FN Thomson Reuters Web of Science™ VR 1.0 PT J AU MazzolaPomietto, P Aulakh, CS Tolliver, T Murphy, DL AF MazzolaPomietto, P Aulakh, CS Tolliver, T Murphy, DL TI Functional subsensitivity of 5-HT2A and 5-HT2C receptors mediating hyperthermia following acute and chronic treatment with 5-HT2A/2C receptor antagonists SO PSYCHOPHARMACOLOGY LA English DT Article DE metergoline; mesulergine; mianserin; ritanserin; m-chlorophenylpiperazine; (+/-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane ID CENTRAL SEROTONIN RECEPTORS; MIANSERIN TREATMENT; CHOROID-PLEXUS; BINDING-SITES; RATS; BRAIN; HYPOPHAGIA; AGONISTS; BEHAVIOR; DOI AB In the present study, we investigated the duration of attenuation of the temperature increases produced by (+/-) 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and m-chlorophenylpiperazine (m-CPP) which followed pretreatment with four serotonin (5-HT) antagonists; metergoline, mesulergine, mianserin and ritanserin. The duration of attenuation of m-CPP-induced hyperthermia lasted less than I day for ritanserin, more than 1 day for the 5 mg/kg doses of both mianserin and metergoline and more than 2 days for the 5 mg/kg dose mesulergine. The duration of attenuation of DOI-induced hyperthermia lasted less than 1 day for ritanserin, more than 1 day for mianserin, more than 2 days for the 5 mg/kg dose of metergoline and more than 4 days for mesulergine. Daily administration of a low (1.0 mg/kg per day) dose of ritanserin for 14 days led to an attenuation of the temperature increases produced by m-CPP given 24 h after the last dose of ritanserin, but did not cause a similar desensitization of DOI-induced hyperthermia. On the other hand, daily administration of both low (1.0 mg/kg per day) and high (5.0 mg/kg per day) doses of mianserin for 14 days caused desensitization of DOI-induced hyperthermia but did not cause desensitization of m-CPP-induced hyperthermia when these agonists were administered 48 h after the last dose of mianserin. These findings demonstrate functional subsensitivity of both 5-HT2A and 5-HT2C receptors mediating hyperthermia following both acute and chronic administration of 5-HT2A/5-HT2C receptor antagonists: some differences in time course and in responses to individual antagonists at 5-HT2A versus 5-HT2C sites were also observed. RP MazzolaPomietto, P (reprint author), NIMH,CLIN SCI LAB,10 CTR DR MSC 1264,BLDG 10,ROOM 3D41,BETHESDA,MD 20892, USA. NR 38 TC 21 Z9 22 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD MAR PY 1997 VL 130 IS 2 BP 144 EP 151 DI 10.1007/s002130050222 PG 8 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA WQ445 UT WOS:A1997WQ44500010 PM 9106912 ER PT J AU Kleinman, DV AF Kleinman, DV TI Designing technologies - Commentary SO PUBLIC HEALTH REPORTS LA English DT Editorial Material RP Kleinman, DV (reprint author), NIDR,NIH,BLDG 31,RM 2C39,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPT OF DOCUMENTS, WASHINGTON, DC 20402-9325 SN 0033-3549 J9 PUBLIC HEALTH REP JI Public Health Rep. PD MAR-APR PY 1997 VL 112 IS 2 BP 107 EP 107 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA WN191 UT WOS:A1997WN19100021 ER PT J AU Dancey, J Zee, B Osoba, D Whitehead, M Lu, F Kaizer, L Latreille, J Pater, JL AF Dancey, J Zee, B Osoba, D Whitehead, M Lu, F Kaizer, L Latreille, J Pater, JL TI Quality of life scores: An independent prognostic variable in a general population of cancer patients receiving chemotherapy SO QUALITY OF LIFE RESEARCH LA English DT Article DE EORTC QLQ-C30; multicentre trials; prognosis; quality of life ID ADVANCED BREAST-CANCER; OF-LIFE; LUNG-CANCER; CLINICAL-TRIALS; INDEX; DEXAMETHASONE; SURVIVAL; EFFICACY; QLQ-C30 AB This report examines the prognostic associations between QOL scores measured by the EORTC QLQ-C30 and survival in a large heterogeneous population of cancer patients. Eight hundred and fifty-one cancer patients who were to receive chemotherapy were enrolled in two National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) antiemetic trials. All patients completed the EORTC QLQ-C30 immediately prior to their first chemotherapy. Survival data were available and obtained for 474 of 639 patients (74%). Cox's proportional hazards model was used to assess the independent impact of QOL and demographic variables on survival. Presence of metastatic disease, diagnosis of lung or ovarian cancer, ECOG performance status, global quality of life and emotional functioning were significantly associated with survival. Global QOL was predictive in all patients, in subgroups of patients with metastatic disease, with breast and lung cancer and other tumour types. In patients with low global quality of life scores, patients with low emotional functioning ratings lived longer than did patients with high emotional functioning ratings. Patients with high global QOL live significantly longer than do patients with low global QOL. The relationship between emotional functioning in patients with low global QOL and survival needs confirmation. C1 QUEENS UNIV,NCI,CLIN TRIALS GRP,KINGSTON,ON K7L 3N6,CANADA. BRITISH COLUMBIA CANC AGCY,VANCOUVER,BC V5Z 4E6,CANADA. UNIV BRITISH COLUMBIA,VANCOUVER,BC V5Z 1M9,CANADA. CREDIT VALLEY HOSP,MISSISSAUGA,ON,CANADA. UNIV TORONTO,MISSISSAUGA,ON L5L 1C6,CANADA. MONTREAL GEN HOSP,HOTEL DIEU,MONTREAL,PQ H3G 1A4,CANADA. UNIV MONTREAL,MONTREAL,PQ,CANADA. OI Zee, Benny Chung-Ying/0000-0002-7238-845X NR 18 TC 162 Z9 165 U1 0 U2 3 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0962-9343 J9 QUAL LIFE RES JI Qual. Life Res. PD MAR PY 1997 VL 6 IS 2 BP 151 EP 158 PG 8 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA WW416 UT WOS:A1997WW41600007 PM 9161115 ER PT J AU Miller, RW Boice, JD AF Miller, RW Boice, JD TI Cancer after intrauterine exposure to the atomic bomb SO RADIATION RESEARCH LA English DT Editorial Material ID SURVIVORS; RISK C1 INT EPIDEMIOL INST,ROCKVILLE,MD 20850. RP Miller, RW (reprint author), NCI,GENET EPIDEMIOL BRANCH,EPN 400,BETHESDA,MD 20892, USA. NR 14 TC 14 Z9 14 U1 0 U2 2 PU RADIATION RESEARCH SOC PI OAK BROOK PA 2021 SPRING RD, STE 600, OAK BROOK, IL 60521 SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD MAR PY 1997 VL 147 IS 3 BP 396 EP 397 DI 10.2307/3579349 PG 2 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA WL732 UT WOS:A1997WL73200017 PM 9052688 ER PT J AU Scialli, AR Swan, SH Amler, RW Baird, DD Eskenazi, B Gist, G Hatch, MC Kesner, JS Lemasters, GK Marcus, M Paul, ME Schulte, P Taylor, Z Wilcox, AJ Zahniser, C AF Scialli, AR Swan, SH Amler, RW Baird, DD Eskenazi, B Gist, G Hatch, MC Kesner, JS Lemasters, GK Marcus, M Paul, ME Schulte, P Taylor, Z Wilcox, AJ Zahniser, C TI Assessment of reproductive disorders and birth defects in communities near hazardous chemical sites .2. Female reproductive disorders SO REPRODUCTIVE TOXICOLOGY LA English DT Article ID FOLLICLE-STIMULATING-HORMONE; LUTEINIZING-HORMONE; PREGNANCY OUTCOMES; OVARIAN TOXICITY; OVULATION; WOMEN; CALIFORNIA; ACCURACY; LEVEL; WATER AB Members of the workgroup on female reproductive disorders discussed methods to evaluate five principal functions: menstrual dysfunction, infertility, pregnancy loss, lactation disorders, and pregnancy complications. To test each function, a nested strategy was considered, based on progressive levels of effort available to conduct field investigations. This strategy mas analogous to the three-tier classification of biomarkers used by other workshops. The lowest level of effort, corresponding to Tier 1, consists only of questionnaires, diaries, and reviews of maternal and infant medical records. The medium level of effort (Tier 2) collects data from questionnaires and diaries, and some biologic specimens, Suggested laboratory analyses included measurement of progesterone in saliva and several glycoprotein hormones in urine that evaluate menstrual dysfunction, infertility, and pregnancy loss. The highest level of effort (Tier 3) involves prospective collection of diary information and simultaneous collection of biological specimens. (C) 1997 Elsevier Science Inc. C1 GEORGETOWN UNIV,MED CTR,WASHINGTON,DC 20057. CALIF DEPT HLTH SERV,BERKELEY,CA 94704. AGCY TOX SUBST & DIS REGISTRY,ATLANTA,GA. NIEHS,RES TRIANGLE PK,NC 27709. UNIV CALIF BERKELEY,BERKELEY,CA 94720. COLUMBIA UNIV,SCH PUBL HLTH,NEW YORK,NY 10027. NIOSH,CINCINNATI,OH 45226. UNIV CINCINNATI,CINCINNATI,OH 45221. UNIV MASSACHUSETTS,MED CTR,WORCESTER,MA. CTR DIS CONTROL & PREVENT,ATLANTA,GA. NR 31 TC 12 Z9 13 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0890-6238 J9 REPROD TOXICOL JI Reprod. Toxicol. PD MAR-JUN PY 1997 VL 11 IS 2-3 BP 231 EP 242 DI 10.1016/S0890-6238(96)00107-4 PG 12 WC Reproductive Biology; Toxicology SC Reproductive Biology; Toxicology GA WQ840 UT WOS:A1997WQ84000010 PM 9100298 ER PT J AU Bishop, JB Kimmel, CA AF Bishop, JB Kimmel, CA TI Molecular and cellular mechanisms of early mammalian development: An overview of NIEHS/EPA developmental toxicity workshops SO REPRODUCTIVE TOXICOLOGY LA English DT Article ID ETHYLENE-OXIDE; FETAL ANOMALIES; ZYGOTES; DEATH; MICE C1 US EPA,NATL CTR ENVIRONM ASSESSMENT,WASHINGTON,DC 20460. RP Bishop, JB (reprint author), NIEHS,ENVIRONM TOXICOL PROGRAM,REPROD TOXICOL GRP,POB 12233 A2-10,RES TRIANGLE PK,NC 27709, USA. NR 13 TC 3 Z9 3 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0890-6238 J9 REPROD TOXICOL JI Reprod. Toxicol. PD MAR-JUN PY 1997 VL 11 IS 2-3 BP 285 EP 291 DI 10.1016/S0890-6238(96)00211-0 PG 7 WC Reproductive Biology; Toxicology SC Reproductive Biology; Toxicology GA WQ840 UT WOS:A1997WQ84000019 PM 9100303 ER PT J AU Gonzalez, FJ AF Gonzalez, FJ TI The role of carcinogen-metabolizing enzyme polymorphisms in cancer susceptibility SO REPRODUCTIVE TOXICOLOGY LA English DT Article ID ARYL-HYDROCARBON HYDROXYLASE; S-TRANSFERASE M1; FRAGMENT-LENGTH-POLYMORPHISM; TRANS-STILBENE OXIDE; GSTM1 NULL GENOTYPE; HUMAN CYP1A1 GENE; FLAVIN-CONTAINING MONOOXYGENASES; HUMAN CYTOCHROME-P450IIE1 GENE; N-ACETYLTRANSFERASE PHENOTYPE; MICROSOMAL EPOXIDE HYDROLASE RP Gonzalez, FJ (reprint author), NCI,NIH,BLDG 37,ROOM 3E-24,BETHESDA,MD 20892, USA. NR 211 TC 34 Z9 34 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0890-6238 J9 REPROD TOXICOL JI Reprod. Toxicol. PD MAR-JUN PY 1997 VL 11 IS 2-3 BP 397 EP 412 DI 10.1016/S0890-6238(96)00154-2 PG 16 WC Reproductive Biology; Toxicology SC Reproductive Biology; Toxicology GA WQ840 UT WOS:A1997WQ84000033 PM 9100315 ER PT J AU Bigelow, LB Cervenak, J Herman, MM Kleinman, JE Torrey, EF AF Bigelow, LB Cervenak, J Herman, MM Kleinman, JE Torrey, EF TI Regional measurement of pH in postmortem brain tissue SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract C1 NIMH,CTR NEUROSCI,CLIN BRAIN DISORDERS BRANCH,WASHINGTON,DC 20032. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAR PY 1997 VL 24 IS 1-2 BP 31 EP 31 DI 10.1016/S0920-9964(97)82085-3 PG 1 WC Psychiatry SC Psychiatry GA WP196 UT WOS:A1997WP19600078 ER PT J AU Noga, JT Hyde, TM Bachus, SE Herman, MM Weinberger, DR Kleinman, JE AF Noga, JT Hyde, TM Bachus, SE Herman, MM Weinberger, DR Kleinman, JE TI Postmortem glutamate receptor binding in the prefrontal cortex of schizophrenics and controls SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract C1 EMORY UNIV,DEPT PSYCHIAT,ATLANTA,GA 30322. NIMH,CLIN BRAIN DISORDERS BRANCH,WASHINGTON,DC. 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 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAR PY 1997 VL 24 IS 1-2 BP 35 EP 35 DI 10.1016/S0920-9964(97)82098-1 PG 1 WC Psychiatry SC Psychiatry GA WP196 UT WOS:A1997WP19600091 ER PT J AU Damadzic, R Goldenson, DA Saunders, RC Krimer, LS Bigelow, LB Herman, MM Kleinman, JE AF Damadzic, R Goldenson, DA Saunders, RC Krimer, LS Bigelow, LB Herman, MM Kleinman, JE TI An immunohistochemical study of astrocytes in the entorhinal cortex in schizophrenia: Absence of significant gliosis SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract C1 NIMH,INTRAMURAL RES PROGRAM,CLIN BRAIN DISORDERS BRANCH,NEUROSCI CTR ST ELIZABETHS,NIH,WASHINGTON,DC 20032. 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 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAR PY 1997 VL 24 IS 1-2 BP 37 EP 37 DI 10.1016/S0920-9964(97)82104-4 PG 1 WC Psychiatry SC Psychiatry GA WP196 UT WOS:A1997WP19600097 ER PT J AU PaltanOrtiz, JD Helmkamp, CE Bigelow, LB Torrey, EF Kleinman, JE Herman, MM AF PaltanOrtiz, JD Helmkamp, CE Bigelow, LB Torrey, EF Kleinman, JE Herman, MM TI An assessment of Purkinje cell placement in the superior cerebellar vermis in mental disease SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract C1 NIMH,ST ELIZABETHS HOSP,CTR NEUROSCI,CLIN BRAIN DISORDERS BRANCH,IRP,NIH,WASHINGTON,DC 20032. 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 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAR PY 1997 VL 24 IS 1-2 BP 40 EP 40 DI 10.1016/S0920-9964(97)82112-3 PG 1 WC Psychiatry SC Psychiatry GA WP196 UT WOS:A1997WP19600105 ER PT J AU Webster, MJ Vawter, M Freed, WJ AF Webster, MJ Vawter, M Freed, WJ TI Thy-1 distribution in human frontal cortex from controls and patients with schizophrenia or bipolar disorder SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract C1 NIMH,ST ELIZABETHS HOSP,CTR NEUROSCI,STANLEY FDN,RES PROGRAM,WASHINGTON,DC 20032. NIMH,ST ELIZABETHS HOSP,CTR NEUROSCI,NEUROPSYCHIAT BRANCH,WASHINGTON,DC 20032. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAR PY 1997 VL 24 IS 1-2 BP 42 EP 42 DI 10.1016/S0920-9964(97)82118-4 PG 1 WC Psychiatry SC Psychiatry GA WP196 UT WOS:A1997WP19600111 ER PT J AU Ingraham, LJ AF Ingraham, LJ TI Characterizing heritable psychopathology among the biological relatives of individuals with schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract C1 NIMH,PSYCHOL & PSYCHOPATHOL LAB,INTRAMURAL RES PROGRAM,BETHESDA,MD 20892. 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 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAR PY 1997 VL 24 IS 1-2 BP 43 EP 43 DI 10.1016/S0920-9964(97)82120-2 PG 1 WC Psychiatry SC Psychiatry GA WP196 UT WOS:A1997WP19600113 ER PT J AU Moldin, SO AF Moldin, SO TI Mapping genes for schizophrenia with discordant sib-pair sampling SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract C1 NIMH,SCHIZOPHRENIA RES BRANCH,NIH,ROCKVILLE,MD 20857. 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 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAR PY 1997 VL 24 IS 1-2 BP 56 EP 57 DI 10.1016/S0920-9964(97)82162-7 PG 2 WC Psychiatry SC Psychiatry GA WP196 UT WOS:A1997WP19600155 ER PT J AU Moldin, SO Wynne, D Shore, D AF Moldin, SO Wynne, D Shore, D TI The NIMH schizophrenia genetics initiative: A new scientific resource SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract C1 NIMH,SCHIZOPHRENIA RES BRANCH,NIH,ROCKVILLE,MD 20857. 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 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAR PY 1997 VL 24 IS 1-2 BP 57 EP 57 DI 10.1016/S0920-9964(97)82163-9 PG 1 WC Psychiatry SC Psychiatry GA WP196 UT WOS:A1997WP19600156 ER PT J AU Paylor, R Pickar, D Crawley, JN AF Paylor, R Pickar, D Crawley, JN TI Characterization of inbred mouse strain differences in startle and the prepulse inhibition model of schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract C1 NIMH,EXPT THERAPEUT BRANCH,BETHESDA,MD. 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 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAR PY 1997 VL 24 IS 1-2 BP 59 EP 59 DI 10.1016/S0920-9964(97)82165-2 PG 1 WC Psychiatry SC Psychiatry GA WP196 UT WOS:A1997WP19600158 ER PT J AU Kolachana, BS Saunders, RC Bachevalier, J Weinberger, DR AF Kolachana, BS Saunders, RC Bachevalier, J Weinberger, DR TI Cortical regulation of subcortical dopamine release in rhesus monkeys with neonatal medial temporal-limbic lesions: Implications for the developmental hypothesis of schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract C1 NIMH,NEUROSCI CTR ST ELIZABETHS,CLIN BRAIN DISORDERS BRANCH,WASHINGTON,DC 20032. 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 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAR PY 1997 VL 24 IS 1-2 BP 78 EP 78 DI 10.1016/S0920-9964(97)82212-8 PG 1 WC Psychiatry SC Psychiatry GA WP196 UT WOS:A1997WP19600205 ER PT J AU Bachus, SE Hyde, TM Herman, MM Kleinman, JE AF Bachus, SE Hyde, TM Herman, MM Kleinman, JE TI Effect of chronic neuroleptic exposure on mRNA for the AMPA-A subunit of the AMPA glutamate receptor in postmortem human basal ganglia SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract C1 NIMH,NEUROSCI CTR ST ELIZABETHS,CLIN BRAIN DISORDERS BRANCH,WASHINGTON,DC 20032. NR 2 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAR PY 1997 VL 24 IS 1-2 BP 85 EP 85 DI 10.1016/S0920-9964(97)82229-3 PG 1 WC Psychiatry SC Psychiatry GA WP196 UT WOS:A1997WP19600222 ER PT J AU Elvevaag, B Duncan, J McKenna, PJ AF Elvevaag, B Duncan, J McKenna, PJ TI Inhibition of dominant response tendencies in schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract C1 NIMH,NEUROSCI CTR ST ELIZABETHS,CLIN BRAIN DISORDERS BRANCH,WASHINGTON,DC 20032. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAR PY 1997 VL 24 IS 1-2 BP 102 EP 102 DI 10.1016/S0920-9964(97)82279-7 PG 1 WC Psychiatry SC Psychiatry GA WP196 UT WOS:A1997WP19600272 ER PT J AU Schooler, C Roberts, B Zahn, T Cohen, R AF Schooler, C Roberts, B Zahn, T Cohen, R TI Ocular, cognitive and social interference in schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract C1 NIMH,NIH,LAB SOCIOENVIRONM STUDIES,BETHESDA,MD 20892. 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 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAR PY 1997 VL 24 IS 1-2 BP 124 EP 124 DI 10.1016/S0920-9964(97)82349-3 PG 1 WC Psychiatry SC Psychiatry GA WP196 UT WOS:A1997WP19600342 ER PT J AU Roberts, B Schooler, C AF Roberts, B Schooler, C TI Effect of stimulus meaningfulness on CPT performance SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract C1 NIMH,LAB SOCIOENVIRONM STUDIES,BETHESDA,MD 20892. 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 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAR PY 1997 VL 24 IS 1-2 BP 136 EP 136 DI 10.1016/S0920-9964(97)82386-9 PG 1 WC Psychiatry SC Psychiatry GA WP196 UT WOS:A1997WP19600379 ER PT J AU Kumra, S Giedd, J Jacobsen, L McKenna, K Frazier, J Gordon, C Lenane, M Hamburger, S Smith, A Rapoport, J AF Kumra, S Giedd, J Jacobsen, L McKenna, K Frazier, J Gordon, C Lenane, M Hamburger, S Smith, A Rapoport, J TI Brain anatomic magnetic resonance imaging in pediatric patients with psychosis NOS SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract C1 NIMH,CHILD PSYCHIAT BRANCH,BETHESDA,MD 20892. RI Giedd, Jay/A-3080-2008; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015 OI Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978 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 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAR PY 1997 VL 24 IS 1-2 BP 149 EP 150 DI 10.1016/S0920-9964(97)82427-9 PG 2 WC Psychiatry SC Psychiatry GA WP196 UT WOS:A1997WP19600420 ER PT J AU Rapoport, JL Giedd, J AlaghbandRad, J Jacobsen, L Kumra, S Lenane, M AF Rapoport, JL Giedd, J AlaghbandRad, J Jacobsen, L Kumra, S Lenane, M TI Accelerated increase brain ventricular volume at 2-year rescan for childhood onset schizophrenics SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract C1 NIMH,CHILD PSYCHIAT BRANCH,BETHESDA,MD 20892. RI Giedd, Jay/A-3080-2008; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015 OI Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978 NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAR PY 1997 VL 24 IS 1-2 BP 154 EP 154 DI 10.1016/S0920-9964(97)82442-5 PG 1 WC Psychiatry SC Psychiatry GA WP196 UT WOS:A1997WP19600435 ER PT J AU Jacobsen, LK Hamburger, SD VanHorn, JD Vaituzis, AC McKenna, K Frazier, JA Gordon, CT Lenane, MC Rapoport, JL Zametkin, AJ AF Jacobsen, LK Hamburger, SD VanHorn, JD Vaituzis, AC McKenna, K Frazier, JA Gordon, CT Lenane, MC Rapoport, JL Zametkin, AJ TI Cerebral glucose metabolism in childhood onset schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract C1 NIMH,CHILD PSYCHIAT BRANCH,BETHESDA,MD 20892. 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 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAR PY 1997 VL 24 IS 1-2 BP 166 EP 167 DI 10.1016/S0920-9964(97)82478-4 PG 2 WC Psychiatry SC Psychiatry GA WP196 UT WOS:A1997WP19600471 ER PT J AU Breier, A Su, TP Saunders, R Carson, RE Kolachana, BS Weisenfeld, N Malhotra, AK Elman, I Eckelman, WC Pickar, D AF Breier, A Su, TP Saunders, R Carson, RE Kolachana, BS Weisenfeld, N Malhotra, AK Elman, I Eckelman, WC Pickar, D TI Assessment of synaptic dopamine concentrations in schizophrenia with PET SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract C1 NIMH,EXPT THERAPEUT BRANCH,NIH,BETHESDA,MD 20892. RI Carson, Richard/H-3250-2011 OI Carson, Richard/0000-0002-9338-7966 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 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAR PY 1997 VL 24 IS 1-2 BP 176 EP 176 DI 10.1016/S0920-9964(97)82506-6 PG 1 WC Psychiatry SC Psychiatry GA WP196 UT WOS:A1997WP19600499 ER PT J AU Elman, I Goldstein, DS Holmes, C Adler, C Pickar, D Breier, A AF Elman, I Goldstein, DS Holmes, C Adler, C Pickar, D Breier, A TI The effects of clozapine on plasma norepinephrine kinetics in schizophrenic patients SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract C1 NIMH,EXPT THERAPEUT BRANCH,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAR PY 1997 VL 24 IS 1-2 BP 214 EP 214 DI 10.1016/S0920-9964(97)82612-6 PG 1 WC Psychiatry SC Psychiatry GA WP196 UT WOS:A1997WP19600605 ER PT J AU Malhotra, AK Breier, A Buchanan, R Goldman, D Pickar, D AF Malhotra, AK Breier, A Buchanan, R Goldman, D Pickar, D TI The NMDA receptor and schizophrenia: From phenotype to genotype SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract C1 NIMH,UNIT PHARMACOGENET,EXPT THERAPEUT BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAR PY 1997 VL 24 IS 1-2 BP 215 EP 215 DI 10.1016/S0920-9964(97)82616-3 PG 1 WC Psychiatry SC Psychiatry GA WP196 UT WOS:A1997WP19600609 ER PT J AU Pickar, D Goldman, D Buchanan, R Breier, A Malhotra, AK AF Pickar, D Goldman, D Buchanan, R Breier, A Malhotra, AK TI Predicting clozapine response: Systematic evaluation of allelic variation in candidate genes SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract C1 NIMH,EXPT THERAPEUT BRANCH,BETHESDA,MD 20892. 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 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAR PY 1997 VL 24 IS 1-2 BP 216 EP 216 DI 10.1016/S0920-9964(97)82620-5 PG 1 WC Psychiatry SC Psychiatry GA WP196 UT WOS:A1997WP19600613 ER PT J AU Torrey, EF Miller, J Rawlings, R Yolken, RH AF Torrey, EF Miller, J Rawlings, R Yolken, RH TI Seasonality of births in schizophrenia and bipolar disorder: A review of the literature SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract C1 NIMH,CTR NEUROSCI,WASHINGTON,DC 20032. NR 0 TC 3 Z9 3 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAR PY 1997 VL 24 IS 1-2 BP 260 EP 260 DI 10.1016/S0920-9964(97)82751-X PG 1 WC Psychiatry SC Psychiatry GA WP196 UT WOS:A1997WP19600744 ER PT J AU Taylor, J Miller, M AF Taylor, J Miller, M TI When timeout works some of the rime: The importance of treatment integrity and functional assessment SO SCHOOL PSYCHOLOGY QUARTERLY LA English DT Article ID SELF-INJURIOUS-BEHAVIOR; RETARDED-CHILDREN; TASK-DIFFICULTY; REINFORCEMENT; DETERMINANTS; ESCAPE AB The empirical effectiveness of timeout to reduce student behavior problems is well-documented. Nonetheless, in some instances, timeout is ineffective. Some of these failures may be attributable to poor treatment integrity i.e. (incorrect, inconsistent, or inadequate treatment implementation). However, timeout sometimes fails even when it is implemented consistently and correctly. In these cases, timeout may be unsuccessful because it does not address the function of student behavior problems. This hypothesis was tested in the present investigation. Results indicated that both treatment integrity and the function of student behavior problems were related to treatment success and failure. Implications concerning the function of student behavior problems, treatment selection, treatment integrity, and treatment efficacy are discussed. C1 NIMH,BETHESDA,MD 20892. RP Taylor, J (reprint author), PRESSLEY RIDGE SCH,530 MARSHALL AVE,PITTSBURGH,PA 15214, USA. NR 34 TC 27 Z9 27 U1 0 U2 0 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 SN 1045-3830 J9 SCHOOL PSYCHOL QUART JI Sch. Psychol. Q. PD SPR PY 1997 VL 12 IS 1 BP 4 EP 22 DI 10.1037/h0088943 PG 19 WC Psychology, Educational SC Psychology GA WW421 UT WOS:A1997WW42100002 ER PT J AU Nelson, RG Meyer, TW Myers, BD Bennett, PH AF Nelson, RG Meyer, TW Myers, BD Bennett, PH TI Clinical and pathological course of renal disease in non-insulin-dependent diabetes mellitus: The Pima Indian experience SO SEMINARS IN NEPHROLOGY LA English DT Article ID GLOMERULAR-FILTRATION RATE; URINARY ALBUMIN EXCRETION; OVERT NEPHROPATHY; BLOOD-PRESSURE; PROGRESSION; PROTEINURIA; DETERMINANTS; PREVALENCE; ONSET; RISK C1 STANFORD UNIV,SCH MED,STANFORD,CA 94305. VA PALO ALTO HEALTHCARE SYST,DEPT MED,STANFORD,CA. STANFORD UNIV,SCH MED,DIV NEPHROL,STANFORD,CA 94305. 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 FU NIDDK NIH HHS [N01-DK-6-2285, N01-DK-7-2291] NR 33 TC 26 Z9 28 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9295 J9 SEMIN NEPHROL JI Semin. Nephrol. PD MAR PY 1997 VL 17 IS 2 BP 124 EP 131 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA WN103 UT WOS:A1997WN10300006 PM 9148378 ER PT J AU Rosa, PA AF Rosa, PA TI Microbiology of Borrelia burgdorferi SO SEMINARS IN NEUROLOGY LA English DT Article DE Borrelia burgdorferi; Lyme disease spirochete; microbiology; growth; taxonomy; structure; genome ID LYME-DISEASE SPIROCHETE; OUTER-SURFACE-PROTEIN; WHITE-FOOTED MICE; RIBOSOMAL-RNA GENES; CIRCULAR-PLASMID; IXODES-DAMMINI; LINEAR CHROMOSOME; PEROMYSCUS-LEUCOPUS; ANTIGENIC VARIATION; CAUSATIVE AGENT AB This article reviews the natural history, taxonomy, physical structure, growth requirements, and molecular structure of Borrelia burgdorferi sensu lato, the causative agent of Lyme disease. These spirochetal bacteria are maintained in nature through an infectious cycle between wild mammals and ticks. Borreliae are fastidious, slow-growing bacteria, found only in association with their arthropod or mammalian hosts in nature, and propagatable in the laboratory in a rich growth medium. The characteristic shape of borreliae is imposed by periplasmic flagella, located beneath the outer membrane and attached to the protoplasmic cylinder. The outer membrane of borreliae contains a number of abundant lipoproteins that are of serodiagnostic utility and currently under consideration as vaccine targets. The borrelial genome is unique in structure, organization, and copy number. Recent experiments demonstrate the feasibility of specific gene inactivation as a means with which to study the biology of borreliae and the pathogenesis of Lyme disease. RP Rosa, PA (reprint author), NIAID,MICROBIAL STRUCT & FUNCT LAB,ROCKY MT LABS,NIH,903 S 4TH ST,HAMILTON,MT 59840, USA. NR 83 TC 10 Z9 10 U1 1 U2 1 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 SN 0271-8235 J9 SEMIN NEUROL JI Semin. Neurol. PD MAR PY 1997 VL 17 IS 1 BP 5 EP 10 DI 10.1055/s-2008-1040906 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA WZ712 UT WOS:A1997WZ71200003 PM 9166953 ER PT J AU Vrhel, MJ Lee, C Unser, M AF Vrhel, MJ Lee, C Unser, M TI Fast continuous wavelet transform: A least-squares formulation SO SIGNAL PROCESSING LA English DT Article DE wavelet transform; approximation theory; B-splines ID REPRESENTATION; ALGORITHMS; DISCRETE AB We introduce a general framework for the efficient computation of the real continuous wavelet transform (CWT) using a filter bank. The method allows arbitrary sampling along the scale axis, and achieves O(N) complexity per scale where N is the length of the signal. Previous algorithms that calculated non-dyadic samples along the scale axis had O(N log(N)) computations per scale. Our approach approximates the analyzing wavelet by its orthogonal projection (least-squares solution) onto a space defined by a compactly supported scaling function. We discuss the theory which uses a duality principle and recursive digital filtering for rapid calculation of the CWT. We derive error bounds on the wavelet approximation and show how to obtain any desired level of accuracy through the use of longer filters. Finally, we present examples of implementation for real symmetric and anti-symmetric wavelets. (C) 1997 Published by Elsevier Science B.V. RP Vrhel, MJ (reprint author), NIH,NATL CTR RES RESOURCES,BIOMED ENGN & INSTRUMENTAT PROGRAM,BLDG 13,ROOM 3N17,BETHESDA,MD 20892, USA. RI Unser, Michael/A-1550-2008 NR 18 TC 4 Z9 5 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-1684 J9 SIGNAL PROCESS JI Signal Process. PD MAR PY 1997 VL 57 IS 2 BP 103 EP 119 DI 10.1016/S0165-1684(96)00189-2 PG 17 WC Engineering, Electrical & Electronic SC Engineering GA XB446 UT WOS:A1997XB44600001 ER PT J AU Hosono, M Kobayashi, H Fujimoto, R Kotoura, Y Tsuboyama, T Matsusue, Y Nakamura, T Itoh, T Konishi, J AF Hosono, M Kobayashi, H Fujimoto, R Kotoura, Y Tsuboyama, T Matsusue, Y Nakamura, T Itoh, T Konishi, J TI Septum-like structures in lipoma and liposarcoma: MR imaging and pathologic correlation SO SKELETAL RADIOLOGY LA English DT Article DE lipoma; liposarcoma; soft tissue tumor; MRI AB Objective. To-investigate the septum-like structures in predominantly lipomatous tumors, by correlating fat-suppressed MR images with histopathologic findings. Design and patients. The MR findings of three cases of well-differentiated liposarcoma (atypical lipoma), one case of lipoma-like component of dedifferentiated liposarcoma. and nine cases of lipoma were analyzed. T1-, T2-, and fat-suppressed T1- weighted images after Gd-DTPA administration were obtained. Surgical specimens from five patients (four with liposarcoma and one with lipoma) were also scanned with a MR unit, and compared with the pathologic findings. Results and conclusions. Enhancement features of lipoma and liposarcoma were well visualized on fat-suppressed T1-weighted images after Gd-DTPA administration. The septum-like structures of liposarcoma are thick and enhanced considerably, while septa of lipoma are thin and enhanced only slightly. Pathologically, the septum-like structures of Liposarcoma contained muscle fibers and the septa of lipoma represented fibrous capsule, Identification of well-enhanced septa in a predominantly lipomatous tumor helps to differentiate malignant tumors horn lipomas. As the septum-like structures of liposarcoma contain a skeletal muscle component the tumor might need more extensive surgical procedures including resection of adjacent muscles. C1 NATL INST HLTH,DEPT NUCL MED,BETHESDA,MD 20892. KYOTO UNIV,FAC MED,DEPT NUCL MED,SAKYO KU,KYOTO 60601,JAPAN. NAGAHAMA CITY HOSP,DEPT ORTHOPAED SURG,SHIGA,JAPAN. KYOTO UNIV,DEPT ORTHOPAED SURG,KYOTO,JAPAN. S KYOTO NATL HOSP,DEPT RADIOL,KYOTO,JAPAN. NR 3 TC 49 Z9 51 U1 1 U2 3 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0364-2348 J9 SKELETAL RADIOL JI Skeletal Radiol. PD MAR PY 1997 VL 26 IS 3 BP 150 EP 154 PG 5 WC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging SC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging GA WQ493 UT WOS:A1997WQ49300003 PM 9108224 ER PT J AU Gift, HC Atchison, KA Dayton, CM AF Gift, HC Atchison, KA Dayton, CM TI Conceptualizing oral health and oral health-related quality of life SO SOCIAL SCIENCE & MEDICINE LA English DT Article DE quality of life; oral health AB This investigation considers oral health from a health-related quality of life perspective using a multidimensional concept representing a combination of impairment, function, perceptions, and/or opportunity. A subset of dentate individuals aged 18 and older from a national probability sample of the U.S. was selected for the reported analysis with data available from personal interviews, self-administered questionnaires, and oral examinations. Impairment was represented by clinically assessed active diseases and sequelae of diseases and self-reported acute symptoms. Other domains are represented by self-reported problems with function, perception of control over oral health, satisfaction with teeth, value attributed to oral health, and opportunity to obtain dental care. Principal components analysis with varimax rotation provided a structure to interpret four factors: accumulated oral neglect, self-perceived symptoms and problems, reparable oral diseases, and oral health values and priorities. Approximately 50% of the variance was explained by these four factors. Factor-based scores, envisioned as an index or summary measure representing the combination of variables identified in each factor, were used to assess potential validity. Whites had lower levels of accumulated oral neglect, fewer symptoms, and less reparable oral disease, but similar oral health values, than non-whites. Level of formal education was associated with each of the four factor-based scores. Age was directly associated with accumulated oral neglect, but the youngest age group had significantly more reparable oral diseases. Individuals with a dental visit in the past two years had considerably less accumulated oral neglect, fewer self-perceived problems, less reparable oral disease, and higher values of oral health than those without a dental visit in the past two years. Ordinary least square regressions were performed on each of the four factor-based scores using eight sociodemographic and economic variables. All four regression models were significant, with only the education variable being significant across all models. These analyses provide no evidence for one unique factor representing oral health. Rather, a conceptual framework for oral health appears to be represented by a set of reasonably independent components, including two groups of clinically assessed oral health, which together more fully represent oral health than any one single variable. Conceptualizing and measuring oral health multidimensionally leads us closer to examining it as part of general health. Copyright (C) 1996 Elsevier Science Ltd C1 UNIV CALIF LOS ANGELES,SANTA MONICA,CA 90402. UNIV MARYLAND,ANNAPOLIS,MD 21401. RP Gift, HC (reprint author), NIH,45 CTR DR,3AN-44D,BETHESDA,MD 20892, USA. NR 24 TC 64 Z9 68 U1 1 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0277-9536 J9 SOC SCI MED JI Soc. Sci. Med. PD MAR PY 1997 VL 44 IS 5 BP 601 EP 608 DI 10.1016/S0277-9536(96)00211-0 PG 8 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA WF205 UT WOS:A1997WF20500006 PM 9032828 ER PT J AU Ambrosio, E Sharpe, LG Pilotte, NS AF Ambrosio, E Sharpe, LG Pilotte, NS TI Regional binding to corticotropin releasing factor receptors in brain of rats exposed to chronic cocaine and cocaine withdrawal SO SYNAPSE LA English DT Article DE I-125-Tyr-oCRF; amygdala; CRF(1) receptors; autoradiography ID NEUROENDOCRINE RESPONSES; NUCLEUS-ACCUMBENS; LEWIS RATS; BEHAVIORAL-RESPONSES; AMYGDALOID COMPLEX; FACTOR ANTAGONIST; SPRAGUE-DAWLEY; STRESS; CRF; MORPHINE AB Cocaine, as does exposure to other physiological stressors, releases brain corticotropin releasing factor (CRF), and this release habituates during the course of repeated cocaine administration in animals. Due to the many signs of anxiety and responses to stress that are produced by cocaine withdrawal in humans, the present study was designed to assess the effects of chronic cocaine and its withdrawal on regional I-125-Tyr-oCRF binding to the CRF(1) receptor in brains of male Lewis rats. Cocaine or saline was intravenously infused for 10 days in a regimen that resembled a self-administration paradigm (1 mg/kg every 12 min for 2 h each day). Tissues were harvested either 15 min after or 10 days after the last cocaine infusion, and the brains were sectioned and prepared for CRF(1) receptor autoradiography. Compared with findings in saline controls, there was a 31% lower level of CRF binding sites in the basolateral nucleus of the amygdala immediately after the last cocaine infusion, but not 10 days later. Neuroendocrine and non-neuroendocrine mechanisms associated with CRF(1) receptors do not appear to contribute to long-term withdrawal effects. (C) 1997 Wiley-Liss, Inc. C1 NIDA, ADDICT RES CTR, DIV INTRAMURAL RES, NEUROSCI LABS, BALTIMORE, MD 21224 USA. NR 44 TC 34 Z9 35 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0887-4476 J9 SYNAPSE JI Synapse PD MAR PY 1997 VL 25 IS 3 BP 272 EP 276 DI 10.1002/(SICI)1098-2396(199703)25:3<272::AID-SYN6>3.0.CO;2-8 PG 5 WC Neurosciences SC Neurosciences & Neurology GA WM014 UT WOS:A1997WM01400006 PM 9068125 ER PT J AU Kolachana, BS Saunders, RC Weinberger, DR AF Kolachana, BS Saunders, RC Weinberger, DR TI In vivo characterization of extracellular GABA release in the caudate nucleus and prefrontal cortex of the rhesus monkey SO SYNAPSE LA English DT Article DE microdialysis; monkey; caudate nucleus; gamma-aminobutyric acid; high potassium; veratridine; tetrodotoxin; nipecotic acid; Ca2+ dependency ID GAMMA-AMINOBUTYRIC-ACID; EXCITATORY AMINO-ACIDS; DOPAMINE RELEASE; IN-VIVO; BRAIN MICRODIALYSIS; INVIVO RELEASE; INTRACEREBRAL MICRODIALYSIS; DORSOLATERAL STRIATUM; EVOKED RELEASE; CONSCIOUS RATS AB Extracellular gamma amino butyric acid (GABA) levels were measured in the caudate nucleus and the prefrontal cortex of the rhesus monkey brain using in vivo microdialysis under isofluorane gas anesthesia. Evoked GABA release was investigated for voltage sensitivity and calcium (Ca2+) dependency. There was a multifold increase in extracellular GABA levels following local perfusion with: (1) high potassium (50 mM, KCl), (2) veratridine (10 mu M), and (3) the GABA releasing agent and uptake blocker, (-) nipecotic acid (1 mM). Release of GABA was significantly reduced when veratridine or (-) nipecotic acid were coinfused in Ca2+-free cerebrospinal fluid (CSF). Coinfusion of nipecotic acid with TTX (10 mu M) also resulted in attenuation of evoked GABA release. These results suggest that GABA levels recovered using in vivo microdialysis, from the caudate nucleus and the prefrontal cortex in the rhesus monkey, derive in significant part from vesicular pools and the exocytotic process is both Ca2+-dependent and voltage-sensitive. (C) 1997 Wiiey-Liss, Inc. C1 NIMH,NEUROSCI CTR ST ELIZABETHS,CLIN BRAIN DISORDERS BRANCH,INTRAMURAL RES PROGRAM,NIH,WASHINGTON,DC 20032. NR 45 TC 6 Z9 6 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0887-4476 J9 SYNAPSE JI Synapse PD MAR PY 1997 VL 25 IS 3 BP 285 EP 292 PG 8 WC Neurosciences SC Neurosciences & Neurology GA WM014 UT WOS:A1997WM01400008 PM 9068127 ER PT J AU Heinz, A Jones, DW Gorey, JG Knable, MB Lee, KS Saunders, RC Weinberger, DR AF Heinz, A Jones, DW Gorey, JG Knable, MB Lee, KS Saunders, RC Weinberger, DR TI Analysis of the metabolites of [I-123] beta-CIT in plasma of human and nonhuman primates SO SYNAPSE LA English DT Article DE 2 beta-carbomethoxy-3 beta-(4-iodophenyl)tropane; metabolism; dopamine transporter; 5-HT transporter; HPLC; SPET; single photon emission computed tomography ID DOPAMINE AB [I-123] beta-CIT is a single photon emission computed tomography (SPECT) radioligand that has been used for in vivo studies of the dopamine and serotonin transporters. Two metabolite peaks of beta-CIT have been observed by high performance liquid chromatography (HPLC), but neither has been chemically identified. One major metabolite is clearly hydrophilic. Previous reports have not agreed on the amount of the second metabolite and the extent to which it may cross the blood-brain barrier. To clarify this controversy, we have studied beta-CIT metabolites using a protein precipitation method and an organic extraction method followed by HPLC separation. Plasma from both human and nonhuman (rhesus) primates was analyzed. Concentrations of the second metabolite were substantially lower in rhesus than in human for nearly equal parent concentrations. Furthermore, in rhesus the second metabolite is partially soluble in the organic solvent ethyl acetate, whereas in human it is essentially insoluble. These observations account for the contradictions in the literature. The hydrophilic nature of the human metabolite renders it unlikely that it crosses the blood-brain barrier in sufficient quantities to interfere with the quantitative assessment of dopamine transporter densities. (C) 1997 Wiley-Liss, Inc. C1 NIMH,NEUROSCI CTR ST ELIZABETHS,CLIN BRAIN DISORDERS BRANCH,INTRAMURAL RES PROGRAM,NIH,WASHINGTON,DC 20032. NR 4 TC 6 Z9 6 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0887-4476 J9 SYNAPSE JI Synapse PD MAR PY 1997 VL 25 IS 3 BP 306 EP 308 DI 10.1002/(SICI)1098-2396(199703)25:3<306::AID-SYN10>3.0.CO;2-U PG 3 WC Neurosciences SC Neurosciences & Neurology GA WM014 UT WOS:A1997WM01400010 PM 9068129 ER PT J AU Boorman, GA Botts, S Bunton, TE Fournie, JW Harshbarger, JC Hawkins, WE Hinton, DE Jokinen, MP Okihiro, MS Wolfe, MJ AF Boorman, GA Botts, S Bunton, TE Fournie, JW Harshbarger, JC Hawkins, WE Hinton, DE Jokinen, MP Okihiro, MS Wolfe, MJ TI Diagnostic criteria for degenerative, inflammatory, proliferative nonneoplastic and neoplastic liver lesions in medaka (Oryzias latipes): Consensus of a national toxicology program pathology working group SO TOXICOLOGIC PATHOLOGY LA English DT Article DE carcinogenesis; bioassay; histopathology fish; alternative species; diethylnitrosamine ID SPONGIOSIS HEPATIS; INDUCED HEPATOCARCINOGENESIS; DIETHYLNITROSAMINE; FISH; RATS; MICE AB Diagnostic criteria are presented for degenerative, inflammatory, nonncoplastic proliferative, and neoplastic lesions in the liver of medaka (Oryzias latipes), a small fish species frequently used in carcinogenesis studies. The criteria are the consensus of a Pathology Working Group (PWG) convened by the National Toxicology Program. The material examined by the PWG was from medaka exposed to N-nihosodiethylamine for 28 days, removed to clean water, and sacrificed 4, 6, or 9 mo after initiation of exposure. Degenerative lesions included hepatocellular intracytoplasmic vacuolation, hepatocellular necrosis, spongiosis hepatis, hepatic cysts, and hepatocellular hyalinization. Inflammatory lesions consisted of granulomas, chronic inflammation, macrophage aggregates, and focal lymphocytic infiltration. Nonneoplastic proliferative lesions comprised foci of cellular alteration (basophilic focus, eosinophilic focus, vacuolated focus, and clear cell focus) and bile duct hyperplasia. Neoplastic lesions included hepatocellular adenoma, hepatocellular carcinoma, cholangioma, and cholangiocarcinoma. Two lesions composed mainly of spindle cells were noted, hemangiopericytoma and spindle cell proliferation. Rather than being an exhaustive treatment of medaka liver lesions, this report draws from the published literature on carcinogen-induced liver lesions in medaka and other fish species and attempts to consolidate lesion criteria into a simplified scheme that might be useful to pathologists and other researchers using medaka lesions for risk assessment or regulatory purposes. RP Boorman, GA (reprint author), NIEHS,NATL TOXICOL PROGRAM,LAB EXPT PATHOL,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 32 TC 87 Z9 94 U1 0 U2 2 PU SOC TOXICOLOGIC PATHOLOGISTS PI LAWRENCE PA 1041 NEW HAMPSHIRE ST PO BOX 368, LAWRENCE, KS 66044 SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD MAR-APR PY 1997 VL 25 IS 2 BP 202 EP 210 PG 9 WC Pathology; Toxicology SC Pathology; Toxicology GA WV024 UT WOS:A1997WV02400010 PM 9125779 ER PT J AU Tennant, R AF Tennant, R TI Identifying carcinogens - A strategy for use of abbreviated models SO TOXICOLOGIC PATHOLOGY LA English DT Editorial Material RP Tennant, R (reprint author), NIEHS,MOL CARCINOGENESIS LAB,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 0 TC 11 Z9 11 U1 0 U2 0 PU SOC TOXICOLOGIC PATHOLOGISTS PI LAWRENCE PA 1041 NEW HAMPSHIRE ST PO BOX 368, LAWRENCE, KS 66044 SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD MAR-APR PY 1997 VL 25 IS 2 BP 240 EP 241 PG 2 WC Pathology; Toxicology SC Pathology; Toxicology GA WV024 UT WOS:A1997WV02400018 PM 9125786 ER PT J AU Cohen, SD Pumford, NR Khairallah, EA Boekelheide, K Pohl, LR Amouzadeh, HR Hinson, JA AF Cohen, SD Pumford, NR Khairallah, EA Boekelheide, K Pohl, LR Amouzadeh, HR Hinson, JA TI Selective protein covalent binding and target organ toxicity SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article; Proceedings Paper CT 34th Annual Meeting of the Society-of-Toxicology CY MAR 05-09, 1995 CL BALTIMORE, MD SP Soc Toxicol ID ANTIINFLAMMATORY DRUG DICLOFENAC; ENDOPLASMIC-RETICULUM ANTIBODIES; 2,5-HEXANEDIONE EXPOSURE ALTERS; HALOTHANE HEPATITIS PATIENTS; SUBCELLULAR LIVER FRACTIONS; ACETAMINOPHEN-TREATED MICE; 56-KDA SELENIUM-BINDING; TUBULE FLUID SECRETION; RAT TESTIS; IMMUNOHISTOCHEMICAL LOCALIZATION AB Protein covalent binding by xenobiotic metabolites has long been associated with target organ toxicity but mechanistic involvement of such binding has not been widely demonstrated, Modern biochemical, molecular, and immunochemical approaches have facilitated identification of specific protein targets of xenobiotic covalent binding, Such studies have revealed that protein covalent binding is not random, but rather selective with respect to the proteins targeted. Selective binding to specific cellular target proteins may better correlate with toxicity than total protein covalent binding. Current research is directed at characterizing and identifying the targeted proteins and clarifying the effect of such binding on their structure, function, and potential roles in target organ toxicity. The approaches employed to detect and identify the targeted proteins are described, Metabolites of acetaminophen, halothane, and 2,5-hexanedione form covalently bound adducts to recently identified protein targets. The selective binding may influence homeostatic or other cellular responses which in turn contribute to drug toxicity, hypersensitivity, or autoimmunity. (C) 1997 Academic Press. C1 UNIV CONNECTICUT,DEPT MOL & CELL BIOL,STORRS,CT 06269. UNIV ARKANSAS MED SCI HOSP,DIV TOXICOL,LITTLE ROCK,AR 72205. BROWN UNIV,DEPT PATHOL & LAB MED,PROVIDENCE,RI 02912. NHLBI,MOL & CELLULAR TOXICOL SECT,NIH,BETHESDA,MD 20892. RP Cohen, SD (reprint author), UNIV CONNECTICUT,DEPT PHARMACEUT SCI,372 FAIRFIELD RD,STORRS,CT 06269, USA. FU NIEHS NIH HHS [R01 ES05033]; NIGMS NIH HHS [1 R01 GM48749, R01 GM31460] NR 97 TC 203 Z9 206 U1 0 U2 10 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD MAR PY 1997 VL 143 IS 1 BP 1 EP 12 DI 10.1006/taap.1996.8074 PG 12 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA WN302 UT WOS:A1997WN30200001 PM 9073586 ER PT J AU Fox, TR McMillen, PJ Maronpot, RR Goldsworthy, TL AF Fox, TR McMillen, PJ Maronpot, RR Goldsworthy, TL TI Genomic instability, as measured by microsatellite alterations, is not associated with liver tumor development in the genetically susceptible B6C3F1 mouse SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article ID H-RAS ONCOGENE; MUTATOR PHENOTYPE; COLON-CANCER; DNA; MUTATIONS; HETEROZYGOSITY; CARCINOGENESIS; PROTOONCOGENE; HOMOLOG AB Certain human heritable forms of colon cancer have characteristically high frequencies of microsatellite alterations, These microsatellite changes are markers of genomic instability and the direct consequence of mutations in genes involved with DNA mismatch repair processes, which are in part responsible for maintaining the sequence integrity of the genome. Given that the B6C3F1 mouse is genetically predisposed to develop liver tumors we were interested in determining whether tumors derived in this strain of mouse may contain alterations in microsatellite sequences. The analysis of 48 tumors at 24 different microsatellite loci revealed that microsatellite alterations were detected in 12 of 48 tumors (25%). Although this frequency is relatively high, 11 of the 12 tumors exhibited only a single alteration and in 10 of those tumors this change was at the same microsatellite locus. Microsatellite alterations were also detected in the DNA isolated from 6 of 22 (27%) normal liver tissues with 4 of the 6 occurring at the same locus where the majority of changes were observed in the tumors. Based on these results, we conclude that the microsatellite alterations present in the mouse liver tumor tissue are most likely the result of spontaneous mutational events. Consequently, the genomic instability operational in a particular type of hereditary human colon cancer does not appear to be operational in the genetically predisposed B6C3F1 mouse liver. In addition, we demonstrated that the activation of the H-ras gene, which causes some forms of genetic instability in vitro, does not contribute to genetic instability within liver tumors as measured by microsatellite alterations. (C) 1997 Academic Press. C1 NIEHS,RES TRIANGLE PK,NC 27709. RP Fox, TR (reprint author), CHEM IND INST TOXICOL,6 DAVIS DR,POB 12137,RES TRIANGLE PK,NC 27709, USA. NR 26 TC 2 Z9 2 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD MAR PY 1997 VL 143 IS 1 BP 167 EP 172 DI 10.1006/taap.1996.8065 PG 6 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA WN302 UT WOS:A1997WN30200019 PM 9073604 ER PT J AU Gaido, KW Leonard, LS Lovell, S Gould, JC Babai, D Portier, CJ McDonnell, DP AF Gaido, KW Leonard, LS Lovell, S Gould, JC Babai, D Portier, CJ McDonnell, DP TI Evaluation of chemicals with endocrine modulating activity in a yeast-based steroid hormone receptor gene transcription assay SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article ID HUMAN ESTROGEN-RECEPTOR; SACCHAROMYCES-CEREVISIAE; ENVIRONMENTAL ESTROGENS; BREAST-CANCER; METHOXYCHLOR; EXPRESSION; PROGESTERONE; CELLS; RAT; DDT AB There is a concern that chemicals in our environment are affecting human health by disrupting normal endocrine function. Much of the concern has focused on chemicals that can interact directly with steroid hormone receptors. We have used a yeast-based assay to assess chemical interactions with the estrogen, androgen, and progesterone receptors. The yeast transformants used in this study contained the human estrogen, androgen, or progesterone receptor along with the appropriate steroid responsive elements upstream of the P-galactosidase reporter gene. Chemicals were added to yeast cultures in doses ranging from 10(-12) to 10(-4) M and following incubation, the yeasts were then lysed and assayed for beta-galactosidase activity. Diethylstilbesterol and 17-beta estradiol were most active in the estrogen receptor assay, followed by the phytoestrogen, coumestrol. p-Nonylphenol and bisphenol A were approximately 5000- and 15,000-fold less active, respectively, than estradiol. Methoxychlor, DDT and its metabolites, o,p'-DDD, and o,p'-DDE ranged in potency from 5 to 24 x 10(6) less potent than estradiol. Testosterone and dihydrotestosterone were most potent in the androgen receptor assay, followed by estradiol and progesterone. p,p'-DDE was approximately 10(6)-fold less potent than testosterone. None of the industrial chemicals tested interacted with the progesterone receptor. These data demonstrate the utility of using yeast-based receptor assays for detecting chemical interaction with steroid receptors and these assays should serve as a useful component of an in vitro-in vivo strategy to assess the effects of chemicals on endocrine function. (C) 1997 Academic Press. C1 NIEHS, RES TRIANGLE PK, NC 27709 USA. DUKE UNIV, MED CTR, DEPT PHARMACOL, DURHAM, NC 27710 USA. RP Gaido, KW (reprint author), CHEM IND INST TOXICOL, POB 12137, RES TRIANGLE PK, NC 27709 USA. RI Portier, Christopher/A-3160-2010 OI Portier, Christopher/0000-0002-0954-0279 NR 55 TC 549 Z9 581 U1 6 U2 56 PU ACADEMIC PRESS INC ELSEVIER SCIENCE 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 MAR PY 1997 VL 143 IS 1 BP 205 EP 212 DI 10.1006/taap.1996.8069 PG 8 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA WN302 UT WOS:A1997WN30200024 PM 9073609 ER PT J AU Hengen, PN AF Hengen, PN TI Methods and reagents - Reducing background colonies with positive selection vectors SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Editorial Material ID CELL-DIVISION; DNA AB Methods and reagents is a unique monthly column that highlights current discussions in the newsgroup bionet.molbio.methds-reagnts, available on the Internet. This month's column discusses the pros and cons of eliminating unwanted background colonies by using the positive selection vector pZErO. For details on how to partake in the newsgroup, see the accompanying box. RP Hengen, PN (reprint author), NCI,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702, USA. NR 6 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0968-0004 J9 TRENDS BIOCHEM SCI JI Trends Biochem.Sci. PD MAR PY 1997 VL 22 IS 3 BP 105 EP 106 DI 10.1016/S0968-0004(97)01009-8 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WM129 UT WOS:A1997WM12900009 PM 9066262 ER PT J AU Shearer, GM Clerici, M AF Shearer, GM Clerici, M TI Vaccine strategies: Selective elicitation of cellular or humoral immunity? SO TRENDS IN BIOTECHNOLOGY LA English