions in free recall than the 4-year-olds in the watch condition. There were no effects of interaction on responses to misleading questions. The 6- and 9-year-olds were more accurate at answering questions related to actions they themselves had performed than actions performed by the experimenter, although this pattern was reversed for the 4-year-olds. The results are discussed in terms of children's eyewitness memory. (C) 1998 John Wiley & Sons, Ltd. C1 Univ Sheffield, Sheffield S10 2TN, S Yorkshire, England. RP Roberts, KP (reprint author), NICH, Sect Social & Emot Dev, 9190 Rockville Pike, Bethesda, MD 20814 USA. NR 33 TC 32 Z9 34 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0888-4080 J9 APPL COGNITIVE PSYCH JI Appl. Cogn. Psychol. PD OCT PY 1998 VL 12 IS 5 BP 489 EP 503 DI 10.1002/(SICI)1099-0720(199810)12:5<489::AID-ACP535>3.0.CO;2-# PG 15 WC Psychology, Experimental SC Psychology GA 130QX UT WOS:000076532500006 ER PT J AU Pan, CJ Lei, KJ Chen, HW Ward, JM Chou, JY AF Pan, CJ Lei, KJ Chen, HW Ward, JM Chou, JY TI Ontogeny of the murine glucose-6-phosphatase system SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE glycogen storage disease type 1; glucose 6-phosphatase catalysis; glucose 6-phosphate transport; in situ hybridization; mRNA expression ID GLYCOGEN-STORAGE-DISEASE; MICROSOMAL GLUCOSE-6-PHOSPHATASE; RAT-LIVER; ENZYME-DEFICIENT; MESSENGER-RNA; GENE; TRANSPORT; MUTATIONS; TRANSPLANTATION; MEMBRANE AB A deficiency in microsomal glucose-6-phosphatase (G6Pase) activity causes glycogen storage disease type 1 (GSD-1), a clinically and biochemically heterogeneous group of diseases. It has been suggested that catalysis by G6Pase involves multiple components, with defects in the G6Pase catalytic unit causing GSD-1a and defects in the putative substrate and product translocases causing GSD-1b, 1c, and 1d. However, this model is open to debate. To elucidate the G6Pase system, we have examined G6Pase mRNA expression, G6Pase activity, and glucose 6-phosphate (G6P) transport activity in the murine liver and kidney during normal development. In the liver, G6Pase mRNA and enzymatic activity were detected at 18 days gestation and increased markedly at parturition, before leveling off to adult levels, In the kidney, G6Pase mRNA and enzymatic activity appeared at 19 days gestation and peaked at weaning, suggesting that kidney G6Pase may have a different metabolic role. In situ hybridization analysis demonstrated that, in addition to the liver and kidney, the intestine expressed G6Pase. Despite the expression of G6Pase in the embryonic liver, microsomal G6P transport activity was not detectable until birth, peaking at about age 4 weeks. Our study strongly supports the multicomponent model for the G6Pase system. (C) 1998 Academic Press. C1 NICHHD, Heritable Disorders Branch, NIH, Bethesda, MD 20892 USA. NCI, Vet & Tumor Pathol Sect, Off Lab Anim Sci, Frederick, MD 21702 USA. RP Chou, JY (reprint author), NICHHD, Heritable Disorders Branch, NIH, Bldg 10,Room 9S241, Bethesda, MD 20892 USA. NR 43 TC 52 Z9 56 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD OCT 1 PY 1998 VL 358 IS 1 BP 17 EP 24 DI 10.1006/abbi.1998.0849 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 127YD UT WOS:000076377400002 PM 9750160 ER PT J AU Adali, O Carver, GC Philpot, RM AF Adali, O Carver, GC Philpot, RM TI Modulation of human flavin-containing monooxygenase 3 activity by tricyclic antidepressants and other agents: Importance of residue 428 SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE FMO; FMO3; drug metabolism; imipramine; human ID ADULT HUMAN LIVER; ESCHERICHIA-COLI; SUBSTRATE-SPECIFICITY; PRIMARY ALKYLAMINES; MULTIPLE FORMS; GENE FAMILY; AMINES; SULFOXIDATION; OXIDATION; FMO3 AB Human flavin-containing monooxygenase 3 (FMO3) is subject to modulation by tricyclic antidepressants and other agents. Imipramine activates FMO3-catalyzed metabolism of methimazole at all substrate concentrations tested. This distinguishes FMO3 from rabbit FMO1 and FMO2, which are activated at high substrate concentration and inhibited at low substrate concentration, and pig FMO1, which is inhibited at all substrate concentrations. The response of FMO3 is also unique in that chlorpromazine is markedly more effective as a modulator than is imipramine. n-Octylamine,MgCl2, and HgCl2 all inhibit FMO3, the frst two in a biphasic manner. Substitution of lysine for threonine at position 428 significantly alters the response of FMO3 to modulators without changing the kinetic parameters for the metabolism of the substrate. Activation by imipramine and chlorpromazine is reduced or abolished and inhibition, most obvious at low substrate concentrations, is observed. This is consistent with elimination of self-activation in the metabolism of imipramine. The mutation at 428 also eliminates the biphasic nature of the inhibition by n-octylamine and MgCl2, but does not alter the effect of HgCl2. Our findings show that the activity of FMO3 can be modulated by large drug molecules as well as short-chain amines and metal ions. This modulation can be markedly altered by changing a single amino acid in the enzyme. (C) 1998 Academic Press. C1 NIEHS, Lab Signal Transduct, Res Triangle Pk, NC 27709 USA. RP Philpot, RM (reprint author), NIEHS, Lab Signal Transduct, POB 12233, Res Triangle Pk, NC 27709 USA. NR 26 TC 12 Z9 12 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD OCT 1 PY 1998 VL 358 IS 1 BP 92 EP 97 DI 10.1006/abbi.1998.0835 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 127YD UT WOS:000076377400011 PM 9750169 ER PT J AU Schwartz, PJ Rosenthal, NE Wehr, TA AF Schwartz, PJ Rosenthal, NE Wehr, TA TI Serotonin 1A receptors, melatonin, and the proportional control thermostat in patients with winter depression SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID SEASONAL AFFECTIVE-DISORDER; BODY-TEMPERATURE; META-CHLOROPHENYLPIPERAZINE; HYPOTHERMIC RESPONSE; ENDOCRINE RESPONSES; RECOGNITION SITES; CORE TEMPERATURE; MAJOR DEPRESSION; INDUCED DECREASE; HUMANS AB Background: In patients with seasonal affective disorder, light treatment lowers core temperature during sleep in proportion to its antidepressant efficacy. The regulation of the level of core temperature during sleep is linked with a proportional control thermostat in the central nervous system whose operation appears abnormal in patients with seasonal affective disorder. Because both melatonin and serotonin 1A receptor activation also lower core temperature, we investigated the relationship between ii) endogenous melatonin and core temperature profiles, (2) the proportional control thermostat, and (3) the core hypothermic response to the serotonin 1A receptor partial agonist ipsapirone hydrochloride in patients with seasonal affective disorder and healthy controls. Methods: Eighteen patients with seasonal affective disorder and 18 controls first completed a 24-hour study in which their melatonin profiles were characterized. Subjects then returned 3 to 5 days later for the first of 2 drug challenges (ipsapirone hydrochloride, 0.3 mg/kg, or placebo), each separated by 3 to 5 days. Overnight rectal and facial temperatures were recorded before and after each drug challenge. Results: The magnitudes of the core hypothermic responses to ipsapirone were (1) not different between groups and (2) independently correlated with both the levels of the previous nights' core temperature-minima (P = .002) and the amounts of nocturnal melatonin secreted (P<.001). Conclusion: The daytime regulation of core temperature by serotonin 1A receptors appears normal in seasonal affective disorder. The magnitude of serotonin 1A receptor-activated hypothermia is governed by a central nervous system proportional control thermostat whose operation appears modulated by both melatonin and the level of the core temperature minimum. C1 NIMH, Clin Psychobiol Branch, Bethesda, MD 20892 USA. RP Rosenthal, NE (reprint author), NIMH, Clin Psychobiol Branch, Bldg 10,Room 3S-231,10 Ctr Dr,MSC-1390, Bethesda, MD 20892 USA. EM pjs4@popd.ix.netcom.com RI Schwartz, Peter/J-4267-2016 OI Schwartz, Peter/0000-0003-0367-1048 NR 60 TC 12 Z9 12 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD OCT PY 1998 VL 55 IS 10 BP 897 EP 903 DI 10.1001/archpsyc.55.10.897 PG 7 WC Psychiatry SC Psychiatry GA 128PR UT WOS:000076415500007 PM 9783560 ER PT J AU Mazzanti, CM Lappalainen, J Long, JC Bengel, D Naukkarinen, H Eggert, M Virkkunen, M Linnoila, M Goldman, D AF Mazzanti, CM Lappalainen, J Long, JC Bengel, D Naukkarinen, H Eggert, M Virkkunen, M Linnoila, M Goldman, D TI Role of the serotonin transporter promoter polymorphism in anxiety-related traits SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID TRIDIMENSIONAL PERSONALITY QUESTIONNAIRE; MAJOR DEPRESSION; GENE; STATES; SUSCEPTIBILITY; DISORDERS; LINKAGE; MOOD AB Background: The heritability of interindividual variation in anxiety and other aspects of personality establishes that variants of genes influence these traits. A functional polymorphism in the promoter of the human serotonin transporter gene (SLC6A4*C) was identified and found to be linked to an anxiety-related personality trait, Neuroticism. The polymorphism affects gene transcription and, ultimately, gene function. We have attempted to confirm the role of SLC6A4*C in anxiety-related personality traits by sibpair analysis and association studies. Methods: Sibpair linkage analysis and association study were performed in 655 Finns. The index cases were 182 alcoholic criminal offenders, through which 255 relatives were ascertained to obtain 366 sibpairs. In addition, 215 unrelated population controls were collected. Each individual was psychiatrically interviewed, blind-rated for DSM-III-R diagnoses, and assessed with the Tridimensional Personality Questionnaire. Results: The sibpair analysis revealed a positive linkage between SLC6A4*C and the 2 anxiety-related subdimensions of Harm Avoidance: HA1 (Anticipatory Worry) and HA2 (Fear of Uncertainty) (P=.003). How ever; there was no consistent association between SLC6A4*C and any Tridimensional Personality Questionnaire trait. Conclusions: In the present study we replicated the relationship of SLC6A4*C to anxiety by sibpair linkage analysis but found no evidence of association, raising the question of whether SLCM4"C locus is itself affecting anxiety or is linked to another still unknown functional variant. C1 NIAAA, Neurogenet Lab, NIH, Rockville, MD 20852 USA. NIAAA, Sect Populat Genet & Linkage, NIH, Rockville, MD 20852 USA. NIAAA, Clin Studies Lab, NIH, Rockville, MD 20852 USA. Univ Helsinki, Dept Psychiat, SF-00180 Helsinki, Finland. NIMH, Clin Sci Lab, NIH, Bethesda, MD 20892 USA. RP Goldman, D (reprint author), NIAAA, Neurogenet Lab, NIH, 12420 Parklawn Dr,Pk 5 Bldg,Room 451, Rockville, MD 20852 USA. RI Goldman, David/F-9772-2010 OI Goldman, David/0000-0002-1724-5405 FU NCRR NIH HHS [1 P41 RR03655] NR 20 TC 183 Z9 185 U1 1 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD OCT PY 1998 VL 55 IS 10 BP 936 EP 940 DI 10.1001/archpsyc.55.10.936 PG 5 WC Psychiatry SC Psychiatry GA 128PR UT WOS:000076415500012 PM 9783565 ER PT J AU Litvan, I Paulsen, JS Mega, MS Cummings, JL AF Litvan, I Paulsen, JS Mega, MS Cummings, JL TI Neuropsychiatric assessment of patients with hyperkinetic and hypokinetic movement disorders SO ARCHIVES OF NEUROLOGY LA English DT Article ID PROGRESSIVE SUPRANUCLEAR PALSY; OBSESSIVE-COMPULSIVE DISORDER; FRONTAL-SUBCORTICAL CIRCUITS; RICHARDSON-OLSZEWSKI-SYNDROME; POSITRON EMISSION TOMOGRAPHY; MULTIPLE SYSTEM ATROPHY; CEREBRAL BLOOD-FLOW; BASAL GANGLIA; HUNTINGTONS-DISEASE; PARKINSONS-DISEASE AB Background: The role of the basal ganglia in neuropsychiatric behaviors is not well known. Anatomical, neurophysiological, and neurochemical evidence supports the notion of parallel direct and indirect basal ganglia thalamocortical motor systems, the differential involvement of which accounts for the hypokinesia or hyperkinesia observed in basal ganglia disorders. Objectives: To evaluate the neuropsychiatric manifestations of patients with a hyperkinetic movement disorder, such as Huntington disease (HD), vs a hypokinetic disease, such as progressive supranuclear palsy (PSP). To verify if patients with HD show a greater frequency of hyperactive behaviors leg, agitation, irritation, euphoria, or anxiety), while those with PSP exhibit hypoactive behaviors leg, apathy). Patients and Methods: The Neuropsychiatric Inventory, a tool with established validity and reliability, was administered to 29 patients with HD (mean +/- SD age, 43.8 +/- 2 years) and 34 with PSP (mean +/- SD age, 66.6 +/- 1.2 years), matched for education, symptom duration, and overall degree of dementia. Results: There was no difference between the groups in the total Neuropsychiatric inventory scores. However, there was a double dissociation in behaviors: patients with HD exhibited significantly more agitation (45%), irritability (38%), and anxiety (34%), whereas patients with PSP exhibited more apathy (82%) (P<.01). Euphoria was present only in patients with HD. Conclusions: We found that patients with HD manifested predominantly hyperactive behaviors, while those with PSP manifested hypoactive behaviors. Based on our findings and the anatomical lesions known to occur in these disorders, we suggest that the hyperactive behaviors in HD are secondary to an excitatory subcortical output through the medial and orbitofrontal cortical circuits, while in PSP the hypoactive behaviors are secondary to hypostimulation. C1 NINDS, Med Neurol Branch, NIH, Bethesda, MD 20892 USA. Henry M Jackson Fdn, Def & Vet Head Injury Program, Neuropharmacol Unit, Bethesda, MD USA. Univ Iowa, Dept Psychiat, Iowa City, IA 52242 USA. Univ Iowa, Dept Neurol, Iowa City, IA 52242 USA. Univ Calif Los Angeles, Sch Med, Dept Neurol, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. RP Litvan, I (reprint author), NINDS, Med Neurol Branch, NIH, Fed Bldg,Room 714, Bethesda, MD 20892 USA. EM litvan1@helix.nih.gov OI Litvan, Irene/0000-0002-3485-3445 FU NIA NIH HHS [AG10123] NR 57 TC 69 Z9 71 U1 3 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD OCT PY 1998 VL 55 IS 10 BP 1313 EP 1319 DI 10.1001/archneur.55.10.1313 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 127YR UT WOS:000076378800006 PM 9779658 ER PT J AU Burke, HB Henson, DE AF Burke, HB Henson, DE TI Specimen banks for cancer prognostic factor research SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID MARKER-IMMUNOSTAINING INTENSITY; PARAFFIN-EMBEDDED TISSUE; BREAST-CANCER; MOLECULAR PATHOLOGY; DNA; SLIDES; NETWORK AB Prognostic factors are necessary for determining whether a patient will require therapy, for selecting the optimal therapy, and for evaluating the effectiveness of the therapy chosen. Research in prognostic factors has been hampered by long waiting times and a paucity of outcomes. Specimen banks can solve these problems, but their implementation and use give rise to many important and complex issues. This paper presents an overview of some of the issues related to the use of specimen banks in prognostic factor research. C1 New York Med Coll, Dept Med, Valhalla, NY 10595 USA. NCI, Early Detect Branch, Div Canc Prevent, Rockville, MD USA. RP Burke, HB (reprint author), New York Med Coll, Dept Med, Valhalla, NY 10595 USA. NR 38 TC 10 Z9 10 U1 0 U2 0 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD OCT PY 1998 VL 122 IS 10 BP 871 EP 874 PG 4 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 128BC UT WOS:000076384500003 PM 9786346 ER PT J AU Usuki, L Horiba, K Chu, SC Moss, L Ferrans, VJ AF Usuki, L Horiba, K Chu, SC Moss, L Ferrans, VJ TI Immunohistochemical analysis of proteins of the bcl-2 family in pulmonary lymphangioleiomyomatosis - Association of Bcl-2 expression with hormone receptor status SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID PROGRAMMED CELL-DEATH; BREAST-CANCER-CELLS; C-MYC; STEROID-RECEPTORS; IN-VIVO; APOPTOSIS; TISSUES; BAX; LYMPHANGIOMYOMATOSIS; DIFFERENTIATION AB Background.-Pulmonary lymphangioleiomyomatosis (LAM), a disease of young women, is characterized by proliferation of abnormal smooth muscle cells (LAM cells) which often differ from normal pulmonary smooth muscle cells by frequently having estrogen and progesterone receptors. Objective.-To evaluate the relationships among several factors related to proliferation and apoptosis in LAM cells, we employed immunohistochemical methods for the localization of Bcl-2 and Mcl-1 (inhibitors of apoptosis), Bax (a promoter of apoptosis), c-Myc (an apoptosis-related oncoprotein), proliferating cell nuclear antigen (an indicator of mitotic activity), and nick end labeling (to identify apoptotic cells) in lung tissues of 9 patients with LAM. Results.-In all patients, most LAM cells reacted positively for Bax. The LAM cells were positive for both Bcl-2 and estrogen receptor in 5 patients, positive for only Bcl-2 in 1 patient, positive for only estrogen receptor in another patient, and negative for both in 2 patients. More than 50% of the Bcl-2-positive LAM cells were also positive for estrogen receptor. The reaction for c-Myc was positive in all patients. The immunoreactivity for Bcl-2 and Mcl-1, which inhibit apoptosis, was more intense in LAM cells than in normal vascular and bronchial smooth muscle cells. In 6 patients, more than 50% of the LAM cells were positive for proliferating cell nuclear antigen. Apoptosis was infrequent in LAM cells. Conclusions.-Our results suggest that the expression of Bcl-2 in LAM cells may be related to hormonal regulation, and that by decreasing apoptosis, Bcl-2 and related proteins contribute to the imbalance between proliferation and death of LAM cells. C1 NHLBI, Pathol Sect, NIH, Bethesda, MD 20892 USA. NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. RP Ferrans, VJ (reprint author), NHLBI, Pathol Sect, NIH, Bldg 10,Rm 2N240,10 Ctr Dr,MSC-1518, Bethesda, MD 20892 USA. NR 35 TC 12 Z9 12 U1 0 U2 0 PU COLL AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 EI 1543-2165 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD OCT PY 1998 VL 122 IS 10 BP 895 EP 902 PG 8 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 128BC UT WOS:000076384500007 ER PT J AU Cooper, GS Dooley, MA Treadwell, EL St Clair, EW Parks, CG Gilkeson, GS AF Cooper, GS Dooley, MA Treadwell, EL St Clair, EW Parks, CG Gilkeson, GS TI Hormonal, environmental, and infectious risk factors for developing systemic lupus erythematosus SO ARTHRITIS AND RHEUMATISM LA English DT Review ID AUTOIMMUNE-DISEASE; ANTINUCLEAR ANTIBODIES; RHEUMATOID-ARTHRITIS; ESTROGEN METABOLISM; ORAL-CONTRACEPTIVES; OCCASIONAL SERIES; AFRICAN-AMERICANS; CELL ACTIVATION; BETA-CAROTENE; SEX-HORMONES C1 NIEHS, Epidemiol Branch A3 05, Durham, NC 27709 USA. Univ N Carolina, Chapel Hill, NC 27515 USA. E Carolina Univ, Sch Med, Greenville, NC 27858 USA. Duke Univ, Med Ctr, Durham, NC 27706 USA. Med Univ S Carolina, Charleston, SC 29425 USA. Ralph H Johnson Vet Adm Med Ctr, Charleston, SC USA. RP Cooper, GS (reprint author), NIEHS, Epidemiol Branch A3 05, POB 12233, Durham, NC 27709 USA. OI Parks, Christine/0000-0002-5734-3456 NR 99 TC 122 Z9 128 U1 1 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD OCT PY 1998 VL 41 IS 10 BP 1714 EP 1724 DI 10.1002/1529-0131(199810)41:10<1714::AID-ART3>3.0.CO;2-U PG 11 WC Rheumatology SC Rheumatology GA 127FZ UT WOS:000076341300002 PM 9778212 ER PT J AU Zhang, YQ McAlindon, TE Hannan, MT Chaisson, CE Klein, R Wilson, PWF Felson, DT AF Zhang, YQ McAlindon, TE Hannan, MT Chaisson, CE Klein, R Wilson, PWF Felson, DT TI Estrogen replacement therapy and worsening of radiographic knee osteoarthritis SO ARTHRITIS AND RHEUMATISM LA English DT Article ID FRAMINGHAM OSTEOARTHRITIS; ELDERLY WOMEN; HIP; RISK; OSTEOPOROSIS; PREVALENCE; DENSITY; HAND AB Objective. To examine whether estrogen replacement therapy (ERT) prevents worsening of radiographic knee osteoarthritis (OA) in elderly women, Methods. A total of 551 women ages 63-91 years (mean age 71) in the Framingham Study were followed up from biennial examination 18 (1983-1985) to examination 22 (1992-1993), Data on postmenopausal ERT were obtained every 2 a-ears. Subjects were classified into 3 groups according to their estrogen use at biennial examination 18: never users (n = 349), past users (n 162), and current users (n = 40), Women received anteroposterior weight-bearing knee radiographs at examinations 18 and 22, Using the Kellgren and Lawrence criteria, global radiographic knee OA was assessed, (grade range 0-4) and individual radiographic features, such as osteophytes and joint space narrowing, were scored from 0 to 3, Worsening was defined as either development of radiographic OA that was not present at baseline (incident OA) or progression of baseline radiographic OA by greater than or equal to 1 Kellgren and Lawrence grade (progressive OA). Potential confounding factors included age, body mass index, weight change, smoking, knee injury, physical activity level, and bone mineral density at the femoral neck. Results. During 8 Sears of followup, 17.4% of knee radiographic scores worsened by I grade and 5.8% by 2 or 3 grades among never users of ERT, Among current estrogen users, only 11.7% of knee radiographic scores worsened by 1 grade and none worsened by more than I grade. After adjusting for age and other potential confounding factors, the relative risk of incident radiographic knee OA in comparison with never users of estrogen was 0.8 (95% confidence interval [95% CI] 0.5-1.4) in past users and 0.4 (95% 0.1-3.0) in current users. Current use of estrogen also showed a trend toward decreased risk of progressive knee OA compared with never use (odds ratio [OR] 0.5, 95% CI 0.1-2.9), When both incident and progressive radiographic knee OA cases were combined, current ERT use had a 60% decreased risk compared with never use (OR 0.4, 95% CI 0.1-1.5), Conclusion. This is the first prospective cohort study to examine the effects of ERT on radiographic knee OA, The results indicate that current use of ERT had a moderate, but not statistically significant, protective effect against worsening of radiographic knee OA among elderly white women. These findings corroborate those of cross-sectional studies and point further to a potential benefit of female hormones in OA. C1 Boston Univ, Med Ctr, Boston, MA 02215 USA. Hebrew Rehabil Ctr Aged, Boston, MA 02131 USA. Harvard Univ, Sch Med, Boston, MA USA. NHLBI, Framingham Heart Study, NIH, Bethesda, MD USA. RP Zhang, YQ (reprint author), Boston Univ, Med Ctr, Room A-203,80 E Concord St, Boston, MA 02215 USA. FU NIA NIH HHS [AG-09300]; NIAMS NIH HHS [AR-20613] NR 25 TC 101 Z9 107 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD OCT PY 1998 VL 41 IS 10 BP 1867 EP 1873 DI 10.1002/1529-0131(199810)41:10<1867::AID-ART20>3.0.CO;2-W PG 7 WC Rheumatology SC Rheumatology GA 127FZ UT WOS:000076341300019 PM 9778229 ER PT J AU Magruder, KM AF Magruder, KM TI Behavioral medicine in the mainstream primary care setting SO BEHAVIORAL HEALTHCARE TOMORROW LA English DT Article ID MENTAL-DISORDERS; MANAGEMENT; GUIDELINES; DEPRESSION C1 NIMH, Div Epidemiol & Serv Res, Bethesda, MD 20892 USA. RP Magruder, KM (reprint author), NIMH, Div Epidemiol & Serv Res, Bethesda, MD 20892 USA. NR 8 TC 0 Z9 0 U1 0 U2 0 PU CENTRALINK PUBLICATIONS PI TIBURON PA 1110 MAR WEST ST STE E, TIBURON, CA 94920-1879 USA SN 1063-8490 J9 BEHAV HEALTHC TOM JI Behav. Healthcare Tomorrow PD OCT PY 1998 VL 7 IS 5 BP 55 EP 56 PG 2 WC Psychology, Clinical; Health Policy & Services SC Psychology; Health Care Sciences & Services GA 125NM UT WOS:000076243700034 PM 10185203 ER PT J AU Pommier, Y Pourquier, P Fan, Y Strumberg, D AF Pommier, Y Pourquier, P Fan, Y Strumberg, D TI Mechanism of action of eukaryotic DNA topoisomerase I and drugs targeted to the enzyme SO BIOCHIMICA ET BIOPHYSICA ACTA-GENE STRUCTURE AND EXPRESSION LA English DT Review DE camptothecin; DNA repair; DNA replication; recombination; gene regulation; DNA break ID SIMIAN VIRUS-40 DNA; SINGLE-STRANDED-DNA; RNA-POLYMERASE-II; PROTEIN-KINASE-C; COMPOUND 6-N-FORMYLAMINO-12,13-DIHYDRO-1,11-DIHYDROXY-13-(BETA-D-GLUCOPYRANOSYL); NICKING-CLOSING ENZYME; HUMAN COLON-CARCINOMA; HUMAN-LEUKEMIA-CELLS; HAMSTER DC3F CELLS; HEAT-SHOCK GENES AB DNA topoisomerase I is essential for cellular metabolism and survival. It is also the target of a novel class of anticancer drugs active against previously refractory solid tumors, the camptothecins. The present review describes the topoisomerase I catalytic mechanisms with particular emphasis on the cleavage complex that represents the enzyme's catalytic intermediate and the site of action for camptothecins. Roles of topoisomerase I in DNA replication, transcription and recombination are also reviewed, Because of the importance of topoisomerase I as a chemotherapeutic target, we review the mechanisms of action of camptothecins and the other topoisomerase I inhibitors identified to date. 0167-4781/98/$ - see front matter (C) 1998 Elsevier Science B.V. All rights reserved. C1 NCI, Mol Pharmacol Lab, Div Basic Sci, Bethesda, MD 20892 USA. RP Pommier, Y (reprint author), NCI, Mol Pharmacol Lab, Div Basic Sci, Bethesda, MD 20892 USA. EM pommier@nih.gov NR 276 TC 490 Z9 494 U1 2 U2 29 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4781 J9 BBA-GENE STRUCT EXPR JI Biochim. Biophys. Acta-Gene Struct. Expression PD OCT 1 PY 1998 VL 1400 IS 1-3 BP 83 EP 106 DI 10.1016/S0167-4781(98)00129-8 PG 24 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 129AH UT WOS:000076440500007 PM 9748515 ER PT J AU Takimoto, CH Wright, J Arbuck, SG AF Takimoto, CH Wright, J Arbuck, SG TI Clinical applications of the camptothecins SO BIOCHIMICA ET BIOPHYSICA ACTA-GENE STRUCTURE AND EXPRESSION LA English DT Review DE camptothecin; topoisomerase I; irinotecan; topotecan ID TOPOISOMERASE-I-INHIBITOR; CELL LUNG-CANCER; EVERY 3 WEEKS; IRINOTECAN HYDROCHLORIDE CPT-11; 24-HOUR CONTINUOUS-INFUSION; COLONY-STIMULATING FACTOR; ADVANCED SOLID TUMORS; METASTATIC COLORECTAL-CANCER; EPITHELIAL OVARIAN-CANCER; ACTIVE METABOLITE SN-38 AB The camptothecin topoisomerase I-targeting agents are new class of antitumor drugs with demonstrated clinical activity in human malignancies, such as colorectal cancer and ovarian cancer. Currently, irinotecan and topotecan are the most widely used camptothecin analogs in clinical use and clinical trials are ongoing to better characterize their spectra of clinical activity, to determine their optimal schedules of administration and to define their use in combination with other chemotherapeutic agents. Newer camptothecin analogs in clinical development, such as 9-aminocamptothecin, 9-nitrocamptothecin, GI147211 and DX-8951f, are also being studied to determine if they have improved toxicity and efficacy profiles compared with existing analogs. Other potential clinical applications include the use of camptothecin derivatives as radiation sensitizers or as antiviral agents. The successful development of the camptothecins as antitumor agents highlights the importance of topoisomerase I as a target for cancer chemotherapy. 0167-4781/98/$ - see front matter (C) 1998 Elsevier Science B.V. All rights reserved. C1 Bethesda Naval Hosp, Dev Therapeut Dept, Med Branch, Div Clin Sci,NCI, Bethesda, MD 20892 USA. NCI, Invest Drug Branch, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. RP Takimoto, CH (reprint author), Bethesda Naval Hosp, Dev Therapeut Dept, Med Branch, Div Clin Sci,NCI, Bldg 8,Room 5101, Bethesda, MD 20892 USA. EM ctakim@helix.nih.gov NR 146 TC 162 Z9 168 U1 3 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4781 J9 BBA-GENE STRUCT EXPR JI Biochim. Biophys. Acta-Gene Struct. Expression PD OCT 1 PY 1998 VL 1400 IS 1-3 BP 107 EP 119 DI 10.1016/S0167-4781(98)00130-4 PG 13 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 129AH UT WOS:000076440500008 PM 9748525 ER PT J AU Vriesendorp, HM Quadri, SM Borchardt, PE AF Vriesendorp, HM Quadri, SM Borchardt, PE TI Tumour therapy with radiolabelled antibodies - Optimisation of therapy SO BIODRUGS LA English DT Article ID B-CELL LYMPHOMA; I-131-LABELED MONOCLONAL-ANTIBODY; BIFUNCTIONAL CHELATING-AGENTS; PHASE-I TRIAL; OVARIAN-CANCER; IMMUNOGLOBULIN THERAPY; ANTI-CD37 ANTIBODY; HODGKINS-DISEASE; BEAGLE DOGS; METAL-IONS AB The promise of radiolabelled immunoglobulin therapy (RIT) for selective, patient friendly, cancer treatment has not yet been fulfilled. Only patients with haematological malignancies show sizable response rates after RIT. With solid tumours, intravenous administration of radiolabelled antibodies does not provide sufficient tumour targeting. However, intracompartmental administration may solve this problem, particularly if tumour reactive IgM is used. Clinical progress in RIT depends on understanding the important RIT variables: antigen, antibody, radioisotope, conjugation chemistry, activity escalation, fractionation and protein dose. These are reviewed and a new translational decision tree/flow diagram is presented that can limit analysis to the most important RIT variables for a particular disease. These variables may differ depending on the type and stage of cancer, but the guiding principles in RIT development remain the same: selectivity and accountability. The proper application of these principles leads to the definition of a new series of phase I, ii, III studies. These studies are more appropriate for the clinical exploration of RIT and place an emphasis on therapeutic ratio rather than toxicity. C1 Arlington Canc Ctr, Arlington, TX 76012 USA. NIH, Ctr Sci Review, Bethesda, MD 20892 USA. RP Vriesendorp, HM (reprint author), Arlington Canc Ctr, 906 W Randol Mill Rd, Arlington, TX 76012 USA. EM acchmv@ix.netcom.com NR 86 TC 5 Z9 6 U1 0 U2 0 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND SN 1173-8804 J9 BIODRUGS JI Biodrugs PD OCT PY 1998 VL 10 IS 4 BP 275 EP 293 DI 10.2165/00063030-199810040-00003 PG 19 WC Oncology; Immunology; Pharmacology & Pharmacy SC Oncology; Immunology; Pharmacology & Pharmacy GA 134BH UT WOS:000076722600003 PM 18020601 ER PT J AU Baumann, MH Rothman, RB AF Baumann, MH Rothman, RB TI Alterations in serotonergic responsiveness during cocaine withdrawal in rats: Similarities to major depression in humans SO BIOLOGICAL PSYCHIATRY LA English DT Review DE cocaine withdrawal; serotonin neurons; serotonin (1A); receptors; serotonin(2); receptors; depression ID ADRENERGIC-RECEPTOR BINDING; NEURO-ENDOCRINE RESPONSES; NEW-YORK-CITY; NEUROENDOCRINE RESPONSES; SUICIDE VICTIMS; D-FENFLURAMINE; ADRENOCORTICOTROPIC HORMONE; INTRAVENOUS TRYPTOPHAN; PARA-CHLOROAMPHETAMINE; MOLECULAR MECHANISMS AB Background: Withdrawal from long-term cocaine us is accompanied by symptoms resembling major depression. because acute cocaine affects serotonin (5-HT) neurons, and 5-HT dysfunction is implicated in the pathophysiology of depression, we evaluated the effects to 5-HT agonists in rats withdrawn from repeated injections of cocaine (15 mg/kg IP, b.i.d., 7 days) or saline. Methods: In the first study, prolactin (PRL) responses elicited by the 5-HT-releasing agent fenfluramine, the 5- HT(1A) agonist (+/-)-8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), and the 5-HT(2A/2C) agonist (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI) were examined as indicates of postynaptic 5-HT receptor function. In a second study, specific responses induced by 8-OH-DPAT, namely inhibition of brain 5-HT synthesis and stimulation of feeding, were examined as correlates of 5-HT(1A) autoreceptor function. Results: Prior treatment with cocaine did not modify fenfluramine-evoked PRL release; however, the PRL secretory response to 8-OH-DPAT was blunted and the PRL response to DOI was potentiated after chronic cocaine treatment. Cocaine exposure did not alter the inhibitory effect of 8-OH-DPAT on 5-HT synthesis. 8-OH-DPAT-induced feeding was influenced by prior cocaine, but this effect was secondary to pronounced baseline hyperphagia in the cocaine-treated group. Conclusions: These data indicate that withdrawal from chronic cocaine renders specific subpopulations of postsynaptic 5-HT(1A) receptors subsensitive and 5-HT(2A/2C) receptors supersensitive. No evidence for cocacine-induced changes in 5-HT(1A) autoreceptor responsiveness was found. A survey of the literature reveals similarities in the profile of 5-HT dysfunction between rats withdrawn from cocaine and humans diagnosed with depression. We propose that withdrawal from chronic cocaine in rats may serve as a useful animal model of depressive disorders. (C) 1998 Society of Biological Psychiatry. C1 NIDA, Clin Psychopharmacol Sect, IRP, NIH, Baltimore, MD 21224 USA. RP Baumann, MH (reprint author), NIDA, Clin Psychopharmacol Sect, IRP, NIH, POB 5180,5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 122 TC 73 Z9 73 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD OCT 1 PY 1998 VL 44 IS 7 BP 578 EP 591 DI 10.1016/S0006-3223(98)00123-1 PG 14 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 126AV UT WOS:000076271300008 PM 9787882 ER PT J AU Duesbery, NS Vande Woude, GF AF Duesbery, NS Vande Woude, GF TI Cytoplasmic control of nuclear behavior during meiotic maturation of frog oocytes SO BIOLOGY OF THE CELL LA English DT Article DE oocyte; meiosis; maturation; MPF; CSF ID GERMINAL VESICLE BREAKDOWN; ACTIVATED PROTEIN-KINASE; XENOPUS-LAEVIS OOCYTES; MOS MESSENGER-RNA; CYCLIC-AMP LEVELS; MAP KINASE; CELL-CYCLE; PROMOTING FACTOR; SACCHAROMYCES-CEREVISIAE; ONCOGENE PRODUCT AB The title of this article is taken from a 1971 publication by Yoshio Masui and Clement Markert in which they describe the discoveries of the meiotic regulatory activities maturation promoting factor and cytostatic factor. Here we review the experiments that led to these discoveries and discuss their relation to our current knowledge of the biochemistry of oocyte maturation. ((C) Elsevier, Paris). C1 NCI, ABL Basic Res Program, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Vande Woude, GF (reprint author), NCI, ABL Basic Res Program, Frederick Canc Res & Dev Ctr, POB B, Frederick, MD 21702 USA. OI DUESBERY, NICK/0000-0002-4258-5655 NR 72 TC 3 Z9 3 U1 1 U2 10 PU EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS CEDEX 15 PA 23 RUE LINOIS, 75724 PARIS CEDEX 15, FRANCE SN 0248-4900 J9 BIOL CELL JI Biol. Cell PD OCT PY 1998 VL 90 IS 6-7 BP 461 EP 466 PG 6 WC Cell Biology SC Cell Biology GA 159XM UT WOS:000078200700004 PM 9923071 ER PT J AU Sassaman, MB Giovanelli, J Sood, VK Eckelman, WC AF Sassaman, MB Giovanelli, J Sood, VK Eckelman, WC TI Synthesis and screening of conformationally restricted and conformationally free N-(tertiary aminoalkyl)dithiocarbamic acids and esters as inhibitors of neuronal nitric oxide synthase SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article DE inhibitors; nitric oxide synthase; tetrahydrobiopterin; dithiocarbamic acid; dithiocarbamic ester ID POTENT INHIBITORS; L-THIOCITRULLINE; L-ARGININE; RAT-BRAIN; TETRAHYDROBIOPTERIN; BINDING; ENZYME; HEME; CYTOCHROME-P-450; REDUCTASE AB N-(Tertiary aminoalkyl)dithiocarbamic acids and esters were synthesized and evaluated for their ability to inhibit neuronal nitric oxide synthase. Preliminary results show these compounds are able to act at the binding site for L-arginine and the conformationally restricted esters may have a second site of activity involving the cofactor (6R)-5,6,7,8-tetrahydro-L-biopterin. Published by Elsevier Science Ltd. C1 NIH, Warren G Magnuson Clin Ctr, Positron Emiss Tomog Dept, Bethesda, MD 20892 USA. NIMH, Neurochem Lab, Bethesda, MD 20892 USA. George Washington Univ, Med Ctr, Dept Radiol, Washington, DC 20037 USA. RP Sassaman, MB (reprint author), NIH, Warren G Magnuson Clin Ctr, Positron Emiss Tomog Dept, Bethesda, MD 20892 USA. RI Sood, Vinay/B-7109-2008 FU NIMH NIH HHS [N01MH20003] NR 33 TC 4 Z9 4 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0968-0896 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD OCT PY 1998 VL 6 IS 10 BP 1759 EP 1766 DI 10.1016/S0968-0896(98)00132-1 PG 8 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 136KM UT WOS:000076858000009 PM 9839005 ER PT J AU Yao, ZJ Ye, B Wu, XW Wang, SM Wu, L Zhang, ZY Burke, TR AF Yao, ZJ Ye, B Wu, XW Wang, SM Wu, L Zhang, ZY Burke, TR TI Structure-based design and synthesis of small molecule protein-tyrosine phosphatase 1B inhibitors SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article; Proceedings Paper CT 213th National ACS Meeting CY 1997 CL SAN FRANCISCO, CALIFORNIA SP ACS DE amino acids and derivatives; mimetics; phosphonic acids and derivatives; phosphorylation ID SOLID-PHASE SYNTHESIS; O-PHOSPHOTYROSINE; SUBSTRATE-SPECIFICITY; MULTIPOLE METHOD; PEPTIDES; SIMULATIONS; RECOGNITION; ANALOGS AB Protein-tyrosine phosphatase (PTP) inhibitors are attractive as potential signal transduction-directed therapeutics which may be useful in the treatment of a variety of diseases. We have previously reported the X-ray structure of 1,1-difluoro-1-(2-naphthalenyl)methyl] phosphonic acid (4) complexed with the human the protein-tyrosine phosphatase 1B (PTP1B) and its use in the design of an analogue which binds with higher affinity within the catalytic site (Burke, T. R., Jr. et al. Biochemistry 1996, 35, 15989). In the current study, new naphthyldifluoromethyl phosphonic acids were designed bearing acidic functionality intended to interact with the PTP1B Arg47, which is situated just outside the catalytic pocket. This residue has been shown previously to provide key interactions with acidic residues of phosphotyrosyl-containing peptide substrates. Consistent with trends predicted by molecular dynamics calculations, the new analogues bound with 7- to 14-fold higher affinity than the parent 4, in principal validating the design rationale. (C) 1998 Elsevier Science Ltd. All rights reserved. C1 NCI, Div Basic Sci, Med Chem Lab, NIH, Bethesda, MD 20892 USA. Georgetown Univ, Med Ctr, Inst Cognit & Computat Sci, Washington, DC 20007 USA. Albert Einstein Coll Med, Dept Mol Pharmacol, Bronx, NY 10461 USA. RP Burke, TR (reprint author), NCI, Div Basic Sci, Med Chem Lab, NIH, Bethesda, MD 20892 USA. RI Burke, Terrence/N-2601-2014; Yao, Zhu-Jun/E-7635-2015 NR 29 TC 50 Z9 50 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0968-0896 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD OCT PY 1998 VL 6 IS 10 BP 1799 EP 1810 DI 10.1016/S0968-0896(98)00140-0 PG 12 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 136KM UT WOS:000076858000014 PM 9839010 ER PT J AU Lee, YS Chen, Z Kador, PF AF Lee, YS Chen, Z Kador, PF TI Molecular modeling studies of the binding modes of aldose reductase inhibitors at the active site of human aldose reductase SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article DE aldose reductase inhibitors; hydrogen bond; charge interaction; aromatic-aromatic interaction; pharmacophore requirements ID DIABETIC COMPLICATIONS; ALDEHYDE REDUCTASE; SUBSTRATE; ZOPOLRESTAT; MECHANISM; ACIDS AB Molecular modeling studies using the CHARMM method have been conducted to study the binding modes of aldose reductase inhibitors at the active site of aldose reductase. The energy minimized structures of aldose reductase with six structurally diverse inhibitors (spirofluorene-9,5'-imidazolidine-2',4'-dione (1), 9-fluoreneacetic acid (2), AL1576 (3), 2,7-difluoro-9-fluoreneacetic acid (4), FK366 (5), and Epalrestat (9)) indicate that the side chains of Tyr48, His110, and Trp111 can form numerous hydrogen bonds with either the carboxylate or the hydantoin group of the inhibitors while the side chains of Trp20, Trp111, and Phe122 are positioned to form aromatic-aromatic interactions. Of the three residues (Tyr 48, His 110, and Trp 111) that can form hydrogen bonds with the ionized portion of aldose reductase inhibitors, protonated His110 appears to play an important role in directing charged inhibitors to bind at the active site through charge interaction. Based on the binding mode of the inhibitors and their observed inhibitory activities, pharmacophore requirements for aldose reductase inhibitors are discussed. Published by Elsevier Science Ltd. C1 NEI, NIH, Bethesda, MD 20892 USA. RP Lee, YS (reprint author), NEI, NIH, Bethesda, MD 20892 USA. EM yongslee@helix.nih.gov NR 35 TC 48 Z9 48 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0968-0896 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD OCT PY 1998 VL 6 IS 10 BP 1811 EP 1819 DI 10.1016/S0968-0896(98)00139-4 PG 9 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 136KM UT WOS:000076858000015 PM 9839011 ER PT J AU Rostovtseva, TK Aguilella, VM Vodyanoy, I Bezrukov, SM Parsegian, VA AF Rostovtseva, TK Aguilella, VM Vodyanoy, I Bezrukov, SM Parsegian, VA TI Membrane surface-charge titration probed by gramicidin A channel conductance SO BIOPHYSICAL JOURNAL LA English DT Article ID PHOSPHOLIPID-BILAYERS; PHASE-TRANSITION; LIPID BILAYERS; ION BINDING; K+ CHANNEL; A CHANNEL; PHOSPHATIDYLSERINE; PHOSPHATIDYLCHOLINE; MONOLAYERS; DIVALENT AB We manipulate lipid bilayer surface charge and gauge its influence on gramicidin A channel conductance by two strategies: titration of the lipid charge through bulk solution pH and dilution of a charged lipid by neutral. Using diphytanoyl phosphatidylserine (PS) bilayers with CsCl aqueous solutions, we show that the effects of lipid charge titration on channel conductance are masked 1) by conductance saturation with Cs+ ions in the neutral pH range and 2) by increased proton concentration when the bathing solution pH is less than 3. A smeared charge model permits us to separate different contributions to the channel conductance and to introduce a new method for "bilayer pKa" determination. We use the Gouy-Chapman expression for the charged surface potential to obtain equilibria of protons and cations with lipid charges. To calculate cation concentration at the channel mouth, we compare different models for the ion distribution, exact and linearized forms of the planar Poisson-Boltzmann equation, as well as the construction of a "Gibbs dividing surface" between salt bath and charged membrane. All approximations yield the intrinsic pK(a)(in) of PS lipid in 0.1 M CsCl to be in the range 2.5-3.0. By diluting PS surface charge at a fixed pH with admired neutral diphytanoyl phosphatidylcholine (PC), we obtain a conductance decrease in magnitude greater than expected from the electrostatic model. This observation is in accord with the different conductance saturation values for PS and PC lipids reported earlier (Apell et al. 1979, Biochim. Biophys. Acta. 552:369-378) and verified in the present work for solvent-free membranes. In addition to electrostatic effects of surface charge, gramicidin A channel conductance is also influenced by lipid-dependent structural factors. C1 NICHD, Lab Phys & Struct Biol, NIH, Bethesda, MD 20892 USA. Univ Jaume 1, Dept Ciencias Expt, Castellon de La Plana 12080, Spain. Off Naval Res Europe, London NW1 5TH, England. St Petersburg Nucl Phys Inst, Gatchina 188350, Russia. RP Parsegian, VA (reprint author), NICHD, Lab Phys & Struct Biol, NIH, Bldg 12A,Rm 20-41, Bethesda, MD 20892 USA. EM vap@cu.nih.gov RI Aguilella, Vicente/B-7592-2008 OI Aguilella, Vicente/0000-0002-2420-2649 NR 39 TC 75 Z9 76 U1 1 U2 6 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD OCT PY 1998 VL 75 IS 4 BP 1783 EP 1792 PG 10 WC Biophysics SC Biophysics GA 123UT UT WOS:000076144000018 PM 9746520 ER PT J AU Hagiwara, K Freeman, AAH McMenamin, MG Harris, CC AF Hagiwara, K Freeman, AAH McMenamin, MG Harris, CC TI Screening cloned PCR fragments by restriction endonuclease finger-printing to obtain wild-type sequences SO BIOTECHNIQUES LA English DT Article ID POLYMERASE CHAIN-REACTION; DNA; LONG; POLYMORPHISMS; MUTATIONS C1 NCI, Human Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. RP Harris, CC (reprint author), NCI, Human Carcinogenesis Lab, NIH, 37 Convent Dr,37-2C05, Bethesda, MD 20892 USA. EM Curtis_Harris@nih.gov NR 9 TC 1 Z9 1 U1 0 U2 0 PU EATON PUBLISHING CO PI NATICK PA 154 E. CENTRAL ST, NATICK, MA 01760 USA SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD OCT PY 1998 VL 25 IS 4 BP 554 EP + PG 3 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 128RL UT WOS:000076420100001 PM 9793631 ER PT J AU Foundas, AL Eure, KF Luevano, LF Weinberger, DR AF Foundas, AL Eure, KF Luevano, LF Weinberger, DR TI MRI asymmetries of Broca's area: The pars triangularis and pars opercularis SO BRAIN AND LANGUAGE LA English DT Article; Proceedings Paper CT 48th Annual Meeting of the American-Academy-of-Neurology CY MAR 23-30, 1996 CL SAN FRANCISCO, CALIFORNIA SP Amer Acad Neurol ID PLANUM TEMPORALE ASYMMETRY; ANTERIOR SPEECH REGION; CEREBRAL LATERALIZATION; HEMISPHERIC-DIFFERENCES; BIOLOGICAL MECHANISMS; LANGUAGE LOCALIZATION; APHASIA; ORGANIZATION; HANDEDNESS; DOMINANCE AB Broca's area. which includes the pars triangularis (PTR) and pars opercularis (POP), is a neuroanatomic region important in speech-language production. Previous data demonstrated that PTR asymmetries are highly correlated with language dominance determined by selective hemispheric anesthesia or Wada testing, suggesting that asymmetries of the PTR may, in part, predict language dominance, The POP, however. has not been measured on volumetric magnetic resonance imaging (MRI), and therefore, it is unclear whether morphological asymmetries of the POP exist, and whether these asymmetries differ in right- and left-handers. The purpose of this study was to determine if measurable asymmetries of the POP exist on MRI, and whether the direction of the asymmetries differ in right- and left-handers. The PTR and POP were measured on volumetric MRI scans of 16 right-handers and 16 left-handers matched for age and gender. There was a significant leftward asymmetry of the PTR in right- and left-handers, although the asymmetry was reduced in the left-handers. In contrast, there was a leftward asymmetry of the POP in right-handers, and a rightward asymmetry in the left-handers. Handedness, derived from a handedness inventory, was positively correlated with POP asymmetry. (C) 1998 Academic Press. C1 Tulane Univ, Sch Med, Dept Psychiat & Neurol, New Orleans, LA 70112 USA. Vet Affairs Med Ctr, Neurol Serv, New Orleans, LA USA. NIMH, Intramural Res Program, Neurosci Ctr St Elizabeths, Clin Brain Disorders Branch, Washington, DC 20032 USA. RP Foundas, AL (reprint author), Tulane Univ, Sch Med, Dept Psychiat & Neurol, SL-23,1430 Tulane Ave, New Orleans, LA 70112 USA. EM foundas@mailhost.tcs.tulane.edu FU NIDCD NIH HHS [K08-DC99135-01] NR 67 TC 101 Z9 102 U1 1 U2 4 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0093-934X J9 BRAIN LANG JI Brain Lang. PD OCT 1 PY 1998 VL 64 IS 3 BP 282 EP 296 DI 10.1006/brln.1998.1974 PG 15 WC Audiology & Speech-Language Pathology; Linguistics; Neurosciences; Psychology, Experimental SC Audiology & Speech-Language Pathology; Linguistics; Neurosciences & Neurology; Psychology GA 122EE UT WOS:000076058300002 PM 9743543 ER PT J AU Fujimoto, W Ishida-Yamamoto, A Hsu, R Nagao, Y Iizuka, H Yancey, KB Arata, J AF Fujimoto, W Ishida-Yamamoto, A Hsu, R Nagao, Y Iizuka, H Yancey, KB Arata, J TI Anti-epiligrin cicatricial pemphigoid: a case associated with gastric carcinoma and features resembling epidermolysis bullosa acquisita SO BRITISH JOURNAL OF DERMATOLOGY LA English DT Article ID EPIDERMAL BASEMENT-MEMBRANE; EXTRACELLULAR DOMAIN; ANCHORING FILAMENTS; AUTOANTIBODIES; LAMININ-5; SKIN; IDENTIFICATION; SPECIFICITY; MOLECULES; DISEASES AB A 48-year-old woman with anti-epiligrin cicatricial pemphigoid (CP) who showed clinical features resembling epidermolysis bullosa acquisita was found to have adenocarcinoma of the stomach. Histological examination of lesional skin demonstrated a subepidermal blister. Direct immunofluorescence microscopy of perilesional skin revealed linear deposits of IgG and C3 at the basement membrane zone. The patient's serum contained IgG autoantibodies that bound to the dermal side of 1 mol/L NaCl-split normal human skin as determined by indirect immunofluorescence microscopy, and the lamina lucida as determined by indirect immunoelectron microscopy. The patient's serum immunoprecipitated laminin-5 from extracts and media of biosynthetically radiorabelled human keratinocytes, Immunoblot studies showed that the patient's autoantibodies specifically bound the alpha 3 subunit of this laminin isoform. Fragility of the skin and bullous lesions disappeared after total gastrectomy, but soon reappeared possibly in association with metastatic disease in a lymph node. The possibility that anti-epiligrin CP may develop paraneoplastically in some patients is discussed. C1 Okayama Univ, Sch Med, Dept Dermatol, Okayama 700, Japan. Asahikawa Med Coll, Dept Dermatol, Asahikawa, Hokkaido 078, Japan. NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. Okayama Red Cross Hosp, Dept Dermatol, Okayama 700, Japan. RP Fujimoto, W (reprint author), Okayama Univ, Sch Med, Dept Dermatol, 2-5-1 Shikata, Okayama 700, Japan. NR 28 TC 33 Z9 34 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0007-0963 J9 BRIT J DERMATOL JI Br. J. Dermatol. PD OCT PY 1998 VL 139 IS 4 BP 682 EP 687 PG 6 WC Dermatology SC Dermatology GA 131YV UT WOS:000076603600020 PM 10025973 ER PT J AU Roberge, FG de Smet, MD Benichou, J Kriete, MF Raber, J Hakimi, J AF Roberge, FG de Smet, MD Benichou, J Kriete, MF Raber, J Hakimi, J TI Treatment of uveitis with recombinant human interleukin-13 SO BRITISH JOURNAL OF OPHTHALMOLOGY LA English DT Article ID LOW-DOSE CYCLOSPORINE; HUMAN MONOCYTES; IFN-GAMMA; CYTOKINE PRODUCTION; TNF-ALPHA; IL-13; CELLS; MODULATION; THERAPY; LYMPHOCYTES AB Aim-To evaluate the anti-inflammatory cytokine interleukin-13 (IL-13) for the treatment of uveitis. Methods-Uveitis was induced in monkeys by immunisation with human retinal S-antigen. Starting at the onset of disease, the animals were treated with IL-13 at 25 mu g/kg, or vehicle control, injected subcutaneously once a day for 28 days. Intraocular inflammation was scored by indirect ophthalmoscopy for a period of 56 days. Circulating leucocyte levels were monitored. Results-Uveitis started unilaterally in all but one animal. IL-13 inhibited inflammation both in the eyes in which the disease was present when the treatment was initiated (p=0.0001), and in the contralateral initially negative eyes (p=0.0001). After cessation of therapy, there was a progressive increase of inflammation in the IL-13 treated group. However, the beneficial effect of IL-13 extended into the 4 week follow up period. IL-13 produced an increase in circulating polymorphonuclear neutrophils and a decrease in lymphocytes. Conclusion-Administration of IL-13 appears to be a promising modality of treatment for severe uveitis. C1 NEI, NIH, Bethesda, MD 20892 USA. NCI, Biostat Branch, NIH, Bethesda, MD 20892 USA. Hoffmann La Roche Inc, Roche Res Ctr, Inflammat & Autoimmune Dis, Nutley, NJ 07110 USA. RP Roberge, FG (reprint author), Hop La Pitie Salpetriere, Dept Ophthalmol, 47-83 Blvd Hop,Bat Babinski, F-75013 Paris, France. OI de Smet, Marc/0000-0002-9217-5603 NR 30 TC 11 Z9 11 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0007-1161 J9 BRIT J OPHTHALMOL JI Br. J. Ophthalmol. PD OCT PY 1998 VL 82 IS 10 BP 1195 EP 1198 DI 10.1136/bjo.82.10.1195 PG 4 WC Ophthalmology SC Ophthalmology GA 128LW UT WOS:000076409100025 PM 9924310 ER PT J AU Lyon, BJ Stavri, PZ Hochstein, DC Nardini, HG AF Lyon, BJ Stavri, PZ Hochstein, DC Nardini, HG TI Internet access in the libraries of the National Network of Libraries of Medicine SO BULLETIN OF THE MEDICAL LIBRARY ASSOCIATION LA English DT Article AB As the National Library of Medicine expands access to its products and services by making them available on the Internet, more accurate information about current and future access in medical libraries is needed. The National Network Office of the National Library of Medicine conducted a survey of all network member libraries to determine the extent of connectivity and the barriers preventing 100% connectivity. Respondents called a toll-free number and, using interactive voice technology, answered questions concerning Internet access in their library. Seventy-eight percent of the network member libraries responded. Four percent of academic libraries, 27% of hospital libraries, and 10% of "other" libraries reported that they were not connected. Computer cost, lack of in-house expertise, and lack of management support were the highest ranked barriers to connecting. The National Library of Medicine and the Regional Medical Libraries will use information from this survey to develop strategies to help all member libraries achieve full connectivity. C1 Natl Lib Med, Natl Network Off, Bethesda, MD 20894 USA. Natl Lib Med, Associate Fellowship Program, Bethesda, MD 20894 USA. Johns Hopkins Univ, SAIS Bologna Ctr, Bologna, Italy. RP Lyon, BJ (reprint author), Natl Lib Med, Natl Network Off, 8600 Rockville Pike, Bethesda, MD 20894 USA. NR 6 TC 1 Z9 1 U1 0 U2 1 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 OCT PY 1998 VL 86 IS 4 BP 486 EP 490 PG 5 WC Information Science & Library Science SC Information Science & Library Science GA 130EP UT WOS:000076507200004 PM 9803289 ER PT J AU Roberts, RL Miller, AK Taymans, SE Carter, CS AF Roberts, RL Miller, AK Taymans, SE Carter, CS TI Role of social and endocrine factors in alloparental behavior of prairie voles (Microtus ochrogaster) SO CANADIAN JOURNAL OF ZOOLOGY-REVUE CANADIENNE DE ZOOLOGIE LA English DT Article ID PARENTAL BEHAVIOR; PATERNAL BEHAVIOR; PENNSYLVANICUS; ENVIRONMENT; PHILOPATRY AB Young, sexually naive prairie voles (Microtus ochrogaster, 21-60 days of age, of both sexes readily exhibit alloparental behavior toward pups without apparent hormonal or experiential priming. The goal of the present study was to quantify the incidence of spontaneously evoked alloparental behavior in young prairie voles and determine prior pup experience fi), gender-related (ii) and age-related (iii) characteristics, and hormonal (iv) and housing (v) conditions associated with alloparental behavior. Overall, 70% of all prairie voles between 21 and 60 days of age exhibited alloparental behavior regardless of hormonal condition or postweaning housing condition (single versus sib-group housing). Experience with pups prior to weaning was associated with a greater percentage of prairie voles exhibiting alloparental responding in comparison with prairie voles that had never been exposed to pups. Male prairie voles were more likely to be alloparental than were females, although most females (64%) exhibited alloparental behavior. Differences in qualitative variables associated with alloparental responsiveness were present between prairie voles <40 days of age and those <40 days of age, although both age groups responded parentally in equal numbers. This study suggests that although a short period of prior experience may promote the expression of alloparental behavior in young prairie voles, alloparental behavior occurs in most animals in all groups examined. Hormonal, sex-related or age-related changes that might be associated with development, reproductive suppression, or social stress are not related to the differential expression of alloparental behavior. C1 Univ Maryland, Dept Zool, College Pk, MD 20742 USA. RP Roberts, RL (reprint author), NICHHD, Comparat Ethol Lab, NIH, Anim Ctr, POB 529, Poolesville, MD 20837 USA. NR 35 TC 44 Z9 45 U1 0 U2 7 PU NATL RESEARCH COUNCIL CANADA PI OTTAWA PA RESEARCH JOURNALS, MONTREAL RD, OTTAWA, ONTARIO K1A 0R6, CANADA SN 0008-4301 J9 CAN J ZOOL JI Can. J. Zool.-Rev. Can. Zool. PD OCT PY 1998 VL 76 IS 10 BP 1862 EP 1868 DI 10.1139/cjz-76-10-1862 PG 7 WC Zoology SC Zoology GA 189KH UT WOS:000079903300008 ER PT J AU Swan, J Wingo, P Clive, R West, D Miller, D Hutchison, C Sondik, EJ Edwards, BK AF Swan, J Wingo, P Clive, R West, D Miller, D Hutchison, C Sondik, EJ Edwards, BK TI Cancer surveillance in the US - Can we have a national system? SO CANCER LA English DT Editorial Material DE cancer control; cancer registry; cancer surveillance; registrar AB Cancer-related services are consuming ever-increasing health resources; along with this trend, health care costs are rising. As health care planners, researchers, and policymakers formulate strategies to meet this challenge, they are looking to cancer registries and the health information system built around them as collectors of the most extensive information regarding cancer treatment in the U.S. Currently, there are multiple programs collecting and reporting data regarding cancer incidence, morbidity, mortality, and survival. This report profiles cancer surveillance efforts in the U.S. and describes the National Coordinating Council for Cancer Surveillance, which was organized in 1995 to facilitate a collaborative approach among the organizations involved. Cancer 1998;83:1282-91. (C) 1998 American Cancer Society. C1 NCI, Canc Surveillance Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20895 USA. Amer Canc Soc, Dept Epidemiol & Surveillance Res, Atlanta, GA 30329 USA. Amer Coll Surgeons, Commiss Canc, Chicago, IL USA. No Calif Canc Ctr, Union City, CA USA. Ctr Dis Control & Prevent, Natl Program Canc Registries, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA USA. Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Columbus, OH USA. RP Swan, J (reprint author), NCI, Canc Surveillance Res Program, Div Canc Control & Populat Sci, EPN 343,6130 Execut Blvd, Bethesda, MD 20895 USA. NR 16 TC 25 Z9 25 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0008-543X J9 CANCER JI Cancer PD OCT 1 PY 1998 VL 83 IS 7 BP 1282 EP 1291 DI 10.1002/(SICI)1097-0142(19981001)83:7<1282::AID-CNCR3>3.0.CO;2-L PG 10 WC Oncology SC Oncology GA 122KF UT WOS:000076070200003 PM 9762927 ER PT J AU Mannion, C Park, WS Man, YG Zhuang, ZP Albores-Saavedra, J Tavassoli, FA AF Mannion, C Park, WS Man, YG Zhuang, ZP Albores-Saavedra, J Tavassoli, FA TI Endocrine tumors of the cervix - Morphologic assessment, expression of human papillomavirus, and evaluation for loss of heterozygosity on 1p, 3p, 11q, and 17p SO CANCER LA English DT Article; Proceedings Paper CT 86th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 01-08, 1997 CL ORLANDO, FLORIDA SP US & Canadian Acad Pathol DE cervical carcinoma; endocrine carcinoma; small cell carcinoma; human papillomavirus; in situ hybridization; loss of heterozygosity; 3p; p53 ID SMALL-CELL-CARCINOMA; DIGOXIGENIN LABELED PROBES; UTERINE CERVIX; LUNG-CANCER; NEUROENDOCRINE CARCINOMA; CHROMOSOME 3P; SHORT ARM; P53 GENE; DELETION; TYPE-18 AB BACKGROUND. Cervical endocrine tumors are rare lesions, with a varied diagnostic nomenclature. A recent consensus meeting proposed a standardized terminology. This study evaluated: 1) applicability of histopathologic guidelines; 2) evidence of loss of heterozygosity (LOH) at selected sites; and 3) the presence of human papillomavirus (HPV) detected by nonisotopic in situ hybridization (ISH). METHODS. Thirty-eight cases (patient age range, 19-88 years; mean, 48 years) were retrieved. Outcome data were available for 32 patients. Classification was based on architectural and cytologic features. Tissue was available from 15 cases for LOH analysis with D3S1234(3p14), D3S1289(3p21), THRB(3p24), TP53(17p13), D1S468(1p36), and INT-2(11q13). In ten cases, tissue was analyzed by nonisotopic ISH with HPV probes for types 6/11, 16/18, and 31/33. RESULTS. Tumors were divided into four groups: small cell carcinoma (SCC) (n = 25); large cell neuroendocrine carcinoma (LCNC) (n = 5); SCC with focal LCNC differentiation (n = 3), and carcinoid tumor (n = 5). Tumors defined as exclusively or predominantly SCC had a particularly poor prognosis, with 20 patients dead of disease (<6 years after diagnosis) and 6 alive with disease (after <3 years of follow-up). LOH at various 3p loci (3p14, 3p21, and 3p24) was observed in eight cases. One patient demonstrated LOH on 17p(TP53). Eight of ten cases assessed by ISH showed nuclear staining using a combined HPV-16/18 probe. CONCLUSIONS. Cervical endocrine tumors are highly aggressive and can be subdivided into definable categories. LOH at 3p loci is a frequent finding, as is nuclear staining with a combined HPV-16/18 probe. LOH at 17p(TP53 locus) appears to be relatively uncommon, suggesting that p53 mutations may not be developmentally significant. Cancer 1998;83:1391-400. (C) 1998 American Cancer Society. C1 Univ Texas, SW Med Ctr, Dept Anat Pathol, Dallas, TX 75235 USA. Armed Forces Inst Pathol, Dept Gynecol & Breast Pathol, Washington, DC 20306 USA. Armed Forces Inst Pathol, Lab Gynecol & Breast Pathol, Washington, DC 20306 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. RP Albores-Saavedra, J (reprint author), Univ Texas, SW Med Ctr, Dept Anat Pathol, 5323 Harry Hines Blvd, Dallas, TX 75235 USA. NR 78 TC 41 Z9 43 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0008-543X J9 CANCER JI Cancer PD OCT 1 PY 1998 VL 83 IS 7 BP 1391 EP 1400 DI 10.1002/(SICI)1097-0142(19981001)83:7<1391::AID-CNCR17>3.0.CO;2-# PG 10 WC Oncology SC Oncology GA 122KF UT WOS:000076070200017 PM 9762941 ER PT J AU Krebs-Smith, SM AF Krebs-Smith, SM TI Progress in improving diet to reduce cancer risk SO CANCER LA English DT Article DE diet surveys; fruit; vegetables; grains; dietary fat; alcohol; dietary trends; cancer ID UNITED-STATES; TRENDS; CONSUMPTION; PREVENTION AB BACKGROUND. In an effort to decrease cancer risk among the population, national health objectives for the year 2000 included recommendations to decrease intake of dietary fat and alcohol and increase intake of fruits, vegetables, and grains. The purpose of this article is to assess trends in the intake of these dietary components relative to the national health objectives. METHODS. National food supply data and food consumption survey data were reviewed for their appropriateness for monitoring intake trends. Recent data from both sources are described and interpreted. RESULTS. Americans have made modest but important improvements in their diets in recent years and may meet the "Healthy People 2000" dietary objectives aimed at decreasing cancer risk. Intake of fruits, vegetables, and grains are higher, and those of fat and alcohol are lower than they were at the beginning of the decade. These trends are consistent with recent improvements in mortality rates for those cancer sites with the strongest associations with diet: the colon/rectum, prostate, and breast. CONCLUSIONS. Although the average intake of fruits, vegetables, and grain products is higher, it should be noted that the objective represents the minimum recommendations. Within each of these major food groups, further improvements can be made. In addition, special efforts should be made to guide children toward improvements in their diets and to monitor the diets of children and other subgroups. [See editorial on pages 1278-81, this issue.] Cancer 1998;83:1425-32. (C) 1998 American Cancer Society. C1 NCI, Risk Factor Monitoring & Methodol Sect, Appl Res Branch, Canc Surveillance Res Program,DCCPS,NIH, Bethesda, MD 20892 USA. RP Krebs-Smith, SM (reprint author), NCI, Risk Factor Monitoring & Methodol Sect, Appl Res Branch, Canc Surveillance Res Program,DCCPS,NIH, Execut Plaza N,Rm 313,6130 Execut Blvd,MSC 7344, Bethesda, MD 20892 USA. NR 41 TC 29 Z9 29 U1 1 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0008-543X J9 CANCER JI Cancer PD OCT 1 PY 1998 VL 83 IS 7 BP 1425 EP 1432 DI 10.1002/(SICI)1097-0142(19981001)83:7<1425::AID-CNCR21>3.0.CO;2-5 PG 8 WC Oncology SC Oncology GA 122KF UT WOS:000076070200021 PM 9762945 ER PT J AU Brown, LM Swanson, CA Gridley, G Swanson, GM Silverman, DT Greenberg, RS Hayes, RB Schoenberg, JB Pottern, LM Schwartz, AG Liff, JM Hoover, R Fraumeni, JF AF Brown, LM Swanson, CA Gridley, G Swanson, GM Silverman, DT Greenberg, RS Hayes, RB Schoenberg, JB Pottern, LM Schwartz, AG Liff, JM Hoover, R Fraumeni, JF TI Dietary factors and the risk of squamous cell esophageal cancer among black and white men in the United States SO CANCER CAUSES & CONTROL LA English DT Article DE case-control studies; diet; esophageal neoplasms; raw fruit; raw vegetables ID GASTRIC CARDIA; ALCOHOL; ADENOCARCINOMA; VEGETABLES; TOBACCO; FRUIT AB Objectives: To investigate dietary factors for squamous cell esophageal cancer and whether these factors may contribute to the five-fold higher incidence of this cancer in the black versus white population of the United States. Methods: Data from a food frequency questionnaire were analyzed for 114 white men and 219 black men with squamous cell esophageal cancer, and 681 white and 557 black male controls from three areas of the United States who participated in a population-based case-control study of esophageal cancer. Results: Protective effects were associated with intake of raw fruits and vegetables (odds ratio for high versus low consumers = 0.3 in both white and black men) and use of vitamin supplements (especially vitamin C; odds ratio for high versus low consumers = 0.4 in both races), with the frequency of consumption of raw fruits and vegetables and vitamin supplements being greater for white than black controls. In addition, elevated risks were associated with high versus low intake of red meat (OR = 2.7 for blacks and 1.5 for whites) and processed meat (OR = 1.6 for blacks and 1.7 for whites), with the levels of consumption being greater for black than white controls. Conclusions: In the United States, these dietary factors may contribute in part to the much higher incidence of squamous cell esophageal cancer among black compared to white men. C1 NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. Michigan Canc Fdn, Detroit, MI 48201 USA. Michigan State Univ, Ctr Canc, E Lansing, MI 48824 USA. Allegheny Univ Hlth Sci, Dept Human Genet, Pittsburgh, PA USA. Emory Univ, Rollins Sch Publ Hlth, Atlanta, GA USA. New Jersey State Dept Hlth, Trenton, NJ 08625 USA. RP Brown, LM (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Execut Plaza N,Room 415,6130 Execut Blvd,MSC 7368, Bethesda, MD 20892 USA. FU NCI NIH HHS [N01-CP-51092, N01-CP-51090, N01-CP-51089] NR 22 TC 50 Z9 50 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD OCT PY 1998 VL 9 IS 5 BP 467 EP 474 DI 10.1023/A:1008861806923 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 163AH UT WOS:000078379700001 PM 9934713 ER PT J AU Legler, JM Feuer, EJ Potosky, AL Merrill, RM Kramer, BS AF Legler, JM Feuer, EJ Potosky, AL Merrill, RM Kramer, BS TI The role of prostate-specific antigen (PSA) testing patterns in the recent prostate cancer incidence decline in the United States SO CANCER CAUSES & CONTROL LA English DT Article DE population-based sample; prevalent tests; prostate cancer; serum prostate-specific antigen (PSA) ID SCREENING TRIAL; INCIDENCE RATES; CARCINOMA; TRENDS; SERUM; MEN; MORTALITY; REGISTRY; AGE AB Objectives: Trends in first-time and later PSA procedure rates are ascertained using longitudinal data from a population-based cohort. These trends are compared to trends in prostate cancer incidence to determine the role of PSA in the recent decline in prostate cancer incidence. Methods: Medicare data were linked with tumor registry data from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Program. A 5 percent random sample (n = 39 985) of Medicare beneficiaries from the SEER areas without a previous diagnosis of prostate cancer as of January 1, 1988 was followed through 1994. Trends in first-time PSA use were distinguished from those of second or later for men without diagnosed prostate cancer. Results: Trends in the rate of first-time PSA procedures track closely with trends in prostate cancer incidence rates, increasing until. 