DT Article ID T-HELPER CELL; HIV; INFECTION; TH1; IMMUNIZATION; INDUCTION AB The discovery of immunoregulatory cytokines and the fact that they modulate the cellular and humoral arms of the immune system, generally in opposing directions raises fundamental questions concerning vaccine development. Because antibiotic-resistant infectious organisms are appearing at an increasingly rapid rate, more emphasis will need to be placed on prevention of infection/disease via immunization and less on post-infection antibiotics. To accomplish this task effectively, immune regulation should be integrated into vaccine design. Here we consider the opposing potentials of cytokine-regulated cellular and humoral immunity, and question whether the 'best of both worlds' is possible or desirable. C1 UNIV MILAN,CATTEDRA IMMUNOL,MILAN,ITALY. RP Shearer, GM (reprint author), NCI,EXPT IMMUNOL BRANCH,NIH,BLDG 10,BETHESDA,MD 20892, USA. NR 19 TC 14 Z9 18 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0167-7799 J9 TRENDS BIOTECHNOL JI Trends Biotechnol. PD MAR PY 1997 VL 15 IS 3 BP 106 EP 109 DI 10.1016/S0167-7799(97)01011-1 PG 4 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA WM680 UT WOS:A1997WM68000007 PM 9080716 ER PT J AU Marks, MS Ohno, H Kirchhausen, T Bonifacino, SJ AF Marks, MS Ohno, H Kirchhausen, T Bonifacino, SJ TI Protein sorting by tyrosine-based signals: Adapting to the Ys and wherefores SO TRENDS IN CELL BIOLOGY LA English DT Article ID LYSOSOMAL ACID-PHOSPHATASE; TRANS-GOLGI NETWORK; ENDOCYTIC PATHWAY; CYTOPLASMIC TAIL; PLASMA-MEMBRANE; CELL-SURFACE; COATED VESICLES; ASIALOGLYCOPROTEIN RECEPTOR; INTERNALIZATION SIGNAL; INVITRO BINDING AB The endocytic and secretory pathways of eukaryotic cells consist of an away of membrane-bound compartments, each of which contains a characteristic cohort of transmembrane proteins. Understanding how these proteins are targeted to and maintained within their appropriate compartments will be crucial for unravelling the mysteries of organelle biogenesis and function. A common event in the sorting of many transmembrane proteins is the interaction between a sorting signal in the cytosolic domain of the targeted protein and a component of an organellar protein coat. Here, we summarize recent findings on the mechanism of sorting by one type of signal, characterized by the presence of a critical tyrosine (Y) residue, and attempt to integrate these findings into a hypothetical model for protein sorting in the endocytic and late (post-Golgi) secretory pathways. C1 NICHHD,CELL BIOL & METAB BRANCH,NIH,BETHESDA,MD 20892. HARVARD UNIV,SCH MED,DEPT CELL BIOL,BOSTON,MA 02115. CTR BLOOD RES,BOSTON,MA 02115. RP Marks, MS (reprint author), UNIV PENN,SCH MED,DEPT PATHOL & LAB MED,PHILADELPHIA,PA 19104, USA. RI Ohno, Hiroshi/L-7899-2014; OI Ohno, Hiroshi/0000-0001-8776-9661; Marks, Michael/0000-0001-7435-7262; Bonifacino, Juan S./0000-0002-5673-6370 NR 48 TC 268 Z9 269 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0962-8924 J9 TRENDS CELL BIOL JI Trends Cell Biol. PD MAR PY 1997 VL 7 IS 3 BP 124 EP 128 DI 10.1016/S0962-8924(96)10057-X PG 5 WC Cell Biology SC Cell Biology GA WK360 UT WOS:A1997WK36000010 PM 17708922 ER PT J AU Lopez, JV Stephens, JC OBrien, SJ AF Lopez, JV Stephens, JC OBrien, SJ TI The long and short of nuclear mitochondrial DNA (Numt) lineages SO TRENDS IN ECOLOGY & EVOLUTION LA English DT Letter C1 NCI,LAG GEN DIVERS,FREDERICK,MD 21702. RP Lopez, JV (reprint author), SMITHSONIAN TROP RES INST,NAOS MARINE LAB,UNIT 0948,APO,AA 34002, USA. RI Lopez, Jose/F-8809-2011 OI Lopez, Jose/0000-0002-1637-4125 NR 11 TC 3 Z9 3 U1 2 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0169-5347 J9 TRENDS ECOL EVOL JI Trends Ecol. Evol. PD MAR PY 1997 VL 12 IS 3 BP 114 EP 114 DI 10.1016/S0169-5347(97)84925-7 PG 1 WC Ecology; Evolutionary Biology; Genetics & Heredity SC Environmental Sciences & Ecology; Evolutionary Biology; Genetics & Heredity GA WJ600 UT WOS:A1997WJ60000017 PM 21238001 ER PT J AU Fredholm, BB Abbracchio, MP Burnstock, G Dubyak, GR Harden, TK Jacobson, KA Schwabe, U Williams, M AF Fredholm, BB Abbracchio, MP Burnstock, G Dubyak, GR Harden, TK Jacobson, KA Schwabe, U Williams, M TI Towards a revised nomenclature for P1 and P2 receptors SO TRENDS IN PHARMACOLOGICAL SCIENCES LA English DT Article ID AGONIST H-3 CGS-21680; ATP RECEPTOR; NUCLEOTIDE RECEPTOR; ADENOSINE RECEPTOR; SENSORY NEURONS; RAT-BRAIN; CLONING; PURINOCEPTORS; EXPRESSION; BINDING C1 UNIV MILAN, INST PHARMACOL SCI, I-20133 MILAN, ITALY. UCL, DEPT ANAT & DEV BIOL, LONDON WC1 6BT, ENGLAND. CASE WESTERN RESERVE UNIV, SCH MED, DEPT PHYSIOL & BIOPHYS, CLEVELAND, OH 44106 USA. UNIV N CAROLINA, SCH MED, DEPT PHARMACOL, CHAPEL HILL, NC 27599 USA. NIH, MOL RECOGNIT SECT, BETHESDA, MD 20892 USA. UNIV HEIDELBERG, INST PHARMAKOL, D-69120 HEIDELBERG, GERMANY. ABBOTT LABS, NEUROSCI RES, ABBOTT PK, IL 60064 USA. RP Fredholm, BB (reprint author), KAROLINSKA INST, DEPT PHYSIOL & PHARMACOL, S-17177 STOCKHOLM, SWEDEN. RI Jacobson, Kenneth/A-1530-2009; Abbracchio, Maria Pia/B-9342-2014 OI Jacobson, Kenneth/0000-0001-8104-1493; Abbracchio, Maria Pia/0000-0002-7833-3388 FU Intramural NIH HHS [Z01 DK031116-20, Z99 DK999999] NR 49 TC 308 Z9 311 U1 0 U2 8 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0165-6147 J9 TRENDS PHARMACOL SCI JI Trends Pharmacol. Sci. PD MAR PY 1997 VL 18 IS 3 BP 79 EP 82 DI 10.1016/S0165-6147(96)01038-3 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA WU150 UT WOS:A1997WU15000005 PM 9133776 ER PT J AU Carter, HB Partin, AW Luderer, AA Metter, EJ Landis, P Chan, DW Fozard, JL Pearson, JD AF Carter, HB Partin, AW Luderer, AA Metter, EJ Landis, P Chan, DW Fozard, JL Pearson, JD TI Percentage of free prostate-specific antigen in sera predicts aggressiveness of prostate cancer a decade before diagnosis SO UROLOGY LA English DT Article ID ALPHA-1-ANTICHYMOTRYPSIN; COMPLEX; ALPHA(1)-ANTICHYMOTRYPSIN; ASSAY; CELLS AB Objectives. To evaluate serial measurements of free and total prostate-specific antigen (PSA) as a predictor of prostate cancer aggressiveness. Methods. Twenty men diagnosed with adenocarcinoma of the prostate in the pre-PSA era had serum PSA measurements made on multiple stored frozen sera samples available for up to 18 years prior to diagnosis. Subjects were categorized as having aggressive cancer (n = 12) based on the presence of clinical Stage T3, or nodal or bone metastases (N+, M+), or pathologic positive-margin disease, or a Gleason score of 7 or greater; nonaggressive cancer (n = 8) was identified by the absence of these criteria. Results. There was no statistically significant difference in free PSA levels among men with aggressive and nonaggressive prostate cancers from 0 to 15 years before diagnosis. Total PSA levels were significantly different between the groups by 5 years before diagnosis (P = 0.04). At a time when total PSA levels were not different between groups (10 years before diagnosis), there was a statistically significant difference in the percentage of free PSA between aggressive and nonaggressive cancers (P = 0.008). Among 14 men who had sera available for analysis at 10 years before diagnosis, all 8 men with aggressive cancers had a percent free PSA of 0.14 or less; this compares with only 2 of 6 men (33%) with nonaggressive cancer. Conclusions. These data suggest that the percentage of free PSA in sera is predictive of tumor behavior at a time when total PSA levels provide no information on tumor aggressiveness. Evaluation of the percentage of free serum PSA may be helpful in making the decision between expectant management and treatment for those men who are diagnosed with early prostate cancers by PSA testing. (C) 1997, Elsevier Science Inc. C1 JOHNS HOPKINS UNIV,JOHNS HOPKINS HOSP,SCH MED,JAMES BUCHANAN BRADY UROL INST,DEPT PATHOL,BALTIMORE,MD 21287. DIANON SYST INC,DEPT RES & DEV,STRATFORD,CT. NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. MERCK SHARP & DOHME RES LABS,DEPT EPIDEMIOL,BLUE BELL,PA. RP Carter, HB (reprint author), JOHNS HOPKINS UNIV,JOHNS HOPKINS HOSP,SCH MED,JAMES BUCHANAN BRADY UROL INST,DEPT UROL,BALTIMORE,MD 21287, USA. RI Fozard, James Leonard/B-3660-2009 NR 17 TC 63 Z9 63 U1 0 U2 0 PU CAHNERS PUBL CO PI NEW YORK PA 249 WEST 17 STREET, NEW YORK, NY 10011 SN 0090-4295 J9 UROLOGY JI UROLOGY PD MAR PY 1997 VL 49 IS 3 BP 379 EP 384 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA WN960 UT WOS:A1997WN96000015 PM 9123702 ER PT J AU Carroll, MW Overwijk, WW Chamberlain, RS Rosenberg, SA Moss, B Restifo, NP AF Carroll, MW Overwijk, WW Chamberlain, RS Rosenberg, SA Moss, B Restifo, NP TI Highly attenuated modified vaccinia virus Ankara (MVA) as an effective recombinant vector: A murine tumor model SO VACCINE LA English DT Article DE modified vaccinia virus Ankara (MVA); vaccinia virus; cancer immunotherapy ID BROAD SPECIES-SPECIFICITY; HERPES-SIMPLEX VIRUS; T-CELL MEMORY; THYMIDINE KINASE; ANTIGEN; EXPRESSION; IMMUNIZATION; GENES; DNA; IMMUNOTHERAPY AB Modified vaccinia virus Ankara (MVA), a highly attenuated strain of vaccinia virus (VV) that is unable to replicate in most mammalian cells, was evaluated as an expression vector for a model turner associated antigen (TAA) and as a potential anti-cancer vaccine. We employed an experimental murine model in which an adenocarcinoma turner line, CT26.CL25, was stably transfected with a model TAA, beta-galactosidase (beta-gal). Mice injected intramuscularly with a recombinant MVA (rMVA) expressing beta-gal (MVA-LZ), were protected from a lethal intravenous (i.v.) challenge with CT26.CL25. In addition, splenocytes from mice primed with MVA-LZ were therapeutically effective upon adoptive transfer to mice bearing pulmonary metastases of the CT26.CL25 tumor established 3 days earlier. Most importantly, i.v. inoculation with MVA-LZ resulted in significantly prolonged survival of mice bearing three day old pulmonary metastases. This prolonged survival compared favorably to mice treated with a replication competent recombinant VV expressing beta-gal. These findings indicate that rMVA is an efficacious alternative to the more commonly used replication competent VV for the development of new recombinant anti-cancer vaccines. Published by Elsevier Science Ltd. C1 NCI, SURG BRANCH, NATL INST HLTH, BETHESDA, MD 20892 USA. NIAID, VIRAL DIS LAB, NATL INST HLTH, BETHESDA, MD 20892 USA. RI Restifo, Nicholas/A-5713-2008; OI Restifo, Nicholas P./0000-0003-4229-4580 FU Intramural NIH HHS [Z01 BC010763-01, Z99 CA999999] NR 48 TC 85 Z9 87 U1 0 U2 2 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 MAR PY 1997 VL 15 IS 4 BP 387 EP 394 DI 10.1016/S0264-410X(96)00195-8 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA WT721 UT WOS:A1997WT72100009 PM 9141209 ER PT J AU delGuercio, MF Alexander, J Kubo, RT Arrhenius, T Maewal, A Appella, E Hoffman, SL Jones, T Valmori, D Sakaguchi, K Grey, HM Sette, A AF delGuercio, MF Alexander, J Kubo, RT Arrhenius, T Maewal, A Appella, E Hoffman, SL Jones, T Valmori, D Sakaguchi, K Grey, HM Sette, A TI Potent immunogenic short linear peptide constructs composed of B cell epitopes and Pan DR T Helper Epitopes (PADRE) for antibody responses in vivo SO VACCINE LA English DT Article DE short linear peptide; peptide based vaccine; humoral immunity; malaria; PAN DR T helper epitopes ID CIRCUMSPOROZOITE PROTEIN; PLASMODIUM-FALCIPARUM; MONOCLONAL-ANTIBODIES; SURFACE-ANTIGEN; MALARIA VACCINE; LIPID-A; SPOROZOITE; INDUCTION; RESTRICTION; INFECTION AB Induction of humoral immune responses against protein antigen requires that two independent signals be delivered to B cells. It is currently assumed that simple monovalent synthetic peptides would not be effective immunogens for antibody responses because they would not be anticipated to effectively generate the necessary signals unless conjugated to a complex carrier system. In this study, the immunogenicity;of short linear peptide constructs comprising Plasmodium vivax B cell epitopes (PVB) and non-natural Pan-DR T helper cell epitopes (PADRE) was assessed in mice and compared to other types of antigen constructs. The 33-residue PADRE-PVB linear constructs were highly immunogenic and induced responses comparable to those obtained with the multiple antigen peptides (MAP) constructs, both in terms of absolute titers and quality of antibody responses. The anti-PVB antibody responses were of long duration, composed mostly of IgG and reactive with intact sporozoites. The PADRE-PVB constructs were immunogenic when formulated in adjuvants such as Alum and Montanide ISA 51 underlining the relevance of these findings for vaccine development. (C) 1997 Elsevier Science Ltd. C1 NCI,CELL BIOL LAB,BETHESDA,MD 20892. USN,MED RES INST,MALARIA PROGRAM,ROCKVILLE,MD 20852. LA JOLLA INST ALLERGY & IMMUNOL,LA JOLLA,CA 92037. RP delGuercio, MF (reprint author), CYTEL CORP,3525 JOHN HOPKINS COURT,SAN DIEGO,CA 92121, USA. RI Valmori, Danila/K-2439-2015 FU NIAID NIH HHS [N01-AI-45241] NR 37 TC 67 Z9 68 U1 1 U2 13 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0264-410X J9 VACCINE JI Vaccine PD MAR PY 1997 VL 15 IS 4 BP 441 EP 448 DI 10.1016/S0264-410X(97)00186-2 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA WT721 UT WOS:A1997WT72100016 PM 9141216 ER PT J AU Snider, TG Hoyt, PG Jenny, BF Coats, KSC Luther, DG Storts, RW Battles, JK Gonda, MA AF Snider, TG Hoyt, PG Jenny, BF Coats, KSC Luther, DG Storts, RW Battles, JK Gonda, MA TI Natural and experimental bovine immunodeficiency virus infection in cattle SO VETERINARY CLINICS OF NORTH AMERICA-FOOD ANIMAL PRACTICE LA English DT Article ID ARTHRITIS-ENCEPHALITIS VIRUS; LONG TERMINAL REPEAT; MULTIPLE RETROVIRAL INFECTIONS; BIOLOGICALLY-ACTIVE PROVIRUSES; POLYMERASE CHAIN-REACTION; MISSISSIPPI DAIRY-CATTLE; LEUKEMIA-VIRUS; CAPRINE ARTHRITIS; MANAGEMENT-PRACTICES; ANEMIA VIRUS AB The principal diseases associated with bovine immunodeficiency virus (BTV) infection in a production dairy were bacterial infections. The infections were associated with histologic evidence of compromise of the immune system. The disease were most apparent after parturition and during early lactation. Two hundred twenty-seven different diseases were identified in 89 cows between 1989 and 1995. Fifty-two diseases were identified in 19 cows between 1995 and 1996. The primary lesions were encephalitis and lymphoid tissue hyperplasia followed by lymphoid tissue, exhaustion, and laminitis. Weight loss, decreased milk production, and reproductive inefficiency were secondary to the primary lesions. Many cows responded poorly to therapy. Epidemiologic and economic research are needed to clarify the association between BIV and bovine diseases and the economic impact of the infection in beef and dairy production units. C1 LOUISIANA STATE UNIV,CTR AGR,LOUISIANA AGR EXPT STN,DEPT DAIRY SCI,BATON ROUGE,LA 70803. MISSISSIPPI STATE UNIV,DEPT SCI BIOL,MISSISSAUGA,ON,CANADA. TEXAS A&M UNIV,COLL VET MED,TEXAS VET MED CTR,DEPT PATHOBIOL,COLLEGE STN,TX 77843. NCI,FREDERICK CANC RES & DEV CTR,APPL GENET SECT,LAB CELL & MOL STRUCT,SAIC FREDERICK,FREDERICK,MD. GENOVO INC,DISCOVERY RES,PHILADELPHIA,PA. RP Snider, TG (reprint author), LOUISIANA STATE UNIV & A&M COLL,SCH VET MED,DEPT VET PATHOL,S STADIUM RD,BATON ROUGE,LA 70803, USA. NR 94 TC 22 Z9 22 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0749-0720 J9 VET CLIN N AM-FOOD A JI Vet. Clin. N. Am.-Food Anim. Pract. PD MAR PY 1997 VL 13 IS 1 BP 151 EP & PG 27 WC Veterinary Sciences SC Veterinary Sciences GA WM534 UT WOS:A1997WM53400012 PM 9071752 ER PT J AU Jakowlew, SB Mathias, A Lillehoj, HS AF Jakowlew, SB Mathias, A Lillehoj, HS TI Transforming growth factor-beta isoforms in the developing chicken intestine and spleen: Increase in transforming growth factor-beta 4 with coccidia infection SO VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY LA English DT Article DE TGF-beta; expression; development; chicken; intestine; spleen; coccidia ID DEOXYRIBONUCLEIC-ACID CLONING; MESSENGER RIBONUCLEIC-ACID; EMBRYO CHONDROCYTES; TGF-BETA; INTRAEPITHELIAL LYMPHOCYTES; EXPRESSION PATTERNS; ADULT TISSUES; MOUSE EMBRYO; RNA; CELLS AB Expression of transforming growth factor-betas 2, 3 and 4 (TGF-beta) in the developing chicken intestine and spleen was investigated using specific cDNA probes and antibodies for the different TGF-beta isoforms, Coordinate expression of the mRNAs for TGF-beta s 2, 3 and 4 was detected in the embryonic intestine by 8 days, with maximal expression of the mRNAs for TGF-beta s 2 and 4 occurring at 12 and 19 days, respectively, while expression of TGF-beta 3 mRNA remained constant during this time. While specific antibodies for TGF-beta s 2, 3 and 4 could detect only weak immunohistochemical staining of the intestinal epithelium in 4-, 12- and 16-day-old embryos, intense staining for TGF-beta s 2, 3 and 4 was detected in the tips of the intestinal villi of 19-day-old embryos, In the spleen, expression of the mRNAs for TGF-beta s 2 and 3 increased in the newly hatched chick compared with the embryo and then decreased in the adult to levels that were lower than in the embryo; expression of TGF-beta 4 mRNA increased progressively with developmental age, with expression in the adult spleen being significantly higher than in the embryonic and hatchling spleen, Immunohistochemical staining of spleens showed a selective increase in the level of reactive TGF-beta 4 with increasing developmental age, while staining for TGF-beta s 2 and 3 was constant during development. After infection of 1-month-old chickens with coccidian parasite, expression of TGF-beta 4 mRNAs increased 5-8-fold in intestinal intra-epithelial lymphocytes and 2.5-fold in spleen cells, while expression of the mRNAs for TGF-beta s 2 and 3 remained constant in these cells. The results of this study suggest that TGF-beta may play a role in development of the intestine and spleen in the chicken and that TGF-beta 4 in particular increases after infection of coccidia in the chicken. (C) Elsevier Science B.V. C1 USDA,PROTOZOAN DIS LAB,INST LIVESTOCK & POULTRY SCI,BELTSVILLE AGR RES CTR,BELTSVILLE,MD 20705. RP Jakowlew, SB (reprint author), NCI,BIOMARKERS & PREVENT RES BRANCH,9610 MED CTR DR,SUITE C300,ROCKVILLE,MD 20850, USA. NR 58 TC 30 Z9 31 U1 0 U2 4 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 MAR PY 1997 VL 55 IS 4 BP 321 EP 339 DI 10.1016/S0165-2427(96)05628-0 PG 19 WC Immunology; Veterinary Sciences SC Immunology; Veterinary Sciences GA WY051 UT WOS:A1997WY05100007 PM 9151404 ER PT J AU Simmons, BR Lush, RM Figg, WD AF Simmons, BR Lush, RM Figg, WD TI A reversed-phase high performance liquid chromatography method using solid phase extraction to quantitate thalidomide in human serum SO ANALYTICA CHIMICA ACTA LA English DT Article DE thalidomide; high performance liquid chromatography; serum; assay; chromatography ID PLASMA AB Thalidomide, a drug developed in the mid 1950s for sedation and used in the treatment of leprosy for several years, has recently been shown to have anti-angiogenic activity in the rabbit cornea micropocket model. Phase II clinical trials have been initiated in several tumor types, including prostate, brain, breast, and Kaposi's sarcoma. Thus, we developed a high performance liquid chromatography (HPLC) assay to monitor thalidomide serum concentrations. A Hewlett-Packard 1090 Series II Liquid Chromatograph equipped with a photodiode-array detector was used for the chromatographic analysis. A Waters Nova-Pak C-18 (3.9x300 mm) column was used. Thalidomide and phenacetin (internal standard) were detected at UV wavelengths of 220 and 248 nm, respectively, with a run time of 16 min. A gradient mobile phase of water, acetonitrile, and a 0.5 M NaH2PO4 buffer (pH 3.0) was run at a flow rate of 1 mi min(-1). Thalidomide was isolated from serum by solid phase extraction. 10% H2SO4 (7.5 mu l) was added to the serum to halt degradation. Standard curves were prepared between 50 and 10 000 ng ml(-1) and linearity was demonstrated in this range of concentrations (r(2)=0.9996+/-0.0011) (n=6). Intra-assay and inter-assay imprecision was <4.0% with an error of accuracy of <7.0%. In conclusion, the assay was shown to be reproducible and acceptable for clinical monitoring of thalidomide concentrations in human serum. C1 NCI,CLIN PHARMACOL BRANCH,DIV CLIN SCI,NIH,BETHESDA,MD 20892. RI Figg Sr, William/M-2411-2016 NR 12 TC 20 Z9 20 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0003-2670 J9 ANAL CHIM ACTA JI Anal. Chim. Acta PD FEB 28 PY 1997 VL 339 IS 1-2 BP 91 EP 97 DI 10.1016/S0003-2670(96)00494-1 PG 7 WC Chemistry, Analytical SC Chemistry GA WL898 UT WOS:A1997WL89800007 ER PT J AU Dawson, DA Ruetzler, CA Hallenbeck, JM AF Dawson, DA Ruetzler, CA Hallenbeck, JM TI Temporal impairment of microcirculatory perfusion following focal cerebral ischemia in the spontaneously hypertensive rat SO BRAIN RESEARCH LA English DT Article DE focal cerebral ischemia; microcirculation; perfusion; spontaneously hypertensive rat; fluorescence microscopy; Evans blue; phenylephrine; hypertension ID ARTERY OCCLUSION; CAPILLARY NETWORK; BLOOD-FLOW; FOREBRAIN ISCHEMIA; NO-REFLOW; BRAIN; REPERFUSION; HYPOTENSION; BABOONS; DAMAGE AB Microcirculatory impairments have theoretically been proposed as a potential factor in the development of ischemic injury, but few attempts have been made to directly assess microvascular patency following stroke. To address this issue we investigated the temporal changes in microvascular perfusion induced by permanent focal ischemia. Halothane-anesthetized spontaneously hypertensive rats were subjected to middle cerebral artery occlusion (MCAO) of 5 min to 4 h duration. Two fluorescent tracers (FITC-dextran and Evans blue) were then sequentially administered i.v. and allowed to circulate for 10 and 5 s respectively. Tissue sections were examined by fluorescent microscopy, and the mean number of perfused microvessels/mm(2) calculated for cortical areas representing non-ischemic (Region A), perifocal/penumbral (Region B) and core ischemic (Region C) regions. For sham-operated controls, virtually all microvessels perfused with tracer within 5 s. In contrast MCAO induced significant reductions in the number of perfused microvessels in Regions B and C. The most marked impairments in perfusion were observed in core MCA territory (e.g. 2-10% of control values for 5 s circulation period) while, initially, the deficit was less severe in penumbral cortex. However, a secondary perfusion impairment developed over time in the perifocal/penumbral region, so that the deficit was greater 4 h after MCAO than at earlier time points (e.g. 72%, 71% and 22% of control value for 0.5, 1 and 4 h MCAO respectively; 10 s circulation period). In conclusion, MCAO induced severe impairments in microcirculatory perfusion within the core ischemic region, and to a lesser extent in the penumbra. However, the development of a more severe perfusion deficit in the penumbra within 4 h of MCAO supports the hypothesis that microcirculatory failure in this region contributes to its recruitment to the ischemic infarct. (C) 1997 Elsevier Science B.V. RP Dawson, DA (reprint author), NINCDS,NIH,STROKE BRANCH,BLDG 36-4A03,36 CONVENT DR MSC 4128,BETHESDA,MD 20892, USA. NR 33 TC 32 Z9 33 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 FEB 28 PY 1997 VL 749 IS 2 BP 200 EP 208 DI 10.1016/S0006-8993(96)01166-3 PG 9 WC Neurosciences SC Neurosciences & Neurology GA WM838 UT WOS:A1997WM83800003 PM 9138719 ER PT J AU Ginns, SN Nielsen, S Knepper, MA Kishore, BK AF Ginns, SN Nielsen, S Knepper, MA Kishore, BK TI Immunolocalization of extracellular nucleotide receptor (P2u) in renal inner medulla. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI,NIH,BETHESDA,MD 20892. AARHUS UNIV,AARHUS,DENMARK. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB 28 PY 1997 VL 11 IS 3 BP 50 EP 50 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA WL530 UT WOS:A1997WL53000052 ER PT J AU Hu, N Smith, BR Lai, CT Keller, BB AF Hu, N Smith, BR Lai, CT Keller, BB TI Dependence of aortic arch morphogenesis on intracardiac blood flow in the chick embryo. SO FASEB JOURNAL LA English DT Meeting Abstract C1 UNIV ROCHESTER,NIH,SCOR PED CARDIOVASC DIS,ROCHESTER,NY 14642. DUKE UNIV,MED CTR,DURHAM,NC 27710. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB 28 PY 1997 VL 11 IS 3 BP 89 EP 89 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA WL530 UT WOS:A1997WL53000091 ER PT J AU Damay, E Morio, D Lottenberg, R Noguchi, C Schechter, A TranSonTay, R AF Damay, E Morio, D Lottenberg, R Noguchi, C Schechter, A TranSonTay, R TI Effects of deoxygenation on the rheology of sickle red blood cell suspensions and sickle hemoglobin solutions. SO FASEB JOURNAL LA English DT Meeting Abstract C1 UNIV FLORIDA,GAINESVILLE,FL 32611. NIDDK,BIOL CHEM LAB,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB 28 PY 1997 VL 11 IS 3 BP 107 EP 107 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA WL530 UT WOS:A1997WL53000109 ER PT J AU Chou, CL Knepper, MA AF Chou, CL Knepper, MA TI Calcium-dependence of vasopressin-stimulated osmotic water permeability increase in rat collecting duct. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB 28 PY 1997 VL 11 IS 3 BP 130 EP 130 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA WL530 UT WOS:A1997WL53000130 ER PT J AU Inoue, T Nielsen, S Chou, CL Knepper, MA AF Inoue, T Nielsen, S Chou, CL Knepper, MA TI Vasopressin effects on trafficking of aquaporin-2 and vasopressin-regulated urea transporter (VRUT) in renal collecting duct. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI,NIH,BETHESDA,MD 20892. AARHUS UNIV,AARHUS,DENMARK. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB 28 PY 1997 VL 11 IS 3 BP 132 EP 132 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA WL530 UT WOS:A1997WL53000131 ER PT J AU Terris, JM Ecelbarger, CA Knepper, MA AF Terris, JM Ecelbarger, CA Knepper, MA TI Long-term regulation of vasopressin-regulated urea transporter (VRUT) expression in renal medulla. SO FASEB JOURNAL LA English DT Meeting Abstract C1 UNIFORMED SERV UNIV HLTH SCI,DEPT PHYSIOL,BETHESDA,MD 20814. NIH,KIDNEY & ELECTROLYTE METAB LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB 28 PY 1997 VL 11 IS 3 BP 134 EP 134 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA WL530 UT WOS:A1997WL53000132 ER PT J AU Bradford, AD Lee, AJ Ecelbarger, CA Chou, CL Terris, JM Knepper, MA AF Bradford, AD Lee, AJ Ecelbarger, CA Chou, CL Terris, JM Knepper, MA TI Oligomeric structure of the vasopressin-regulated urea transporter (VRUT). SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI,RENAL MECH SECT,BETHESDA,MD 20892. UNIFORMED SERV UNIV HLTH SCI,DEPT PHYSIOL,BETHESDA,MD 20814. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB 28 PY 1997 VL 11 IS 3 BP 136 EP 136 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA WL530 UT WOS:A1997WL53000136 ER PT J AU Kultz, D GarciaPerez, A Ferraris, JD Burg, MB AF Kultz, D GarciaPerez, A Ferraris, JD Burg, MB TI Distinct regulation of osmoprotective genes in yeast and mammals: p38 and SAPK/JNK do not induce mammalian ore. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB 28 PY 1997 VL 11 IS 3 BP 144 EP 144 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA WL530 UT WOS:A1997WL53000143 ER PT J AU Oriji, GK FelixCastaneda, E Madison, S Keiser, HR AF Oriji, GK FelixCastaneda, E Madison, S Keiser, HR TI Role of nitric oxide in cyclosporine A-induced hypertension. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI,HYPERTENS ENDOCRINE BRANCH,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB 28 PY 1997 VL 11 IS 3 BP 226 EP 226 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA WL530 UT WOS:A1997WL53000227 ER PT J AU Dobbins, D Kelly, J Allegra, C Grem, J AF Dobbins, D Kelly, J Allegra, C Grem, J TI Intravenous infusion of cyclopentenyl-cytosine (CPE-C) in the canine markedly inhibits the response to bilateral carotid occlusion. SO FASEB JOURNAL LA English DT Meeting Abstract C1 UNIFORMED SERV UNIV HLTH SCI,DEPT PHYSIOL,BETHESDA,MD 20814. NCI,MED CHEM LAB,NIH,BETHESDA,MD 20892. NCI,NAVY MED ONCOL,NNMC,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB 28 PY 1997 VL 11 IS 3 BP 291 EP 291 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA WL530 UT WOS:A1997WL53000292 ER PT J AU Gala, R Shevach, E AF Gala, R Shevach, E TI The immunomodulatory effects of a recombinant bovine prolactin (rbPRL) are secondary to endotoxin contamination. SO FASEB JOURNAL LA English DT Meeting Abstract C1 WAYNE STATE UNIV,SCH MED,DETROIT,MI 48201. NIAID,LI,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB 28 PY 1997 VL 11 IS 3 BP 581 EP 581 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA WL530 UT WOS:A1997WL53000581 ER PT J AU Gretz, JE Anderson, AO Shaw, S AF Gretz, JE Anderson, AO Shaw, S TI Lymph node reticulum - Conduit facilitating immune surveillance SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI,NIH,BETHESDA,MD 20892. USA,MED RES INST INFECT DIS,DEPT RESP & MUCOSAL IMMUNOL,FREDERICK,MD 21702. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB 28 PY 1997 VL 11 IS 3 BP 687 EP 687 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA WL530 UT WOS:A1997WL53000687 ER PT J AU Bhathena, SJ Bigner, M Martinez, A Elsasser, TH Miller, MJ Cuttitta, F AF Bhathena, SJ Bigner, M Martinez, A Elsasser, TH Miller, MJ Cuttitta, F TI Effect of adrenomedullin on plasma glucose and insulin in SHR/N-CP rat - A genetic model of diabetes and hypertension. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI,ROCKVILLE,MD 20850. USDA ARS,BHNRC,BELTSVILLE,MD 20705. USDA ARS,GGPL,BELTSVILLE,MD 20705. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB 28 PY 1997 VL 11 IS 3 BP 915 EP 915 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA WL530 UT WOS:A1997WL53000914 ER PT J AU Kant, AK Graubard, B Schatzkin, A AF Kant, AK Graubard, B Schatzkin, A TI Variability in two indexes of dietary diversity in the US population. SO FASEB JOURNAL LA English DT Meeting Abstract C1 CUNY QUEENS COLL,FLUSHING,NY 11367. NCI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB 28 PY 1997 VL 11 IS 3 BP 945 EP 945 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA WL530 UT WOS:A1997WL53000943 ER PT J AU Smith, JC Koshiya, N AF Smith, JC Koshiya, N TI The neuronal kernel for respiratory rhythm generation in the pre-Botzinger complex: Experimental analysis in vitro and computational model. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NINCDS,NEURAL CONTROL LAB,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB 28 PY 1997 VL 11 IS 3 BP 1196 EP 1196 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA WL530 UT WOS:A1997WL53001197 ER PT J AU Zelazowska, EB Singh, A Petrides, JS Galliven, EA Gold, PW Deuster, PA AF Zelazowska, EB Singh, A Petrides, JS Galliven, EA Gold, PW Deuster, PA TI Expression of lymphocyte subsets after exercise and dexamethasone in high and low responders. SO FASEB JOURNAL LA English DT Meeting Abstract C1 UNIFORMED SERV UNIV HLTH SCI,DEPT MIL & EMERGENCY MED,BETHESDA,MD 20814. NIMH,BETHESDA,MD 20892. RI Deuster, Patricia/G-3838-2015 OI Deuster, Patricia/0000-0002-7895-0888 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB 28 PY 1997 VL 11 IS 3 BP 1237 EP 1237 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA WL530 UT WOS:A1997WL53001237 ER PT J AU SantoniRugiu, E Thorgeirsson, SS AF SantoniRugiu, E Thorgeirsson, SS TI Alterations of cell cycle control and apoptosis during hepatic tumor progression in c-myc and c-myc/TGF alpha transgenic mice. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI,LEC,DBS,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB 28 PY 1997 VL 11 IS 3 BP 1313 EP 1313 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA WL530 UT WOS:A1997WL53001311 ER PT J AU Gladyshev, VN Jeang, KT Hatfield, DL Stadtman, TC AF Gladyshev, VN Jeang, KT Hatfield, DL Stadtman, TC TI Selenium in normal and HIV-infected human T cells: Discovery of a novel selenoprotein. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI,LD,NIH,BETHESDA,MD 20892. NHLBI,LB,NIH,BETHESDA,MD 20892. NIAID,LMM,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB 28 PY 1997 VL 11 IS 3 BP 1363 EP 1363 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA WL530 UT WOS:A1997WL53001365 ER PT J AU Hatfield, D Park, SI Park, JM Chittum, HS Beck, HJ Gladyshev, VN Yang, ES Carlson, BA Choi, IS Moustafa, ME Lee, BJ AF Hatfield, D Park, SI Park, JM Chittum, HS Beck, HJ Gladyshev, VN Yang, ES Carlson, BA Choi, IS Moustafa, ME Lee, BJ TI Expression, biosynthesis and function of selenocysteine (Sec) tRNAs as central components of Sec insertion into protein. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI,LD,DBS,NIH,BETHESDA,MD 20892. SEOUL NATL UNIV,LMG,IMBG,SEOUL 151742,SOUTH KOREA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB 28 PY 1997 VL 11 IS 3 BP 1367 EP 1367 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA WL530 UT WOS:A1997WL53001367 ER PT J AU Sweet, DH Wolff, NA Pritchard, JB AF Sweet, DH Wolff, NA Pritchard, JB TI Expression cloning and characterization of a novel organic anion transporter from rat kidney. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIEHS,LAB PHARMACOL & CHEM,NIH,RES TRIANGLE PK,NC 27709. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB 28 PY 1997 VL 11 IS 3 BP 1613 EP 1613 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA WL530 UT WOS:A1997WL53001615 ER PT J AU Pritchard, JB Walsh, RC Sweet, DH AF Pritchard, JB Walsh, RC Sweet, DH TI Characterization of organic cation transporter 2 (OCT2) isolated from rat kidney. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIEHS,PHARMACOL & CHEM LAB,NIH,RES TRIANGLE PK,NC 27709. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB 28 PY 1997 VL 11 IS 3 BP 1614 EP 1614 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA WL530 UT WOS:A1997WL53001613 ER PT J AU Miller, DS AF Miller, DS TI Regulation of organic anion (fluorescein, FL) secretion in renal proximal tubule by protein kinase C (PKC). SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIEHS,NIH,RES TRIANGLE PK,NC 27709. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB 28 PY 1997 VL 11 IS 3 BP 1615 EP 1615 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA WL530 UT WOS:A1997WL53001616 ER PT J AU Chen, N Chrambach, A AF Chen, N Chrambach, A TI Electrophoretic components of rat liver microsomes. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NICHHD,SMA,LTPB,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB 28 PY 1997 VL 11 IS 3 BP 1716 EP 1716 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA WL530 UT WOS:A1997WL53001714 ER PT J AU MooreHoon, ML Turner, RJ AF MooreHoon, ML Turner, RJ TI Induction of the secretory NaKCl cotransporter by differentiation of HT29-18 cells. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIDR,CLIN INVEST & PATIENT CARE BRANCH,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB 28 PY 1997 VL 11 IS 3 BP 1745 EP 1745 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA WL530 UT WOS:A1997WL53001745 ER PT J AU Ryan, R Weber, HC Sainz, E Mantey, S Battey, J Jensen, R AF Ryan, R Weber, HC Sainz, E Mantey, S Battey, J Jensen, R TI Pharmacology and intracellular signaling of the human orphan receptor, BRS-3. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB 28 PY 1997 VL 11 IS 3 BP 1873 EP 1873 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA WL530 UT WOS:A1997WL53001873 ER PT J AU Rodgers, BD Bernier, M MontroseRafizadeh, C AF Rodgers, BD Bernier, M MontroseRafizadeh, C TI Functional insulin receptors upregulate a novel G-protein beta subunit homologue. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIA,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB 28 PY 1997 VL 11 IS 3 BP 1883 EP 1883 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA WL530 UT WOS:A1997WL53001881 ER PT J AU Ali, S Jacobson, KA Mustafa, SJ AF Ali, S Jacobson, KA Mustafa, SJ TI A(3) adenosine receptor in the airways of allergic rabbits SO FASEB JOURNAL LA English DT Meeting Abstract C1 E CAROLINA UNIV,DEPT PHARMACOL,GREENVILLE,NC 27858. NIDDK,MOL RECOGNIT SECT,LBC,NIH,BETHESDA,MD 20892. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB 28 PY 1997 VL 11 IS 3 BP 2010 EP 2010 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA WL530 UT WOS:A1997WL53002010 ER PT J AU Weinstein, S Ziegler, R Vaught, J Maller, S AF Weinstein, S Ziegler, R Vaught, J Maller, S TI Folate and cervical cancer in US woman: An epidemiologic study with serum and red blood cell folate measured by microbiologic and radiobinding assays SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB 28 PY 1997 VL 11 IS 3 BP 2049 EP 2049 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA WL530 UT WOS:A1997WL53002048 ER PT J AU Potischman, N Weiss, HA Coates, RJ Stanford, JL Schoenberg, JB Gammon, MD Brinton, LA AF Potischman, N Weiss, HA Coates, RJ Stanford, JL Schoenberg, JB Gammon, MD Brinton, LA TI Adolescent diet and risk of early onset breast cancer SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI,NIH,BETHESDA,MD 20892. EMORY UNIV,ATLANTA,GA 30322. FRED HUTCHINSON CANC RES CTR,SEATTLE,WA 98104. NJ STATE DEPT HLTH,TRENTON,NJ. COLUMBIA UNIV,NEW YORK,NY. RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB 28 PY 1997 VL 11 IS 3 BP 2053 EP 2053 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA WL530 UT WOS:A1997WL53002052 ER PT J AU Patterson, B Zech, L Veillon, C Levander, O AF Patterson, B Zech, L Veillon, C Levander, O TI Application of a model of human selenium metabolism to cancer chemoprevention trials. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. USDA,BELTSVILLE,MD 20705. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB 28 PY 1997 VL 11 IS 3 BP 2078 EP 2078 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA WL530 UT WOS:A1997WL53002078 ER PT J AU Forman, MR Johnson, EJ Lanza, E Graubard, BI Beecher, GR Muesing, R AF Forman, MR Johnson, EJ Lanza, E Graubard, BI Beecher, GR Muesing, R TI Distribution of carotenoids in lipoproteins of premenopausal women SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. TUFTS UNIV,HUMAN NUTR RES CTR AGING,BOSTON,MA 02111. USDA ARS,BELTSVILLE AGR RES CTR,HUMAN NUTR RES CTR,BELTSVILLE,MD 20705. GEORGE WASHINGTON UNIV,MED CTR,WASHINGTON,DC 20037. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB 28 PY 1997 VL 11 IS 3 BP 2266 EP 2266 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA WL530 UT WOS:A1997WL53002266 ER PT J AU Park, SI Choi, JK Lee, BJ Hatfield, D AF Park, SI Choi, JK Lee, BJ Hatfield, D TI Selenium metabolism in Drosophila. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI,LD,DBS,NIH,BETHESDA,MD 20892. SEOUL NATL UNIV,IMBG,LMG,SEOUL 151742,SOUTH KOREA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB 28 PY 1997 VL 11 IS 3 BP 2325 EP 2325 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA WL530 UT WOS:A1997WL53002325 ER PT J AU Beck, HJ Chittum, HS Kuehn, M Diamond, AM FernandezSalguero, P Gonzalez, F Ohama, T Hatfield, D Lee, BJ AF Beck, HJ Chittum, HS Kuehn, M Diamond, AM FernandezSalguero, P Gonzalez, F Ohama, T Hatfield, D Lee, BJ TI Analysis of the selenocysteine (Sec) tRNA population in mouse embryonic stem (ES) cells heterozygous for the Sec tRNA gene. SO FASEB JOURNAL LA English DT Meeting Abstract C1 SEOUL NATL UNIV,IMBG,LMG,SEOUL 151742,SOUTH KOREA. NCI,EXPT IMMUNOL BRANCH,LMC,DBS,NIH,BETHESDA,MD 20892. UNIV CHICAGO,DEPT CELL RAD ONC,CHICAGO,IL 60637. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB 28 PY 1997 VL 11 IS 3 BP 2326 EP 2326 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA WL530 UT WOS:A1997WL53002328 ER PT J AU Chittum, HS Carlson, BA Hill, KE Burk, RF Lee, BJ Hatfield, D AF Chittum, HS Carlson, BA Hill, KE Burk, RF Lee, BJ Hatfield, D TI Analysis of the selenocysteine (Sec) tRNA population in selenium (Se)-deficient rat tissues resupplemented with Se. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI,LB,DBS,NIH,BETHESDA,MD 20892. VANDERBILT UNIV,SCH MED,CTR MOL TOXICOL,DEPT MED,NASHVILLE,TN 37292. SEOUL NATL UNIV,LMG,IMBG,SEOUL 151742,SOUTH KOREA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB 28 PY 1997 VL 11 IS 3 BP 2338 EP 2338 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA WL530 UT WOS:A1997WL53002340 ER PT J AU Vieira, NE Marini, JC Hopkins, E Yergey, AL AF Vieira, NE Marini, JC Hopkins, E Yergey, AL TI Effect of growth hormone (GH) treatment on calcium kinetics in patients with osteogenesis imperfecta (OI) type III and IV SO FASEB JOURNAL LA English DT Meeting Abstract C1 NICHHD,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB 28 PY 1997 VL 11 IS 3 BP 2366 EP 2366 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA WL530 UT WOS:A1997WL53002366 ER PT J AU Lewis, KC Phang, JM AF Lewis, KC Phang, JM TI Studies of retinoid interactions: Differential effects of synthetic retinoids in tissues. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI,FREDERICK CANC RES & DEV CTR,LAB NUTR & MOL REGULAT,NIH,FREDERICK,MD 21702. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB 28 PY 1997 VL 11 IS 3 BP 2374 EP 2374 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA WL530 UT WOS:A1997WL53002373 ER PT J AU Swanson, CA Coates, RJ Malone, KF Gammon, MD Schoenberg, JB Brinton, LA AF Swanson, CA Coates, RJ Malone, KF Gammon, MD Schoenberg, JB Brinton, LA TI Alcohol consumption and breast cancer risk among young women. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI,NIH,BETHESDA,MD 20892. EMORY UNIV,ATLANTA,GA 30322. FRED HUTCHINSON CANC RES CTR,SEATTLE,WA 98104. NEW JERSEY STATE DEPT HLTH,TRENTON,NJ 08625. RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB 28 PY 1997 VL 11 IS 3 BP 2545 EP 2545 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA WL530 UT WOS:A1997WL53002547 ER PT J AU Andreola, F FernandezSalguero, P Gonzalez, FJ De Luca, LM AF Andreola, F FernandezSalguero, P Gonzalez, FJ De Luca, LM TI Aryl hydrocarbon receptor deficient mice (Ahr-/-) exhibit an accumulation of liver retinylpalmitate. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIH, BETHESDA, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB 28 PY 1997 VL 11 IS 3 BP 2546 EP 2546 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA WL530 UT WOS:A1997WL53002545 ER PT J AU Hastings, SB Gallagher, J Bell, DA Watson, MA Schell, MJ Kohlmeier, L AF Hastings, SB Gallagher, J Bell, DA Watson, MA Schell, MJ Kohlmeier, L TI Effect of NAT1*10 genotype on ex vivo induced calf thymus DNA adducts by human bile SO FASEB JOURNAL LA English DT Meeting Abstract C1 UNIV N CAROLINA,CHAPEL HILL,NC 27599. US EPA,CHAPEL HILL,NC 27514. NIEHS,RES TRIANGLE PK,NC 27709. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB 28 PY 1997 VL 11 IS 3 BP 2550 EP 2550 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA WL530 UT WOS:A1997WL53002550 ER PT J AU Southan, GJ Gauld, D Lubeskie, A Zingarelli, B Cuzzocrea, S Salzman, AL Wolff, DJ Szabo, C AF Southan, GJ Gauld, D Lubeskie, A Zingarelli, B Cuzzocrea, S Salzman, AL Wolff, DJ Szabo, C TI Pyrazole-1-carboxamidine and related compounds and novel inhibitors of nitric oxide synthase: Pharmacological characterization in cultured cells and vascular rings. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. UNIV MED & DENT NEW JERSEY,ROBERT WOOD JOHNSON MED SCH,DEPT PHARMACOL,PISCATAWAY,NJ 08854. CHILDRENS HOSP,MED CTR,DIV CRIT CARE,CINCINNATI,OH 45229. NR 0 TC 0 Z9 0 U1 0 U2 4 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB 28 PY 1997 VL 11 IS 3 BP 2755 EP 2755 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA WL530 UT WOS:A1997WL53002753 ER PT J AU Alkayed, NJ Kimes, AS London, ED Traystman, RJ Hurn, PD AF Alkayed, NJ Kimes, AS London, ED Traystman, RJ Hurn, PD TI Mechanism of estrogen-mediated neuroprotection in brain. SO FASEB JOURNAL LA English DT Meeting Abstract C1 JOHNS HOPKINS MED INST,BALTIMORE,MD 21287. NATL INST DRUG ABUSE,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB 28 PY 1997 VL 11 IS 3 BP 2793 EP 2793 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA WL530 UT WOS:A1997WL53002795 ER PT J AU Singh, A Petrides, JS Galliven, EA Gold, PW Deuster, PA AF Singh, A Petrides, JS Galliven, EA Gold, PW Deuster, PA TI Concordance of the endocrine responses to physical and mental stress. SO FASEB JOURNAL LA English DT Meeting Abstract C1 UNIFORMED SERV UNIV HLTH SCI,DEPT MIL & EMERGENCY MED,BETHESDA,MD 20814. NIMH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB 28 PY 1997 VL 11 IS 3 BP 3030 EP 3030 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA WL530 UT WOS:A1997WL53003032 ER PT J AU Munoz, ML Leon, G Salazar, I SanchezSalas, JL Tovar, R Moreno, M Fiori, C Das, P AF Munoz, ML Leon, G Salazar, I SanchezSalas, JL Tovar, R Moreno, M Fiori, C Das, P TI Entamoeba histolytica: The relationship among cytoskeleton rearrangement, gene expression and electron-dense granules. SO FASEB JOURNAL LA English DT Meeting Abstract C1 CINVESTAV IPN,IPN,MEXICO CITY 14000,DF,MEXICO. NIH,NATL CTR RES RESOURCES,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB 28 PY 1997 VL 11 IS 3 BP 3080 EP 3080 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA WL530 UT WOS:A1997WL53003080 ER PT J AU Chang, SH Phelps, PC Berezesky, IK Wang, XW Elmore, L Harris, CC Trump, BF AF Chang, SH Phelps, PC Berezesky, IK Wang, XW Elmore, L Harris, CC Trump, BF TI H-ras transformed NRK-52E cell lines resist apoptosis induced by microinjection of p53 genes. SO FASEB JOURNAL LA English DT Meeting Abstract C1 UNIV MARYLAND,SCH MED,DEPT PATHOL,BALTIMORE,MD 21201. NCI,HUMAN CARCINOGENESIS LAB,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB 28 PY 1997 VL 11 IS 3 BP 3127 EP 3127 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA WL530 UT WOS:A1997WL53003127 ER PT J AU Atchison, C Osina, T Hargus, S Daiker, D Aronson, J West, A Moslen, M AF Atchison, C Osina, T Hargus, S Daiker, D Aronson, J West, A Moslen, M TI Comparison of the distribution of diclofenac protein adducts between rats and mice. SO FASEB JOURNAL LA English DT Meeting Abstract C1 UNIV TEXAS,MED BRANCH,GALVESTON,TX 77555. NIH,BETHESDA,MD 20814. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB 28 PY 1997 VL 11 IS 3 BP 3165 EP 3165 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA WL530 UT WOS:A1997WL53003166 ER PT J AU Vu, D Abad, L Wilson, PWF Harris, TB Roubenoff, R AF Vu, D Abad, L Wilson, PWF Harris, TB Roubenoff, R TI Are antioxidant vitamins acute phase reactants in the elderly? SO FASEB JOURNAL LA English DT Meeting Abstract C1 TUFTS UNIV,USDA,HUMAN NUTR RES CTR AGING,BOSTON,MA 02111. FRAMINGHAM HEART DIS EPIDEMIOL STUDY,FRAMINGHAM,MA 01701. NIA,EDBP,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB 28 PY 1997 VL 11 IS 3 BP 3388 EP 3388 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA WL530 UT WOS:A1997WL53003390 ER PT J AU Castonguay, T Beaulieu, S Eskay, R Barden, N Kamara, K Khozin, S Lustberg, L Brown, L AF Castonguay, T Beaulieu, S Eskay, R Barden, N Kamara, K Khozin, S Lustberg, L Brown, L TI The effects of adrenalectomy (ADX) and aldosterone (ALDO) replacement in transgenic mice expressing antisense RNA to the glucocorticoid receptor (GR) SO FASEB JOURNAL LA English DT Meeting Abstract C1 UNIV MARYLAND,DEPT NUTR & FOOD SCI,COLLEGE PK,MD 20742. NIMH,BETHESDA,MD 20892. NIAAA,BETHESDA,MD. LAVAL UNIV HOSP,MOL PSYCHOGENET LAB,ST FOY,PQ,CANADA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB 28 PY 1997 VL 11 IS 3 BP 3429 EP 3429 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA WL530 UT WOS:A1997WL53003428 ER PT J AU Jourdheuil, D Miles, AM Wink, DA Grisham, MB AF Jourdheuil, D Miles, AM Wink, DA Grisham, MB TI Decomposition of S-nitrosoglutathione by Cu,Zn superoxide dismutase. SO FASEB JOURNAL LA English DT Meeting Abstract C1 LOUISIANA STATE UNIV,MED CTR,SHREVEPORT,LA 71130. NCI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB 28 PY 1997 VL 11 IS 3 BP 3710 EP 3710 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA WL530 UT WOS:A1997WL53003711 ER PT J AU Kullo, IJ Schwartz, RS Tsutsui, M Milstien, S Katusic, ZS OBrien, T AF Kullo, IJ Schwartz, RS Tsutsui, M Milstien, S Katusic, ZS OBrien, T TI Tetrahydrobiopterin increases activity of recombinant endothelial nitric oxide synthase. SO FASEB JOURNAL LA English DT Meeting Abstract C1 MAYO CLIN,ROCHESTER,MN 55905. NIMH,NIH,BETHESDA,MD 20814. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB 28 PY 1997 VL 11 IS 3 BP 3718 EP 3718 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA WL530 UT WOS:A1997WL53003718 ER PT J AU Visser, M Kiel, DP Langlois, J Wilson, PWF Hannan, MT Harris, T AF Visser, M Kiel, DP Langlois, J Wilson, PWF Hannan, MT Harris, T TI Muscle loss in older men and women: Prevalence and predictors in the Framingham heart study SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIA,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB 28 PY 1997 VL 11 IS 3 BP 3768 EP 3768 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA WL530 UT WOS:A1997WL53003769 ER PT J AU Schreurs, BG AF Schreurs, BG TI Classical conditioning results in long term changes in Purkinje cell dendritic excitability in rabbit cerebellar slice SO FASEB JOURNAL LA English DT Meeting Abstract C1 NINCDS,BEHAV NEUROSCI UNIT,LAS,NIH,BETHESDA,MD. NR 0 TC 1 Z9 1 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB 28 PY 1997 VL 11 IS 3 BP 3790 EP 3790 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA WL530 UT WOS:A1997WL53003789 ER PT J AU McGowan, MH Neubauer, JA Stolle, CA AF McGowan, MH Neubauer, JA Stolle, CA TI Characterization of the rat carbonic anhydrase II gene structure: Sequence analysis of the 5' flanking region and 3' UTR SO GENE LA English DT Article DE recombinant DNA; splice junctions; polyadenylation signals; 5' flanking sequence; CpG island; tissue expression ID AMINO-ACID-SEQUENCE; METHYLATION PATTERNS; GENOMIC ORGANIZATION; NUCLEOTIDE-SEQUENCE; DNA METHYLATION; TRANSCRIPTION; LOCALIZATION; SITE; EXPRESSION; UPSTREAM AB The rat carbonic anhydrase II gene was characterized and found to be approximately 15.5 kb in length and to contain 7 exons and 6 introns. All intron/exon junction and branch point sequences conform to consensus sequences, and the overall rat CA II genomic structure appears to be conserved upon comparison with mouse, human, and chicken CA II genes. The putative cis-acting elements within the analyzed 1014 bp 5' flanking region include: TATA box, 4 Sp1 binding sites, 2 AP2 sites and putative tissue-specific beta-globin-like repeat elements. A CpG island of approximately 800 bp was identified that begins about 600 bp upstream of exon 1 and extends about 200 bp into intron 1. In the 3' UTR, two polyadenylation signals (AATAAA) are present, the second of which is believed to be utilized. Northern blot analysis reveals that the 1.7 kb rat CA II mRNA is abundantly expressed in adult male brain and kidney, while negligible amounts are detected in heart and liver. C1 UNIV MED & DENT NEW JERSEY,ROBERT WOOD JOHNSON MED SCH,DEPT MED,NEW BRUNSWICK,NJ 08903. UNIV PENN,SCH MED,DEPT GENET,PHILADELPHIA,PA 19104. RP McGowan, MH (reprint author), NEI,NIH,BLDG 6,ROOM 232,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. FU NHLBI NIH HHS [HL16022]; NIAMS NIH HHS [AR40566] NR 38 TC 3 Z9 5 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD FEB 28 PY 1997 VL 186 IS 2 BP 181 EP 188 DI 10.1016/S0378-1119(96)00700-7 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA WM011 UT WOS:A1997WM01100005 PM 9074494 ER PT J AU Freije, JMP Blay, P MacDonald, NJ Manrow, RE Steeg, PS AF Freije, JMP Blay, P MacDonald, NJ Manrow, RE Steeg, PS TI Site-directed mutation of nm23-H1 - Mutations lacking motility suppressive capacity upon transfection are deficient in histidine-dependent protein phosphotransferase pathways in vitro SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NUCLEOSIDE DIPHOSPHATE-KINASE; GTP-BINDING PROTEINS; TUMOR-METASTASIS; DROSOPHILA DEVELOPMENT; TRANSCRIPTION FACTOR; SIGNAL-TRANSDUCTION; MYXOCOCCUS-XANTHUS; MELANOMA-CELLS; GENE; PHOSPHORYLATION AB We previously compared the structure and motility suppressive capacity of nm23-H1 by transfection of wild type and site-directed mutant forms into breast carcinoma cells, Wild type nm23-H1 and an nm23-H1(S44A) (serine 44 to alanine) mutant suppressed motility, whereas the nm23-H1(P96S), nm23-H1(S120G), and to a lesser extent, nm23-H1(S120A) mutant forms failed to do so, In the present study wild type and mutant recombinant Nm23-H1 proteins have been produced, purified, and assayed for phosphorylation and phosphotransfer activities, We report the first association of Nm23-H1 mutations lacking motility suppressive capacity with decreased in vitro activity in histidine-dependent protein phosphotransferase assays. Nm23-H1(P96S), a Drosophila developmental mutation homolog, exhibited normal autophosphorylation and nucleoside-diphosphate kinase (NDPK) characteristics but deficient phosphotransfer activity in three histidine protein kinase assays, using succinic thiokinase, Nm23-H2, and GST-Nm23-H1 as substrates. Nm23-H1(S120G), found in advanced human neuroblastomas, exhibited deficient activity in several histidine-dependent protein phosphotransfer reactions, including histidine autophosphorylation, downstream phosphorylation on serines, and slightly decreased histidine protein kinase activity; significant NDPK activity was observed. The Nm23-H1(S120A) mutant was deficient in only histidine-dependent serine autophosphorylation. Nm23-H1 and Nm23-H1(S44A) exhibited normal activity in all assays conducted. Based on this correlation, we hypothesize that a histidine-dependent protein phosphotransfer activity of Nm23-H1 may be responsible for its biological suppressive effects. C1 NCI, WOMENS CANC SECT, PATHOL LAB, DIV CLIN SCI, NIH, BETHESDA, MD 20892 USA. RI Freije, Jose M.P./A-6535-2008 OI Freije, Jose M.P./0000-0002-4688-8266 NR 61 TC 107 Z9 111 U1 0 U2 3 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 FEB 28 PY 1997 VL 272 IS 9 BP 5525 EP 5532 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WK747 UT WOS:A1997WK74700026 PM 9038158 ER PT J AU Barsony, J Renyi, I McKoy, W AF Barsony, J Renyi, I McKoy, W TI Subcellular distribution of normal and mutant vitamin D receptors in living cells - Studies with a novel fluorescent ligand SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ENDOPLASMIC-RETICULUM; GLUCOCORTICOID RECEPTOR; GENE-EXPRESSION; 1,25-DIHYDROXYVITAMIN-D3; CALRETICULIN; BINDING; LOCALIZATION; FIBROBLASTS; ASSOCIATION; PROTEIN AB To understand the subcellular localization of the vitamin D receptor (VDR) and to measure VDR content in single cells, we recently developed a fluorescent labeled ligand, 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY)-calcitriol. This tagged hormone has intact biological activity, high affinity and specific binding to the receptor, and enhanced fluorescent emission upon receptor binding. Using BODIPY-calcitriol, here we monitored the subcellular distribution of VDR in Living cultured cells by microscopy, Time course studies showed that an equilibrium between the cytoplasmic and nuclear hormone binding developed within 5 min and was maintained thereafter, We found a substantial proportion of VDR residing in the cytoplasm, colocalized with endoplasmic reticulum, the Golgi complex, and microtubules. Confocal microscopy clarified the presence of VDR within discrete regions of the nucleus and along the nuclear envelope, There was no VDR in the plasma membrane, Low affinity BODIPY-calcitriol binding sites were in the mitochondria. Mutations in the VDR gene selectively and specifically altered BODIPY-calcitriol distribution, Defects in the hormone binding region of VDR prevented both nuclear and cytoplasmic hormone binding, Defects in the DNA binding region decreased the nuclear retention of VDR and prevented localization to nuclear foci, These results with BODIPY-calcitriol reveal cytoplasmic VDR localization in living cells and open the possibility of studying the three-dimensional architecture of intranuclear target sites. RP Barsony, J (reprint author), NIDDK,NIH,LAB CELL BIOCHEM & BIOL,BETHESDA,MD 20892, USA. NR 45 TC 89 Z9 91 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD FEB 28 PY 1997 VL 272 IS 9 BP 5774 EP 5782 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WK747 UT WOS:A1997WK74700059 PM 9038191 ER PT J AU Bai, G Kusiak, JW AF Bai, G Kusiak, JW TI Nerve growth factor up-regulates the N-methyl-D-aspartate receptor subunit 1 promoter in PC12 cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MESSENGER-RNA LEVELS; CEREBELLAR GRANULE CELLS; NMDA RECEPTOR; NEUROTROPHIC FACTOR; GENE-EXPRESSION; RAT-BRAIN; TRANSCRIPTIONAL ACTIVATION; DIFFERENTIAL REGULATION; FOREBRAIN ISCHEMIA; MOLECULAR-CLONING AB The N-methyl-D-aspartate (NMDA) subtype of glutamate receptor plays important roles in synaptic plasticity, the induction of long term potentiation, and excitotoxicity. Mechanisms governing the regulation of expression of its subunit genes remain largely unknown. The promoter of the essential subunit of the NMDA receptor heteromer, NMDAR1, contains DNA binding elements recognized by the nerve growth factor-inducible/early growth reaction factor (NGFI/Egr) family of transcription factors that are rapidly induced by neurotrophins, such as nerve growth factor (NGF), This study examined the effect of NGF on the activity of the N-methyl-D-aspartate receptor subunit 1 (NMDAR1) promoter/luciferase reporter constructs in PC12 cells, which contain the high affinity TrkA receptor for NGF and the low affinity p75(NTR) receptor for neurotrophins. NGF up-regulated the activity of the NMDAR1 promoter by 3-4-fold in a time- and dose-dependent manner. 