1992 and decreasing thereafter. Similar patterns were observed by race and age group. Geographic variability in the dissemination of PSA screening was observed, yet the association between testing and incidence remained. Men in the cohort had a 4.7 percent chance of being diagnosed within three months of an initial PSA test, with the percentage falling for subsequent tests. Conclusions: It is informative to distinguish first from later tests when assessing the effect of the diffusion of a test in a population. Taking this approach was useful in illuminating the role of PSA testing in a reversal of a long-term increase in prostate cancer incidence rates. C1 NCI, Surveillance Modeling & Methods Sect, Appl Res Branch, Bethesda, MD 20852 USA. NCI, Div Canc Control & Populat Sci, Bethesda, MD 20852 USA. NCI, Div Canc Prevent, Bethesda, MD 20852 USA. RP Legler, JM (reprint author), NCI, Surveillance Modeling & Methods Sect, Appl Res Branch, EPN 313,6130 Execut Blvd, Bethesda, MD 20852 USA. NR 42 TC 97 Z9 99 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD OCT PY 1998 VL 9 IS 5 BP 519 EP 527 DI 10.1023/A:1008805718310 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 163AH UT WOS:000078379700005 PM 9934717 ER PT J AU Helzlsouer, KJ Huang, HY Strickland, PT Hoffman, S Alberg, AJ Comstock, GW Bell, DA AF Helzlsouer, KJ Huang, HY Strickland, PT Hoffman, S Alberg, AJ Comstock, GW Bell, DA TI Association between CYP17 polymorphisms and the development of breast cancer SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID SERUM HORMONE CONCENTRATIONS; DEHYDROEPIANDROSTERONE-SULFATE; POSTMENOPAUSAL WOMEN; RISK; TRANSCRIPTION; PROMOTER; GUERNSEY; ISLAND; CELLS AB A nested case-control study was conducted to determine whether a genetic polymorphism in the CYP17 gene, which encodes for an enzyme that mediates steroid hormone metabolism, was associated with an increased risk of breast cancer, No association was found between the presence of an A2 allele and the subsequent development of breast cancer [A1/A2 odds ratio, 0.61 (95% confidence interval, 0.33-1.14); A2/A2 odds ratio, 0.89 (95% confidence interval, 0.41-1.95)]. No significant association was observed with risk factors presumed to be surrogates for endogenous estrogen exposure, nor was there an association observed with the stage of disease at diagnosis, Genotype frequencies in this Caucasian population were similar to those reported for African-American, Asian, and Latino women, Additional studies of larger size are needed to achieve a consensus regarding the relevance of CYP17 genotypes to the risk of developing breast cancer. C1 Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Environm Hlth Sci, Baltimore, MD 21205 USA. NIEHS, Genet Risk Grp, Lab Computat Biol & Risk Assessment, NIH, Res Triangle Pk, NC 27709 USA. RP Helzlsouer, KJ (reprint author), Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Epidemiol, Room E-6132,615 N Wolfe St, Baltimore, MD 21205 USA. FU NCI NIH HHS [CA62988]; NHLBI NIH HHS [HL21670]; NIEHS NIH HHS [ES03819] NR 19 TC 79 Z9 81 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD OCT PY 1998 VL 7 IS 10 BP 945 EP 949 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 127TK UT WOS:000076366500018 PM 9796641 ER PT J AU Meissner, HI Breen, N Coyne, C Legler, JM Green, DT Edwards, BK AF Meissner, HI Breen, N Coyne, C Legler, JM Green, DT Edwards, BK TI Breast and cervical cancer screening interventions: An assessment of the literature SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID INCREASE MAMMOGRAPHY UTILIZATION; PRIMARY CARE PHYSICIANS; RANDOMIZED TRIAL; COMPUTERIZED REMINDERS; PROMOTE MAMMOGRAPHY; PREVENTIVE CARE; BLACK-WOMEN; PROGRAM; IMPACT; STRATEGIES AB An extensive body of intervention research to promote breast and cervical cancer screening has accumulated over the last three decades, but its coverage and comprehensiveness have not been assessed. We evaluated published reports of these interventions and propose a framework of critical elements for authors and researchers to use when contributing to this literature, We identified all articles describing breast and cervical cancer screening interventions published between January 1960 and May 1997 in the United States and abstracted specified critical elements in the broad areas of: (a) needs assessment; (b) intervention study design; and (c) analysis methods and study outcomes from each article using a template developed for that purpose. Fifty-eight studies met our criteria for inclusion. Thirty-eight focused exclusively on breast cancer screening, 7 promoted cervical cancer screening, and 13 were designed to promote screening for both cancers. The amount of detail reported varied among the 58 studies. All studies reported the outcome measures used to assess the effectiveness of the intervention, yet only 40% of the studies reported the investigators' original hypotheses or research questions. Needs assessment data were reported in 84% of the studies, Data sources ranged from national surveys to local intervention baseline surveys. Population characteristics reported also varied, with most studies reporting age and race of the study population (78 and 71%, respectively), and fewer studies reporting income and education (53 and 38%, respectively). As the field of behavioral intervention research progressed, we found that more recent studies included and reported many of the parameters we had identified as critical. If this trend continues, it will enhance the reproducibility of studies, enable comparisons between interventions, and provide a reference point for measuring progress in this area. To facilitate this trend toward uniform reporting, we propose an evaluative framework of critical elements for authors to use when developing and reporting their research, The comprehensive assessment of literature that this article provides should be useful background to investigators planning and reporting cancer control interventions, to funding agencies choosing and guiding quality research, and to publishers to help them enhance the quality and utility of their publications. C1 NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Baltimore, MD 21205 USA. RP Meissner, HI (reprint author), NCI, Div Canc Control & Populat Sci, EPN 232,MSC 7330,6130 Execut Blvd, Bethesda, MD 20892 USA. EM hm36d@nih.gov NR 88 TC 39 Z9 39 U1 2 U2 3 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD OCT PY 1998 VL 7 IS 10 BP 951 EP 961 PG 11 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 127TK UT WOS:000076366500019 PM 9796642 ER PT J AU Agarwal, SK Schrock, E Kester, MB Burns, AL Heffess, CS Ried, T Marx, SJ AF Agarwal, SK Schrock, E Kester, MB Burns, AL Heffess, CS Ried, T Marx, SJ TI Comparative genomic hybridization analysis of human parathyroid tumors SO CANCER GENETICS AND CYTOGENETICS LA English DT Article ID MOLECULAR CYTOGENETIC ANALYSIS; SUPPRESSOR GENE; CHROMOSOMAL GAINS; PROSTATE-CANCER; SOLID TUMORS; BREAST-CANCER; ALLELIC LOSS; COPY NUMBER; DNA; CARCINOMA AB Primary hyperparathyroidism is characterized by hypercalcemia and elevated parathyroid hormone levels. It can be caused by overactivity of one (adenoma or carcinoma) or more (hyperplasia or multiple adenoma) parathyroid glands. Parathyroid adenoma and hyperplasia are usually mono- or oligoclonal neoplasms. To establish whether parathyroid cancer has a genetic composition distinct from parathyroid adenoma, we analyzed 10 adenoma and 10 carcinoma cases by comparative genomic hybridization (CGH). Results show clear differences between the constitution of adenoma and carcinoma genomic DNA. The most frequent genomic alterations in adenoma included deletions on chromosomes 11, 17 (5 of 10 cases), and 22 (7 of 10 cases). In parathyroid carcinoma, frequent chromosomal deletions were on chromosome arm 1p (4 of 10 cases) and chromosome 17 (3 of 10 cases), and gains were on chromosome 5 (3 of 10 cases). Our data indicate that different genetic changes could contribute to the development of parathyroid adenoma and carcinoma; genomic losses predominate in adenoma, and gains along with some losses are found in carcinoma. Furthermore, the CGH results implicate several chromosomal regions that may harbor genes that could be potentially involved in the development of parathyroid adenoma and carcinoma. Published by Elsevier Science Inc. C1 NIDDK, Genet & Endocrinol Sect, Metab Dis Branch, NIH, Bethesda, MD USA. NHGRI, Genome Technol Branch, NIH, Bethesda, MD USA. Armed Forces Inst Pathol, Dept Endocrine & Otolaryng Head & Neck Pathol, Washington, DC 20306 USA. RP Marx, SJ (reprint author), NIDDK, Genet & Endocrinol Sect, Metab Dis Branch, NIH, Bldg 10,Room 9C-101,10 Ctr Dr,MSC 1802, Bethesda, MD USA. RI Agarwal, Sunita/D-1428-2016 OI Agarwal, Sunita/0000-0002-7557-3191 NR 42 TC 59 Z9 60 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0165-4608 J9 CANCER GENET CYTOGEN JI Cancer Genet. Cytogenet. PD OCT 1 PY 1998 VL 106 IS 1 BP 30 EP 36 DI 10.1016/S0165-4608(98)00049-1 PG 7 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA 123QC UT WOS:000076135000005 PM 9772906 ER PT J AU Boyer, JC Risinger, JI Farber, RA AF Boyer, JC Risinger, JI Farber, RA TI Stability of microsatellites in myeloid neoplasias SO CANCER GENETICS AND CYTOGENETICS LA English DT Article ID MISMATCH REPAIR GENE; REPLICATION ERROR PHENOTYPE; SACCHAROMYCES-CEREVISIAE; MYELODYSPLASTIC SYNDROME; LYMPHOPROLIFERATIVE DISORDERS; REPEAT POLYMORPHISM; MYELOCYTIC-LEUKEMIA; MUTATOR PHENOTYPE; COLORECTAL-CANCER; LYMPHOID TUMORS AB Microsatellites are short, repeated DNA sequences that exist throughout the genome. Instability of these sequences, associated with defects in the DNA mismatch repair system, is the hallmark of hereditary non-polyposis colorectal cancer (HNPCC), and is also found in many sporadic cancers. Although many types of solid tumors exhibit this type of genetic instability, its involvement in hematologic cancers is less evident. We have investigated whether microstatellite instability (MSI) is involved in the transformation of myeloid cells to myelodysplastic syndrome (MDS) and/or acute myelogenous leukemia (AML). Both de novo and treatment-associated neoplasias were studied. Only one example of MSI was found in 48 patients, using a panel of 14 different microsatellite loci consisting of repeats of one to four base pairs. These results suggest that the genes responsible for MSI are not involved in the transformation of normal myeloid cells to MDS or AML. (C) Elsevier Science, Inc., 1998. C1 Univ N Carolina, Dept Pathol, Chapel Hill, NC 27599 USA. Univ N Carolina, Curriculum Genet & Mol Biol, Chapel Hill, NC 27599 USA. Univ N Carolina, Lineberger Comprehens Canc Res Ctr, Chapel Hill, NC 27599 USA. NIEHS, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. RP Boyer, JC (reprint author), Univ N Carolina, Dept Pathol, CB 7525, Chapel Hill, NC 27599 USA. FU NCI NIH HHS [CA49039, CA63264, CA40046] NR 52 TC 18 Z9 18 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0165-4608 J9 CANCER GENET CYTOGEN JI Cancer Genet. Cytogenet. PD OCT 1 PY 1998 VL 106 IS 1 BP 54 EP 61 DI 10.1016/S0165-4608(98)00043-0 PG 8 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA 123QC UT WOS:000076135000009 PM 9772910 ER PT J AU Chappell, DB Restifo, NP AF Chappell, DB Restifo, NP TI T cell-tumor cell: a fatal interaction? SO CANCER IMMUNOLOGY IMMUNOTHERAPY LA English DT Review DE FasL; cancer; immunotherapy; caspase; apoptosis ID FAS LIGAND EXPRESSION; AUTOIMMUNE LYMPHOPROLIFERATIVE SYNDROME; APO-1/FAS RECEPTOR/LIGAND SYSTEM; DRUG-INDUCED APOPTOSIS; COLON-CARCINOMA CELLS; MYC-INDUCED APOPTOSIS; IMMUNE PRIVILEGE; LYMPHOCYTE APOPTOSIS; GENE-MUTATIONS; CANCER-THERAPY AB Fas (Apo-1/CD95) is a cell-surface protein that is responsible for initiating a cascade of proteases (caspases) culminating in apoptotic cell death in a variety of cell types. The function of the Fas/FasL system in the dampening of immune responses to infectious agents through the autocrine deletion of activated T cells has been well documented. More recently, it has been proposed that tumor cells express Fast, presumably to avoid immune detection. In this review, we focus on the role of the interaction of Fas and Fast in the modulation of antitumor responses. We critically examine the evidence that Fast is expressed by tumor cells and explore alternative explanations for the observed phenomena in vitro and in vivo. By reviewing data that we have generated in our laboratory as well as reports from the literature, we will argue that the Fas/FasL system is a generalized mechanism used in an autocrine fashion to regulate cell survival and expansion in response to environmental and cellular cues. We propose that Fast expression by tumor cells, when present, is indicative of a perturbed balance in the control of proliferation while Immune privilege Is established by "suicide" of activated antitumor T cells, a form of activation-induced cell death. C1 NIH, Surg Branch, Bethesda, MD 20892 USA. NIH, Howard Hughes Med Inst, Res Scholars Program, Bethesda, MD 20814 USA. RP Restifo, NP (reprint author), NIH, Surg Branch, 10 Ctr Dr MSC-1502, Bethesda, MD 20892 USA. RI Restifo, Nicholas/A-5713-2008; OI Restifo, Nicholas P./0000-0003-4229-4580 FU Intramural NIH HHS [Z99 CA999999, Z01 BC010763-01] NR 54 TC 51 Z9 52 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0340-7004 J9 CANCER IMMUNOL IMMUN JI Cancer Immunol. Immunother. PD OCT PY 1998 VL 47 IS 2 BP 65 EP 71 DI 10.1007/s002620050505 PG 7 WC Oncology; Immunology SC Oncology; Immunology GA 123PT UT WOS:000076134100001 PM 9769114 ER PT J AU Wang, W Kumar, P Wang, WZ Epstein, J Helman, L Moore, JV Kumar, S AF Wang, W Kumar, P Wang, WZ Epstein, J Helman, L Moore, JV Kumar, S TI Insulin-like growth factor II and PAX3-FKHR cooperate in the oncogenesis of rhabdomyosarcoma SO CANCER RESEARCH LA English DT Article ID ALVEOLAR RHABDOMYOSARCOMA; FUSION PROTEIN; TRANSCRIPTIONAL ACTIVATOR; AUTOCRINE GROWTH; PAX-3 EXPRESSION; CELLS; GENE; DIFFERENTIATION; TRANSLOCATION; MYOGENESIS AB The mouse myoblast C2C12 cell line transfected singly with cDNA for Pax-3, PAX3-FKMR, or insulin-like growth factor (IGF) II or cotransfected with IGF-II plus Pax-3 or with IGF-II plus PAX3-FKHR genes showed an altered morphology;, a lack of differentiation, and higher proliferation rates in vitro. On s.c. injection into nude mice, tumors grew from transfected cell lines but not from cells transfected with the empty vector. Tumors derived from IGF-II/PAX3-FKHR- and IGF-II-transfected cells grew most rapidly. Cotransfection of IGF-II plus Pax-3 induced tumors comprised highly differentiated striated muscle cells; Pax-3, PAX3-FKHR, or IGF-II transfection produced tumors at varying stages of differentiation, Tumors derived from IGF-II plus PAX3-FKHR-co-transfected cells were composed of undifferentiated cells. This was the only tumor type to infiltrate the underlying muscle. The most angiogenesis and the least apoptosis were observed in the latter tumors. These results support the hypothesis that PAX3-FKHR interacts with IGF-II to play a critical role in the oncogenesis of rhabdomyosarcoma. C1 Manchester Metropolitan Univ, Dept Sci Biol, Manchester M13 9PT, Lancs, England. Univ Penn, Philadelphia, PA 19104 USA. NCI, Pediat Branch, Bethesda, MD 20892 USA. Christie Hosp NHS Trust, Manchester M20 4BX, Lancs, England. Univ Manchester, Manchester M13 9PT, Lancs, England. RP Kumar, P (reprint author), Manchester Metropolitan Univ, Dept Sci Biol, Oxford Rd, Manchester M13 9PT, Lancs, England. OI Wang, Weiguang/0000-0003-0509-2605 NR 36 TC 55 Z9 60 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD OCT 1 PY 1998 VL 58 IS 19 BP 4426 EP 4433 PG 8 WC Oncology SC Oncology GA 125CD UT WOS:000076219100037 PM 9766674 ER PT J AU Reed, E AF Reed, E TI Platinum-DNA adduct, nucleotide excision repair and platinum based anti-cancer chemotherapy SO CANCER TREATMENT REVIEWS LA English DT Review ID HUMAN OVARIAN-CANCER; MESSENGER-RNA LEVELS; ACQUIRED CISPLATIN RESISTANCE; PATIENTS RECEIVING CISPLATIN; INTERSTRAND CROSS-LINKS; MISMATCH REPAIR; LEUKOCYTE DNA; GENE ERCC-1; CELL-LINES; O-6-ALKYLGUANINE-DNA ALKYLTRANSFERASE C1 NCI, Med Branch, Div Clin Sci, Med Ovarian Canc Sect, Bethesda, MD 20892 USA. RP Reed, E (reprint author), NCI, Med Branch, Div Clin Sci, Med Ovarian Canc Sect, Bldg 10,Room 12N226, Bethesda, MD 20892 USA. NR 97 TC 290 Z9 309 U1 2 U2 22 PU W B SAUNDERS CO LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0305-7372 J9 CANCER TREAT REV JI Cancer Treat. Rev. PD OCT PY 1998 VL 24 IS 5 BP 331 EP 344 DI 10.1016/S0305-7372(98)90056-1 PG 14 WC Oncology SC Oncology GA 142HR UT WOS:000077195200003 PM 9861196 ER PT J AU Katoh, T Kaneko, S Boissy, R Watson, M Ikemura, K Bell, DA AF Katoh, T Kaneko, S Boissy, R Watson, M Ikemura, K Bell, DA TI A pilot study testing the association between N-acetyltransferases 1 and 2 and risk of oral squamous cell carcinoma in Japanese people SO CARCINOGENESIS LA English DT Article ID COLORECTAL-CANCER; NAT1; POLYMORPHISM; BLADDER; ACETYLATION; PHENOTYPE; ALLELE; GENES; ASSAY AB Risk of oral cancer has been associated with exposure to tobacco smoke, alcohol and with genetic predisposition. The aromatic amines and their metabolites, a class of carcinogens present in tobacco smoke, undergo metabolism (activation or detoxification) through an N- or O-acetylation pathway by the polymorphic enzymes, N-acetyltransferases (NAT)1 or NAT2, The genes that encode these enzymes, NAT1 and NAT2, have a variety of high and low activity alleles and we analyzed these genetic polymorphisms in 62 oral squamous cell carcinoma cases, and 122 healthy control subjects from Japan. NAT1 alleles tested were NAT1*3 (C1095A), NAT1*4 (functional reference allele), NAT1*10 (T1088A,C1095A), NAT1*11 (9 bp deletion), NAT1*14 (G560A), NAT1*15 (C559T) and NAT1*17 (C190T). No low activity alleles (NAT1*14, NAT1*15 and NAT1*17) were observed in these Japanese subjects. We observed significantly increased risk [odds ratio 3.72; 95% confidence interval (CI) 1.56-8.90; P < 0.01] associated with the NAT1*10 allele, an allele that contains a variant polyadenylation signal. Stratifying by smoking status we found odds ratios of 5.9 (95% CI 1.13-30.6; P < 0.05) for non-smokers with the NAT1*10 allele and 3.1 (95% CI 1.09-9.07; P < 0.05) for smokers, but these risks were not significantly different from each other. Thus, we did not observe that NAT1*10 alleles confer differential risk among smokers and non-smokers. NAT2 rapid acetylation genotype was not a significant risk factor for oral cancer in this Japanese study population. This is the first study to test for oral cancer risk associated with polymorphism in the NAT1 and NAT2 genes, and these positive findings in our pilot study, while based on small numbers, suggest that the NAT1*10 allele may be a genetic determinant of oral squamous cell carcinoma among Japanese people. C1 NIEHS, Res Triangle Pk, NC 27709 USA. Univ Occupat & Environm Hlth, Sch Hlth Sci, Occupat Hlth Sci Course, Kitakyushu, Fukuoka 807, Japan. Univ Occupat & Environm Hlth, Sch Med, Dept Oral Surg, Kitakyushu, Fukuoka 807, Japan. RP Bell, DA (reprint author), NIEHS, POB 12233, Res Triangle Pk, NC 27709 USA. EM bell1@niehs.nih.gov NR 27 TC 56 Z9 57 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD OCT PY 1998 VL 19 IS 10 BP 1803 EP 1807 DI 10.1093/carcin/19.10.1803 PG 5 WC Oncology SC Oncology GA 130GL UT WOS:000076511800014 PM 9806162 ER PT J AU Hansen, LA Malarkey, DE Wilkinson, JE Rosenberg, M Woychik, RE Tennant, RW AF Hansen, LA Malarkey, DE Wilkinson, JE Rosenberg, M Woychik, RE Tennant, RW TI Effect of the viable-yellow (A(vy)) agouti allele on skin tumorigenesis and humoral hypercalcemia in v-Ha-ras transgenic TG.AC mice SO CARCINOGENESIS LA English DT Article ID MOUSE SKIN; GENE; PROLIFERATION; CARCINOMAS; MUTATION; GROWTH; TUMORS; COLOR AB We previously reported that papillomas can arise from the follicular epithelium of v-Ha-ras transgenic TG.AC mice. Since the viable-yellow mutation (A(vy)) Of the mouse agouti gene which regulates coat color pigmentation by acting within the micro-environment of the hair follicle has been shown to function as a tumor promoter in the liver, we hypothesized that it may also play a role in TG.AC skin tumorigenesis. Endogenous agouti protein product was detected in the outer root sheath of anagen hair follicles following plucking of the hair shaft, but not in the interfollicular epithelium, in TG.AC mice on an FVB/N genetic background. It was also detected in papillomas from these mice produced by 12-O-tetradecanoylphorbol-13-acetate (TPA) treatment or plucking. Expression of the A(vy) allele in the v-Ha-ms transgenic TG.AC mouse line results in an similar to 2-fold increase in papilloma development compared with controls which did not carry the A(vy) allele following twice-weekly treatment with 1.25, 2.5 or 5.0 mu g TPA. In addition, TPA-treated, papilloma-bearing F-1 mice which carried the A(vy) allele, but not F-1 mice which did not carry the A(vy) allele, exhibited a syndrome of humoral hypercalcemia mediated by parathyroid hormone-related protein (PTHrP) that led to weight loss, hypercalcemia and hypophosphatemia, Thus, we conclude that the A(vy) allele can influence the development of skin tumors and PTHrP-mediated humoral hypercalcemia in v-Ha-ras transgenic TG.AC mice. C1 NIEHS, Lab Environm Carcinogenesis & Mutagenesis, Res Triangle Pk, NC 27709 USA. NIEHS, Lab Expt Pathol, Res Triangle Pk, NC 27709 USA. Univ Tennessee, Knoxville, TN USA. Glaxo Wellcome Inc, Res Triangle Pk, NC 27709 USA. Oak Ridge Natl Labs, Oak Ridge, TN USA. RP Hansen, LA (reprint author), NCI, Cellular Carcinogenesis & Tumor Promot Lab, Bldg 37,Room 3B17,37 Convent Dr,MSC 4255, Bethesda, MD 20892 USA. NR 22 TC 8 Z9 8 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD OCT PY 1998 VL 19 IS 10 BP 1837 EP 1845 DI 10.1093/carcin/19.10.1837 PG 9 WC Oncology SC Oncology GA 130GL UT WOS:000076511800019 PM 9806167 ER PT J AU Davatzikos, C Resnick, SM AF Davatzikos, C Resnick, SM TI Sex differences in anatomic measures of interhemispheric connectivity: Correlations with cognition in women but not men SO CEREBRAL CORTEX LA English DT Article ID HUMAN CORPUS-CALLOSUM; BRAIN; DIMORPHISM; ORGANIZATION; LANGUAGE; ATLAS; SIZE AB A robust sex difference in the splenium of the corpus callosum, reflecting greater interhemispheric connectivity in women, was observed on magnetic resonance images from 114 individuals. In addition, bulbosity of the corpus callosum correlated with better cognitive performance in women but not in men, indicating that the degree of interhemispheric connectivity has different implications for men and women. These findings were based on a new image analysis technique which allows investigation of local variability in brain morphology. C1 Johns Hopkins Univ, Dept Radiol, Baltimore, MD 21218 USA. NIA, Lab Personal & Cognit, Baltimore, MD 21224 USA. RP Davatzikos, C (reprint author), Johns Hopkins Univ, Dept Radiol, Baltimore, MD 21218 USA. FU NIA NIH HHS [N01-AG-3-2124] NR 38 TC 99 Z9 101 U1 1 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 J9 CEREB CORTEX JI Cereb. Cortex PD OCT-NOV PY 1998 VL 8 IS 7 BP 635 EP 640 DI 10.1093/cercor/8.7.635 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 131TK UT WOS:000076591200007 PM 9823484 ER PT J AU Erve, JCL Amarnath, V Sills, RC Morgan, DL Valentine, WM AF Erve, JCL Amarnath, V Sills, RC Morgan, DL Valentine, WM TI Characterization of a valine-lysine thiourea cross-link on rat globin produced by carbon disulfide or N,N-diethyldithiocarbamate in vivo SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID TANDEM MASS-SPECTROMETRY; OCCUPATIONAL EXPOSURE; ERYTHROCYTE SPECTRIN; HEMOGLOBIN ADDUCTS; EDMAN DEGRADATION; IN-VIVO; PROTEINS; ACID; CS2 AB Previous in vivo studies have supported protein cross-linking by CS2 as both a mechanism of neurotoxicity and a potential biomarker of effect through the detection of a structure responsible for CS2-mediated protein cross-linking, namely, lysine-lysine thiourea. In this study, the structure of a previously uncharacterized stable protein cross-link produced by CS2 in vivo involving lysine and the N-terminal valine of globin has been determined. Rats were exposed to 50, 500, and 800 ppm CS2 for 2, 4, 8, and 13 weeks by inhalation or to 3 mmol/kg N,N-diethyldithiocarbamate administered orally on alternating days for 8 and 16 weeks. acid hydrolysis, using 6 N HCl, of globin from control and exposed rats caused cyclization of the valine-lysine thiourea cross-link in treated rats to isopropyl norleucyl thiohydantoin. The hydrolysate was separated by size-exclusion chromatography, and the fraction that coeluted with the synthetic deuterated isopropyl norleucyl thiohydantoin internal standard was derivatized with 3-[4'-(ethylene-N,N,N-trimethylamino)phenyl]-2-isothiocyanate and analyzed by liquid chromatography/tandem mass spectrometry using selected reaction monitoring detection. Derivatized isopropyl norleucyl thiohydantoin obtained from CS2-treated rats displayed a cumulative dose response and was detectable at the lowest exposure (50 ppm, 2 weeks) at levels of approximately 50 pmol/g of globin. N,N-Diethyldithiocarbamate-treated rats, but not controls, also contained a CS2-generated valine-lysine thiourea cross-link on globin. In vitro incubation of human hemoglobin with either CS2 or N,N-diethyldithiocarbamate also resulted in the formation of CS2-generated valine-lysine thiourea. These observations demonstrate the potential of thiourea cross-linking involving a free amino terminus and epsilon-amino groups of lysine to accumulate in a long-lived globular protein and suggest that cross-linking of globin may provide a specific dosimeter of internal exposure for CS2 capable of assessing exposure over subchronic periods. C1 Vanderbilt Univ, Med Ctr, Dept Pathol, Nashville, TN 37232 USA. Vanderbilt Univ, Med Ctr, Ctr Mol Toxicol, Nashville, TN 37232 USA. NIEHS, Environm Toxicol Program, Res Triangle Pk, NC 27709 USA. RP Erve, JCL (reprint author), Vanderbilt Univ, Med Ctr, Dept Pathol, Nashville, TN 37232 USA. FU NIEHS NIH HHS [P30 ES00267, ES05764, ES06387] NR 26 TC 8 Z9 8 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD OCT PY 1998 VL 11 IS 10 BP 1128 EP 1136 DI 10.1021/tx980077p PG 9 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 132QX UT WOS:000076642000002 PM 9778308 ER PT J AU Schecter, A Dellarco, M Papke, O Olson, J AF Schecter, A Dellarco, M Papke, O Olson, J TI A comparison of dioxins, dibenzofurans and coplanar PCBs in uncooked and broiled ground beef, catfish and bacon SO CHEMOSPHERE LA English DT Article; Proceedings Paper CT 16th Symposium on Chlorinated Dioxins and Related Compounds CY AUG 12-16, 1996 CL AMSTERDAM, NETHERLANDS DE dioxins; dibenzofurans; coplanar PCBs; cooked food; uncooked food; meat; fish AB The primary source of dioxins (PCDDs), dibenzofurans (PCDFs) and coplanar PCBs for the general population is food, especially meat, fish, and dairy products. However, most data on the levels of these chemicals is from food in the raw or uncooked state. We report here the effect of one type of cooking (broiling) on the levels of PCDDs, PCDFs, and coplanar PCBs in ground beef (hamburger), bacon and catfish. Samples of hamburger, bacon, and catfish were broiled and compared to uncooked samples in order to measure changes in the amounts of dioxins in cooked food. The total amount of PCDD, PCDF, and coplanar PCB TEQ decreased by approximately 50% on average for each portion as a result of broiling the hamburger, bacon and catfish specimens. The mean concentration (pg TEQ/kg, wet weight) of PCDDs, PCDFs, and coplanar PCBs, however, remained the same in the hamburger, increased by 83% in the bacon, and decreased by 34% in the catfish. On average, the total measured concentration (pg/kg) of the congeners of PCDDs, PCDFs, and coplanar PCBs increased 14% in the hamburger, increased 29% in the bacon, and decreased 33% in the catfish. (C) 1998 Elsevier Science Ltd. All rights reserved. C1 SUNY Hlth Sci Ctr, Dept Prevent Med, Binghamton, NY 13903 USA. US EPA, Natl Ctr Environm Assessment, Washington, DC 20460 USA. ERGO Forsch Gesell MbH, D-22305 Hamburg, Germany. SUNY Buffalo, Dept Pharmacol & Toxicol, Buffalo, NY 14214 USA. RP Schecter, A (reprint author), NIEHS, MD A3-02,POB 12233, Res Triangle Pk, NC 27709 USA. NR 9 TC 41 Z9 42 U1 1 U2 15 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0045-6535 J9 CHEMOSPHERE JI Chemosphere PD OCT-NOV PY 1998 VL 37 IS 9-12 BP 1723 EP 1730 DI 10.1016/S0045-6535(98)00237-9 PG 8 WC Environmental Sciences SC Environmental Sciences & Ecology GA 132FB UT WOS:000076618700008 PM 9828300 ER PT J AU Schecter, A Ryan, JJ Papke, O AF Schecter, A Ryan, JJ Papke, O TI Decrease in levels and body burden of dioxins, dibenzofurans, PCBs, DDE, and HCB in blood and milk in a mother nursing twins over a thirty-eight month period SO CHEMOSPHERE LA English DT Article; Proceedings Paper CT 16th Symposium on Chlorinated Dioxins and Related Compounds CY AUG 12-16, 1996 CL AMSTERDAM, NETHERLANDS DE dioxins; dibenzofurans; PCBs; DDE; HCB; decrease during nursing ID WHOLE-BLOOD; PCDDS; PCDFS; GERMANY; SAMPLES; TISSUE; FOOD AB This paper presents measured dioxin, dibenzofuran, PCB, DDE and HCB blood and milk levels and estimated body burdens in a mother who nursed twins for thirty-eight months. A total of thirteen milk samples and three blood samples were collected and analyzed. Measured PCDD and PCDF levels in milk decreased from 309 and 21 ng/kg (ppt) to 173 and 9 ng/kg, respectively, between March 1993 and September 1995. Based on the decrease in breast milk dioxin levels, we estimate that the nursing mother reduced her dioxin body burden from 310 to 96 ng dioxin toxic equivalents (TEQs), or approximately 69%. In two and one half years the level of HCB in the mother's milk decreased from 10.7 to less than 1.8 ng/g (ppb), the level of DDE decreased from 246 to 46 ng/g and the total level of non-coplanar PCBs decreased from 285 to 63 ng/g, on a lipid basis. We estimate that the twin's consumption of dioxins, dibenzofurans, and coplanar PCBs from breast feeding was approximately 115 ng TEQ per twin. (C) 1998 Elsevier Science Ltd. All rights reserved. C1 SUNY Hlth Sci Ctr, Dept Prevent Med, Binghamton, NY 13903 USA. Hlth Canada, Ottawa, ON K1A 0L2, Canada. ERGO Forsch Gesell mbH, D-22305 Hamburg, Germany. RP Schecter, A (reprint author), NIEHS, MD A3-02,POB 12233, Res Triangle Pk, NC 27709 USA. NR 14 TC 46 Z9 48 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0045-6535 J9 CHEMOSPHERE JI Chemosphere PD OCT-NOV PY 1998 VL 37 IS 9-12 BP 1807 EP 1816 DI 10.1016/S0045-6535(98)00246-X PG 10 WC Environmental Sciences SC Environmental Sciences & Ecology GA 132FB UT WOS:000076618700017 PM 9828309 ER PT J AU Schecter, A Kassis, I Papke, O AF Schecter, A Kassis, I Papke, O TI Partitioning of dioxins, dibenzofurans, and coplanar PCBs in blood, milk, adipose tissue, placenta and cord blood from five American women SO CHEMOSPHERE LA English DT Article; Proceedings Paper CT 16th Symposium on Chlorinated Dioxins and Related Compounds CY AUG 12-16, 1996 CL AMSTERDAM, NETHERLANDS DE dioxins; dibenzofurans; coplanar PCBs; partitioning; blood; milk; placenta; adipose tissue; cord blood ID WHOLE-BLOOD; SAMPLES; HUMANS AB Partitioning of dioxins, dibenzofurans and the dioxin-like coplanar PCBs was determined by congener-specific high resolution gc-ms analysis of compounds in 6 tissue samples each from 5 women. Samples were whole blood obtained prior to delivery; maternal adipose tissue, cord blood and placenta obtained during cesarean section delivery; and whole blood and milk taken at the time of first obstetrical follow-up examination, one to two months following delivery. All women lived in upstate New York. Specimens were collected in late 1995 and early 1996. Mean measured levels of total PCDDs, PCDFs and coplanar PCBs were 352 pg/g for adipose tissue, 526 pg/g for predelivery blood, 182 pg/g for placenta, 165 pg/g for cord blood, 352 pg/g for postpartum blood and 220 pg/g for milk. Mean total TEQ levels were 11.6 pg/g TEQ for adipose tissue, 12.1 pg/g TEQ for predelivery blood, 10.5 pg/g TEQ for placenta, 5.8 pg/g TEQ for cord blood, 10.0 pg/g TEQ for postpartum blood and 10.2 pg/g TEQ for milk. (C) 