5' deletional analysis of the promoter indicated that the responsive element(s) resides in the proximal region containing GSG and Spl sites. Mutational analysis of these sites revealed that both were important for NGF regulation. Transient expression of Egr-1 increased activity of the wild type promoter but failed to increase activity of a GSG mutant promoter. Other neurotrophins did not activate the promoter, while K-252a inhibited the action of NGF, These results suggest that the NGF effect is mediated by the high affinity NGF receptor, Trk A and that neurotrophin binding to the low affinity neurotrophin receptor, p75(NTR), alone does not affect the promoter activity. Our results suggest that NGF is able to up-regulate the activity of the NMDAR1 promoter and may play a role in controlling the expression levels of NMDA receptors. RP Bai, G (reprint author), NIA,GERONTOL RES CTR,MOL NEUROBIOL UNIT,NIH,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. NR 64 TC 53 Z9 55 U1 1 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD FEB 28 PY 1997 VL 272 IS 9 BP 5936 EP 5942 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WK747 UT WOS:A1997WK74700081 PM 9038213 ER PT J AU Wang, SB Yan, L Wesley, RA Danner, RL AF Wang, SB Yan, L Wesley, RA Danner, RL TI Nitric oxide increases tumor necrosis factor production in differentiated U937 cells by decreasing cyclic AMP SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PURIFIED GUANYLATE-CYCLASE; BLOOD MONONUCLEAR-CELLS; TNF-ALPHA PRODUCTION; ADENYLYL-CYCLASE; ENDOTHELIAL-CELLS; MOLECULAR-CLONING; HUMAN-NEUTROPHILS; S-NITROSYLATION; GENE-EXPRESSION; LINE U937 AB Nitric oxide (NO) increases tumor necrosis factor (TNF) synthesis in human peripheral blood mononuclear cells by a cGMP-independent mechanism, NO has been shown to inhibit adenylate cyclase in cell membranes, Since cAMP down-regulates TNF transcription, we examined the possibility that NO enhances TNF synthesis by decreasing cAMP. U937 cells were induced to differentiate using phorbol myristate acetate (100 nM for 48 h) and then were incubated for 24 h with sodium nitroprusside (SNP) or S-nitroso-N-acetylpenicillamine (SNAP). These NO donors increased TNF production (7.0- and 15.6-fold, respectively, at 500 mu M) in a dose-dependent manner (p = 0.002), However, SNP and SNAP did not elevate cGMP levels in U937 cell cultures, and the cGMP analog, 8-bromo-cGMP, had no effect on TNF production, In contrast, SNP (p = 0.001) and SNAP (p = 0.009) decreased intracellular cAMP levels by up to 51.5% over 24 h and, in the presence of a phosphodiesterase inhibitor, blunted isoproterenol-stimulated increases in cAMP by 21.8% (p = 0.004) and 27.6% (p = 0.008), respectively. H89, an inhibitor of cAMP-dependent protein kinase, dose dependently increased TNF production in phorbol myristate acetate-differentiated U937 cells in the absence (6.5-fold at 30 mu M;p = 0.035), but not in the presence (p = 0.77) of SNAP, Conversely, the cAMP analog dibutyryl cAMP (Bt(2)cAMP) blocked SNAP-induced TNF production (p = 0.001), SNP and SNAP (500 mu M) increased relative TNF mRNA levels by 57.5% (p = 0.045) and 66.2% (p = 0.001), respectively, This effect was prevented by Bt(2)cAMP. These results indicate that NO up-regulates TNF production by decreasing intracellular cAMP. C1 NIH,DEPT CRIT CARE MED,WARREN GRANT MAGNUSON CLIN CTR,BETHESDA,MD 20892. NR 60 TC 56 Z9 62 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD FEB 28 PY 1997 VL 272 IS 9 BP 5959 EP 5965 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WK747 UT WOS:A1997WK74700084 PM 9038216 ER PT J AU Calderon, SN Rice, KC Rothman, RB Porreca, F FlippenAnderson, JL Kayakiri, H Xu, H Becketts, K Smith, LE Bilsky, EJ Davis, P Horvath, R AF Calderon, SN Rice, KC Rothman, RB Porreca, F FlippenAnderson, JL Kayakiri, H Xu, H Becketts, K Smith, LE Bilsky, EJ Davis, P Horvath, R TI Probes for narcotic receptor mediated phenomena .23. Synthesis, opioid receptor binding, and bioassay of the highly selective delta agonist (+)-4-[(alpha R)-alpha-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]-N ,N-diethylbenzamide (SNC 80) and related novel nonpeptide delta opioid receptor ligands SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID BW373U86; RAT; PEPTIDES; MICE; MORPHINE; COCAINE; DRUGS; BRAIN; MOUSE; ANTINOCICEPTION AB The highly selective delta (delta) opioid receptor agonist SNC 80 [(+)-4-[(alpha R)-alpha-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]-N,N-diethylbenzamide, (+)-21] and novel optically pure derivatives were synthesized from the enantiomers of 1-allyl-trans-2,5-dimethylpiperazine (2). The piperazine (+/-)-2 was synthesized, and its enantiomers were obtained on a multigram scale in > 99% optical purity by optical resolution of the racemate with the camphoric acids. The absolute configuration of (+)-2 was determined to be 2S,5R by X-ray analysis of the salt with (+)-camphoric acid. Since the chirality of the starting material was known, and the relative configuration of compounds (-)-21, (-)-22, and (+)-23 were obtained by single-crystal X-ray analysis, the assignment of the absolute stereochemistry of the entire series could be made. Radioreceptor binding studies in rat brain preparations showed that methyl ethers (+)-21 (SNC 80) and (-)-25 exhibited strong selectivity for rat delta receptors with low nanomolar affinity to delta receptors and only micromolar affinity for rat mu (mu) opioid receptors. Compounds (-)-21, (-)-22, and (-)-23 showed micromolar affinities for mu opioid receptors. The unsubstituted derivative (+)-22 and the fluorinated derivative (-)-27 showed >2659- and >2105-fold delta/mu binding selectivity, respectively. The latter derivatives are the most selective ligands described in the new series. Studies with some of the compounds described in the isolated mouse vas deferens and guinea pig ileum bioassays revealed that all were agonists with different degrees of selectivity for the delta opioid receptor. These data show that (+)-21 and (+)-22 are potent delta receptor agonists and suggest that these compounds will be valuable tools for further study of the delta opioid receptor at the molecular level, including its function and role in analgesia and drug abuse. C1 NIDDKD, MED CHEM LAB, NIH, BETHESDA, MD 20892 USA. NIDA, ADDICT RES CTR, CLIN PSYCHOPHARMACOL SECT, BALTIMORE, MD 21224 USA. USN, RES LAB, STRUCT MATTER LAB, WASHINGTON, DC 20375 USA. UNIV ARIZONA, ARIZONA HLTH SCI CTR, DEPT PHARMACOL, TUCSON, AZ 85724 USA. NR 57 TC 64 Z9 64 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 FEB 28 PY 1997 VL 40 IS 5 BP 695 EP 704 DI 10.1021/jm960319n PG 10 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA WK726 UT WOS:A1997WK72600008 PM 9057856 ER PT J AU Matecka, D Lewis, D Rothman, RB Dersch, CM Wojnicki, FHE Glowa, JR DeVries, AC Pert, A Rice, KC AF Matecka, D Lewis, D Rothman, RB Dersch, CM Wojnicki, FHE Glowa, JR DeVries, AC Pert, A Rice, KC TI Heteroaromatic analogs of 1-[2-(diphenylmethoxy)ethyl]- and 1-[2-[bis(4-fluorophenyl)methoxy]ethyl]-4-(3-phenylpropyl)piperazines (GBR 12935 and GBR 12909) as high-affinity dopamine reuptake inhibitors SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID BIOGENIC-AMINE TRANSPORTERS; RAT CAUDATE MEMBRANES; BINDING-SITES; COCAINE ANTAGONISTS; POTENT INHIBITORS; PHARMACOLOGY; GBR-12909; RECEPTORS; GBR12935; INVITRO AB A new series of heteroaromatic GBR 12935 [1-[2-(diphenylmethoxy)ethyl]-4-(3-phenylpropyl)-piperazine] (1) and GBR 12909 [1-[2-[bis(4-fluorophenyl)methoxy]ethyl]-4-(3-phenylpropyl)-piperazine] (2) analogs was synthesized and evaluated as dopamine transporter (DAT) ligands. Analogs 5-16, in which the benzene ring in the phenylpropyl side chain of the GBR molecule had been replaced with a thiophene, furan, or pyridine ring, exhibited high affinity and selectivity for the DAT vs serotonin transporter (SERT) and stimulated locomotor activity in rats in a manner similar to the parent compound 2. In cocaine and food self-administration studies in rhesus monkeys, both thiophene-containing (6 and 8) and pyridine-containing (14 and 16) derivatives displayed potency comparable to 2 in decreasing the cocaine-maintained responding at the doses tested (0.3, 1.7, and 3 mg/kg). However, these compounds did not produce the degree of separation between food- and cocaine-maintained responding that was seen with 2. Among the bicyclic fused-ring congeners 17-38, the indole-containing analog of 2, 22, showed the greatest affinity for binding to the DAT, with IC50 = 0.7 nM, whereas the corresponding indole-containing derivative of 1, 21, displayed the highest selectivity (over 600-fold) at this site vs the SEPT site. C1 NIDDKD, MED CHEM LAB, NIH, BETHESDA, MD 20892 USA. NIDA, ADDICT RES CTR,IRP,CLIN PSYCHOPHARMACOL SECT,NIH, BALTIMORE, MD 21224 USA. NIMH, BIOL PSYCHIAT BRANCH, NIH, BETHESDA, MD 20892 USA. NR 45 TC 61 Z9 62 U1 1 U2 4 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 FEB 28 PY 1997 VL 40 IS 5 BP 705 EP 716 DI 10.1021/jm9606599 PG 12 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA WK726 UT WOS:A1997WK72600009 PM 9057857 ER PT J AU Park, JM Hatfield, DL Lee, BJ AF Park, JM Hatfield, DL Lee, BJ TI Cross-competition for TATA-binding protein between TATA boxes of the selenocysteine tRNA([Ser]Sec) promoter and RNA polymerase II promoters SO MOLECULES AND CELLS LA English DT Article ID PHOSPHOSERINE TRANSFER-RNA; TRANSCRIPTION FACTOR; GENE; TFIIIB; ELEMENTS; COMPLEX; INITIATION; COMPONENTS; POINT; LESS AB In this study we show that the TATA-binding protein (TBP) interacts with the selenocysteine tRNA([Ser]Sec) TATA element in a fashion analogous to the TBP-TATA interaction in RNA polymerase (Pol) II-transcribed genes even though the gene is transcribed by Pol III. Recombinant TBPs expressed in Escherichia coli bound to the tRNA([Ser]Sec) TATA element. A factor was detected in Xenopus oocyte extracts which contain TBP and bind to the TATA boxes of the tRNA([Ser]Sec) gene and various class II genes. Transcription of the microinjected tRNA([Ser]Sec) gene was inhibited in Xenopus oocytes by coinjection with the TATA box of the adenovirus major late promoter (AdMLP). Transcription of a 5S gene was not affected under these conditions. These results suggest that the tRNA([Ser]Sec) gene recruits TBP in a manner similar to that of TATA-dependent Pol II-transcribed genes and differently from that of Pol III-transcribed genes lacking a TATA box. C1 SEOUL NATL UNIV,INST MOL BIOL & GENET,LAB MOL GENET,SEOUL 151742,SOUTH KOREA. NCI,NIH,DIV BASIC SCI,LAB BASIC SCI,SECT MOL BIOL SELENIUM,BETHESDA,MD 20892. NR 25 TC 3 Z9 3 U1 0 U2 0 PU KOREAN SOC MOLECULAR BIOLOGY PI SEOUL PA KOREA SCI TECHNOLOGY CENTER, ROOM 815, 635-4 YEOGSAM-DONG KANGNAM-GU, SEOUL 135-703, SOUTH KOREA SN 1016-8478 J9 MOL CELLS JI Mol. Cells PD FEB 28 PY 1997 VL 7 IS 1 BP 72 EP 77 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA WK979 UT WOS:A1997WK97900011 PM 9085268 ER PT J AU Waltrip, RW Buchanan, RW William, TC Kirkpatrick, B Summerfelt, A Breier, A Rubin, SA Carbone, KM AF Waltrip, RW Buchanan, RW William, TC Kirkpatrick, B Summerfelt, A Breier, A Rubin, SA Carbone, KM TI Borna disease virus antibodies and the deficit syndrome of schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Borna disease virus; schizophrenia; deficit syndrome ID ABNORMALITIES; RATS; INFECTION; CELLS; BRAIN; RNA AB We detected anti-Borna disease virus (BDV) antibodies at a 14.4% rate in patients with schizophrenia. The hypothesis of a higher rate of BDV seropositivity in deficit syndrome was borne out in a subset of 64 patients categorized according to the Schedule for the Deficit Syndrome with 5/15 seropositive deficit and 4/49 seropositive nondeficit (p<0.05). This suggests that the antibodies and possibly a BDV-like virus are pathogenetically linked to this form of schizophrenia. C1 NIMH,EXPT THERAPEUT BRANCH,UNIT PATHOPHYSIOL & TREATMENT,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT & RES,NEUROIMMUNOPATHOGENESIS SECT,LAB PEDIAT VIRAL DIS & RESP VIRUSES,BETHESDA,MD. RP Waltrip, RW (reprint author), UNIV MARYLAND,MARYLAND PSYCHIAT RES CTR,DEPT PSYCHIAT,CATONSVILLE,MD 21228, USA. FU NIMH NIH HHS [MH40279, MH00814, MH44211] NR 34 TC 66 Z9 67 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD FEB 28 PY 1997 VL 23 IS 3 BP 253 EP 257 DI 10.1016/S0920-9964(96)00114-4 PG 5 WC Psychiatry SC Psychiatry GA WM020 UT WOS:A1997WM02000009 PM 9075304 ER PT J AU Boyington, JC Gladyshev, VN Khangulov, SV Stadtman, TC Sun, PD AF Boyington, JC Gladyshev, VN Khangulov, SV Stadtman, TC Sun, PD TI Crystal structure of formate dehydrogenase H: Catalysis involving Mo, molybdopterin, selenocysteine, and an Fe4S4 cluster SO SCIENCE LA English DT Article ID ESCHERICHIA-COLI; SELENIUM; OXIDOREDUCTASE; PROGRAM AB Formate dehydrogenase H from Escherichia coli contains selenocysteine (SeCys), molybdenum, two molybdopterin guanine dinucleotide (MGD) cofactors, and an Fe4S4 cluster at the active site and catalyzes the two-electron oxidation of formate to carbon dioxide. The crystal structures of the oxidized [Mo(VI), Fe4S4(ox)] form of formate dehydrogenase H (with and without bound inhibitor) and the reduced [Mo(IV), Fe4S4(red)] form have been determined, revealing a four-domain alpha beta structure with the molybdenum directly coordinated to selenium and both MGD cofactors. These structures suggest a reaction mechanism that directly involves SeCys(140) and His(141) in proton abstraction and the molybdenum, molybdopterin, Lys(44), and the Fe4S4 cluster in electron transfer. C1 NIAID,STRUCT BIOL SECT,MOL STRUCT LAB,NIH,ROCKVILLE,MD 20852. NHLBI,BIOCHEM LAB,BETHESDA,MD 20892. PRINCETON UNIV,HOYT LAB,DEPT CHEM,PRINCETON,NJ 08544. NR 31 TC 372 Z9 379 U1 7 U2 55 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD FEB 28 PY 1997 VL 275 IS 5304 BP 1305 EP 1308 DI 10.1126/science.275.5304.1305 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WK644 UT WOS:A1997WK64400042 PM 9036855 ER PT J AU Abraham, EH Okunieff, P Scala, S Vos, P Oosterveld, MJS Chen, AY Shrivastav, B Guidotti, G AF Abraham, EH Okunieff, P Scala, S Vos, P Oosterveld, MJS Chen, AY Shrivastav, B Guidotti, G TI Cystic fibrosis transmembrane conductance regulator and adenosine triphosphate SO SCIENCE LA English DT Article ID ATP; CHANNELS; RESISTANCE; MECHANISM; MDR1; CFTR; ABC C1 HARVARD UNIV,DEPT CELLULAR & MOL BIOL,CAMBRIDGE,MA 02138. RP Abraham, EH (reprint author), NCI,DIV CLIN SCI,NIH,BETHESDA,MD 20892, USA. RI Scala, Stefania/K-1380-2016 OI Scala, Stefania/0000-0001-9524-2616 NR 19 TC 60 Z9 60 U1 0 U2 3 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD FEB 28 PY 1997 VL 275 IS 5304 BP 1324 EP 1325 DI 10.1126/science.275.5304.1324 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WK644 UT WOS:A1997WK64400048 PM 9064787 ER PT J AU Bell, DA Taylor, JA AF Bell, DA Taylor, JA TI Genetic analysis of complex diseases SO SCIENCE LA English DT Article ID EXPOSURE C1 NIEHS,EPIDEMIOL BRANCH,RES TRIANGLE PK,NC 27709. RP Bell, DA (reprint author), NIEHS,LAB COMPUTAT BIOL & RISK ANAL,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 4 TC 12 Z9 12 U1 0 U2 2 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD FEB 28 PY 1997 VL 275 IS 5304 BP 1327 EP 1328 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WK644 UT WOS:A1997WK64400052 PM 9064789 ER PT J AU RussekCohen, E Simon, RM AF RussekCohen, E Simon, RM TI Evaluating treatments when a gender by treatment interaction may exist SO STATISTICS IN MEDICINE LA English DT Article ID CLINICAL-TRIALS AB We propose a two-stage procedure for investigating whether males and females respond differently to treatment. The size of the first stage is based on the assumption of homogeneity of treatment effects across genders. Using stage I, we test for a gender by treatment interaction, If non-significant, we compute an overall average treatment effect and terminate the study. If we find an apparent interaction at the end of the first stage, we consider each gender separately. Because we now need to estimate treatment effects separately for each gender, we may have a need to collect additional information in a second stage. We consider the performance of our procedure for a normally distributed endpoint as well as for a survival model. C1 NCI,BIOMETR RES BRANCH,BETHESDA,MD 20892. RP RussekCohen, E (reprint author), UNIV MARYLAND,DEPT ANIM SCI,COLLEGE PK,MD 20742, USA. NR 12 TC 10 Z9 10 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0277-6715 J9 STAT MED JI Stat. Med. PD FEB 28 PY 1997 VL 16 IS 4 BP 455 EP 464 PG 10 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 WK019 UT WOS:A1997WK01900010 PM 9044532 ER PT J AU Misra, RR Crance, KA Bare, RM Waalkes, MP AF Misra, RR Crance, KA Bare, RM Waalkes, MP TI Lack of correlation between the inducibility of metallothionein mRNA and metallothionein protein in cadmium-exposed rodents SO TOXICOLOGY LA English DT Article ID INBRED STRAINS; MICE; EXPRESSION; RESISTANCE; LIVER; CARCINOGENESIS; DEGRADATION; SPECIFICITY; CELLS; GENE AB Cadmium (Cd) is carcinogenic in humans and laboratory animals. Depending on the duration and route of exposure, Cd can also induce damage in the liver, kidneys and lungs. In certain tissues, metallothionein (MT) proteins are induced by Cd exposure and associated with native and acquired tolerance to the metal. Rats are generally more sensitive than mice to Cd carcinogenicity; however, sensitivity can vary markedly between different strains of the same rodent species. To further define the role of MT in Cd toxicity and carcinogenesis, adult male Wistar rats and adult male C57 and DBA mice were treated with CdCl2, and liver, kidney, and lung were analyzed for Cd, MT mRNA, and MT protein 24 h later. Dose-related increases in Cd were detected in the livers and kidneys of all animals tested; however, increases in pulmonary Cd were observed only in C57 mice, and only at the highest CdCl2 dose. While hepatic Cd concentrations were similar in the rats and mice, renal Cd concentrations were similar in the rats and DBA mice but were nearly 2-fold higher in C57 mice at the highest CdCl2 dose. Dose-related increases in MT mRNA occurred in the livers and lungs of all animals tested. Hepatic MT mRNA concentrations were highest in the rats, and C57 mice exhibited the greatest magnitude of hepatic MT mRNA induction. Dose-related increases in renal MT mRNA were also detected in both strains of mice, but between the two strains, C57 mice exhibited substantially higher levels of renal MT mRNA induction. Basal levels of renal MT mRNA were higher in the rats than in the mice, and transcription of the MT gene was not inducible in the rat kidney at any of the CdCl2 doses used. In comparison, basal levels of pulmonary MT mRNA were similar in the rats and DBA mice, were substantially lower in C57 mice, and increases in pulmonary MT mRNA were most pronounced in the rats. Analysis of MT protein revealed dose-related increases in the livers and kidneys of all animals tested. C57 mice had the lowest basal and induced levels of hepatic MT, and basal levels of renal MT were much higher in the rats than in mice of either strain. Although dose-related increases in pulmonary MT were similar in both strains of mice, pulmonary MT levels were much lower and not inducible in the rats. Overall our experiments revealed complex profiles of Cd distribution and MT expression that varied between tissues, species and strains, and often did not directly correlate with sensitivity to damage. The results suggest that Cd distribution, inducibility of the MT gene, and levels of MT protein, must all be considered when predicting susceptibility to Cd toxicity and carcinogenicity at particular target sites. (C) 1997 Elsevier Science Ireland Ltd. C1 NCI,FREDERICK CANC RES & DEV CTR,INORGAN CARCINOGENESIS SECT,LAB COMPARAT CARCINOGENESIS,FREDERICK,MD 21702. NR 28 TC 29 Z9 29 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0300-483X J9 TOXICOLOGY JI Toxicology PD FEB 28 PY 1997 VL 117 IS 2-3 BP 99 EP 109 PG 11 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA WK634 UT WOS:A1997WK63400002 PM 9057889 ER PT J AU Stewart, C AF Stewart, C TI Nuclear Transplantation - An udder way of making lambs SO NATURE LA English DT Editorial Material ID SHEEP EMBRYOS; CLEAVAGE; MICE RP Stewart, C (reprint author), NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,CANC & DEV BIOL LAB,FREDERICK,MD 21702, USA. NR 10 TC 12 Z9 12 U1 0 U2 2 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD FEB 27 PY 1997 VL 385 IS 6619 BP 769 EP & DI 10.1038/385769a0 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WK570 UT WOS:A1997WK57000024 PM 9039905 ER PT J AU Petosa, C Collier, RJ Klimpel, KR Leppla, SH Liddington, RC AF Petosa, C Collier, RJ Klimpel, KR Leppla, SH Liddington, RC TI Crystal structure of the anthrax toxin protective antigen SO NATURE LA English DT Article ID LETHAL FACTOR; MAMMALIAN-CELLS; MEMBRANE; CHANNELS AB Protective antigen (PA) is the central component of the three-part protein toxin secreted by Bacillus anthracis, the organism responsible for anthrax(1). After proteolytic activation on the host cell surface, PA forms a membrane-inserting heptamer that translocates the toxic enzymes, oedema factor and lethal factor, into the cytosol(2-4). PA, which has a relative molecular mass of 83,000 (M(r) 83K), can also translocate heterologous proteins, and is being evaluated for use as a general protein delivery system(5,6). Here we report the crystal structure of monomeric PA at 2.1 Angstrom resolution and the water-soluble heptamer at 4.5 Angstrom resolution, The monomer is organized mainly into antiparallel beta-sheets and has four domains: an amino-terminal domain (domain 1) containing two calcium ions and the cleavage site for activating proteases; a heptamerization domain (domain 2) containing a large flexible loop implicated in membrane insertion; a small domain of unknown function (domain 3); and a carboxy-terminal receptor-binding domain (domain 4). Removal of a 20K amino-terminal fragment from domain 1 allows the assembly of the heptamer, a ring-shaped structure with a negatively charged lumen, and exposes a large hydrophobic surface for binding the toxic enzymes. We propose a model of pH-dependent membrane insertion involving the formation of a porin-like, membrane-spanning beta-barrel. C1 HARVARD UNIV,SCH MED,DEPT MICROBIOL & MOL GENET,BOSTON,MA 02115. NIDR,MICROBIAL ECOL LAB,NIH,BETHESDA,MD 20982. RP Petosa, C (reprint author), UNIV LEICESTER,DEPT BIOCHEM,LEICESTER LE1 7RH,LEICS,ENGLAND. OI Collier, R John/0000-0002-2427-4239 NR 30 TC 563 Z9 584 U1 6 U2 42 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD FEB 27 PY 1997 VL 385 IS 6619 BP 833 EP 838 DI 10.1038/385833a0 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WK570 UT WOS:A1997WK57000058 PM 9039918 ER PT J AU Stork, E Gorjanc, E Verter, J Younes, N Stenzel, BA Powers, T Sokol, G Wright, LL Yaffe, SJ Catz, C VanMeurs, K Rhine, W Ball, B Brilli, R Moles, L Crowley, M Backstrom, C Crouse, D Hudson, T Konduri, G Bara, R Kleinman, M Hensman, A Rothstein, RW Ehrenkranz, RA Solimano, A Germain, F Walker, R Ramirez, AM Singhal, N Bourcier, L Fajardo, C Cook, V Kirpalani, H Monkman, S Johnston, A Mullahoo, K Finer, NN Peliowski, A Etches, P Kamstra, B Sankarhan, K Riehl, A Blanchard, P Gouin, R Wearden, M Gomez, M Moon, Y Bauer, CR Donovan, EF Fanaroff, AA Korones, SB Lemons, JA Oh, W Papile, LA Shankaran, S Stoll, BJ Tyson, JE Avery, G DAlton, M Bracken, MB Gleason, CA Maguire, M Redmond, C Silverman, W Sinclair, J AF Stork, E Gorjanc, E Verter, J Younes, N Stenzel, BA Powers, T Sokol, G Wright, LL Yaffe, SJ Catz, C VanMeurs, K Rhine, W Ball, B Brilli, R Moles, L Crowley, M Backstrom, C Crouse, D Hudson, T Konduri, G Bara, R Kleinman, M Hensman, A Rothstein, RW Ehrenkranz, RA Solimano, A Germain, F Walker, R Ramirez, AM Singhal, N Bourcier, L Fajardo, C Cook, V Kirpalani, H Monkman, S Johnston, A Mullahoo, K Finer, NN Peliowski, A Etches, P Kamstra, B Sankarhan, K Riehl, A Blanchard, P Gouin, R Wearden, M Gomez, M Moon, Y Bauer, CR Donovan, EF Fanaroff, AA Korones, SB Lemons, JA Oh, W Papile, LA Shankaran, S Stoll, BJ Tyson, JE Avery, G DAlton, M Bracken, MB Gleason, CA Maguire, M Redmond, C Silverman, W Sinclair, J TI Inhaled nitric oxide in full-term and nearly full-term infants with hypoxic respiratory failure SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID PERSISTENT PULMONARY-HYPERTENSION; EXTRACORPOREAL MEMBRANE-OXYGENATION; RELAXING FACTOR; BLEEDING-TIME; NEWBORN; VASOCONSTRICTION; HYPERVENTILATION; VASODILATOR; PEROXYNITRITE; MANAGEMENT AB Background Neonates with pulmonary hypertension have been treated with inhaled nitric oxide because of studies suggesting that it is a selective pulmonary vasodilator. We conducted a randomized, multicenter, controlled trial to determine whether inhaled nitric oxide would reduce mortality or the initiation of extracorporeal membrane oxygenation in infants with hypoxic respiratory failure, Methods Infants born after a gestation of greater than or equal to 34 weeks who were 14 days old or less, had no structural heart disease, and required assisted ventilation and whose oxygenation index was 25 or higher on two measurements were eligible for the study. The infants were randomly assigned to receive nitric oxide at a concentration of 20 ppm or 100 percent oxygen (as a control). Infants whose partial pressure of arterial oxygen (PaO2) increased by 20 mm Hg or less after 30 minutes were studied for a response to 80-ppm nitric oxide or control gas, Results The 121 infants in the control group and the 114 in the nitric oxide group had similar base-line clinical characteristics. Sixty-four percent of the control group and 46 percent of the nitric oxide group died within 120 days or were treated with extracorporeal membrane oxygenation (P=0.006). Seventeen percent of the control group and 14 percent of the nitric oxide group died (P not significant), but significantly fewer in the nitric oxide group received extracorporeal membrane oxygenation (39 percent vs. 54 percent, P=0.014). The nitric oxide group had significantly greater improvement in PaO2 (mean [+/-SD] increase, 58.2+/-85.2 mm Hg, vs. 9.7+/-51.7 mm Hg in the controls; P<0.001) and in the oxygenation index (a decrease of 14.1+/-21.1, vs, an increase of 0.8+/-21.1 in the controls; P<0,001). The study gas was not discontinued in any infant because of toxicity. Conclusions Nitric oxide therapy reduced the use of extracorporeal membrane oxygenation, but had no apparent effect on mortality, in critically ill infants with hypoxic respiratory failure. (C) 1997, Massachusetts Medical Society. C1 YALE UNIV,SCH MED,DEPT PEDIAT,NEW HAVEN,CT 06520. CASE WESTERN RESERVE UNIV,CLEVELAND,OH 44106. GEORGE WASHINGTON UNIV,CTR BIOSTAT,ROCKVILLE,MD. INDIANA UNIV,INDIANAPOLIS,IN 46204. NICHHD,BETHESDA,MD. STANFORD UNIV,PALO ALTO,CA 94304. UNIV CINCINNATI,CINCINNATI,OH. UNIV NEW MEXICO,ALBUQUERQUE,NM 87131. UNIV TENNESSEE,MEMPHIS,TN. WAYNE STATE UNIV,DETROIT,MI. BROWN UNIV,WOMEN & INFANTS HOSP,PROVIDENCE,RI. BRITISH COLUMBIA CHILDRENS HOSP,VANCOUVER,BC V6H 3V4,CANADA. CHILDRENS HOSP EASTERN ONTARIO,OTTAWA,ON K1H 8L1,CANADA. FOOTHILLS PROV GEN HOSP,CALGARY,AB T2N 2T9,CANADA. CTR HLTH SCI,WINNIPEG,MB,CANADA. MCMASTER UNIV,HAMILTON,ON,CANADA. MONTREAL CHILDRENS HOSP,MONTREAL,PQ H3H 1P3,CANADA. ROYAL ALEXANDRA HOSP,EDMONTON,AB,CANADA. ROYAL UNIV HOSP,SASKATOON,SK S7N 0W8,CANADA. UNIV SHERBROOKE,SHERBROOKE,PQ J1K 2R1,CANADA. TEXAS CHILDRENS HOSP,HOUSTON,TX 77030. UNIV MIAMI,MIAMI,FL 33152. EMORY UNIV,ATLANTA,GA 30322. UNIV TEXAS,SW MED CTR,DALLAS,TX 75235. CHILDRENS HOSP,NATL MED CTR,WASHINGTON,DC 20010. TUFTS UNIV NEW ENGLAND MED CTR,BOSTON,MA 02111. JOHNS HOPKINS UNIV HOSP,BALTIMORE,MD 21287. UNIV PENN,PHILADELPHIA,PA 19104. UNIV PITTSBURGH,PITTSBURGH,PA. NR 32 TC 460 Z9 468 U1 1 U2 7 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD FEB 27 PY 1997 VL 336 IS 9 BP 597 EP 604 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA WK028 UT WOS:A1997WK02800001 ER PT J AU Zhang, YQ Kiel, DP Kreger, BE Cupples, LA Ellison, RC Dorgan, JF Schatzkin, A Levy, D Felson, DT AF Zhang, YQ Kiel, DP Kreger, BE Cupples, LA Ellison, RC Dorgan, JF Schatzkin, A Levy, D Felson, DT TI Bone mass and the risk of breast cancer among postmenopausal women SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID ESTROGEN REPLACEMENT THERAPY; HORMONE-BINDING GLOBULIN; MINERAL DENSITY; ELDERLY WOMEN; SEX-HORMONES; ENDOGENOUS HORMONES; MENSTRUAL-CYCLE; HIP-FRACTURES; METAANALYSIS; COMMUNITY AB Background Recent studies have shown a direct relation between serum estrogen levels assessed at a single point in time and the risk of breast cancer, but no evidence links estrogen levels assessed repeatedly over an extended interval to the risk of breast cancer. Bone mass has been proposed as a marker of cumulative exposure to estrogen in women. We therefore studied the association between bone mass and the incidence of breast cancer. Methods Between 1967 and 1970, 1373 women who were 47 to 80 years old and had no history of breast cancer underwent posteroanterior hand radiography in the Framingham Study. We used radiogrametry to measure the cortical width cif each woman's second metacarpal. Participants were followed until the end of 1993. All incident cases of breast cancer were confirmed by pathological reports. We used a Cox proportional-hazards model to examine the relation of metacarpal bone mass to the risk of postmenopausal breast cancer. Results Postmenopausal breast cancer developed in 91 subjects. Incidence rates per 1000 person-years increased from 2.0 among the women in the lowest age-specific quartile of metacarpal bone mass to 2.6, 2.71 and 7.0 among the women in the second, third, and highest quartiles, respectively. After adjustments for age and other potential confounding factors, the rate ratios for the risk of breast cancer were 1.0, 1.3, 1.3, and 3.5 from the lowest quartile to the highest (P for trend, <0.001). Conclusions Women in the highest quartile of bone mass are at higher risk for postmenopausal breast cancer than those in the lowest quartile. The mechanisms underlying this relation are not understood, but cumulative exposure to estrogen may play a part. (C) 1997, Massachusetts Medical Society. C1 BOSTON UNIV,SCH MED,EVANS DEPT MED,PREVENT MED & EPIDEMIOL SECT,BOSTON,MA 02118. BOSTON UNIV,SCH MED,EVANS DEPT MED,GEN INTERNAL MED SECT,BOSTON,MA 02118. HARVARD UNIV,SCH MED,HEBREW REHABIL CTR AGED,BOSTON,MA. HARVARD UNIV,SCH MED,DIV AGING,BOSTON,MA 02115. BOSTON UNIV,SCH PUBL HLTH,DEPT EPIDEMIOL & BIOSTAT,BOSTON,MA. NCI,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20892. FRAMINGHAM HEART DIS EPIDEMIOL STUDY,FRAMINGHAM,MA. NHLBI,BETHESDA,MD 20892. RP Zhang, YQ (reprint author), BOSTON UNIV,MED CTR,CTR ARTHRITIS,RM B-612,88 E NEWTON ST,BOSTON,MA 02118, USA. OI Kiel, Douglas/0000-0001-8474-0310 FU NHLBI NIH HHS [N01-HC-38038]; NIAMS NIH HHS [AR20613, AR41398] NR 60 TC 207 Z9 209 U1 0 U2 1 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD FEB 27 PY 1997 VL 336 IS 9 BP 611 EP 617 DI 10.1056/NEJM199702273360903 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA WK028 UT WOS:A1997WK02800003 PM 9032046 ER PT J AU LeRoith, D King, G Flier, JS AF LeRoith, D King, G Flier, JS TI Insulin-like growth factors SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Review ID FACTOR-I THERAPY; DEPENDENT DIABETES-MELLITUS; MESSENGER RIBONUCLEIC-ACID; NONISLET CELL TUMORS; BINDING-PROTEINS; HYPOGLYCEMIA; RESISTANCE; SERUM; MECHANISMS; RECEPTORS RP LeRoith, D (reprint author), NIH,DIABET BRANCH,RM 85235A,BLDG 10,BETHESDA,MD 20892, USA. NR 41 TC 380 Z9 389 U1 0 U2 13 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD FEB 27 PY 1997 VL 336 IS 9 BP 633 EP 640 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA WK028 UT WOS:A1997WK02800007 PM 9032050 ER PT J AU Gorospe, M Cirielli, C Wang, XT Seth, P Capogrossi, MC Holbrook, NJ AF Gorospe, M Cirielli, C Wang, XT Seth, P Capogrossi, MC Holbrook, NJ TI p21(Waf1/Cip1) protects against p53-mediated apoptosis of human melanoma cells SO ONCOGENE LA English DT Article DE melanoma; p53; p21; apoptosis ID CYCLE CONTROL; G(1) ARREST; P53; EXPRESSION; ADENOVIRUS; CANCER; P21 AB The tumor suppressive effect of p53 is believed to be rooted in its two primary functions: the implementation of cellular growth arrest and the execution of apoptotic cell death, While p53-regulated expression of the cyclin-dependent kinase inhibitor p21(Waf1/Cip1) appears to be central for the implementation of G(1) arrest, the participation of p21(Waf1/Cip1) in p53-triggered cell death remains controversial, In the present study, overexpression of p53 in human melanoma SK-MEL-110 cells through use of an adenoviral expression vector (AdCMV,p53) was found to result in apoptosis, while similar infection of primary vascular smooth muscle cells (VSMC) instead resulted in a moderate inhibition of growth, Expression of p21(Waf1/Cip1) was strongly elevated in VSMC, but showed little change in SK-MEL-110 cells, although expression of another p53-regulated gene (GADD45) was comparable in both AdCMV.p53-infected cell types, Evidence that p21(Waf1/Cip1) expression may be required for surviving p53-induced cell death was further supported by the finding that p53 overexpression was highly toxic for p21-deficient mouse embryonal fibroblasts (p21(-/-) MEFs), In both SK-MEL-110 and p21(-/-) MEFs, adenovirus-driven ectopic expression of p21(Waf1/Cip1) resulted in a substantial protection against p53-induced apoptosis, indicating that p21(Waf1/Cip1) rescued cells from a path of programmed cell death to one of enhanced survival. C1 NIA,NIH,CELLULAR & MOL BIOL LAB,BALTIMORE,MD 21224. NIA,NIH,CARDIOVASC SCI LAB,BALTIMORE,MD 21224. NCI,MED BRANCH,MED BREAST CANC SECT,NIH,BETHESDA,MD 20892. IST DERMOPAT IMMACOLATA,LAB PATOL VASCOLARE,I-00167 ROME,ITALY. NR 35 TC 274 Z9 279 U1 2 U2 4 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD FEB 27 PY 1997 VL 14 IS 8 BP 929 EP 935 DI 10.1038/sj.onc.1200897 PG 7 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA WK344 UT WOS:A1997WK34400006 PM 9050992 ER PT J AU Hamburger, AW Smith, T Elliget, K Hagiwara, K Gerwin, BI AF Hamburger, AW Smith, T Elliget, K Hagiwara, K Gerwin, BI TI TGF-beta 1 resistance is not associated with alterations in TGF-beta type II receptors in immortalized human lung epithelial cells SO CANCER LETTERS LA English DT Article DE TGF-beta; cancer cells; TGF-beta gamma receptors ID GROWTH-FACTOR-BETA; COLON-CANCER CELLS; MICROSATELLITE INSTABILITY; REGION; VIRUS; GENES; SV40 AB A frequent cause of TGF-beta resistance is decreased expression or mutation of TGF-beta receptor Type II (TGF beta RII) protein. We previously isolated two isogeneic subclones of the human bronchial epithelial cell line BEAS-2B that are respectively resistant (R.1) or sensitive (S.6) to the growth inhibitory effects of TGF-beta 1. In this study, we examined TGF beta IIR expression, ability to bind TGF-beta 1, and cDNA sequence in the resistant cell line. Immunofluorescent analyses with antibody to TGF beta RII indicated that this protein was expressed at the surface of R.1 cells. Affinity binding studies showed that TGF-beta 1 bound equally well to the resistant (R.1) and sensitive (S.6) cell lines. PCR cloning and sequencing of TGF beta RII cDNA revealed no changes from wild type in the resistant cell line. We conclude that alterations in TGF-beta Type II receptor are not responsible for TGF-beta resistance in this cell line. (C) 1997 Elsevier Science Ireland Ltd. C1 DEPT PATHOL, BALTIMORE, MD USA. NCI, HUMAN CARCINOGENESIS LAB, BETHESDA, MD 20892 USA. RP Hamburger, AW (reprint author), UNIV MARYLAND, CTR CANC, 655 W BALTIMORE ST, ROOM 9-046 BRB, BALTIMORE, MD 21201 USA. FU NCI NIH HHS [F33CA63763] NR 22 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD FEB 26 PY 1997 VL 113 IS 1-2 BP 65 EP 70 DI 10.1016/S0304-3835(97)04596-5 PG 6 WC Oncology SC Oncology GA WK873 UT WOS:A1997WK87300010 PM 9065803 ER PT J AU Felix, K Potter, M Bornkamm, GW Janz, S AF Felix, K Potter, M Bornkamm, GW Janz, S TI In vitro mutagenicity of the plasmacytomagenic agent pristane (2,6,10,14-tetramethylpentadecane) SO CANCER LETTERS LA English DT Article DE pristane; lacI; plasmacytoma; B lymphocyte; fibroblast ID ALKANE PRISTANE; CELLS; GENE; MICE; ACTIVATION; FLUIDITY; BILAYERS; ASSAY; RATS; DNA AB Pristane is known to induce a distinct type of B-cell-derived malignant lymphoma, plasmacytoma, after administration into the peritoneal cavity of genetically susceptible BALB/cAnPt mice. Since the mechanism of pristane-induced plasmacytoma development is poorly understood, we chose to examine the possibility that pristane is mutagenic in rodent cells and decided to use bacteriophage lambda-derived lacI/lacZ genes as target/reporter to quantitate mutagenesis. Here we show that in vitro exposure to micromolar amounts of pristane, delivered as an inclusion complex with beta-cyclodextrin, resulted in 1.7-fold and 6.2-fold increases of mutant frequencies over controls in a cell line of rat fibroblasts and primary mouse B lymphocytes, respectively. We conclude that pristane can be mutagenic to mammalian cells, yet are currently unable to explain the mechanism of mutagenicity. It is suggested that B-cell mutagenesis contributes to the plasmacytomagenic activity of pristane in vivo. (C) 1997 Elsevier Science Ireland Ltd. C1 NCI,GENET LAB,DBS,NIH,BETHESDA,MD 20892. RP Felix, K (reprint author), GSF MUNICH,INST KLIN MOL BIOL & TUMORGENET,D-81377 MUNICH,GERMANY. NR 23 TC 4 Z9 4 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD FEB 26 PY 1997 VL 113 IS 1-2 BP 71 EP 76 DI 10.1016/S0304-3835(97)04597-7 PG 6 WC Oncology SC Oncology GA WK873 UT WOS:A1997WK87300011 PM 9065804 ER PT J AU Dixon, SC Zalles, A Giordano, C Lush, RM Venzon, D Reed, E Figg, WD AF Dixon, SC Zalles, A Giordano, C Lush, RM Venzon, D Reed, E Figg, WD TI In vitro effect of gallium nitrate when combined with ketoconazole in the prostate cancer cell line PC-3 SO CANCER LETTERS LA English DT Article DE prostate; carcinoma; cell culture; antiproliferative; androgen-independence; hormone refractory ID INVITRO; INVIVO AB Secondary hormonal manipulations are common following the failure of combined androgen blockade in patients with metastatic prostate cancer. Ketoconazole has been shown to have activity in this disease by inhibiting cytochrome P450 steroid hormone biosynthesis, thus inducing androgen deprivation. Gallium nitrate has been reported to target tumor tissue in vitro and some preliminary data suggests activity in patients with prostate cancer. Thus, we conducted a Phase II study of gallium nitrate in patients with androgen-independent prostate cancer. Two patients with progressive prostate cancer were removed from this study and subsequently placed on ketoconazole, as a palliative agent. Surprisingly, both of these patients had a greater than 50% decline in their prostate specific antigen (PSA) with this secondary endocrine maneuver. Based on this clinical observation, we conducted the following in vitro study to determine if there was a substantial additive effect of gallium nitrate followed by ketoconazole. Gallium nitrate or ketoconazole was added to the androgen-independent prostatic epithelial cell line, PC-3. One hundred and twenty hours (120 h) following the addition of one of the agents, the media was aspirated and the second agent was added to the wells. One plate was assayed every 24 h for cell viability using a non-isotopic cell proliferation assay kit. Cells treated with gallium nitrate followed by ketoconazole were 70-100% of control at the end of the gallium nitrate treatment; ketoconazole was then added and viability either remained constant or dropped steadily. Gallium nitrate by itself had a weak inhibitory effect on cell viability that only became apparent at the highest concentration evaluated. Ketoconazole, on the other hand, showed a substantial growth inhibition that was concentration-dependent. Cells treated with this agent alone showed a pronounced steady decrease in viability. Exposure to ketoconazole for 120 h followed by incubation in culture medium alone for 120 h caused a decrease in cell viability to 26.0% of control. Our in vitro results suggest that the combination of gallium nitrate and ketoconazole has no additive activity in the PC-3 cell line- Furthermore, this study confirms that ketoconazole added to prostate cancer cells has antiproliferative activity. The in vitro activity of ketoconazole has traditionally been thought to result from its inhibition of cytochrome P450-dependent enzymes responsible for steroidogenesis; however, an alternative hypothesis is necessary to explain the cytotoxic effect in the absence of adrenal and testicular androgen production as found in an in vitro system. C1 NCI,MED BRANCH,DIV CLIN SCI,BETHESDA,MD 20892. RI Venzon, David/B-3078-2008; Figg Sr, William/M-2411-2016 NR 13 TC 12 Z9 12 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD FEB 26 PY 1997 VL 113 IS 1-2 BP 111 EP 116 DI 10.1016/S0304-3835(97)04603-X PG 6 WC Oncology SC Oncology GA WK873 UT WOS:A1997WK87300016 PM 9065809 ER PT J AU Paolini, M Mesirca, R Pozzetti, L Sapone, A CantelliForti, G AF Paolini, M Mesirca, R Pozzetti, L Sapone, A CantelliForti, G TI Biomarkers of effect in evaluating dithianon cocarcinogenesis: Selective induction and suppression of murine CYP3A isoform SO CANCER LETTERS LA English DT Article DE dithianon; cytochrome P450; monooxygenases; pesticide; enzyme induction ID SENSITIVE ASSAY; PESTICIDES; RAT; PENTOXYRESORUFIN; OXIDATION; CYP2B1; LUNG AB The ability of dithianon, whose mutagenic/cocarcinogenic activity has as yet not been clarified, to affect specific biomarkers of effect related to non-genotoxic cocarcinogenesis was investigated. For this purpose, several CYP-dependent reactions have been studied in liver, kidney and lung microsomes derived from male and female Swiss Albino CD1 mice treated i.p. with single (3 or 6 mg kg(-1) b.w.) or repeated (3 mg kg(-1) b.w., daily for 3 days) administrations of such fungicide. No significant changes in both absolute and relative liver, kidney and lung weights were achieved after dithianon treatment. Whereas a single dose was able to significantly induce certain monooxygenases, with repeated treatments a loss of activity was observed. For example, a similar to 2.4-fold increase of CYP3A-dependent activity, probed by N-demethylation of aminopyrine, was achieved in the liver (both sexes, lower dose) and, to a lesser extent, in lung. A small, but significant increase in the hydroxylation of p-nitrophenol (2E1) and in the O-deethylation of ethoxycoumarin (mixed) was also found in liver. With the exception of a similar to 46% loss in the 3A-like activity, no appreciable changes of the selected biomarkers were observed in kidney. Repeated dithianon doses were able to significantly reduce the 3A- and 2E1-dependent monooxygenases (similar to 30% and similar to 30% loss, respectively, averaged between male and female), as well as ethoxycoumarin O-deethylase activity (similar to 54% loss) in the liver. On the contrary, no significant CYP modulation in both kidney and lung was recorded. On the whole, dithianon has a complex pattern of CYP induction or suppression in various tissues of both sexes, suggesting the possible toxic/cotoxic and cocarcinogenic potential of this fungicide. These data can contribute to a better understanding of its toxicological profile, providing more information concerning the risk associated to human exposure. C1 UNIV AUTONOMA MADRID,CTR NATL BIOTECNOL,MADRID 28048,SPAIN. NCI,NIH,LABS MOL CARCINOGENESIS,BETHESDA,MD 20872. UNIV TEXAS,MED BRANCH,DEPT PREVENT MED & COMMUNITY HLTH,GALVESTON,TX 77550. RP Paolini, M (reprint author), UNIV BOLOGNA,BIOCHEM TOXICOL UNIT,DEPT PHARMACOL,VIA INERIO 48,I-40126 BOLOGNA,ITALY. RI Sapone, Andrea/E-6704-2013; OI Sapone, Andrea/0000-0001-8496-6977; paolini, moreno/0000-0002-2338-8859 NR 31 TC 6 Z9 6 U1 1 U2 6 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD FEB 26 PY 1997 VL 113 IS 1-2 BP 221 EP 228 DI 10.1016/S0304-3835(97)04711-3 PG 8 WC Oncology SC Oncology GA WK873 UT WOS:A1997WK87300032 PM 9065825 ER PT J AU Badio, B Garraffo, HM Plummer, CV Padgett, WL Daly, JW AF Badio, B Garraffo, HM Plummer, CV Padgett, WL Daly, JW TI Synthesis and nicotinic activity of epiboxidine: An isoxazole analogue of epibatidine SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE epibatidine; epiboxidine; ABT 418; nicotinic receptor; analgesia ID ACETYLCHOLINE-RECEPTORS; COMPARATIVE PHARMACOLOGY; ALKALOID EPIBATIDINE; AGONIST; ABT-418; DIVERSITY AB Synthetic (+/-)-epiboxidine (exo-2-(3-methyl-5-isoxazolyl)-7-azabicyclo[2.2.1]heptane) is a methylisoxazole analog of the alkaloid epibatidine, itself a potent nicotinic receptor agonist with antinociceptive activity. Epiboxidine contains a methylisoxazolyl ring replacing the chloropyridinyl ring of epibatidine. Thus, it is also an analog of another nicotinic receptor agonist, ABT 418 ((S)-3-methyl-5-(1-methyl-2-pyrrolidinyl)isoxazole), in which the pyridinyl ring of nicotine has been replaced by the methylisoxazolyl ring. Epiboxidine was about 10-fold less potent than epibatidine and about 17-fold more potent than ABT 418 in inhibiting [H-3]nicotine binding to alpha(4) beta(2) nicotinic receptors in rat cerebral cortical membranes. In cultured cells with functional ion flux assays, epiboxidine was nearly equipotent to epibatidine and 200-fold more potent than ABT 418 alpha(3) beta(4(5)) nicotinic receptors in PCl2 cells. Epiboxidine was about 5-fold less potent than epibatidine and about 30-fold more potent than ABT 418 in TE671 cells with alpha(1) beta(1) gamma delta nicotinic receptors. In a hot-plate antinociceptive assay with mice, epiboxidine was about 10-fold less potent than epibatidine. However, epiboxidine was also much less toxic than epibatidine in mice. C1 NIDDKD,BIOORGAN CHEM LAB,NIH,BETHESDA,MD 20892. NR 18 TC 78 Z9 79 U1 1 U2 13 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 FEB 26 PY 1997 VL 321 IS 2 BP 189 EP 194 DI 10.1016/S0014-2999(96)00939-9 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA WL457 UT WOS:A1997WL45700007 PM 9063687 ER PT J AU Gallin, JI Smits, HL AF Gallin, JI Smits, HL TI Managing the interface between medical schools, hospitals, and clinical research SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article AB Objective.-To review how academic health centers are coping with the changing environment of health care delivery with special emphasis on the impact of the changing health care system on clinical research. Design.-In response to Health and Human Services Secretary Donna Shalala's 1995 mandated review of the National Institutes of Health (NIH) Warren Grant Magnuson Clinical Center, an NIH review team visited 30 health facilities and government-owned organizations throughout the country. The review team determined what strategies are used by academic health centers to survive and thrive in the changing health care marketplace. The findings have implications for the NIH Clinical Center as well as academic health centers. Conclusions.