1998 Elsevier Science Ltd. All rights reserved. C1 SUNY Hlth Sci Ctr, Dept Prevent Med, Binghamton, NY 13903 USA. SUNY Hlth Sci Ctr, Dept Obstet & Gynecol, Binghamton, NY 13902 USA. ERGO Forsch Gesell mbH, D-22305 Hamburg, Germany. RP Schecter, A (reprint author), NIEHS, MD A3-02,POB 12233, Res Triangle Pk, NC 27709 USA. NR 10 TC 66 Z9 69 U1 2 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0045-6535 J9 CHEMOSPHERE JI Chemosphere PD OCT-NOV PY 1998 VL 37 IS 9-12 BP 1817 EP 1823 DI 10.1016/S0045-6535(98)00247-1 PG 7 WC Environmental Sciences SC Environmental Sciences & Ecology GA 132FB UT WOS:000076618700018 PM 9828310 ER PT J AU Rossi, N Kolobow, T Aprigliano, M Tsuno, K Giacomini, M AF Rossi, N Kolobow, T Aprigliano, M Tsuno, K Giacomini, M TI Intratracheal pulmonary ventilation at low airway pressures in a ventilator-induced model of acute respiratory failure improves lung function and survival SO CHEST LA English DT Article DE acute respiratory failure; barotrauma; intratracheal pulmonary ventilation; tracheal gas insufflation ID TRACHEAL GAS INSUFFLATION; END-EXPIRATORY PRESSURE; FREQUENCY OSCILLATORY VENTILATION; MECHANICAL VENTILATION; DISTRESS SYNDROME; TIDAL VOLUME; CATHETER; EXCHANGE; INJURY; DOGS AB Study objective: The pulmonary parenchyma in patients with acute respiratory failure (ARF) is commonly not involved in a homogenous disease process. Conventional mechanical ventilation (MV) are elevated positive end-expiratory pressure (PEEP) and peak inspiratory pressure (PIP) aims at recruiting collapsed or nonventilated lung units. Invariably, those pressures are also transmitted to the healthiest regions, with possible extension of the disease process (barotrauma). During intratracheal pulmonary ventilation (ITPV), a continuous flow of fresh gas is delivered directly at the carina, bypassing the dead space proximal to the catheter tip. In healthy sheep, it allows lowering tidal volume (VT) to as low as 1.0 mL/kg, at respiratory rates (RR) up to 120 breaths/min, while maintaining normocapnia. In a model of ventilator-induced lung injury, we wished to explore whether ITPV, applied at low VT and low PEEP and tailored to ventilate the healthiest regions of the lungs, could provide adequate oxygenation and alveolar ventilation, without any attempt to recruit lungs. Design: Randomized study in sheep. Setting: Animal research laboratory. Participants: We induced ARF in 12 sheep following 1 to 2 days of MV at a PIP of 50 cm H2O, except that 5 to 8% of lungs were kept on apneic oxygenation of 5 cm H2O, sparing those regions from the injury process. Interventions: Sheep were randomized to volume-controlled MV (control group) (n = 6) with VT of s to 12 mL/kg, PEEP of 5 to 10 cm H2O, or to ITPV (n = 6) at PEEP of 3 to 5 cm H2O, VT of 2.5 to 4 mL/kg, PIP of <20 cm H2O, at RRs sufficient to sustain normocapnia. Measurements ana results: Hemodynamic status in the ITPV group progressively improved, and all six sheep were weaned to room air within 83 +/- 54 h. Sheep in the control group had progressively deteriorating conditions and all animals died after a mean of 50 +/- 39 h. Barotrauna and postmortem histopathologic changes were more pronounced in the control group. Conclusion: In this model of ventilator-induced lung injury, low PEEP-low VT ventilation with ITPV sustained normocapnia and prevented further lung injury, allowing weaning to room air ventilation. C1 NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. RP Kolobow, T (reprint author), NHLBI, Pulm Crit Care Med Branch, NIH, 10 Ctr Dr,MSC 1590,Bldg 10,Room 5D-17, Bethesda, MD 20892 USA. NR 33 TC 10 Z9 10 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD OCT PY 1998 VL 114 IS 4 BP 1147 EP 1157 DI 10.1378/chest.114.4.1147 PG 11 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 130AX UT WOS:000076498000036 PM 9792591 ER PT J AU Brody, D Metcalfe, DD AF Brody, D Metcalfe, DD TI Mast cells: a unique and functional diversity SO CLINICAL AND EXPERIMENTAL ALLERGY LA English DT Editorial Material ID NECROSIS-FACTOR-ALPHA; ANTIGEN-SPECIFIC IGE; TRICHINELLA-SPIRALIS; CHOLERA-TOXIN; NU MICE; RAT; ADHESION; RELEASE; PROLIFERATION; ANGIOGENESIS C1 NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. RP Metcalfe, DD (reprint author), NIAID, Lab Allerg Dis, NIH, Bldg 10,Room 11C205,10 Ctr Dr,MSC 1881, Bethesda, MD 20892 USA. NR 55 TC 9 Z9 9 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0954-7894 J9 CLIN EXP ALLERGY JI Clin. Exp. Allergy PD OCT PY 1998 VL 28 IS 10 BP 1167 EP 1170 PG 4 WC Allergy; Immunology SC Allergy; Immunology GA 163UJ UT WOS:000078424500001 PM 9824380 ER PT J AU Alexander, HR Brown, CK Bartlett, DL Libutti, SK Figg, WD Raje, S Turner, E AF Alexander, HR Brown, CK Bartlett, DL Libutti, SK Figg, WD Raje, S Turner, E TI Augmented capillary leak during isolated hepatic perfusion (IHP) occurs via tumor necrosis factor-independent mechanisms SO CLINICAL CANCER RESEARCH LA English DT Article ID ISOLATED LIMB PERFUSION; SOFT-TISSUE SARCOMAS; FACTOR-ALPHA; INTERFERON-GAMMA; PLASMA-LEVELS; TNF-ALPHA; MELPHALAN; MELANOMA; COMBINATION; SEPSIS AB Isolated organ perfusion of the liver or extremity with tumor necrosis factor (TNF) and melphalan results in regression of bulky tumors in the majority of patients, The efficacy of TNF in this setting is not known, although data suggest that it may exert antitumor effects primarily on tumor-associated neovasculature. We studied the effects of TNF on capillary leak in liver and tumor tissue during isolated hepatic perfusion (IHP) with melphalan, Twenty-seven patients with unresectable cancer confined to the liver underwent a 60-min hyperthermic IHP using 1.5 mg/kg melphalan alone (n = 7) or with 1.0 mg of TNF (n = 20), Complete vascular isolation was confirmed in all patients using an intraoperative leak monitoring I-131 radiolabeled albumin technique. Samples of tumor and liver were collected just prior to and immediately after IHP, There was no difference in I-131 radiolabeled cpm/g of tissue (cpm) in liver versus tumor at baseline (P-2 = 0.44), After IHP, I-131 albumin cpm were higher in tumor versus liver (10,999 a 1,976 versus 3,821 +/- 780, respectively; P-2 < 0.005), However, I-131 albumin cpm in tumor were not effected by TNF (11,636 +/- 2,518 with TNF versus 9,180 +/- 2,674 without TNF; P-2 = 0.59), TNF did not affect melphalan concentrations in tumor (1,883 +/- 540 ng/g versus 1,854 +/- 861 ng/g without TNF; P-2 = 0,9), Capillary leak, as reflected by diffusion of I-131 radiolabeled albumin into the interstitial space, is comparable in liver and tumor before IHP but is significantly higher in tumor after IHP, The increased diffusion in the capillary tumor bed must occur through TNF-independent mechanisms such as intrinsic features of tumor neovasculature, hyperthermia, or other unrecognized perfusion-related factors. These data indicate that TNF must continue to be critically evaluated in clinical trials before it is routinely used with melphalan in isolated organ perfusion. C1 NCI, Surg Metab Sect, Surg Branch, NIH, Bethesda, MD 20892 USA. NCI, Clin Pharmacokinet Sect, Med Branch, Div Clin Sci, Bethesda, MD 20892 USA. RP Alexander, HR (reprint author), NCI, Surg Metab Sect, Surg Branch, NIH, Bldg 10,Room 2B07, Bethesda, MD 20892 USA. RI Figg Sr, William/M-2411-2016 NR 24 TC 25 Z9 25 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD OCT PY 1998 VL 4 IS 10 BP 2357 EP 2362 PG 6 WC Oncology SC Oncology GA 127TM UT WOS:000076366700009 PM 9796965 ER PT J AU Aquino, A Prete, SP Greiner, JW Giuliani, A Graziani, G Turriziani, M De Filippi, R Masci, G Bonmassar, E De Vecchis, L AF Aquino, A Prete, SP Greiner, JW Giuliani, A Graziani, G Turriziani, M De Filippi, R Masci, G Bonmassar, E De Vecchis, L TI Effect of the combined treatment with 5-fluorouracil, gamma-interferon or folinic acid on carcinoembryonic antigen expression in colon cancer cells SO CLINICAL CANCER RESEARCH LA English DT Article ID HUMAN RECOMBINANT INTERFERONS; MONOCLONAL-ANTIBODY; MESSENGER-RNA; COLORECTAL-CANCER; CARCINOMA-CELLS; NUCLEAR-RNA; IN-VITRO; VACCINE; LINES; GENE AB 5-Fluorouracil (5-FU) and human recombinant gamma-interferon (gamma-IFN) were found to increase the expression of carcinoembryonic antigen (CEA) in human cancer cells in vitro. In the present study, the antimetabolite was associated with gamma-IFN or folinic acid (FA), a biochemical modulator of cellular metabolism of 5-FU, able to increase its antineoplastic activity. Treatment of two human colon cancer cell lines (HT-29 and WiDr) with 5-FU + gamma-IFN resulted in an increase of CEA expression higher than that obtainable with both agents alone, although no synergistic effects were obtained. This was demonstrated in terms of: (a) mRNA transcripts (HT-29); (b) cytoplasm and membrane CEA protein levels detected by Western blot analysis (HT-29); and (c) plasma membrane reactivity determined by flow cytometry analysis (HT-29 and WiDr). Moreover, 5-FU + gamma-IFN increased HLA class I molecules in the HT-29 cell membrane over that obtainable with gamma-IFN alone. In contrast, both agents did not induce the expression of the costimulatory molecule B7-1. Treatment with FA enhanced the antitumor effect of 5-FU but not its ability to augment CEA expression. This suggests that the FA-sensitive biochemical mechanism of action of 5-FU is not involved in its effect on CEA expression. In vivo studies showed, for the first time, that 5-FU, alone or combined with gamma-IFN, increases the amount of CEA protein over controls, either in cancer cells or in peripheral blood of nude mice bearing HT-29 cells. These results could be of potential diagnostic and/or therapeutic value when CEA protein is the target of humoral or cell-mediated immunity. C1 Univ Roma Tor Vergata, Dept Neurosci, Sect Pharmacol & Med Oncol, I-00133 Rome, Italy. NCI, Tumor Immunol & Biol Lab, NIH, Bethesda, MD 20892 USA. Ist Dermopatico Immacolata, I-00167 Rome, Italy. Univ Udine, Dept Pathol & Expt & Clin Med, I-33100 Udine, Italy. CNR, Natl Res Council, Inst Expt Med, I-00137 Rome, Italy. RP Aquino, A (reprint author), Univ Roma Tor Vergata, Dept Neurosci, Sect Pharmacol & Med Oncol, Via Tor Vergata 135, I-00133 Rome, Italy. RI Graziani, Grazia/G-5747-2012 NR 50 TC 33 Z9 33 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD OCT PY 1998 VL 4 IS 10 BP 2473 EP 2481 PG 9 WC Oncology SC Oncology GA 127TM UT WOS:000076366700024 PM 9796980 ER PT J AU Olivero, OA Gomez, DE AF Olivero, OA Gomez, DE TI S. M. Melana et al., Inhibition of cell growth and telomerase activity of breast cancer cells in vitro by 3 '-azido-3 '-deoxythymidine. Clin. Cancer Res., 4 : 693-696, 1998 SO CLINICAL CANCER RESEARCH LA English DT Letter ID PREFERENTIAL INCORPORATION; 3'-AZIDO-2',3'-DIDEOXYTHYMIDINE C1 NCI, Bethesda, MD 20892 USA. Quilmes Natl Univ, RA-1878 Buenos Aires, DF, Argentina. RP Olivero, OA (reprint author), NCI, Bethesda, MD 20892 USA. NR 6 TC 2 Z9 2 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD OCT PY 1998 VL 4 IS 10 BP 2569 EP 2569 PG 1 WC Oncology SC Oncology GA 127TM UT WOS:000076366700037 PM 9796993 ER PT J AU Michigami, T Nomizu, M Yamada, Y Dunstan, C Williams, PJ Munday, GR Yoneda, T AF Michigami, T Nomizu, M Yamada, Y Dunstan, C Williams, PJ Munday, GR Yoneda, T TI Growth and dissemination of a newly-established murine B-cell lymphoma cell line is inhibited by multimeric YIGSR peptide SO CLINICAL & EXPERIMENTAL METASTASIS LA English DT Article DE B-cell lymphoma; laminin; angiogenesis; osteolysis; osteoclast ID SER-ARG YIGSR; MULTIPLE-MYELOMA; EXPERIMENTAL METASTASIS; V(D)J RECOMBINATION; TUMOR-GROWTH; BONE-MARROW; ANGIOGENESIS; HYPERCALCEMIA; LAMININ; MICE AB B-cell lymphoma frequently shows simultaneous dissemination to multiple organs. It also occasionally involves bone and causes osteolytic lesions. To study the mechanisms responsible for this capacity of lymphoma cells to grow in different tissue microenvironments and search for effective therapeutic interventions for this hematological malignancy, we established a new murine B-cell lymphoma cell line named MH-95. The tumor disseminated to multiple organs including the lung, liver, kidney, spleen and lymph nodes within 2 weeks after subcutaneous inoculation in nude mice. In addition, the tumor also grew in bone and caused osteoclastic osteolytic lesions. Thus, this tumor model mimics the behavior in many ways of B-cell lymphoma in humans. We studied the role of laminin, a major component of the basement membrane, in this model, since although it has been implicated in solid tumor metastasis, little is known about the involvement of laminin in the growth of B-cell lymphoma in bone and other organs. Immunohistochemical examination showed strong laminin expression in the stroma of the primary subcutaneous tumor and tumors in the bone and other organs. Systemic administration of the antagonistic laminin peptide YIGSR decreased primary tumor growth and tumor cell deposit in the bone, liver and kidney. In addition, the peptide also decreased apparent neovascularization in the tumor, suggesting that the peptide suppressed angiogenesis presumably due to inhibition of laminin binding to its receptors. These results demonstrate that the MH-95 B-cell lymphoma cells express laminin and suggest that laminin plays a critical role in the growth and simultaneous dissemination of tumor cells to multiple organs, similar to what has been described in solid tumors. The results also suggest that suppression of angiogenesis through interfering with laminin actions may be a useful adjuvant therapy for B-cell lymphoma. C1 Univ Texas, Hlth Sci Ctr, Dept Med, Div Endocrinol & Metab, San Antonio, TX 78284 USA. NIDR, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD 20892 USA. Osaka Univ, Fac Dent, Dept Biochem, Osaka 565, Japan. Osaka Med Ctr Mat & Child Hlth, Res Inst, Dept Environm Med, Osaka 590, Japan. RP Yoneda, T (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, Div Endocrinol & Metab, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. EM yoneda@uthscsa.edu RI Dunstan, Colin/G-6214-2013 OI Dunstan, Colin/0000-0001-7586-4071 FU NCI NIH HHS [P01-CA40035, P01-CA58183, R01-CA63628] NR 29 TC 6 Z9 6 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0262-0898 J9 CLIN EXP METASTAS JI Clin. Exp. Metastasis PD OCT PY 1998 VL 16 IS 7 BP 645 EP 654 DI 10.1023/A:1006502528268 PG 10 WC Oncology SC Oncology GA 162TQ UT WOS:000078363200008 PM 9932611 ER PT J AU Smith, CW Chen, Z Dong, G Loukinova, E Pegram, MY Nicholas-Figueroa, L Van Waes, C AF Smith, CW Chen, Z Dong, G Loukinova, E Pegram, MY Nicholas-Figueroa, L Van Waes, C TI The host environment promotes the development of primary and metastatic squamous cell carcinomas that constitutively express proinflammatory cytokines IL-1 alpha, IL-6, GM-CSF, and KC SO CLINICAL & EXPERIMENTAL METASTASIS LA English DT Article DE proinflammatory cytokines; IL-1 alpha; IL-6; IL-8 and GM-CSF; squamous cell carcinoma ID COLONY-STIMULATING FACTOR; HUMAN-MELANOMA CELLS; NUDE-MICE; INTERLEUKIN-8 EXPRESSION; SUPPRESSOR CELLS; TUMOR-GROWTH; NECK-CANCER; HEAD; HYPERCALCEMIA; INHIBITION AB Human and murine squamous cell carcinomas (SCC) have been reported to produce proinflammatory cytokines IL-1 alpha, IL-6, GM-CSF, and IL-8 or KC. Production of individual members of the proinflammatory cytokine family has been associated with increased tumor growth or metastasis in a variety of neoplasms. In this study, we determined whether the expression of these cytokines occurs as a result of the events of cellular transformation or culture, or is promoted by interaction of neoplastic cells with factors or cells in the host environment. We compared the expression of proinflammatory cytokines following the spontaneous transformation of murine keratinocytes in vitro, and following the formation of tumors and metastases from these transformed keratinocytes in syngeneic recipients in vivo. Using sensitive ELISA assays, we found that cultures of the in vitro transformed Balb/c SCC line Pam 212 do not produce elevated levels of proinflammatory cytokines IL-1 alpha, IL-6, GM-CSF and KC, indicating that transformation or culture alone is insufficient to account for the level of cytokine expression detected in patient and experimental tumors. In contrast, Pam reisolates from primary and metastatic tumors were obtained which constitutively produce markedly elevated levels of cytokines IL-1 alpha, IL-6, KC and GM-CSF. The increase in the expression of these cytokines by SCC in vivo occurred independent of T and B lymphocyte-mediated immunity, since increases in expression of the cytokines was observed in lines reisolated from immunodeficient athymic nude and SCID Balb/c congenic mice. The increased expression of cytokines appeared to result from additional events in vivo, rather than due to selection of a pre-existing cytokine-producing subpopulation, since clones of the parental cell line expressed lower cytokine levels than cloned reisolates, and clones of the non-secreting parental cell line that formed tumors in vive secreted elevated levels of cytokines following reisolation. We conclude that the development of SCC that express proinflammatory cytokines is promoted by tumor-host interaction(s) that are independent of specific T and B cell immunity. C1 NIDOCD, Tumor Biol Sect, Head & Neck Surg Branch, NIH, Bethesda, MD USA. RP Van Waes, C (reprint author), Bldg 10,Rm 5D55,MSC-1419, Bethesda, MD 20892 USA. FU NIDCD NIH HHS [Z01-DC-00016] NR 40 TC 55 Z9 56 U1 1 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0262-0898 J9 CLIN EXP METASTAS JI Clin. Exp. Metastasis PD OCT PY 1998 VL 16 IS 7 BP 655 EP 664 DI 10.1023/A:1006559811429 PG 10 WC Oncology SC Oncology GA 162TQ UT WOS:000078363200009 PM 9932612 ER PT J AU Vesterhus, P Holland, SM Abrahamsen, TG Bjerknes, R AF Vesterhus, P Holland, SM Abrahamsen, TG Bjerknes, R TI Familial disseminated infection due to atypical mycobacteria with childhood onset SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID GAMMA-RECEPTOR DEFICIENCY; INTERFERON-GAMMA; SUSCEPTIBILITY; GENE AB We describe two brothers of consanguineous Pakistani parents who lived in Norway and had disseminated infections due to nontuberculous mycobacteria, The first boy developed clinical signs of disseminated BCG infection after vaccination. He was successfully treated with antimycobacterial agents. Two and one-half years later, he developed disseminated Mycobacterium avium complex infection and died at 6 years of age. The second boy, born 5 years after the death of his brother, did not receive BCG vaccine, At 2 years of age, he developed disseminated M. avium complex infection, Because he responded only partly to specific chemotherapy, empirical interferon gamma treatment was added to the antimycobacterial regimen. After 2 years of combined therapy, his condition is stable. Studies of peripheral blood mononuclear cells from the second boy demonstrated reduced surface expression of the ligand binding chain of interferon gamma receptor 1, This defect explains the increased susceptibility to mycobacterial disease in the two brothers. C1 Vest Agder Cty Hosp, Dept Pediat, N-4604 Kristiansand, Norway. Univ Bergen, Haukeland Hosp, Dept Pediat, N-5021 Bergen, Norway. Univ Oslo, Natl Hosp, Dept Pediat, Oslo, Norway. NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. RP Vesterhus, P (reprint author), Vest Agder Cty Hosp, Dept Pediat, N-4604 Kristiansand, Norway. NR 15 TC 21 Z9 21 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD OCT PY 1998 VL 27 IS 4 BP 822 EP 825 DI 10.1086/514939 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 129ZF UT WOS:000076493400028 PM 9798040 ER PT J AU Beason-Held, LL Purpura, KP Krasuski, JS Maisog, JM Daly, EM Mangot, DJ Desmond, RE Optican, LM Schapiro, MB VanMeter, JW AF Beason-Held, LL Purpura, KP Krasuski, JS Maisog, JM Daly, EM Mangot, DJ Desmond, RE Optican, LM Schapiro, MB VanMeter, JW TI Cortical regions involved in visual texture perception: a fMRI study SO COGNITIVE BRAIN RESEARCH LA English DT Article DE form; striate; extrastriate; functional magnetic resonance imaging; human; brain ID POSITRON EMISSION TOMOGRAPHY; INFERIOR TEMPORAL NEURONS; METRIC-SPACE ANALYSIS; CORTEX; BRAIN; FORM; PET; DISCRIMINATION; ORGANIZATION; STATISTICS AB To determine visual areas of the human brain involved in elementary form processing, functional magnetic resonance imaging (fMRI) was used to measure regional responses to two types of achromatic textures. Healthy young adults were presented with 'random' textures which lacked spatial organization of the black and white pixels that make up the image, and 'correlated' textures in which the pixels were ordered to produce extended contours and rectangular blocks at multiple spatial scales. Relative to a fixation condition, random texture stimulation resulted in increased signal intensity primarily in the striate cortex, with slight involvement of the cuneus and middle occipital, lingual and fusiform gyri. Correlated texture stimulation also resulted in activation of these areas, yet the regional extent of this activation was significantly greater than that produced by random textures. Unlike random stimulation, correlated stimulation additionally resulted in middle temporal activation. Direct comparison of the two stimulation conditions revealed significant differences most consistently in the anterior fusiform gyrus, but also in striate, middle occipital, lingual and posterior temporal regions in subjects with robust activation patterns. While both random and correlated stimulation produced activation in similar areas of the occipital lobe, the increase in regional activation during the correlated condition suggests increased recruitment of neuronal populations occurs in response to textures containing visually salient features. This increased recruitment occurs within striate, extrastriate and temporal regions of the brain, also suggesting the presence of receptive field mechanisms in the ventral visual pathway that are sensitive to features produced by higher-order spatial correlations. (C) 1998 Elsevier Science B.V. All rights reserved. C1 NIA, Neurosci Lab, NIH, Bethesda, MD 20892 USA. Cornell Univ, Coll Med, Dept Neurol & Neurosci, New York, NY USA. NIMH, Psychol & Psychopathol Lab, NIH, Bethesda, MD USA. NEI, Sect Neural Modeling, NIH, Bethesda, MD 20892 USA. RP Beason-Held, LL (reprint author), NIA, Neurosci Lab, NIH, Bldg 10,Rm 6C414,9000 Rockville Pike, Bethesda, MD 20892 USA. EM lbh@box-1.nih.gov OI Daly, Eileen/0000-0003-3625-3467 NR 43 TC 21 Z9 21 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0926-6410 J9 COGNITIVE BRAIN RES JI Cognit. Brain Res. PD OCT PY 1998 VL 7 IS 2 BP 111 EP 118 DI 10.1016/S0926-6410(98)00015-9 PG 8 WC Computer Science, Artificial Intelligence; Neurosciences; Neuroimaging SC Computer Science; Neurosciences & Neurology GA 131KG UT WOS:000076574400002 ER PT J AU Moon, HS Jung, JY Horowitz, AM Ma, DS Paik, DI AF Moon, HS Jung, JY Horowitz, AM Ma, DS Paik, DI TI Korean dental hygienists' knowledge and opinions about etiology and prevention of dental caries SO COMMUNITY DENTISTRY AND ORAL EPIDEMIOLOGY LA English DT Article DE knowledge of caries etiology and prevention; Korean dental hygienists; perceived effectiveness of preventive procedures ID FISSURE SEALANTS; FLUORIDE; STATES; PIT AB Objectives: Because of their formal education Korean dental hygienists have the potential to be the primary source of information on caries prevention for patients and the general public, and influence the use and adoption of caries preventive procedures. The purposes of this study were to determine the knowledge and opinions about caries etiology and prevention among Korean dental hygienists, and to describe associated factors. Methods: A pre-tested, 20-item questionnaire was mailed to 1120 dental hygienists selected by stratified random sampling and allocated proportionately. A postcard reminder was sent to all dental hygienists after 1 week. Non-respondents were sent additional complete mailings after 3 and 7 weeks. The response rate was 77% (n=863). Results: Analysis of six factors thought to be related to knowledge about caries etiology and prevention showed that dental hygienists who were taught to provide oral health education and believe that it is desirable to practice oral health education during dental hygiene school and those employed in health centers were likely to be more knowledgeable about caries etiology and prevention than other hygienists (P<0.05). In regression analysis of the perceived effectiveness of caries preventive procedures, hygienists who provided oral health education during their formal training tended to rate caries preventive procedures as being more effective than other dental hygienists (P<0.05). Conclusions: Overall, the results of this study suggest that most dental hygienists do not have up-to-date information on the etiology and prevention of dental caries, mechanisms of action of fluoride and effectiveness of preventive procedures. Efforts to increase the level of knowledge of Korean dental hygienists about caries prevention should focus on strategies to educate dental hygienists who have not been taught to provide oral health education, who do not have favorable opinions about the desirability of oral health education, and who had no experience with providing oral health education as part of their work, especially hygienists working in private clinics. Further, these efforts should include the revision of dental hygiene curricula and continuing education courses. C1 NIDR, NIH, Bethesda, MD 20892 USA. Seoul Natl Univ, Coll Dent, Dept Prevent & Publ Hlth Dent, Seoul, South Korea. Suwon Womens Jr Coll, Dept Oral Hyg, Suwon, South Korea. Natl Univ, Coll Dent, Dept Prevent & Publ Hlth Dent, Kangnung, South Korea. RP Horowitz, AM (reprint author), NIDR, NIH, Natcher Bldg Room 3AN-44B,45 Ctr Dr MSC 6401, Bethesda, MD 20892 USA. NR 31 TC 2 Z9 2 U1 0 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0301-5661 J9 COMMUNITY DENT ORAL JI Community Dentist. Oral Epidemiol. PD OCT PY 1998 VL 26 IS 5 BP 296 EP 302 DI 10.1111/j.1600-0528.1998.tb01964.x PG 7 WC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health SC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health GA 128ZU UT WOS:000076438900002 PM 9792120 ER PT J AU Knatterud, GL Rockhold, FW George, SL Barton, FB Davis, CE Fairweather, WR Honohan, T Mowery, R O'Neill, R AF Knatterud, GL Rockhold, FW George, SL Barton, FB Davis, CE Fairweather, WR Honohan, T Mowery, R O'Neill, R TI Guidelines for quality assurance in multicenter trials: A position paper SO CONTROLLED CLINICAL TRIALS LA English DT Article DE quality control; monitoring; data integrity; auditing; errors; scientific misconduct ID BREAST-CANCER TRIALS; CLINICAL-TRIALS; CRITERIA; OUTCOMES; SYSTEMS AB In the wake of reports of falsified data in one of the trials of the National Surgical Adjuvant Project for Breast and Bowel Cancer supported by the National Cancer Institute, clinical trials came under close scrutiny by the public, the press, and Congress. Questions were asked about the quality and integrity of the collected data and the analyses and conclusions of trials. In 1995, the leaders of the Society for Clinical Trials (the Chair of the Policy Committee, Dr. David DeMets, and the President of the Society, Dr. Sylvan Green) asked two members of the Society (Dr. Genell Knatterud and Dr. Frank Rockhold) to act as co-chairs of a newly formed subcommittee to discuss the issues of data integrity and auditing. In consultation with Drs. DeMets and Green, the co-chairs selected other members (Ms. France Barton, Dr. C.E. Davis, Dr. Bill Fairweather, Dr. Stephen George, Mr. Tom Honohan, Dr. Richard Mowery, and Dr. Robert O'Neill) to serve on the subcommittee. The subcommittee considered "how clean clinical trial data should be, to what extent auditing procedures are required, and who should conduct audits and how often." During the initial discussions, the subcommittee concluded that data auditing was insufficient to achieve data integrity. Accordingly, the subcommittee prepared this set of guidelines for standards of quality assurance for multicenter clinical trials. We include recommendations for appropriate action if problems are detected. (C) Elsevier Science Inc. 1998. C1 Maryland Med Res Inst, Baltimore, MD 21210 USA. Merck Res Labs, W Point, PA USA. Univ N Carolina, Chapel Hill, NC USA. US FDA, Rockville, MD 20857 USA. Duke Univ, Med Ctr, Durham, NC USA. Rhone Poulenc Rorer, Collegeville, PA USA. NCI, Bethesda, MD 20892 USA. RP Knatterud, GL (reprint author), Maryland Med Res Inst, 600 Wyndhurst Ave, Baltimore, MD 21210 USA. NR 35 TC 40 Z9 43 U1 0 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0197-2456 J9 CONTROL CLIN TRIALS JI Controlled Clin. Trials PD OCT PY 1998 VL 19 IS 5 BP 477 EP 493 DI 10.1016/S0197-2456(98)00033-6 PG 17 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 115WC UT WOS:000075688400007 PM 9741868 ER PT J AU Clore, GM Gronenborn, AM AF Clore, GM Gronenborn, AM TI NMR structure determination of proteins and protein complexes larger than 20 kDa SO CURRENT OPINION IN CHEMICAL BIOLOGY LA English DT Review ID MAGNETIC-RESONANCE SPECTROSCOPY; RESOLUTION 3-DIMENSIONAL STRUCTURE; MULTIDIMENSIONAL NMR; BIOLOGICAL MACROMOLECULES; GLOBAL FOLDS; COUPLINGS; RELAXATION; ANISOTROPY; ANGLES; THIOREDOXIN AB Recent advances in multidimensional nuclear magnetic resonance methodology to obtain H-1, N-15 and C-13 resonance assignments, interproton distance and torsion angle restraints, and restraints that characterize long-range order, coupled with new methods of structure refinement and novel methods for reducing linewidths, have permitted three-dimensional solution structures of single chain proteins in excess of 250 residues and multimeric proteins in excess of 40 kDa to be solved. These developments may permit the determination by nuclear magnetic resonance of macromolecular structures up to molecular weights in the 50-60 kDa range, thereby bringing into reach numerous systems of considerable biological interest, including a large variety of protein-protein and protein-nucleic acid complexes. C1 NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Clore, GM (reprint author), NIDDKD, Chem Phys Lab, NIH, Bldg 2, Bethesda, MD 20892 USA. RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 NR 51 TC 81 Z9 83 U1 1 U2 11 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON W1P 6LE, ENGLAND SN 1367-5931 J9 CURR OPIN CHEM BIOL JI Curr. Opin. Chem. Biol. PD OCT PY 1998 VL 2 IS 5 BP 564 EP 570 DI 10.1016/S1367-5931(98)80084-7 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 135YT UT WOS:000076831100002 PM 9818180 ER PT J AU Podgornik, R Strey, HH Parsegian, VA AF Podgornik, R Strey, HH Parsegian, VA TI Colloidal DNA SO CURRENT OPINION IN COLLOID & INTERFACE SCIENCE LA English DT Review ID ENHANCED ELECTROSTATIC FORCES; LIPOSOME COMPLEXES; PHASE-TRANSITIONS; HYDRATION FORCES; LIQUID-CRYSTALS; GENE-THERAPY; DOUBLE-LAYER; CONDENSATION; POLYMERS; PACKING AB For practical and fundamental reasons, DNA assemblies have become rewarding objects of study. Colloid physics is now learning to connect the structures of these assemblies with the measurable physical forces that organize them. The subject has ripened to the point where systematic inquiry and rigorous testing of theories is to be expected. C1 NIH, Bethesda, MD 20892 USA. Univ Massachusetts, Dept Polymer Sci & Engn, Amherst, MA 01003 USA. RP Podgornik, R (reprint author), NIH, Bldg 12A,Room 2041, Bethesda, MD 20892 USA. EM rudi@helix.nih.gov; VAP@cu.nih.gov; strey@helix.nih.gov RI Strey, Helmut/B-5456-2009; Podgornik, Rudolf/C-6209-2008 OI Podgornik, Rudolf/0000-0002-3855-4637 NR 61 TC 41 Z9 41 U1 0 U2 9 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1359-0294 J9 CURR OPIN COLLOID IN JI Curr. Opin. Colloid Interface Sci. PD OCT PY 1998 VL 3 IS 5 BP 534 EP 539 PG 6 WC Chemistry, Physical SC Chemistry GA 130FT UT WOS:000076509800012 ER PT J AU Waldmann, TA O'Shea, J AF Waldmann, TA O'Shea, J TI The use of antibodies against the IL-2 receptor in transplantation SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID CARDIAC ALLOGRAFT SURVIVAL; T-CELL LEUKEMIA; YTTRIUM-90-LABELED ANTI-TAC; JAK-3 JANUS KINASE; MICE LACKING JAK3; INTERLEUKIN-2 RECEPTOR; MONOCLONAL-ANTIBODY; HUMANIZED ANTIBODY; BETA-CHAIN; GAMMA-CHAIN AB Humanized monoclonal antibodies that recognize the a chain of the IL-2 receptor (e.g. daclizumab) have been used to prevent allograft rejection, since this chain is expressed by T cells participating in allograft rejection but not by resting T cells. In a randomized trial, when added to standard cyclosporin-based immunosuppression, daclizumab significantly reduced the frequency of acute rejection of renal transplants. C1 NCI, NIH, Bethesda, MD 20892 USA. NIAMSD, NIH, Bethesda, MD 20892 USA. RP Waldmann, TA (reprint author), NCI, NIH, 10 Ctr Dr,MSC 1374,10-4N115, Bethesda, MD 20892 USA. NR 66 TC 102 Z9 102 U1 1 U2 4 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON W1P 6LE, ENGLAND SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD OCT PY 1998 VL 10 IS 5 BP 507 EP 512 DI 10.1016/S0952-7915(98)80215-X PG 6 WC Immunology SC Immunology GA 128MC UT WOS:000076409700004 PM 9794841 ER PT J AU Pardoll, DM Topalian, SL AF Pardoll, DM Topalian, SL TI The role of CD4(+) T cell responses in antitumor immunity SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID RESTRICTED TUMOR-ANTIGENS; PEPTIDE VACCINATION; ESTABLISHED TUMORS; MURINE LEUKEMIA; IMMUNOTHERAPY; LYMPHOCYTES; RECOGNIZE; CANCER; CARCINOMA; SARCOMA AB While most of the focus in cancer immunology is on CD8+ cytotoxic T lymphocyte responses, recent evidence indicates that CD4+ T cells are an equally critical component of the antitumor immune response. Successful immunity to cancer will therefore require activation of tumor-specific CD4+ T cells. Tumor antigens recognized by CD4+ T cells that are restricted by MHC class II are beginning to be defined in both murine and human tumors. These will provide the basis for new generations of antigen-specific tumor vaccines. C1 Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA. NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. RP Pardoll, DM (reprint author), Johns Hopkins Univ, Sch Med, Dept Oncol, 720 Rutland Ave,Ross 364, Baltimore, MD 21205 USA. NR 49 TC 464 Z9 471 U1 3 U2 15 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON W1P 6LE, ENGLAND SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD OCT PY 1998 VL 10 IS 5 BP 588 EP 594 DI 10.1016/S0952-7915(98)80228-8 PG 7 WC Immunology SC Immunology GA 128MC UT WOS:000076409700017 PM 9794842 ER PT J AU Cameron, HA McKay, R AF Cameron, HA McKay, R TI Discussion point - Stem cells and neurogenesis in the adult brain SO CURRENT OPINION IN NEUROBIOLOGY LA English DT Editorial Material ID CENTRAL-NERVOUS-SYSTEM; NMDA RECEPTOR ACTIVATION; FIBROBLAST GROWTH-FACTOR; DENTATE GYRUS; SUBVENTRICULAR ZONE; MAMMALIAN FOREBRAIN; OLFACTORY-BULB; GRANULE CELLS; MOUSE BRAIN; RAT AB A new interest in replacing neurons lost to trauma or disease has been generated by findings that challenge the traditional view of the static (irreparable) adult brain. The discovery of stem cells and neurogenesis in the adult central nervous system is responsible for much of this interest. C1 NINDS, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP NINDS, Mol Biol Lab, NIH, Room 5A29,Bldg 36, Bethesda, MD 20892 USA. RI Cameron, Heather/E-6221-2011 OI Cameron, Heather/0000-0002-3245-5777 NR 45 TC 111 Z9 114 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0959-4388 EI 1873-6882 J9 CURR OPIN NEUROBIOL JI Curr. Opin. Neurobiol. PD OCT PY 1998 VL 8 IS 5 BP 677 EP 680 DI 10.1016/S0959-4388(98)80099-8 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 135NQ UT WOS:000076809300019 PM 9811628 ER PT J AU Zenger, VE Vogt, R Mandy, F Schwartz, A Marti, GE AF Zenger, VE Vogt, R Mandy, F Schwartz, A Marti, GE TI Quantitative flow cytometry: Inter-laboratory variation SO CYTOMETRY LA English DT Article; Proceedings Paper CT Conference on Quantitative Immunofluorescence Measurement CY NOV, 1997 CL OTTAWA, CANADA DE quantitative flow cytometry; molecular equivalent of soluble fluorochrome; antibody-binding capacity; microbead standards; calibration curve ID EXPRESSION; ANTIGENS; LYMPHOCYTES; STANDARDS; CELLS AB Quantitative how cytometry (QFCM) offers a means of standardization within and between flow cytometers, QFCM parameters were set by determining the antibody-binding capacity (ABC) of CD4, CD8, and CD3 cells from 10 normal donors with the use of eight FACScan flow cytometers. QC3 beads and a certified blank bead were used to set up the instruments. Fluorescein isothiocyanate (FITC) conjugated to molecular equivalents of soluble fluorochrome (MESF) microbead standards was used before and after the donor samples were run to ensure that the machines were operating consistently. Lyophilized cells (Cytotrol) were used as a target, to control for antigen expression in the cell preparation, Quantitative Simply Cellular (QSC) beads were used to establish a standard calibration curve for each of the FITC and phycoerythrin antibody conjugates on each of the instruments. Single-parameter fluorescent histograms derived from list-mode files were used to calculate the slope (coefficient of response), intercept (zero channel), number of channels per decade, and ABC or MESF threshold (blank bead). The fluorescence intensity (geometric mean) of the positive and negative donor cell populations was compared with the standard curves, and the ABCs were calculated. The results show consistent instrument performance between laboratories. However, after standardization of CD3, CD4, and CD8 ABCs to microbeads, large variations were noted between donors and laboratories. The source of this variation does not appear to be in the instrumentation but may be due to the lack of an unified set-up protocol, introducing issues of antibody saturation, methods for whole blood lysis and fixation, and the behavior of the microbead standards. (C) 1998 Wiley-Liss,Inc.