-Management strategies in successful academic health centers include streamlined governance structures whereby small groups of highly empowered group leaders allow institutions to move quickly and decisively; an active strategic planning process; close integration of hospital and medical school management; heavy investment in information systems; and new structures for patient care delivery. Successful centers are initiating discussions with third-party payers and are implementing new initiatives, such as establishing their own managed care organizations, purchasing physician practices, or owning hospitals. Other approaches include establishing revenue-generating centers for clinical research and new relations with industry. Attention to the infrastructure required to support the training and conduct of clinical research is essential for the future vitality of medical schools. C1 US DEPT HHS,US HLTH CARE FINANCING ADM,BETHESDA,MD. RP Gallin, JI (reprint author), NIH,CTR CLIN,WARREN GRANT MAGNUSON CLIN CTR,BLDG 10,ROOM 2C128,BETHESDA,MD 20892, USA. NR 8 TC 28 Z9 28 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD FEB 26 PY 1997 VL 277 IS 8 BP 651 EP 654 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA WJ498 UT WOS:A1997WJ49800034 PM 9039884 ER PT J AU Shi, JG Ghirlando, R Beavil, RL Beavil, AJ Keown, MB Young, RJ Owens, RJ Sutton, BJ Gould, HJ AF Shi, JG Ghirlando, R Beavil, RL Beavil, AJ Keown, MB Young, RJ Owens, RJ Sutton, BJ Gould, HJ TI Interaction of the low-affinity receptor CD23/Fc epsilon RII lectin domain with the Fc epsilon 3-4 fragment of human immunoglobulin E SO BIOCHEMISTRY LA English DT Article ID MANNOSE-BINDING PROTEIN; HELICAL COILED-COIL; HUMAN IGE-FC; NEUTRON-SCATTERING; ANTIBODY-RESPONSE; HUMAN-LYMPHOCYTES; ANIMAL LECTINS; IN-VIVO; CD23; CELLS AB CD23/Fc epsilon RII, the low-affinity receptor for IgE, is a multifunctional protein of importance in blood cell development and the immune system. We have studied the interaction of CD23 with IgE in solution using hydrodynamic methods applied to recombinant fragments of both ligands: sCD23, corresponding to the soluble lectin domain of CD23, and Fc epsilon 3-4, a dimer of the C epsilon 3-C epsilon 4 sequence of IgE. The hydrodynamic, spectroscopic, and biological properties of these fragments suggest that they have a fully native structure. Sedimentation equilibrium studies on mixtures of sCD23 and Fc epsilon 3-4 indicate that IgE has two binding sites for CD23, each characterized by affinities of approximately 10(5) M(-1). Analysis of the sedimentation as a function of temperature allows conclusions to be drawn about the thermodynamics of binding at the two sites. Binding at the first site is characterized by large changes in enthalpy (Delta H degrees(T0) = -2.1 +/- 3.3 kcal mol(-1)) and heat capacity (Delta Cp degrees = -320 +/- 320 cal mol(-1) K-1), whereas binding at the second site is characterized by small changes in enthalpy (Delta H degrees(T0) = 0.1 +/- 5.6 kcal mol(-1)) and heat capacity (Delta Cp degrees = -140 +/- 550 cal mol(-1) K-1). In native CD23, there are two or three lectin domains, associated through an alpha-helical coiled-coil stalk. The predicted structure of the CD23 oligomers and symmetry considerations rule out the possibility of two lectin domains from one oligomer binding to identical sites in IgE. The notion of two types of interaction in the 2:1 complex between CD23 and IgE is consistent with the thermodynamic data presented. C1 UNIV LONDON KINGS COLL,RANDALL INST,LONDON WC2B 5RL,ENGLAND. CELLTECH LTD,SLOUGH SL1 4EN,BERKS,ENGLAND. NIDDKD,MOL BIOL LAB,BETHESDA,MD 20892. RI Ghirlando, Rodolfo/A-8880-2009; Beavil, Andrew/B-5624-2009 OI Beavil, Andrew/0000-0002-0768-122X FU Wellcome Trust NR 50 TC 49 Z9 49 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD FEB 25 PY 1997 VL 36 IS 8 BP 2112 EP 2122 DI 10.1021/bi961231e PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WK479 UT WOS:A1997WK47900020 PM 9047310 ER PT J AU Li, LP Darden, TA Freedman, SJ Furie, BC Furie, B Baleja, JD Smith, H Hiskey, RG Pedersen, LG AF Li, LP Darden, TA Freedman, SJ Furie, BC Furie, B Baleja, JD Smith, H Hiskey, RG Pedersen, LG TI Refinement of the NMR solution structure of the gamma-carboxyglutamic acid domain of coagulation factor IX using molecular dynamics simulation with initial Ca2+ positions determined by a genetic algorithm SO BIOCHEMISTRY LA English DT Article ID PARTICLE MESH EWALD; PROTHROMBIN FRAGMENT-1; MEMBRANE-BINDING; GLA DOMAIN; PROTEINS; ION; MINIMIZATION; CONSTRAINTS; LIBRARIES; RESIDUES AB A genetic algorithm (GA) successfully identified the calcium positions in the crystal structure of bovine prothrombin fragment 1 bound with calcium ions (bfl/Ca). The same protocol was then used to determine the calcium positions in a closely related fragment, the Gla domain of coagulation factor IX, the structure of which had previously been determined by NMR spectroscopy in the presence of calcium ions. The most frequently occurring low-energy structure found by GA was used as the starting structure for a molecular dynamics refinement. The molecular dynamics simulation was performed using explicit water and the Particle-Mesh Ewald method to accommodate the long-range electrostatic forces. While the overall conformation of the NMR structure was preserved, significant refinement is apparent when comparing the simulation average structure with its NMR precursor in terms of the N-terminal (Tyr1-N) network, the total number of hydrogen bonds, the calcium ion coordinations, and the compactness of the structure. It is likely that the placement of calcium ions in the protein is critical for refinement. The calcium ions apparently induce structural changes during the course of the simulation that result in a more compact structure. C1 NIEHS,RES TRIANGLE PK,NC 27709. UNIV N CAROLINA,DEPT CHEM,CHAPEL HILL,NC 27599. TUFTS UNIV NEW ENGLAND MED CTR,CTR HEMOSTASIS & THROMBOSIS RES,DIV HEMATOL ONCOL,BOSTON,MA 02111. TUFTS UNIV,SCH MED,DEPT MED & BIOCHEM,BOSTON,MA 02111. SACKLER SCH GRAD BIOMED SCI,BOSTON,MA 02111. RI Pedersen, Lee/E-3405-2013 OI Pedersen, Lee/0000-0003-1262-9861 FU NHLBI NIH HHS [HL27995, HL06350, HL42443] NR 35 TC 37 Z9 38 U1 2 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD FEB 25 PY 1997 VL 36 IS 8 BP 2132 EP 2138 DI 10.1021/bi962250r PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WK479 UT WOS:A1997WK47900022 PM 9047312 ER PT J AU Stebbins, JW Jaffe, H Fales, HM Moller, JR AF Stebbins, JW Jaffe, H Fales, HM Moller, JR TI Determination of a native proteolytic site in myelin-associated glycoprotein SO BIOCHEMISTRY LA English DT Article ID MULTIPLE-SCLEROSIS LESIONS; BASIC-PROTEIN; RAT-BRAIN; NEUTRAL PROTEASE; CDNA CLONING; CATHEPSIN-B; QUANTITATION; SEQUENCE; PEPTIDES AB Myelin-associated glycoprotein (MAG) is a transmembrane structural protein that is thought to be involved in the formation and/or maintenance of the myelin sheath. MAG is proteolyzed at a discrete location near its transmembrane domain by a calcium activated myelin-associated cysteine protease in the central nervous system. The soluble proteolysis product, dMAG, can be found in the cerebrospinal fluid. The proteolysis of MAG may be involved in the molecular mechanism of demyelination, as the proteolytic degradation of myelin proteins has been observed in disease states. The site for the proteolysis of MAG to dMAG was identified. This was accomplished by developing a protocol for the purification of soluble dMAG and by protein sequencing of short peptides containing the carboxy-terminus of dMAG. The results from these experiments indicated that the native proteolytic site in MAG was located extracellularly and occurred between residues 512 (Ala) and 513 (Lys), with a large hydrophobic residue at the P-2 position (Trp-511). This finding in turn indicated that the protease for which MAG was a substrate had cathepsin L-like activity. Cathepsin L-like activity in myelin was confirmed by peptidolysis experiments using known cathepsin L substrates. Additional experiments are in progress to determine the identity of this protease. C1 NINCDS,DEMYELINATING DISORDERS UNIT,LMCN,NIH,BETHESDA,MD 20892. NINCDS,LNC,PROTEIN PEPTIDE SEQUENCING FACIL,NIH,BETHESDA,MD 20892. NHLBI,BIOPHYS CHEM LAB,NIH,BETHESDA,MD 20892. NR 33 TC 20 Z9 21 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD FEB 25 PY 1997 VL 36 IS 8 BP 2221 EP 2226 DI 10.1021/bi962385x PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WK479 UT WOS:A1997WK47900033 PM 9047323 ER PT J AU Beaty, MW Fetsch, P Wilder, AM Marincola, F Abati, A AF Beaty, MW Fetsch, P Wilder, AM Marincola, F Abati, A TI Effusion cytology of malignant melanoma - A morphologic and immunocytochemical analysis including application of the MART-1 antibody SO CANCER CYTOPATHOLOGY LA English DT Article DE melanoma; effusion; immunocytochemistry; MART-1 antibody; triage ID TUMOR-INFILTRATING LYMPHOCYTES; SEROUS EFFUSIONS; ANTIGEN; MESOTHELIOMA; DIAGNOSIS; CELLS; IDENTIFICATION; ADENOCARCINOMA AB BACKGROUND. Malignant effusions are complications of metastatic malignant melanoma (MM). Differential diagnosis often involves distinguishing MM from adenocarcinoma and reactive mesothelial cells. Descriptions in the literature of the morphologic and immunocytochemical (IM) staining characteristics of MM in effusions are sparse. A combination of morphology and immunocytochemistry should yield the most accurate diagnostic results. The MART-I antigen, a transmembrane protein, is specifically expressed in melanocytes and MM. A recently developed monoclonal antibody to the MART-1 antigen may represent a useful marker for the identification of MM in effusions. METHODS, The authors conducted a retrospective review of 32 effusion samples diagnosed as MM. The review consisted of morphologic and IM analyses of the effusion samples with antibodies to MART 1, HMB45, S-100, and cytokeratins (AE1/AE3). MM stains were performed on cell block or cytospin material, depending on availability. In the morphologic review, emphasis was placed on Diff Quik-stained material, due to its enhanced cytoplasmic volume and detail. RESULTS, Predominant cytologic features noted were lack of cellular cohesion (in 100% of cases), large eccentric nuclei with prominent nucleoli (in 100%), multinucleation (in 84%), variable cytoplasmic vacuolization (in 75%), pigment (in 72%), and cell-in-cell engulfment (in 47%]. All immunoreactive cases with sufficient material stained with at least one of the markers used. Tumor cells were positive with IM stains to MART-1 in 78% of cases, HMB45 in 81%, and S-100 in 81%. Coexpression of MART-1, HMB45, and S-100 was noted in 63% of cases. Of cases that showed expression for only 1 of the 3 antigens, the MART-1 was positive in 1 case, and HMB45 and S-100 were positive in 2 cases each. Three cases showed immunoreactivity for cytokeratins in the melanoma cells. CONCLUSIONS. The diagnosis of MM in effusions can be made reliably through a combination of morphologic and IM features. Differential diagnosis often involves distinguishing MM from adenocarcinoma or reactive mesothelial cells. Cytoplasmic vacuolization, multinucleation, prominent nucleoli, and cell-in-cell engulfment are cytologic features common to all three. The lack of IM staining for cytokeratins alone cannot reliably distinguish MM; 11% of cases showed positive staining with this antibody in the melanoma cells. The use of a panel of antibodies increases the accuracy of diagnosing MM. In this study, MART-I proved a useful adjunct to the HMB45/S-100/cytokeratin panel for the diagnosis of MM in effusions, staining 78% of the immunoreactive cases, with positivity in 1 case that was negative for HMB45 and S-100. (C) 1997 American Cancer Society. C1 NCI,CYTOPATHOL SECT,NIH,BETHESDA,MD 20892. NCI,SURG BRANCH,NIH,BETHESDA,MD 20892. NR 23 TC 45 Z9 46 U1 1 U2 1 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER CYTOPATHOL JI Cancer Cytopathol. PD FEB 25 PY 1997 VL 81 IS 1 BP 57 EP 63 DI 10.1002/(SICI)1097-0142(19970225)81:1<57::AID-CNCR12>3.0.CO;2-B PG 7 WC Oncology; Pathology SC Oncology; Pathology GA XP558 UT WOS:A1997XP55800012 PM 9100543 ER PT J AU Yamashita, Y Hirano, H Hodes, RJ AF Yamashita, Y Hirano, H Hodes, RJ TI Tissue-specific and growth-regulated expression of CD44 variable exon determinants in the mouse SO CELLULAR IMMUNOLOGY LA English DT Article ID LYMPHOCYTE HOMING RECEPTOR; METASTASIS-ASSOCIATED VARIANT; T-CELL; MONOCLONAL-ANTIBODIES; HEMATOPOIETIC-CELLS; SPLICE VARIANTS; IN-VIVO; B-CELLS; ISOFORMS; BINDING AB CD44 is a polymorphic transmembrane glycoprotein widely expressed in lymphocytes and epithelial cells. CD44 polymorphism reflects both posttranslational modification and alternative splicing of up to 10 variably expressed exons in the membrane-proximal CD44 extracellular domain. An analysis of CD44 variable exon-containing isoforms in the mouse was carried out by generating a panel of monoclonal antibodies against variable region determinants of CD44. Immunohistochemical analysis demonstrated selective patterns of expression of CD44 variable exon determinants in normal tissues, and how cytometric analysis identified expression of CD44 variable exon-dependent determinants in epithelial and lymphoid cell lines. Regulation of alternative splicing was studied by characterization of cell surface expression of CD44 variable exon determinants on HC11 mammary epithelial cells, and it was demonstrated that variably spliced isoforms are selectively regulated as a function of growth phase in vitro. These results demonstrate the tissue-specific and growth-regulated expression of the CD44 isoform at the level of cell surface protein products and identify isoform-specific determinants that can be targeted in analysis of isoform-specific function. (C) 1997 Academic Press. C1 NIA,BETHESDA,MD 20892. OSAKA UNIV,FAC DENT,DEPT PERIODONTOL & ENDODONTOL,SUITA,OSAKA 565,JAPAN. RP Yamashita, Y (reprint author), NCI,EXPT IMMUNOL BRANCH,NIH,BLDG 10,ROOM 4B17,10 CTR DR MSC 1360,BETHESDA,MD 20892, USA. NR 62 TC 3 Z9 3 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD FEB 25 PY 1997 VL 176 IS 1 BP 22 EP 33 DI 10.1006/cimm.1996.1056 PG 12 WC Cell Biology; Immunology SC Cell Biology; Immunology GA WL822 UT WOS:A1997WL82200003 PM 9070314 ER PT J AU Siebenlist, U AF Siebenlist, U TI NF kappa B/I kappa B proteins. Their role in cell growth, differentiation and development. Madrid, Spain, July 7-10, 1996 SO BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER LA English DT Editorial Material ID TARGETED DISRUPTION; MICE LACKING; ACTIVATION; EXPRESSION; LETHALITY; DEFECTS; FAMILY; RELB RP Siebenlist, U (reprint author), NIH,IMMUNOREGULAT LAB,BLDG 10,RM 11B16,BETHESDA,MD 20892, USA. NR 25 TC 15 Z9 15 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-419X J9 BBA-REV CANCER JI Biochim. Biophys. Acta-Rev. Cancer PD FEB 22 PY 1997 VL 1332 IS 1 BP R7 EP R13 DI 10.1016/S0304-419X(96)00038-8 PG 7 WC Biochemistry & Molecular Biology; Biophysics; Oncology SC Biochemistry & Molecular Biology; Biophysics; Oncology GA WK297 UT WOS:A1997WK29700008 PM 9061013 ER PT J AU Spence, MA Flodman, PL Sadovnik, AD Ameli, H BaileyWilson, JE Remick, RA AF Spence, MA Flodman, PL Sadovnik, AD Ameli, H BaileyWilson, JE Remick, RA TI Single major locus models for bipolar disorder are implausible - Response SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Letter ID 2-LOCUS MODELS; LINKAGE; HETEROGENEITY C1 UNIV CALIF IRVINE,DEPT PEDIAT,ORANGE,CA 92668. NCHGR,NIH,TRIAD TECHNOL CTR,BALTIMORE,MD. UNIV BRITISH COLUMBIA,COLL MED,DEPT MED GENET,VANCOUVER,BC V5Z 1M9,CANADA. ST PAULS HOSP,DEPT PSYCHIAT,VANCOUVER,BC V6Z 1Y6,CANADA. NR 12 TC 2 Z9 2 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD FEB 21 PY 1997 VL 74 IS 1 BP 19 EP 20 DI 10.1002/(SICI)1096-8628(19970221)74:1<19::AID-AJMG5>3.0.CO;2-Q PG 2 WC Genetics & Heredity SC Genetics & Heredity GA WG273 UT WOS:A1997WG27300005 ER PT J AU Koley, AP Robinson, RC Markowitz, A Friedman, FK AF Koley, AP Robinson, RC Markowitz, A Friedman, FK TI Drug-drug interactions: Effect of quinidine on nifedipine binding to human cytochrome P450 3A4 SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE nifedipine; quinidine; drug interactions; cytochrome P450 ID CO BINDING; CONSEQUENCES; METABOLISM; KINETICS AB Quinidine is a known inhibitor of cytochrome P450-mediated nifedipine metabolism. The interactions of nifedipine and quinidine with human cytochrome P450 3A4, which metabolizes these drugs, were examined using the kinetics of CO binding to this P450 as a rapid kinetic probe of protein conformation and dynamics. This approach showed that nifedipine and quinidine bind to different P450 3A4 species, respectively termed species I and II, with distinct conformations. When both drugs were present simultaneously, nifedipine interacted with the quinidine-bound P450 species II, but not species I. These findings indicate that quinidine acts as an allosteric inhibitor by switching nifedipine binding from nifedipine-metabolizing species I to the nonmetabolizing species II. C1 NCI,MOL CARCINOGENESIS LAB,BETHESDA,MD 20892. NIH,BIOMED ENGN & INSTRUMENTAT PROGRAM,BETHESDA,MD 20892. RI Friedman, Fred/D-4208-2016 NR 18 TC 48 Z9 48 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD FEB 21 PY 1997 VL 53 IS 4 BP 455 EP 460 DI 10.1016/S0006-2952(96)00836-2 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA WN672 UT WOS:A1997WN67200002 PM 9105395 ER PT J AU Sriram, K Pai, KS Boyd, MR Ravindranath, V AF Sriram, K Pai, KS Boyd, MR Ravindranath, V TI Evidence for generation of oxidative stress in brain by MPTP: In vitro and in vivo studies in mice SO BRAIN RESEARCH LA English DT Article DE MPTP; oxidative stress; glutathione; reactive oxygen species; brain slice; brain; neurotoxicity; Complex I ID NADH DEHYDROGENASE; INDUCED TOXICITY; GLUTATHIONE; MPP+; 1-METHYL-4-PHENYLPYRIDINIUM; NEUROTOXICITY; SUPEROXIDE; PROTECTION; MITOCHONDRIA; MOUSE AB The role of oxidative stress in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-mediated neurotoxicity is as yet unclear and the evidence for generation of oxygen free radicals as a primary event in the neurotoxicity is yet to be demonstrated. The present study was undertaken to ascertain the potential role of oxidative damage, and the protective role, if any, of the antioxidant, glutathione (GSH), in MPTP-induced neurotoxicity. Exposure of sagittal slices of mouse brain to MPTP resulted in significant increases of reactive oxygen species (ROS) and malondialdehyde (MDA, the product of lipid peroxidation) and decreases in GSH content. Pretreatment of mouse brain slices, in vitro, with GSH or GSH isopropyl ester attenuated MPTP toxicity as assessed by the tissue activity of the mitochondrial enzyme, NADH-dehydrogenase (NADH-DH), and by leakage of the cytosolic enzyme, lactate dehydrogenase (LDH), from the slice into the medium. In vivo administration of MPTP (30 mg/kg body weight, s.c.), to mice resulted in significant lowering of GSH in the striatum and midbrain, 2 h after dosage; ROS levels in the striatum and midbrain increased after 3 and 8 h, respectively. In the striatum significant inhibition of rotenone-sensitive NADH ubiquinone-l oxido-reductase (Complex 1) was observed transiently 1 h after MPTP administration. The enzyme activity recovered thereafter; significant inhibition of mitochondrial Complex I was observed in the striatum only 18 h after MPTP dose. In the midbrain, mitochondrial Complex I was inhibited only 18 h after MPTP dose; no change was observed at the early time points examined. Thus, the depletion of GSH and increased ROS formation preceded the inhibition of the mitochondrial enzyme in the midbrain. Evidence presented herein from both in vitro and in vivo studies support that MPTP exposure generates ROS resulting in oxidative stress. C1 NATL INST MENTAL HLTH & NEUROSCI,DEPT NEUROCHEM,BANGALORE 560029,KARNATAKA,INDIA. NCI,FREDERICK CANC RES & DEV CTR,DEV THERAPEUT PROGRAM,LAB DRUG DISCOVERY RES & DEV,FREDERICK,MD 21702. NR 34 TC 168 Z9 169 U1 2 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD FEB 21 PY 1997 VL 749 IS 1 BP 44 EP 52 DI 10.1016/S0006-8993(96)01271-1 PG 9 WC Neurosciences SC Neurosciences & Neurology GA WL911 UT WOS:A1997WL91100006 PM 9070626 ER PT J AU Bruning, JC Winnay, J BonnerWeir, S Taylor, SI Accili, D Kahn, CR AF Bruning, JC Winnay, J BonnerWeir, S Taylor, SI Accili, D Kahn, CR TI Development of a novel polygenic model of NIDDM in mice heterozygous for IR and IRS-1 null alleles SO CELL LA English DT Article ID INSULIN-RECEPTOR SUBSTRATE-1; DEPENDENT DIABETES-MELLITUS; BETA-CELL MASS; PHOSPHATIDYLINOSITOL 3-KINASE; SIGNAL-TRANSDUCTION; SKELETAL-MUSCLE; KINASE-ACTIVITY; OBESE SUBJECTS; RESISTANCE; GENE AB NIDDM is a polygenic disease characterized by insulin resistance in muscle, fat, and liver, followed by a failure of pancreatic beta cells to adequately compensate for this resistance despite increased insulin secretion. Mice double heterozygous for null alleles in the insulin receptor and insulin receptor substrate-1 genes exhibit the expected similar to 50% reduction in expression of these two proteins, but a synergism at a level of insulin resistance with 5- to 50-fold elevated plasma insulin levels and comparable levels of beta cell hyperplasia. At 4-6 months of age, 40% of these double heterozygotes become overtly diabetic. This NIDDM mouse model in which diabetes arises in an age-dependent manner from the interaction between two genetically determined, subclinical defects in the insulin signaling cascade demonstrates the role of epistatic interactions in the pathogenesis of common diseases with non-Mendelian genetics. C1 HARVARD UNIV,SCH MED,DIV RES,JOSLIN DIABET CTR,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02215. NIDDK,DIABET BRANCH,NATL INST HLTH,BETHESDA,MD 20892. NICHHD,DEV ENDOCRINOL BRANCH,NATL INST HLTH,BETHESDA,MD 20892. FU NIDDK NIH HHS [DK 31036, DK 33201, DK 44523] NR 52 TC 391 Z9 400 U1 1 U2 8 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD FEB 21 PY 1997 VL 88 IS 4 BP 561 EP 572 DI 10.1016/S0092-8674(00)81896-6 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA WJ691 UT WOS:A1997WJ69100016 PM 9038347 ER PT J AU HernandezSanchez, C Werner, H Roberts, CT Woo, EJ Hum, DW Rosenthal, SM LeRoith, D AF HernandezSanchez, C Werner, H Roberts, CT Woo, EJ Hum, DW Rosenthal, SM LeRoith, D TI Differential regulation of insulin-like growth factor-I (IGF-I) receptor gene expression by IGF-I and basic fibroblastic growth factor SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FACTOR BINDING-PROTEINS; BC3H-1 MUSCLE-CELLS; RIBONUCLEIC-ACID; RESPONSE ELEMENT; CYCLIC-AMP; INDUCTION; SERUM; INHIBITION; INCREASES; PROMOTER AB Insulin-like growth factor-I receptor (IGF-IR) gene expression is regulated by various stimuli, including hormones, growth factors, and nutritional status. We have investigated the molecular mechanism by which two growth factors, insulin-like growth factor-I (IGF-I) and basic fibroblast growth factor (bFGF) regulate IGF-IR gene expression. bFGF increases the endogenous IGF-IR mRNA levels and IGF-IR promoter activity. This effect is mediated by a region of the IGF-IR promoter located between nucleotides -476 and -188 in the 5'-flanking region. In contrast, IGF-I decreases the IGF-IR mRNA levels. IGF-I down-regulates IGF-IR transcriptional activity as deduced from experiments in which the levels of pre-mRNA and mRNA were measured. IGF-I reduced pre-mRNA and mRNA levels in parallel, while the mRNA stability was found to be unchanged by IGF-I treatment. While these results strongly suggest an effect of IGF-I on IGF-IR transcriptional activity, no specific IGF-I response element was demonstrated in the 5'-untranslated region or 5'-flanking region studied, Thus, bFGF and IGF-I have differential effects on IGF-IR gene transcription, with the IGF-I response region as yet unidentified. C1 UNIV CALIF SAN FRANCISCO,DEPT PEDIAT,SAN FRANCISCO,CA 94143. RP HernandezSanchez, C (reprint author), NIDDK,SECT MOL & CELLULAR PHYSIOL,DIABET BRANCH,NIH,RM 8S235A,BLDG 10,BETHESDA,MD 20892, USA. RI Hernandez Sanchez, Catalina/N-1737-2014; OI Hernandez Sanchez, Catalina/0000-0002-0846-5019; Roberts, Charles/0000-0003-1756-5772 NR 38 TC 73 Z9 77 U1 1 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD FEB 21 PY 1997 VL 272 IS 8 BP 4663 EP 4670 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WJ855 UT WOS:A1997WJ85500005 PM 9030517 ER PT J AU Dittmer, J PiseMasison, CA Clemens, KE Choi, KS Brady, JN AF Dittmer, J PiseMasison, CA Clemens, KE Choi, KS Brady, JN TI Interaction of human T-cell lymphotropic virus type I Tax, Ets1, and Sp1 in transactivation of the PTHrP P2 promoter SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HORMONE-RELATED PROTEIN; NF-KAPPA-B; RECEPTOR GENE-EXPRESSION; LONG TERMINAL REPEAT; TROPICAL SPASTIC PARAPARESIS; BOX-BINDING-PROTEINS; HTLV-I; TRANSCRIPTIONAL ACTIVATION; DNA-BINDING; NUCLEAR TRANSLOCATION AB We have previously shown that the parathyroid hormone-related protein (PTHrP) promoter contains binding sites for transcription factors Ets1 and Spl and that human T-cell lymphotropic virus type I (HTLV I) Tax cooperates with Ets1 to transactivate the PTHrP P2 promoter. Using the yeast two-hybrid interaction system, we now provide evidence that Tax interacts with Ets1. Moreover, a double mutation (D22A,C23S) in the Tax protein that abrogated the Tax/Ets1 interaction also inhibited the Tax/Ets1 cooperative effect, suggesting that the interaction between Tax and Ets1 is important for transactivation of the PTHrP promoter. In coimmunoprecipitation assays, we find that Tax facilitates the interaction between Ets1 and Spl, forming a ternary complex. When the Spl site in the PTHrP promoter was mutated, the Tax/Ets1 cooperative effect was dramatically decreased. This suggests that Spl plays an important role in the Ets1-dependent Tax transactivation of the PTHrP P2 promoter, Finally, we demonstrate that Gal4-Tax is a strong activator of the Gal PTHrP promoter, implying that Tax contributes directly to the transcriptional activation of the promoter. We propose a model in which the Tax/Ets1 cooperative effect on the PTHrP P2 promoter is based on the ability of Tax, Ets1, and Sp1 to form a ternary complex on the template DNA, Tax facilitates the interaction of Ets1/Sp1 and participates directly in the transcription initiation process. C1 NCI,NIH,VIRUS TUMOR BIOL SECT,MOL VIROL LAB,BETHESDA,MD 20892. RI Dittmer, Juergen/G-1160-2011 NR 84 TC 62 Z9 62 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD FEB 21 PY 1997 VL 272 IS 8 BP 4953 EP 4958 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WJ855 UT WOS:A1997WJ85500043 PM 9030555 ER PT J AU Kim, DS Jung, HH Park, SH Chin, H AF Kim, DS Jung, HH Park, SH Chin, H TI Isolation and characterization of the 5'-upstream region of the human N-type calcium channel alpha(1B) subunit gene - Chromosomal localization and promoter analysis SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID UPSTREAM REGULATORY ELEMENTS; NEURON-SPECIFIC EXPRESSION; FUNCTIONAL EXPRESSION; TRANSCRIPTION INVITRO; NEGATIVE REGULATION; ALPHA-1 SUBUNIT; MOLECULAR-BASIS; CORE PROMOTER; DIVERSITY; PROTEIN AB omega-Conotoxin-sensitive N-type Ca2+ channels, unlike dihydropyridine-sensitive L-type channels, are exclusively expressed in nervous tissues. To understand the molecular basis for neuron-specific expression of the N-type channel, we have isolated genomic clones encoding the human alpha(1B) subunit gene, localized to the long arm of chromosome 9 (9q34) by fluorescence in. situ hybridization, and characterized its 5'-upstream region. The proximal promoter of the alpha(1B) subunit gene lacks a typical TATA box, is highly GC-rich, and contains several sequences for transcription factor binding. Primer extension experiments revealed the presence of two transcription start sites. In vitro transfection study of the alpha(1B) subunit-luciferase fusion gene showed that the 4.0-kb 5'-flanking region of the alpha(1B) gene functions as an efficient promoter in neuronal cells but not in glioma or nonneuronal cells, consistent with the patterns of the endogenous alpha(1B) gene expression in these cells. Deletion analysis of alpha(1B) subunit-luciferase fusion gene constructs further revealed the presence of several cis-acting regulatory elements, including a potential repressor located in the distal upstream region (-3992 to -1788) that may be important for the neuron-specific expression of the N-type Ca2+ channel alpha(1B) subunit gene. C1 NINCDS,NEUROCHEM LAB,NIH,BETHESDA,MD 20892. KOREA UNIV,COLL MED,DEPT ANAT,SEOUL 136701,SOUTH KOREA. NR 43 TC 17 Z9 19 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD FEB 21 PY 1997 VL 272 IS 8 BP 5098 EP 5104 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WJ855 UT WOS:A1997WJ85500063 PM 9030575 ER PT J AU Hunyady, B Mezey, E Pacak, K Palkovits, M AF Hunyady, B Mezey, E Pacak, K Palkovits, M TI Demonstration of muscarinic receptor mRNAs in parietal cells, enteric ganglia and immune cells of rat stomach by in situ hybridization histochemistry SO LIFE SCIENCES LA English DT Meeting Abstract C1 NIMH,NIH,BETHESDA,MD 20892. NINCDS,NIH,BETHESDA,MD 20892. MED UNIV PECS,DEPT MED 1,PECS,HUNGARY. RI Palkovits, Miklos/F-2707-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0024-3205 J9 LIFE SCI JI Life Sci. PD FEB 21 PY 1997 VL 60 IS 13-14 BP 71 EP 71 PG 1 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA WM778 UT WOS:A1997WM77800097 ER PT J AU Kiesewetter, DO Jagoda, E Carson, RE Endres, CJ Herscovitch, P Eckelman, WC AF Kiesewetter, DO Jagoda, E Carson, RE Endres, CJ Herscovitch, P Eckelman, WC TI Biodistribution and PET imaging of muscarinic subtype selective 3-(3-(3-fluoropropylthio)-1,2,5-thiadiazol-4-YL)-tetrahydro-1-methylpyri dine (FP-TZTP) and R 3-quinuclidinyl S-fluoromethyl benzilate (FMeQNB) SO LIFE SCIENCES LA English DT Meeting Abstract C1 NIH,PET DEPT,CTR CLIN,BETHESDA,MD 20892. RI Carson, Richard/H-3250-2011 OI Carson, Richard/0000-0002-9338-7966 NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0024-3205 J9 LIFE SCI JI Life Sci. PD FEB 21 PY 1997 VL 60 IS 13-14 BP 85 EP 85 PG 1 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA WM778 UT WOS:A1997WM77800110 ER PT J AU Gutkind, JS Crespo, P Xu, NZ Teramoto, H Coso, OA AF Gutkind, JS Crespo, P Xu, NZ Teramoto, H Coso, OA TI The pathway connecting m2 receptors to the nucleus involves small GTP-binding proteins acting on divergent MAP kinase cascades SO LIFE SCIENCES LA English DT Article; Proceedings Paper CT 7th International Symposium on Subtypes of Muscarinic Receptors CY NOV 12-15, 1996 CL VIENNA, VA SP Boston Univ Sch Med, Johann Wolfgang Goethe Univ DE G proteins; muscarinic receptors; MAP kinase; JNK; Ras; signal transduction ID RAS-DEPENDENT ACTIVATION; BETA-GAMMA-DIMERS; SIGNALING PATHWAY; FIBROBLASTS; DOMAIN; CDC42; RAC1 AB m1 and m2 receptors are traditionally linked to tissue specific functions performed by fully differentiated cells. However, these receptors have been also implicated in growth stimulation. The mechanisms whereby these receptors regulate proliferative signaling pathways are still poorly understood. Furthermore, pharmacological evidence suggest that many growth promoting agents act on G(i) coupled receptors, but there is no formal proof that induction of DNA-synthesis results from decreased intracellular levels of cAMP. In our laboratory, we have used the expression of m1 and m2 receptors as a model for studying proliferative signaling through G protein-coupled receptors. Currently available evidence suggest that these receptors signal to distinct members of the MAP kinase superfamily, MAP kinase and JNK, through beta gamma subunits of heterotrimeric G proteins acting, respectively, on a Ras and Rac1 dependent pathway. RP Gutkind, JS (reprint author), NIDR,MOL SIGNALLING UNIT,ORAL & PHARYNGEAL CANC BRANCH,NIH,CONVENT DR 30,ROOM 211,BETHESDA,MD 20892, USA. RI Gutkind, J. Silvio/A-1053-2009; Crespo, Piero/M-3273-2014 OI Crespo, Piero/0000-0003-2825-7783 NR 19 TC 18 Z9 18 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0024-3205 J9 LIFE SCI JI Life Sci. PD FEB 21 PY 1997 VL 60 IS 13-14 BP 999 EP 1006 PG 8 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA WM778 UT WOS:A1997WM77800006 PM 9121367 ER PT J AU Wess, J Liu, J Blin, N Yun, J Lerche, C Kostenis, E AF Wess, J Liu, J Blin, N Yun, J Lerche, C Kostenis, E TI Structural basis of receptor G protein coupling selectivity studied with muscarinic receptors as model systems SO LIFE SCIENCES LA English DT Article; Proceedings Paper CT 7th International Symposium on Subtypes of Muscarinic Receptors CY NOV 12-15, 1996 CL VIENNA, VA SP Boston Univ Sch Med, Johann Wolfgang Goethe Univ DE site-directed mutagenesis; G protein-coupled receptors; G protein alpha-subunits ID ACETYLCHOLINE-RECEPTOR; AMINO-ACID; SPECIFICITY; IDENTIFICATION; ACTIVATION; HYDROLYSIS; SUBTYPES; MUTAGENESIS; ELEMENTS; G(Q/11) AB Different muscarinic acetylcholine receptor subtypes were used as model systems to study the structural basis of receptor/G protein coupling selectivity. Extensive mutagenesis studies have previously led to the identification of single amino acids on the m3 muscarinic receptor protein (located in the second intracellular loop (i2) and at the N- and C-terminus of the third intracellular loop (i3)) that dictate selective recognition of Gq/11 proteins by this receptor subtype. Based on these results, we proposed a model of the intracellular m3 receptor surface in which the functionally critical residues project into the interior of the transmembrane receptor core. To identify specific regions on the G protein(s) that are contacted by these different, functionally critical receptor sites, we recently employed a novel experimental strategy involving the coexpression of hybrid m2/m3 muscarinic receptors with hybrid G alpha-subunits. Using this approach, we could demonstrate that the C-terminus of G protein alpha(i)/(0)-subunits is recognized by a short sequence element in the m2 muscarinic receptor (''VTIL'') that is located at the junction between the sixth transmembrane domain (TM VI) and the i3 loop. We could show that this interaction is critically involved in determining coupling selectivity and triggering G protein activation. By using a similar strategy (coexpression of mutant muscarinic receptors with hybrid G alpha-subunits), other major receptor/G protein contact sites are currently being identified. These studies, complemented by biochemical and biophysical approaches, should eventually lead to a detailed structural model of the ligand-receptor-G protein complex. RP Wess, J (reprint author), NIDDKD,BIOORGAN CHEM LAB,NIH,BLDG 8A,ROOM B1A-09,BETHESDA,MD 20892, USA. NR 33 TC 48 Z9 52 U1 0 U2 7 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0024-3205 J9 LIFE SCI JI Life Sci. PD FEB 21 PY 1997 VL 60 IS 13-14 BP 1007 EP 1014 DI 10.1016/S0024-3205(97)00041-6 PG 8 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA WM778 UT WOS:A1997WM77800007 PM 9121341 ER PT J AU Laurila, AL Anttila, T Laara, E Bloigu, A Virtamo, J Albanes, D Leinonen, M Saikku, P AF Laurila, AL Anttila, T Laara, E Bloigu, A Virtamo, J Albanes, D Leinonen, M Saikku, P TI Serological evidence of an association between Chlamydia pneumoniae infection and lung cancer SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID CORONARY HEART-DISEASE; ANTIBODY PREVALENCE; TWAR; RISK AB Epidemiological evidence suggests that airway obstruction is an independent risk factor for lung cancer and that this cannot be explained by active or passive smoking alone. Chlamydia pneumoniae infection has been associated with chronic bronchitis and its exacerbates. Our aim was to evaluate the association between chronic C. pneumoniae infection and risk of lung cancer among male smokers. Smoking males with lung cancer (n = 230) and their age- and locality-matched controls were selected among participants of the Alpha-Tocopherol. Beta-Carotene Cancer Prevention Study. The presence of C. pneumoniae infection was assessed by analyzing specific antibodies and immune complexes in 2 serum samples collected with a 3-year interval before the lung cancer diagnosis. The diagnosis of chronic infection was based on stable levels of positive specific IgA antibody (titer greater than or equal to 16) and immune complex (titer greater than or equal to 4). Relative risks were estimated by odds ratios (OR) adjusted for age, locality and smoking history by a conditional logistic regression model. Markers suggesting chronic C. pneumoniae infection were present in 52% of cases and 45% of controls and hence were positively associated with the incidence of lung cancer (OR 1.6; 95% confidence interval [CI] 1.0-2.3). The incidence was especially increased in men younger than 60 years (OR 2.9; 95% CI 1.5-5.4) but not in the older age group (OR 0.9; 95% CI 0.5-1.6). Before concluding that C. pneumoniae infection is a new independent risk factor for lung cancer, corroboration from other studies with larger number of cases and longer follow-up is needed. (C) 1997 Wiley-Liss, Inc,. C1 UNIV OULU,DEPT MATH SCI,OULU,FINLAND. NATL PUBL HLTH INST,HELSINKI,FINLAND. NCI,BETHESDA,MD 20892. RP Laurila, AL (reprint author), NATL PUBL HLTH INST,DEPT OULU,POB 310,FIN-90101 OULU,FINLAND. RI Albanes, Demetrius/B-9749-2015 FU NCI NIH HHS [N01-CN-45165] NR 21 TC 83 Z9 89 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD FEB 20 PY 1997 VL 74 IS 1 BP 31 EP 34 DI 10.1002/(SICI)1097-0215(19970220)74:1<31::AID-IJC6>3.0.CO;2-1 PG 4 WC Oncology SC Oncology GA XA678 UT WOS:A1997XA67800006 PM 9036866 ER PT J AU Schwendel, A Langreck, H Reichel, M Schrock, E Ried, T Dietel, M Petersen, I AF Schwendel, A Langreck, H Reichel, M Schrock, E Ried, T Dietel, M Petersen, I TI Primary small-cell lung carcinomas and their metastases are characterized by a recurrent pattern of genetic alterations SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID COMPARATIVE GENOMIC HYBRIDIZATION; CANCER; TUMORS; LINES; AMPLIFICATION; INVOLVEMENT; DELETION; FREQUENT; FAMILY AB Small-cell lung cancer (SCLC) represents a group of highly malignant tumors giving rise to early and widespread metastases. We used comparative genomic hybridization in autoptic tumor specimens from 10 patients to discover genetic alterations that are associated with tumor progression and potentially with the metastatic phenotype. Ten primary SCLC and 16 corresponding metastases were investigated with a maximum of 4 tumors per case. Prevalent changes observed in more than 60% of the primary tumors and their metastases included deletions on chromosomes 3p, 4q, 5q, 10q, 13q and 17p, and DNA over-representations on chromosomes 3q and 5p. The number of common alterations in the primary tumors and the related metastases outnumbered the differences, indicating a clonal relationship. Within the lesions of the same patient, differences were found between the primary tumor and the metastases as well as between metastases of distinct organ sites. However, no specific alteration was significantly associated with the metastatic phenotype. We suggest that the high malignancy of SCLC is defined by the above-mentioned pattern of aberrations. (C) 1997 Wiley-Liss, Inc,. C1 HUMBOLDT UNIV BERLIN,HOSP CHARITE,INST PATHOL,D-10098 BERLIN,GERMANY. NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. UNIV ZURICH HOSP,DEPT PATHOL,INST NEUROPATHOL,CH-8091 ZURICH,SWITZERLAND. NR 21 TC 66 Z9 69 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD FEB 20 PY 1997 VL 74 IS 1 BP 86 EP 93 DI 10.1002/(SICI)1097-0215(19970220)74:1<86::AID-IJC15>3.0.CO;2-G PG 8 WC Oncology SC Oncology GA XA678 UT WOS:A1997XA67800015 PM 9036875 ER PT J AU Misik, V Riesz, P AF Misik, V Riesz, P TI Effect of Cd2+ on the center dot H atom yield in the sonolysis of water. Evidence against the formation of hydrated electrons SO JOURNAL OF PHYSICAL CHEMISTRY A LA English DT Article ID AQUEOUS-SOLUTIONS; SONOCHEMISTRY; ULTRASOUND; SONOLUMINESCENCE; CAVITATION; OH AB The formation of hydrated electrons in neutral aqueous ultrasound-exposed solutions has been postulated previously, and several arguments were presented in favor and against their existence. In this work we use a sensitive method for detecting the presence of hydrated electrons in argon-saturated water exposed to 50 kHz ultrasound. This method is based on the fact that hydrated electrons, but not hydrogen atoms, can be scavenged by Cd2+ to prevent their reaction with the nitrone spin trap alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone (POBN) to form the EPR-detectable adduct POBN/H-.. No detectable yield of hydrated electrons in argon-saturated aqueous solutions at neutral pH was found. These results are evidence against the formation of hydrated electrons as reactive intermediates in the sonochemistry of neutral aqueous solutions. C1 NCI,NIH,RADIAT BIOL BRANCH,BETHESDA,MD 20892. NR 35 TC 9 Z9 9 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 1089-5639 J9 J PHYS CHEM A JI J. Phys. Chem. A PD FEB 20 PY 1997 VL 101 IS 8 BP 1441 EP 1444 DI 10.1021/jp963342t PG 4 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA WL095 UT WOS:A1997WL09500004 ER PT J AU Zhou, YF Waclawiw, MA Epstein, SE AF Zhou, YF Waclawiw, MA Epstein, SE TI Association between prior cytomegalovirus infection and the risk of restenosis after coronary atherectomy - Reply SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter RP Zhou, YF (reprint author), NHLBI,BLDG 10,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD FEB 20 PY 1997 VL 336 IS 8 BP 588 EP 588 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA WJ240 UT WOS:A1997WJ24000025 ER PT J AU Zahm, SH Figgs, LW Bulbulyan, M Zaridze, DG AF Zahm, SH Figgs, LW Bulbulyan, M Zaridze, DG TI Genetic polymorphisms and breast cancer risk SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter ID BLADDER-CANCER; WORKERS C1 ST LOUIS UNIV, ST LOUIS, MO 63103 USA. NN BLOKHIN CANC RES CTR, INST CARCINOGENESIS, MOSCOW, RUSSIA. RP Zahm, SH (reprint author), NCI, ROCKVILLE, MD 20857 USA. RI Zahm, Shelia/B-5025-2015 NR 5 TC 1 Z9 1 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD FEB 19 PY 1997 VL 277 IS 7 BP 533 EP 534 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA WH297 UT WOS:A1997WH29700025 PM 9032158 ER PT J AU Ambrosone, CB Freudenheim, JL Shields, PG AF Ambrosone, CB Freudenheim, JL Shields, PG TI Genetic polymorphisms and breast cancer risk - Reply SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 NATL CANC INST, BETHESDA, MD USA. SUNY BUFFALO, BUFFALO, NY USA. RP Ambrosone, CB (reprint author), NATL CTR TOXICOL RES, JEFFERSON, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD FEB 19 PY 1997 VL 277 IS 7 BP 534 EP 534 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA WH297 UT WOS:A1997WH29700026 ER PT J AU Hu, JS Grzesiek, S Bax, A AF Hu, JS Grzesiek, S Bax, A TI Two-dimensional NMR methods for determining (chi 1) angles of aromatic residues in proteins from three-bond J(C'C gamma) and J(NC gamma) couplings SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID PEPTIDE COMPLEX; RESONANCE; ASSIGNMENT; CALMODULIN; H2O C1 NIDDKD,CHEM PHYS LAB,NIH,BETHESDA,MD 20892. NR 17 TC 94 Z9 95 U1 0 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD FEB 19 PY 1997 VL 119 IS 7 BP 1803 EP 1804 DI 10.1021/ja963625z PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA WJ097 UT WOS:A1997WJ09700043 ER PT J AU Fenton, RG Longo, DL AF Fenton, RG Longo, DL TI Danger versus tolerance: Paradigms for future studies of tumor-specific cytotoxic T lymphocytes SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID CELLS; EXPRESSION C1 NCI,FREDERICK CANC RES & DEV CTR,DIV CLIN SCI,NAVY MED ONCOL BRANCH,BETHESDA,MD 20892. NIA,CTR GERONTOL RES,BALTIMORE,MD. NR 28 TC 18 Z9 18 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD FEB 19 PY 1997 VL 89 IS 4 BP 272 EP 275 DI 10.1093/jnci/89.4.272 PG 4 WC Oncology SC Oncology GA WH830 UT WOS:A1997WH83000002 PM 9048827 ER PT J AU Feuer, EJ AF Feuer, EJ TI Stat bite - Lifetime probability of cancer SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material RP Feuer, EJ (reprint author), NCI,BETHESDA,MD 20892, USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD FEB 19 PY 1997 VL 89 IS 4 BP 279 EP 279 PG 1 WC Oncology SC Oncology GA WH830 UT WOS:A1997WH83000005 ER PT J AU Correale, P Walmsley, K Nieroda, C Zaremba, S Zhu, MZ Schlom, J Tsang, KY AF Correale, P Walmsley, K Nieroda, C Zaremba, S Zhu, MZ Schlom, J Tsang, KY TI In vitro generation of human cytotoxic T lymphocytes specific for peptides derived from prostate-specific antigen SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID VACCINIA VIRUS-VACCINE; HUMAN-MELANOMA; TUMOR-CELLS; IN-VITRO; NONHUMAN PRIMATE; RECOGNITION; EPITOPES; IDENTIFICATION; CANCER; GENE AB Background: Protein antigens are presented to cytotoxic T lymphocytes as small peptides (approximately 9-10 amino acids long) bound to class I molecules of the major histocompatibility complex, The identification of tumor-associated antigens and specific peptide epitopes (i.e., antigenic determinants) may be useful in the development of anticancer vaccines, The generation of a cytotoxic T-cell response to one peptide epitope (amino acids 146-154) of human prostate-specific antigen (PSA) has been reported, Purpose: Our aim was to identify novel PSA peptides capable of eliciting specific cytotoxic T-cell responses, Methods: Candidate peptides were identified on the basis of the following criteria: 1) they contained consensus amino acid motifs for binding to HLA-A2, which is the most common type of class I molecule; 2) they lacked strong homology with PSA-related kallikrein proteins; and 3) they were capable of stabilizing HLA-A2 class I molecules on the surface of human T2 (transport deletion mutant) cells, which are defective in antigen presentation, T-cell lines capable of killing (i.e., lysing) T2 target cells that had been pulsed with specific PSA peptides were generated from three different males (two disease-free individuals and one patient with prostate cancer) by incubating peripheral blood mononuclear cells with the peptides and interleukin 2, Specific cell lysis was monitored by the release of radioactivity from target cells that had been labeled with [In-111]oxyquinoline. Results: Two novel PSA peptides capable of eliciting cytotoxic T-cell responses were identified; these peptides were designated PSA-1 (amino acids 141-150) and PSA-3 (amino acids 154-163), Four different cytotoxic T-cell lines were generated in response to these peptides-three against PSA-3 and one against PSA-1, Specific lysis of peptide-pulsed T2 cells by the T-cell lines was blocked by the addition of a monoclonal antibody directed against class I molecules, The T-cell lines were also capable of lysing PSA-positive, HLA-Aa-positive LNCaP cells (human prostate carcinoma cells), The specificity of LNCaP cell lysis was shown by the following: 1) the inability of added human K562 (chronic myelogenous leukemia) cells to inhibit it, 2) the ability of added anti-HLA-A2 antibodies to block it, and 3) the inability of the T-cell lines to induce substantial lysis of PSA-negative, HLA-A2-positive human cancer cells, Implications: Our studies form a rational basis for the use of PSA peptides or recombinant vectors encoding PSA in the development of anticancer vaccine immunotherapy protocols for patients with prostate cancer. C1 NCI,DIV BASIC SCI,TUMOR IMMUNOL & BIOL LAB,NIH,BETHESDA,MD 20892. NIH,HOWARD HUGHES MED INST,RES SCHOLARS PROGRAM,BETHESDA,MD. RI Correale, Pierpaolo/K-1640-2016 OI Correale, Pierpaolo/0000-0003-2154-6734 NR 42 TC 174 Z9 175 U1 0 U2 1 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD FEB 19 PY 1997 VL 89 IS 4 BP 293 EP 300 DI 10.1093/jnci/89.4.293 PG 8 WC Oncology SC Oncology GA WH830 UT WOS:A1997WH83000011 PM 9048833 ER PT J AU Johnston, PG Mick, R Recant, W Behan, KA Dolan, ME Ratain, MJ Beckmann, E Weichselbaum, RR Allegra, CJ Vokes, EE AF Johnston, PG Mick, R Recant, W Behan, KA Dolan, ME Ratain, MJ Beckmann, E Weichselbaum, RR Allegra, CJ Vokes, EE TI Thymidylate synthase expression and response to neoadjuvant chemotherapy in patients with advanced head and neck cancer SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID HIGH-DOSE LEUCOVORIN; LOCALLY ADVANCED HEAD; CONCOMITANT CHEMORADIOTHERAPY; INDUCTION CHEMOTHERAPY; 5-FLUOROURACIL; FLUOROURACIL; CISPLATIN; INTERFERON; CELLS; CARCINOMA AB Background: Thymidylate synthase (TS), an essential enzyme in DNA synthesis, is a target for the fluoropyrimidines, an important group of antineoplastic agents used widely in the treatment of head and neck cancer, Purpose: We evaluated relationships between the level and/or pattern of tumor TS expression and response to fluorouracil (5-FU)-based neoadjuvant chemotherapy in patients with advanced head and neck cancer, Methods: Tumor specimens from 86 patients were available for this retrospective analysis, The patients were enrolled in four consecutive phase II studies that tested combinations of 5-FU, leucovorin, and cisplatin with or without added methotrexate plus piritrexim or interferon alfa-2b (IFN alpha-2b), TS protein expression in the tumors was assessed by use of the TS 106 monoclonal antibody and standard immunohistochemical staining techniques, TS immunostaining was classified according to its level of intensity (TS 0-1 = low, TS 2 = intermediate, and TS 3 = high) and according to its extent (focal pattern = less than 25% of tumor cells positive; diffuse pattern = greater than or equal to 25% of tumor cells positive), Data from 79 patients were available for an analysis of tumor TS expression and patient/tumor characteristics; 70 patients were assessable for their response to neoadjuvant chemotherapy. Results: There was a statistically significant association between the level of tumor TS expression and the degree of tumor differentiation; a higher proportion of patients whose tumors exhibited TS 0-1 immunostaining had undifferentiated or poorly differentiated tumors than patients whose tumors exhibited TS 2 or TS 3 immunostaining (P = .03, Jonckheere-Terpstra trend test), Among the 70 patients who were assessable for response to neoadjuvant chemotherapy, TS 3 tumor immunostaining was associated with a lower rate of complete response (i.e., complete disappearance of clinically detectable disease for a minimum of 4 weeks from time of initial determination) than was TS 2 or TS 0-1 immunostaining, but this association was not statistically significant (P = .09, exact trend test); among the 39 patients who were treated with regimens that included 5-FU, leucovorin, cisplatin, and IFN alpha-2b, this inverse association between TS immunostaining intensity and response was statistically significant (P = .02, exact trend test), Tumor TS immunostaining intensity and overall survival were not found to be associated, Patients with tumors exhibiting a focal pattern of TS immunostaining have experienced significantly longer survival than patients with tumors exhibiting a diffuse pattern; for the 53 patients with diffuse tumor TS immunostaining, the median survival was 24.7 months, whereas the median survival has not yet been reached for the 22 patients with focal tumor TS immunostaining (P = .04, two-tailed logrank test), However, the survival advantage for the focal versus diffuse TS immunostaining pattern was limited to patients whose tumors also exhibited a TS 3 level of immunostaining intensity. Conclusions and Implications: Characterization of tumor TS expression may he of value in identifying patients with advanced head and neck cancer who would benefit from fluoropyrimidine-based neoadjuvant chemotherapy. C1 NCI,USN,MED ONCOL BRANCH,DIV CLIN SCI,BETHESDA,MD. UNIV CHICAGO,DEPT MED,CHICAGO,IL 60637. UNIV CHICAGO,DEPT PATHOL,CHICAGO,IL 60637. UNIV CHICAGO,DEPT RADIAT & CELLULAR ONCOL,CANC RES CTR,CHICAGO,IL 60637. MICHAEL REESE HOSP & MED CTR,DEPT PATHOL,CHICAGO,IL 60616. NR 31 TC 67 Z9 67 U1 0 U2 1 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD FEB 19 PY 1997 VL 89 IS 4 BP 308 EP 313 DI 10.1093/jnci/89.4.308 PG 6 WC Oncology SC Oncology GA WH830 UT WOS:A1997WH83000013 PM 9048835 ER PT J AU Adami, HO Ekbom, A Chow, WH Nyren, O Wolk, A Berne, C Linet, MS Fraumeni, JF McLaughlin, JK AF Adami, HO Ekbom, A Chow, WH Nyren, O Wolk, A Berne, C Linet, MS Fraumeni, JF McLaughlin, JK TI Excess risk of primary liver cancer in patients with diabetes mellitus - Response SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter C1 HARVARD UNIV,SCH PUBL HLTH,DEPT EPIDEMIOL,BOSTON,MA 02115. INT EPIDEMIOL INST,ROCKVILLE,MD. NCI,DIV CANC EPIDEMIOL & GENET,BETHESDA,MD 20892. UNIV UPPSALA HOSP,DEPT INTERNAL MED,S-75185 UPPSALA,SWEDEN. RP Adami, HO (reprint author), UNIV UPPSALA HOSP,DEPT CANC EPIDEMIOL,S-75185 UPPSALA,SWEDEN. NR 0 TC 2 Z9 2 U1 0 U2 1 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD FEB 19 PY 1997 VL 89 IS 4 BP 327 EP 328 PG 2 WC Oncology SC Oncology GA WH830 UT WOS:A1997WH83000021 ER PT J AU Cohn, JN Bristow, MR Chien, KR Colucci, WS Frazier, H Leinwand, LA Lorell, BH Moss, AJ Sonnenblick, EH Walsh, RA Mockrin, SC Reinlib, L AF Cohn, JN Bristow, MR Chien, KR Colucci, WS Frazier, H Leinwand, LA Lorell, BH Moss, AJ Sonnenblick, EH Walsh, RA Mockrin, SC Reinlib, L TI Report of the National Heart, Lung, and Blood Institute Special Emphasis Panel on Heart Failure Research SO CIRCULATION LA English DT Editorial Material DE cardiovascular diseases; heart diseases; heart failure C1 NHLBI,BETHESDA,MD 20892. RI bristow, michael/G-7850-2011 NR 0 TC 158 Z9 174 U1 1 U2 5 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD FEB 18 PY 1997 VL 95 IS 4 BP 766 EP 770 PG 5 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA WJ282 UT WOS:A1997WJ28200003 PM 9054723 ER PT J AU Lenfant, C AF Lenfant, C TI Fixing the failing heart SO CIRCULATION LA English DT Editorial Material DE aging; cardiovascular diseases; heart failure RP Lenfant, C (reprint author), NHLBI,NIH,31 CTR DR,BLDG 31,MSC 2486,BETHESDA,MD 20892, USA. NR 0 TC 17 Z9 18 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD FEB 18 PY 1997 VL 95 IS 4 BP 771 EP 772 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA WJ282 UT WOS:A1997WJ28200004 PM 9054724 ER PT J AU Rundqvist, B Eisenhofer, G Elam, M Friberg, P AF Rundqvist, B Eisenhofer, G Elam, M Friberg, P TI Attenuated cardiac sympathetic responsiveness during dynamic exercise in patients with heart failure SO CIRCULATION LA English DT Article DE norepinephrine; heart failure; nervous system, autonomic; exercise ID CONGESTIVE CARDIOMYOPATHY; NOREPINEPHRINE SPILLOVER; NERVOUS ACTIVITY; PLASMA; SCINTIGRAPHY; CAPACITY; RELEASE; HUMANS AB Background Cardiac norepinephrine (NE) spillover is increased in patients with chronic heart failure. This elevation is partly due to augmented NE release but also to reduced capacity for cardiac NE removal processes. in patients with mild to moderate heart failure, it is not known