(dagger). C1 NIH, US FDA, Div Cellular & Gene Therapies, Off Therapeut Res & Review,Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. Ctr Dis Control, Atlanta, GA 30333 USA. Lab Ctr Dis Control, Ottawa, ON, Canada. Carribean Microparticles, Hato Rey, PR USA. RP Marti, GE (reprint author), NIH, US FDA, Div Cellular & Gene Therapies, Off Therapeut Res & Review,Ctr Biol Evaluat & Res, Bldg 29B,Rm 2NN08,8800 Rockville Pike, Bethesda, MD 20892 USA. NR 21 TC 40 Z9 40 U1 0 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0196-4763 J9 CYTOMETRY JI Cytometry PD OCT 1 PY 1998 VL 33 IS 2 BP 138 EP 145 DI 10.1002/(SICI)1097-0320(19981001)33:2<138::AID-CYTO8>3.0.CO;2-F PG 8 WC Biochemical Research Methods; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 124WL UT WOS:000076205700007 PM 9773874 ER PT J AU Balint-Kurti, P Ginsburg, GT Liu, JC Kimmel, AR AF Balint-Kurti, P Ginsburg, GT Liu, JC Kimmel, AR TI Non-autonomous regulation of a graded, PKA-mediated transcriptional activation signal for cell patterning SO DEVELOPMENT LA English DT Article DE cAMP protein kinases; Dictyostelium; gene expression; rZIP; cell patterning ID DEPENDENT PROTEIN-KINASE; DICTYOSTELIUM DEVELOPMENT; EXTRACELLULAR CAMP; GENE-EXPRESSION; TIP FORMATION; PRESPORE; DIFFERENTIATION; DISCOIDEUM; FATE; GRADIENT AB The pseudoplasmodium or migrating slug of Dictyostelium is composed of non-terminally differentiated cells, organized along an anteroposterior axis. Cells in the anterior region of the slug define the prestalk compartment, whereas most of the posterior zone consists of prespore cells, We now present evidence that the cAMP-dependent protein kinase (PKA) and the RING domain/leucine zipper protein rZIP interact genetically to mediate a transcriptional activation gradient that regulates the differentiation of prespore cells within the posterior compartment of the slug. PKA is absolutely required for prespore differentiation. In contrast, rZIP negatively regulates prespore patterning; rzpA(-) cells, which lack rZIP, have reduced prestalk differentiation and a corresponding increase in prespore-specific gene expression. Using cell-specific markers and chimaeras of wild-type and rzpA-cells, we show that rZIP functions non-autonomously to establish a graded, prespore gene activation signal but autonomously to localize prespore expression. Overexpression of either the catalytic subunit or a dominant-negative regulatory subunit of PKA further demonstrates that PKA lies within the intracellular pathway that mediates the extracellular signal and regulates prespore patterning. Finally, we show that a 5'-distal segment within a prespore promoter that is responsive to a graded signal is also sensitive to PKA and rZIP: indicating that it acts directly at the level of prespore-specific gene transcription for regulation. C1 NIDDK, Cellular & Dev Biol Lab, MMDS, NIH, Bethesda, MD 20892 USA. RP Kimmel, AR (reprint author), NIDDK, Cellular & Dev Biol Lab, MMDS, NIH, Bldg 6-BI-22, Bethesda, MD 20892 USA. OI Balint-Kurti, Peter/0000-0002-3916-194X NR 43 TC 10 Z9 11 U1 0 U2 1 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 OCT PY 1998 VL 125 IS 20 BP 3947 EP 3954 PG 8 WC Developmental Biology SC Developmental Biology GA 164TW UT WOS:000078480500003 PM 9735356 ER PT J AU Barlow, C Liyanage, M Moens, PB Tarsounas, M Nagashima, K Brown, K Rottinghaus, S Jackson, SP Tagle, D Ried, T Wynshaw-Boris, A AF Barlow, C Liyanage, M Moens, PB Tarsounas, M Nagashima, K Brown, K Rottinghaus, S Jackson, SP Tagle, D Ried, T Wynshaw-Boris, A TI Atm deficiency results in severe meiotic disruption as early as leptonema of prophase I SO DEVELOPMENT LA English DT Article DE ATM; meiosis; prophase I; ATR; DMC1; electron microscopy; immunolocalization; mouse ID ATAXIA-TELANGIECTASIA GENE; MITOTIC CHECKPOINT GENES; CELL-CYCLE CHECKPOINT; SYNAPTONEMAL COMPLEX; DROSOPHILA-MELANOGASTER; CHROMOSOME SYNAPSIS; DNA-DAMAGE; RECOMBINATION; MEIOSIS; PROTEIN AB Infertility is a common feature of the human disorder ataxia-telangiectasia and Aml-deficient mice are completely infertile, To gain further insight into the role of ATM in meiosis, we examined meiotic cells in Atm-deficient mice during development. Spermatocyte degeneration begins between postnatal days 8 and 16.5, soon after entry into prophase I of meiosis, while oocytes degenerate late in embryogenesis prior to dictyate arrest. Using electron microscopy and immunolocalization of meiotic proteins in mutant adult spermatocytes, we found that male and female gametogenesis is severely disrupted in Atm-deficient mice as early as leptonema of prophase I, resulting in apoptotic degeneration, A small number of mutant cells progress into later stages of meiosis, but no cells proceed beyond prophase I. ATR, a protein related to ATM, DMC1, a RAD51 family member, and RAD51 are mislocalized to chromatin and have reduced localization to developing synaptonemal complexes in spermatocytes from At,ll-deficient mice, suggesting dysregulation of the orderly progression of meiotic events. ATM protein is normally present at high levels primarily in ova cytoplasm of developing ovarian follicles, and in the nucleus of spermatogonia and to a lesser extent in spermatoctyes, but without localization to the synaptonemal complex. We propose a model in which ATM acts to monitor meiosis by participation in the regulation or surveillance of meiotic progression, similar to its role as a monitor of mitotic cell cycle progression. C1 NIH, Natl Human Genome Res Inst, Genet Dis Res Branch, Bethesda, MD 20892 USA. NIH, Natl Human Genome Res Inst, Genome Technol Branch, Bethesda, MD 20892 USA. NIH, Natl Human Genome Res Inst, Mol Genet & Biol Branch, Bethesda, MD 20892 USA. NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick, Lab Cell & Mol Struct, Frederick, MD USA. York Univ, Dept Biol, N York, ON M3J 1P3, Canada. Wellcome CRC Inst, Cambridge CB2 1QR, England. RP Wynshaw-Boris, A (reprint author), NIH, Natl Human Genome Res Inst, Genet Dis Res Branch, Bldg 10, Bethesda, MD 20892 USA. EM tonywb@nhgri.nih.gov RI Dry, Kate/I-2328-2014 FU Wellcome Trust NR 40 TC 189 Z9 191 U1 3 U2 4 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 OCT PY 1998 VL 125 IS 20 BP 4007 EP 4017 PG 11 WC Developmental Biology SC Developmental Biology GA 164TW UT WOS:000078480500009 PM 9735362 ER PT J AU Ohtaka-Maruyama, C Hanaoka, F Chepelinsky, AB AF Ohtaka-Maruyama, C Hanaoka, F Chepelinsky, AB TI A novel alternative spliced variant of the transcription factor AP2 alpha is expressed in the murine ocular lens SO DEVELOPMENTAL BIOLOGY LA English DT Article ID FACTOR AP-2; GENE-EXPRESSION; DNA-BINDING; MULTIPLE ISOFORMS; MESSENGER-RNA; RETINOIC ACID; CELL-DEATH; CRYSTALLIN; PROTEINS; EYE AB The AP2 alpha gene encodes a transcription factor containing a basic, helix-span-helix DNA-binding/dimerization domain, which is developmentally regulated and retinoic acid inducible. Recent reports about AP2 alpha null mice indicate that AP2 alpha plays an important role in embryogenesis, especially in craniofacial development and midline fusion. Ocular development is also affected in these null mice. As AP2 alpha may be involved in transcriptional regulation in the lens, it was important to examine the expression of the AP2 alpha gene in the lens. Flour AP2 alpha mRNA variants have been previously isolated from whole mouse embryos. Variants 1, 3, and 4 are transcriptional activators that are transcribed from different promoters and variant 2 is a repressor lacking the activation domain encoded by exon 2. Using in situ-PCR, we found that AP2 alpha is expressed in the lens epithelia but not in the lens fibers. RT-PCR analysis of lens mRNA with amplimers specific for each variant revealed that AP2 alpha variants 1, 2, and 3 are expressed ill newborn mouse lenses. However, variant 4 is not expressed in the lens. In this report we characterized a novel isoform, which we named variant 5, expressed in the lens and kidney. Variant 5, which is generated by alternative splicing, may function as a repressor due to the partial deletion of the proline-rich transactivation domain encoded by exon 2. This is the first molecular characterization of AP2 alpha gene expression in the lens. Our results indicate that two activator and two repressor AP2 alpha isoforms may play a role in regulating gene expression in the lens. (C) 1998 Academic Press. C1 NEI, Mol & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. Inst Phys & Chem Res, Cellular Physiol Lab, Wako, Saitama 35101, Japan. RP Chepelinsky, AB (reprint author), NEI, Mol & Dev Biol Lab, NIH, 6 Ctr Dr MSC 2730,Bldg 6,Room 211, Bethesda, MD 20892 USA. RI Ohtaka-Maruyama, chiaki/G-6943-2013 NR 57 TC 21 Z9 21 U1 0 U2 4 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD OCT 1 PY 1998 VL 202 IS 1 BP 125 EP 135 DI 10.1006/dbio.1998.8997 PG 11 WC Developmental Biology SC Developmental Biology GA 128FZ UT WOS:000076396200010 PM 9758708 ER PT J AU Savagner, P Karavanova, I Perantoni, A Thiery, JP Yamada, KM AF Savagner, P Karavanova, I Perantoni, A Thiery, JP Yamada, KM TI Slug mRNA is expressed by specific mesodermal derivatives during rodent organogenesis SO DEVELOPMENTAL DYNAMICS LA English DT Article DE lungs; neural crest; sclerotome; slug; snail; somite; splanchnopleure; zinc-finger ID ZINC-FINGER GENE; NEURAL CREST; TRANSCRIPTION FACTOR; DROSOPHILA-MELANOGASTER; SNAIL; ESCARGOT; PATTERN; GASTRULATION; MUTATIONS; ABLATION AB We describe the expression pattern of the zinc-finger protein slug during rat and mouse embryonic development, Expression was mostly confined to migratory neural crest cells and several mesodermal derivatives. We could not detect slug expression in premigratory rodent neural crest cells, unlike previously studied vertebrates; the earliest substantial expression of slug was found in migratory cranial neural crest cells invading the first branchial arch, Their derivatives, comprising most of the craniofacial region, continued to express slug. Concomitantly, slug was expressed in sclerotome precursor cells prior to their separation from the differentiating somites. During organogenesis, slug was expressed in mesenchymal components of lung, digestive tract, meso- and metanephros until late stages. Slug was also found in mesenchymal cells undergoing cartilage and bone differentiation. Expression was down-regulated in parallel with chondrocyte phenotypic differentiation. Overall, slug appeared to be expressed by mesenchymal cells at predifferentiation stages involving cell migration and phenotype modulation. Expression was generally down-regulated afterwards. However, residual slug mRNA was found in several adult tissues, including liver and lung. Dev. Dyn. 1998;213:182-187. (C) 1998 Wiley-Liss, Inc. C1 Inst Curie, CNRS, F-75231 Paris, France. NIDR, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD 20892 USA. NCI, Comparat Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. RP Savagner, P (reprint author), Fac Pharm, INSERM, U456, 2 Ave Pr Leon Bernard, F-35043 Rennes, France. OI Yamada, Kenneth/0000-0003-1512-6805 NR 21 TC 29 Z9 29 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD OCT PY 1998 VL 213 IS 2 BP 182 EP 187 DI 10.1002/(SICI)1097-0177(199810)213:2<182::AID-AJA3>3.0.CO;2-C PG 6 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 125QP UT WOS:000076248800003 PM 9786418 ER PT J AU Weyer, C Tataranni, PA Snitker, S Danforth, E Ravussin, E AF Weyer, C Tataranni, PA Snitker, S Danforth, E Ravussin, E TI Increase in insulin action and fat oxidation after treatment with CL 316,243, a highly selective beta(3)-adrenoceptor agonist in humans SO DIABETES LA English DT Article ID BETA-ADRENOCEPTOR AGONIST; 24-HOUR ENERGY-EXPENDITURE; WHITE ADIPOSE-TISSUE; BETA-3-ADRENERGIC RECEPTOR; ADRENERGIC-RECEPTORS; ANTIOBESITY; OBESITY; CL-316,243; MICE; BRL-26830A AB Stimulation of beta(3)-adrenoceptors by selective agonists improves insulin action and stimulates energy metabolism in various rodent models of obesity and type 2 diabetes. Whether selective beta(3)-adrenoceptor stimulation exerts metabolic actions in humans remains to be proven. The effects of a highly selective beta(3)-adrenoceptor agonist on insulin action, energy metabolism, and body composition were assessed in 14 healthy young lean male volunteers (age 22.5 +/- 3.3 years, 15 +/- 5% body fat [mean +/- SD]) randomly assigned to 8 weeks of treatment with either 1,500 mg/day of CL 316,243 (n = 10) or placebo (n = 4). Insulin-mediated glucose disposal (IMGD), nonoxidative glucose disposal(NOGD), oxidative glucose disposal(OGD) (indirect calorimetry), and splanchnic glucose output (SGO; 3-[H-3]glucose) were determined during a 100-min hyperinsulinemic-euglycemic glucose clamp (40 mU.m(-2).min(-l)) before and after 4 and 8 weeks of treatment. The 24-h energy expenditure (24-EE), 24-h respiratory quotient (24-RQ), and the oxidation rates of fat and carbohydrate were determined in a respiratory chamber before and after 8 weeks. After 4 weeks, treatment with CL 316,243 increased IMGD (+45%, P < 0.01) in a plasma concentration-dependent manner (r = 0.76, P < 0.02). This effect was due to an 82% increase in NOGD (P < 0.01), while OGD and SGO remained unchanged. The effects on insulin action were markedly diminished after 8 weeks; this was significantly related to an unexpected decline in the plasma concentrations of CL 316,243 (-36%, P = 0.08). At this time, 24-RQ was lowered (P < 0.001), corresponding to a 23% increase in fat oxidation (P < 0.01) and a 17% decrease in carbohydrate oxidation (P = 0.05). The 24-EE after 8 weeks did not differ from baseline, and there was no change in body weight or body composition. Plasma concentrations of glucose, insulin, and leptin were unaffected by treatment, while free fatty acid concentrations increased by 41% (P < 0.05), again linearly with the achieved plasma concentration of CL 316,243 (r = 0.67, P < 0.05). Treatment with CL 316,243 had no effect on heart rate or blood pressure and caused no cases of tremors. We conclude that treatment of lean male subjects with CL 316,243 increases insulin action and fat oxidation, both in a plasma concentration-dependent manner. This is the first study to demonstrate unequivocal metabolic effects of a highly selective beta(3)-adrenoceptor agonist in humans. C1 NIDDKD, Clin Diabet & Nutr Sect, NIH, Phoenix, AZ 85016 USA. RP Weyer, C (reprint author), NIDDKD, Clin Diabet & Nutr Sect, NIH, 4212 N 16th St,Room 5-41, Phoenix, AZ 85016 USA. EM cweyer@phx.niddk.nih.gov NR 54 TC 112 Z9 114 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD OCT PY 1998 VL 47 IS 10 BP 1555 EP 1561 DI 10.2337/diabetes.47.10.1555 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 122FM UT WOS:000076061300004 PM 9753292 ER PT J AU Wilson, PWF AF Wilson, PWF TI Do estrogens reduce glycemic levels? SO DIABETES CARE LA English DT Editorial Material ID DEPENDENT DIABETES-MELLITUS; POLYCYSTIC-OVARY-SYNDROME; POSTMENOPAUSAL WOMEN; REPLACEMENT THERAPY; INSULIN SENSITIVITY; RISK; METABOLISM; GLUCOSE; DISEASE; RATS C1 NHLBI, Framingham, MA USA. RP Wilson, PWF (reprint author), Framington Heart Study, 5 Thurber St, Framingham, MA 01701 USA. EM peter@fram.nhlbi.nih.gov FU NHLBI NIH HHS [N01-HC-38038] NR 30 TC 6 Z9 8 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD OCT PY 1998 VL 21 IS 10 BP 1585 EP 1586 DI 10.2337/diacare.21.10.1585 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 122FH UT WOS:000076060900001 PM 9773714 ER PT J AU Espeland, MA Hogan, PE Fineberg, SE Howard, G Schrott, H Waclawiw, MA Bush, TL AF Espeland, MA Hogan, PE Fineberg, SE Howard, G Schrott, H Waclawiw, MA Bush, TL TI Effect of postmenopausal hormone therapy on glucose and insulin concentrations SO DIABETES CARE LA English DT Article ID CLINICAL-TRIALS; CARBOHYDRATE-METABOLISM; REPLACEMENT THERAPY; PEPI TRIAL; WOMEN; ESTROGEN; SENSITIVITY; ELIMINATION; RESISTANCE; SECRETION AB OBJECTIVE - To characterize the long-term impact of four hormone therapy regimens on insulin and glucose concentrations measured during a standard oral glucose tolerance test. RESEARCH DESIGN AND METHODS - The Postmenopausal Estrogen/Progestin Intervention Study was a 3-year placebo-controlled randomized trial to assess effects of four hormone regimens on cardiovascular risk factors. This efficacy analysis describes glucose and insulin concentrations from 788 adherent women at baseline and at 1 and 3 years' postrandomization. RESULTS - When compared with women taking placebo, those taking conjugated equine estrogen (CEE) at 0.625 mg/day with or without a progestational agent had mean fasting insulin levels that were 16.1% lower, mean fasting glucose levels 2.2 mg/dl lower and mean 2-h glucose levels 6.4 mg/dl higher (each nominal P < 0.05). No significant differences were apparent between women taking CEE only Versus the three progestin regimens: medroxyprogesterone acetate (MPA) at 2.5 mg daily (continuous MPA), MPA at 10 mg on days 1-12 (cyclical MPA), and micronized progesterone (MP) (cyclical) at 200 mg on days 1-12. The impact of hormone therapy on insulin and glucose depended on baseline levels of fasting insulin and l-h glucose (P < 0.05). However, the treatment effects on carbohydrate metabolism appeared to be consistent across participant subgroups formed by lifestyle, clinical, and demographic characteristics. CONCLUSIONS - Oral hormone therapy involving 0.625 mg/day of CEE may modestly decrease fasting levels of insulin and glucose. Postchallenge glucose concentrations are increased, however, which may indicate delayed glucose clearance. C1 Wake Forest Univ, Sch Med, Biostat Sect, Winston Salem, NC 27157 USA. Indiana Univ, Sch Med, Indianapolis, IN USA. Univ Iowa, Lipid Res Clin, Iowa City, IA USA. NHLBI, Bethesda, MD 20892 USA. Univ Maryland, Sch Med, Baltimore, MD 21201 USA. RP Espeland, MA (reprint author), Wake Forest Univ, Sch Med, Biostat Sect, Med Ctr Blvd, Winston Salem, NC 27157 USA. EM mespelan@rc.phs.wfubmc.edu FU NHLBI NIH HHS [U01-HL40154, U01-HL40185, U01-HL40195] NR 40 TC 127 Z9 129 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD OCT PY 1998 VL 21 IS 10 BP 1589 EP 1595 DI 10.2337/diacare.21.10.1589 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 122FH UT WOS:000076060900003 PM 9773716 ER PT J AU Salbe, AD Fontvieille, AM Pettitt, DJ Ravussin, E AF Salbe, AD Fontvieille, AM Pettitt, DJ Ravussin, E TI Maternal diabetes status does not influence energy expenditure or physical activity in 5-year-old Pima Indian children SO DIABETOLOGIA LA English DT Article DE gestational diabetes; energy metabolism; pre-school aged children; doubly labelled water; body composition ID BODY-WEIGHT GAIN; DOUBLY LABELED WATER; GLUCOSE-TOLERANCE; CAUCASIAN CHILDREN; OBESITY; PREGNANCY; WOMEN; ADIPOSITY; RISK; FAT AB Children of women who have diabetes during pregnancy are more likely to become obese by early adulthood than those of women with normal glucose tolerance during pregnancy. Obesity can result from either excess food intake, low levels of energy expenditure or both. In our study, we tested whether maternal diabetes status influences total energy expenditure (TEE by doubly labelled water), resting metabolic rate (RMR by ventilated hood) and physical activity level (PAL = TEE/RMR and assessed by activity questionnaire). Measurements were taken in 88 5-year-old Pima Indian children, 24 children of women with diabetes (2-h plasma glucose greater than or equal to 11.1 mmol/l) diagnosed before or during pregnancy and 64 children of women with normal glucose tolerance (2-h plasma glucose < 7.8 mmol/l during pregnancy and no prior history of abnormal glucose tolerance). Although birth weight was higher in children of diabetic than of nondiabetic women (mean +/- SD; 3.8 +/- 0.6 vs 3.5 +/- 0.4 kg, p < 0.03), there were no differences in weight (26.4 +/- 6.9 vs 24.2 +/- 5.6 kg) or per cent body fat (O-18 dilution; 33 +/- 8 vs 31 +/- 8 %) between the groups at 5 years of age. There was no difference in TEE (6508 +/- 1109 vs 6175 +/- 942 kJ/d) or in RMR (4674 +/- 786 vs 4483 +/- 603 kJ/d) expressed as absolute values or after adjustment for weight and sex (TEE) or fat-free mass, fat mass, and sex (RMR). Physical activity level was also similar between the groups (1.40 +/- 0.12 vs 1.38 +/- 0.12). These results suggest that maternal diabetes status does not influence energy expenditure in the children by 5 years of age. Thus the greater obesity seen at older ages in the children of women with diabetes could be due to excess energy intake. Alternatively, if energy expenditure does have a role in the aetiology of obesity in these children, perhaps it does so only in older children. C1 NIDDKD, Clin Diabet & Nutr Sect, NIH, Phoenix, AZ 85016 USA. NIDDKD, Diabet & Arthritis Epidemiol Sect, NIH, Phoenix, AZ USA. RP Salbe, AD (reprint author), NIDDK, NIH, CDNS,4212 N 16th St,Rm 541, Phoenix, AZ 85016 USA. NR 36 TC 9 Z9 10 U1 0 U2 2 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD OCT PY 1998 VL 41 IS 10 BP 1157 EP 1162 DI 10.1007/s001250051045 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 125QQ UT WOS:000076248900005 PM 9794101 ER PT J AU Chia, SC Bergasa, NV Kleiner, DE Goodman, Z Hoofnagle, JH Di Bisceglie, AM AF Chia, SC Bergasa, NV Kleiner, DE Goodman, Z Hoofnagle, JH Di Bisceglie, AM TI Pruritus as a presenting symptom of chronic hepatitis C SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE cirrhosis; cholestasis; hepatitis C virus; primary biliary cirrhosis; itching; bile acids ID PRIMARY BILIARY-CIRRHOSIS; PLACEBO-CONTROLLED TRIAL; DOUBLE-BLIND; NALOXONE INFUSIONS; ALPHA-INTERFERON; CHOLESTASIS; THERAPY; VARIANT AB Pruritus is a common symptom in cholestatic liver disease but is rare in chronic hepatitis C, Eight patients with chronic hepatitis C and severe pruritus were compared with regard to biochemical, serological, and histological features to eight disease controls with primary biliary cirrhosis and seven with cirrhosis due to hepatitis C. Among those with severe pruritus associated with chronic hepatitis C, serum aminotransferases were raised in all, alkaline phosphatase in four, and gamma-glutamyl-transpeptidase levels in all except one. Serum cholylglycine levels were elevated in seven of eight patients. Liver biopsies showed moderate to severe fibrosis in all patients and cirrhosis in five. Compared to control subjects with cirrhosis due to hepatitis C but no pruritus, ductopenia, and cholestatic changes were prominent, although less so than in controls with primary biliary cirrhosis. Chronic hepatitis C with moderate to severe fibrosis may result in low-grade cholestasis with pruritus, possibly in association with bile duct disappearance. C1 NIDDKD, Liver Dis Sect, NIH, Bethesda, MD 20892 USA. NCI, NIH, Bethesda, MD 20892 USA. Armed Forces Inst Pathol, Hepat Pathol Branch, Washington, DC 20306 USA. RP Hoofnagle, JH (reprint author), NIDDKD, Liver Dis Sect, NIH, Bldg 10,Room 9B 07, Bethesda, MD 20892 USA. OI Kleiner, David/0000-0003-3442-4453 NR 18 TC 42 Z9 42 U1 0 U2 1 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD OCT PY 1998 VL 43 IS 10 BP 2177 EP 2183 DI 10.1023/A:1026646017851 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 129KN UT WOS:000076462500003 PM 9790451 ER PT J AU Hou, EW Li, SSL AF Hou, EW Li, SSL TI Genomic organization and chromosome localization to band 19p13.3 of the human AES gene: Gene product exhibits strong similarity to the N-terminal domain of Drosophila enhancer of Split Groucho protein SO DNA AND CELL BIOLOGY LA English DT Article ID MOLECULAR-CLONING; BETA-SUBUNIT; LOCUS; MOUSE; EXPRESSION; TRANSCRIPT; HOMOLOGY; COMPLEX; GRG AB The human Amino Enhancer of Split (AES) gene encodes a protein of 197 amino acids exhibiting strong similarity to the N-terminal domain of Drosophila Enhancer of Split Groucho (ESG) protein. The nucleotide sequence of approximately 12 kb from the human AES gene was determined, and its protein-encoding sequence was shown to be interrupted by six introns. The human AES gene was further localized by fluorescence in situ hybridization to chromosome band 19p13.3 near the transcription factor 3 (TCF3) gene. C1 NIEHS, Div Intramural Res, NIH, Res Triangle Pk, NC 27709 USA. RP Li, SSL (reprint author), NIEHS, Div Intramural Res, NIH, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. NR 12 TC 0 Z9 1 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1044-5498 J9 DNA CELL BIOL JI DNA Cell Biol. PD OCT PY 1998 VL 17 IS 10 BP 911 EP 913 DI 10.1089/dna.1998.17.911 PG 3 WC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity GA 136AG UT WOS:000076834900009 PM 9809752 ER PT J AU Kim, YC Camaioni, E Ziganshin, AU Ji, XD King, BF Wildman, SS Rychkov, A Yoburn, J Kim, H Mohanram, A Harden, T Boyer, JL Burnstock, G Jacobson, KA AF Kim, YC Camaioni, E Ziganshin, AU Ji, XD King, BF Wildman, SS Rychkov, A Yoburn, J Kim, H Mohanram, A Harden, T Boyer, JL Burnstock, G Jacobson, KA TI Synthesis and structure-activity relationships of pyridoxal-6-arylazo-5 '-phosphate and phosphonate derivatives as P2 receptor antagonists SO DRUG DEVELOPMENT RESEARCH LA English DT Article DE ATP; nucleotides; ion channels; phospholipase C; smooth muscle; guinea pig; turkey erythrocytes ID PHOSPHOLIPASE-C; P-2-PURINOCEPTOR ANTAGONISTS; P-2 PURINOCEPTORS; PPADS; RESPONSES; NUCLEOTIDES; AGONISTS; P-2Y-PURINOCEPTORS; P-2X-PURINOCEPTORS; ACTIVATION AB Novel analogs of the P2 receptor antagonist pyridoxal-5'-phosphate-6-phenylazo-2',4'-disulfonate (PPADS) were synthesized. Modifications were made through functional group substitution on the sulfophenyl ring and at the phosphate moiety through the inclusion of phosphonates, demonstrating that a phosphate linkage is not required for P2 receptor antagonism. Substituted 6-phenylazo and 6-naphthylazo derivatives were also evaluated. Among the 6-phenylazo derivatives, 5'-methyl, ethyl, propyl, vinyl, and allyl phosphonates were included. The compounds were tested as antagonists at turkey erythrocyte and guinea-pig taenia coli P2Y(1) receptors, in guinea-pig vas deferens and bladder P2X(1) receptors, and in ion flux experiments by using recombinant rat P2X(2) receptors expressed in Xenopus oocytes. Competitive binding assay at human P2X(1) receptors in differentiated HL-60 cell membranes was carried out by using [S-35]ATP-gamma-S. A 2'-chloro-5'-sulfo analog of PPADS (C14H12O9N3ClPSNa), a vinyl phosphonate derivative (C15H12O11N3PS2Na3), and a naphthylazo derivative (C18H14O12N3PS2Na2), were particularly potent in binding to human P2X(1) receptors. The potencies of phosphate derivatives at P2Y(1) receptors were generally similar to PPADS itself, except for the p-carboxyphenylazo phosphate derivative C15H13O8N3PNa and its m-chloro analog C15H12O8N3ClPNa, which were selective for P2X vs. P2Y(1) receptors. C15H12O8N3ClPNa was very potent at rat P2X(2) receptors with an IC50 value of 0.82 mu M. Among the phosphonate derivatives, [4-formyl-3-hydroxy-2-methyl-6-(2-chloro-5-sulfonylphenylazo)-pyrid-5-yl]methylphosphonic acid (C14H12O8N3ClPSNa) showed high potency at P2Y(1) receptors with an IC50 of 7.23 mu M. The corresponding 2,5-disulfonylphenyl derivative was nearly inactive at turkey erythrocyte P2Y(1) receptors, whereas at recombinant P2X(2) receptors had an IC50 value of 1.1 mu M. An ethyl phosphonate derivative (C15H15O11N3PS2Na3), whereas inactive at turkey erythrocyte P2Y(1) receptors, was particularly potent at recombinant P2X(2) receptors. (C) 1998 Wiley-Liss, Inc.dagger C1 NIDDK, LBC, NIH, Bethesda, MD 20892 USA. Royal Free Hosp, Sch Med, Auton Neurosci Inst, London, England. Kazan Med Inst, Kazan, Russia. Univ N Carolina, Sch Med, Dept Pharmacol, Chapel Hill, NC USA. RP Jacobson, KA (reprint author), NIDDK, LBC, NIH, Bldg 8A,Rm B1A-19, Bethesda, MD 20892 USA. EM kajacobs@helix.nih.gov RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS [Z01 DK031115-24, Z99 DK999999]; NHLBI NIH HHS [R01 HL054889, R29 HL054889]; NIGMS NIH HHS [R01 GM038213] NR 46 TC 28 Z9 29 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0272-4391 J9 DRUG DEVELOP RES JI Drug Dev. Res. PD OCT PY 1998 VL 45 IS 2 BP 52 EP 66 DI 10.1002/(SICI)1098-2299(199810)45:2<52::AID-DDR2>3.0.CO;2-V PG 15 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 149RL UT WOS:000077619100002 PM 22922976 ER PT J AU Lin, MH AF Lin, MH TI Ethical considerations in clinical trials: An international perspective SO DRUG INFORMATION JOURNAL LA English DT Article DE ethical conduct; institutional review board; protection of human subjects; ethical principles and guidelines AB Ethical conduct of biomedical research involving human subjects is one of the critical elements for a successful outcome of a clinical trial. Many national and international guidelines and regulations have been established to address the ethical conduct of clinical trials. This paper will describe the roles and functions of the institutional review board and the involvement of the Office for Protection from Research Risks and the Food and Drug Administration in protecting human subjects involved in clinical trials in the United States. It will highlight the international ethical principles and guidelines. Comparison of the international ethical guidelines with United States regulations will also be provided, with emphasis on ethical review and informed consent. C1 NIH, Off Protect Res Risks, Bethesda, MD 20892 USA. RP Lin, MH (reprint author), NIH, Off Protect Res Risks, 6100 Execut Blvd,Suite 3B01,MSC 7507, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU DRUG INFORMATION ASSOCIATION PI FORT WASHINGTON PA 501 OFFICE CENTER DR, STE 450, FORT WASHINGTON, PA 19034-3212 USA SN 0092-8615 J9 DRUG INF J JI Drug Inf. J. PD OCT-DEC PY 1998 VL 32 SU S BP 1293S EP 1297S PG 5 WC Health Care Sciences & Services; Pharmacology & Pharmacy SC Health Care Sciences & Services; Pharmacology & Pharmacy GA V2590 UT WOS:000165531400022 ER PT J AU Zhai, S Dai, RK Friedman, FK Vestal, RE AF Zhai, S Dai, RK Friedman, FK Vestal, RE TI Comparative inhibition of human cytochromes P450 1A1 and 1A2 by flavonoids SO DRUG METABOLISM AND DISPOSITION LA English DT Article ID RAT-LIVER MICROSOMES; INDUCED MICRONUCLEI; NATURAL FLAVONOIDS; CYP1A1 GENE; CANCER; MICE; METABOLISM; ENZYMES; SUSCEPTIBILITY AB Flavonoids are a class of dietary phytochemicals that modulate various biological activities. The effects of flavone and five hydroxylated derivatives on the methoxyresorufin O-demethylase activity catalyzed by cDNA-expressed human cytochromes P450 (CYP)1A1 and 1A2 were examined. Flavone was a less potent inhibitor of CYP1A1 (IC50 = 0.14 mu M) than CYP1A2 (IC50 = 0.066 mu M). Four hydroxylated flavone derivatives (3-hydroxy-, 5-hydroxy-, 7-hydroxy-, and 3,7-dihydroxyflavone) were also potent inhibitors of CYP1A1 (IC50 < 0.1 mu M) and CYP1A2 (IC50 < 0.3 mu M). For CYP1A1, 7-hydroxyflavone exhibited a competitive mode of inhibition, with a K-i value of 0.015 mu M and 6-fold selectivity for CYP1A1 over CYP1A2. 3,5,7-Trihydroxyflavone (galangin) showed the highest potency toward CYP1A2. The inhibition by galangin of the methoxyresorufin O-demethylase activity of CYP1A2 was mixed-type, with a K-i value of 0.008 mu M. Galangin showed 5-fold selectivity in its inhibition of CYP1A2 over CYP1A1. The results indicate that some flavonoids have high potencies and selectivities for inhibition of CYP1A isozymes. This may have important implications for cancer prevention, as well as other pharmacological and toxicological effects of these compounds. C1 Idaho State Univ, Dept Vet Affairs Med Ctr, Clin Pharmacol & Gerontol Res Unit, Pocatello, ID 83209 USA. Idaho State Univ, Mt States Med Res Inst, Pocatello, ID 83209 USA. Idaho State Univ, Coll Pharm, Dept Pharmaceut Sci, Pocatello, ID 83209 USA. NCI, Mol Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Pharmacol, Seattle, WA 98195 USA. RP Vestal, RE (reprint author), VA Med Ctr, Res Serv 151, 500 W Ft St, Boise, ID 83702 USA. RI Friedman, Fred/D-4208-2016 NR 36 TC 92 Z9 97 U1 1 U2 4 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0090-9556 J9 DRUG METAB DISPOS JI Drug Metab. Dispos. PD OCT PY 1998 VL 26 IS 10 BP 989 EP 992 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 128FY UT WOS:000076396100007 PM 9763404 ER PT J AU Gerloff, C Uenishi, N Nagamine, T Kunieda, T Hallett, M Shibasaki, H AF Gerloff, C Uenishi, N Nagamine, T Kunieda, T Hallett, M Shibasaki, H TI Cortical activation during fast repetitive finger movements in humans: steady-state movement-related magnetic fields and their cortical generators SO ELECTROMYOGRAPHY AND MOTOR CONTROL-ELECTROENCEPHALOGRAPHY AND CLINICAL NEUROPHYSIOLOGY LA English DT Article DE movement-related potentials; bereitschaftspotential; readiness held; sensorimotor cortex; topographic mapping; dipole analysis; cortical physiology; magnetoencephalography ID SUPPLEMENTARY MOTOR AREA; PRECEDING VOLUNTARY MOVEMENT; NEURONAL-ACTIVITY; SEQUENTIAL MOVEMENTS; CEREBRAL-CORTEX; PREMOTOR CORTEX; POTENTIALS; MONKEY; STIMULATION; EEG AB Objective: To study the cortical physiology of fast repetitive linger movements. Methods: We recorded steady-state movement-related magnetic fields (ssMRMFs) associated with self-paced, repetitive, 2-Hz finger movements in a 122-channel whole-head magnetometer. The ssMRMF generators were determined by equivalent current dipole (ECD) modeling and co-registered with anatomical magnetic resonance images (MRIs). Results: Two major ssMRMF components occurred in proximity to EMG onset: a motor field CMF) peaking at 37 +/- 11 ms after EMG onset, and a postmovement held (post-MF), with inverse polarity, peaking at 102 +/- 13 ms after EMG onset. The ECD for the MF was located in the primary motor cortex (M1), and the ECD for the post-MF in the primary somatosensory cortex (S1). The MF was probably closely related to the generation of corticospinal volleys, whereas the post-MF most likely represented reafferent feedback processing. Conclusions: The present data offer further evidence that the main phasic changes of cortical activity occur in direct proximity to repetitive EMG bursts in the contralateral M1 and S1. They complement previous electroencephalography (EEC) findings on steady-state movement-related cortical potentials (ssMRCPs) by providing more precise anatomical information, and thereby enhance the potential value of ssMRCPs and ssMRMFs for studying human sensorimotor cortex activation non-invasively and with high temporal resolution. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved. C1 NINDS, Human Motor Control Sect, Med Neurol Branch, NIH, Bethesda, MD 20892 USA. Kyoto Univ, Sch Med, Dept Brain Pathophysiol, Sakyo Ku, Kyoto 6068507, Japan. RP Gerloff, C (reprint author), Univ Tubingen, Dept Neurol, Cort Physiol Res Grp, Hoppe Seyler Str 3, D-72076 Tubingen, Germany. NR 47 TC 50 Z9 50 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0924-980X J9 ELECTROMYOGR MOTOR C JI Electromyogr. Mot. Control-Electroencephalogr. Clin. Neurophysiol. PD OCT PY 1998 VL 109 IS 5 BP 444 EP 453 DI 10.1016/S0924-980X(98)00045-9 PG 10 WC Engineering, Biomedical; Neurosciences SC Engineering; Neurosciences & Neurology GA 143FR UT WOS:000077245000009 PM 9851302 ER PT J AU Radko, SP Chrambach, A AF Radko, SP Chrambach, A TI Mechanistic insights derived from retardation and peak broadening of particles up to 200 nm in diameter in electrophoresis in semidilute polyacrylamide solutions SO ELECTROPHORESIS LA English DT Article DE polymer solution; capillary zone electrophoresis; rigid spherical particles; retardation; peak width ID ENTANGLED POLYMER-SOLUTIONS; CAPILLARY-ZONE-ELECTROPHORESIS; LATEX-PARTICLES; DNA; DEPLETION; ADSORPTION; SEPARATION; DEXTRAN; LAYERS; MODEL AB Rigid spherical particles in the size range of 5-200 nm diameter were subjected to capillary zone electrophoresis (CZE) in semidilute solutions of uncross-linked polyacrylamide of M-r 5, 7 and 18 X 10(6) (PA-5, -7 and -18, respectively) of varying concentrations up to 1.6% and at field strengths varying from 68 to 270 V/cm. For all particles under study, the experimental Ferguson plots, log(mobility) vs, polymer concentration, permit a linear approximation. Their slope, the retardation coefficient K-R= partial derivative log(mobility)/partial derivative(concentration), for particles smaller than 30 nm in diameter increased with particle size in PA-5 and -7 independently of electric field strength and polymer M-r. The K-R of particles of 30 nm in diameter or more was found to be independent of particle size at the lowest field strength used but to decrease with it at the higher values of field strength. The decrease was parallel but shifted to higher values of retardation when the polymer M-r increased from 5 to 7 X 106. With a decreasing ratio of average mesh size of the polymer network, xi, to particle radius, R, the approach to "continuity" of the polymeric medium (xi/R much less than 1) with both increasing particle size and polymer concentration does not result in the retardation behavior expected according to the macroscopic (bulk) viscosity of the solution. These experimental observations were hypothetically interpreted in terms of a transition to a retardation mechanism comprising the formation of a polymer depletion layer near the particle surface - polymer solution interface. Peak width exhibited an overall increase with PA-7 concentration for all particles studied. For particles of 30 nm in diameter or less, the increase was steepest when the radius of the particle was approximately commensurate with 5 at a given polymer concentration. For the largest particle, 205 nm in diameter, peak broadening with polymer concentration was found to correlate linearly with peak asymmetry. CZE of the particles in PA-18 solutions revealed abnormal behavior, with both mobility and peak width remaining near-constant up to a concentration of 0.08 % and sharply declining at higher concentrations. The decline of relative mobility is the same for the entire particle size range used, while peak width declines in direct relation to particle size. C1 NICHHD, Macromol Anal Sect, Lab Cellular & Mol Biophys, NIH, Bethesda, MD 20892 USA. RP Chrambach, A (reprint author), NICHHD, Macromol Anal Sect, Lab Cellular & Mol Biophys, NIH, Bldg 10,Rm 9D50, Bethesda, MD 20892 USA. NR 29 TC 7 Z9 7 U1 0 U2 4 PU WILEY-V C H VERLAG GMBH PI BERLIN PA MUHLENSTRASSE 33-34, D-13187 BERLIN, GERMANY SN 0173-0835 J9 ELECTROPHORESIS JI Electrophoresis PD OCT PY 1998 VL 19 IS 14 BP 2423 EP 2431 DI 10.1002/elps.1150191412 PG 9 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 134AY UT WOS:000076721400011 PM 9820962 ER PT J AU Giometti, CS Tollaksen, SL Liang, XL Cunningham, ML AF Giometti, CS Tollaksen, SL Liang, XL Cunningham, ML TI A comparison of lives protein changes in mice and hamsters treated with the peroxisome proliferator Wy-14,643 SO ELECTROPHORESIS LA English DT Article DE two-dimensional electrophoresis; liver proteins; hamster; mouse ID 2-DIMENSIONAL GEL DATABASE; RAT-LIVER; TISSUE PROTEINS; GENE-REGULATION; CELL FRACTIONS; ELECTROPHORESIS; IDENTIFICATION; DEHYDROGENASE; INDUCTION; SERUM AB Interspecies differences in the liver response to Wy-14,643, a potent peroxisome proliferator in rats and mice, have been demonstrated, While both rats and mice show dramatic increases in the number of peroxisomes, the activity of peroxisomal enzymes involved in the P-oxidation of fatty acids, and heptocyte replication, Syrian hamsters have a more moderate peroxisome proliferation response and no sustained increase in cell replication. Rats and mice, but not hamsters, develop hepatocellular carcinoma after prolonged exposure to Wy-14,643. To further characterize this species difference, two-dimensional gel electrophoresis (2-DE) has been used to compare the effect of 14-day exposure to various dietary concentrations of Wy-14,643 on liver protein expression in male mice and hamsters. Digitized images of the 2-DE protein maps were searched for significant changes. The peroxisome bifunctional enzyme (PBE) enoyl CoA hydratase/3-hydroxyacyl dehydrogenase, which migrates to the same position in mouse and hamster liver protein 2-DE patterns, increased in abundance by more than three times the control level in both mice and hamsters. In addition to the quantitative change in PBE, significant quantitative changes (P < 0.001) were found in 49 mouse liver proteins (47 decreasing and 2 increasing) and in 35 hamster liver proteins (27 decreasing and 8 increasing). There was little overlap in the mouse and hamster proteins showing quantitative changes in response to Wy-14,643, with the exception of PBE and one unidentified liver protein with an approximate molecular weight of 50 000. These results show that although peroxisome proliferation occurs in the livers of both mice and hamsters exposed to Wy-14,643, other species-specific changes in proteins occur that are independent of the peroxisome proliferation response and that could be related to species-specific susceptibility or resistance to liver tumor induction. C1 Argonne Natl Lab, Ctr Mechanist Biol & Biotechnol, Argonne, IL 60439 USA. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. RP Giometti, CS (reprint author), Argonne Natl Lab, Ctr Mechanist Biol & Biotechnol, 9700 S Cass Ave,Bldg 2092,Room B 117, Argonne, IL 60439 USA. EM csgiometti@anl.gov FU NIEHS NIH HHS [1-YOI ES-50262] NR 22 TC 11 Z9 11 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0173-0835 J9 ELECTROPHORESIS JI Electrophoresis PD OCT PY 1998 VL 19 IS 14 BP 2498 EP 2505 DI 10.1002/elps.1150191424 PG 8 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 134AY UT WOS:000076721400023 PM 9820974 ER PT J AU Esposito, D Craigie, R AF Esposito, D Craigie, R TI Sequence specificity of viral end DNA binding by HIV-1 integrase reveals critical regions for protein-DNA interaction SO EMBO JOURNAL LA English DT Article DE HIV 1; integrase; photocrosslinking; protein-DNA interactions; specific DNA binding ID HUMAN-IMMUNODEFICIENCY-VIRUS; PHOTO-CROSS-LINKING; CARBOXYL-TERMINAL DOMAINS; TARGET SITE SELECTION; RETROVIRAL INTEGRASES; IN-VITRO; SUBSTRATE-SPECIFICITY; MUTATIONAL ANALYSIS; FUNCTIONAL DOMAINS; CATALYTIC DOMAIN AB HIV-1 integrase specifically recognizes and cleaves viral end DNA during the initial step of retroviral integration. The protein and DNA determinants of the specificity of viral end DNA binding have not been clearly identified, We have used mutational analysis of the viral end LTR sequence, in vitro selection of optimal viral end sequences, and specific photocrosslinking to identify regions of integrase that interact with specific bases in the LTR termini. The results highlight the involvement of the disordered loop of the integrase core domain, specifically residues Q148 and Y143, in binding to th terminal portion of the viral DNA ends. Additionally, we have identified positions upstream in the LTR termini which interact with the C-terminal domain of integrase, providing evidence for the role of that domain in stabilization of viral DNA binding. Finally, we have located a region centered 12 bases from the viral DNA terminus which appears essential for viral end DNA binding in the presence of magnesium, but not in the presence of manganese, suggesting a differential effect of divalent cations on sequence-specific binding. These results help to define important regions of contact between integrase and viral DNA, and assist in the formulation of a molecular model of this vital interaction. C1 NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Craigie, R (reprint author), NIDDK, Mol Biol Lab, NIH, 5 Ctr Dr MSC0560, Bethesda, MD 20892 USA. NR 56 TC 228 Z9 235 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD OCT 1 PY 1998 VL 17 IS 19 BP 5832 EP 5843 DI 10.1093/emboj/17.19.5832 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 129KW UT WOS:000076463200033 PM 9755183 ER PT J AU Krsmanovic, LZ Mores, N Navarro, CE Saeed, SA Arora, KK Catt, KJ AF Krsmanovic, LZ Mores, N Navarro, CE Saeed, SA Arora, KK Catt, KJ TI Muscarinic regulation of intracellular signaling and neurosecretion in gonadotropin-releasing hormone neurons SO ENDOCRINOLOGY LA English DT Article ID HYPOTHALAMIC GT1-7 NEURONS; GNRH NEURONS; ACETYLCHOLINE-RECEPTORS; NEUROPEPTIDE RELEASE; OVARIECTOMIZED RATS; MEDIAN-EMINENCE; CYCLIC-AMP; G-PROTEINS; CHO-CELLS; SECRETION AB Agonist activation of cholinergic receptors expressed in perifused hypothalamic and immortalized GnRH-producing (GT1-7) cells induced prominent peaks in GnRH release, each followed by a rapid decrease, a transient plateau, and a decline to below basal levels. The complex profile of GnRH release suggested that acetylcholine (ACh) acts through different cholinergic receptor subtypes to exert stimulatory and inhibitory effects on GnRH release. Whereas activation of nicotinic receptors caused a transient increase in GnRH release, activation of muscarinic receptors inhibited basal GnRH release. Nanomolar concentrations of ACh caused dose-dependent inhibition of cAMP production that was prevented by pertussis toxin (PTX), consistent with the activation of a plasma-membrane G(i) protein. Micromolar concentrations of ACh also caused an increase in phosphoinositide hydrolysis that was inhibited by the M-1 receptor antagonist, pirenzepine. In ACh-treated cells, immunoblot analysis revealed that membrane-associated G(alpha q/11) immunoreactivity was decreased after 5 min but was restored at later times. In contrast, immunoreactive G(alpha i3) was decreased for up to 120 min after ACh treatment. The agonist-induced changes in G protein alpha-subunits liberated during activation of muscarinic receptors were correlated with regulation of their respective transduction pathways. These results indicate that ACh modulates GnRH release from hypothalamic neurons through both M-1 and M-2 muscarinic receptors. These receptor subtypes are coupled to G(q) and G(i) proteins that respectively influence the activities of PLC and adenylyl cyclase/ion channels, with consequent effects on neurosecretion. C1 NICHD, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA. RP Catt, KJ (reprint author), NICHD, Endocrinol & Reprod Res Branch, NIH, Bldg 49,Room 6A-36, Bethesda, MD 20892 USA. EM catt@helix.nih.gov OI MORES, Nadia/0000-0002-4197-0914 NR 50 TC 53 Z9 54 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD OCT PY 1998 VL 139 IS 10 BP 4037 EP 4043 DI 10.1210/en.139.10.4037 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 121WE UT WOS:000076038100003 PM 9751480 ER PT J AU Lindzey, J Wetsel, WC Couse, JF Stoker, T Cooper, R Korach, KS AF Lindzey, J Wetsel, WC Couse, JF Stoker, T Cooper, R Korach, KS TI Effects of castration and chronic steroid treatments on hypothalamic gonadotropin-releasing hormone content and pituitary gonadotropins in male wild-type and estrogen receptor-alpha knockout mice SO ENDOCRINOLOGY LA English DT Article ID MESSENGER-RIBONUCLEIC-ACID; FOLLICLE-STIMULATING-HORMONE; ADULT MALE-RAT; INSITU HYBRIDIZATION; BASAL HYPOTHALAMUS; ANDROGEN RECEPTOR; GONADAL-STEROIDS; GENE DISRUPTION; PULSE FREQUENCY; PREOPTIC AREA AB Testicular androgens are integral components of the hormonal feedback loops that regulate circulating levels of LH and FSH. The sites of feedback include hypothalamic areas regulating GnRH neurons and pituitary gonadotropes. To better define the roles of androgen receptor (AR), estrogen receptor-alpha (ER alpha), and estrogen receptor-beta (ER beta) in mediating feedback effects of sex steroids on reproductive neuroendocrine function, we have determined the effects of castration and steroid replacement therapy on hypothalamic GnRH content, pituitary LH beta and FSH beta messenger RNA (mRNA) levels, and serum gonadotropins in male wild-type (WT) and estrogen receptor-alpha knockout (ERKO) mice. Hypothalami from intact WT and ERKO males contained similar amounts of GnRH, whereas castration significantly reduced GnRH contents in both genotypes. Replacement therapy with estradiol (E-2), testosterone (T), or dihydrotestosterone (DHT) restored hypothalamic GnRH content in castrated (CAST) WT mice; only the androgens were effective in CAST ERKOs. Analyses of pituitary function revealed that LH beta mRNA and serum LH levels in intact ERKOs were 2-fold higher than those in intact WT males. Castration increased levels of LH beta mRNA (1.5- to 2-fold) and serum LH (4- to 5-fold) in both genotypes. Both E-2 and T treatments significantly suppressed LH beta mRNA and serum LH levels in CAST WT males. However, E-2 was completely ineffective, and T was only partially effective in suppressing these two indexes in the CAST ERKO males. DHT treatments stimulated a 50% increase in LH beta mRNA and serum LH levels in WT males, whereas serum LH was significantly suppressed in DHT-treated ERKO males. Although the pituitaries from intact ERKO males contained similar amounts of FSH beta mRNA, serum FSH levels were 20% higher than those in the intact WT males. Castration increased FSH beta mRNA levels only in WT males, but significantly increased serum FSH levels in both genotypes. Both E-2 and T treatments significantly suppressed serum FSH in CAST WT males, whereas only E-2 suppressed FSH beta mRNA. DHT treatments of CAST WT mice stimulated a small increase in serum FSH, but failed to alter FSH beta mRNA levels. None of the steroid treatments exerted any significant effect on FSH beta mRNA or serum FSH levels in CAST ERKOs. These data suggest that hypothalamic GnRH contents can be maintained solely through AR signaling pathways. However, normal regulation of gonadotrope function requires aromatization of T and activation of ER alpha signaling pathways in the gonadotrope. In addition, serum FSH levels in male ERKOs appear to be regulated largely by nonsteroidal testicular factors such as inhibin. Finally, these data suggest that hypothalamic ERP may not be involved in mediating the negative feedback effects of T on serum LII and FSH in male mice. C1 NIEHS, Reprod & Dev Toxicol Lab, Receptor Biol Sect, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Hormone Act Grp, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA. Duke Univ, Dept Psychiat & Behav Sci, Durham, NC 27710 USA. US EPA, Reprod Toxicol Div, Res Triangle Pk, NC 27711 USA. RP NIEHS, Reprod & Dev Toxicol Lab, Receptor Biol Sect, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM korach@niehs.nih.gov OI Korach, Kenneth/0000-0002-7765-418X NR 60 TC 120 Z9 121 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD OCT PY 1998 VL 139 IS 10 BP 4092 EP 4101 DI 10.1210/en.139.10.4092 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 121WE UT WOS:000076038100010 PM 9751487 ER PT J AU Chen, H Srinivas, PR Cong, LN Li, YH Grunberger, G Quon, MJ AF Chen, H Srinivas, PR Cong, LN Li, YH Grunberger, G Quon, MJ TI alpha(2)-Heremans Schmid glycoprotein inhibits insulin-stimulated Elk-1 phosphorylation, but not glucose transport, in rat adipose cells SO ENDOCRINOLOGY LA English DT Article ID RECEPTOR TYROSINE KINASE; ALPHA-2 HS-GLYCOPROTEIN; NATURAL INHIBITOR; APATITE FORMATION; GROWTH-FACTOR; IN-VITRO; FETUIN; TRANSLOCATION; GLUT4; PROTEIN AB alpha(2)-Heremans Schmid glycoprotein (alpha(2)-HSG) is a member of the fetuin family of serum proteins whose biological functions are not completely understood. There is a consensus that alpha(2)-HSG plays a role in the regulation of tissue mineralization. However, one aspect of alpha(2)-HSG function that remains controversial is its ability to inhibit the insulin receptor tyrosine kinase and the biological actions of insulin. Interestingly, some studies suggest that alpha(2),-HSG differentially inhibits mitogenic, but not metabolic, actions of insulin. However, these previous studies were not carried out in bona fide insulin target cells. Therefore, in the present study we investigate the effects of alpha(2)-HSG in the physiologically relevant rat adipose cell. We studied insulin-stimulated translocation of the insulin-responsive glucose transporter GLUT4 in transfected rat adipose cells overexpressing human alpha(2)-HSG. In addition, we measured insulin-stimulated glucose transport in adipose cells cultured with conditioned medium from the transfected cells as well as in freshly isolated adipose cells treated with purified human alpha(2)-HSG. Compared with control cells, we were unable to demonstrate any significant effect of alpha(2)-HSG on insulin-stimulated translocation of GLUT4 or glucose transport. in contrast, we did demonstrate that overexpression of alpha(2)-HSG in adipose cells inhibits both basal and insulin-stimulated phosphorylation of Elk-1 (a transcription factor phosphorylated and activated by mitogen-activated protein kinase and other related upstream kinases). Interestingly, we did not observe any major effects of alpha(2)-HSG to inhibit insulin-stimulated phosphorylation of the insulin receptor, insulin receptor substrate-1, -2, or -3, in either transfected or freshly isolated adipose cells. We conclude that alpha(2)-HSG inhibits insulin-stimulated Elk-l phosphorylation, but not glucose transport, in adipose cells by a mechanism that may involve effector molecules downstream of insulin receptor substrate proteins. C1 NHLBI, Hypertens Endocrine Branch, NIH, Bethesda, MD 20892 USA. Wayne State Univ, Sch Med, Ctr Mol Med & Genet, Dept Internal Med, Detroit, MI 48201 USA. RP Quon, MJ (reprint author), NHLBI, Hypertens Endocrine Branch, NIH, Bldg 10,Room 8C-103,10 Ctr Dr MSC 1754, Bethesda, MD 20892 USA. EM quonm@gwgate.nhlbi.nih.gov RI Quon, Michael/B-1970-2008; OI Quon, Michael/0000-0002-9601-9915 NR 34 TC 17 Z9 18 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD OCT PY 1998 VL 139 IS 10 BP 4147 EP 4154 DI 10.1210/en.139.10.4147 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 121WE UT WOS:000076038100017 PM 9751494 ER PT J AU Liu, Y Takeshita, A Misiti, S Chin, WW Yen, PM AF Liu, Y Takeshita, A Misiti, S Chin, WW Yen, PM TI Lack of coactivator interaction can be a mechanism for dominant negative activity by mutant thyroid hormone receptors SO ENDOCRINOLOGY LA English DT Article ID CO-REPRESSOR; GENERALIZED RESISTANCE; TRANSACTIVATION DOMAIN; LIGAND-BINDING; BETA-RECEPTOR; V-ERBA; EXPRESSION; GENE; HETERODIMERS; ACTIVATION AB We studied the interactions of two natural thyroid hormone receptor (TR) mutants from patients with resistance to thyroid hormone (RTH) and an artificial TR mutant with a nuclear receptor corepressor, N-CoR, and a steroid receptor coactivator, SRC-I. In electrophoretic mobility shift assays, wild-type TR beta-1 interacted with N-CoR in the absence of ligand, whereas T-3 caused dissociation of the TR beta-1/N-CoR complex and formation of TR beta-1/SRC-1 complex. In contrast, a natural mutant (G345R) with poor T-3-binding affinity formed TR beta-1/N-CoR complex, both in the absence and presence of T-3, but could not form TR beta-1/SRC-1 complex. Another TR mutant, which bound T-3 with normal affinity and containing a mutation in the AF-2 region (E457D), had normal interactions with N-CoR but could not bind SRC-1. Both these mutants had strong dominant negative activity on wild-type TR transactivation. Studies with a TR mutant that had slightly decreased T-3-binding affinity (R320H) showed a T-3-dependent decrease in binding to N-CoR and increase in binding to SRC-1 that reflected its decreased ligand binding affinity. Additionally, when N-CoR and SRC-1 were added to these receptors at various T-3 concentrations in electrophoretic mobility shift assays, TR/N-CoR and TR/SRC-1 complexes, but not intermediate complexes were observed, suggesting that N-CoR release is necessary before SRC-1 binding to TR. Our data provide new insight on the molecular mechanisms of dominant negative activity in RTH and suggest that the inability of mutant TRs to interact with coactivators such as SRC-1, which results from reduced T-3-binding affinity, is a determinant of dominant negative activity. C1 NIDDK, Mol & Cellular Endocrinol Branch, NIH, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Yen, PM (reprint author), NIDDK, Mol & Cellular Endocrinol Branch, NIH, Bldg 10,Room 8D04,9000 Rockville Pike, Bethesda, MD 20892 USA. EM PaulY@Bdg10.NIDDK.NIH.Gov NR 44 TC 41 Z9 42 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD OCT PY 1998 VL 139 IS 10 BP 4197 EP 4204 DI 10.1210/en.139.10.4197 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 121WE UT WOS:000076038100023 PM 9751500 ER PT J AU Benvenga, S Robbins, J AF Benvenga, S Robbins, J TI Thyroid hormone efflux from monolayer cultures of human fibroblasts and hepatocytes. Effect of lipoproteins and other thyroxine transport proteins SO ENDOCRINOLOGY LA English DT Article ID HIGH-DENSITY-LIPOPROTEIN; REVERSE CHOLESTEROL TRANSPORT; SMOOTH-MUSCLE CELLS; PLASMA-LIPOPROTEINS; HEPATOMA-CELLS; BINDING-SITES; RAT-LIVER; RECEPTOR; IDENTIFICATION; ENHANCEMENT AB We have previously shown that human skin fibroblasts exposed to preformed low density lipoprotein (LDL)-thyroxine (T-4) complexes internalize more T-4 than they do when exposed to T-4 alone. The system is set to function when the LDL receptor is up-regulated by reducing the intracellular concentration of cholesterol, and the LDL concentration outside the cell is in the range of the kDa of the receptor. High density lipoproteins (HDL), albumin (HSA), transthyretin (TTR), and thyroxine-binding globulin (TBG) interfere with, rather than facilitate, T-4 entry. Of the three classes of lipoproteins (VLDL, LDL, and HDL), HDL is the major carrier of thyroid hormones. While LDL delivers cholesterol (and T-4) to cells, HDL is the scavenger of cholesterol. We thus hypothesized that HDL could also facilitate thyroid hormone exit from cells. This hypothesis was tested on two human cell lines: skin fibroblasts and hepatocytes (Hep G2), using physiological concentrations of HDL or, as control, physiological concentrations of LDL, HSA, TTR, and TBG or buffer. Because cell surface receptors for HDL are regulated by intracellular cholesterol in a manner opposite to that of LDL receptors, we evaluated the effect of HDL land other proteins) in three states: normal, high, and low intracellular cholesterol content (i.e. normal, high, and low expression of HDL receptors). In both cell lines and with either T-4 or T-3, we found that: 1) HDL as well as the other proteins tested increased the efflux and augmented both the initial rate of exit and the equilibrium value. 2) The efflux did not saturate over a wide range of protein concentrations. 3) The effect of HDL, LDL, and the other proteins on the fractional efflux rate of thyroid hormones remained the same irrespective of the intracellular cholesterol content (and, therefore, irrespective of the expression of either LDL or HDL receptors). 4) HSA, TTR, and TBG were, on a mass basis, equipotent and more efficient than lipoproteins. However, the effect of Lipoproteins - whose Ka for T-4 is comparable to that of HSA - was disproportionately high. On a molar basis, LDL (about 80% of the weight being accounted for by lipids) was more effective than HDL2 (about 60% lipids) and HDL, was more effective than HDL3 (about 40% lipids), suggesting that the disproportionate effect of lipoproteins was due to transfer of the lypophylic thyroid hormones to the lipid moiety of Lipoproteins. 