whether the described alteration in cardiac sympathetic function also affects cardiac NE spillover during intense sympathetic activation and whether other organs respond in proportion to the heart. Methods and Results Twenty-two patients with heart failure and 15 age-matched healthy subjects were studied. Whole-body and regional (NE) spillovers from the heart and kidneys were assessed at baseline and during supine cycling exercise (10 minutes) with the use of steady-state infusions of tritiated NE (isotope dilution). Cardiac performance was evaluated by means of catheterization of the right side of the heart. Cardiac NE spillover was higher (P<.05) at baseline in the patient soup than in healthy subjects, whereas renal and whole-body NE spillovers were similar between the study groups. During exercise, cardiac NE spillover increased 13-fold (P<.05) in healthy subjects but only 5-fold (P<.05) in the cardiac failure group, the latter reaching a lower peak value (P<.05). In contrast, there was no difference between the study groups in either renal or whole-body NE spillover responsiveness to exercise. Conclusions Patients with mild to moderate heart failure demonstrated a selective attenuation of cardiac sympathetic responsiveness during dynamic exercise. This attenuation may convey reduced inotropic and chronotropic support to the failing heart. C1 SAHLGRENS UNIV HOSP,DEPT CLIN PHYSIOL,INST HEART & LUNG DIS,S-41345 GOTHENBURG,SWEDEN. SAHLGRENS UNIV HOSP,DEPT NEUROPHYSIOL,INST CLIN NEUROSCI,S-41345 GOTHENBURG,SWEDEN. NINCDS,CLIN NEUROSCI BRANCH,NIH,BETHESDA,MD 20892. RP Rundqvist, B (reprint author), SAHLGRENS UNIV HOSP,DEPT CARDIOL,INST HEART & LUNG DIS,S-41345 GOTHENBURG,SWEDEN. NR 30 TC 39 Z9 39 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD FEB 18 PY 1997 VL 95 IS 4 BP 940 EP 945 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA WJ282 UT WOS:A1997WJ28200033 PM 9054754 ER PT J AU Li, HP Liu, ZM Nirenberg, M AF Li, HP Liu, ZM Nirenberg, M TI Kinesin-73 in the nervous system of Drosophila embryos SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE kinesin-73 heavy chain cDNA; cystoskeleton-associated protein Gly-rich domain ID AXONAL-TRANSPORT; C-ELEGANS; MONOMERIC MOTOR; PROTEIN; GENE; SEQUENCE; SUPERFAMILY; COMPONENT; VESICLES; UNC-104 AB Kinesin-73 cDNA was shown to encode a kinesin heavy chain protein that contains an N-terminal motor domain and a long central region that lacks extensive coiled-coils, The amino acid sequence of the motor domain of kinesin-73 protein is most closely related to the motor domains of Caenorhabditis elegans unc-104 and mouse KIF1A, The central region of kinesin-73 protein also is related to unc-104 and KIF1A, but the homology is lower than that of the motor domain, The C-terminal region of kinesin-73 protein contains a cytoskeleton associated protein Gly-rich domain, which is a putative microtubule binding site that is present in some cytoskeleton or dynein-associated proteins, Kinesin-73 mRNA was shown by in situ hybridization to be maternally expressed and widely distributed in the syncytial blastoderm embryo, However, later in Drosophila embryo development, expression of the kinesin-73 gene becomes restricted mostly to the central and peripheral nervous systems. C1 NHLBI,LAB BIOCHEM GENET,NIH,BETHESDA,MD 20892. NR 35 TC 22 Z9 22 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 18 PY 1997 VL 94 IS 4 BP 1086 EP 1091 DI 10.1073/pnas.94.4.1086 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WJ621 UT WOS:A1997WJ62100008 PM 9037010 ER PT J AU Brzeska, H Knaus, UG Wang, ZY Bokoch, GM Korn, ED AF Brzeska, H Knaus, UG Wang, ZY Bokoch, GM Korn, ED TI p21-activated kinase has substrate specificity similar to Acanthamoeba myosin I heavy chain kinase and activates Acanthamoeba myosin I SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ACTIN-BINDING-SITES; PROTEIN-KINASE; AUTOPHOSPHORYLATION; PHOSPHORYLATION; LOCALIZATION; CDC42; SEQUENCE; ATPASE; TAIL; RHO AB Acanthamoeba class I myosins are unconventional, single-headed myosins that express actin-activated Mg2+-ATPase and in vitro motility activities only when a single serine or threonine in the heavy chain is phosphorylated by myosin I heavy chain kinase (MIHCK). Some other, but not most, class I myosins have the same consensus phosphorylation site sequence, and the two known class VI myosins have a phosphorylatable residue in the homologous position, where most myosins have an aspartate or glutamate residue, Recently, we found that the catalytic domain of Acanthamoeba MIHCK has extensive sequence similarity to the p21-activated kinase (PAK)/STE20 family of kinases from mammals and yeast, which are activated by small GTP-binding proteins, The physiological substrates of the PAK/STE20 kinases are not well characterized, In this paper we show that PAK1 has similar substrate specificity as MIHCK when assayed against synthetic substrates and that PAK1 phosphorylates the heavy chain (1 mol of P-i per mol) and activates Acanthamoeba myosin I as MIHCK does, These results, together with the known involvement of Acanthamoeba myosin I, yeast myosin I, STE20, PAK, and small GTP-binding proteins in membrane- and cytoskeleton-associated morphogenetic transformations and activities, suggest that myosins may be physiological substrates for the PAK/STE20 family and thus mediators of these events. C1 NHLBI, CELL BIOL LAB, BETHESDA, MD 20892 USA. Scripps Res Inst, DEPT IMMUNOL, LA JOLLA, CA 92037 USA. Scripps Res Inst, DEPT CELL BIOL, LA JOLLA, CA 92037 USA. RI Korn, Edward/F-9929-2012 FU NIGMS NIH HHS [GM39434, R01 GM039434]; PHS HHS [A135947] NR 52 TC 65 Z9 66 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 18 PY 1997 VL 94 IS 4 BP 1092 EP 1095 DI 10.1073/pnas.94.4.1092 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WJ621 UT WOS:A1997WJ62100009 PM 9037011 ER PT J AU Bertin, J Armstrong, RC Ottilie, S Martin, DA Wang, Y Banks, S Wang, GH Senkevich, TG Alnemri, ES Moss, B Lenardo, MJ Tomaselli, KJ Cohen, JI AF Bertin, J Armstrong, RC Ottilie, S Martin, DA Wang, Y Banks, S Wang, GH Senkevich, TG Alnemri, ES Moss, B Lenardo, MJ Tomaselli, KJ Cohen, JI TI Death effector domain-containing herpesvirus and poxvirus proteins inhibit both Fas- and TNFR1-induced apoptosis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE FADD; caspase; tumor necrosis factor; molluscum contagiosum virus; equine herpesvirus type 2 ID INTERLEUKIN-1-BETA CONVERTING-ENZYME; BACULOVIRUS P35 PROTEIN; EQUINE HERPESVIRUS-2; VIRUS-REPLICATION; CELLS; CRMA; CYTOTOXICITY; INTERACTS; SEQUENCE; RECEPTOR AB To identify novel antiapoptotic proteins encoded by DNA viruses, we searched viral genomes for proteins that might interfere with Fas and TNFR1 apoptotic signaling pathways. We report here that equine herpesvirus type 2 E8 protein and molluscum contagiosum virus MC159 protein both show sequence similarity to the death effector domains (DEDs) of the Fas/TNFR1 signaling components FADD and caspase-8. Yeast two-hybrid analysis revealed that E8 protein interacted with the caspase-8 prodomain whereas MC159 protein interacted with FADD, Furthermore, expression of either E8 protein or MC159 protein protected cells from Fas-and TNFR1-induced apoptosis indicating that certain herpesviruses and poxviruses use DED-mediated interactions to interfere with apoptotic signaling pathways, These findings identify a novel control point exploited by viruses to regulate Fas- and TNFR1-mediated apoptosis. C1 NIAID,CLIN INVEST LAB,NIH,BETHESDA,MD 20892. NIAID,IMMUNOL LAB,NIH,BETHESDA,MD 20892. NIAID,VIRAL DIS LAB,NIH,BETHESDA,MD 20892. IUDN PHARMACEUT INC,LA JOLLA,CA 92037. THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,CTR APOPTOSIS RES,PHILADELPHIA,PA 19107. THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,KIMMEL CANC INST,PHILADELPHIA,PA 19107. NR 47 TC 338 Z9 348 U1 0 U2 6 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 18 PY 1997 VL 94 IS 4 BP 1172 EP 1176 DI 10.1073/pnas.94.4.1172 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WJ621 UT WOS:A1997WJ62100023 PM 9037025 ER PT J AU Torigoe, C Goldstein, B Wofsy, C Metzger, H AF Torigoe, C Goldstein, B Wofsy, C Metzger, H TI Shuttling of initiating kinase between discrete aggregates of the high affinity receptor for IgE regulates the cellular response SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID BASOPHILIC LEUKEMIA-CELLS; IMMUNOGLOBULIN-E; TYROSINE KINASES; FC-EPSILON; PHOSPHORYLATION; DESENSITIZATION; ACTIVATION; ENGAGEMENT; SIGNAL; BIND AB Using defined oligomers of IgE, our group previously studied the quantitative relationship between the aggregation of the high affinity receptors for IgE (Fc epsilon RI) and the earliest signals initiated by such aggregation: the phosphorylation of tyrosines on the receptor, Notably, at certain doses of the oligomers such phosphorylation reached a plateau level well before the aggregation of the receptors had reached a maximum, These findings and others led us to propose that aggregates of the receptor were competing for a limited amount of the critical kinase-thought to be Lyn in this system, This paper describes a test of this proposal, We incubated cells with two distinguishable IgEs and examined the effect of aggregating one or the other or both types on the phosphorylation, When receptors binding antigen-specific IgE were aggregated with polyvalent antigen, they became rapidly phosphorylated as expected, Remarkably, however, Fc epsilon RI that had already been phosphorylated by the binding of dimers of IgE, became dephosphorylated simultaneously, Furthermore, when the antigen-driven aggregates were dissociated with hapten, the phosphorylation pattern reverted to that seen prior to the addition of antigen: as the antigen-driven aggregates became dephosphorylated, the receptors stably aggregated by the bound oligomers became rapidly rephosphorylated, Dephosphorylation of oligomer-driven aggregates was also partially reversed during the ''spontaneous'' dephosphorylation of the antigen-driven receptors seen at longer times after addition of antigen. Thus signal transduction in this system is in part regulated by the shuttling of limited amounts of the kinase that initiates the cascade of phosphorylations. C1 LOS ALAMOS NATL LAB,DIV THEORET,THEORET BIOL & BIOPHYS GRP,LOS ALAMOS,NM 87545. UNIV NEW MEXICO,DEPT MATH & STAT,ALBUQUERQUE,NM 87131. RP Torigoe, C (reprint author), NIAMSD,ARTHRITIS & RHEUMATISM BRANCH,NIH,BETHESDA,MD 20892, USA. FU NIGMS NIH HHS [GM35556, R01 GM035556, R37 GM035556] NR 22 TC 47 Z9 47 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 18 PY 1997 VL 94 IS 4 BP 1372 EP 1377 DI 10.1073/pnas.94.4.1372 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WJ621 UT WOS:A1997WJ62100058 PM 9037060 ER PT J AU Ogawa, S Lubahn, DB Korach, KS Pfaff, DW AF Ogawa, S Lubahn, DB Korach, KS Pfaff, DW TI Behavioral effects of estrogen receptor gene disruption in male mice SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE sexual behavior; aggression; open-field behavior; androgen receptors; aromatization ID AGGRESSIVE-BEHAVIOR; RAT-BRAIN; ANDROGEN; MOUSE; ANIMALS AB Gonadal steroid hormones regulate sexually dimorphic development of brain functions and behaviors. Their nuclear receptors offer the opportunity to relate molecular events in neurons to simple instinctive mammalian behaviors, We have determined the role of estrogen receptor (ER) activation by endogenous estrogen in the development of male-typical behaviors by the use of transgenic estrogen-receptor-deficient (ERKO) mice. Surprisingly, in spite of the fact that they are infertile, ERKO mice showed normal motivation to mount females but they achieved less intromissions and virtually no ejaculations, Aggressive behaviors were dramatically reduced and male-typical offensive attacks were rarely displayed by ERKO males. Moreover, ER gene disruption demasculinized open-field behaviors, In the brain, despite the evident loss of functional ER protein, the androgen-dependent system appears to be normally present in ERKO mice, Together, these findings indicate that ER gene expression during development plays a major role in the organization of male-typical aggressive and emotional behaviors in addition to simple sexual behaviors. C1 UNIV MISSOURI,DEPT BIOCHEM,COLUMBIA,MO 65211. UNIV MISSOURI,DEPT CHILD HLTH,COLUMBIA,MO 65211. NIEHS,REPROD & DEV TOXICOL LAB,RES TRIANGLE PK,NC 27709. RP Ogawa, S (reprint author), ROCKEFELLER UNIV,NEUROBIOL & BEHAV LAB,1230 YORK AVE,NEW YORK,NY 10021, USA. OI Korach, Kenneth/0000-0002-7765-418X FU NICHD NIH HHS [R01 HD005751, HD-05751, R37 HD005751] NR 28 TC 305 Z9 309 U1 3 U2 10 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 18 PY 1997 VL 94 IS 4 BP 1476 EP 1481 DI 10.1073/pnas.94.4.1476 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WJ621 UT WOS:A1997WJ62100076 PM 9037078 ER PT J AU Murphy, DD Segal, M AF Murphy, DD Segal, M TI Morphological plasticity of dendritic spines in central neurons is mediated by activation of cAMP response element binding protein SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HIPPOCAMPAL-NEURONS; STIMULATION; EXPRESSION; DENSITY; SLICE AB While evidence has accumulated in favor of cAMP-associated genomic involvement in long-term synaptic plasticity, the mechanisms downstream of the activated nucleus that underlie these changes in neuronal function remain mostly unknown. Dendritic spines, the locus of excitatory interaction among central neurons, are prime candidates for long-term synaptic modifications. We now present evidence that links phosphorylation of the cAMP response element binding protein (CREB) to formation of new spines; exposure to estradiol doubles the density of dendritic spines in cultured hippocampal neurons, and concomitantly causes a large increase in phosphorylated CREB and in CREB binding protein, Blockade of cAMP-regulated protein kinase A eliminates estradiol-evoked spine formation, as well as the CREB and CREB binding protein responses. A specific antisense oligonucleotide eliminates the phosphorylated CREB response to estradiol as well as the formation of new dendritic spines. These results indicate that CREE phosphorylation is a necessary step in the process leading to generation of new dendritic spines. C1 WEIZMANN INST SCI,DEPT NEUROBIOL,IL-76100 REHOVOT,ISRAEL. RP Murphy, DD (reprint author), NINCDS,NEUROBIOL LAB,NIH,BLDG 36,ROOM 2A21,BETHESDA,MD 20892, USA. NR 25 TC 219 Z9 222 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 18 PY 1997 VL 94 IS 4 BP 1482 EP 1487 DI 10.1073/pnas.94.4.1482 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WJ621 UT WOS:A1997WJ62100077 PM 9037079 ER PT J AU Sora, I Takahashi, N Funada, M Ujike, H Revay, RS Donovan, DM Miner, LL Uhl, GR AF Sora, I Takahashi, N Funada, M Ujike, H Revay, RS Donovan, DM Miner, LL Uhl, GR TI Opiate receptor knockout mice define mu receptor roles in endogenous nociceptive responses and morphine-induced analgesia SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID DELTA-OPIOID RECEPTOR; MESSENGER-RNA EXPRESSION; SPINAL-CORD; IMMUNOHISTOCHEMICAL LOCALIZATION; PHARMACOLOGICAL CHARACTERIZATION; FUNCTIONAL EXPRESSION; MOLECULAR-CLONING; NUCLEUS CAUDALIS; BRAIN-STEM; RAT-BRAIN AB Morphine produces analgesia at opiate receptors expressed in nociceptive circuits, mu, delta, and kappa opiate receptor subtypes are expressed in circuits that can modulate nociception and receive inputs from endogenous opioid neuropeptide ligands, The roles played by each receptor subtype in nociceptive processing in drug-free and morphine-treated states have not been clear, however, We produced homologous, recombinant mu, opiate receptor, heterozygous and homozygous knockout animals that displayed approximate to 54% and 0% of wild-type levels of mu receptor expression, respectively, These mice expressed kappa receptors and delta receptors at near wild-type levels, Untreated knockout mice displayed shorter latencies on tail flick and hot plate tests for spinal and supraspinal nociceptive responses than wild-type mice. These findings support a significant role for endogenous opioid-peptide interactions with mu opiate receptors in normal nociceptive processing, Morphine failed to significantly reduce nociceptive responses in trot plate or tail flick tests of homozygous mu receptor knockout mice, and heterozygote mice displayed right and downward shifts in morphine analgesia dose-effect relationships, These results implicate endogenous opioid-peptide actions at mu opiate receptors in several tests of nociceptive responsiveness and support mu receptor mediation of morphine-induced analgesia in tests of spinal and supraspinal analgesia. C1 NIDA,MOL NEUROBIOL BRANCH,INTRAMURAL RES PROGRAM,NIH,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROL,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROSCI,BALTIMORE,MD 21224. NR 48 TC 382 Z9 389 U1 2 U2 9 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 18 PY 1997 VL 94 IS 4 BP 1544 EP 1549 DI 10.1073/pnas.94.4.1544 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WJ621 UT WOS:A1997WJ62100088 PM 9037090 ER PT J AU Zheng, LX Krsmanovic, LZ Vergara, LA Catt, KJ Stojilkovic, SS AF Zheng, LX Krsmanovic, LZ Vergara, LA Catt, KJ Stojilkovic, SS TI Dependence of intracellular signaling and neurosecretion on phospholipase D activation in immortalized gonadotropin-releasing hormone neurons SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID PROTEIN-KINASE-C; PITUITARY GONADOTROPHS; HYPOTHALAMIC NEURONS; PULSE-GENERATOR; PHOSPHATIDYLCHOLINE HYDROLYSIS; CA2+ OSCILLATIONS; RHESUS-MONKEY; KIDNEY-CELLS; NITRIC-OXIDE; SECRETION AB The excitability of gonadotropin-releasing hormone (GnRH) neurons is essential for episodic neuropeptide release, but the mechanism by which electrical activity controls GnRH secretion is not well characterized, The role of phospholipase D (PLD) in mediating the activity-dependent secretory pathway was investigated in immortalized GT1 neurons, which both secrete GnRH and express GnRH receptors, Activation of these Ca2+-mobilizing receptors was associated with transient hyperpolarization of GT1 cells, followed by sustained firing of action potentials, This was accompanied by an increase in PLD activity, as indicated by elevated phosphatidylethanol (PEt) production. GnRH-induced PEt production was reduced by inhibition of phospholipase C-dependent phosphoinositide hydrolysis by U73122 and neomycin, suggesting that signaling from phospholipase C led to activation of PLD. The intermediate role of protein kinase C (PKC) in this process was indicated by the ability of phorbol 12-myristate 13-acetate to induce time- and dose-dependent increases in PEt and diacylglycerol, but not inositol trisphosphate, and by reduction of GnRH-induced PEt accumulation in PKC-depleted cells, Consistent with the role of action potential-driven Ca2+ entry in this process, agonist-induced PLD activity was also reduced by nifedipine and low extracellular Ca2+. Inhibition of the PLD pathway by ethanol and propranolol reduced diacylglycerol production and caused a concomitant fall in GnRH release. These data indicate that voltage-gated Ca2+ entry and PKC act in an independent but cooperative manner to regulate PLD activity, which contributes to the secretory response in GT1 cells, Thus, the electrical activity of the GnRH-secreting neuron participates in the functional coupling between GnRH receptors and PLD pathway. C1 NICHHD,ENDOCRINOL & REPROD RES BRANCH,NIH,BETHESDA,MD 20892. NR 56 TC 25 Z9 25 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 18 PY 1997 VL 94 IS 4 BP 1573 EP 1578 DI 10.1073/pnas.94.4.1573 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WJ621 UT WOS:A1997WJ62100093 PM 9037095 ER PT J AU Brooks, AG Posch, PE Scorzelli, CJ Borrego, F Coligan, JE AF Brooks, AG Posch, PE Scorzelli, CJ Borrego, F Coligan, JE TI NKG2A complexed with CD94 defines a novel inhibitory natural killer cell receptor SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID NK CELL; MULTIGENE FAMILY; CDNA CLONES; HLA-C; MOLECULES; SUSCEPTIBILITY; ANTIGEN; PROTEINS; CLONING; GENES AB CD94 is a C-type lectin expressed by natural killer (NK) cells and a subset of T cells. Blocking studies using anti-CD94 mAbs have suggested that it is a receptor for human leukocyte antigen class I molecules. CD94 has recently been shown to be a 26-kD protein covalently associated with an unidentified 43-kD protein(s). This report shows that NKG2A, a 43-kD protein, is covalently associated with CD94 on the surface of NK cells. Cell surface expression of NKG2A is dependent on the association with CD94 as glycosylation patterns characteristic of mature proteins are found only in NKG2A that is associated with CD94. Analysis of NK cell clones showed that NKG2A was expressed in all NK cell clones whose CD16-dependent killing was inhibited by cross-linking CD94. The induction of an inhibitory signal is consistent with the presence of two immunoreceptor tyrosine-based inhibitory motifs (V/LXYXXL) on the cytoplasmic domain of NKG2A. Similar motifs are found on Ly49 and killer cell inhibitory receptors, which also transmit negative signals to NK cells. C1 NIAID,MOL STRUCT LAB,NIH,ROCKVILLE,MD 20852. NR 27 TC 177 Z9 178 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD FEB 17 PY 1997 VL 185 IS 4 BP 795 EP 800 DI 10.1084/jem.185.4.795 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA WK038 UT WOS:A1997WK03800021 PM 9034158 ER PT J AU Jain, R Cohen, LA ElKadi, NA King, MM AF Jain, R Cohen, LA ElKadi, NA King, MM TI Regiospecific alkylation of histidine and histamine at C-2 SO TETRAHEDRON LA English DT Article ID HETEROAROMATIC BASES; ANALOGS AB The first regiospecific synthesis of 2-alkyl-L-histidines and 2-alkylhistamines starting from fully protected L-histidine and histamine via silver catalyzed radical decarboxylative oxidation of alkylcarboxylic acids by ammonium persulfate in 10% H2SO4 is described. (C) 1997, Elsevier Science Ltd. C1 GEORGE WASHINGTON UNIV,DEPT CHEM,WASHINGTON,DC 20052. RP Jain, R (reprint author), NIDDK,BIOORGAN CHEM LAB,NIH,BETHESDA,MD 20892, USA. NR 22 TC 26 Z9 26 U1 0 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0040-4020 J9 TETRAHEDRON JI Tetrahedron PD FEB 17 PY 1997 VL 53 IS 7 BP 2365 EP 2370 DI 10.1016/S0040-4020(96)01193-3 PG 6 WC Chemistry, Organic SC Chemistry GA WJ211 UT WOS:A1997WJ21100004 ER PT J AU Spencer, JV Trus, BL Booy, FP Steven, AC Newcomb, WW Brown, JC AF Spencer, JV Trus, BL Booy, FP Steven, AC Newcomb, WW Brown, JC TI Structure of the herpes simplex virus capsid: Peptide A862-H880 of the major capsid protein is displayed on the rim of the capsomer protrusions SO VIROLOGY LA English DT Article ID VP26; BACTERIOPHAGE-PHI-X174; IDENTIFICATION; LOCALIZATION; RESOLUTION; COMPLEX; PENTONS AB The herpes simplex virus-1 (HSV-1) capsid shell has 162 capsomers arranged on a T=16 icosahedral lattice. The major capsid protein, VP5 (MW=149,075) is the structural component of the capsomers. VP5 is an unusually large viral capsid protein and has been shown to consist of multiple domains. To study the conformation of VP5 as it is folded into capsid protomers, we identified the sequence recognized by a VP5-specific monoclonal antibody and localized the epitope on the capsid surface by cryoelectron microscopy and image reconstruction. The epitope of mAb 6F10 was mapped to residues 862-880 by immunoblotting experiments performed with (1) proteolytic fragments of VP5, (2) GST-fusion proteins containing VP5 domains, and (3) synthetic VP5 peptides. As visualized in a three-dimensional density map of 6F10-precipitated capsids, the antibody was found to bind at sites on the outer surface of the capsid just inside the openings of the trans-capsomeric channels. We conclude that these sites are occupied by peptide 862-880 in the mature HSV-1 capsid. (C) 1997 Academic Press. C1 UNIV VIRGINIA,HLTH SCI CTR,DEPT MICROBIOL,CHARLOTTESVILLE,VA 22908. UNIV VIRGINIA,HLTH SCI CTR,CTR CANC,CHARLOTTESVILLE,VA 22908. NIAMSD,STRUCT BIOL LAB,NIH,BETHESDA,MD 20892. NIH,COMPUTAT BIOSCI & ENGN LAB,DIV COMP RES & TECHNOL,BETHESDA,MD 20892. FU NIAID NIH HHS [AI-137549] NR 30 TC 28 Z9 28 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD FEB 17 PY 1997 VL 228 IS 2 BP 229 EP 235 DI 10.1006/viro.1996.8392 PG 7 WC Virology SC Virology GA WK177 UT WOS:A1997WK17700012 PM 9123829 ER PT J AU Shinohara, T Nagashima, K Major, EO AF Shinohara, T Nagashima, K Major, EO TI Propagation of the human polyomavirus, JCV, in human neuroblastoma cell lines SO VIROLOGY LA English DT Article ID NUCLEAR FACTOR-I; FETAL GLIAL-CELLS; HUMAN-BRAIN CELLS; TRANSCRIPTIONAL ACTIVATION; REGULATORY REGION; BINDING-PROTEINS; DNA-REPLICATION; VIRUS; EXPRESSION; ENHANCER AB Susceptibility to infection by the human polyomavirus, JCV, is determined by intracellular mechanisms which control transcription and replication. Originally thought to propagate well only in human cells of oligodendroglial lineage, JCV has recently been shown to infect astrocytes, astrogliomas, and a neuroblastoma cell line. The data reported here describe two cell types that have been subcultured from a human neuroblastoma cell line, SK-N-SH. The SH-SY5Y subclone displays neuronal phenotypes and is not susceptible to JCV infection, while the SH-EP subclone displays glial cell phenotypes and is susceptible to infection. Binding of nuclear proteins from the permissive SH-EP cells to the nuclear factor-1 (NF-1) site in the JCV regulatory DNA sequences results in a gel shift pattern that is different from the nonpermissive SH-SY5Y cell proteins. Northern analysis of mRNA for the four classes of NF-1 proteins showed a predominance of the NF-1/X class in SH-EP cells similar to the highly permissive human fetal glial cells. Very low levels of mRNA for NF-1/X were seen in the nonpermissive SH-SY5Y cells, similar to that seen for the nonpermissive HeLa cells. Several other cell lines tested that were permissive for JCV infection also showed synthesis of the NF-1/X class of proteins. SH-EP cells represent a cell line in a glial cell lineage which is susceptible to JCV multiplication. These cells may be a useful cell culture system for the investigation of DNA binding factors which correlates with viral susceptibility. (C) 1997 Academic Press. C1 NINCDS,LAB MOL MED & NEUROSCI,NIH,BETHESDA,MD 20892. HOKKAIDO UNIV,SCH MED,DEPT PATHOL,SAPPORO,HOKKAIDO 060,JAPAN. NR 44 TC 21 Z9 21 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD FEB 17 PY 1997 VL 228 IS 2 BP 269 EP 277 DI 10.1006/viro.1996.8409 PG 9 WC Virology SC Virology GA WK177 UT WOS:A1997WK17700017 PM 9123834 ER PT J AU Morozov, VA Copeland, TD Nagashima, K Gonda, MA Oroszlan, S AF Morozov, VA Copeland, TD Nagashima, K Gonda, MA Oroszlan, S TI Protein composition and morphology of human foamy virus intracellular cores and extracellular particles SO VIROLOGY LA English DT Article ID HUMAN SYNCYTIAL VIRUS; HUMAN SPUMARETROVIRUS; TRANSGENIC MICE; GAG; DNA; IDENTIFICATION; BINDING; CELLS; GENES; ENCEPHALOPATHY AB Characterization of human foamy virus (HFV) gag-encoded precursors and the search for a Gag-Pol polyprotein and mature proteins derived from proteolytic processing were carried out in HFV-infected cells and with purified preassembled cores and extracellular virus by Western blotting and radioimmunoprecipitation using antisera against synthetic peptides corresponding to putative Gag and protease proteins. Precursor proteins, Pr78(gag)/74(gag) and Pr135(pol), were found in the nucleus of epithelial and fibroblast cells 3-4 days after HFV infection. Kinetic analysis of HFV Pr78(gag) and Pr74(gag) indicated that Pr78(gag) is a precursor to pr74(gag). South-Western blot analysis indicated that Pr78(gag) and Pr74(gag) have properties associated with nucleic acid binding protein although they lack the typical zinc-finger motifs found in retroviral nucleocapsid proteins. Western blot analyses of preassembled HFV cores isolated from the cytoplasm of infected cells and purified by sucrose gradient centrifugation demonstrated the presence of Pr78(gag)/74(gag) and Pr135(pol), but no proteolytically processed Gag proteins were observed. The majority of extracellular HFV particles were found to have pentagon-shaped cores, as observed intracellularly, and are believed to be the immature extracellular form of the virus. The highest concentration of extracellular particles, estimated by EM, Western blot, and reverse transcriptase assays were found in sucrose gradient fractions having a density of 1.21-1.24 g/cm(3). Western blot analysis revealed that Pr78(gag)/74(gag) and Pr135(pol) were the major viral proteins associated with these extracellular particles, as only small amounts of putative proteolytically cleaved capsid (p32) were observed. Our results support the notion that Pol is translated independent of Gag in HFV-infected cells. (C) 1997 Academic Press. C1 NCI,FREDERICK CANC RES & DEV CTR,SAIC FREDERICK,ABL BASIC RES PROGRAM,SPECIAL PROGRAM PROT CHEM,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,SAIC FREDERICK,LAB CELL & MOL STRUCT,FREDERICK,MD 21702. RP Morozov, VA (reprint author), NCI,FREDERICK CANC RES & DEV CTR,SAIC FREDERICK,LAB MOL VIROL & CARCINOGENESIS,FREDERICK,MD 21702, USA. NR 35 TC 25 Z9 26 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD FEB 17 PY 1997 VL 228 IS 2 BP 307 EP 317 DI 10.1006/viro.1996.8379 PG 11 WC Virology SC Virology GA WK177 UT WOS:A1997WK17700021 PM 9123838 ER PT J AU Romanov, VI Zolotukhin, AS Aleksandroff, NN DaSilva, PP Felber, BK AF Romanov, VI Zolotukhin, AS Aleksandroff, NN DaSilva, PP Felber, BK TI Posttranscriptional regulation by Rev protein of human immunodeficiency virus type 1 results in nonrandom nuclear localization of gag mRNA SO VIROLOGY LA English DT Article ID VIRAL MESSENGER-RNA; IN-SITU HYBRIDIZATION; HIV-1 REV; RESPONSIVE ELEMENT; TARGET SEQUENCE; GENE-PRODUCT; SUBCELLULAR-LOCALIZATION; INSITU HYBRIDIZATION; SECONDARY STRUCTURE; ACTIVATION DOMAIN AB The expression of the human immunodeficiency virus type I mRNAs containing the Rev-responsive element is regulated at the posttranscriptional level by the viral Rev protein. Rev increases the nucleocytoplasmic export of these mRNAs, leading to high expression. Using in situ hybridization and electron microscopy, we investigated the localization of a subgenomic gag mRNA in the absence and presence of Rev. In addition to the previously shown cytoplasmic accumulation of the Rev-dependent mRNA, we observed that in the presence of Rev the nuclear gag mRNA accumulates nonrandomly and forms specific localization patterns at the nuclear membrane and in the nucleoplasm. Cellular mRNAs for beta-actin and glyceralde-hyde-3-phosphate dehydrogenase were not found to form such patterns. These data suggest that Rev leads the gag mRNA to specific subnuclear locations, which further supports the transport function of Rev. (C) 1997 Academic Press. C1 NCI, FREDERICK CANC RES & DEV CTR, HUMAN RETROVIRUS PATHOGENESIS GRP, ABL BASIC RES PROGRAM, FREDERICK, MD 21702 USA. NCI, FREDERICK CANC RES & DEV CTR, MATH BIOL LAB, MEMBRANE BIOL SECT, FREDERICK, MD 21702 USA. NCI, FREDERICK CANC RES & DEV CTR, MATH BIOL LAB, MEMBRANE BIOL SECT, FREDERICK, MD 21702 USA. NR 52 TC 10 Z9 10 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 0042-6822 J9 VIROLOGY JI Virology PD FEB 17 PY 1997 VL 228 IS 2 BP 360 EP 370 DI 10.1006/viro.1996.8398 PG 11 WC Virology SC Virology GA WK177 UT WOS:A1997WK17700026 PM 9123843 ER PT J AU Guo, HG Browning, P Nicholas, J Hayward, GS Tschachler, E Jiang, YW Sadowska, M Raffeld, M Colombini, S Gallo, RC Reitz, MS AF Guo, HG Browning, P Nicholas, J Hayward, GS Tschachler, E Jiang, YW Sadowska, M Raffeld, M Colombini, S Gallo, RC Reitz, MS TI Characterization of a chemokine receptor-related gene in human herpesvirus 8 and its expression in Kaposi's sarcoma SO VIROLOGY LA English DT Article ID DNA-SEQUENCES; PERIPHERAL-BLOOD; IDENTIFICATION; INDIVIDUALS; SAIMIRI; AFRICAN; FORMS AB Human herpesvirus 8 (HHV-8) is a recently discovered virus that is highly associated with Kaposi's sarcoma (KS) and AIDS-associated body cavity lymphomas, although it is also found in some normal individuals. HHV-8 is related by nucleotide sequence homology to herpesvirus saimiri (HVS), which causes T cell lymphomas in some New World monkeys, and to Epstein-Barr virus (EBV), a human herpesvirus linked etiologically with Burkitt's lymphoma and nasopharyngeal carcinoma. We report that, like HVS but unlike EBV, HHV-8 contains a gene (ORF74) with significant sequence homology to the high-affinity IL-8 receptor, a member of the alpha (CXC) chemokine receptor family of transmembrane G protein-coupled receptors. We also show by reverse transcription PCR that the chemokine receptor-related HHV-8 gene is detectable in some RNA samples from KS tissue, and that its expression varies independently from that of ORF26, a minor capsid protein. The presence of a potential chemokine receptor in HHV-8 and its expression in KS tissue suggests that it may be important in the regulation of viral gene expression and may play a role in the etiology of KS and AIDS-related body cavity lymphomas. (C) 1997 Academic Press. C1 UNIV MARYLAND,INST BIOTECHNOL,CTR MED BIOTECHNOL,INST HUMAN VIROL,BALTIMORE,MD 21201. VANDERBILT UNIV,VANDERBILT CANC CTR,NASHVILLE,TN 37232. JOHNS HOPKINS UNIV,SCH MED,DEPT ONCOL,BALTIMORE,MD 21205. UNIV VIENNA,SCH MED,DEPT DERMATOL,VIENNA,AUSTRIA. ADV BIOSCI LABS,KENSINGTON,MD 20895. NCI,PATHOL LAB,BETHESDA,MD 20892. NR 40 TC 92 Z9 93 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD FEB 17 PY 1997 VL 228 IS 2 BP 371 EP 378 DI 10.1006/viro.1996.8386 PG 8 WC Virology SC Virology GA WK177 UT WOS:A1997WK17700027 PM 9123844 ER PT J AU Horton, D Liu, QJ Luck, RL Silverton, JV AF Horton, D Liu, QJ Luck, RL Silverton, JV TI (6S)-8-C-chloro-6,7,8-trideoxy-1,2:3,4-di-O-isopropylidene-alpha-D-galac to-octa-6,7-dienopyranose SO ACTA CRYSTALLOGRAPHICA SECTION C-CRYSTAL STRUCTURE COMMUNICATIONS LA English DT Article AB The title structure, C14H19ClO5, consists of an allene substituted with a Cl atom at one end joined at the other end to a D-galactopyranose ring bearing two fused isopropylidene groups. C1 NHLBI,BIOPHYS CHEM LAB,NIH,BETHESDA,MD 20892. RP Horton, D (reprint author), AMERICAN UNIV,DEPT CHEM,440 MASSACHUSETTS AVE NW,WASHINGTON,DC 20016, USA. NR 5 TC 1 Z9 1 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0108-2701 J9 ACTA CRYSTALLOGR C JI Acta Crystallogr. Sect. C-Cryst. Struct. Commun. PD FEB 15 PY 1997 VL 53 BP 236 EP 238 DI 10.1107/S0108270196012851 PN 2 PG 3 WC Chemistry, Multidisciplinary; Crystallography SC Chemistry; Crystallography GA WL369 UT WOS:A1997WL36900034 PM 9062982 ER PT J AU Miller, CE Kovac, P Glaudemans, CPJ AF Miller, CE Kovac, P Glaudemans, CPJ TI Recovery of monoclonal antibody from its complex with ligand SO ANALYTICAL BIOCHEMISTRY LA English DT Article ID BINDING; CONSTANTS AB The separation of antibody from its excess and bound ligand is important following affinity chromatography or the use of methods requiring large amounts of antibody, such as microcalorimetry. Using radioactively labeled ligands we show that these separations can be effected by using commercially available, short polyacrylamide size-exclusion columns. By using both low (k(a) = 5 x 10(2) M(-1)) and medium high-affinity (K-a = 0.6 x 10(6) M(-1)) ligands in the presence of antibody, it is shown that the latter system requires more dilute loading concentrations than the former system does in order to achieve acceptable separation. Since the degree of association between a protein and a ligand is solely governed by the affinity constant for the binding equilibrium, these results are applicable to any system represented by this range of binding constants. C1 NIDDKD,NIH,BETHESDA,MD 20892. NR 15 TC 1 Z9 1 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD FEB 15 PY 1997 VL 245 IS 2 BP 179 EP 183 DI 10.1006/abio.1996.9969 PG 5 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA WK041 UT WOS:A1997WK04100010 PM 9056209 ER PT J AU Lewis, RA Carr, LM Doyle, K Fainstein, V Gross, R OrengoNania, S Samo, TC Shigley, JW Spencer, SS Weinert, M Dunn, JP Bartlett, J Becker, R Feinberg, J Jabs, DA Johnson, DA LaSalvia, S Miller, T Neisser, LG Semba, RD TayKearney, ML Tucker, P Barron, B Jarrott, C Peyman, G Swenie, D Friedman, AH Ginsburg, R Sacks, H Severin, C Teich, S Wallach, F Rescigno, R Cowan, J Horan, C Kloser, P Wanner, M Friedberg, DN Addessi, A Chachoua, A Dieterich, D Hill, J Hutt, R Ligh, J LorenzoLatkany, M Pei, M Powers, T Scoppe, C Weinberg, DV Jampol, LM Lyon, AT Munana, A Murphy, R Palella, F Richine, L Strugala, Z Valadez, G Holland, GN Carlson, ME Chafey, S Hardy, WD Johiro, AK MacarthurChang, L Martin, MA Moe, AA Strong, CA Tufail, A Ugalat, PS Weisz, JM Freeman, WR ArevaloColina, JF Clark, T Jarman, CL Meixner, L Meng, TC Spector, S Taskintuna, I Torriani, FJ ODonnell, J Alfred, P Ballesteros, F Clay, D Coleman, R Gumbley, D Hoffman, J Irvine, A Jacobson, M Larson, J Macalalag, L Narahara, M Payne, M Seiff, S Wilson, S Woodring, H Davis, J Mendez, P Murray, T Simmons, T vanderHorst, C Kylstra, J Wohl, D Ziman, K Pavan, PR Bergen, GA Cohen, SM Craig, JA Dehler, RL Elbert, E Fox, RW Grizzard, WS Hammer, ME Hernandez, LS Herrera, S Holt, D Kemp, S Larkin, JA Ledford, DK Lockey, RF Menosky, MM Millard, S Nadler, JP Nelson, RP Norris, D Ormerod, LD Pautler, SE Poblete, SJ Rodriguez, D Rosenbach, KP Seekins, DW Toney, JR Dodge, JM Klemstine, JL Schuerholtz, TA Stevens, M Meinert, CL AmendLibercci, D Coleson, L Collins, KL Collison, BJ Dawson, C Dodge, J Donithan, M Ewing, C Fink, N Gerczak, C Harle, J Holbrook, JT Huffman, R Isaacson, MR Gilpin, AMK Lane, M Levine, CR Martin, B Meinert, J Nowakowski, DJ Owens, RM Piantadosi, B Saah, A Smith, M Tonascia, J VanNatta, ML Davis, MD Armstrong, J Brickbauer, J Brothers, R Chop, M Hubbard, L Hurlburt, D Kastorff, L Magli, Y Neider, M Onofrey, J Stoppenbach, V VanderhoofYoung, M Walls, M Hughes, R Kurinij, N Mowery, RL Alston, B Foulkes, M Freeman, W Holbrook, J Meinert, C Mowery, R Polsky, B Duncan, WR Kessler, H Lambert, AG Powderly, W Schnittman, S Spector, S Brown, BW Conway, B Grizzle, J Nussenblatt, R Phair, JP Smith, H Whitley, R Cheng, B Frost, K Marco, M AF Lewis, RA Carr, LM Doyle, K Fainstein, V Gross, R OrengoNania, S Samo, TC Shigley, JW Spencer, SS Weinert, M Dunn, JP Bartlett, J Becker, R Feinberg, J Jabs, DA Johnson, DA LaSalvia, S Miller, T Neisser, LG Semba, RD TayKearney, ML Tucker, P Barron, B Jarrott, C Peyman, G Swenie, D Friedman, AH Ginsburg, R Sacks, H Severin, C Teich, S Wallach, F Rescigno, R Cowan, J Horan, C Kloser, P Wanner, M Friedberg, DN Addessi, A Chachoua, A Dieterich, D Hill, J Hutt, R Ligh, J LorenzoLatkany, M Pei, M Powers, T Scoppe, C Weinberg, DV Jampol, LM Lyon, AT Munana, A Murphy, R Palella, F Richine, L Strugala, Z Valadez, G Holland, GN Carlson, ME Chafey, S Hardy, WD Johiro, AK MacarthurChang, L Martin, MA Moe, AA Strong, CA Tufail, A Ugalat, PS Weisz, JM Freeman, WR ArevaloColina, JF Clark, T Jarman, CL Meixner, L Meng, TC Spector, S Taskintuna, I Torriani, FJ ODonnell, J Alfred, P Ballesteros, F Clay, D Coleman, R Gumbley, D Hoffman, J Irvine, A Jacobson, M Larson, J Macalalag, L Narahara, M Payne, M Seiff, S Wilson, S Woodring, H Davis, J Mendez, P Murray, T Simmons, T vanderHorst, C Kylstra, J Wohl, D Ziman, K Pavan, PR Bergen, GA Cohen, SM Craig, JA Dehler, RL Elbert, E Fox, RW Grizzard, WS Hammer, ME Hernandez, LS Herrera, S Holt, D Kemp, S Larkin, JA Ledford, DK Lockey, RF Menosky, MM Millard, S Nadler, JP Nelson, RP Norris, D Ormerod, LD Pautler, SE Poblete, SJ Rodriguez, D Rosenbach, KP Seekins, DW Toney, JR Dodge, JM Klemstine, JL Schuerholtz, TA Stevens, M Meinert, CL AmendLibercci, D Coleson, L Collins, KL Collison, BJ Dawson, C Dodge, J Donithan, M Ewing, C Fink, N Gerczak, C Harle, J Holbrook, JT Huffman, R Isaacson, MR Gilpin, AMK Lane, M Levine, CR Martin, B Meinert, J Nowakowski, DJ Owens, RM Piantadosi, B Saah, A Smith, M Tonascia, J VanNatta, ML Davis, MD Armstrong, J Brickbauer, J Brothers, R Chop, M Hubbard, L Hurlburt, D Kastorff, L Magli, Y Neider, M Onofrey, J Stoppenbach, V VanderhoofYoung, M Walls, M Hughes, R Kurinij, N Mowery, RL Alston, B Foulkes, M Freeman, W Holbrook, J Meinert, C Mowery, R Polsky, B Duncan, WR Kessler, H Lambert, AG Powderly, W Schnittman, S Spector, S Brown, BW Conway, B Grizzle, J Nussenblatt, R Phair, JP Smith, H Whitley, R Cheng, B Frost, K Marco, M TI Parenteral cidofovir for cytomegalovirus retinitis in patients with AIDS: The HPMPC peripheral cytomegalovirus retinitis trial - A randomized, controlled trial SO ANNALS OF INTERNAL MEDICINE LA English DT Article DE cidofovir; cytomegalovirus retinitis; acquired immunodeficiency syndrome; vision disorders; probenecid ID HUMAN-IMMUNODEFICIENCY-VIRUS; NUCLEOTIDE ANALOG; GANCICLOVIR; (S)-1-<3-HYDROXY-2-(PHOSPHONYLMETHOXY)PROPYL>CYTOSINE; (S)-1-(3-HYDROXY-2-PHOSPHONYLMETHOXYPROPYL)CYTOSINE; ZIDOVUDINE; INFECTION; DISEASE; MODELS AB Background: Cytomegalovirus (CMV) retinitis is a common infection and a major cause of visual loss in patients with the acquired immunodeficiency syndrome (AIDS). Objective: To evaluate intravenous cidofovir as a treatment for CMV retinitis. Design: Two-stage, multicenter, phase II/III, randomized, controlled clinical trial. Setting: Ophthalmology and AIDS services at tertiary care medical centers. Patients: 64 patients with AIDS and previously untreated, small, peripheral CMV retinitis lesions (that is, patients at low risk for loss of visual acuity). Intervention: Patients were randomly assigned to one of three groups: the deferral group, in which treatment was deferred until retinitis progressed; the low-dose cidofovir group, which received cidofovir, 5 mg/kg of body weight once weekly for 2 weeks, then maintenance therapy with cidofovir, 3 mg/kg once every 2 weeks; or the high-dose cidofovir group, which received cidofovir, 5 mg/kg once weekly for 2 weeks, then maintenance therapy with cidofovir, 5 mg/kg once every 2 weeks. To minimize nephrotoxicity, cidofovir was administered with hydration and probenecid. Measurements: Progression of retinitis, evaluated in a masked manner by a fundus photograph reading center; the amount of retinal area involved by CMV; the loss of visual acuity; and morbidity. Results: Median time to progression was 64 days in the low-dose cidofovir group and 21 days in the deferral group (P = 0.052, log-rank test). The median time to progression was not reached in the high-dose cidofovir group but was 20 days in the deferral group (P = 0.009, log-rank test). Analysis of the rates of increase in the retinal area affected by CMV confirmed the data on time to progression. The three groups had similar rates of visual loss. Proteinuria of 2+ or more occurred at rates of 2.6 per person-year in the deferral group, 2.8 per person-year in the low-dose cidofovir group (P > 0.2), and 6.8 per person-year in the high-dose cidofovir group (P = 0.135). No patient developed 4+ proteinuria, but two cidofovir recipients developed persistent elevations of serum creatinine levels at more than 177 mu mol/L (2.0 mg/dL). Reactions to probenecid occurred at a rate of 0.70 per person-year. Conclusions: Intravenous cidofovir, high- or low-dose, effectively slowed the progression of CMV retinitis. Concomitant probenecid and hydration therapy, intermittent dosing, and monitoring for proteinuria seemed to minimize but not eliminate the risk for nephrotoxicity. C1 BAYLOR COLL MED, HOUSTON, TX 77030 USA. CULLEN EYE INST, HOUSTON, TX USA. JOHNS HOPKINS UNIV, SCH MED, BALTIMORE, MD USA. LOUISIANA STATE UNIV, MED CTR, NEW ORLEANS, LA USA. MT SINAI SCH MED, NEW YORK, NY USA. UNIV MED & DENT NEW JERSEY, NEW JERSEY MED SCH, NEWARK, NJ 07103 USA. NYU, MED CTR, NEW YORK, NY 10016 USA. NORTHWESTERN UNIV, CHICAGO, IL 60611 USA. UNIV CALIF LOS ANGELES, LOS ANGELES, CA 90024 USA. UNIV CALIF SAN DIEGO, SAN DIEGO, CA 92103 USA. UNIV CALIF SAN FRANCISCO, SAN FRANCISCO, CA 94143 USA. UNIV MIAMI, SCH MED, MIAMI, FL USA. UNIV N CAROLINA, CHAPEL HILL, NC 27515 USA. UNIV S FLORIDA, TAMPA, FL USA. JOHNS HOPKINS UNIV, SCH HYG & PUBL HLTH, BALTIMORE, MD 21218 USA. UNIV WISCONSIN, PHOTOGRAPH READING CTR, MADISON, WI USA. MCKESSON BIOSERV CORP, DRUG DISTRIBUT CTR, ROCKVILLE, MD USA. NEI, BETHESDA, MD 20892 USA. NIAID, BETHESDA, MD 20892 USA. RP Lewis, RA (reprint author), JOHNS HOPKINS UNIV, WILMER OPHTHALMOL INST,AIDS CHAIRMANS OFF,SCH MED, 550 N BROADWAY, SUITE 700, BALTIMORE, MD 21205 USA. NR 37 TC 130 Z9 130 U1 2 U2 3 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD FEB 15 PY 1997 VL 126 IS 4 BP 264 EP + PG 0 WC Medicine, General & Internal SC General & Internal Medicine GA WH068 UT WOS:A1997WH06800004 ER PT J AU Park, EA Song, SL Olive, M Roesler, WJ AF Park, EA Song, SL Olive, M Roesler, WJ TI CCAAT-enhancer-binding protein a (C/EBP alpha) is required for the thyroid hormone but not the retinoic acid induction of phosphoenolpyruvate carboxykinase (PEPCK) gene transcription SO BIOCHEMICAL JOURNAL LA English DT Article ID RESPONSE ELEMENT; RAT-LIVER; GTP GENE; RECEPTOR; EXPRESSION; PROMOTER; IDENTIFICATION; ACTIVATION; TRIIODOTHYRONINE; SYNERGISM AB Transcription of the gene for phosphoenolpyruvate carboxy-kinase (PEPCK) is stimulated by cAMP, the thyroid hormone tri-iodothyronine (T-3) and retinoic acid (RA), Regulation of PEPCK transcription by T-3 involves two sites in the promoter including a thyroid-hormone-response element (TRE) and a CCAAT-enhancer-binding protein (C/EBP) binding site called P3(I). Mutation of either the TRE or P3(I) eliminates the T-3 response. In this study, we examined the role of C/EBPs in the induction of PEPCK transcription by T-3 and RA, PEPCK-CAT vectors were transfected into HepG2 cells. Co-transfection of a dominant negative C/EBP eliminated the T-3 stimulation indicating that a member of the C/EBP family is required. To determine which C/EBP isoform was required, Gal4 fusion proteins were created that contained the Gal4 DNA-binding domain ligated to the transcriptional activation domain of C/EBP alpha, C/EBP beta or the cAMP-responsive-element-binding protein. A Gal4 DNA-binding site was introduced into the P3(I) site of the PEPCK-CAT vector. Only co-transfection of the Gal4-C/EBP alpha vector was able to restore T-3 responsiveness to the PEPCK-CAT vector, The T-3 and RA receptors are members of the nuclear receptor superfamily and bind to repeats of the AGGTCA motif. We found that the RA receptor can bind to sequences within the PEPCK-TRE and contribute to RA responsiveness of the PEPCK gene, However, the RA induction of PEPCK transcription was found to be independent of C/EBPs, further demonstrating the specificity of the involvement of C/EBP alpha in the T-3 effect. C1 UNIV SASKATCHEWAN,DEPT BIOCHEM,SASKATOON,SK S7N 5E5,CANADA. NCI,BIOCHEM LAB,NIH,BETHESDA,MD 20892. RP Park, EA (reprint author), UNIV TENNESSEE,CTR HLTH SCI,DEPT PHARMACOL,COLL MED,874 UNION AVE,MEMPHIS,TN 38163, USA. FU NIDDK NIH HHS [DK46399] NR 39 TC 33 Z9 33 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 FEB 15 PY 1997 VL 322 BP 343 EP 349 PN 1 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WL282 UT WOS:A1997WL28200047 PM 9078282 ER PT J AU Maciejewski, JP Sloand, EM Sato, T Anderson, S Young, NS AF Maciejewski, JP Sloand, EM Sato, T Anderson, S Young, NS TI Impaired hematopoiesis in paroxysmal nocturnal hemoglobinuria/aplastic anemia is not associated with a selective proliferative defect in the glycosylphosphatidylinositol-anchored protein-deficient clone SO BLOOD LA English DT Article ID SEVERE APLASTIC-ANEMIA; DECAY-ACCELERATING FACTOR; HUMAN-BONE-MARROW; PIG-A GENE; PERIPHERAL-BLOOD; STEM-CELLS; PATHOGENETIC LINK; LIMITING DILUTION; MOLECULAR-BASIS; FLOW-CYTOMETRY AB Paroxysmal nocturnal hemoglobinuria (PNH) results from somatic mutations in the PIG-A gene, leading to poor presentation of glycosylphosphatidylinositol (GPI)-anchored surface proteins. PNH frequently occurs in association with suppressed hematopoiesis, including frank aplastic anemia (AA). The relationship between GPI-anchored protein expression and bone marrow (BM) failure is unknown. To assess the hematopoietic defect in PNH, the numbers of CD34(+) cells, committed progenitors (primary colony-forming cells [CFCs]), and long-term culture-initiating cells (LTC-ICs; a stem cell surrogate) were measured in BM and peripheral blood (PB) of patients with PNH/AA syndrome or patients with predominantly hemolytic PNH. LTC-IC numbers were extrapolated from secondary CFC numbers after 5 weeks of culture, and clonogenicity of LTC-ICs was determined by limiting dilution assays. When compared with normal volunteers (n = 13), PNH patients (n = 14) showed a 4.7-fold decrease in CD34(+) cells and an 8.2-fold decrease in CFCs. LTC-ICs in BM and in PB were decreased 7.3-fold and 50-fold, respectively. Purified CD34(+) cells from PNH patients had markedly lower clonogenicity in both primary colony cultures and in the LTC-IC assays. As expected, GPI-anchored proteins were decreased on PB cells of PNH patients. On average, 23% of monocytes were deficient in CD14, and 47% of granulocytes and 58% of platelets lacked CD16 and CD55, respectively. In PNH BM, 27% of CD34(+) cells showed abnormal GPI-anchored protein expression when assessed by CD59 expression. To directly measure the colony-forming ability of GPI-anchored protein-deficient CD34(+) cells, we separated CD34(+) cells from PNH patients for the GPI(+) and GPI(-) phenotype; CD59 expression was chosen as a marker of the PNH phenotype based on high and homogeneous expression on fluorescent staining. CD34(+)CD59(+) and CD34(+)CD59(-) cells from PNH/AA patients showed similarly impaired primary and secondary clonogeneic efficiency. The progeny derived from CD34(+)CD59(-) cells were both CD59(-) and CD55(-). A very small population of CD34(+)CD59(-) cells was also detected in some normal volunteers; after sorting, these CD34(+)CD59(-) cells formed normal numbers of colonies, but their progeny showed lower CD59 levels. Our results are consistent with the existence of PIG-A-deficient clones in some normal individuals. In PNH/AA, progenitor and stem cells are decreased in number and function, but the proliferation in vitro is affected similarly in GPI-protein-deficient clones and in phenotypically normal cells. As measured in the in vitro assays, expansion of PIG-A(-) clones appears not be caused by an intrinsic growth advantage of cells with the PNH phenotype. (C) 1997 by The American Society of Hematology. C1 NHLBI,HEMATOL BRANCH,NATL INST HLTH,BETHESDA,MD 20892. NR 42 TC 81 Z9 87 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD FEB 15 PY 1997 VL 89 IS 4 BP 1173 EP 1181 PG 9 WC Hematology SC Hematology GA WG797 UT WOS:A1997WG79700007 PM 9028939 ER PT J AU Munshi, NC Govindarajan, R Drake, R Ding, LM Iyer, R Saylors, R Kornbluth, J Marcus, S Chiang, Y Ennist, D Kwak, L Reynolds, C Tricot, G Barlogie, B AF Munshi, NC Govindarajan, R Drake, R Ding, LM Iyer, R Saylors, R Kornbluth, J Marcus, S Chiang, Y Ennist, D Kwak, L Reynolds, C Tricot, G Barlogie, B TI Thymidine kinase (TK) gene-transduced human lymphocytes can be highly purified, remain fully functional, and are killed efficiently with ganciclovir SO BLOOD LA English DT Article ID BONE-MARROW TRANSPLANTATION; VERSUS-HOST DISEASE; CHRONIC MYELOGENOUS LEUKEMIA; PERIPHERAL-BLOOD LYMPHOCYTES; CHRONIC MYELOID-LEUKEMIA; CELL DEPLETION; ADOPTIVE IMMUNOTHERAPY; SELECTIVE DEPLETION; GRAFT; RELAPSE AB A graft-versus-leukemia (GVL) effect has been considered a major factor responsible for cures in patients with hematologic malignancies undergoing allogeneic bone marrow transplantation; however, associated graft-versus-host disease (GVHD) results in significant morbidity and mortality. T-cell depletion reduces the incidence and severity of GVHD but eliminates, at least partially, the GVL effect. Reinfusion of donor T lymphocytes at relapse posttransplantation can induce a potent antitumor response, but GVHD still occurs in the majority of patients. Prior transduction of T lymphocytes with the suicide gene, the viral thymidine kinase (TK), permits specific cell kill on administration of ganciclovir (GCV). Therefore, infusion of TK-transduced T lymphocytes may induce GVL effect and allow for their subsequent selective elimination in case GVHD develops. To evaluate the efficacy and feasibility of this promising approach, anti-CD3-stimulated primary human lymphocytes cultured in interleukin-2 were TK-transduced by a retroviral vector carrying both TK and neomycin-resistance genes. After selection in G418, more than 90% of the cells contained the TK gene as shown by a semiquantitative polymerase chain reaction. In addition, 1 to 5 days of GCV exposure, at clinically achievable concentrations of 20 to 50 mu mol/L, induced greater than or equal to 90% killing of G418-selected cells without affecting nontransduced cells. Correlation of the extent of T-cell kill and the proportion of TK-gene-transduced cells is consistent with the absence of a bystander effect. Transduced cells were CD3(+) and either CD8(+) or CD4(+) and retained functional properties of untransduced cells. In vivo administration of GCV prevented tumor development after