5. A mixture of HDL and LDL gave the same efflux rate as a mixture of HSA, TTR, and TBG. The data indicate that the efflux of T-4 and T-3 from cells is rapid and appears not to be mediated by a particular lipoprotein. The disproportionately large effect of lipoproteins, which are low affinity thyroid hormone carriers, compared with nonlipoprotein carriers, and the greater effect of LDL compared with HDL, might indicate that the lipoproteins establish a nonspecific physical contact with the plasma membrane and that their hydrophobic nature favors the release of the similarly hydrophobic thyroid hormones. C1 NIDDK, Genet & Biochem Branch, NIH, Bethesda, MD 20892 USA. Univ Messina, Sch Med, Cattedra & Serv Autonomo Endocrinol, I-98125 Messina, Italy. RP Robbins, J (reprint author), NIDDK, Genet & Biochem Branch, NIH, Bldg 10,Room 6C 201A,10 Ctr Dr,MSC 1587, Bethesda, MD 20892 USA. NR 30 TC 18 Z9 18 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD OCT PY 1998 VL 139 IS 10 BP 4311 EP 4318 DI 10.1210/en.139.10.4311 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 121WE UT WOS:000076038100037 PM 9751514 ER PT J AU Hunyady, B Zolyomi, A Hoffman, BJ Mezey, E AF Hunyady, B Zolyomi, A Hoffman, BJ Mezey, E TI Gastrin-producing endocrine cells: A novel source of histamine in the rat stomach SO ENDOCRINOLOGY LA English DT Article ID VESICULAR MONOAMINE TRANSPORTER; HISTIDINE-DECARBOXYLASE; GASTROINTESTINAL-TRACT; ACID-SECRETION; NERVOUS-SYSTEM; SUBSTANCE-P; NEURONS; EXPRESSION; ANTISERA; IMMUNOREACTIVITIES AB Gastrin and histamine both potently stimulate secretion of acid into the gastric lumen. How these agents interact and how their release is controlled is poorly understood. Therefore, we decided to look for histamine in the antral portion of the rat stomach where the gastrin-producing G cells are located. We used immunocytochemical methods to visualize histamine, histidine decarboxylase (HDC, the enzyme that converts histidine to histamine), and the type 1 vesicular monoamine transporter (VMAT1, the protein responsible for moving histamine into vesicles for storage and release). We were surprised to find that histamine, HDC, and VMAT1 were all present in G cells. Our results suggest that G cells synthesize and secrete gastrin and histamine. Whether histamine acts in concert with gastrin to stimulate acid secretion, or functions as an autocrine inhibitor of gastrin release remains to be seen. C1 NIMH, NIH, Bethesda, MD 20892 USA. NICHD, NIH, Bethesda, MD 20892 USA. Univ Pecs, Dept Med 1, H-7643 Pecs, Hungary. RP Mezey, E (reprint author), NINDS, BNP, NIH, Bldg 36 Rm 3A17,9000 Rockville Pike, Bethesda, MD 20892 USA. EM mezey@codon.nih.gov NR 43 TC 14 Z9 14 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD OCT PY 1998 VL 139 IS 10 BP 4404 EP 4415 DI 10.1210/en.139.10.4404 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 121WE UT WOS:000076038100048 PM 9751525 ER PT J AU Bucher, JR AF Bucher, JR TI Update on National Toxicology Program (NTP) assays with genetically altered or "transgenic" mice SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Editorial Material DE alternative; cancer assays; genetically altered mice; transgenic mice; NTP Board of Scientific Counselors review AB The NTP is evaluating several lines of genetically altered mice for possible use in identifying and assessing carcinogens. The NIEHS/NTP programs and progress in this area were recently reviewed by the NTP Board of Scientific Counselors (BSC). A number of comments and concerns were raised. This commentary summarizes and responds to the BSC review and offers some thoughts on future directions for this line of research as well as possible ways genetically altered mice might be integrated into a comprehensive testing strategy. C1 NIEHS, Res Triangle Pk, NC 27709 USA. RP Bucher, JR (reprint author), NIEHS, POB 12233,MD B3-04, Res Triangle Pk, NC 27709 USA. NR 6 TC 22 Z9 22 U1 1 U2 1 PU US DEPT HEALTH HUMAN SERVICES PUBLIC HEALTH SERVICE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SERVICES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD OCT PY 1998 VL 106 IS 10 BP 619 EP 621 DI 10.1289/ehp.98106619 PG 3 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 134AX UT WOS:000076721200014 PM 9755135 ER PT J AU Lucier, GW Schecter, A AF Lucier, GW Schecter, A TI Human exposure assessment and the National Toxicology Program SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Editorial Material DE exposure assessment; gene/environment mixtures; National Toxicology Program; risk assessment; sensitive subpopulations ID UNITED-STATES; RISK ASSESSMENT; BLOOD AB The National Institute of Environmental Health Sciences/National Toxicology Program (NIEHS/NTP) is developing a new interagency initiative in exposure assessment. This initiative involves the NIEHS, the Centers for Disease Control and Prevention through its National Center for Environmental Health, the National Institute for Occupational Safety and Health, the EPA, and other participating institutes and agencies of the NTP. This initiative will benefit public health and priority setting in a number of ways. First, as discussed above, it will strengthen the scientific foundation for risk assessments by the development of more credible exposure/response relationships in people by improving cross-species extrapolation, the development of biologically based dose-response models, and the identification of sensitive subpopulations and for "margin of exposure" based estimates of risk Second, it will provide the kind of information necessary for deciding which chemicals should be studied with the limited resources available for toxicological testing. For example, there are 85,000 chemicals in commerce today, and the NTP can only provide toxicological evaluations on 10-20 per year. Third, we would use the information obtained from the exposure initiative to focus our research on mixtures that are actually present in people's bodies. Fourth, we would obtain information on the kinds and amount of chemicals in children and other potentially sensitive subpopulations. Determinations of whether additional safety factors need to be applied to children must rest, in part, upon comparative exposure analyses between children and adults. Fifth, this initiative, taken together with the environmental genome initiative, will provide the science base essential for meaningful studies on gene/environment interactions, particularly for strengthening the evaluation of epidemiology studies. Sixth, efficacy of public health policies aimed at reducing human exposure to chemical agents could be evaluated in a more meaningful way if body burden data were available over time, including remediation around Superfund sites and efforts to achieve environmental justice. The exposure assessment initiative is needed to address public health needs. It is feasible because of recent advances in analytical technology and molecular biology, and it is an example of how different agencies can work together to better fulfill their respective missions. C1 NIEHS, Environm Toxicol Program, Res Triangle Pk, NC 27709 USA. RP Lucier, GW (reprint author), NIEHS, Environm Toxicol Program, POB 12233,MD A3-02, Res Triangle Pk, NC 27709 USA. NR 21 TC 19 Z9 19 U1 0 U2 5 PU US DEPT HEALTH HUMAN SERVICES PUBLIC HEALTH SERVICE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SERVICES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD OCT PY 1998 VL 106 IS 10 BP 623 EP 627 DI 10.2307/3434088 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 134AX UT WOS:000076721200015 PM 9755136 ER PT J AU Gulson, BL Jameson, CW Mahaffey, KR Mizon, KJ Patison, N Law, AJ Korsch, MJ Salter, MA AF Gulson, BL Jameson, CW Mahaffey, KR Mizon, KJ Patison, N Law, AJ Korsch, MJ Salter, MA TI Relationships of lead in breast milk to lead in blood, urine, and diet of the infant and mother SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE blood; breast milk; infant; intake; isotopes; lead; mother; urine ID MATERNAL BLOOD; RURAL MOTHERS; CADMIUM; ABSORPTION; WOMEN; BONE; MOBILIZATION; PREGNANCY; LACTATION; CHILDREN AB We have obtained stable lead isotope and lead concentration data from a longitudinal study of mobilization of lead from the maternal skeleton during pregnancy and lactation and in which the newly born infants were monitored for 6 months postpartum to evaluate the effects of the local environment on lead body burden of the infant. Samples of maternal and infant blood, urine, and diet and especially breast milk were measured for 21 mothers and 24 infants. Blood lead concentrations were less than 5 mu g/dl in all except one subject. The mean lead concentration in breast milk +/- standard deviation was 0.73 +/- 0.70 mu g/kg. In seven subjects for whom serial breast milk sampling was possible, the lead concentration varied by factors of from 2 to 4, and for three subjects there was an increase at or after 90 days postpartum. For the first 60-90 days postpartum, the contribution from breast milk to blood lead in the infants varied from 36 to 80%. Multiple linear regress;on analyses indicated statistically significant relationships for some of the variables of isotope ratios and lead concentrations between breast milk, blood, urine, and diet for infants and mothers. For example, the analyses revealed that both a mother's breast milk Pb-207/Pb-206 and Pb-206/Pb-204 ratios and lead concentration provide information to predict her infant's blood Pb-207/Pb-206 and Pb-206/Pb-204 ratios. The major sources of lead in breast milk are from the maternal bone and diet. An evaluation of breast milk lead concentrations published over the last 15 years indicates that studies in which the ratio of lead concentrations in breast milk to lead concentrations in whole maternal blood (x100) were greater than 15 should be viewed with caution because of potential contamination during sampling and/or laboratory analyses. Selected studies also appear to show a linear relationship between breast milk and maternal whole blood, with the percentage of lead in breast milk compared with whole blood of <3% in subjects with blood lead levels ranging from 2 to 34 mu g/dl. The levels of lead in breast milk are thus similar to those in plasma. Breast-fed infants are only at risk if the mother is exposed to high concentrations of contaminants either from endogenous sources such as the skeleton or exogenous sources. C1 Macquarie Univ, Grad Sch Environm, Sydney, NSW 2109, Australia. CSIRO, Div Explorat & Min, N Ryde, NSW 2113, Australia. NIEHS, Res Triangle Pk, NC 27709 USA. US EPA, Natl Ctr Environm Assessment, Cincinnati, OH 45268 USA. RP Gulson, BL (reprint author), Macquarie Univ, Grad Sch Environm, Sydney, NSW 2109, Australia. FU NIEHS NIH HHS [N01-ES-05292] NR 49 TC 73 Z9 78 U1 2 U2 10 PU US DEPT HEALTH HUMAN SERVICES PUBLIC HEALTH SERVICE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SERVICES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD OCT PY 1998 VL 106 IS 10 BP 667 EP 674 DI 10.1289/ehp.98106667 PG 8 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 134AX UT WOS:000076721200023 PM 9755144 ER PT J AU Lucier, GW Barrett, JC AF Lucier, GW Barrett, JC TI Public health policy and the National Toxicology Program SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Editorial Material C1 NIEHS, Res Triangle Pk, NC 27709 USA. RP Lucier, GW (reprint author), NIEHS, POB 12233, Res Triangle Pk, NC 27709 USA. NR 8 TC 2 Z9 2 U1 0 U2 0 PU US DEPT HEALTH HUMAN SERVICES PUBLIC HEALTH SERVICE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SERVICES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD OCT PY 1998 VL 106 IS 10 BP A470 EP A471 DI 10.2307/3434074 PG 2 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 134AX UT WOS:000076721200001 PM 9755146 ER PT J AU Karp, CL Wysocka, M Ma, XJ Marovich, M Factor, RE Nutman, T Armant, M Wahl, L Cuomo, P Trinchieri, G AF Karp, CL Wysocka, M Ma, XJ Marovich, M Factor, RE Nutman, T Armant, M Wahl, L Cuomo, P Trinchieri, G TI Potent suppression of IL-12 production from monocytes and dendritic cells during endotoxin tolerance SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE IL-12; endotoxin tolerance; monocyte; macrophage; dendritic cell; sepsis ID TUMOR-NECROSIS-FACTOR; COLONY-STIMULATING FACTOR; IFN-GAMMA; INTERFERON-GAMMA; IN-VIVO; SHWARTZMAN REACTION; CYTOKINE PRODUCTION; SEPTIC PATIENTS; DOWN-REGULATION; PROTECTS MICE AB Endotoxin tolerance, the down-regulation of a subset of endotoxin-driven responses after an initial exposure to endotoxin, may provide protection from the uncontrolled immunological activation of acute endotoxic shock. Recent data suggest, however, that the inhibition of monocyte/macrophage function associated with endotoxin tolerance can lead to an inability to respond appropriately to secondary infections in survivors of endotoxic shock. IL-12 production by antigen-presenting cells is central to the orchestration of both innate and acquired cell-mediated immune responses to many pathogens. IL-12 has also been shown to play an important role in pathological responses to endotoxin. We therefore examined the regulation of IL-12 during endotoxin tolerance. Priming doses of lipopolysaccharide ablate the IL-12 productive capacity of primary human monocytes. This suppression of IL-12 production is primarily transcriptional. Unlike the down-regulation of TNF-alpha under such conditions, the mechanism of IL-12 suppression during endotoxin tolerance is not dependent upon IL-10 or transforming growth factor-beta, nor is IL-12 production rescued by IFN-gamma or granulocyte-macrophage colony-stimulating factor. Of note, human dendritic cells also undergo endotoxin tolerance, with potent down-regulation of IL-12 production. Endotoxin tolerance-related suppression of IL-12 production provides a likely mechanism for the anergy seen during the immunological paralysis which follows septic shock. C1 Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Dept Med, Baltimore, MD USA. Wistar Inst, Philadelphia, PA 19104 USA. NIAID, Bethesda, MD 20892 USA. NIDR, Bethesda, MD 20892 USA. RP Karp, CL (reprint author), Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Mol Microbiol & Immunol, 615 N Wolfe St,E5008, Baltimore, MD 21205 USA. OI Karp, Christopher/0000-0002-0832-2659 FU NCI NIH HHS [CA20833]; NIAID NIH HHS [AI40507]; NIDCR NIH HHS [DE12167] NR 35 TC 114 Z9 118 U1 0 U2 2 PU WILEY-V C H VERLAG GMBH PI BERLIN PA MUHLENSTRASSE 33-34, D-13187 BERLIN, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD OCT PY 1998 VL 28 IS 10 BP 3128 EP 3136 DI 10.1002/(SICI)1521-4141(199810)28:10<3128::AID-IMMU3128>3.0.CO;2-T PG 9 WC Immunology SC Immunology GA 131CY UT WOS:000076559200015 PM 9808181 ER PT J AU Chen, HJ Paul, WE AF Chen, HJ Paul, WE TI A population of CD62L(low) NK1.1(-) CD4(+) T cells that resembles NK1.1(+) CD4(+) T cells SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE cytokine; lymphocyte; CD1; activation ID COMPLEX CLASS-I; IMMUNOGLOBULIN-E PRODUCTION; RECEPTOR-ALPHA/BETA(+) CELLS; INTERLEUKIN-4 PRODUCTION; ANTIGEN RECEPTOR; DEFICIENT MICE; IL-4; MOLECULES; CD4+; CD1 AB In MHC class II-/- C57BL/6 (II-/-) mouse spleen, a small population of CD4(+) T cells is present of which NK1.1(+) CD4(+) (NK) T cells comprise 40 to 45%. We report here that many of the NK1.1(-) CD4(+) T cells derived from II-/- mice are also NK T cells. They produce large amounts of IL-4 in response to anti-CD3 ligation and do so without any requirement for the presence of IL-4 in the priming culture, a property characteristic of NK T cells. Their IFN-gamma production is large and is enhanced by IL-12. In addition, II-/- NK1.1(-) CD4(+) T cells produce IL-4 as a result of culture with L cells expressing murine CD1 (L-CD1). We report that CD49b, a component of integrin VLA-2, is expressed on the majority of both NK1.1(+) and NK1.1(-) NKT cells. NK1.1(-) NK T cells also exist in wild-type C57BL/6 mice. Evidence supporting this is that V beta 8 usage by CD62L(low)NK1.1(-)CD4(+) T cells was similar to 5% higher than that by CD62L(high)CD4(+) T cells in wild-type mice in keeping with the estimated proportion of NK1.1(-) NK T cells in the CD62L(low) population. CD62L(low)CD4(+) T cells from beta 2-m-/- mice, which lack NK T cells, showed no increase in V beta 8 usage. When activated by anti-CD3 or L-CD1, CD62L(low) NK1.1(-) CD4(+) T cells from conventional but not beta 2-m-/- and CD1-/- mice produce IL-4 in a manner indistinguishable from II-/- NK1.1(-) CD4(+) T cells. NK1.1(-) NK T cells in normal mouse spleens are approximately as numerous as NK1.1(+) NK T cells. C1 NIAID, NIH, Immunol Lab, Bethesda, MD 20892 USA. RP Paul, WE (reprint author), NIAID, NIH, Immunol Lab, Bldg 10,Rm IIN311,10 Ctr Dr,MSC 1892, Bethesda, MD 20892 USA. EM wpaul@niaid.nih.gov NR 42 TC 21 Z9 22 U1 0 U2 0 PU WILEY-V C H VERLAG GMBH PI BERLIN PA MUHLENSTRASSE 33-34, D-13187 BERLIN, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD OCT PY 1998 VL 28 IS 10 BP 3172 EP 3182 DI 10.1002/(SICI)1521-4141(199810)28:10<3172::AID-IMMU3172>3.0.CO;2-I PG 11 WC Immunology SC Immunology GA 131CY UT WOS:000076559200020 PM 9808186 ER PT J AU Suzuki, H Guinter, TI Koyasu, S Singer, A AF Suzuki, H Guinter, TI Koyasu, S Singer, A TI Positive selection of CD4(+) T cells by TCR-specific antibodies requires low valency TCR cross-linking: implications for repertoire selection in the thymus SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE positive selection; thymus; TCR signal; cross-linking ID CHAIN CONSTANT-REGION; ANTIGEN RECEPTOR TCR; TCR/CD3 COMPLEX; CLASS-II; PEPTIDE; THYMOCYTES; MHC; MICE; LYMPHOCYTES; ENGAGEMENT AB The developmental fate of immature CD4(+) 8(+) thymocytes is determined by intrathymic signals transduced by surface TCR complexes. In particular, TCR signals are required for immature CD4(+) 8(+) thymocytes to further differentiate into CD4(+) 8(-) or CD4(-) 8(+) T cells, a process referred to as positive selection. It is generally thought that positive selection results from low affinity TCR interactions with self antigens which engage the relatively few surface TCR complexes that are on immature CD4(+) 8(+) thymocytes. However, we now demonstrate with TCR-specific antibodies that positive selection of CD4(+) T cells requires low valency crosslinking of surface TCR complexes on immature thymocytes. That is, positive selection signals are only generated within a narrow range of TCR cross-linking: cross-linking either too few or too many surface TCR complexes fails to signal positive selection. We interpret these results as indicating that positive selection of CD4(+) T cells is not signaled by low affinity TCR interactions per se, but rather can be signaled by any combination of TCR affinity and ligand density that induces low valency TCR cross-linking on immature thymocytes. C1 NCI, Expt Immunol Branch, Bethesda, MD 20892 USA. Keio Univ, Sch Med, Dept Immunol, Tokyo, Japan. RP Singer, A (reprint author), Bldg 10,Room 4B-17, Bethesda, MD 20892 USA. EM SingerA@nih.gov RI Suzuki, Harumi/L-1271-2013; Koyasu, Shigeo/J-5583-2015 OI Suzuki, Harumi/0000-0003-3616-9361; Koyasu, Shigeo/0000-0001-9585-3038 NR 35 TC 12 Z9 13 U1 1 U2 3 PU WILEY-V C H VERLAG GMBH PI BERLIN PA MUHLENSTRASSE 33-34, D-13187 BERLIN, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD OCT PY 1998 VL 28 IS 10 BP 3252 EP 3258 DI 10.1002/(SICI)1521-4141(199810)28:10<3252::AID-IMMU3252>3.0.CO;2-G PG 7 WC Immunology SC Immunology GA 131CY UT WOS:000076559200028 PM 9808194 ER PT J AU Asai, M Kitamura, H Yanagibashi, T Asukai, K Katagiri, N AF Asai, M Kitamura, H Yanagibashi, T Asukai, K Katagiri, N TI Case of acrania associated with congenital medulloblastoma SO EUROPEAN JOURNAL OF OBSTETRICS GYNECOLOGY AND REPRODUCTIVE BIOLOGY LA English DT Article DE acrania; congenital malformation; congenital medulloblastoma; dysplasia of nasal ala; sonography ID FETAL ACRANIA; SONOGRAPHIC DIAGNOSIS AB A case of acrania associated with medulloblastoma, agenesis of the cerebellum, and nasoshizis, is reported. The diagnosis of acrania was made at the 20th gestational week by sonographic examination. To our knowledge, this is the first report of fetal acrania associated with congenital brain tumor. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved. C1 Yokohama Minami Kyosai Hosp, Dept Obstet & Gynecol, Kanazawa Ku, Yokohama, Kanagawa 236, Japan. Yokohama Minami Kyosai Hosp, Dept Pathol, Kanazawa Ku, Yokohama, Kanagawa 236, Japan. RP Asai, M (reprint author), NIH, Lab Tumor Immunol & Biol, Bldg 10,Room 5B56, Bethesda, MD 20892 USA. NR 10 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0301-2115 J9 EUR J OBSTET GYN R B JI Eur. J. Obstet. Gynecol. Reprod. Biol. PD OCT PY 1998 VL 81 IS 1 BP 115 EP 117 DI 10.1016/S0301-2115(98)00135-3 PG 3 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 142BF UT WOS:000077179500021 PM 9846725 ER PT J AU Cartwright, WS AF Cartwright, WS TI Cost-benefit and cost-effectiveness analysis of drug abuse treatment services SO EVALUATION REVIEW LA English DT Article ID HEALTH; CONSEQUENCES AB The foundations of cost-benefit analysis and cost-effectiveness analysis (CB/CEA) for drug abuse treatment are developed An economic model of addict choice and drug markets is presented This model is synthesized with the current "cost of illness" methods used to measure the burden of the disease to society The problem of doing cost-effectiveness studies in the presence of large nonhealth benefits is examined, and guidance is offered to clinical studies with a cost-effectiveness component or to stand-alone cost-effectiveness studies. References and an extensive bibliography on drug abuse treatment-related CB/CEA studies are appended. C1 NIH, Bethesda, MD 20892 USA. RP Cartwright, WS (reprint author), NIH, Bethesda, MD 20892 USA. NR 32 TC 35 Z9 35 U1 1 U2 4 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0193-841X J9 EVALUATION REV JI Eval. Rev. PD OCT PY 1998 VL 22 IS 5 BP 609 EP 636 DI 10.1177/0193841X9802200503 PG 28 WC Social Sciences, Interdisciplinary SC Social Sciences - Other Topics GA 127BH UT WOS:000076330300003 PM 10186896 ER PT J AU Golski, S Zonderman, AB Malamut, BL Resnick, SM AF Golski, S Zonderman, AB Malamut, BL Resnick, SM TI Verbal and figural recognition memory: Task development and age associations SO EXPERIMENTAL AGING RESEARCH LA English DT Article ID IMMEDIATE VISUAL MEMORY; CEREBRAL BLOOD-FLOW; EPISODIC MEMORY; ALZHEIMERS TYPE; RETENTION TEST; DEMENTIA; RECALL; RETRIEVAL; ADULTS; YOUNG AB The goal of the present study was to develop and validate parallel tests of verbal and figural delayed-recognition memory with similar task demands and difficulty levels. Such tasks would allow examination of age differences and longitudinal age changes in visual recognition memory for two types of stimuli, activate divergent neural systems, and allow us to use the same procedures within the confines of functional neuroimaging as those we use in standard neuropsychological administration. The tasks introduced here include a delay between target presentation and test phase, are matched in difficulty, and yield moderate levels of performance. Individual and group differences in task performance were examined in 80 cognitively normal men and women in two older age groups: 60 to 69 and 70 to 85. Accuracy averaged 74% in both tasks, with lower performance in the oldest age group. Although accuracy was equivalent between tasks, subjects had a more liberal response bias in the figural than verbal task. Performance on the new recognition memory tests was significantly related to Benton Visual Retention Test (BVRT; Benton [1963]. New York: The Psychological Corporation) and California Verbal Learning Test (CVLT; Delis, Kramer, Kaplan, & Ober [1987]. New York: The Psychological Corporation) performance measures. The absence of floor ol ceiling effects, wide range of individual variability, and demonstrated concurrent validity of the present tasks suggest their potential utility in functional neuroimaging studies and in the early detection of cognitive decline. C1 NIA, Gerontol Res Ctr, Lab Personal & Cognit, Baltimore, MD 21224 USA. Thomas Jefferson Univ, Dept Neurol, Epilepsy Ctr, Philadelphia, PA 19107 USA. RP Golski, S (reprint author), NIA, Gerontol Res Ctr, Lab Personal & Cognit, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM sgolski@lpc.grc.nia.nih.gov OI Zonderman, Alan B/0000-0002-6523-4778 NR 62 TC 10 Z9 11 U1 1 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0361-073X J9 EXP AGING RES JI Exp. Aging Res. PD OCT-DEC PY 1998 VL 24 IS 4 BP 359 EP 385 PG 27 WC Geriatrics & Gerontology; Psychology SC Geriatrics & Gerontology; Psychology GA 122GX UT WOS:000076064600003 PM 9783155 ER PT J AU Sloand, EM Young, NS Sato, T Kim, S Maciejewski, JP AF Sloand, EM Young, NS Sato, T Kim, S Maciejewski, JP TI Inhibition of interleukin-1 beta-converting enzyme in human hematopoietic progenitor cells results in blockade of cytokine-mediated apoptosis and expansion of their proliferative potential SO EXPERIMENTAL HEMATOLOGY LA English DT Article DE apoptosis; CD34(+) cells; interleukin-1 beta-converting enzyme; progenitors ID TUMOR-NECROSIS-FACTOR; ACQUIRED APLASTIC-ANEMIA; MARROW CD34(+) CELLS; INTERFERON-GAMMA; BONE-MARROW; ICE/CED-3 FAMILY; FACTOR-ALPHA; PERIPHERAL-BLOOD; GENE-EXPRESSION; FAS ANTIGEN AB Inhibitory and stimulatory cytokines regulate the function and survival of hematopoietic progenitor cells. Interactions between cytokines and progenitor cells may result in programmed cell death. Apoptosis of hematopoietic cells ultimately serves to diminish the size of the stem cell compartment in bone marrow (BM) failure, and this has frustrated efforts at ex vivo expansion of hematopoietic stem cells for BM transplantation. We previously demonstrated that triggering of the Fas-receptor, which is expressed on BM CD34(+) cells, mediates apoptosis of progenitor cells. Although interleukin-1 beta-converting enzyme (ICE) appears to be an important factor in the signaling cascade regulating Fas-mediated apoptosis of lymphoid cells, its role in apoptosis of CD34(+) cells has not been explored. In this study, we determined whether ICE protein was present in CD34(+) cells and assessed its role in limiting expansion of hematopoietic stem cells by apoptosis. We demonstrated that ICE mRNA was constitutively produced in CD34(+) cells, although the active form of ICE protein was not detected in fresh, unstimulated CD34(+) cells from healthy donors. ICE protein could be induced in these CD34(+) cells when they were cultured for 24 hours in the presence of hematopoietic growth factors. Interferon (IFN)-gamma and Fas agonist (CH11 monoclonal antibody) enhanced ICE expression and triggered CD34(+) cell apoptosis and cell death.: In both short- and long-term BM cultures, hematopoietic colony-forming cell numbers were increased after ICE blockade with a synthetic ICE inhibitor (Ac-Tyr-Val-Ala-Asp-aldehyde), even in the absence of IFN-gamma, suggesting that ICE regulates the proliferation and cell death of committed and primitive progenitor cells. The suppressive effect of IFN-gamma and Fas agonist on colony formation was also antagonized by ICE inhibitor. The effects of ICE blockade on proliferation of hematopoietic progenitors cells were related to inhibition of apoptosis, as demonstrated by annexin staining and in situ terminal dideoxytransferase apoptosis assays. Our results suggest that ICE protein is present in CD34(+) cells after exposure to cytokines, that regulation of the levels of ICE protein in CD34(+) cells is posttranscriptional, and that ICE plays a role in the regulation of apoptosis and expansion of primitive hematopoietic cells. ICE inhibition could potentially be used to reverse intrinsic and cytokine-mediated apoptotic signals for the purpose of stem and progenitor cell expansion. C1 NHLBI, NIH, Bethesda, MD 20892 USA. Univ Nevada, Sch Med, Reno, NV 89557 USA. RP Maciejewski, JP (reprint author), 31 Ctr Dr MSC 2490,Bldg 31,Rm 4A11, Bethesda, MD 20892 USA. NR 24 TC 14 Z9 15 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD OCT PY 1998 VL 26 IS 11 BP 1093 EP 1099 PG 7 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 124PL UT WOS:000076190800015 PM 9766451 ER PT J AU Blanchet, PJ Konitsiotis, S Hyland, K Arnold, LA Pettigrew, KD Chase, TN AF Blanchet, PJ Konitsiotis, S Hyland, K Arnold, LA Pettigrew, KD Chase, TN TI Chronic exposure to MPTP as a primate model of progressive parkinsonism: A pilot study with a free radical scavenger SO EXPERIMENTAL NEUROLOGY LA English DT Article DE Parkinson's disease; MPTP; monkeys; neuroprotection; oxidative stress; antioxidant ID STRIATAL DOPAMINE DEFICIENCY; 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE MPTP; CEREBROSPINAL-FLUID; SUBSTANTIA-NIGRA; LIQUID-CHROMATOGRAPHY; MONOAMINE METABOLISM; OXIDATIVE STRESS; COMMON MARMOSETS; DISEASE; NEUROTOXICITY AB The development of a validated primate model of progressive parkinsonism is a critical step in the evaluation of drugs that might halt or slow progression of Parkinson's disease, In this pilot study, we gradually exposed 14 cynomolgus monkeys to 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP), at a weekly dose of 0.5 mg/kg s.c. for 10 weeks, to determine their probability of not reaching a predetermined endpoint on a disability scale by Kaplan-Meier analysis. Four other MPTP-exposed animals were coadministered the potent free radical scavenger 7-hydroxy-1-[4-(3-methoxyphenyl)-1-piperazinyl]acetylamino-2,2,4,6- tetramethylindan (OPC-14117)as a single oral daily dose of 0.6 g/kg, starting 2 weeks before MPTP initiation. The risk of reaching endpoint by week 10 was 79% and mean time before reaching endpoint was 6 weeks. Global motor activity, recorded in a subset of animals using a portable activity monitor, declined following the first MPTP dose and never recovered. Several cerebrospinal fluid indices of central monoamine metabolism collected by suboccipital puncture at 0, 5, and 10 weeks, including HVA, DOPAC, and tetrahydrobiopterin but not MHPG, were found to be "trait" markers for MPTP exposure, whereas CSF DOPAC and tetrahydrobiopterin constituted potential "state" markers for reaching endpoint, The antioxidant OPC-14117 did not protect against MPTP-induced parkinsonism. Further attempts to validate this incremental model of neurotoxin-induced parkinsonism as a predictor of patient responses to putative neuroprotective agents appear warranted. C1 NINDS, Expt Therapeut Branch, NIH, Bethesda, MD 20892 USA. Baylor Univ, Med Ctr, Kimberly H Courtwright & Joseph W Summers Inst Me, Dallas, TX USA. Univ Texas, SW Med Ctr, Dept Neurol, Dallas, TX USA. NIMH, Div Epidemiol & Res Serv, NIH, Bethesda, MD 20892 USA. RP Chase, TN (reprint author), NINDS, Expt Therapeut Branch, NIH, Bldg 10,Room 5C103,10 Ctr Dr MSC 1406, Bethesda, MD 20892 USA. EM chase@helix.nih.gov NR 68 TC 16 Z9 18 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD OCT PY 1998 VL 153 IS 2 BP 214 EP 222 DI 10.1006/exnr.1998.6906 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 134YK UT WOS:000076771200005 PM 9784281 ER PT J AU David, DJ Zahniser, NR Hoffer, BJ Gerhardt, GA AF David, DJ Zahniser, NR Hoffer, BJ Gerhardt, GA TI In vivo electrochemical studies of dopamine clearance in subregions of rat nucleus accumbens: Differential properties of the core and shell SO EXPERIMENTAL NEUROLOGY LA English DT Article ID INCREASE EXTRACELLULAR DOPAMINE; VENTRAL STRIATOPALLIDAL PARTS; MEDIAL PREFRONTAL CORTEX; DORSAL STRIATUM; IN-VIVO; EXOGENOUS DOPAMINE; REPEATED COCAINE; EFFERENT PROJECTIONS; BASAL GANGLIA; UPTAKE SITES AB The dopamine (DA) uptake/clearance properties of the DA transporter (DAT) in the core and shell of the nucleus accumbens were measured using in vivo electrochemical recordings. Calibrated amounts of a DA solution were pressure-ejected from a micropipette/ electrode assembly placed in the core or shell of the nucleus accumbens in anesthetized male Fischer 344 rats. Initial studies in the two brain regions revealed that the core and shell have different DA clearance properties as measured by the extracellular DA signal amplitudes, clearance times, and clearance rates. Although the same number of picomoles of DA were applied, DA clearance signals recorded in shell had significantly greater amplitudes but faster clearance rates than those recorded in the core, Systemic administration of 20 mg/kg cocaine, a monoamine transporter inhibitor, greatly increased the signal amplitude from the locally applied DA in both the core and shell. Signal amplitudes were increased to a greater extent in the shell, compared with the core, after cocaine administration. However, cocaine affected the clearance time of DA only in the core and the DA clearance rate only in the shell. Taken together with previously reported data, these studies further support differential activity of the DAT in the core versus shell subregions of the nucleus accumbens. In addition, these data indicate that DATs are more sensitive to the effects of psychomotor stimulants, such as cocaine, in the shell of the nucleus accumbens. (C) 1998 Academic Press. C1 Univ Colorado, Hlth Sci Ctr, Neurosci Training Program, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Pharmacol, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Psychiat, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Rocky Mt Ctr Sensor Technol, Denver, CO 80262 USA. NIDA, Bethesda, MD USA. RP David, DJ (reprint author), Univ Colorado, Hlth Sci Ctr, Neurosci Training Program, 4200 E 9th Ave, Denver, CO 80262 USA. FU NIA NIH HHS [AG06434]; NIMH NIH HHS [MH01245]; NINDS NIH HHS [NS09199] NR 71 TC 44 Z9 44 U1 0 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD OCT PY 1998 VL 153 IS 2 BP 277 EP 286 DI 10.1006/exnr.1998.6898 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 134YK UT WOS:000076771200011 PM 9784287 ER PT J AU Freed, W AF Freed, W TI Fifth Annual Conference of the American Society for Neural Transplantation - Introduction SO EXPERIMENTAL NEUROLOGY LA English DT Editorial Material C1 NIDA, Intramural Res Program, Baltimore, MD 21222 USA. RP Freed, W (reprint author), NIDA, Intramural Res Program, 5500 Nathan Shock Dr, Baltimore, MD 21222 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD OCT PY 1998 VL 153 IS 2 BP 368 EP 369 PG 2 WC Neurosciences SC Neurosciences & Neurology GA 134YK UT WOS:000076771200019 ER PT J AU Freed, WJ Federoff, HJ Bohn, MC AF Freed, WJ Federoff, HJ Bohn, MC TI Viral vectors and neural transplantation: An introduction SO EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract C1 Natl Inst Drug Abuse, IRP, Baltimore, MD 21224 USA. Univ Rochester, Dept Neurol, Rochester, NY 14642 USA. Northwestern Univ, Sch Med, Dept Pediat, Chicago, IL 60614 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD OCT PY 1998 VL 153 IS 2 BP 376 EP 376 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 134YK UT WOS:000076771200041 ER PT J AU Granholm, AC Sanders, LA Reyland, ME Hoernig, GR Shen, L Westphal, H AF Granholm, AC Sanders, LA Reyland, ME Hoernig, GR Shen, L Westphal, H TI Transplantation of fetal tissues from trophic factor knockout mice to wildtype and heterozygous siblings SO EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract C1 Univ Colorado, Hlth Sci Ctr, Dept Basic Sci, Denver, CO USA. NICHHD, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD OCT PY 1998 VL 153 IS 2 BP 377 EP 378 PG 2 WC Neurosciences SC Neurosciences & Neurology GA 134YK UT WOS:000076771200046 ER PT J AU Chiang, YH Chiou, AL Lin, SZ Hoffer, BJ Wang, Y AF Chiang, YH Chiou, AL Lin, SZ Hoffer, BJ Wang, Y TI Transplantation of fetal kidney tissue reduces infarction volume of cerebral cortex in adult rats SO EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract C1 Natl Def Med Ctr, Dept Neurosurg, Taipei, Taiwan. Natl Def Med Ctr, Dept Pharmacol, Taipei, Taiwan. NIDA, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD OCT PY 1998 VL 153 IS 2 BP 381 EP 382 PG 2 WC Neurosciences SC Neurosciences & Neurology GA 134YK UT WOS:000076771200064 