subcutaneous injection of TK-transduced murine myeloma cells (MOPC-11), whereas such an effect was not observed on injection of untransduced cells into the opposite flank. Our studies provide critical information that (1) adequate numbers of TK-transduced lymphocytes can be selected efficiently with greater than or equal to 90% purity, (2) selected cells remain functional, (3) 24 hours of exposure to GCV at clinically achievable concentration effects greater than or equal to 90% killing of selected cells, and (4) GCV is effective in vivo in killing TK-transduced cells. Based on these data, a clinical study has been initiated in patients with multiple myeloma with persistent or relapsing disease after T-cell-depleted allogeneic transplants. (C) 1997 by The American Society of Hematology. C1 JOHN L MCCLELLAN MEM VET ADM MED CTR,LITTLE ROCK,AR 72205. GENET THERAPY INC,GAITHERSBURG,MD. FREDERICK CANC RES & DEV CTR,FREDERICK,MD. RP Munshi, NC (reprint author), UNIV ARKANSAS MED SCI HOSP,4301 W MARKHAM,SLOT 508,LITTLE ROCK,AR 72205, USA. FU NCI NIH HHS [CA71092, CA55819]; NHLBI NIH HHS [HL55695] NR 35 TC 72 Z9 76 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD FEB 15 PY 1997 VL 89 IS 4 BP 1334 EP 1340 PG 7 WC Hematology SC Hematology GA WG797 UT WOS:A1997WG79700024 PM 9028956 ER PT J AU Sneller, MC Wang, J Dale, JK Strober, W Middelton, LA Choi, YN Fleisher, TA Lim, MS Jaffe, ES Puck, JM Lenardo, MJ Straus, SE AF Sneller, MC Wang, J Dale, JK Strober, W Middelton, LA Choi, YN Fleisher, TA Lim, MS Jaffe, ES Puck, JM Lenardo, MJ Straus, SE TI Clinical, immunologic, and genetic features of an autoimmune lymphoproliferative syndrome associated with abnormal lymphocyte apoptosis SO BLOOD LA English DT Article ID HUMAN B-LYMPHOCYTES; MATURE T-CELLS; LPR/LPR MICE; DEATH DOMAIN; FAS; DISEASE; MUTATIONS; INTERACTS; PROTEASE; LIGAND AB Programmed cell death (apoptosis) of activated lymphocytes is critical to immune homeostasis. The cell surface protein Pas (CD95) and its ligand play a pivotal role in regulating lymphocyte apoptosis, and defective expression of either Pas or Pas ligand results in marked over accumulation of mature lymphocytes and autoimmune disease in mice. The results of recent studies suggest that defective lymphocyte apoptosis caused by mutations of the Pas gene can result in a severe autoimmune lymphoproliferative syndrome (ALPS) in humans. To define the clinical, genetic, and immunologic spectrum of ALPS, 9 patients and their families were extensively evaluated with routine clinical studies, lymphocyte phenotyping, genotyping, and in vitro assays for lymphocyte apoptosis. Individual patients were followed up for 3 months to 6 years. ALPS was identified in 9 unrelated children as manifested by moderate to massive splenomegaly and lymphadenopathy, hypergammaglobulinemia, autoimmunity, B-cell lymphocytosis, and the expansion of an unusual population of CD4(-)CD8(-) T cells that express the alpha/beta T-cell receptor (TCR). All patients showed defective lymphocyte apoptosis in vitro. Heterozygous mutations of the Fas gene were detected in 8 patients. One ALPS patient lacked a Pas gene mutation. Healthy relatives with Pas mutations were identified in 7 of 8 ALPS kindreds. These relatives also showed in vitro abnormalities of Pas-mediated lymphocyte apoptosis, but clinical features of ALPS were not present in the vast majority of these individuals. ALPS is a unique clinical syndrome in which in vitro abnormalities of lymphocyte apoptosis are associated with abnormal lymphoproliferation and autoimmunity. These findings provide evidence that apoptosis of activated lymphocytes is an important mechanism for maintaining immunologic homeostasis and self-tolerance in humans, Fas gene mutations account for impaired lymphocyte apoptosis in only a subset of patients with ALPS. (C) 1997 by The American Society of Hematology. C1 NIAID,CLIN INVEST LAB,NIH,BETHESDA,MD 20892. NIAID,IMMUNOL LAB,NIH,BETHESDA,MD 20892. NCI,LAB GENE TRANSFER,MED GENET BRANCH,NATL CTR HUMAN GENOME RES,NIH,BETHESDA,MD 20892. NCI,PATHOL LAB,CTR CLIN,NIH,BETHESDA,MD 20892. RP Sneller, MC (reprint author), NIAID,IMMUNOREGULAT LAB,NIH,BLDG 10,RM 11B-13,BETHESDA,MD 20892, USA. NR 28 TC 261 Z9 266 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD FEB 15 PY 1997 VL 89 IS 4 BP 1341 EP 1348 PG 8 WC Hematology SC Hematology GA WG797 UT WOS:A1997WG79700025 PM 9028957 ER PT J AU Sloand, EM Young, NS Kumar, P Weichold, FF Sato, T Maciejewski, JP AF Sloand, EM Young, NS Kumar, P Weichold, FF Sato, T Maciejewski, JP TI Role of Fas ligand and receptor in the mechanism of T-cell depletion in acquired immunodeficiency syndrome: Effect on CD4(+) lymphocyte depletion and human immunodeficiency virus replication SO BLOOD LA English DT Article ID TUMOR-NECROSIS-FACTOR; INTERFERON-GAMMA; HIV-INFECTION; FACTOR-ALPHA; APOPTOSIS; DEATH; ACTIVATION; ANTIGEN; EXPRESSION; DISEASE AB Direct killing of CD4(+) lymphocytes by human immunodeficiency virus-1 (HIV-1) probably cannot account for the magnitude of the loss of these cells during the course of HIV-1 infection. Experimental evidence supports a pathophysiologic role of the apoptotic process in depletion of CD4 cells in acquired immunodeficiency syndrome (AIDS). The Fas-receptor/Fas-ligand (Fas-R/Fas-L) system mediates signals for apoptosis of susceptible lymphocytes and lympoblastoid cell lines. A number of investigators have recently reported increased expression of the Fas receptor in individuals with HIV infection, along with increased sensitivity of their lymphocytes to anti-Fas antibody mimicking Fas ligand. We attempted to determine the role of Fas-mediated apoptosis in disease progression and viral replication. Increased Fas-receptor (CD95) expression on CD4(+) and CD8(+) lymphocytes was found in a large group of HIV-1-infected patients compared with normal controls; individuals with a diagnosis of AIDS and a history of opportunistic infection had significantly more Fas receptor expression than did asymptomatic HIV-infected persons and normal blood donor controls (P < .01). Triggering of the Fas-R by agonistic anti-Fas monoclonal antibody, CH11, was preferentially associated with apoptosis in the CD4(+) cells; this effect was more pronounced in lymphocytes derived from HIV+ individuals, Soluble and membrane-bound forms of Fas-L were produced in greater amounts in peripheral blood mononuclear cells (PBMC) cultures and in plasma obtained from HIV-1-infected persons than from normal controls, Furthermore, triggering of lymphocytes from HIV-infected persons by CH11 increased levels of interleukin-1 beta converting enzyme (ICE), a protein associated with apoptosis. When PBMC were cultured in the presence of CH11, p24 production per number of viable cells was decreased as compared with the same PBMC without CH11 (P <.01). These findings suggest that multiple mechanisms, including increased production of Fas-L by infected PBMC, increased Fas-R expression, and induction of a protease of ICE family, may play roles in the apoptotic depletion of CD4(+) cells in HIV infection. (C) 1997 by The American Society of Hematology. C1 NHLBI,BETHESDA,MD 20892. GEORGETOWN UNIV,MED CTR,WASHINGTON,DC 20007. NR 36 TC 129 Z9 130 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD FEB 15 PY 1997 VL 89 IS 4 BP 1357 EP 1363 PG 7 WC Hematology SC Hematology GA WG797 UT WOS:A1997WG79700027 PM 9028959 ER PT J AU Burke, HB Goodman, PH Rosen, DB Henson, DE Weinstein, JN Harrell, FE Marks, JR Winchester, DP Bostwick, DG AF Burke, HB Goodman, PH Rosen, DB Henson, DE Weinstein, JN Harrell, FE Marks, JR Winchester, DP Bostwick, DG TI Artificial neural networks improve the accuracy of cancer survival prediction SO CANCER LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Joint-Committee-on-Cancer CY JAN 14, 1995 CL SCOTTSDALE, AZ SP Amer Joint Comm Canc DE TNM staging system; artificial neural networks; prognostic factors; breast carcinoma; colorectal carcinoma; survival; outcomes; decision-making; clinical trials; quality assurance ID DIAGNOSIS; SYSTEM; AREA AB BACKGROUND. The TNM staging system originated as a response to the need for an accurate, consistent, universal cancer outcome prediction system. Since the TNM staging system was introduced in the 1950s, new prognostic factors have been identified and new methods for integrating prognostic factors have been developed. This study compares the prediction accuracy of the TNM staging system with that of artificial neural network statistical models. METHODS. For 5-year survival of patients with breast or colorectal carcinoma, the authors compared the TNM staging system's predictive accuracy with that of artificial neural networks (ANN). The area under the receiver operating characteristic curve, as applied to an independent validation data set, was the measure of accuracy. RESULTS. For the American College of Surgeons' Patient Care Evaluation (PCE) data set, using only the TNM variables (tumor size, number of positive regional lymph nodes, and distant metastasis), the artificial neural network's predictions of the 5-year survival of patients with breast carcinoma were significantly more accurate than those of the TNM staging system (TNM, 0.720; ANN, 0.770; P < 0.001). For the National Cancer Institute's Surveillance, Epidemiology, and End Results breast carcinoma data set, using only the TNM variables, the artificial neural network's predictions of 10-year survival were significantly more accurate than those of the TNM staging system (TNM, 0.692; ANN, 0.730; P < 0.01). For the PCE colorectal data set, using only the TNM variables, the artificial neural network's predictions of the 5-year survival of patients with colorectal carcinoma were significantly more accurate than those of the TNM staging system (TNM, 0.737; ANN, 0.815; Pt 0.001). Adding commonly collected demographic and anatomic variables to the TNM variables further increased the accuracy of the artificial neural network's predictions of breast carcinoma survival (0.784) and colorectal carcinoma survival (0.869). CONCLUSIONS. Artificial neural networks are significantly more accurate than the TNM staging system when both use the TNM prognostic factors alone. New prognostic factors can be added to artificial neural networks to increase prognostic accuracy further. These results are robust across different data sets and cancer sites. (C) 1997 American Cancer Society. C1 UNIV NEVADA,SCH MED,DEPT MED,RENO,NV 89557. NCI,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20892. NCI,DIV CANC TREATMENT,BETHESDA,MD 20892. UNIV VIRGINIA,SCH MED,DEPT HLTH EVALUAT SCI,CHARLOTTESVILLE,VA 22908. DUKE UNIV,MED CTR,DEPT SURG,DURHAM,NC 27710. AMER COLL SURG,COMMISS CANC,CHICAGO,IL. EVANSTON HOSP CORP,DEPT SURG,EVANSTON,IL. MAYO CLIN & MAYO FDN,DEPT PATHOL,ROCHESTER,MN 55905. RP Burke, HB (reprint author), NEW YORK MED COLL,DEPT MED,BIOINFORMAT & HLTH SERV RES,VALHALLA,NY 10595, USA. FU AHRQ HHS [HS 06830]; NCI NIH HHS [CA 11606-17] NR 20 TC 161 Z9 165 U1 1 U2 12 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD FEB 15 PY 1997 VL 79 IS 4 BP 857 EP 862 DI 10.1002/(SICI)1097-0142(19970215)79:4<857::AID-CNCR24>3.0.CO;2-Y PG 6 WC Oncology SC Oncology GA WG451 UT WOS:A1997WG45100024 PM 9024725 ER PT J AU Rhim, JS Jin, SJ Jung, M Thraves, PJ Kuettel, MR Webber, MM Hukku, B AF Rhim, JS Jin, SJ Jung, M Thraves, PJ Kuettel, MR Webber, MM Hukku, B TI Malignant transformation of human prostate epithelial cells by N-nitroso-N-methylurea SO CANCER RESEARCH LA English DT Article ID CANCER; CARCINOMA; DNA AB We report the malignant transformation of adult human prostate epithelial cells after multiple exposures to the chemical carcinogen N-nitroso-N-methylurea. Such transformants showed morphological alterations and anchorage-independent growth in soft agar and induced carcinomas when transplanted into nude mice, No p53 or ms mutations were observed, Stepwise chromosomal changes in the progression to tumorigenicity were observed. Loss of the p arms of chromosome 8 (p10>pter) and chromosome 10 (p10>pter) and gain of the q arm of chromosome 8 (q10>qter) were only observed in the tumor outgrows, These findings provide the first evidence of malignant transformation of human prostate epithelial cells exposed to a chemical carcinogen. C1 GEORGETOWN UNIV,SCH MED,DEPT RADIAT MED,VINCENT T LOMBARDI CANC CTR,WASHINGTON,DC. MICHIGAN STATE UNIV,DEPT MED,E LANSING,MI 48824. MICHIGAN STATE UNIV,DEPT ZOOL,E LANSING,MI 48824. CHILDRENS HOSP MICHIGAN,CELL CULTURE LAB,DETROIT,MI 48201. RP Rhim, JS (reprint author), NCI,LAB BIOCHEM PHYSIOL,BLDG 567,FREDERICK,MD 21702, USA. NR 25 TC 30 Z9 30 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD FEB 15 PY 1997 VL 57 IS 4 BP 576 EP 580 PG 5 WC Oncology SC Oncology GA WH815 UT WOS:A1997WH81500006 PM 9044828 ER PT J AU Tozser, J Yin, FH Cheng, YSE Bagossi, P Weber, IT Harrison, RW Oroszlan, S AF Tozser, J Yin, FH Cheng, YSE Bagossi, P Weber, IT Harrison, RW Oroszlan, S TI Activity of tethered human immunodeficiency virus 1 protease containing mutations in the flap region of one subunit SO EUROPEAN JOURNAL OF BIOCHEMISTRY LA English DT Article DE human immunodeficiency virus protease; flap mutants; oligopeptide substrate; substrate specificity; enzyme kinetics ID HIV-1 PROTEASE; MOLECULAR-DYNAMICS; CHEMICAL SYNTHESIS; PROTEINASE; SUBSTRATE; INHIBITORS; DIMER; CHAIN; INFECTIVITY; PRECURSOR AB The tethered-dimer protease of human immunodeficiency virus 1 (HIV-1) [Cheng Y.-S. E., Yin, F. H., Foundling, S., Blomstrom, D. & Kettner, C. A. (1990) Proc. Natl Acad. Sci. USA 87, 9660-9664] and its mutants containing amino acid substitutions or deletions or both in only one flap region were expressed in Escherichia coli. These mutant enzymes showed various degrees of self-processing and significantly reduced catalytic activity toward oligopeptide substrates compared with the wild type. Kinetic parameters determined for one of the oligopeptide substrates showed a dramatic increase in K-m and decrease in k(cat) values. Unexpectedly, the substrate cleavage was more efficient in low salt concentration for a mutant containing a shortened hydrophilic flap. Assays with oligopeptides representing naturally occurring cleavage sites or oligopeptides containing single amino acid substitutions at the P-2 and P-2' substrate positions showed only moderate changes in the substrate specificity of the mutant proteases. Predicted structures for the mutants were constructed by molecular modeling and used to interpret the results of kinetic measurements. In general, the data suggest that the mutated part of the flaps does not have a major role in determining substrate specificity; rather, it provides the hydrophobic environment and hydrogen-bond interactions with the conserved water that are necessary for efficient substrate binding and catalysis. C1 DUPONT MERCK PHARMACEUT CO,EXPT STN,WILMINGTON,DE 19880. THOMAS JEFFERSON UNIV,JEFFERSON CANC INST,DEPT PHARMACOL,PHILADELPHIA,PA 19107. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MOL VIROL & CARCINOGENESIS LAB,FREDERICK,MD 21701. RP Tozser, J (reprint author), DEBRECEN UNIV MED,SCH MED,DEPT BIOCHEM,POB 6,H-4012 DEBRECEN,HUNGARY. RI Tozser, Jozsef/A-7840-2008; OI Tozser, Jozsef/0000-0003-0274-0056; Tozser, Jozsef/0000-0001-5076-8729 FU NCI NIH HHS [CA58166] NR 41 TC 16 Z9 16 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0014-2956 J9 EUR J BIOCHEM JI Eur. J. Biochem. PD FEB 15 PY 1997 VL 244 IS 1 BP 235 EP 241 DI 10.1111/j.1432-1033.1997.00235.x PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WJ176 UT WOS:A1997WJ17600031 PM 9063469 ER PT J AU Juan, TSC McNiece, IK Argento, JM Jenkins, NA Gilbert, DJ Copeland, NG Fletcher, FA AF Juan, TSC McNiece, IK Argento, JM Jenkins, NA Gilbert, DJ Copeland, NG Fletcher, FA TI Identification and mapping of Casp7, a cysteine protease resembling CPP32 beta, interleukin-1 beta converting enzyme, and CED-3 SO GENOMICS LA English DT Article ID PROGRAMMED CELL-DEATH; C-ELEGANS; IL-1-BETA-CONVERTING ENZYME; CAENORHABDITIS-ELEGANS; GENE CED-3; POLY(ADP-RIBOSE) POLYMERASE; MOLECULAR-CLONING; MAMMALIAN HOMOLOG; MICE DEFICIENT; APOPTOSIS AB Cloning of interleukin-1 beta converting enzyme (ICE) and Caenorhabditis elegans death protein CED-3 revealed the structural and functional homology between these two proteases. It also suggested the involvement of ICE-like cysteine protease in apoptosis. Several CED-3- and ICE-like cysteine proteases have been described, including Nedd2/Ich-1, CPP32 beta, Tx, ICE(rel)3, and Mch2. We have previously described a mouse ortholog of cysteine protease CPP32 beta that shares strong homology with ICE and CED-3. Here, we describe the cloning of mouse and human Casp7, another member of this family of cysteine proteases. Mouse Casp7 encodes a putative 340-amino-acid polypeptide that contains all the known conserved residues required for protease function, including the QACRG sequence, aspartic acid residues for internal cleavage sites, and the residues required for substrate binding. Three RNA variants of human Casp7 were also cloned. Amino acid sequence analysis indicated that Casp7 shared high homology with CPP32 beta/Casp3 and Mch2/Casp6. Northern blot analysis demonstrated that a 2.6-kb Casp7 mRNA was expressed in various tissues except brain. Mouse interspecific backcross mapping allowed localization of Casp7 to the distal region of mouse chromosome 19, linked to Mxi1, Adra2a, and Aop1., (C) 1997 Academic Press. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. RP Juan, TSC (reprint author), AMGEN INC,DEPT DEV HEMATOL,1840 DEHAVILLAND DR,THOUSAND OAKS,CA 91320, USA. NR 41 TC 34 Z9 37 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD FEB 15 PY 1997 VL 40 IS 1 BP 86 EP 93 DI 10.1006/geno.1996.4548 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA WJ336 UT WOS:A1997WJ33600011 PM 9070923 ER PT J AU SimonsEvelyn, M Young, HA Anderson, SK AF SimonsEvelyn, M Young, HA Anderson, SK TI Characterization of the mouse Nktr gene and promoter SO GENOMICS LA English DT Article ID SR PROTEINS; CELL-LINE; CYCLOPHILIN; SEQUENCE; RECEPTOR AB We have cloned and determined the structure of the 5' region of the mouse Nktr gene located on the distal end of mouse chromosome 9. This gene encodes an NK-cell-specific 150-kDa protein (NK-TR) homologous to cyclophilin, Nopp140, and SR-containing proteins. NK-TR expression is important for maintaining the lyric activity of natural killer cells. The region of the Nktr gene cloned in this study spans 25 kb and contains the promoter, eight exons, and a single alternative exon. The boundaries of exons 6-8 and the alternate splicing events in this region are identical to those previously described for the human NKTR gene. The Nktr promoter region has features that are typical of a housekeeping gene, including high G + C content, high frequency of CpG dinucleotides, and a lack of canonical TATAA and CCAAT boxes. The activity of Nktr promoter/beta-gal reporter constructs was equivalent in lymphocyte and fibroblast cell lines, suggesting that NKTR protein expression is regulated by posttranscriptional mechanisms. In support of this hypothesis, two levels of splicing control have been identified within the Nktr gene. A 10-kb intron was found to remain in mRNAs produced in bone marrow, and an alternative exon capable of interrupting the Nktr open reading frame was found in immature NK cells. A conserved intronic sequence has been identified that may be important for the regulation of the Nktr gene by pre-mRNA splicing. (C) 1997 Academic Press. C1 NCI,FREDERICK CANC RES & DEV CTR,EXPT IMMUNOL LAB,DBS,FREDERICK,MD 21702. SAIC FREDERICK,INTRAMURAL RES SUPPORT PROGRAM,FREDERICK,MD 21702. RI Anderson, Stephen/B-1727-2012 OI Anderson, Stephen/0000-0002-7856-4266 NR 18 TC 2 Z9 3 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD FEB 15 PY 1997 VL 40 IS 1 BP 94 EP 100 DI 10.1006/geno.1996.4562 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA WJ336 UT WOS:A1997WJ33600012 PM 9070924 ER PT J AU Liao, F Lee, HH Farber, JM AF Liao, F Lee, HH Farber, JM TI Cloning of STRL22, a new human gene encoding a G-protein-coupled receptor related to chemokine receptors and located on chromosome 6q27 SO GENOMICS LA English DT Article ID ORGANIZATION; MIP-1-ALPHA; SEQUENCE; RANTES AB Using PCR with pools of primers based on conserved sequences in chemokine receptors, we have cloned a human member of the G-protein-coupled receptor gene family. The new gene, which we have named STRL22, is predicted to encode a receptor related to chemokine receptors, including IL8RA (CXCR1), IL8RB (CXCR2), and CXCR4/fusin, and to the orphan receptors EBI1 and BLR1. Consistent with a role in leukocyte biology, STRL22 is expressed in lymphocytes and in lymphoid tissue. We have mapped STRL22 to chromosome 6q27. STRL22 cDNAs reflect alternative (or incomplete) mRNA processing in the 5'-nontranslated region, a phenomenon found in analysis of other chemoattractant receptor genes. In contrast to most chemokine receptor genes, the STRL22 coding sequence is not limited to a Single exon. (C) 1997 Academic Press. C1 NIAID,CLIN INVEST LAB,NIH,BETHESDA,MD 20892. NR 17 TC 46 Z9 48 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD FEB 15 PY 1997 VL 40 IS 1 BP 175 EP 180 DI 10.1006/geno.1996.4544 PG 6 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA WJ336 UT WOS:A1997WJ33600025 PM 9070937 ER PT J AU DiLeone, RJ King, JA Storm, EE Copeland, NG Jenkins, NA Kingsley, DM AF DiLeone, RJ King, JA Storm, EE Copeland, NG Jenkins, NA Kingsley, DM TI The Bmp8 gene is expressed in developing skeletal tissue and maps near the Achondroplasia locus on mouse chromosome 4 SO GENOMICS LA English DT Article ID BETA SUPERFAMILY; PROTEINS; MEMBERS C1 STANFORD UNIV,SCH MED,BECKMAN CTR B300,DEPT DEV BIOL,PALO ALTO,CA 94304. NCI,MAMMALIAN GENET LAB,ABL,BASIC RES PROGRAM,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. OI DiLeone, Ralph/0000-0002-4770-2590 NR 15 TC 16 Z9 18 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD FEB 15 PY 1997 VL 40 IS 1 BP 196 EP 198 DI 10.1006/geno.1996.4533 PG 3 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA WJ336 UT WOS:A1997WJ33600032 PM 9070944 ER PT J AU Zwanzig, R AF Zwanzig, R TI Effect of close contacts on the radius of gyration of a polymer SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article AB The mean squared radius of gyration S-2 of a Short Rouse model polymer composed of N (less than or equal to 50) monomers is determined as a function of the number M (less than or equal to 25) of imposed contacts. The contacts are modelled by extra harmonic potentials between the specified monomers. A Green's function method is used to follow the effects of sequential addition of contacts. Averaging over random sequences of contacts leads to the estimate [S-2](M)=[S-2](0)/(1+0.43M). (C) 1997 American Institute of Physics. RP Zwanzig, R (reprint author), NIDDK,CHEM PHYS LAB,NIH,BLDG 5,ROOM 116,BETHESDA,MD 20892, USA. NR 4 TC 1 Z9 1 U1 0 U2 5 PU AMER INST PHYSICS PI WOODBURY PA CIRCULATION FULFILLMENT DIV, 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2999 SN 0021-9606 J9 J CHEM PHYS JI J. Chem. Phys. PD FEB 15 PY 1997 VL 106 IS 7 BP 2824 EP 2827 DI 10.1063/1.473379 PG 4 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA WH024 UT WOS:A1997WH02400032 ER PT J AU Salbe, AD Nicolson, M Ravussin, E AF Salbe, AD Nicolson, M Ravussin, E TI Total energy expenditure and the level of physical activity correlate with plasma leptin concentrations in five-year-old children SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE obesity; preschool-aged children; doubly labeled water; Pima Indian; energy metabolism ID DOUBLY LABELED WATER; OBESE GENE-PRODUCT; PROTEIN AB Leptin, the product of the ob gene, is a hormone secreted by adipocytes that is known to decrease food intake and increase energy expenditure in ob/ob mice. In humans, variants in the OB gene have not been detected and very little is known about the action of leptin on food intake and energy expenditure, although circulating leptin concentrations are positively correlated to body fat stores. The purpose of this study was to assess the relationship between fasting plasma leptin concentrations and energy expenditure in 123 5-yr-old Pima Indian children (67 males/76 females). Body composition was assessed by isotopic water dilution (O-18) whereas total energy expenditure (TEE) and resting metabolic rate (RMR) were measured using doubly labeled water and indirect calorimetry, respectively, The physical activity level was calculated as the ratio of TEE:RMR. Plasma leptin concentrations were positively correlated to percent body fat (r = 0.84, P < 0.0001), but were similar in boys and girls after adjusting for percent body fat. Most importantly, we found that, independent of the percentage of body fat, plasma leptin concentrations correlated with TEE (in absolute values, r = 0.37, P < 0.0001, or adjusted for body size r = 0.42; P < 0.0001) and with physical activity level (r = 0.26, P < 0.01), but not RMR. These results suggest that, as in animal models, leptin plays a role in energy expenditure in humans. C1 AMGEN INC,THOUSAND OAKS,CA 91320. RP Salbe, AD (reprint author), NIDDKD,CLIN DIABET & NUTR SECT,4212 N 16TH ST,RM 541,PHOENIX,AZ 85016, USA. NR 25 TC 108 Z9 109 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD FEB 15 PY 1997 VL 99 IS 4 BP 592 EP 595 DI 10.1172/JCI119200 PG 4 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA WK408 UT WOS:A1997WK40800009 PM 9045859 ER PT J AU Deng, YP Yewdell, JW Eisenlohr, LC Bennink, JR AF Deng, YP Yewdell, JW Eisenlohr, LC Bennink, JR TI MHC affinity, peptide liberation, T cell repertoire, and immunodominance all contribute to the paucity of MHC class I-restricted peptides recognized by antiviral CTL SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TOXIC LYMPHOCYTES-T; ENDOGENOUSLY SYNTHESIZED PEPTIDE; ENDOPLASMIC-RETICULUM; ANTIGENIC PEPTIDES; ANCHOR RESIDUES; MOLECULES; BINDING; PROTEASOME; SELECTION; PROTEINS AB MHC class I-restricted T cell responses to viral proteins focus on a limited set of peptides. To better understand this phenomenon, we examined all of the 26 nonameric peptides encoded by the influenza virus A/Puerto Rico/8/34 (PR8) conforming to the canonical K-d binding motif. Ten peptides bound strongly to K-d as assessed by a cell surface stabilization assay, Five of these 10 induced in vitro secondary CD8(+) T cell responses from splenocytes derived from PR8-immunized mice. The strongest responses were induced by the two previously defined antigenic peptides, which ranked only second and fifth in relative binding affinity. To examine the limiting factors in the immunogenicity of K-d-binding peptides, we produced recombinant vaccinia viruses (rVVs) expressing cytosolic or endoplasmic reticulum (ER)-targeted peptides, rVVs expressing ER-targeted versions of the 7 peptides with the highest relative affinities for K-d rescued K-d cell surface expression in T2 cells, while those expressing the 3 lowest affinity peptides did not. The immunogenicity of several, but not all, of the highest affinity peptides was greatly enhanced when expressed as VV-encoded cytosolic or ER-targeted peptides as compared with full length proteins. We conclude that limitations in the immunogenicity of class I binding peptides reflects, in order of decreasing importance, peptide liberation by cellular proteases, T cell repertoire, and TAP-mediated peptide transport. We also observed an additional important contributing factor: suppression of T cell responses to nondominant peptides by an immunodominant peptide located in the same protein. C1 NIAID,VIRAL DIS LAB,NIH,BETHESDA,MD 20892. RI yewdell, jyewdell@nih.gov/A-1702-2012 NR 46 TC 174 Z9 175 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD FEB 15 PY 1997 VL 158 IS 4 BP 1507 EP 1515 PG 9 WC Immunology SC Immunology GA WG304 UT WOS:A1997WG30400002 PM 9029084 ER PT J AU Tsai, V Southwood, S Sidney, J Sakaguchi, K Kawakami, Y Appella, E Sette, A Celis, E AF Tsai, V Southwood, S Sidney, J Sakaguchi, K Kawakami, Y Appella, E Sette, A Celis, E TI Identification of subdominant CTL epitopes of the GP100 melanoma-associated tumor antigen by primary in vitro immunization with peptide-pulsed dendritic cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; CYTOTOXIC T-LYMPHOCYTES; IN-VITRO; INFILTRATING LYMPHOCYTES; SYNTHETIC PEPTIDE; ANCHOR RESIDUES; INDUCTION; BINDING; RESPONSES; MOTIFS AB The gp100 melanoma-associated tumor Ag was selected as a model system to study the diversity of human antitumor cytotoxic T cell responses. First, peptides corresponding to dominant gp100 HLA-A2.1-restricted CTL epitopes were tested using lymphocytes from normal volunteers and an in vitro priming protocol that uses peptide-pulsed dendritic cells as APCs and IL-7 and IL-10 as immune-enhancing cytokines. High CTL activity toward both peptide-pulsed target cells and gp100(+) melanoma cells was obtained with four out of five peptides tested. Second, HLA-A2.1-binding peptides from gp100 that do not appear to represent CTL epitopes in melanoma patients were also tested for their capacity to induce CTL using the in vitro priming protocol, Three of six peptides tested induced CTL in lymphocytes from normal volunteers. One of these peptides was also immunogenic for lymphocytes derived from a melanoma patient in remission, Because these three CTL epitopes were not recognized in the natural immune response in melanoma patients but do appear as immunogens when peptides are used to induce the T cell response, they may be considered as typical ''subdominant'' epitopes. The results are discussed in the context of the usefulness of this approach to detail the immunologic potential of a given tumor-associated Ag and its relevance for the design of effective immune-based therapies. C1 CYTEL CORP,SAN DIEGO,CA 92121. NCI,SURG BRANCH,NIH,BETHESDA,MD 20205. NCI,CELL BIOL LAB,NIH,BETHESDA,MD 20205. RI Kawakami, Yutaka /E-7429-2013 OI Kawakami, Yutaka /0000-0003-4836-2855 NR 49 TC 158 Z9 160 U1 0 U2 4 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD FEB 15 PY 1997 VL 158 IS 4 BP 1796 EP 1802 PG 7 WC Immunology SC Immunology GA WG304 UT WOS:A1997WG30400036 PM 9029118 ER PT J AU Dastych, J Hardison, MC Metcalfe, DD AF Dastych, J Hardison, MC Metcalfe, DD TI Aggregation of low affinity IgG receptors induces mast cell adherence to fibronectin - Requirement for the common FcR gamma-chain SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; EPSILON-RI; MEDIATOR RELEASE; EXPRESSION; SUBUNIT; LAMININ; PERITONITIS; ADHESION; NUMBERS; MIGRATE AB Mast cells have been reported to increase at sites of immune complex-induced inflammation where these cells appear to potentiate the inflammatory response. The mechanism by which mast cells accumulate at these sites is unknown. One possibility is that aggregation of low affinity IgG receptors could signal mast cells to adhere to components of the connective tissue matrix. To test this hypothesis, we first added aggregated IgG to a mast cell-adhesion assay employing fibronectin as a matrix component and observed an increase in cell adhesion. Even a small amount of aggregated IgG (<60 ng/ml) demonstrated by fast protein liquid chromatography in untreated IgG preparations was sufficient to increase mast cell adhesion by 100%. We next explored the Fc gamma receptors involved. Fc gamma RII/III, which are receptors for oligomeric IgG and were first verified as present on these mast cells by FAGS analysis and immunoprecipitation, signaled mast cells to rapidly adhere to fibronectin when aggregated with the anti-receptor Ab2.4G2. The adhesion process mediated by Fc gamma RII/III was not associated with beta-hexosaminidase release. Bone marrow-cultured mast cells from common gamma-chain deficient mice, unlike mast cells cultured from +/+ mice, did not respond to Fc gamma RII/III aggregation. This demonstrated requirement for a gamma-chain implicates oligomeric Fc gamma RIII in the adhesion process. Thus, aggregation of Fc gamma RIII on mast cells leads to mast cell adhesion, demonstrating a previously unknown biological function for this receptor on mast cells and providing a mechanism for mast cell accumulation in immune complex-dependent inflammation. C1 NIAID,LAB ALLERG DIS,NIH,BETHESDA,MD 20892. NR 31 TC 23 Z9 23 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD FEB 15 PY 1997 VL 158 IS 4 BP 1803 EP 1809 PG 7 WC Immunology SC Immunology GA WG304 UT WOS:A1997WG30400037 PM 9029119 ER PT J AU Samaniego, F Markham, PD Gendelman, R Gallo, RC Ensoli, B AF Samaniego, F Markham, PD Gendelman, R Gallo, RC Ensoli, B TI Inflammatory cytokines induce endothelial cells to produce and release basic fibroblast growth factor and to promote Kaposi's sarcoma-like lesions in nude mice SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; TUMOR NECROSIS FACTOR; VON-WILLEBRAND-FACTOR; VONWILLEBRAND-FACTOR; GENE-EXPRESSION; HIV-INFECTION; ADHESION MOLECULE-1; HOMOSEXUAL MEN; SPINDLE CELLS; FACTOR-ALPHA AB Inflammatory cytokines including TNF-alpha, IL-1 beta, and IFN-gamma are increased in sera and lesions of Kaposi's sarcoma (KS) patients. Previous data have indicated that the combination of these cytokines as found in conditioned media from activated T cells induces normal endothelial cells to acquire the features of KS spindle cells (KS cells) including spindle morphology, marker expression, and the responsiveness to the effects of HIV-1 Tat protein. Conditioned media from activated T cells or the single cytokines also induce AIDS-KS cells to produce and release basic fibroblast growth factor (bFCF). bFCF is highly expressed also by in situ KS cells and mediates KS-like lesion formation after inoculation of the cells in nude mice. Here we show that both large and small vessel endothelial cells chronically exposed to inflammatory cytokines produce and release bioactive bFGF in the absence of cell death. In addition, after this treatment, endothelial cells acquire angiogenic capability and induce KS-like lesions after inoculation in nude mice. Production and release of bFCF is induced in a synergistic fashion by TNF-alpha, IL-1 beta, and IFN-gamma, and its release is further promoted by low cell density and by the serine proteases plasmin and thrombin. These results indicate that inflammatory cytokines induce endothelial cells to export bFGF and to acquire angiogenic properties, a key feature of the KS cell phenotype, and suggest a mechanism by which these cytokines can cooperate in the induction of KS. C1 NATL INST HLTH,VIROL LAB,I-00161 ROME,ITALY. UNIV MARYLAND,UNIV MARYLAND BIOTECHNOL INST,INST HUMAN VIROL,BALTIMORE,MD 21201. NCI,TUMOR CELL BIOL LAB,NIH,BETHESDA,MD 20892. ADV BIOSCI LABS INC,KENSINGTON,MD 20895. RI Ensoli, Barbara/J-9169-2016 OI Ensoli, Barbara/0000-0002-0545-8737 NR 45 TC 89 Z9 89 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD FEB 15 PY 1997 VL 158 IS 4 BP 1887 EP 1894 PG 8 WC Immunology SC Immunology GA WG304 UT WOS:A1997WG30400048 PM 9029130 ER PT J AU Fuss, IJ Strober, W Dale, JK Fritz, S Pearlstein, GR Puck, JM Lenardo, MJ Straus, SE AF Fuss, IJ Strober, W Dale, JK Fritz, S Pearlstein, GR Puck, JM Lenardo, MJ Straus, SE TI Characteristic T helper 2 T cell cytokine abnormalities in autoimmune lymphoproliferative syndrome, a syndrome marked by defective apoptosis and humoral autoimmunity SO JOURNAL OF IMMUNOLOGY LA English DT Article ID SYSTEMIC LUPUS-ERYTHEMATOSUS; B-LYMPHOCYTE HYPERACTIVITY; FAS-LIGAND; RHEUMATOID-ARTHRITIS; LPR/LPR MICE; INTERLEUKIN-10; ACTIVATION; ANTIBODY; DEATH; GENE AB Autoimmune lymphoproliferative syndrome (ALPS) is marked by massive lymphadenopathy, hepatosplenomegaly, autoimmunity and the presence of increased numbers of circulating and tissue TCR-alpha beta, CD4(-)CD8(-) T cells. The underlying defect is that of decreased T cell and B cell apoptosis, due in most, but not all, cases to heterozygous mutations of the Fas gene and corresponding defective Fas signaling function. Here we measure in vivo and in vitro cytokine secretion in ALPS to shed light on the relation of apoptosis defects to the development of autoimmunity. In in vivo studies, ALPS patients manifested greatly increased circulating levels of IL-10 (>100-fold), compared with both healthy individuals and various disease controls; in contrast, their levels of IL-1 beta, IL-4, and IFN-gamma were normal and their levels of IL-2 and TNF-alpha were marginally increased. in parallel in vitro studies, ALPS patients CD4(+)DR(+) T cells stimulated either with anti-CD3/CD28 or anti-CD2/CD28 produced increased amounts of IL-4 and IL-5 (10 to 20-fold) and decreased amounts of IFN-gamma, (4-fold) as compared with those of control CD4(+)DR(+) T cells. In contrast, ALPS patients' CD4(-)/CD8(-) T cells produced very low amounts of cytokines. Finally, ALPS patients' peripheral monocytes/macrophages produced decreased amounts of IL-12 (30-fold) and increased amounts of IL-10 (5-fold). In conclusion, ALPS is marked by the presence of DR(+) T cells that exhibit a skewed Th2 cytokine response upon various forms of stimulation. This cytokine response, in the presence of increased circulating IL-10 levels, is likely to define the cytokine milieu that accounts for the humoral autoimmune features of ALPS and, perhaps, of other humoral autoimmune states. C1 NIAID,MUCOSAL IMMUN SECT,CLIN INVEST LAB,NIH,BETHESDA,MD 20892. NIAID,MED VIROL SECT,CLIN INVEST LAB,NIH,BETHESDA,MD 20892. NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. SCI APPLICAT INT CORP,FREDERICK,MD 21702. NR 33 TC 85 Z9 86 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD FEB 15 PY 1997 VL 158 IS 4 BP 1912 EP 1918 PG 7 WC Immunology SC Immunology GA WG304 UT WOS:A1997WG30400051 PM 9029133 ER PT J AU Pende, M Fisher, TL Simpson, PB Russell, JT Blenis, J Gallo, V AF Pende, M Fisher, TL Simpson, PB Russell, JT Blenis, J Gallo, V TI Neurotransmitter- and growth factor-induced cAMP response element binding protein phosphorylation in glial cell progenitors: Role of calcium ions, protein kinase C, and mitogen-activated protein kinase/ribosomal S6 kinase pathway SO JOURNAL OF NEUROSCIENCE LA English DT Article DE non-NMDA receptors; muscarinic receptors; basic fibroblast growth factor; ribosomal S6 kinase; transcription factor; oligodendrocytes ID RAT OPTIC-NERVE; GENE-EXPRESSION; OLIGODENDROCYTE PROGENITORS; MEMBRANE DEPOLARIZATION; INTRACELLULAR CALCIUM; FOS TRANSCRIPTION; FACTOR CREB; MAP KINASE; RECEPTORS; ASTROCYTES AB To understand how extracellular signals may produce long-term effects in neural cells, we have analyzed the mechanism by which neurotransmitters and growth factors induce phosphorylation of the transcription factor cAMP response element binding protein (CREB) in cortical oligodendrocyte progenitor (OP) cells. Activation of glutamate receptor channels by kainate, as well as stimulation of G-protein-coupled cholinergic receptors by carbachol and tyrosine kinase receptors by basic fibroblast growth factor (bFGF), rapidly leads to mitogen activated protein kinase (MAPK) phosphorylation and ribosomal S6 kinase (RSK) activation. Kainate and carbachol activation of the MAPK pathway requires extracellular calcium influx and is accompanied by protein kinase C (PKC) induction, with no significant increase in GTP binding to Ras. Conversely, growth factor-stimulated MAPK phosphorylation is independent of extracellular calcium and is accompanied by Ras activation. Both basal and stimulated MAPK activity in OP cells are influenced by cytoplasmic calcium levels, as shown by their sensitivity to the calcium chelator bis(2-aminophenoxy)ethane-N, N,N',N'-tetra-acetic acid. The kinetics of CREB phosphorylation in response to the various agonists corresponds to that of MAPK activation. Moreover, CREB phosphorylation and MAPK activation are similarly affected by calcium ions. The MEK inhibitor PD 098059, which selectively prevents activation of the MAPK pathway, strongly reduces induction of CREB phosphorylation by kainate, carbachol, bFGF, and the phorbol ester TPA. We propose that in OPs the MAPK/RSK pathway mediates CREB phosphorylation in response to calcium influx, PKC activation, and growth factor stimulation. C1 NICHHD,LAB CELLULAR & MOL NEUROPHYSIOL,NIH,BETHESDA,MD 20892. HARVARD UNIV,SCH MED,DEPT CELL BIOL,BOSTON,MA 02115. NR 68 TC 167 Z9 167 U1 0 U2 1 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD FEB 15 PY 1997 VL 17 IS 4 BP 1291 EP 1301 PG 11 WC Neurosciences SC Neurosciences & Neurology GA WF083 UT WOS:A1997WF08300009 PM 9006973 ER PT J AU Shinkai, T Zhang, L Mathias, SA Roth, GS AF Shinkai, T Zhang, L Mathias, SA Roth, GS TI Dopamine induces apoptosis in cultured rat striatal neurons; Possible mechanism of D-2-dopamine receptor neuron loss during aging SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE dopamine; D-2-dopamine receptor; neurons; apoptosis; striatal cell culture ID PROGRAMMED CELL-DEATH; MESSENGER-RNA; OXIDATIVE STRESS; IN-SITU; 6-HYDROXYDOPAMINE; TOXICITY; BRAIN AB We examined D-2-dopamine receptor containing neurons in cultures of neonatal rat striatum for apoptosis following dopamine treatment. Exposure to cultures to micromolar concentrations of dopamine resulted in 60-70% killing of D-2-dopamine receptor neurons within 24 hr. We also utilized a double labeling procedure to determine that treatment with dopamine induced apoptosis in D-2-dopamine receptor containing neurons. These results suggest that loss of D-2-dopamine receptor containing neurons during aging could be due to an apoptotic effect of dopamine. (C) 1997 Wiley-Liss, Inc.(dagger) C1 NIA,GERONTOL RES CTR,CELLULAR & MOL BIOL LAB,MOL PHYSIOL & GENET SECT,NIH,BALTIMORE,MD 21224. NR 21 TC 49 Z9 50 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD FEB 15 PY 1997 VL 47 IS 4 BP 393 EP 399 PG 7 WC Neurosciences SC Neurosciences & Neurology GA WK582 UT WOS:A1997WK58200004 PM 9057132 ER PT J AU Gilon, P Yakel, J Gromada, J Zhu, Y Henquin, JC Rorsman, P AF Gilon, P Yakel, J Gromada, J Zhu, Y Henquin, JC Rorsman, P TI G protein-dependent inhibition of L-type Ca2+ currents by acetylcholine in mouse pancreatic B-cells SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID MUSCARINIC RECEPTOR SUBTYPES; RAT SYMPATHETIC NEURONS; BETA-CELLS; CALCIUM CHANNELS; INSULIN RELEASE; GLUCOSE-DEPENDENCE; KINASE-C; N-TYPE; ACTIVATION; MODULATION AB 1. The effect of acetylcholine (ACh) on voltage-dependent Ca2+ currents in mouse pancreatic B-cells was studied using the whole-cell configuration of the patch-clamp technique. 2. ACh (0.25-250 mu M) reversibly and dose-dependently inhibited the Ca2+ current elicited by depolarizations from -80 mV to +10 mV. Maximal inhibition was observed at concentrations > 25 mu M where it amounted to similar to 35%. The effect was voltage independent and prevented by atropine (10 mu M) suggesting that it wax mediated by muscarinic receptors. 3. The inhibitory action of ACh on the Ca2+ current was abolished when the cytoplasmic solution contained GDP beta S (2 mM) and became irreversible when the non-hydrolysable GTP analogue GTP gamma S (10 mu M) was included in the pipette. This indicates the participation of G proteins in the inhibitory effect of ACh but pretreatment of the cells with either pertussis or cholera toxin failed to prevent the effect of ACh on the Ca2+ current. 4. ACh remained equally effective as an inhibitor of the whole-cell Ca2+ current in the presence of the L-type Ca2+ channel agonist (-)-Bay K 8644 and after partial inhibition of the current by nifedipine. Addition of omega-agatoxin IVA, omega-conotoxin GVIA or omega-conotoxin MVIIC neither affected the peak Ca2+ current amplitude nor the extent of inhibition produced by ACh. These pharmacological properties indicate that ACh acts by inhibiting L-type Ca2+ channels. 5. The inhibitory action of ACh on the B-cell Ca2+ current was not secondary to elevation of [Ca2+](i) and ACh remained equally effective as an inhibitor when Ba2+ was used as the charge carrier, when [Ca2+](i) was buffered to low concentrations using EGTA and under experimental conditions preventing the mobilization of Ca2+ from intracellular stores. 6. These results suggest that ACh reduces the whole-cell Ca2+ current in the B-cell through a G protein-regulated, voltage- and Ca2+-independent inhibition of L-type Ca2+ channels. C1 NOVO NORDISK AS,ISLET CELL PHYSIOL,DK-2100 COPENHAGEN,DENMARK. NIEHS,CELLULAR & MOL PHARMACOL LAB,RES TRIANGLE PK,NC 27709. UNIV CATHOLIQUE LOUVAIN,FAC MED,UNITE ENDOCRINOL & METAB,B-1200 BRUSSELS,BELGIUM. RI Rorsman, Patrik/A-4331-2016 OI Rorsman, Patrik/0000-0001-7578-0767 NR 39 TC 35 Z9 35 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD FEB 15 PY 1997 VL 499 IS 1 BP 65 EP 76 PG 12 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA WL953 UT WOS:A1997WL95300006 PM 9061640 ER PT J AU Lyubchenko, YL Shlyakhtenko, LS Aki, T Adhya, S AF Lyubchenko, YL Shlyakhtenko, LS Aki, T Adhya, S TI Atomic force microscopic demonstration of DNA looping by GalR and HU SO NUCLEIC ACIDS RESEARCH LA English DT Article ID NUCLEOPROTEIN COMPLEXES; ARCHITECTURAL ELEMENTS; TRANSCRIPTION; PROTEINS; BINDING; RNA AB Regulation of gene transcription in both prokaryotes : and eukaryotes involves formation of various DNA-multiprotein complexes of higher order structure through communication between distant regions of DNA. The communication between distant DNA sites occurs by interaction between proteins bound to the sites by looping out the intervening DNA segments. The repression of transcription of two overlapping promoters of the gal operon in Escherichia coli requires Gal repressor (GalR) and the histone-like protein HU. Both in vivo and in vitro data support a proposed HU containing complex responsive to induction in which GalR molecules bound to two distant operator sites interact by looping out DNA. We successfully applied atomic force microscope (AFM) imaging to visualize gal DNA complexes with proteins. We report GalR mediated DNA looping in which HU plays an obligatory role by helping GalR tetramerization. Supercoliing of DNA, which is also critical for GalR action, may stabilize the DNA loops by providing an energetically favorable geometry of the DNA. C1 NCI, MOL BIOL LAB, NIH, BETHESDA, MD 20892 USA. ARIZONA STATE UNIV, DEPT MICROBIOL, TEMPE, AZ 85287 USA. ARIZONA STATE UNIV, DEPT ZOOL, TEMPE, AZ 85287 USA. HIROSHIMA UNIV, FAC ENGN, LAB IND BIOCHEM, HIGASHIHIROSHIMA 724, JAPAN. RI Aki, Tsunehiro/B-6719-2012 OI Aki, Tsunehiro/0000-0001-9753-2043 FU NIGMS NIH HHS [GM54991-01] NR 19 TC 65 Z9 66 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD FEB 15 PY 1997 VL 25 IS 4 BP 873 EP 876 DI 10.1093/nar/25.4.873 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WJ770 UT WOS:A1997WJ77000027 PM 9016640 ER PT J AU Panyutin, IG Neumann, RD AF Panyutin, IG Neumann, RD TI Radioprobing of DNA: Distribution of DNA breaks produced by decay of I-125 incorporated into a triplex-forming oligonucleotide correlates with geometry of the triplex SO NUCLEIC ACIDS RESEARCH LA English DT Article ID DAMAGE; MODEL; I125 AB The distribution of breaks produced in both strands of a DNA duplex by the decay of I-125 carried by a tripler-forming DNA oligonucleotide was studied at single nucleotide resolution. The I-125 atom was located in the C5 position of a single cytosine residue of an oligonucleotide designed to form a triple helix with the target sequence duplex, The majority of the breaks (90%) are located within 10 bp around the decay site, The addition of the free radical scavenger DMSO produces an insignificant effect on the yield and distribution of the breaks. These results suggest that the majority of these breaks are produced by the direct action of radiation and are not mediated by diffusible free radicals, The frequency of breaks in the purine strand was two times higher that in the pyrimidine strand, This asymmetry in the yield of breaks correlates with the geometry of this type of tripler; the C5 of the cytosine in the third strand is closer to the sugar-phosphate backbone of the purine strand, Moreover, study of molecular models shows that the yield of breaks at individual bases correlates with distance from the I-125 decay site. We suggest the possible use of I-125 decay as a probe for the structure of nucleic acids and nucleoprotein complexes. RP Panyutin, IG (reprint author), NIH,WARREN G MAGNUSON CLIN CTR,DEPT NUCL MED,BETHESDA,MD 20892, USA. NR 20 TC 52 Z9 52 U1 1 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD FEB 15 PY 1997 VL 25 IS 4 BP 883 EP 887 DI 10.1093/nar/25.4.883 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WJ770 UT WOS:A1997WJ77000029 PM 9016642 ER PT J AU Wasilenko, WJ Cooper, J Palad, AJ Somers, KD Blackmore, PF Rhim, JS Wright, GL Schellhammer, PF AF Wasilenko, WJ Cooper, J Palad, AJ Somers, KD Blackmore, PF Rhim, JS Wright, GL Schellhammer, PF TI Calcium signaling in prostate cancer cells: Evidence for multiple receptors and enhanced sensitivity to bombesin/GRP SO PROSTATE LA English DT Article DE signal transduction; neuropeptides; purinergic receptors ID SOMATOSTATIN ANALOG RC-160; INTRACELLULAR CALCIUM; ANTAGONIST RC-3095; EXTRACELLULAR ATP; EPITHELIAL-CELLS; CARCINOMA-CELLS; GROWTH-FACTORS; LUNG-CANCER; NUDE-MICE; TRANSDUCTION AB BACKGROUND. Cellular calcium is an important second messenger for growth regulation. We sought to identify potentially important receptors on prostate tumor cells by screening over 20 agonists for their ability to increase intracellular free calcium ([Ca2+](i)) in several human prostate tumor cell lines. METHODS. Intracellular calcium mobilization was detected using fura-2. RESULTS. We found bombesin, GRP, ATP/UTP, lysophosphatidic acid, thrombin, endothelin, histamine, and bradykinin increased [Ca2+](i) in the advanced tumor cell lines DU-145, PC3, and PPC-1. Bombesin failed to elevate [Ca2+](i) in an immortalized human prostate cell line. Rank-order of potency studies suggested the presence of P-2U nucleotide receptors for ATP/UTP on prostate epithelial cells. Potency studies also revealed GRP>>bombesin>>neuromedin B at elevating [Ca2+](i) in responding tumor cells. CONCLUSIONS. These findings indicate that androgen independent prostate tumor cell lines express multiple receptors capable of elevating intracellular calcium, and suggest that GRP receptors may be selectively expressed and/or coupled to calcium signaling during prostate tumor progression. Calcium sensitive cellular events may therefore contribute to the progression of prostate cancer. (C) 1997 Wiley-Liss, Inc. C1 EASTERN VIRGINIA MED SCH,DEPT UROL,NORFOLK,VA 23510. EASTERN VIRGINIA MED SCH,DEPT PHARMACOL,NORFOLK,VA 23510. EASTERN VIRGINIA MED SCH,VIRGINIA PROSTATE CTR,NORFOLK,VA 23510. NCI,MOL ONCOL LAB,FREDERICK,MD. RP Wasilenko, WJ (reprint author), EASTERN VIRGINIA MED SCH,DEPT MICROBIOL & IMMUNOL,NORFOLK,VA 23510, USA. NR 49 TC 46 Z9 46 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0270-4137 J9 PROSTATE JI Prostate PD FEB 15 PY 1997 VL 30 IS 3 BP 167 EP 173 PG 7 WC Endocrinology & Metabolism; Urology & Nephrology SC Endocrinology & Metabolism; Urology & Nephrology GA WQ447 UT WOS:A1997WQ44700004 PM 9122041 ER PT J AU Gaddipati, JP McLeod, DG Sesterhenn, IA Hussussian, CJ Tong, YA Seth, P Dracopoli, NC Moul, JW Srivastava, S AF Gaddipati, JP McLeod, DG Sesterhenn, IA Hussussian, CJ Tong, YA Seth, P Dracopoli, NC Moul, JW Srivastava, S TI Mutations of the p16 gene product are rare in prostate cancer SO PROSTATE LA English DT Article DE prostate cancer; p16; microsatellite; polymerase chain reaction; single strand conformation polymorphism ID KINASE-4 INHIBITOR GENE; CELL-LINES; HOMOZYGOUS DELETION; CDK4 AMPLIFICATION; SOMATIC MUTATIONS; CARCINOMA; PROTEIN; P53; ADENOCARCINOMA; ACCUMULATION AB BACKGROUND. The p16 gene pro-duct isa negative regulator of cell cycle and has been shown to be deleted or mutated in a number of tumor cell lines and primary tumors. The role of p16 in prostate cancer is not defined. Prostate cancer tissues and cell lines were evaluated for pi gene alterations. METHODS. Five metastatic prostate cancer cell lines were analyzed for p16 gene structure and its expression by Southern and Northern blot analyses. Forty-one DNA specimens from 18 microdissected primary tumor specimens, adjacent normal tissues, and cell lines were amplified by polymerase chain reaction for p16 protein coding and splice junction sequences. Mutations were analyzed by single strand conformation polymorphism and DNA sequencing. RESULTS. DU 145 cell line exhibited a missense mutation in codon 84 (GAC to TAC). With the exception of previously reported polymorphism, no mutation was detected in p16 coding or splice junction sequences in primary prostate cancer specimens. CONCLUSIONS. Inactivation of p16 gene by mutations in the protein coding sequence does not play a major role in the genesis of primary prostate cancer. (C) 1997 Wiley-Lies, Inc. C1 UNIFORMED SERV UNIV HLTH SCI,DEPT SURG,CTR PROSTATE DIS RES,BETHESDA,MD 20814. WALTER REED ARMY MED CTR,UROL SERV,WASHINGTON,DC 20307. ARMED FORCES INST PATHOL,WASHINGTON,DC 20306. NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. NCI,MED BREAST SECT,MED BRANCH,NIH,BETHESDA,MD 20892. NR 32 TC 27 Z9 28 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0270-4137 J9 PROSTATE JI Prostate PD FEB 15 PY 1997 VL 30 IS 3 BP 188 EP 194 PG 7 WC Endocrinology & Metabolism; Urology & Nephrology SC Endocrinology & Metabolism; Urology & Nephrology GA WQ447 UT WOS:A1997WQ44700007 PM 9122044 ER PT J AU Wakayama, I Song, KJ Nerurkar, VR Yoshida, S Garruto, RM AF Wakayama, I Song, KJ Nerurkar, VR Yoshida, S Garruto, RM TI Slow dendritic transport of dissociated mouse hippocampal neurons exposed to aluminum SO BRAIN RESEARCH LA English DT Article DE cell culture; RNA; Alzheimer's disease; amyotrophic lateral sclerosis; Parkinsonism-dementia; Guam; axonal transport; neurotoxin ID AMYOTROPHIC LATERAL SCLEROSIS; ANTERIOR HORN CELLS; NEUROFILAMENT TRANSPORT; NEUROFIBRILLARY CHANGES; DISEASE; GUAM; RNA; NEUROTOXICITY; EXPRESSION; MYELOPATHY AB We determined the influence of aluminum on dendritic transport, using an in vitro system of dissociated mouse hippocampal neurons. Newly synthesized RNA from dissociated mouse hippocampal neurons was more slowly transported into dendrites in the presence of aluminum chloride when compared to those without the addition of aluminum chloride to the culture medium. Suppression of dendritic transport of newly synthesized RNA may be responsible for the dendritic degeneration observed in aluminum neurotoxicity, eventually leading to neuronal degeneration. C1 KANSAI COLL ORIENTAL MED,RES CTR NEUROL DIS,KUMATORI,OSAKA 59004,JAPAN. NINCDS,NIH,CENT NERVOUS SYST STUDIES LAB,BETHESDA,MD 20892. KOREA UNIV,COLL MED,DEPT MICROBIOL,SEOUL 136705,SOUTH KOREA. LEAHI HOSP,PACIFIC BIOMED RES CTR,RETROVIRUS RES LAB,HONOLULU,HI 96816. WAKAYAMA MED COLL,DIV NEUROL DIS,WAKAYAMA 640,JAPAN. OI Song, Ki-Joon/0000-0002-7935-3719 NR 30 TC 6 Z9 7 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 FEB 14 PY 1997 VL 748 IS 1-2 BP 237 EP 240 DI 10.1016/S0006-8993(96)01314-5 PG 4 WC Neurosciences SC Neurosciences & Neurology GA WL749 UT WOS:A1997WL74900030 PM 9067468 ER PT J AU Wagstaff, JD Gibb, JW Hanson, GR AF Wagstaff, JD Gibb, JW Hanson, GR TI Role of dopamine D-1- and NMDA receptors in regulating neurotensin release in the striatum and nucleus accumbens SO BRAIN RESEARCH LA English DT Article DE neurotensin; microdialysis; dopamine; NMDA; striatum; nucleus accumbens ID MESSENGER-RNA; ACUTE METHAMPHETAMINE; RAT STRIATUM; SYSTEMS; NEOSTRIATUM; RESPONSES; REGIONS; DRUGS; D1 AB Stimulation of dopamine D-1-receptors by SKF 82958 increased extracellular neurotensin (NT) levels in the striatum and nucleus accumbens as measured by in vivo microdialysis while blockade of D-1-receptors had no effect. Antagonism of NMDA receptors with MK 801 completely prevented the increased NT release induced by D-1-stimulation in both structures. Tissue content of striatal NT anterior and posterior to the microdialysis probe was oppositely altered by D-1-stimulation: increases were observed in the anterior striatum with decreased NT levels in the posterior striatum. C1 UNIV UTAH,DEPT PHARMACOL & TOXICOL,SALT LAKE CITY,UT 84112. NIMH,NIH,NEUROPHYSIOL LAB,BETHESDA,MD. FU NIDA NIH HHS [DA 00869, DA 09407] NR 18 TC 15 Z9 15 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 FEB 14 PY 1997 VL 748 IS 1-2 BP 241 EP 244 DI 10.1016/S0006-8993(96)01380-7 PG 4 WC Neurosciences SC Neurosciences & Neurology GA WL749 UT WOS:A1997WL74900031 PM 9067469 ER PT J AU Ichikawa, H Jacobowitz, DM Sugimoto, T AF Ichikawa, H Jacobowitz, DM Sugimoto, T TI S100 protein-immunoreactive primary sensory neurons in the trigeminal and dorsal root ganglia of the rat SO BRAIN RESEARCH LA English DT Article DE S100; parvalbumin; calbindin D-28k; calretinin; trigeminal ganglion; dorsal root ganglion ID CELL-SIZE ANALYSIS; TOOTH-PULP; CARBONIC-ANHYDRASE; CALRETININ-IMMUNOREACTIVITY; PERIPHERAL PROJECTIONS; CHICK HINDLIMBS; SUBSTANCE-P; PARVALBUMIN; CALBINDIN-D-28K; BRAIN AB The cell body size (cross-sectional area) of S100-immunoreactive (-ir) primary neurons was measured in the trigeminal (TG) and lumbar dorsal root ganglia (DRG). About a half of neurons exhibited S100-immunoreactivity (-ir) in the DRG (44.0%) and TG (59.0%). DRG neurons with cell bodies >1200 mu m(2) mostly exhibited S100-ir (96.5%), whereas S100-ir DRG neurons <600 mu m(2) were rare (8.0%). 36.6% of DRG neurons in the cell size range 600-1200 mu m(2) showed the ir. TG neurons >800 mu m(2) mostly exhibited S100-ir (93.1%), whereas those <400 mu m(2) were devoid of it (positive cells 10.5%). 58.3% of TG cells in the range 400-800 mu m(2) contained S100-ir. Double-immunofluorescence method revealed the co-expression of S100 and other calcium-binding proteins. Parvalbumin-ir neurons mostly exhibited S100-ir in the DRG (97.4%) and TG (97.0%). The co-expression of S100 and calbindin D-28k was very rare in the DRG, because the DRG contained few calbindin D-28k-ir neurons. Unlike in the DRG, numerous neurons co-expressed S100- and calbindin D-28k-ir in the TG. Most calbindin D-28k-ir TG neurons were also immunoreactive for S100 (90.7%). Sub-populations of calretinin (CR)-ir neurons co-expressed S100-ir in both the DRG (68%) and TG (50.0%). Virtually all CR-ir neurons > 1400 mu m(2) co-expressed S100-ir in the DRG (100%) and TG (95.9%). CR-ir neurons <800 mu m(2) were rarely exhibited S100-ir (DRG 18.0%, TG 21.9%). 71.3 and 60.5% of CR-ir neurons in the range 800-1400 mu m(2) co-expressed S100-ir in the DRG and TG, respectively. The present study indicates that S100 is closely correlated to the primary neuronal cell size in the DRG and TG. C1 NIMH,CLIN SCI LAB,BETHESDA,MD 20892. RP Ichikawa, H (reprint author), OKAYAMA UNIV,SCH DENT,DEPT ORAL ANAT 2,2-5-1 SHIKATA CHO,OKAYAMA 700,JAPAN. NR 21 TC 42 Z9 42 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 FEB 14 PY 1997 VL 748 IS 1-2 BP 253 EP 257 DI 10.1016/S0006-8993(96)01364-9 PG 5 WC Neurosciences SC Neurosciences & Neurology GA WL749 UT WOS:A1997WL74900034 PM 9067472 ER PT J AU Tasaki, K Ruetzler, CA Ohtsuki, T Martin, D Nawashiro, H Hallenbeck, JM AF Tasaki, K Ruetzler, CA Ohtsuki, T Martin, D Nawashiro, H Hallenbeck, JM TI Lipopolysaccharide pre-treatment induces resistance against subsequent focal cerebral ischemic damage in spontaneously hypertensive rats SO BRAIN RESEARCH LA English DT Article DE tolerance; lipopolysaccharide; tumor necrosis factor alpha; endotoxin; cerebral ischemia; rat ID TUMOR-NECROSIS-FACTOR; FACTOR-ALPHA; BRAIN; INTERLEUKIN-1; EXPRESSION; PROTECTS; STRESS; INFARCTION; OCCLUSION; NEURONS AB Ischemic tolerance was induced in spontaneously hypertensive rats (SHR) by injection of a single dose of Lipopolysaccharide (LPS) (0.9 mg/kg, i.v.) 1-7 days prior to permanent middle cerebral artery occlusion (MCAO). Infarct volume, evaluated 24 h after MCAO, was significantly reduced by LPS administration 2, 3 or 4 days prior to MCAO (22.8, 25.9 and 20.5%, respectively). The beneficial effect of LPS pre-treatment was completely nullified by concurrent administration of TNFbp. On this basis, the tolerance to ischemia induced by LPS is likely to be mediated by TNF-alpha. C1 NINCDS,NIH,STROKE BRANCH,BETHESDA,MD 20892. AMGEN BOULDER INC,DEPT PHARMACOL,BOULDER,CO. NR 18 TC 213 Z9 221 U1 2 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD FEB 14 PY 1997 VL 748 IS 1-2 BP 267 EP 270 DI 10.1016/S0006-8993(96)01383-2 PG 4 WC Neurosciences SC Neurosciences & Neurology GA WL749 UT WOS:A1997WL74900037 PM 9067475 ER PT J AU Vitale, N Moss, J Vaughan, M AF Vitale, N Moss, J Vaughan, M TI Interaction of the GTP-binding and GTPase-activating domains of ARD1 involves the effector region of the ADP-ribosylation factor domain SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GUANINE-NUCLEOTIDE; CHOLERA-TOXIN; BREFELDIN-A; PHOSPHOLIPASE-D; AMINO-TERMINUS; BOVINE BRAIN; PROTEIN; GOLGI; ARF; EXPRESSION AB ADP-ribosylation factors (ARFs) are a family of similar to 20-kDa guanine nucleotide-binding proteins and members of the Pas superfamily, originally identified and purified by their ability to enhance the ADP-ribosyltransferase activity of cholera toxin and more recently recognized as critical participants in vesicular trafficking pathways and phospholipase D activation. ARD1 is a 64-kDa protein with an 18-kDa carboxyl-terminal ARF domain (p3) and a 46-kDa amino-terminal extension (p5) that is widely expressed in mammalian tissues. Using recombinant proteins, we showed that p5, the aminoterminal domain of ARD1, stimulates the GTPase activity of p3, the ARF domain, and appears to be the GTPase-activating protein (GAP) component of this bifunctional protein, whereas in other members of the Ras superfamily a separate GAP molecule interacts with the effector region of the GTP-binding protein. p5 stimulated the GTPase activity of p3 but not of ARF1, which differs from p3 in several amino acids in the effector domain. After substitution of 7 amino acids from p3 in the appropriate position in ARF1, the chimeric protein ARF1(39-45p3) bound to p5, which increased its GTPase activity. Specifically, after Gly(40) and Thr(45) in the putative effector domain of ARF1 were replaced with the equivalent Asp and Pro, respectively, from p3, functional interaction of the chimeric ARF1 with p5 was increased. Thus, Asp(25) and pro(30) Of the ARF domain (p3) of ARD1 are involved in its functional and physical interaction with the GTPase-activating (p5) domain of ARD1. After deletion of the amino-terminal 15 amino acids from ARF1(39-45p3), its interaction with p5 was essentially equivalent to that of p3, suggesting that the amino terminus of ARF1(39-45p3) may interfere with binding to p5. These results are consistent with the conclusion that the GAP domain of ARD1 interacts with the effector region of the ARF domain and thereby stimulates GTP hydrolysis. RP Vitale, N (reprint author), NHLBI,PULM CRIT CARE MED BRANCH,NIH,RM 5N-307,BLDG 10,10 CTR DR,BETHESDA,MD 20892, USA. RI Vitale, nicolas/G-5967-2014 OI Vitale, nicolas/0000-0002-4752-4907 NR 45 TC 18 Z9 18 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD FEB 14 PY 1997 VL 272 IS 7 BP 3897 EP 3904 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WH019 UT WOS:A1997WH01900007 PM 9020091 ER PT J AU Ting, YT Bhat, MK Wong, R Cheng, SY AF Ting, YT Bhat, MK Wong, R Cheng, SY TI Tissue-specific stabilization of the thyroid hormone beta 1 nuclear receptor by phosphorylation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BINDING-CAPACITY; CO-REPRESSOR; PROTEIN; ACTIVATION; RAT; PROTEOLYSIS; SEQUENCE; ISOFORMS; KINASE; ACID AB The present study evaluated the expression and regulation of endogenous thyroid hormone receptors (TRs) in cultured cells. In COS-1 cells, the endogenous TR, subtype beta 1 (TR beta 1), but not subtype beta 2 or alpha 1, was induced to express by okadaic acid (OA) in a concentration-dependent manner. The induced TR beta 1 had immunoreactivity and partial V8 proteolytic maps similar to those of the transfected and in vitro translated human TR beta 1 (h-TR beta 1). The OA-induced expression of endogenous TR beta 1 was, however, not observed in a variety of other cultured cell lines tested, indicating that the induction was cell type-dependent. TR beta 1 induced by OA was a multisite phosphorylated protein, in which serine and threonine in a ratio of 10:1 were phosphorylated. The induced TR beta 1 was functional as it could mediate the thyroid hormone-dependent transcriptional activity via several thyroid hormone response elements. The induction of endogenous TR beta 1 expression by OA was not accompanied by an increase in mRNA levels but was the result of an increase in the stability of the TR beta 1 protein. This is the first report to indicate that one of the mechanisms by which the TR isoforms are differentially expressed is via the tissue-specific stabilization of the TR isoform proteins. Furthermore, this selective stability of TR beta 1 could be conferred by phosphorylation. C1 NCI,MOL BIOL LAB,NIH,BETHESDA,MD 20892. NIDDKD,MOL & CELLULAR ENDOCRINOL BRANCH,NIH,BETHESDA,MD 20892. NR 32 TC 23 Z9 24 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD FEB 14 PY 1997 VL 272 IS 7 BP 4129 EP 4134 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WH019 UT WOS:A1997WH01900040 PM 9020124 ER PT J AU VanLeeuwen, JEM Kearse, KP AF VanLeeuwen, JEM Kearse, KP TI Reglucosylation of N-linked glycans is critical for calnexin assembly with T cell receptor (TCR) alpha proteins but not TCR beta proteins SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MOUSE LYMPHOMA-CELLS; GLUCOSE-GLYCOPROTEIN GLUCOSYLTRANSFERASE; HAMSTER OVARY CELLS; ENDOPLASMIC-RETICULUM; ENDOMANNOSIDASE PATHWAY; MOLECULAR CHAPERONE; UDP-GLC; OLIGOSACCHARIDE; ASSOCIATION; BIOSYNTHESIS AB Association of calnexin with newly synthesized glycoproteins involves recognition of monoglucosylated glycans, generated in the endoplasmic reticulum via initial removal of two glucose (Glc) residues from immature glycan chains by glucosidase enzymes (Glc trimming), or addition of a single Glc residue to fully trimmed glycans by glucosyltransferase enzymes (reglucosylation). While it has been established that creation of monoglucosylated glycans is important for chaperone binding, it is unknown if most proteins require both deglucosylation and reglucosylation for calnexin assembly or if initial Glc trimming is sufficient. Here, we studied the deglucosylation and reglucosylation of two related glycoproteins, the alpha and beta subunits of the T cell receptor (TCR) complex, and their assembly with calnexin in BW thymoma cells. Our data demonstrate that TCR alpha/beta glycoproteins undergo multiple cycles of Glc removal and addition within the endoplasmic reticulum and that numerous reglucosylated proteins assemble with calnexin, including TCR alpha/beta glycoproteins. Importantly, the current study shows that TCR beta proteins, but not TCR alpha proteins, effectively associate with calnexin under conditions of functional Glc trimming but impaired reglucosylation. These data demonstrate that reglucosylated proteins associate with lectin-like chaperones in vivo and provide evidence that reglucosylation is of differential importance for the association of individual, indeed similar, glycoproteins with calnexin. C1 NCI,EXPT IMMUNOL BRANCH,NIH,BETHESDA,MD 20892. RI van Leeuwen, Jeroen/G-3555-2010 NR 47 TC 40 Z9 40 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD FEB 14 PY 1997 VL 272 IS 7 BP 4179 EP 4186 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WH019 UT WOS:A1997WH01900047 PM 9020131 ER PT J AU Moss, J Stevens, LA Cavanaugh, E Okazaki, IJ Bortell, R Kanaitsuka, T Mordes, JP Greiner, DL Rossini, AA AF Moss, J Stevens, LA Cavanaugh, E Okazaki, IJ Bortell, R Kanaitsuka, T Mordes, JP Greiner, DL Rossini, AA TI Characterization of mouse Rt6.1 NAD:arginine ADP-ribosyltransferase SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NICOTINAMIDE ADENINE-DINUCLEOTIDE; AUTOIMMUNE DIABETES-MELLITUS; DIFFERENTIATION MARKER RT6; T-CELL SUBSET; TURKEY ERYTHROCYTES; SKELETAL-MUSCLE; ALLOANTIGEN RT6.1; BB/W RATS; EXPRESSION; RIBOSYLATION AB Rat RT6 proteins, and perhaps mouse Rt6, identify a set of immunoregulatory T lymphocytes. Rat RT6.1 (RT6.1) and rat RT6.2 (RT6.2) are NAD glycohydrolases, which catalyze auto-ADP-ribosylation, but not ADP-ribosylation of exogenous proteins. Mouse Rt6.1 (mRt6.1) also catalyzes auto-ADP-ribosylation. The activity of mouse cytotoxic T lymphocytes is reportedly inhibited by ADP-ribosylation of surface proteins, raising the possibility that mRt6 may participate in this process. The reactions catalyzed by mRt6, would, however, need to be more diverse than those of the rat homologues and include the ADP-ribosylation of accepters other than itself. To test this hypothesis, mRt6.1 and rat RT6.2 were synthesized in Sf9 insect cells and rat mammary adenocarcinoma (NMU) cells. mRt6.1, but not rat RT6.2, catalyzed the ADP-ribosylation of guanidino-containing compounds (e.g. agmatine). Unlike RT6.2, mRt6.1 was a weak NAD glycohydrolase. In the presence of agmatine, however, the ratio of [adenine-C-14]ADP-ribosylagmatine formation from [adenine-C-14]NAD to [carbonyl-C-14]nicotinamide formation from [carbonyl-C-14]NAD was similar to 1.0, demonstrating that mRtG.1 is primarily a transferase. ADP-ribosylarginine hydrolase, which preferentially hydrolyzes the alpha-anomer of ADP-ribosylarginine, released [U-C-14]arginine from ADP-ribosyl[U-C-14] arginine synthesized by mRT6.1, consistent with the conclusion that mRt6.1 catalyzes a stereospecific S(n)2-like reaction. Thus, mRt6.1 is an NAD:arginine ADP-ribosyltransferase capable of catalyzing a multiple turnover, stereospecific S(n)2-like reaction. C1 UNIV MASSACHUSETTS,MED CTR,DIABET DIV,WORCESTER,MA 01605. RP Moss, J (reprint author), NHLBI,PULM CRIT CARE MED BRANCH,NIH,RM 6D-03,BLDG 10,10 CTR DR,MSC 1590,BETHESDA,MD 20892, USA. NR 45 TC 12 Z9 12 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD FEB 14 PY 1997 VL 272 IS 7 BP 4342 EP 4346 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WH019 UT WOS:A1997WH01900070 PM 9020154 ER PT J AU LeGall, AH Powell, SK Yeaman, CA RodriguezBoulan, E AF LeGall, AH Powell, SK Yeaman, CA RodriguezBoulan, E TI The neural cell adhesion molecule expresses a tyrosine-independent basolateral sorting signal SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID POLYMERIC IMMUNOGLOBULIN RECEPTOR; RETINAL-PIGMENT EPITHELIUM; LYSOSOMAL ACID-PHOSPHATASE; CANINE KIDNEY-CELLS; DI-LEUCINE MOTIF; N-CAM; MDCK CELLS; CYTOPLASMIC DOMAIN; INTERNALIZATION SIGNAL; TRANSFERRIN RECEPTOR AB Transmembrane isoforms of the neural cell adhesion molecule, N-CAM (N-CAM-140 and N-CAM-180), are vectorially targeted from the trans-Golgi network to the basolateral domain upon expression in transfected Madin-Darby canine kidney cells (Powell, S. K., Cunningham, B. A. Edelman, G. M., and Rodriguez-Boulan, E. (1991) Nature 353, 76-77), To localize basolateral targeting information, mutant forms of N-CAM-140 were constructed and their surface distribution analyzed in Madin-Darby canine kidney cells. N-CAM-140 deleted of its cytoplasmic domain shows a non-polar steady state distribution, resulting from delivery from the trans-Golgi network to both the apical and basolateral surfaces. This result suggests that entrance into the basolateral pathway may occur without cytoplasmic signals, implying that apical targeting from the trans-Golgi network is not a default mechanism but, rather, requires positive sorting information. Subsequent construction and analysis of a nested set of C-terminal deletion mutants identified a region of 40 amino acids (amino acids 749-788) lacking tyrosine residues required for basolateral targeting. Addition of these 40 amino acids is sufficient to restore basolateral targeting to both the non-polar cytoplasmic deletion mutant of N-CAM as well as to the apically expressed cytoplasmic deletion mutant of the p75 low affinity neurotrophin receptor (p75(NTR)), indicating that this tyrosine-fi ee sequence is capable of functioning independently as a basolateral sorting signal. Deletion of both cytoplasmic and transmembrane domains resulted in apical secretion of N-CAM, demonstrating that the ectodomain of this molecule carries recessive apical sorting information. C1 CORNELL UNIV,COLL MED,DYSON VIS RES INST,DEPT OPHTHALMOL,NEW YORK,NY 10021. NIDR,DEV BIOL LAB,NIH,BETHESDA,MD 20892. OI Yeaman, Charles/0000-0001-6149-628X FU NEI NIH HHS [R01 EY008538, EY08538-02]; NIGMS NIH HHS [GM34107-11, GM41771-05, R01 GM034107] NR 65 TC 49 Z9 51 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD FEB 14 PY 1997 VL 272 IS 7 BP 4559 EP 4567 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WH019 UT WOS:A1997WH01900099 PM 9020183 ER PT J AU Orlandi, PA AF Orlandi, PA TI Protein-disulfide isomerase-mediated reduction of the a subunit of cholera toxin in a human intestinal cell line SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GLUTATHIONE-INSULIN TRANSHYDROGENASE; HEAT-LABILE ENTEROTOXIN; BREFELDIN-A; ENDOPLASMIC-RETICULUM; BACTERIAL ENTEROTOXINS; ADENYLATE-CYCLASE; CULTURED-CELLS; MEMBRANE; RECEPTOR; FUSION AB A key step in the action of cholera toxin (CT) is the reduction of its A subunit to the A(1) peptide, The latter is an ADP-ribosyltransferase, which activates the alpha-subunit of the stimulatory G protein of adenylyl cyclase. In this study, the enzymatic reduction of membrane-bound CT in CaCo-2 human intestinal epithelial cells was characterized, Whereas diphtheria toxin was found to be reduced by a cell surface population of protein-disulfide isomerase (PDI) and its cytotoxicity was inhibited by p-chloromercuribenzenesulfonic acid, bacitracin, or anti-PDI antibodies, these inhibitors had no effect on CT reduction or activity in intact cells, In contrast, the reduction of CT in vitro by either postnuclear supernatants (PNS) or microsomal membranes in the presence of Triton X-100 was significantly inhibited by p-chloromercuribenzenesulfonic acid and bacitracin, Anti-PDI monoclonal antibodies likewise inhibited the in vitro reduction of CT and also were effective in depleting reductase activity from PNS, Since inhibition and depletion were not observed in the absence of detergent, these results suggested that the reductase activity was a soluble component localized to the lumen of microsomal vesicles and correlated with the presence of protein-disulfide isomerase, This was further confirmed by showing a corresponding depletion of reductase activity and PDI in alkali-treated microsomes, This activity was restored when purified bovine PDI was added back to alkali-treated microsomes in a redox buffer that reflected conditions found in the lumen of the endoplasmic reticulum (ER), When the CT-related reductase activity was assayed in subcellular fractions of PNS-derived membranes isolated on a 9-30% Iodixanol gradient, the activity, as measured by CT-A(1) peptide formation localized to those fractions containing PDI. Likewise CT-A(1) peptide formed in intact cells co-localized to those membrane fractions containing the majority of cellular PDI, Furthermore, the banding density corresponded to a region of the gradient containing ER-derived membranes, These results indicated that CT was a substrate for PDI-catalyzed reduction in intact cells and supported the hypothesis that CT reduction and activation occurs in the ER. RP Orlandi, PA (reprint author), NINCDS,MEMBRANE BIOCHEM SECT,MOL & CELLULAR NEUROBIOL LAB,NIH,BLDG 49,ROOM 2A28,BETHESDA,MD 20892, USA. NR 50 TC 86 Z9 89 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD FEB 14 PY 1997 VL 272 IS 7 BP 4591 EP 4599 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WH019 UT WOS:A1997WH01900103 PM 9020187 ER PT J AU GravesWoodward, KL Gottlieb, J Challberg, MD Weller, SK AF GravesWoodward, KL Gottlieb, J Challberg, MD Weller, SK TI Biochemical analyses of mutations in the HSV-1 helicase-primase that alter ATP hydrolysis, DNA unwinding, and coupling between hydrolysis and unwinding SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SIMPLEX VIRUS TYPE-1; NUCLEOTIDE-BINDING SITE; SINGLE-STRANDED-DNA; ELONGATION-FACTOR TU; BOX RNA HELICASE; ESCHERICHIA-COLI; GENE-PRODUCT; NUCLEOSIDE TRIPHOSPHATE; CONFORMATIONAL-CHANGES; TRANSCRIPTION FACTOR AB Herpes simplex virus type 1 encodes a heterotrimeric helicase-primase composed of the products of the UL5, UL52, and UL8 genes. UL5 possesses six motifs conserved among superfamily 1 of helicase proteins. Substitutions of conserved residues in each moth abolishes DNA replication in vivo (Zhu, L., and Weller, S. K. (1992) J. Virol. 66, 469-479). Purified UL5-52 harboring a Gay to Ala change in motif V retains primase and helicase activities in vitro but exhibits a higher K-M for single-stranded DNA and lower DNA-dependent ATPase activity (Graves-Woodward, K. L., and Weller, S. K. (1996) J. Biol. Chem. 272, 13629-13635). We have purified and characterized six other subcomplexes with residue changes in the UL5 helicase motifs. Each variant subcomplex displays at least wild type or greater levels of primase and DNA binding activities, but all are defective in helicase activity. Mutations in motifs I and II exhibit profound decreases in DNA-dependent ATPase activity. Mutations in motifs III-VI decrease DNA-dependent ATPase activity 3-6-fold. Since mutations in motifs III, IV, V, and VI do not eliminate ATP hydrolysis or DNA binding, we propose that they may be involved in the coupling of these two activities to the process of DNA unwinding. This analysis represents the first comprehensive structure-function analysis of the conserved motifs in helicase superfamily 1. C1 UNIV CONNECTICUT,CTR HLTH,DEPT MICROBIOL,FARMINGTON,CT 06030. NIAID,VIRAL DIS LAB,NIH,BETHESDA,MD 20892. OI Weller, Sandra/0000-0002-4519-6276 FU PHS HHS [A121747] NR 71 TC 66 Z9 66 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD FEB 14 PY 1997 VL 272 IS 7 BP 4623 EP 4630 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WH019 UT WOS:A1997WH01900107 PM 9020191 ER PT J AU Leggatt, GR AlexanderMiller, MA Kumar, A Hoffman, SL Berzofsky, JA AF Leggatt, GR AlexanderMiller, MA Kumar, A Hoffman, SL Berzofsky, JA TI Cytotoxic T lymphocyte (CTL) adherence assay (CAA): A non-radioactive assay for murine CTL recognition of peptide-MHC class I complexes SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE cytotoxic T lymphocyte; cell adhesion; chromium release assay; peptide epitope; non-radioactive ID RELEASE-ASSAY; CYTO-TOXICITY; ACTIVATION; ADHESION; EPITOPE; PROTEIN AB Cytotoxic T lymphocytes (CTL) form an important immune surveillance system against intracellular pathogens. Here we describe a simple, visual assay for identifying peptides specifically recognized by CTL, based on the discovery that CTL develop increased adhesive properties upon TCR triggering. Several CTL lines were shown to pellet to the bottom of a round bottom 96-well plate in the absence of peptide. In contrast, these same CTL lines incubated with their cognate peptide, allowing them to present peptide to each other, adhered to the sides of the well and were readily distinguished by macroscopic visual examination of the plate after 4-5 h or overnight incubation. This CTL adherence assay (CAA) demonstrated peptide specificity and MHC restriction, and was titratable with peptide concentration. With this technique, a minimal-sized, malaria CTL epitope was correctly identified from a panel of overlapping nonamers, although the adherence pattern of two mono-substituted, variant peptides was less predictive of lytic activity. Also, substitutions in an HIV-1 envelope CTL epitope that reduced lytic activity were correctly predicted. Inhibitors of RNA and protein synthesis, upon preincubation, abrogated the adherence, indicating, at minimum, a need for live cells. Wortmannin, a PI-3 kinase inhibitor, inhibited the peptide specific adherence, consistent with a role for TCR or integrin signal transduction in CAA. Other cytoskeletal and metabolic inhibitors had no effect. Adherence of the T cells may involve low affinity, nonspecific interactions since wells coated with FCS, BSA or milk powder all produced an effective CAA in the presence of peptide under serum foe conditions. Consequently, CAA may represent a rapid, simple method for screening large numbers of peptides to find cytolytic epitopes for a given CTL line and may identify additional epitopes causing T cell activation and adherence but not cytolytic activity. C1 NCI,MOL IMMUNOGENET & VACCINE RES SECT,METAB BRANCH,NIH,BETHESDA,MD 20892. USN,MED RES INST,MALARIA PROGRAM,BETHESDA,MD 20889. RI Leggatt, Graham/G-1924-2010; OI Leggatt, Graham/0000-0002-4078-5653 NR 27 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-1759 J9 J IMMUNOL METHODS JI J. Immunol. Methods PD FEB 14 PY 1997 VL 201 IS 1 BP 1 EP 10 DI 10.1016/S0022-1759(96)00203-7 PG 10 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA WH620 UT WOS:A1997WH62000001 PM 9053406 ER PT J AU Hamawy, MM Siraganian, RP AF Hamawy, MM Siraganian, RP TI Large scale isolation of intact rat basophilic leukemia (RBL-2H3) cells SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE RBL-2H3 cell; mast cell; basophil; Fc epsilon RI collagenase; cell isolation ID PROTEIN-TYROSINE PHOSPHORYLATION; FC-EPSILON-RI; HIGH-AFFINITY; IMMUNOGLOBULIN-E; RECEPTOR; IGE; AGGREGATION; FIBRONECTIN; COMPONENT; ADHERENCE AB The rat basophilic leukemia RBL-2H3 mast cell line is widely used for studies of the structure and function of the high affinity IgE receptor (Fc epsilon RI). Here we report on a simple method to isolate large numbers of intact RBL-2H3 cells from tumors produced by injection of the cells into newborn rats. Collagenase treatment of rat tumors yields approximately 3.5 x 10(8) viable cells/animal. Aggregating Fc epsilon RI on these cells induced tyrosine phosphorylation of proteins including the protein tyrosine kinase Syk. This procedure should prove useful for the isolation and characterization of cellular molecules important for mast cell and basophil function. RP Hamawy, MM (reprint author), NIDR,IMMUNOL LAB,NIH,BLDG 10,RM 1N106,BETHESDA,MD 20892, USA. NR 12 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-1759 J9 J IMMUNOL METHODS JI J. Immunol. Methods PD FEB 14 PY 1997 VL 201 IS 1 BP 11 EP 14 DI 10.1016/S0022-1759(96)00197-4 PG 4 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA WH620 UT WOS:A1997WH62000002 PM 9032405 ER PT J AU Bahar, I Jernigan, RL AF Bahar, I Jernigan, RL TI Inter-residue potentials in globular proteins and the dominance of highly specific hydrophilic interactions at close separation SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE potentials of mean force; globular protein structures; radial distribution functions; homogeneous interactions; specific interactions ID AMINO-ACID-RESIDUES; SIDE-CHAINS; MEAN FORCE; CONFORMATIONS; HYDROPHOBICITY; PREDICTION; MODELS; SIMULATION; ENSEMBLES; SEQUENCE AB Residue-specific potentials between pairs of side-chains and pairs of sidechain-backbone interaction sites have been generated by collecting radial distribution data for 302 protein structures. Multiple atomic interactions have been utilized to enhance the specificity and smooth the distance-dependence of the potentials. The potentials are demonstrated to successfully discriminate correct sequences in inverse folding experiments. Many specific effects are observable in the non-bonded potentials; grouping of residue types is inappropriate, since each residue type manifests some unique behavior. Only a weak dependence is seen on protein size and composition. Effective contact potentials operating in three different environments (self, solvent-exposed and residue-exposed) and over any distance range are presented. The effective contact potentials obtained from the integration of radial distributions over the distance interval r less than or equal to 6.4 Angstrom are in excellent agreement with published values. The hydrophobic interactions are verified to be dominantly strong in this range. Comparison of these with a newly derived set of effective contact potentials for closer inter-residue separations (r less than or equal to 4.0 Angstrom) demonstrates drastic changes in the most favorable interactions. In the closer approach case, where the number of pairs with a given residue is approximately one, the highly specific interactions between charged and polar side-chains predominate. These closer approach values could be utilized to select successively the relative positions and directions of residue side-chains in protein simulations, following a hierarchical algorithm optimizing side-chain-side-chain interactions over the two successively closer distance ranges. The homogeneous contribution to stability is stronger than the specific contribution by about a factor of 5. Overall, the total non-bonded interaction energy calculated for individual proteins follows a dependence on the number of residues of the form of n(1.28), indicating an enhanced stability for larger proteins. (C) 1997 Academic Press Limited. C1 NCI,MOL STRUCT SECT,MATH BIOL LAB,DIV BASIC SCI,NIH,BETHESDA,MD 20892. BOGAZICI UNIV,DEPT CHEM ENGN,TR-80815 BEBEK,ISTANBUL,TURKEY. BOGAZICI UNIV,CTR POLYMER RES,TR-80815 BEBEK,ISTANBUL,TURKEY. TUBITAK,ADV POLYMER MAT RES CTR,TR-80815 BEBEK,ISTANBUL,TURKEY. RI Jernigan, Robert/A-5421-2012 NR 49 TC 223 Z9 229 U1 1 U2 10 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD FEB 14 PY 1997 VL 266 IS 1 BP 195 EP 214 DI 10.1006/jmbi.1996.0758 PG 20 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WH768 UT WOS:A1997WH76800017 PM 9054980 ER PT J AU Shelby, MD Tindall, KR AF Shelby, MD Tindall, KR TI Mammalian germ cell mutagenicity of ENU, IPMS and MMS, chemicals selected for a transgenic mouse collaborative study SO MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS LA English DT Article DE dominant lethal; heritable translocation; specific locus test; genetic risk; DNA alkylation ID ETHYL-N-NITROSOUREA; MONOFUNCTIONAL ALKYLATING-AGENTS; NUCLEOTIDE EXCISION-REPAIR; DOMINANT-LETHAL MUTATIONS; METHYL METHANESULFONATE; DNA-REPAIR; MOLECULAR ANALYSIS; DROSOPHILA-MELANOGASTER; HPRT LOCUS; MALE-MICE AB A collaborative study to systematically assess transgenic mouse mutation assays as screens for germ cell mutagens has been conducted, Three male mouse germ cell mutagens (ENU, iPMS and MMS) were selected for testing. This paper provides a brief review of the effects reported for those 3 chemicals in the most commonly used non-transgenic germ cell mutagenicity assays, namely the dominant lethal, heritable translocation, and specific locus tests, Additionally, information on the DNA reactivity and the molecular nature of mutations induced by these chemicals is summarized. C1 NIEHS,MOL MUTAGENESIS GRP,RES TRIANGLE PK,NC 27709. RP Shelby, MD (reprint author), NIEHS,REPROD TOXICOL GRP,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 65 TC 16 Z9 18 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1383-5718 J9 MUTAT RES-GEN TOX EN JI Mutat. Res. Genet. Toxicol. Environ. Mutagen. PD FEB 14 PY 1997 VL 388 IS 2-3 BP 99 EP 109 DI 10.1016/S1383-5718(96)00106-4 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA WP827 UT WOS:A1997WP82700002 PM 9057870 ER PT J AU Ashby, J Gorelick, NJ Shelby, MD AF Ashby, J Gorelick, NJ Shelby, MD TI Mutation assays in male germ cells from transgenic mice: Overview of study and conclusions SO MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS LA English DT Article AB Three confirmed mouse germ cell mutagens, ethyl nitrosourea (ENU), isopropyl methanesulphonate (iPMS) and methyl methanesulphonate (MMS), have been evaluated for their activity as mutagens to the germ cell DNA of two strains of transgenic mice (lac I, Big Blue(TM) and LacZ, Muta(TM)Mouse), Both testicular DNA and epididymal sperm DNA were evaluated. A range of sampling times was studied, from 3 days post-dosing to 100 days post-dosing. ENU and iPMS were mutagenic to both testicular DNA and epididymal sperm DNA. Mutant frequencies were higher for both chemicals in DNA recovered from testicular tissue than in epididymal sperm DNA. Likewise, mutant frequencies were higher for both DNA samples at the later sampling times. MMS was not mutagenic under any condition of test. A good level of qualitative agreement in test results was seen for the two assays and for the same assays conducted in different laboratories, The level of quantitative agreement was not as high, but was, nonetheless, generally good. Recommendations for the future conduct of transgenic rodent germ cell mutation assays are made. The test data are discussed within the context of the larger question of how such assays should be integrated into the chemical hazard assessment process. C1 PROCTER & GAMBLE CO,MIAMI VALLEY LABS,CINCINNATI,OH 45253. NIEHS,RES TRIANGLE PK,NC 27709. RP Ashby, J (reprint author), ZENECA CENT TOXICOL LAB,ALDERLEY PK,MACCLESFIELD SK10 4TJ,CHESHIRE,ENGLAND. NR 10 TC 21 Z9 21 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1383-5718 J9 MUTAT RES-GEN TOX EN JI Mutat. Res. Genet. Toxicol. Environ. Mutagen. PD FEB 14 PY 1997 VL 388 IS 2-3 BP 111 EP 122 DI 10.1016/S1383-5718(96)00107-6 PG 12 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA WP827 UT WOS:A1997WP82700003 PM 9057871 ER PT J AU Eglitis, MA Schneiderman, RD AF Eglitis, MA Schneiderman, RD TI Transduction of human hematopoietic progenitor cells with retroviral vectors based on the gibbon ape leukemia virus SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID GENE-TRANSFER; CULTURE AB Gene transfer into human hematopoietic stem cells continues to be complicated by issues of transfer efficiency. We have examined the capacity of newly described retroviral vectors based on the gibbon ape leukemia virus (GaLV) to introduce genes into human hematopoietic progenitor cells. Total nucleated human bone marrow cells were transduced using GaLV vectors packaged with either amphotropic or GaLV envelopes. Transduction efficiency was assayed by the generation of G418-resistant colony forming units. We found that GaLV vectors could transduce both BFU-E and CFU-C hematopoietic progenitors, and that their efficiency was at least equivalent to an amphotropically packaged Moloney mouse leukemia virus (MoMLV)-based vector. Moreover, vectors derived from the GaLV-SEATO strain and bearing amphotropic envelope were best for gene transfer into BFU-E, whereas vectors derived from the GaLV-SF strain and bearing GaLV envelope transduced CFU-C at higher efficiency. Thus, GaLV-based retroviral vectors are promising new tools for gene transfer into human hematopoietic cells. (C) 1997 Academic Press. C1 NIMH,CELL BIOL LAB,BETHESDA,MD 20892. NR 12 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD FEB 13 PY 1997 VL 231 IS 2 BP 477 EP 480 DI 10.1006/bbrc.1997.6130 PG 4 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA WK069 UT WOS:A1997WK06900049 PM 9070304 ER PT J AU Okumura, K Kaneko, Y Nonoguchi, K Nishiyama, H Yokoi, H Higuchi, T Itoh, K Yoshida, O Miki, T Fujita, J AF Okumura, K Kaneko, Y Nonoguchi, K Nishiyama, H Yokoi, H Higuchi, T Itoh, K Yoshida, O Miki, T Fujita, J TI Expression of a novel isoform of Vav, Vav-T, containing a single Src homology 3 domain in murine testicular germ cells SO ONCOGENE LA English DT Article DE testis; vav; vav-T; Src homology 3 ID TYROSINE PHOSPHORYLATION; PROTOONCOGENE PRODUCT; HEMATOPOIETIC-CELLS; EXCHANGE FACTOR; STEEL FACTOR; SH2 DOMAIN; B-CELLS; PROTEIN; KINASE; FIBROBLASTS AB Vav is a signal transducing molecule containing C-terminal Src homology 3 (SH3)-SH2-SH3 domains, and has been thought to be expressed exclusively in hematopoietic and trophoblastic cells, By Northern blot analysis, vav transcripts of unique sizes, 4.8 kb and 1.0 kb, were detected in the testis among various tissues examined, From a mouse spermatocyte cDNA library, a novel isoform of vav (vav-T) was cloned, which corresponded to a part of the 4.8 kb transcript, Vav-T had an alternative 5' sequence up to the middle of SH2-coding region, and encoded 163 amino acids with a single SH3 domain, Northern blot analysis of fractionated testicular cells and in situ hybridization histochemistry demonstrated that vav-T transcripts were expressed in the differentiating germ cells, especially spermatocytes. A 24 kD protein was detected by anti-Vav antibodies in the testis, but not in the spleen or bone marrow, Transcripts of heterogeneous nuclear ribonucleoprotein K, known to associate with the most C-terminal SH3 domain of Vav, were also detected in the differentiating male germ cells, These results demonstrate expression of previously nondescribed Vav-isoform in the testicular germ cells, and suggest that it interacts with RNA-binding proteins and plays an important role in spermatogenesis. C1 KYOTO UNIV,FAC MED,DEPT CLIN MOL BIOL,KYOTO 60601,JAPAN. KYOTO UNIV,FAC MED,DEPT UROL,KYOTO 60601,JAPAN. NCI,CELLULAR & MOL BIOL LAB,NIH,BETHESDA,MD 20892. NR 40 TC 14 Z9 14 U1 0 U2 2 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD FEB 13 PY 1997 VL 14 IS 6 BP 713 EP 720 DI 10.1038/sj.onc.1200878 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA WG430 UT WOS:A1997WG43000010 PM 9038379 ER PT J AU Peters, R Sikorski, R AF Peters, R Sikorski, R TI Navigating to knowledge - Tools for finding information on the Internet SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article C1 HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOL PHARMACOL,BOSTON,MA 02115. NATL CANC INST,BETHESDA,MD. RP Peters, R (reprint author), MASSACHUSETTS GEN HOSP,DEPT MED,WANG BLDG,ACC-1,FRUIT ST,BOSTON,MA 02114, USA. NR 5 TC 15 Z9 15 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD FEB 12 PY 1997 VL 277 IS 6 BP 505 EP 506 DI 10.1001/jama.277.6.505 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA WG054 UT WOS:A1997WG05400042 PM 9020277 ER PT J AU Trouillas, P Takayanagi, T Hallett, M Currier, RD Subramony, SH Wessel, K Bryer, A Diener, HC Massaquoi, S Gomez, CM Coutinho, P BenHamida, M Campanella, G Filla, A Schut, L Timann, D Honnorat, J Nighoghossian, N Manyam, B AF Trouillas, P Takayanagi, T Hallett, M Currier, RD Subramony, SH Wessel, K Bryer, A Diener, HC Massaquoi, S Gomez, CM Coutinho, P BenHamida, M Campanella, G Filla, A Schut, L Timann, D Honnorat, J Nighoghossian, N Manyam, B TI International Cooperative Ataxia Rating Scale for pharmacological assessment of the cerebellar syndrome SO JOURNAL OF THE NEUROLOGICAL SCIENCES LA English DT Article DE cerebellar ataxia; rating scale; controlled double-blind drug placebo studies; cooperative international trials; World Federation of Neurology ID OCULAR REFLEX; ANTERIOR LOBE; EYE-MOVEMENTS; DOUBLE-BLIND; ATROPHY; 5-HYDROXYTRYPTOPHAN; IMPROVEMENT; NYSTAGMUS; TRIAL AB Despite the involvement of cerebellar ataxia in a large variety of conditions and its frequent association with other neurological symptoms, the quantification of the specific core of the cerebellar syndrome is possible and useful in Neurology, Recent studies have shown that cerebellar ataxia might be sensitive to various types of pharmacological agents, but the scales used for assessment were all different. With the long-term goal of double-blind controlled trials-multicentric and international-an ad hoc Committee of the World Federation of Neurology has worked to propose a one-hundred-point semi-quantitative International Cooperative Ataxia Rating Scale (ICARS), The scale proposed involves a compartimentalized quantification of postural and stance disorders, limb ataxia, dysarthria and oculomotor disorders, in order that a subscore concerning these symptoms may be separately studied, The weight of each symptomatologic compartment has been carefully designed, The members of the Committee agreed upon precise definitions of the tests, to minimize interobserver variations. The validation of this scale is in progress. (C) 1997 Elsevier Science B.V. C1 HOP NEUROL, ATAXIA RES CTR, F-69003 LYON, FRANCE. HOP NEUROL, CEREBROVASC UNIT, F-69003 LYON, FRANCE. UNIV LYON 1, F-69003 LYON, FRANCE. NARA MED UNIV, DEPT NEUROL, NARA, JAPAN. NINCDS, NIH, BETHESDA, MD 20892 USA. UNIV MISSISSIPPI, SCH MED, DEPT NEUROL, JACKSON, MI USA. UNIV LUBECK, NEUROL CLIN, D-2400 LUBECK, GERMANY. GROOTE SCHUUR HOSP, NEUROL UNIT, ZA-7925 CAPE TOWN, SOUTH AFRICA. UNIV ESSEN GESAMTHSCH, NEUROL CLIN, ESSEN, GERMANY. UNIV MINNESOTA, ATAXIA CTR, MINNEAPOLIS, MN 55455 USA. SANTO ANTONIO HOSP, NEUROL SERV, OPORTO, PORTUGAL. HOP RABTA, NATL NEUROL CTR, TUNIS, TUNISIA. UNIV NAPLES FEDERICO II, NEUROL CLIN, NAPLES, ITALY. UNITED HOSP, PAIN CTR, ST PAUL, MN USA. SO ILLINOIS UNIV, SCH MED, DEPT NEUROL, SPRINGFIELD, IL USA. RI Coutinho, Paula/K-6053-2013; Nighoghossian, Norbert/H-7492-2014; OI Coutinho, Paula/0000-0002-3461-230X NR 46 TC 655 Z9 668 U1 1 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-510X J9 J NEUROL SCI JI J. Neurol. Sci. PD FEB 12 PY 1997 VL 145 IS 2 BP 205 EP 211 DI 10.1016/S0022-510X(96)00231-6 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA WN171 UT WOS:A1997WN17100012 PM 9094050 ER PT J AU Sanakis, Y Goussias, C Mason, RP Petrouleas, V AF Sanakis, Y Goussias, C Mason, RP Petrouleas, V TI NO interacts with the tyrosine radical Y-D(center dot) of photosystem II to form an iminoxyl radical SO BIOCHEMISTRY LA English DT Article ID ELECTRON-PARAMAGNETIC-RES; SITE-DIRECTED MUTANTS; NITRIC-OXIDE; RIBONUCLEOTIDE REDUCTASE; SPIN RESONANCE; ACCEPTOR-SIDE; OXIDATION; MEMBRANES; PARTICLES; WATER AB Incubation of photosystem II, PSII, membranes with NO for a few minutes results in the reversible elimination of the electron paramagnetic resonance (EPR) signal II from the oxidized Tyr Y-D ., presumably due to the formation of a weak Tyr Y-D .-NO complex [Petrouleas, V., & Diner, B. A. (1990) Biochim. Biophys. Acta 1015, 131-140]. Illumination of such a sample at ambient or cryogenic temperatures produces no new EPR signals. If, however, the incubation with NO is extended to the hours time range, illumination induces an EPR signal with resolved hyperfine structure in the g=2 region. The signal shows the typical features of an immobilized iminoxyl radical (>C=NO .) with hyperfine values A(parallel to)=44 G, A(perpendicular to)=22 G, and A(iso)=29.3 G. The following observations suggest that the iminoxyl signal is associated with PSII: (a) the signal results from an immobilized species at room temperature probably associated with a membrane-bound component, (b) the abundance of the signal is (sub)-stoichiometric to PSII, (c) the signal is light-induced, (d) some of the treatments that affect PSII (Tris, Ca2+ depletion, high-salt wash) severely diminish the size of the signal, and (e) the development of the signal correlates with the release of Mn. In addition, the following observations suggest that the iminoxyl signal results from an interaction of Y-D . with NO: (a) the evolution of the signal correlates with the loss in reversibility of the Tyr Y-D .-NO interaction and (b) the size of the signal correlates with the initial amount of oxidized Tyr Y-D. It is accordingly proposed that during the incubation with NO, a weak Tyr Y-D .