ER PT J AU Misiewicz, B Sternberg, E AF Misiewicz, B Sternberg, E TI Suppression of systemic inflammatory responses by intraventricular hypothalamic transplantations SO EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract C1 George Washington Univ, Med Ctr, Dept Physiol & Expt Med, Washington, DC 20037 USA. NIMH, Neuroendocrinol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD OCT PY 1998 VL 153 IS 2 BP 383 EP 384 PG 2 WC Neurosciences SC Neurosciences & Neurology GA 134YK UT WOS:000076771200073 ER PT J AU Truckenmiller, E Torres, AD Bouvier, MM Tornatore, C Freed, WJ AF Truckenmiller, E Torres, AD Bouvier, MM Tornatore, C Freed, WJ TI Characterization of a rat mesencephalic cell line immortalized with an N-terminal, fragment of SV40 large T. SO EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract C1 NIDA, NIH, Baltimore, MD USA. NINDS, Lab Mol Med & Neurosci, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD OCT PY 1998 VL 153 IS 2 BP 385 EP 385 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 134YK UT WOS:000076771200080 ER PT J AU Conejero, C Tornatore, C Dillon-Carter, O Freed, W AF Conejero, C Tornatore, C Dillon-Carter, O Freed, W TI Human GAD(67) cDNA transduced into immortalized cell lines. SO EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract C1 NIDA, IRP, Baltimore, MD 21224 USA. NINDS, Lab Mol Med & Neurosci, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD OCT PY 1998 VL 153 IS 2 BP 386 EP 386 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 134YK UT WOS:000076771200082 ER PT J AU Chang, JW Goldstein, M Milstien, S Kang, UJ AF Chang, JW Goldstein, M Milstien, S Kang, UJ TI Mutated form of tyrosine hydroxylase reduces feedback inhibition by dopamine in genetically modified grafts implanted in parkinsonian rats. SO EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract C1 Univ Chicago, Dept Neurol, Chicago, IL 60637 USA. NYU Med Ctr, New York, NY 10016 USA. NIMH, Lab Mol & Cellular Regulat, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD OCT PY 1998 VL 153 IS 2 BP 390 EP 391 PG 2 WC Neurosciences SC Neurosciences & Neurology GA 134YK UT WOS:000076771200103 ER PT J AU Misiewicz, B Sternberg, E AF Misiewicz, B Sternberg, E TI Suppression of systemic inflammatory responses by intraventricular hypothalamic transplantations SO EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract C1 George Washington Univ, Med Ctr, Dept Physiol & Expt Med, Washington, DC 20037 USA. NIMH, Neuroendocrinol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD OCT PY 1998 VL 153 IS 2 BP 392 EP 392 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 134YK UT WOS:000076771200110 ER PT J AU Vinetz, JM Kaslow, DC AF Vinetz, JM Kaslow, DC TI Plasmodium gallinaceum: Use of antisera to degenerate synthetic peptides derived from the active site of protozoal chitinases to characterize an ookinete-specific chitinase SO EXPERIMENTAL PARASITOLOGY LA English DT Article ID EXPRESSION; CLONING C1 NIAID, Malaria Vaccines Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Kaslow, DC (reprint author), NIAID, Malaria Vaccines Sect, Parasit Dis Lab, NIH, 9000 Rockville Pike 4,Room 126, Bethesda, MD 20892 USA. EM david_kas-low@nih.gov OI Vinetz, Joseph/0000-0001-8344-2004 NR 12 TC 9 Z9 9 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4894 J9 EXP PARASITOL JI Exp. Parasitol. PD OCT PY 1998 VL 90 IS 2 BP 199 EP 202 DI 10.1006/expr.1998.4322 PG 4 WC Parasitology SC Parasitology GA 128EC UT WOS:000076391500008 PM 9769251 ER PT J AU Van Schooten, FJ Hirvonen, A Maas, LM De Mol, BA Kleinjans, JCS Bell, DA Durrer, JD AF Van Schooten, FJ Hirvonen, A Maas, LM De Mol, BA Kleinjans, JCS Bell, DA Durrer, JD TI Putative susceptibility markers of coronary artery disease: association between VDR genotype, smoking, and aromatic DNA adduct levels in human right atrial tissue SO FASEB JOURNAL LA English DT Article DE smoking related DNA adducts; genetic polymorphisms; CAD ID HUMAN ATHEROSCLEROTIC LESIONS; WHITE BLOOD-CELLS; HEART-DISEASE; VITAMIN-D; CANCER BIOMARKERS; SERUM-CHOLESTEROL; CIGARETTE-SMOKING; LUNG-CANCER; FOLLOW-UP; RISK AB Cancer and cardiovascular diseases share risk factors such as smoking, and the onset of both diseases have been suggested to have a common mechanistic basis. The binding of carcinogens to DNA (carcinogen-DNA adducts), genetic polymorphisms in carcinogen-detoxifying enzymes glutathione Stransferases (GSTs), and genetic polymorphisms in the vitamin D receptor (VDR) are among the candidates for modifiers of cancer risk. We determined whether these biomarkers could be related to individual characteristics of patients suffering from cardiovascular diseases. For that purpose, DNA from the right atrial appendage of 41 patients who underwent open heart surgery was analyzed for smoking-related DNA adducts and polymorphisms in GSTM1, GSTT1, and VDR genes. Statistical analysis was used to identify any patient's characteristics associated with these molecular markers. Our results showed that heart tissue of cigarette smokers contained a variety of aromatic DNA adducts in significantly elevated levels compared to ex-smokers (P<0.01) or nonsmokers (P<0.001). A linear relationship was observed between DNA adduct levels and daily cigarette smoking (r(s)=0.73; P=0.0003). Since cardiac myocytes are terminally differentiated cells that have lost their ability to divide and seemingly have limited DNA repair capacities, their levels might accumulate with time and thereby affect heart cell function or viability. Substantial interindividual differences between DNA adduct levels were observed, and persons with severe coronary artery disease (CAD), as assessed by coronary angiography, had higher DNA adduct levels than persons with no or mild CAD (P=0.04). As polymorphisms in GST genes have been shown to modulate DNA adduct levels and risk for lung cancer in smokers, we explored for the first time whether the GST polymorphisms could also explain deviating; heart DNA adduct levels wand CAD risk. However, no relation could be found between these covariants. In contrast, a VDR genotype, which has been associated with decreased serum levels of the active hormonal form of vitamin D and increased risk for certain cancers, seemed to be related to severity of CAD (P=0.025). Our findings support the hypothesis that smoking-related DNA damage may be involved in the onset of cardiovascular diseases and suggest that VDR genotype may be a useful susceptibility marker of CAD. C1 Univ Limburg, Dept Hlth Risk Anal & Toxicol, NL-6200 MD Maastricht, Netherlands. Finnish Inst Occupat Hlth, Dept Ind Hyg & Toxicol, Helsinki, Finland. Univ Amsterdam, Acad Med Ctr, Dept Cardiol, NL-1105 AZ Amsterdam, Netherlands. Univ Amsterdam, Acad Med Ctr, Dept Cardiothorac Surg, NL-1105 AZ Amsterdam, Netherlands. NIEHS, Biochem Risk Anal Lab, Res Triangle Pk, NC 27709 USA. RP Van Schooten, FJ (reprint author), Univ Limburg, Dept Hlth Risk Anal & Toxicol, NL-6200 MD Maastricht, Netherlands. EM f.vanschooten@grat.unimaas.nl RI Kleinjans, Jos/E-7241-2015 NR 56 TC 56 Z9 58 U1 0 U2 4 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD OCT PY 1998 VL 12 IS 13 BP 1409 EP 1417 PG 9 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 128JE UT WOS:000076402000017 PM 9761785 ER PT J AU Tanaka, H Shimizu, M Horikawa, I Kugoh, H Yokota, J Barrett, JC Oshimura, M AF Tanaka, H Shimizu, M Horikawa, I Kugoh, H Yokota, J Barrett, JC Oshimura, M TI Evidence for a putative telomerase repressor gene in the 3p14.2-p21.1 region SO GENES CHROMOSOMES & CANCER LA English DT Article ID CARCINOMA CELL-LINE; MEDIATED CHROMOSOME TRANSFER; INDEFINITE DIVISION; HUMAN FIBROBLASTS; MICROCELL FUSION; IMMORTAL CELLS; FHIT GENE; SENESCENCE; SUPPRESSION; GROWTH AB Telomeres, which are the repeated sequences located on both ends of chromosomes in eukaryotes, are known to shorten with each cell division, and their eventual loss is thought to result in cellular senescence. Unlike normal somatic cells, most tumor cells show activation of telomerase, a ribonucleoprotein enzyme that stably maintains telomere length by addition of the sequences of TTAGGG repeats to telomeres. The KC12 cell line derived from a renal cell carcinoma in a patient with von Hippel-Lindau disease showed telomerase activity and loss of heterozygosity on the short arm of chromosome 3. Introduction of a normal human chromosome 3 into KC12 cells by microcell fusion induced cellular senescence, accompanied by suppression of telomerase activity and shortening of telomere length. Microcell hybrids that escaped from cellular senescence maintained telomere length and telomerase activity similar to those of the parental KC12 cells. We previously showed a similar suppression of telomerase activity by introduction of chromosome 3 into another renal cell carcinoma cell line, RCC23. The putative telomerase repressor gene was mapped to chromosome region 3p14.2-p21.1 by deletion mapping of KC12 + chromosome 3 revertants that escaped from cellular senescence and by transfer of subchromosomal fragments of chromosome 3 into RCC23 cells. (C) 1998 Wiley-Liss, Inc. C1 Tottori Univ, Fac Med, Sch Life Sci, Dept Mol & Cell Genet, Yonago, Tottori 6838503, Japan. Natl Inst Environm Hlth Sci, Mol Carcinogenesis Lab, Res Triangle Pk, NC USA. Natl Canc Ctr, Res Inst, Div Biol, Tokyo 104, Japan. RP Oshimura, M (reprint author), Tottori Univ, Fac Med, Sch Life Sci, Dept Mol & Cell Genet, Nishimachi 86, Yonago, Tottori 6838503, Japan. NR 41 TC 57 Z9 58 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD OCT PY 1998 VL 23 IS 2 BP 123 EP 133 DI 10.1002/(SICI)1098-2264(199810)23:2<123::AID-GCC5>3.0.CO;2-4 PG 11 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA 114XT UT WOS:000075635000005 PM 9739015 ER PT J AU Grewal, SIS Bonaduce, MJ Klar, AJS AF Grewal, SIS Bonaduce, MJ Klar, AJS TI Histone deacetylase homologs regulate epigenetic inheritance of transcriptional silencing and chromosome segregation in fission yeast SO GENETICS LA English DT Article ID MATING-TYPE REGION; SCHIZOSACCHAROMYCES-POMBE; SACCHAROMYCES-CEREVISIAE; CHROMATIN STRUCTURE; MEIOTIC RECOMBINATION; RPD3; GENE; CENTROMERES; EXPRESSION; LOCI AB Position-effect control at the silent mat2-mat3 interval and at centromeres and telomeres in fission yeast is suggested to be mediated through the assembly of heterochromatin-like structures. Therefore, transacting genes that affect silencing may encode either chromatin proteins, factors that modify them, or factors that affect chromatin assembly. Here, we report the identification of an essential gene, clr6 (cryptic loci regulator), which encodes a putative histone deacetylase that when mutated affects epigenetically maintained repression at the mat2-mat3 region and at centromeres and reduces the fidelity of chromosome segregation. Furthermore, we show that the Clr3 protein, when mutated, alleviates recombination block at mat region as well as silencing at donor loci and at centromeres and telomeres, also shares strong homology to known histone deacetylases. Genetic analyses indicate that silencing might be regulated by at least two overlapping histone deacetylase activities. We also found that transient inhibition of histone deacetylase activity by trichostatin A results in the increased missegregation of chromosomes in subsequent generations and, remarkably, alters the imprint at the mat locus, causing the heritable conversion of the repressed epigenetic state to the expressed state. This work supports the model that the level of histone deacetylation has a role in the assembly of repressive heterochromatin and provides insight into the mechanism of epigenetic inheritance. C1 NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Gene Regulat & Chromosome Biol Lab, Frederick, MD 21702 USA. RP NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Gene Regulat & Chromosome Biol Lab, POB B, Frederick, MD 21702 USA. EM klarmail@ncifcrf.gov NR 56 TC 138 Z9 143 U1 0 U2 3 PU GENETICS SOCIETY AMERICA PI BETHESDA PA 9650 ROCKVILLE AVE, BETHESDA, MD 20814 USA SN 0016-6731 EI 1943-2631 J9 GENETICS JI Genetics PD OCT PY 1998 VL 150 IS 2 BP 563 EP 576 PG 14 WC Genetics & Heredity SC Genetics & Heredity GA 125WG UT WOS:000076259600006 PM 9755190 ER PT J AU Pruitt, KD AF Pruitt, KD TI WebWise: Guide to the Institute for Genomic Research Web site SO GENOME RESEARCH LA English DT Editorial Material C1 NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP Pruitt, KD (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. NR 1 TC 1 Z9 2 U1 0 U2 0 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 1054-9803 J9 GENOME RES JI Genome Res. PD OCT PY 1998 VL 8 IS 10 BP 1000 EP 1004 PG 5 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 136MY UT WOS:000076864200002 PM 9799788 ER PT J AU Mazzarella, R Schlessinger, D AF Mazzarella, R Schlessinger, D TI Pathological consequences of sequence duplications in the human genome SO GENOME RESEARCH LA English DT Review ID SPINAL MUSCULAR-ATROPHY; FACTOR-VIII GENE; POLYCYSTIC KIDNEY-DISEASE; KEARNS-SAYRE-SYNDROME; HUMAN GLUCOCEREBROSIDASE GENE; STEROID 21-HYDROXYLASE GENES; HUMAN MITOCHONDRIAL-DNA; CARDIO-FACIAL SYNDROME; VISUAL PIGMENT GENES; SEVERE HEMOPHILIA-A AB As large-scale sequencing accumulates momentum, an increasing number of instances are being revealed in which genes or other relatively rare sequences are duplicated, either in tandem or at nearby locations. Such duplications are a source of considerable polymorphism in populations, and also increase the evolutionary possibilities for the coregulation of juxtaposed sequences. As a further consequence, they promote inversions and deletions that are responsible for significant inherited pathology. Here we review known examples of genomic duplications present on the human X chromosome and autosomes. C1 NIA, Gerontol Res Ctr, Genet Lab, Baltimore, MD 21224 USA. Washington Univ, Sch Med, Ctr Genet Med, St Louis, MO 63110 USA. Washington Univ, Sch Med, Inst Biomed Comp, St Louis, MO 63110 USA. RP Schlessinger, D (reprint author), NIA, Gerontol Res Ctr, Genet Lab, 4940 Eastern Ave, Baltimore, MD 21224 USA. EM schlessingerd@grc.nia.nih.gov NR 120 TC 78 Z9 78 U1 1 U2 1 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 1054-9803 J9 GENOME RES JI Genome Res. PD OCT PY 1998 VL 8 IS 10 BP 1007 EP 1021 PG 15 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 136MY UT WOS:000076864200003 PM 9799789 ER PT J AU Leonard, CJ Aravind, L Koonin, EV AF Leonard, CJ Aravind, L Koonin, EV TI Novel families of putative protein kinases in bacteria and archaea: Evolution of the "eukaryotic" protein kinase superfamily SO GENOME RESEARCH LA English DT Article ID PROKARYOTE SALMONELLA-TYPHIMURIUM; ESCHERICHIA-COLI; SACCHAROMYCES-CEREVISIAE; MYXOCOCCUS-XANTHUS; PHOSPHORYLATION; GENE; SERINE; PHOSPHATASES; THREONINE; SEQUENCE AB The central role of serine/threonine and tyrosine protein kinases in signal transduction and cellular regulation in eukaryotes is well established and widely documented. Considerably less is known about the prevalence and role of these protein kinases in bacteria and archaea. In order to examine the evolutionary origins of the eukaryotic-type protein kinase (ePK) superfamily, we conducted an extensive analysis of the proteins encoded by the completely sequenced bacterial and archaeal genomes. We detected five distinct families of known and predicted putative protein kinases with representatives in bacteria and archaea that share a common ancestry with the eukaryotic protein kinases. Four of these protein families have not been identified previously as protein kinases. From the phylogenetic distribution of these families, we infer the existence of an ancestral protein kinase(s) prior to the divergence of eukaryotes, bacteria, and archaea. C1 NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. Texas A&M Univ, Dept Biol, College Stn, TX 77843 USA. RP Koonin, EV (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. NR 40 TC 209 Z9 222 U1 1 U2 8 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 1054-9803 J9 GENOME RES JI Genome Res. PD OCT PY 1998 VL 8 IS 10 BP 1038 EP 1047 PG 10 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 136MY UT WOS:000076864200005 PM 9799791 ER PT J AU Kouprina, N Campbell, M Graves, J Campbell, E Meincke, L Tesmer, J Grady, DL Doggett, NA Moyzis, RK Deaven, LL Larionov, V AF Kouprina, N Campbell, M Graves, J Campbell, E Meincke, L Tesmer, J Grady, DL Doggett, NA Moyzis, RK Deaven, LL Larionov, V TI Construction of human chromosome 16- and 5-specific circular YAC/BAC libraries by in vivo recombination in yeast (TAR cloning) SO GENOMICS LA English DT Article ID TRANSFORMATION-ASSOCIATED RECOMBINATION; ARTIFICIAL CHROMOSOMES; HUMAN DNA; VECTORS; PROPAGATION; FRAGMENTS; SEGMENTS; SYSTEM AB Transformation-associated recombination (TAR) in yeast was exploited for the selective isolation of human DNAs as large circular yeast artificial chromosomes (YACs) from two rodent/human hybrid cell lines containing human chromosomes 5 and 16. TAR cloning vectors containing the F-factor origin of replication were constructed for use in these experiments. Presence of the F-factor origin in TAR vectors provides the capability of transferring the YACs generated by in vivo recombination in yeast into Escherichia coli cells and propagating them as bacterial artificial chromosomes (BACs). A high enrichment of human versus rodent YACs was observed during isolation of human DNA from the rodent/human hybrid cell lines. Although <3% of the DNA content in the hybrid cells was human, as many as 75% of the transformants contained human YACs. In contrast to the standard YAC cloning method based on in vitro ligation, no human/mouse chimeras were observed during TAR cloning. The constructed human chromosome 16 YAC library had approximately 2.6x coverage, represented by 4320 YAC clones with an average insert size of 80 kb. YAC clones generated from chromosome 16 were successfully converted into BACs by electroporation of DNA isolated from yeast transformants into E. coli. The BAC clones represent similar to 0.6x chromosomal coverage. Pilot YAC and BAC libraries of chromosome 5 have been also constructed. The chromosomal distribution of YAC/BACs from chromosome 5 and chromosome 16 was evaluated by fluorescence in situ hybridization (FISH). The distribution of FISH signals appeared random along the length of each chromosome. We conclude that TAR cloning provides an efficient means for generating representative chromosome-specific YAC/BAC libraries. (C) 1998 Academic Press. C1 NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. Los Alamos Natl Lab, Div Life Sci, Los Alamos, NM 87545 USA. Los Alamos Natl Lab, Ctr Human Genome Studies, Los Alamos, NM 87545 USA. RP Kouprina, N (reprint author), NIEHS, Mol Genet Lab, Box 12233, Res Triangle Pk, NC 27709 USA. EM kouprina@niehs.nih.gov NR 20 TC 16 Z9 17 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 EI 1089-8646 J9 GENOMICS JI Genomics PD OCT 1 PY 1998 VL 53 IS 1 BP 21 EP 28 DI 10.1006/geno.1998.5469 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 131UK UT WOS:000076593500003 PM 9787074 ER PT J AU Deng, ZM Centola, M Chen, XG Sood, R Vedula, A Fischel-Ghodsian, N Kastner, DL AF Deng, ZM Centola, M Chen, XG Sood, R Vedula, A Fischel-Ghodsian, N Kastner, DL TI Identification of two Kruppel-related zinc finger genes (ZNF200 and ZNF210) from human chromosome 16p13.3 SO GENOMICS LA English DT Article ID PROTEIN; EXPRESSION; REGION AB During the course of cloning the gene for familial Mediterranean fever (FMF), we identified a number of transcripts from a 275-kb genomic region on 16p13.3. Two of the transcripts were found to contain multiple C2H2-type zinc finger motifs in tandem arrays, indicating that they are members of the Kruppel-type family. One transcript was found to be an alternatively spliced form of a previously reported zinc finger gene, ZNF200. The other transcript, ZNF210, is 2017 bp and encodes an open reading frame of 504 aa. Northern blot analysis indicates that ZNF210 is expressed in all the tissues tested with the highest expression in heart, skeletal muscle, pancreas, prostate, ovary, and colon. On the other hand, the strongest expression of ZNF200 is in testis, with very low levels in all the other tissues tested. Sequence analysis reveals eight C2H2 zinc finger motifs at the C-terminus of ZNF210 and five in ZNF200. In addition, ZNF210 also possesses a Kruppel-associated box at its N-terminus, indicating that it might function as a transcription repressor. The intron-exon structures of both genes were determined and showed that ZNF210 has seven exons while the coding part of ZNF200 is distributed in four exons. The locations of ZNF200 and ZNF210 are 10 and 120 kb telomeric to the FMF gene, respectively. (C) 1998 Academic Press. C1 NIAMSD, NIH, Arthrit & Rheumatism Branch, Bethesda, MD 20892 USA. Cedars Sinai Med Ctr, Dept Pediat, Los Angeles, CA 90048 USA. Cedars Sinai Med Ctr, Dept Med Genet, Los Angeles, CA 90048 USA. RP Kastner, DL (reprint author), NIAMSD, NIH, Arthrit & Rheumatism Branch, Bldg 10,Room 9N214, Bethesda, MD 20892 USA. EM kastner@fmf.nia.ms.nih.gov NR 17 TC 7 Z9 10 U1 0 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD OCT 1 PY 1998 VL 53 IS 1 BP 97 EP 103 DI 10.1006/geno.1998.5430 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 131UK UT WOS:000076593500010 PM 9787081 ER PT J AU Steele, VE Boone, CW Lubet, RA Crowell, JA Holmes, CA Sigman, CC Kelloff, GJ AF Steele, VE Boone, CW Lubet, RA Crowell, JA Holmes, CA Sigman, CC Kelloff, GJ TI Preclinical drug development paradigms for chemopreventives SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Review ID MOUSE EPIDERMAL-CELLS; POTENTIAL CANCER CHEMOPREVENTIVES; ORNITHINE DECARBOXYLASE INDUCTION; ANCHORAGE-INDEPENDENT GROWTH; URINARY-BLADDER CANCER; SKIN TUMOR PROMOTION; COLON CARCINOGENESIS; MAMMARY-CANCER; SELECTIVE-INHIBITION; CURRENT PERSPECTIVES AB Preclinical screening studies and animal efficacy testing models currently are used by the National Cancer Institute's chemoprevention drug discovery program to assess and identify chemical agents and natural products that may have the potential to prevent human cancer. Identification of potential cancer preventing agents begins by subjecting each compound to a sequential series of short-term, in vitro prescreens of mechanistic, biochemical assays to provide quantitative data to help establish an early indication of chemopreventive efficacy and to assist in prioritizing agents for further evaluation in longer-term, in vitro transformation bioassays and whole animal models. Promising chemical agents or combinations of agents that work through different inhibitory mechanisms subsequently are tested in well-established, chemically induced, animal tumor models, which include models of the lung, bladder, mammaries, prostate, and skin. These preclinical bioassays afford a strategic framework for evaluating agents according to defined criteria, and not only provide evidence of agent efficacy, but also serve to generate valuable dose-response, toxicity, and pharmacokinetic data required prior to phase I clinical safety testing. Based on preclinical efficacy and toxicity screening studies, only the most successful agents considered to have potential as human chemopreventives progress into clinical chemoprevention trials. C1 NCI, Chemoprevent Branch, Div Canc Chemoprevent DCP, Bethesda, MD 20892 USA. CCS Associates, Mt View, CA USA. RP Steele, VE (reprint author), NCI, Chemoprevent Branch, Div Canc Chemoprevent DCP, EPN 201E,MSC 7322,9000 Rockville Pike,Suite 201, Bethesda, MD 20892 USA. NR 107 TC 18 Z9 20 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0889-8588 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD OCT PY 1998 VL 12 IS 5 BP 943 EP + DI 10.1016/S0889-8588(05)70035-6 PG 21 WC Oncology; Hematology SC Oncology; Hematology GA 133ZJ UT WOS:000076717200003 PM 9888015 ER PT J AU Dunn, BK Kramer, BS Ford, LG AF Dunn, BK Kramer, BS Ford, LG TI Phase III, large-scale chemoprevention trials - Approach to chemoprevention clinical trials and phase III clinical trial of tamoxifen as a chemopreventive for breast cancer - The US National Cancer Institute experience SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article ID RECEPTOR-POSITIVE TUMORS; ADJUVANT TAMOXIFEN; COLORECTAL-CANCER; TUMORIGENESIS; PREVENTION; CARCINOMA; THERAPY; MODEL; LEVEL AB Clinical trials to evaluate interventions for cancer prevention are designed as early (phase I, IIa, and IIb) or late-phase studies. Whereas the former are small and generally rely on intermediate endpoint biomarkers of carcinogenesis, the latter are large-scale, longterm, randomized, phase III studies that address endpoints such as cancer incidence. The Breast Cancer Prevention Trial, P-1, conducted by the National Surgical Adjuvant Breast and Bowel Project (NSABP), is discussed as an example of a large, extended, phase III trial designed to answer the question of whether tamoxifen reduces the incidence of breast cancer in women who ape at increased risk for the disease. C1 NCI, Div Canc Prevent, Early Detect & Community Oncol Program, Rockville, MD 20852 USA. RP Ford, LG (reprint author), NCI, Div Canc Prevent, Early Detect & Community Oncol Program, G130 Execut Blvd,Room 300, Rockville, MD 20852 USA. NR 50 TC 14 Z9 14 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0889-8588 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD OCT PY 1998 VL 12 IS 5 BP 1019 EP + DI 10.1016/S0889-8588(05)70039-3 PG 19 WC Oncology; Hematology SC Oncology; Hematology GA 133ZJ UT WOS:000076717200007 PM 9888019 ER PT J AU Arichi, T Shirai, M Chen, M Nishioka, M Ikeda, K Takahashi, H Enomoto, N Saito, T Major, ME Nakazawa, T Akatsuka, T Feinstone, SM Berzofsky, JA AF Arichi, T Shirai, M Chen, M Nishioka, M Ikeda, K Takahashi, H Enomoto, N Saito, T Major, ME Nakazawa, T Akatsuka, T Feinstone, SM Berzofsky, JA TI T cell recognition of hypervariable region 1 from hepatitis C virus envelope protein with multiple class II MHC molecules in mice and humans: Preferential help for induction of antibodies the hypervariable region. SO HEPATOLOGY LA English DT Meeting Abstract C1 NCI, Metab Branch, NIH, Bethesda, MD 20892 USA. Yamaguchi Univ, Sch Med, Yamaguchi, Japan. Kagawa Med Sch, Dept Internal Med 3, Kagawa 76107, Japan. Kagawa Med Sch, Dept Transfus Med, Kagawa 76107, Japan. Nippon Med Sch, Tokyo 113, Japan. Tokyo Med & Dent Univ, Tokyo 113, Japan. US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Bethesda, MD USA. 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 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1998 VL 28 IS 4 SU S MA 10 BP 165A EP 165A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 125VQ UT WOS:000076258100012 ER PT J AU Cox, J Monga, SPS Mishra, B Mishra, L AF Cox, J Monga, SPS Mishra, B Mishra, L TI Functional characterization of ITIH-4, a scaffolding protein isolated from developing liver. SO HEPATOLOGY LA English DT Meeting Abstract C1 Univ Geneva, Dept Biochem, Geneva, Sweden. DVAMC, Washington, DC USA. Temple Univ, Fels Inst Canc Res & Mol Biol, Philadelphia, PA 19122 USA. NHGRI, CGTB, NIH, Bethesda, MD USA. 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 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1998 VL 28 IS 4 SU S MA 38 BP 172A EP 172A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 125VQ UT WOS:000076258100040 ER PT J AU Wright, EC Seeff, LB Hollinger, FB Alter, HJ Buskell-Bales, Z Cain, C AF Wright, EC Seeff, LB Hollinger, FB Alter, HJ Buskell-Bales, Z Cain, C CA NHLBI Study Grp TI Updated long-term mortality of transfusion-associated hepatitis (TAH), non-A, non-B and C. SO HEPATOLOGY LA English DT Meeting Abstract C1 New England Res Inst, Watertown, MA 02172 USA. Vet Adm Med Ctr, Washington, DC 20422 USA. Baylor Coll Med, Houston, TX 77030 USA. NIH, Blood Bank, Bethesda, MD 20892 USA. Westat, Rockville, MD USA. NR 0 TC 5 Z9 5 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1998 VL 28 IS 4 SU S MA 440 BP 272A EP 272A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 125VQ UT WOS:000076258100440 ER PT J AU Tomizawa, M Garfield, S Xanthopoulos, KG AF Tomizawa, M Garfield, S Xanthopoulos, KG TI Hepatocytes deficient in CCAAT enhancer binding protein alpha (C/EBP alpha) exhibit both hepatocyte and biliary epithelial cell character SO HEPATOLOGY LA English DT Meeting Abstract C1 Natl Human Genome Res Inst, CGTB, NIH, Bethesda, MD USA. NCI, DBS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1998 VL 28 IS 4 SU S MA 528 BP 294A EP 294A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 125VQ UT WOS:000076258100528 ER PT J AU Sakata, H Takayama, H Onodera, K Kato, K Kasai, S LaRochelle, WJ Merlino, G Rubin, JS AF Sakata, H Takayama, H Onodera, K Kato, K Kasai, S LaRochelle, WJ Merlino, G Rubin, JS TI Establishment and characterization of a hepatoblast cell line derived from hepatocyte growth factor scatter factor transgenic mouse. SO HEPATOLOGY LA English DT Meeting Abstract C1 Gunma Univ, Sch Med, Asahikawa Med Coll, Dept Surg 2, Gunma, Japan. Gunma Univ, Sch Med, Dept Internal Med 1, Gunma, Japan. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1998 VL 28 IS 4 SU S MA 529 BP 295A EP 295A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 125VQ UT WOS:000076258100529 ER PT J AU Lau, DTY Ghany, MG Doo, E Herion, D Kleiner, DE Park, Y Schmid, P Liang, TJ Hoofnagle, JH AF Lau, DTY Ghany, MG Doo, E Herion, D Kleiner, DE Park, Y Schmid, P Liang, TJ Hoofnagle, JH TI Features of response and resistance to lamivudine in patients with chronic hepatitis B with and without HBeAg. SO HEPATOLOGY LA English DT Meeting Abstract C1 Natl Inst Genet, Los Angeles, CA USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. NIDDK, Liver Dis Sect, NIH, Bethesda, MD 20205 USA. NR 0 TC 4 Z9 5 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1998 VL 28 IS 4 SU S MA 623 BP 318A EP 318A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 125VQ UT WOS:000076258100622 ER PT J AU Bukh, J Yanagi, M Emerson, SU Purcell, RH AF Bukh, J Yanagi, M Emerson, SU Purcell, RH TI Course of infection and evolution of monoclonal hepatitis C virus (HCV) strain H77 in chimpanzees transfected with RNA transcripts from an infectious cDNA clone. SO HEPATOLOGY LA English DT Meeting Abstract C1 NIAID, Hepatitis Viruses Sect, LID, NIH, Bethesda, MD 20892 USA. NR 0 TC 7 Z9 7 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1998 VL 28 IS 4 SU S MA 628 BP 319A EP 319A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 125VQ UT WOS:000076258100628 ER PT J AU Yanagi, M St Claire, M Shapiro, M Emerson, SU Purcell, RH Bukh, J AF Yanagi, M St Claire, M Shapiro, M Emerson, SU Purcell, RH Bukh, J TI In vivo functional analysis of the 3 ' untranslated region (UTR) of hepatitis C virus (HCV). SO HEPATOLOGY LA English DT Meeting Abstract C1 NIAID, Hepatitis Viruses Sect, LID, NIH, Bethesda, MD 20892 USA. Bioqual Inc, Rockville, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1998 VL 28 IS 4 SU S MA 627 BP 319A EP 319A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 125VQ UT WOS:000076258100626 ER PT J AU Kono, H Yin, M Bradford, BU Gonzalez, FJ Thurman, RG AF Kono, H Yin, M Bradford, BU Gonzalez, FJ Thurman, RG TI Development of a new enteral mouse model using knockout technology to study alcohol-induced liver injury: Is CYP2E1 involved? SO HEPATOLOGY LA English DT Meeting Abstract C1 NCI, Mol Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. Univ N Carolina, Dept Pharmacol, Chapel Hill, NC 27599 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1998 VL 28 IS 4 SU S MA 669 BP 330A EP 330A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 125VQ UT WOS:000076258100669 ER PT J AU Charlton, M Seaberg, E Wiesner, R Paya, C Everhart, J Zetterman, R Lake, J Hoofnagle, J AF Charlton, M Seaberg, E Wiesner, R Paya, C Everhart, J Zetterman, R Lake, J Hoofnagle, J TI Increased mortality following CMV infection in patients transplanted for HCV - Results of the NIDDK liver transplantation database. SO HEPATOLOGY LA English DT Meeting Abstract C1 NIDDK, Liver Transplantat Database, Bethesda, MD 20892 USA. 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 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1998 VL 28 IS 4 SU S MA 729 BP 345A EP 345A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 125VQ UT WOS:000076258100729 ER PT J AU Everhart, JE AF Everhart, JE CA NIDDK Liver Transplantation Database TI Determinants of hepatitis C virus (HCV) infection after liver transplantation (LT) SO HEPATOLOGY LA English DT Meeting Abstract C1 NIDDKD, Bethesda, MD 20892 USA. 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 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1998 VL 28 IS 4 SU S MA 746 BP 349A EP 349A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 125VQ UT WOS:000076258100747 ER PT J AU Everhart, JE AF Everhart, JE CA NIDDK Liver Transplantation Database TI Hepatitis C virus (HCV) infection after liver transplantation (LT) from donors with markers for HCV. SO HEPATOLOGY LA English DT Meeting Abstract C1 NIDDKD, Bethesda, MD 20892 USA. 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 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1998 VL 28 IS 4 SU S MA 745 BP 349A EP 349A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 125VQ UT WOS:000076258100745 ER EF