-NO complex is rapidly formed and is then slowly converted to a tyrosine-nitroso adduct. Light induced oxidation of the latter produces the iminoxyl radical. The nitrosotyrosine is expected to have an oxidation potential significantly lower than the parent tyrosine and can act as an efficient electron donor in PSII even at cryogenic temperatures, It is probably this lowered redox potential of the tyrosine Y-D that explains the release of Mn concomitant with the formation of the nitroso species. C1 NCSR DEMOKRITOS,INST MAT SCI,AGHIA PARASKEVI 15310,ATHENS,GREECE. NIEHS,MOL BIOPHYS LAB,NIH,RES TRIANGLE PK,NC 27709. NR 37 TC 52 Z9 53 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD FEB 11 PY 1997 VL 36 IS 6 BP 1411 EP 1417 DI 10.1021/bi9622074 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WH050 UT WOS:A1997WH05000025 PM 9063889 ER PT J AU Elwood, PC Nachmanoff, K Saikawa, Y Page, ST Pacheco, P Roberts, S Chung, KN AF Elwood, PC Nachmanoff, K Saikawa, Y Page, ST Pacheco, P Roberts, S Chung, KN TI The divergent 5' termini of the alpha human folate receptor (hFR) mRNAs originate from two tissue-specific promoters and alternative splicing: Characterization of the alpha hFR gene structure SO BIOCHEMISTRY LA English DT Article ID HUMAN KB CELLS; BINDING-PROTEIN; GENOMIC ORGANIZATION; FUNCTIONAL-ANALYSIS; HUMAN-PLACENTA; MESSENGER-RNA; RETINOIC ACID; 2 PROMOTERS; EXPRESSION; MEMBRANE AB The human KB cell or alpha folate receptor (alpha hFR) is a membrane glycoprotein of 42 kDa that participates in the internalization of folates and antifolates. Seven independent alpha hFR cDNA isoforms have been reported that contain unique 5' termini but share a common open reading frame (ORF). To investigate the molecular basis of these heterogeneous 5' sequences, we determined the sequence of the alpha hFR gene from two clones isolated from a human lymphocyte lambda DASH genomic library. The gene is composed of seven exons that span 6.8 kb. The ORF is encoded by exons 4 through 7 while the reported 5' termini of the cDNA isoforms (including two novel cDNAs designated KB2 and KB4) are encoded by exons 1 through 4. Using RNase protection assays, we demonstrate that transcripts corresponding to the KB1 and KB4 cDNAs originate from promoters upstream from exon 1 and exon 4, designated P1 and P4, respectively, and that these mRNA isoforms are the most abundant transcripts expressed in KB cells and selected normal tissues (including kidney, lung, and cerebellum). We observed a heterogeneous start site within exon 1 from the P1 promoter while transcripts from the P4 promoter originate from a single site. In addition, we detected tissue specificity for the P1 and P4 promoter utilization. Transcripts originating from the P1 promoter are the most abundant transcripts expressed by human cerebellum and kidney. In contrast, transcripts from the P4 promoter are the most abundant transcripts expressed by human KB cells and lung. Total RNA from KB cells also protects a 66 bp fragment of an exon 3 riboprobe that is consistent with an alternatively spliced transcript. To examine the functional activity of the predicted P1 and P4 promoters, alpha hFR promoter-CAT chimeric plasmids were constructed using sequences flanking exon 1 and exon 4. We observed a 7.5- and 10-fold increase in CAT activity in HeLa cells transiently transfected with the P1 and P4 promoter constructs, respectively. These data demonstrate that a single gene encodes the divergent 5' termini of the alpha hFR cDNAs and that the alpha hFR transcripts are transcribed from two promoters that are activated in a tissue-specific manner. C1 UNIV WASHINGTON,SCH MED,SEATTLE,WA 98105. KANAZAWA UNIV,KANAZAWA,ISHIKAWA 920,JAPAN. BROWN UNIV,SCH MED,PROVIDENCE,RI 02912. RP Elwood, PC (reprint author), NCI,SECT EXPT HEMATOL,MB,DCS,BLDG 10 ROOM 12N226,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Pacheco, Pablo/I-6762-2016 OI Pacheco, Pablo/0000-0001-5692-2627 NR 53 TC 44 Z9 47 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD FEB 11 PY 1997 VL 36 IS 6 BP 1467 EP 1478 DI 10.1021/bi962070h PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WH050 UT WOS:A1997WH05000031 PM 9063895 ER PT J AU Kostenis, E Conklin, BR Wess, J AF Kostenis, E Conklin, BR Wess, J TI Molecular basis of receptor/G protein coupling selectivity studied by coexpression of wild type and mutant m2 muscarinic receptors with mutant G alpha(q) subunits SO BIOCHEMISTRY LA English DT Article ID HETEROTRIMERIC G-PROTEINS; ACETYLCHOLINE-RECEPTOR; PHOSPHOLIPASE-C; ALPHA-SUBUNITS; SPECIFICITY; HYDROLYSIS; ACTIVATION; BINDING; IDENTIFICATION; MUTAGENESIS AB The molecular basis of receptor/G protein coupling selectivity was studied by using the m2 muscarinic receptor, a prototypical G(i/o)-coupled receptor as a model system, We could recently show that the m2 receptor can efficiently interact with mutant G protein alpha(q) subunits in which the last five amino acids were replaced with alpha(i2) or alpha(o) sequence [Liu, J., Conklin, B. R., Blin, N., Yun, J., & Wess, J, (1995) Proc, Natl. Acad. Sci. U.S.A. 92, 11642-1164]. Additional mutagenesis studies led to the identification of a four-amino-acid motif on the m2 receptor (Val(385), Thr(386), Ile(389), and Leu(390)) that is predicted to functionally interact with the C-terminal portion of a(i/o) subunits. To further investigate the structural requirements for this interaction to occur, these four m2 receptor residues were replaced, either individually or in combination: with the corresponding residues present in the G(q/11) coupled muscarinic receptors (m1, m3, and m5). The ability of the resulting mutant m2 receptors to interact with a mutant alpha(q) subunit (qo5) in which the last five amino acids were replaced with alpha(o) sequence was investigated in co-transfected COS-7 cells [studied biochemical response: stimulation of phosphatidyl inositol (PI) hydrolysis]. Our data suggest that the presence of three of the four targeted m2 receptor residues (Val(385), Thr(386), and Ile(389)) is essential for efficient recognition of C-terminal alpha(i/o) sequences. To study which specific amino acids within the C-terminal segment of alpha(i/o) subunits are critical for this interaction to occur, the wild type m2 receptor was co-expressed with a series of mutant a, subunits containing single or multiple alpha(q)-->alpha(il,2) point mutations at their C-terminus. Remarkably, the wild type m2 receptor, while unable to efficiently stimulate wild type alpha(q), gained the ability to productively interact with three alpha(q) single-point mutants, providing the first example that the receptor coupling selectivity of G protein ct subunits can be switched by single amino acid substitutions. Given the high degree of structural homology among different G protein-coupled receptors and among different classes of G protein alpha subunits, our results should be of broad general relevance. C1 NIDDKD,BIOORGAN CHEM LAB,BETHESDA,MD 20892. UNIV CALIF SAN FRANCISCO,GLADSTONE INST CARDIOVASC DIS,DEPT MED,SAN FRANCISCO,CA 94141. UNIV CALIF SAN FRANCISCO,GLADSTONE INST CARDIOVASC DIS,DEPT PHARMACOL,SAN FRANCISCO,CA 94141. NR 42 TC 82 Z9 84 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD FEB 11 PY 1997 VL 36 IS 6 BP 1487 EP 1495 DI 10.1021/bi962554d PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WH050 UT WOS:A1997WH05000033 PM 9063897 ER PT J AU Levin, MD Kubke, MF Schneider, M Wenthold, R Carr, CE AF Levin, MD Kubke, MF Schneider, M Wenthold, R Carr, CE TI Localization of AMPA-selective glutamate receptors in the auditory brainstem of the barn owl SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE excitatory amino acids; glutamate receptor subunits; central auditory system ID AVIAN COCHLEAR NUCLEUS; DIFFERENTIAL EXPRESSION PATTERNS; INTERAURAL TIME DIFFERENCES; D-ASPARTATE RECEPTORS; RAT-BRAIN; SYNAPTIC TRANSMISSION; INFERIOR COLLICULUS; MESSENGER-RNAS; NEURAL MAP; SUPERIOR OLIVE AB AMPA receptor subunit-specific antibodies were used to determine if the distribution of excitatory amino acid receptors in the owl's auditory brainstem and midbrain nuclei reflected specializations for temporal processing. Each auditory nucleus displays characteristic levels of immunostaining for the AMPA receptor subunits GluR1-4, with high levels of the subtypes which exhibit rapid desensitization (GluR4 and 2/3). In the auditory brainstem, levels of GluR2/3 and GluR4 were very high in the cochlear nucleus magnocellularis and the nucleus laminaris. The different cell types of the cochlear nucleus angularis and the superior olive were characterized by heterogeneous GluR2/3 and 4 immunostaining. GluR1 levels were very low or undetectable. In the lemniscal nuclei, most neurons contained low levels of GluR1, and dense GluR2/3 and GluR4 immunoreactivity, with high levels of GluR4 in the dendrites. Levels of GluR4 were higher in the anterior portion of the ventral nucleus of the lateral lemniscus. The divisions of the inferior colliculus could be distinguished on the basis of GluR1-4 immunoreactivity, with high levels of GluR4 and moderate levels of GluR1 in the external nucleus. No major differences were observed between the pathways for encoding time and sound level cues. (C) 1997 Wiley-Liss, Inc. C1 UNIV MARYLAND,DEPT ZOOL,COLLEGE PK,MD 20742. YORK COLL PENN,DEPT BIOL,YORK,PA 17405. NIDCD,NEUROCHEM LAB,NIH,BETHESDA,MD 20892. RI Kubke, Maria Fabiana/E-2472-2011; Kubke, M Fabiana/H-3320-2012; Levin, Mark/B-2723-2009; OI Levin, Mark/0000-0002-2241-9828; Kubke, Maria Fabiana/0000-0002-3351-5225 FU NIDCD NIH HHS [DCD 00436] NR 77 TC 42 Z9 42 U1 0 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD FEB 10 PY 1997 VL 378 IS 2 BP 239 EP 253 DI 10.1002/(SICI)1096-9861(19970210)378:2<239::AID-CNE7>3.0.CO;2-4 PG 15 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA WF855 UT WOS:A1997WF85500007 PM 9120063 ER PT J AU Nakajima, T Wang, RS Elovaara, E Gonzalez, FJ Gelboin, HV Raunio, H Pelkonen, O Vainio, H Aoyama, T AF Nakajima, T Wang, RS Elovaara, E Gonzalez, FJ Gelboin, HV Raunio, H Pelkonen, O Vainio, H Aoyama, T TI Toluene metabolism by cDNA-expressed human hepatic cytochrome P450 SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE human cytochrome P450; rat cytochrome P450; mouse cytochrome P450; toluene metabolism; human liver microsomes; smoking ID INDUCED RAT-LIVER; CATALYTIC ACTIVITY; VACCINIA VIRUS; MUTAGEN ACTIVATION; ACID; SEQUENCE; HYDROXYLATION; MICROSOMES; ISOZYMES; PRODUCT AB The metabolism of toluene in human liver microsomes and by cDNA-expressed human cytochrome P450s (CYPs) was investigated. Toluene was metabolized mainly to benzyl alcohol and slightly to o- and p-cresol by human liver microsomes. Formation of o-cresol was elevated in microsomes from human livers derived from cigarette smokers, but the induced CYP isoforms were not clear. Of the eleven human CYP forms studied, CYP2E1 was the most active in forming benzyl alcohol, followed by CYP2B6, CYP2C8, CYP1A2, and CYP1A1, in that order. The activities of CYP2A6, CYP2C9. CYP2D6, CYP3A3, CYP3A4, and CYP3A5 were negligible. In addition, CYP2B6 and CYP2E1 catalyzed the formation of p-cresol (11-12% of total metabolites), and CYP1A2 catalyzed the formation of both o-(22%) and e-cresol (35%). The relationship between the amino acid sequence of rat CYP2B1 cDNA and the activity for toluene metabolism was investigated using variants, because of great differences in the forming of toluene ring products between CYP2B1 and CYP2B6. These results suggest that the structure of CYP2B1 at the site of Leu 58 rather than Ile-114 and Glu-282 plays an important role in the formation of toluene ring products, whereas in CYP2B1 Ile-114 plays an important role in the formation of benzyl alcohol. These results may explain, In part, the lower activity of CYP2B6, which has Phe at position 58 of the protein, for toluene ring oxidations than that of CYP2B1. Copyright (C) 1997 Elsevier Science Inc. C1 SHINSHU UNIV,SCH MED,DEPT BIOCHEM,MATSUMOTO,NAGANO 390,JAPAN. FINNISH INST OCCUPAT HLTH,DEPT IND HYG & TOXICOL,FIN-00250 HELSINKI,FINLAND. NCI,MOL CARCINOGENESIS LAB,BETHESDA,MD 20892. UNIV OULU,DEPT PHARMACOL & TOXICOL,FIN-90220 OULU,FINLAND. RP Nakajima, T (reprint author), SHINSHU UNIV,SCH MED,DEPT HYG,MATSUMOTO,NAGANO 390,JAPAN. NR 28 TC 35 Z9 43 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD FEB 7 PY 1997 VL 53 IS 3 BP 271 EP 277 DI 10.1016/S0006-2952(96)00652-1 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA WK589 UT WOS:A1997WK58900004 PM 9065730 ER PT J AU Simpson, JN Zhang, WQ Bing, GY Hong, JS AF Simpson, JN Zhang, WQ Bing, GY Hong, JS TI Kainic acid-induced sprouting of dynorphin- and enkephalin-containing mossy fibers in the dentate gyrus of the rat hippocampus SO BRAIN RESEARCH LA English DT Article DE immunocytochemistry; opioid peptide; recurrent seizure; epilepsy; hippocampal plasticity ID TEMPORAL-LOBE EPILEPSY; SYNAPTIC REORGANIZATION; STATUS EPILEPTICUS; FASCIA-DENTATA; IMMUNOREACTIVITY; SEIZURES; TRANSCRIPTION; LOCALIZATION; SYNAPTOSOMES; PLASTICITY AB This study utilized Timm histochemistry and immunocytochemistry to determine the prolonged effects of kainic acid on the distribution of dynorphin- and enkephalin-containing messy fibers in the rat dentate gyrus at progressive time points following kainic acid injection. Beginning 1-2 weeks after kainic acid administration, a progressive increase in the distribution and intensity of staining for supragranular zinc, dynorphin and enkephalin was observed in the dentate gyrus. The kainic acid-induced sprouting of messy fibers containing dynorphin and enkephalin strongly resembles the pattern observed in the dentate gyrus of humans with temporal lobe epilepsy. C1 NIEHS,SYST TOXICOL BRANCH,NEUROPHARMACOL SECT,NIH,RES TRIANGLE PK,NC 27709. UNIV N CAROLINA,CHAPEL HILL,NC 27599. OI Bing, Guoying/0000-0003-0609-8152 NR 41 TC 11 Z9 16 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 FEB 7 PY 1997 VL 747 IS 2 BP 318 EP 323 DI 10.1016/S0006-8993(96)01248-6 PG 6 WC Neurosciences SC Neurosciences & Neurology GA WJ069 UT WOS:A1997WJ06900017 PM 9046008 ER PT J AU Sax, CM Cvekl, A Piatigorsky, J AF Sax, CM Cvekl, A Piatigorsky, J TI Transcriptional regulation of the mouse alpha A-crystallin gene: Binding of USF to the -7/+5 region SO GENE LA English DT Article DE recombinant DNA; gene expression; eye lens ID HEAT-SHOCK PROTEIN; TATA-LESS PROMOTER; B-CRYSTALLIN; STIMULATES TRANSCRIPTION; IMMUNOREACTIVE ALPHA; INITIATOR ELEMENTS; LENS CRYSTALLINS; START SITE; TFII-I; SEQUENCE AB Lens preferred-expression of the mouse alpha A-crystallin gene (alpha A-cry) is regulated at the transcriptional level by multiple elements located in the 5' flanking region of the gene. Here we present the first analysis of the functional role of the mouse alpha A-cry +1 region and the protein(s) which bind to it. The -7/+5 region of this promoter exhibits sequence similarity with the consensus upstream stimulating factor (USF) transcription factor binding site. A wild type oligodeoxyribonucleotide (oligo) spanning the mouse alpha A-cry -15/+15 region specifically inhibited the activity of a mouse alpha A-cry promoter-cat gene fusion (p alpha A111(a)CAT) in competitive co-transfection studies in the mouse alpha TN4-1 lens cell line, as did an oligo containing the adenovirus 2 major late promoter strong USF binding site. In contrast, an alpha A-cry oligo mutated (-3/+3) within the USE-like binding site did not inhibit p alpha A111(a)CAT activity. Western blot analysis indicated that alpha TN4-1 cells express USF1. Co-transfection of p alpha A111(a)CAT and a USF1 cDNA expression vector into alpha TN4-1 cells resulted in a repression of mouse alpha A-cry promoter activity. Electrophoretic mobility shift analyses (EMSA) demonstrated that proteins in an alpha TN4-1 nuclear extract form a single major complex on synthetic oligos spanning the mouse alpha A-cry - 15/+15 region. The formation of this complex was inhibited by the presence of unlabeled -15/+15 oligos or an anti-USF1 antibody. In addition, purified USF1 bound to this region, producing a complex similar in size to that observed with alpha TN4-1 nuclear extracts. Taken together, our findings show that USF can bind to the mouse alpha A-cry +1 site, and support the possibility that USF plays a role in promoter activity of this gene. Sequence similarities surrounding the +1 region of the alpha A-cry gene of the mouse, mole rat, hamster, and human, as well as the previously observed utilization of USF by different cry promoters suggest that USF contributes to the high expression of many crys in the ocular lens of diverse species. RP Sax, CM (reprint author), NEI,MOL & DEV BIOL LAB,NIH,BLDG 6,ROOM 208,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Cvekl, Ales/B-2427-2013 NR 53 TC 14 Z9 14 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD FEB 7 PY 1997 VL 185 IS 2 BP 209 EP 216 DI 10.1016/S0378-1119(96)00643-9 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA WJ327 UT WOS:A1997WJ32700009 PM 9055817 ER PT J AU Koley, AP Buters, JTM Robinson, RC Markowitz, A Friedman, FK AF Koley, AP Buters, JTM Robinson, RC Markowitz, A Friedman, FK TI Differential mechanisms of cytochrome P450 inhibition and activation by alpha-naphthoflavone SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID POLYCYCLIC AROMATIC-HYDROCARBONS; NATURALLY-OCCURRING FLAVONOIDS; CDNA-DIRECTED EXPRESSION; HUMAN-LIVER-MICROSOMES; CO BINDING-KINETICS; ENDOPLASMIC-RETICULUM; ACTIVE-SITE; BENZO(A)PYRENE; METABOLISM; ENZYMES AB The anticarcinogenicity of some flavonoids has been attributed to modulation of the cytochrome P450 enzymes, which metabolize procarcinogens to their activated forms. However, the mechanism by which flavonoids inhibit some P450-mediated activities while activating others is a longstanding, intriguing question, We employed flash photolysis to measure carbon monoxide binding to P450 as a rapid kinetic technique to probe the interaction of the prototype flavonoid alpha-naphthoflavone with human cytochrome P450s 1A1 and 3A4, whose benzo[a]pyrene hydroxylation activities are respectively inhibited and stimulated by this compound, This flavonoid inhibited P450 1A1 binding to benzo[a]pyrene via a classical competitive mechanism. In contrast, alpha-naphthoflavone stimulated P450 3A4 by selectively binding and activating an otherwise inactive subpopulation of this P450 and promoting benzo[a]pyrene binding to the latter. These data indicate that flavonoids enhance activity by increasing the pool of active P450 molecules within this P450 macrosystem. Activators in other biological systems may similarly exert their effect by expanding the population of active receptor molecules. C1 NCI,MOL CARCINOGENESIS LAB,NIH,BETHESDA,MD 20892. NIH,BIOMED ENGN & INSTRUMENTAT PROGRAM,BETHESDA,MD 20892. RI Buters, Jeroen/G-5070-2011; Friedman, Fred/D-4208-2016 NR 41 TC 114 Z9 115 U1 0 U2 6 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD FEB 7 PY 1997 VL 272 IS 6 BP 3149 EP 3152 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WG192 UT WOS:A1997WG19200007 PM 9013547 ER PT J AU Kannan, S DeSantis, M Lohmeyer, M Riese, DJ Smith, GH Hynes, N Seno, M Brandt, R Bianco, C Persico, G Kenney, N Normanno, N MartinezLacaci, I Ciardiello, F Stern, DF Gullick, WJ Salomon, DS AF Kannan, S DeSantis, M Lohmeyer, M Riese, DJ Smith, GH Hynes, N Seno, M Brandt, R Bianco, C Persico, G Kenney, N Normanno, N MartinezLacaci, I Ciardiello, F Stern, DF Gullick, WJ Salomon, DS TI Cripto enhances the tyrosine phosphorylation of Shc and activates mitogen-activated protein kinase (MAPK) in mammary epithelial cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID EPIDERMAL GROWTH-FACTOR; HUMAN BREAST-CANCER; FACTOR RECEPTOR; FAMILY; DIFFERENTIATION; GENE; NEU; AMPHIREGULIN; EXPRESSION; ALPHA AB Cripto-1 (CR-1), a recently discovered protein of the epidermal growth factor (EGF) family; was found to interact with a high affinity, saturable binding site(s) on HC-11 mouse mammary epithelial cells and on several different human breast cancer cell lines. This receptor exhibits specificity for CR-1, since other EGF-related peptides including EGF, transforming growth factor cu, heparin-binding EGF-like growth factor, amphiregulin, epiregulin, betacellulin, or heregulin beta 1 that bind to either the EGF receptor or to other type 1 receptor tyrosine kinases such as erb B-3 or erb B-4 fail to compete for binding, Conversely, CR-1 was found not to directly bind to or to activate the tyrosine kinases associated with Shc EGFR, erb B-2, erb B-3, or erb B-4 either alone or in various pairwise combinations which have been ectopically expressed in Ba/F3 mouse pro-B lymphocyte cells. However, exogenous CR-1 could induce an increase in the tyrosine phosphorylation of 185- and 120-kDa proteins and a rapid (within 3-5 min) increase in the tyrosine phosphorylation of the SH2-containing adaptor proteins p66, p52, and p46 She in mouse mammary HC-11 epithelial cells and in human MDA-MB-453 and SKBr-3 breast cancer cells. CR-1 was also found to promote an increase in the association of the adaptor Grb2-guanine nucleotide exchange factor-mouse son of sevenless (mSOS) signaling complex with tyrosine-phosphorylated She in HC-11 cells. Finally, CR-1 was able to increase p42(erk-2) mitogen-activated protein kinase (MAPK) activity in HC-11 cells within 5-10 min of treatment. These data demonstrate that CR-1 can function through a receptor which activates intracellular components in the ras/raf/MEK/MAPK pathway. C1 NCI,TUMOR IMMUNOL & BIOL LAB,TUMOR GROWTH FACTOR SECT,NIH,BETHESDA,MD 20892. HAMMERSMITH HOSP,ICRF ONCOL UNIT,LONDON,ENGLAND. YALE UNIV,SCH MED,DEPT PATHOL,NEW HAVEN,CT 06520. FRIEDRICH MIESCHER INST,CH-4002 BASEL,SWITZERLAND. IST INT GENET & BIOFIS,NAPLES,ITALY. GEORGETOWN UNIV,VINCENT T LOMBARDI CANC RES CTR,WASHINGTON,DC 20007. UNIV NAPLES,FAC MED & CHIRURG 2,CATTEDRA ONCOL MED 2,I-80131 NAPLES,ITALY. RI SENO, Masaharu /B-2092-2011; OI SENO, Masaharu /0000-0001-8547-6259; Ciardiello, Fortunato/0000-0002-3369-4841; Normanno, Nicola/0000-0002-7158-2605 FU NCI NIH HHS [CA-45708]; NICHD NIH HHS [HD-07149] NR 38 TC 87 Z9 88 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD FEB 7 PY 1997 VL 272 IS 6 BP 3330 EP 3335 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WG192 UT WOS:A1997WG19200033 PM 9013573 ER PT J AU Sanna, MT Razynska, A Karavitis, M Koley, AP Friedman, FK Russu, IM Brinigar, WS Fronticelli, C AF Sanna, MT Razynska, A Karavitis, M Koley, AP Friedman, FK Russu, IM Brinigar, WS Fronticelli, C TI Assembly of human hemoglobin - Studies with Escherichia coli-expressed alpha-globin SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NUCLEAR-MAGNETIC-RESONANCE; HUMAN ADULT HEMOGLOBIN; CONFORMATIONAL DIFFERENCES; BETA-GLOBINS; PROTON-NMR; ASSIGNMENTS; SEQUENCE AB The alpha-globin of human hemoglobin was expressed in Escherichia coli and was refolded with heme in the presence and in the absence of native beta-chains, The functional and structural properties of the expressed alpha-chains were assessed in the isolated state and after assembly into a functional hemoglobin tetramer, The recombinant and native hemoglobins were essentially identical on the basis of sensitivity to effecters (Cl- and 2,3-diphosphaglycerate), Bohr effect, CO binding kinetics, dimer-tetramer association constants, circular dichroism spectra of the heme region, and nuclear magnetic resonance of the residues in the alpha(1) beta(1) and alpha(1) beta(2) interfaces. However, the nuclear magnetic resonance revealed subtle differences in the heme region of the expressed alpha-chain, and the recombinant human normal adult hemoglobin (HbA) exhibited a slightly decreased cooperativity relative to native HbA, These results indicate that subtle conformational changes in the heme pocket can alter hemoglobin cooperativity in the absence of modifications of quaternary interface contacts or protein dynamics, In addition to incorporation into a HbA tetramer, the alpha-globin refolds and incorporates heme in the absence of the partner beta-chain. Although the CO binding kinetics of recombinant alpha-chains were the same as that of native alpha-chains, the ellipticity of the Soret circular dichroism spectrum was decreased and CO binding kinetics revealed an additional faster component. These results show that recombinant alpha-chain assumes alternating conformations in the absence of beta-chain and indicate that the isolated alpha-chain exhibits a higher degree of conformational flexibility than the alpha-chain incorporated into the hemoglobin tetramer. These findings demonstrate the utility of the expressed alpha-globin as a tool for elucidating the role of this chain in hemoglobin structure-function relationships. C1 UNIV MARYLAND,SCH MED,DEPT BIOCHEM & MOL BIOL,BALTIMORE,MD 21201. NCI,MOL CARCINOGENESIS LAB,NIH,BETHESDA,MD 20892. WESLEYAN UNIV,DEPT MOL BIOL & BIOCHEM,HALL ATWATER SHANKLIN LABS,MIDDLETOWN,CT 06459. TEMPLE UNIV,DEPT CHEM,PHILADELPHIA,PA 19122. RI Friedman, Fred/D-4208-2016 FU NHLBI NIH HHS [P01-HL48517] NR 35 TC 15 Z9 15 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD FEB 7 PY 1997 VL 272 IS 6 BP 3478 EP 3486 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WG192 UT WOS:A1997WG19200054 PM 9013594 ER PT J AU Jacobsen, LK Giedd, JN Rajapakse, JC Hamburger, SD Vaituzis, AC Frazier, JA Lenane, MC Rapoport, JL AF Jacobsen, LK Giedd, JN Rajapakse, JC Hamburger, SD Vaituzis, AC Frazier, JA Lenane, MC Rapoport, JL TI Quantitative magnetic resonance imaging of the corpus callosum in childhood onset schizophrenia SO PSYCHIATRY RESEARCH-NEUROIMAGING LA English DT Article DE neurodevelopment; white matter; gray matter; midsagittal ID GRAY-MATTER VOLUME; AFFECTIVE-DISORDER; BRAIN; CHILDREN; SIZE; ABNORMALITIES; MORPHOLOGY; THICKNESS; ORIGINS; ADULTS AB Corpus callosum size has been found to be abnormal in adult schizophrenia, and other studies have implicated abnormal interhemispheric communication in this disorder. To assess continuity with brain abnormalities in the later onset disorder and to further localize brain maldevelopment, this structure was examined in a unique sample of childhood onset schizophrenics. Anatomic brain magnetic resonance imaging scans were acquired for 25 patients (mean age 13.9 +/- 2.1) who had onset of schizophrenia by age 12 (mean age at onset 9.9 +/- 1.9) and 55 normal children. The midsagittal area of the corpus callosum was divided into seven sections. With no adjustment for brain volume, no diagnostic differences were observed. After adjustment for the smaller cerebral volume of the schizophrenics, larger total, anterior and posterior corpus callosum areas emerged for the schizophrenics. These findings provide further evidence for continuity between childhood onset and later onset schizophrenia and support other studies showing white matter sparing in the context of decreased cortical volume. (C) 1997 Elsevier Science Ireland Ltd. C1 HARVARD UNIV,SCH MED,DEPT PSYCHIAT,BOSTON,MA 02114. RP Jacobsen, LK (reprint author), NIMH,CHILD PSYCHIAT BRANCH,BLDG 10,ROOM 6N240,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Giedd, Jay/A-3080-2008; Rajapakse, Jagath/B-8485-2008; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015 OI Rajapakse, Jagath/0000-0001-7944-1658; Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978 NR 59 TC 51 Z9 52 U1 6 U2 6 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0925-4927 J9 PSYCHIAT RES-NEUROIM JI Psychiatry Res. Neuroimaging PD FEB 7 PY 1997 VL 68 IS 2-3 BP 77 EP 86 DI 10.1016/S0925-4927(96)03019-3 PG 10 WC Clinical Neurology; Neuroimaging; Psychiatry SC Neurosciences & Neurology; Psychiatry GA WR770 UT WOS:A1997WR77000002 PM 9104755 ER PT J AU Waddington, JL Torrey, EF Kinsella, A AF Waddington, JL Torrey, EF Kinsella, A TI Local geographical variation in the prevalence of schizophrenia in Co Roscommon, Ireland, in juxtaposition with cases of bipolar disorder SO SCHIZOPHRENIA RESEARCH LA English DT Letter ID RURAL IRELAND C1 ST ELIZABETH HOSP,NIMH,CTR NEUROSCI,WASHINGTON,DC 20032. DUBLIN INST TECHNOL,DEPT MATH,DUBLIN,IRELAND. RP Waddington, JL (reprint author), ROYAL COLL SURGEONS IRELAND,DEPT CLIN PHARMACOL,ST STEPHENS GREEN,DUBLIN 2,IRELAND. NR 5 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD FEB 7 PY 1997 VL 23 IS 2 BP 181 EP 183 DI 10.1016/S0920-9964(96)00100-4 PG 3 WC Psychiatry SC Psychiatry GA WJ126 UT WOS:A1997WJ12600010 PM 9061814 ER PT J AU Klebanoff, MA Levine, RJ DerSimonian, R AF Klebanoff, MA Levine, RJ DerSimonian, R TI Large trials vs meta-analysis of smaller trials SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter RP Klebanoff, MA (reprint author), NIH,BETHESDA,MD 20892, USA. NR 2 TC 5 Z9 5 U1 0 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD FEB 5 PY 1997 VL 277 IS 5 BP 376 EP 377 DI 10.1001/jama.277.5.376 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA WE771 UT WOS:A1997WE77100023 PM 9010166 ER PT J AU Cappelleri, JC Ioannidis, JPA Schmid, CH AF Cappelleri, JC Ioannidis, JPA Schmid, CH TI Large trials vs meta-analysis of smaller trials - Reply SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 NIH,BETHESDA,MD 20892. TUFTS UNIV NEW ENGLAND MED CTR,BOSTON,MA 02111. RP Cappelleri, JC (reprint author), PFIZER INC,PFIZER CENT RES,GROTON,CT 06340, USA. RI Ioannidis, John/G-9836-2011 NR 5 TC 1 Z9 1 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD FEB 5 PY 1997 VL 277 IS 5 BP 377 EP 378 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA WE771 UT WOS:A1997WE77100025 ER PT J AU Ji, BT Shu, XO Linet, MS Zheng, W Wacholder, S Gao, YT Ying, DM Jin, F AF Ji, BT Shu, XO Linet, MS Zheng, W Wacholder, S Gao, YT Ying, DM Jin, F TI Paternal cigarette smoking and the risk of childhood cancer among offspring of nonsmoking mothers SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID MATERNAL SMOKING; BRAIN-TUMORS; ALCOHOL-CONSUMPTION; ENVIRONMENTAL-FACTORS; PASSIVE SMOKING; PREGNANCY; CHILDREN; LEUKEMIA; ETIOLOGY; EXPOSURE AB Background: Cigarette smoking has been shown to increase oxidative DNA damage in human sperm cells. Assessment of the role of cigarette smoking in the etiology of childhood cancer has focused primarily on the effect of maternal smoking. Similar studies in relation to paternal smoking, however, have been inconclusive. Few studies have evaluated the effect of paternal smoking in the preconception period, and most of these could not disentangle the effects of paternal from maternal smoking. Purpose: We investigated the relationship of paternal smoking, particularly in the preconception period, with childhood cancer among offspring of the nonsmoking mothers. Methods: We conducted a population-based, case-control study in Shanghai, People's Republic of China, where the prevalence of smoking is high among men but extremely low among women. The study included 642 childhood cancer case patients (<15 years of age) and their individually matched control subjects. Information concerning parental smoking, alcohol drinking, and other exposures of the index child was obtained by direct interview of both parents of the study subjects. Odds ratios (ORs), derived from conditional logistic regression models, were used to measure the association between paternal smoking and risk of childhood cancers. Results and Conclusions: Paternal preconception smoking was related to a significantly elevated risk of childhood cancers, particularly acute leukemia and lymphoma. The risks rose with increasing pack-years of paternal preconception smoking for acute lymphocytic leukemia (ALL) (P for trend = .01), lymphoma (P for trend = .07), and total cancer (P for trend = .006). Compared with children whose fathers had never smoked cigarettes, children whose fathers smoked more than five pack-years prior to their conception had adjusted ORs of 3.8 (95% confidence interval [CI] = 1.3-12.3) for ALL, 4.5 (95% CI = 1.2-16.8) for lymphoma, 2.7(95% CI = 0.8-9.9) for brain tumors, and 1.7 (95% CI = 1.2-2.5) for all cancers combined. Statistically significant increased risks of cancer were restricted to children under the age of 5 years at diagnosis or those whose fathers had smoked during all of the 5 years prior to conception. Implications: Further studies are needed to confirm the association of paternal smoking with increased risk of cancer in offspring, to clarify the pattern of risks in relation to the timing of cigarette smoking, and to elucidate the biologic mechanism involved in predisposing the offspring to cancer. For example, it may be that paternal smoking induces prezygotic genetic damage that, in turn, acts as the predisposing factor. C1 COLUMBIA UNIV,SCH PUBL HLTH,DIV EPIDEMIOL,NEW YORK,NY. SHANGHAI CANC INST,DEPT EPIDEMIOL,SHANGHAI,PEOPLES R CHINA. UNIV MINNESOTA,DIV EPIDEMIOL & CLIN RES,MINNEAPOLIS,MN 55455. NCI,DIV CANC EPIDEMIOL & GENET,BETHESDA,MD. UNIV MINNESOTA,DIV EPIDEMIOL,MINNEAPOLIS,MN 55455. SHANGHAI XIN HUA HOSP,SHANGHAI,PEOPLES R CHINA. NR 43 TC 249 Z9 254 U1 4 U2 11 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD FEB 5 PY 1997 VL 89 IS 3 BP 238 EP 244 DI 10.1093/jnci/89.3.238 PG 7 WC Oncology SC Oncology GA WG220 UT WOS:A1997WG22000013 PM 9017004 ER PT J AU Clerici, M Merola, M Ferrario, E Trabattoni, D Villa, ML Stefanon, B Venzon, DJ Shearer, GM DePalo, G Clerici, E AF Clerici, M Merola, M Ferrario, E Trabattoni, D Villa, ML Stefanon, B Venzon, DJ Shearer, GM DePalo, G Clerici, E TI Cytokine production patterns in cervical intraepithelial neoplasia: Association with human papillomavirus infection SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; TUMOR-INFILTRATING LYMPHOCYTES; MESSENGER-RNA EXPRESSION; RENAL-CELL CARCINOMA; CLASS-I EXPRESSION; IMMUNE-RESPONSE; HIV-INFECTION; MURINE TUMORS; T-CELLS; IL-10 AB Background: Genital infection with certain strains of human papillomavirus (HPV) is associated with a high risk of malignant transformation, and HPV-associated cervical intraepithelial neoplasia (CIN) can become invasive cancer. Host factors are critical in regulating tumor growth, and cytokines that modulate immunologic control may be of particular importance. The type 1 cytokines interleukin 2 (IL-2) and interferon gamma (IFN gamma) are immunostimulatory and are thus capable of limiting tumor growth. The type 2 cytokines interleukin 4 (IL-4) and interleukin 10 (IL-10) are immunoinhibitory and are thus capable of stimulating tumor growth. Purpose: We analyzed the production of cytokines by peripheral blood mononuclear cells (PBMCs) in women with CIN associated with localized or extensively spread HPV infection. Methods: Thirty women diagnosed with CIN and 10 age- and sex-matched healthy control subjects were enrolled in the study conducted at Istituto Nazionale Tumori, Milan, Italy. The following parameters were analyzed: 1) HPV infection of the cervix and other sites of the lower genital tract by colposcopic, cytologic, and histologic examinations; 2) HPV typing; 3) in vitro production of IL-2 by PBMCs in response to stimulation with soluble antigen (influenza [FLU] antigen) or to cell-associated human leukocyte antigen (HLA) alloantigen; and 4) in vitro production of the type 1 cytokines IL-2 and IFN gamma and of the type 2 cytokines IL-4 and IL-10 by PBMCs in response to mitogen stimulation. Statistical significance was determined by nonparametric tests (two-sided). Results: High-grade CIN associated with HPV infection was detected in all case patients, and HPV type 16 or 18 infection was detected in cervical tissue of 21 (70%) of 30 case patients. HPV infection that had spread to other sites of the lower genital tract, thus resulting in more extensive disease, was detected in 16 (53%) of the 30 individuals with CIN, whereas HPV infection was limited to the portio in 14 (47%). IL-2 production by PBMCs in response to stimulation with soluble antigen or HLA alloantigen was reduced in the group with extensive disease compared with that in the group with localized disease or with that in healthy control subjects. In contrast, IL-4 and IL-10 production in response to mitogen stimulation was elevated in the group with extensive disease compared with that in the group with localized disease or with that in healthy control subjects. The highest production of IL-4 and IL-10 was detected in patients with HPV infection that had extended beyond the genital tract. Conclusions: CIN is characterized by different immunologic profiles, in which HPV infection is or is not confined to the portio. Production of cytokines that mainly enhance potentially protective cell-mediated immunity is defective in the women in whom extended HPV infection was observed. A pronounced shift from type 1 to type 2 cytokine production is associated with more extensive HPV infection. Implications: These data reinforce the need for detailed analyses of immune dysregulation in CIN patients. They also suggest the potential usefulness of the cytokine assays for determining prognosis or deciding whether cytokine-based therapy is indicated. C1 UNIV MILAN,CATTEDRA IMMUNOL,I-20133 MILAN,ITALY. OSPED L SACCO,PADIGLIONE LAB INTERDISCIPLINARE TECHNOL AVANZATE,MILAN,ITALY. IST NAZL TUMORI,MILAN,ITALY. NCI,BETHESDA,MD 20892. RI Venzon, David/B-3078-2008; Trabattoni, Daria/G-7424-2012 NR 39 TC 177 Z9 184 U1 0 U2 4 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD FEB 5 PY 1997 VL 89 IS 3 BP 245 EP 250 DI 10.1093/jnci/89.3.245 PG 6 WC Oncology SC Oncology GA WG220 UT WOS:A1997WG22000014 PM 9017005 ER PT J AU Tarone, RE Chu, KC Gaudette, LA AF Tarone, RE Chu, KC Gaudette, LA TI Birth cohort and calendar period trends in breast cancer mortality in the United States and Canada SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID RATES; WOMEN; PATTERNS; ENGLAND; WALES; AGE AB Background: Previous studies of regional and temporal variation in U.S. breast cancer mortality rates have been confined largely to analyses of rates for white women. Purpose: Breast cancer mortality rates from 1969 through 1992 for white women and black women in four regions of the United States and for all women throughout Canada were compared to identify racial, regional, and temporal differences. Differences and trends in the rates were evaluated in view of breast cancer risk factors and relevant medical interventions. Methods: Age-period-cohort models were fit to the data, and changes in birth cohort trends (suggesting a change in a breast cancer risk factor or protective factor) and calendar period trends (suggesting, in part, the impact of new or improved medical interventions) were examined. Results: Breast cancer mortality rates for white women were significantly higher in the Northeast than in any other region of the United States (two-sided t tests; P < .005); the rates for black women were not. Birth cohort trends for all women were similar until about 1940, with a moderation of mortality risk beginning around 1924. A marked moderation of risk by 4-year birth cohorts was observed for U.S. white women born after 1950, whereas stable or slightly decreasing trends were observed for U.S. black women and Canadian women. For women born from 1924 to around 1938, fertility rates increased for all three groups; after 1950, they declined uniformly. Looking at temporal effects, we found that the slope of the mortality calendar period trend increased in the 1980s compared with the 1970s for all women. In the last calendar period, 1991-1992, a trend of decreasing mortality rates was found for white women in the United States and for Canadian women. Implications: Widespread environmental exposures are unlikely to explain the higher relative breast cancer mortality rates observed for U.S. white women in the Northeast, since the rates for black women in this region were not higher than in other regions. The moderation of breast cancer mortality rates for women born between 1924 and 1938 coincides with increased fertility rates following World War II. Stable or decreasing mortality rates for U.S. women and Canadian women born after 1950 were not expected in view of declining fertility rates, suggesting a change in a breast cancer risk factor or protective factor. The increase in calendar period trend slope in the 1980s likely reflects the coincident rise in breast cancer diagnosis via mammography. The recent decline in calendar period trend for white women in the United States and for Canadian women may be the result of earlier detection and increased use of adjuvant therapy. C1 NCI,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20892. STAT CANADA,HLTH STAT DIV,OTTAWA,ON,CANADA. RP Tarone, RE (reprint author), NCI,DIV CANC EPIDEMIOL & GENET,NIH,EXECUT PLAZA N,RM 403,BETHESDA,MD 20892, USA. NR 32 TC 49 Z9 50 U1 0 U2 1 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD FEB 5 PY 1997 VL 89 IS 3 BP 251 EP 256 DI 10.1093/jnci/89.3.251 PG 6 WC Oncology SC Oncology GA WG220 UT WOS:A1997WG22000015 PM 9017006 ER PT J AU Ueno, T Mitsuya, H AF Ueno, T Mitsuya, H TI Comparative enzymatic study of HIV-1 reverse transcriptase resistant to 2',3'-dideoxynucleotide analogs using the single-nucleotide incorporation assay SO BIOCHEMISTRY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; HIGH-LEVEL RESISTANCE; THYMIDINE 5'-TRIPHOSPHATE; ANTIRETROVIRAL THERAPY; COMBINATION THERAPY; TEMPLATE-PRIMER; ZIDOVUDINE AZT; TYPE-1; MUTATION; DNA AB Employing single-nucleotide incorporation assay using a heteropolymeric RNA template and DNA primers, we defined enzymatic profiles of recombinant human immunodeficiency virus type 1 (HIV-I) reverse transcriptase (RT) containing a set of five mutations [A62V, V75I, F77L, F116Y, and Q151M] which confers resistance to multiple 2',3'-dideoxynucleosides (ddNs) on HIV-1. RTs containing other drug-resistance-associated mutations were also examined. The K-m for dNTPs, the k(cat), and the k(cat)/K-m ratios of mutant RTs were all comparable to those of wild-type RT (RT,,). The processive primer extension activity of mutant RTs was also comparable to that of RT,, as examined in the presence of saturating concentrations of dNTPs and heparin. Determination of the Ki values toward 5'-triphosphates (TP) of various ddNs [3'-azido-2',3'-dideoxythymidine (AZT), 2',3'-didehydro-2',3'-dideoxythymidine (D4T), 2',3'-dideoxycytidine (ddC), (-)-beta-L-2',3'-dideoxy-3'-thiacytidine (3TC), (-)-beta-L-2',3'-dideoxy-5-fluorocytidine (FddC), 2',3'-dideoxyadenosine (ddA), and 2'-beta-fluoro-2',3'-dideoxyadenosine (FddA)1 and 9-(2-phosphonylmethoxyethyl)adenine diphosphate (PMEApp) revealed that RT(A62V/V75I/F77/L/F116Y/Q151M) was insensitive to ddATP, AZTTP, D4TTP. FddATP, and ddCTP, but was sensitive to PMEApr,, 3TCTP, and FddCTP. RT(K65R) was less sensitive to ddATP, FddATP, PMEApp, ddCTP, and 3TCTP, while RT(M184V) was less sensitive only to 3TCTP and ddCTP. The determination of K-i(ddNTP)/Km((dNTP)) ratios showed that AZTTP, D4TTP, and ddCTP are, as substrates, as efficient for RT(wt) as their corresponding dNTPs. that substrate among ddNTPs examined. The observed cross-resistance of HIV-1 RT to various ddNTPs should reflect the alteration of RT's substrate recognition and should provide insights into the molecular mechanis, of RT descrimination of ddNTPs from natural substances. C1 NCI,EXPT RETROVIROL SECT,MED BRANCH,DIV CLIN SCI,NIH,BETHESDA,MD 20892. RI Ueno, Takamasa/F-5788-2013 OI Ueno, Takamasa/0000-0003-4852-4236 NR 51 TC 57 Z9 57 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD FEB 4 PY 1997 VL 36 IS 5 BP 1092 EP 1099 DI 10.1021/bi962393d PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WG072 UT WOS:A1997WG07200014 PM 9033399 ER PT J AU Ikezono, T Wu, T Yao, XL Levine, S Logun, C Angus, CW Shelhamer, JH AF Ikezono, T Wu, T Yao, XL Levine, S Logun, C Angus, CW Shelhamer, JH TI Leukemia inhibitory factor induces the 85-kDa cytosolic phospholipase A(2) gene expression in cultured human bronchial epithelial cells SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH LA English DT Article DE leukemia inhibitory factor; phospholipase A(2); lung; gene expression regulation; arachidonic acid ID TUMOR-NECROSIS-FACTOR; ARACHIDONIC-ACID METABOLISM; STIMULATING FACTOR; BLASTOCYST IMPLANTATION; HUMAN-PLATELETS; MESSENGER-RNA; FACTOR LIF; MICE; ACTIVATION; BINDING AB Leukemia inhibitory factor (LIF) has become increasingly recognized as an important regulator of inflammation. This study is designed to determine whether LIF has an effect on arachidonate metabolism in human airway epithelial cells. LIF (100 ng/ml) induced a significantly increased release of prelabeled [H-3] arachidonic acid (AA) from the human bronchial epithelial cell line (BEAS 2B cell) as well as from the primary cultures of human bronchial epithelial cells. Exposure of the LIF stimulated BEAS 2B cells to calcium ionophore A23187 (10(-5) M, 15 min) caused a further increase of [3H]AA release. To identify the role of cytosolic phospholipase A(2) (cPLA(2)) in this upregulation of AA release, further experiments were performed to determine the expression of cPLA(2) in the BEAS 2B cells. Immunoblot analysis indicated that LIF increased cPLA(2) protein expression. Ribonuclease protection assay showed that LIF induced an increase of cPLA(2) mRNA levels following 3 h to 24 h treatment. Nuclear run-on experiments suggested that LIF upregulated cPLA, gene expression through post-translational regulation. These results demonstrate that LIF induces cPLA(2) gene expression and modulates arachidonate metabolism in airway epithelial cells. C1 NIH,DEPT CRIT CARE MED,BETHESDA,MD 20892. NR 49 TC 13 Z9 14 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4889 J9 BBA-MOL CELL RES JI Biochim. Biophys. Acta-Mol. Cell Res. PD FEB 4 PY 1997 VL 1355 IS 2 BP 121 EP 130 DI 10.1016/S0167-4889(96)00122-X PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA WG591 UT WOS:A1997WG59100005 PM 9042332 ER PT J AU Sugiyama, K Highet, RJ Woods, A Cotter, RJ Osawa, Y AF Sugiyama, K Highet, RJ Woods, A Cotter, RJ Osawa, Y TI Hydrogen peroxide-mediated alteration of the heme prosthetic group of metmyoglobin to an iron chlorin product: Evidence for a novel oxidative pathway SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID PROSTAGLANDIN ENDOPEROXIDE SYNTHASE; OXYGEN RADICALS; PROTEIN DAMAGE; PROPOSED STRUCTURE; ESCHERICHIA-COLI; MYOGLOBIN; DEGRADATION; INACTIVATION; MECHANISMS; INJURY AB Treatment of metmyoglobin with H2O2 is known to lead to the crosslinking of an active site tyrosine residue to the heme [Catalano, C. E., Y. S. Choe, and P. R. Ortiz de Montellano (1989) J. Biol. Chem. 264, 10534-10541]. We have found in this study that this reaction also leads to an altered heme product not covalently bound to the protein. This product was characterized by visible absorption, infrared absorption, and mass and NMR spectrometry as an iron chlorin product formed from the saturation of the double bond between carbon atoms at positions 17 and 18 of pyrrole ring D with concomitant addition of a hydroxyl group on the carbon atom at position 18 and lactonization of the propionic acid to the carbon atom at position 17. Studies with the use of O-18-labeled H2O2, O-2, and H2O clearly indicate that the source of the added oxygen on the heme is water. Evidently, water adds regiospecifically to a cationic site formed on a carbon atom at position 18 after oxidation of the ferric heme prosthetic group with peroxide. Prolonged incubation of the reaction mixture containing the iron hydroxychlorin product led to the formation of an iron dihydroxychlorin product, presumably from a slow addition of water to the initial iron hydroxychlorin. The iron chlorin products characterized in this study are distinct from the meso-oxyheme species, which is thought to be formed during peroxide-mediated degradation of metmyoglobin, cytochrome P450, ferric heme, and model ferric hemes, and give further insight into the mechanism of H2O2-induced heme alterations. C1 UNIV MICHIGAN,SCH MED,DEPT PHARMACOL,ANN ARBOR,MI 48109. NHLBI,CHEM PHARMACOL LAB,NIH,BETHESDA,MD 20892. NHLBI,BIOPHYS CHEM LAB,NIH,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,SCH MED,MIDDLE ATLANTIC MASS SPECTROMETRY LAB,BALTIMORE,MD 21205. NR 44 TC 38 Z9 38 U1 2 U2 6 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 4 PY 1997 VL 94 IS 3 BP 796 EP 801 DI 10.1073/pnas.94.3.796 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WG234 UT WOS:A1997WG23400006 PM 9023336 ER PT J AU Koshiba, M Apasov, S Sverdlov, V Chen, P Erb, L Turner, JT Weisman, GA Sitkovsky, MV AF Koshiba, M Apasov, S Sverdlov, V Chen, P Erb, L Turner, JT Weisman, GA Sitkovsky, MV TI Transient up-regulation of P2Y(2) nucleotide receptor mRNA expression is an immediate early gene response in activated thymocytes SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE receptors purinergic; gene expression; T cell receptor; steroid hormones ID PROGRAMMED CELL-DEATH; EXTRACELLULAR ATP; EFFECTOR FUNCTIONS; LYMPHOCYTES-T; MESSENGER-RNA; PURINOCEPTORS; CLONING; FRAGMENTATION; APOPTOSIS; THYMUS AB In studies designed to understand the roles of P2 nucleotide receptors in differentiation of T lymphocytes, we observed a transient and protein synthesis-independent enhancement of mRNA expression for the G protein-coupled P2Y(2) receptor in mouse thymocytes after the addition of steroid hormone or T cell receptor (TCR) crosslinking by anti-TCR mAb. Conversely, dexamethasone-induced increases in mRNA expression for the ligand-gated ion channel P2X(1) receptor was detected in rat, but not mouse, thymocytes, raising questions about the previously suggested role of P2X(1) receptors in thymocyte apoptosis. Flow cytometry analysis of thymocyte subsets excluded the possibility that the observed increases in P2Y(2) receptor mRNA expression were due to the enrichment of steroid-treated cells with an P2Y(2) mRNA-rich thymocyte subset. Triggering of TCR-mediated intracellular signaling pathways through crosslinking of TCR or by addition of phorbol ester and Ca2+ ionophore also resulted in the up-regulation of P2Y(2), but not P2X(1), receptor mRNA. It is proposed that the rapid increase of P2Y(2) receptor mRNA expression could be a common early event in responses of T cells to different activating stimuli. Taken together with the recently discovered ability of nucleotide receptor-initiated signaling to antagonize or enhance the effects of TCR crosslinking or steroids on thymocytes, the observed rapid up-regulation of P2Y(2) receptor mRNA expression may reflect an immediate early gene response where newly expressed cell surface nucleotide receptors provide regulatory feedback signaling from extracellular ATP in the T cell differentiation process. C1 NIAID,IMMUNOL LAB,NIH,BETHESDA,MD 20892. UNIV MISSOURI,DEPT BIOCHEM,COLUMBIA,MO 65212. UNIV MISSOURI,DEPT PHARMACOL,COLUMBIA,MO 65212. OI Erb, Laurie/0000-0001-6372-3378 NR 37 TC 75 Z9 76 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 4 PY 1997 VL 94 IS 3 BP 831 EP 836 DI 10.1073/pnas.94.3.831 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WG234 UT WOS:A1997WG23400012 PM 9023342 ER PT J AU Brady, JP Garland, D DuglasTabor, Y Robison, WG Groome, A Wawrousek, EF AF Brady, JP Garland, D DuglasTabor, Y Robison, WG Groome, A Wawrousek, EF TI Targeted disruption of the mouse alpha A-crystallin gene induces cataract and cytoplasmic inclusion bodies containing the small heat shock protein alpha B-crystallin SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID SKELETAL-MUSCLE; LENS; EXPRESSION; TISSUES; DIFFERENTIATION; LOCALIZATION; ASSOCIATION; CHAPERONE; VIMENTIN; ACTIN AB alpha A-crystallin (alpha A) and alpha B-crystallin (alpha B) are among the predominant proteins of the vertebrate eye lens. In vitro, the alpha-crystallins, which are isolated together as a high molecular mass aggregate, exhibit a number of properties, the most interesting of which is their ability to function as molecular chaperones for other proteins. Here we begin to examine the in vivo functions of alpha-crystallin by generating mice with a targeted disruption of the alpha A gene. Mice that are homozygous for the disrupted allele produce no detectable alpha A in their lenses, based on protein gel electrophoresis and immunoblot analysis. Initially, the alpha A-deficient lenses appear structurally normal, but they are smaller than the lenses of wild-type littermates. alpha A(-/-) lenses develop an opacification that starts in the nucleus and progresses to a general opacification with age. Light and transmission electron microscopy reveal the presence of dense inclusion bodies in the central lens fiber cells. The inclusions react strongly with antibodies to alpha B but not significantly with antibodies to beta- or gamma-crystallins. In addition, immunoblot analyses demonstrate that a significant portion of the alpha B in alpha A(-/-) lenses shifts into the insoluble fraction. These studies suggest that alpha A is essential for maintaining lens transparency, possibly by ensuring that alpha B or proteins closely associated with this small heat shock protein remain soluble. C1 NEI,NIH,BETHESDA,MD 20892. RI Wawrousek, Eric/A-4547-2008 NR 31 TC 249 Z9 256 U1 0 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 4 PY 1997 VL 94 IS 3 BP 884 EP 889 DI 10.1073/pnas.94.3.884 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WG234 UT WOS:A1997WG23400021 PM 9023351 ER PT J AU Taira, M SaintJeannet, JP Dawid, IB AF Taira, M SaintJeannet, JP Dawid, IB TI Role of the Xlim-1 and Xbra genes in anteroposterior patterning of neural tissue by the head and trunk organizer SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; FIBROBLAST GROWTH-FACTOR; XENOPUS-EMBRYOS; RETINOIC ACID; HOMEOBOX GENE; SPEMANN ORGANIZER; MESODERM FORMATION; SONIC-HEDGEHOG; EXPRESSION; INDUCTION AB Anteroposterior patterning of neural tissue is thought to be directed by the axial mesoderm which is functionally divided into head and trunk organizer. The LIM class homeobox gene Xlim-1 is expressed in the entire axial mesoderm, whereas the distinct transcription factor Xbra is expressed in the notochord but not in the prechordal mesoderm. mRNA injection experiments showed that Xenopus animal explants (caps) expressing an activated form of Xlim-1 (a LIM domain mutant named 3m) induce anterior neural markers whereas caps coexpressing Xlim-1/3m and Xbra induce posterior neural markers. These data indicate that, in terms of neural inducing ability, Xlim-1/3m-expressing caps correspond to the head organizer and Xlim-1/3m plus Xbra-coexpressing caps to the trunk organizer. Thus the expression domains of Xlim-1 and Xbra correlate with, and possibly define, the functional domains of the organizer. In animal caps Xlim-1/3m initiates expression of a neuralizing factor, chordin, whereas Xbra activates embryonic fibroblast growth factor (eFGF) expression, as reported previously; these factors could mediate the neural inducing and patterning effects that were observed. A dominant-negative FGF receptor (XFD) inhibits posteriorization by Xbra in a dose-dependent manner, supporting the suggestion that eFGF or a related factor has posteriorizing influence. C1 NICHHD,NIH,GENET MOL LAB,BETHESDA,MD 20892. NR 60 TC 44 Z9 45 U1 5 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 4 PY 1997 VL 94 IS 3 BP 895 EP 900 DI 10.1073/pnas.94.3.895 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WG234 UT WOS:A1997WG23400023 PM 9023353 ER PT J AU Reddy, N Everhart, A Eling, T Glasgow, W AF Reddy, N Everhart, A Eling, T Glasgow, W TI Characterization of a 15-lipoxygenase in human breast carcinoma BT-20 cells: Stimulation of 13-HODE formation by TGF(alpha)/EGF SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID EPIDERMAL GROWTH-FACTOR; ARACHIDONIC-ACID; DEPENDENT MITOGENESIS; FACTOR RECEPTOR; LINOLEIC-ACID; METABOLITES; FIBROBLASTS; RNA AB Epidemiological and experimental data suggest a role for polyunsaturated fatty acids in the etiology of breast cancer. In this report we have studied arachidonic acid and linoleic acid metabolism in the human breast carcinoma cell line BT-20 which overexpresses both EGF receptor and the homologous erbB-2 oncogene product. EGF and TGF(alpha) stimulated DNA synthesis in these cells which was attenuated by the addition of a lipoxygenase inhibitor, NDGA. The addition of a prostaglandin H synthase inhibitor did not alter DNA synthesis. Analytical studies reveal little arachidonic acid metabolism while linoleic acid was metabolized to 13-hydroxyoctadecadienoic acid (13-HODE). The formation of 13-HODE was inhibited by the addition of NDGA and was dependent on EGF or TGF(alpha). These results suggest the metabolism of linoleic acid by a n-6 or 15-lipoxygenase regulated by EGF/TGF(alpha). RT-PCR was used to isolate a clone, and sequenced the cDNA for this enzyme and it was found to be identical to the human 15-lipoxygenase previously characterized from human pulmonary tissue. EGF/TGF(alpha) did not alter the expression of this enzyme suggesting a potential posttranslational regulation of activity. This study provides a link between metabolism of linoleic acid and growth factor regulation of cell proliferation in a human breast carcinoma cell line. (C) 1997 Academic Press. C1 NIEHS,MOL BIOPHYS LAB,EICOSANOID BIOCHEM SECT,RES TRIANGLE PK,NC 27709. NR 20 TC 36 Z9 37 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD FEB 3 PY 1997 VL 231 IS 1 BP 111 EP 116 DI 10.1006/bbrc.1997.6048 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA WH355 UT WOS:A1997WH35500024 PM 9070230 ER PT J AU Gu, J Irving, SG Iadarola, MJ AF Gu, J Irving, SG Iadarola, MJ TI URE, an initiator (Inr)-like site: Suppresses the promoter of the rat dynorphin gene SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID BINDING PROTEIN; TRANSCRIPTIONAL ACTIVATION; TATA BOX; ELEMENT; INVITRO; HIV-1; REPRESSION; SEQUENCE; CLONING; YY1 AB We previously identified a DNA binding element termed the upstream regulatory element (URE) that contains the consensus initiator sequence (Inr) in the upstream promoter of the rat prodynorphin gene, The URE displays specific binding to the upstream regulatory element binding protein (UREB1), a novel transcription regulator, Here, we report that the URE functions as a suppressor element, A series of chloramphenicol acetyltransferase reporters (pCAT) were constructed by subcloning either wildtype or mutated URE sequences into a pCAT reporter plasmid 5' of bases -135 to +58 of the prodynorphin gene, The basal -135 to +58 dynorphin promoter (pCAT 0.2) has robust transcriptional activity in Chinese hamster ovary (CHO) cells but not in rat pheochromocytoma PC12 cells, This robust transcriptional activity was completely inhibited in the presence of wildtype URE, whereas the mutations of the URE had no effect, Gel mobility shift assays showed that the complex formed by the URE and nuclear protein extracts can be competed by addition of wild-type URE oligonucleotide but not by specific mutations of the URE, defining particular bases required for protein interaction with the URE, The identical URE sequence is also found upstream in the promoter of human macrophage inflammatory protein 1 beta (hMLP 1 beta), The suppressive activity of the rat dynorphin URE can be replaced by the hMIP 1 beta URE, These data suggest that the URE may serve as a suppressor element in the regulation of dynorphin and hMIP 1 beta gene transcription, (C) 1997 Academic Press. C1 NIDR,NEUROBIOL & ANESTHESIOL BRANCH,NIH,BETHESDA,MD 20892. GEORGETOWN UNIV,MED CTR,DEPT PATHOL,WASHINGTON,DC 20007. NR 20 TC 8 Z9 9 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD FEB 3 PY 1997 VL 231 IS 1 BP 172 EP 177 DI 10.1006/bbrc.1997.6067 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA WH355 UT WOS:A1997WH35500037 PM 9070243 ER PT J AU Fukuda, K Hori, H Utani, A Burbelo, PD Yamada, Y AF Fukuda, K Hori, H Utani, A Burbelo, PD Yamada, Y TI Formation of recombinant triple-helical [alpha 1(IV)](2)alpha 2(IV) collagen molecules in CHO coils SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID BASEMENT-MEMBRANE COLLAGEN; 2 DISTINCT CHAINS; ALPHA-1 IV CHAIN; GOODPASTURE; EXPRESSION; GENES; DNA; PROCOLLAGEN; EFFICIENCY; PROTEINS AB Collagen IV molecules represent a major structural component of basement membranes providing a network of support for the supramolecular structure, Like other collagens, collagen IV forms a triple-helical molecule composed of three alpha chains. Six different alpha chains exist for collagen IV, although the most common isoform consists of two alpha 1(IV) and one alpha 2(IV) chain, To understand the molecular mechanism of triple-helical formation of collagen IV, we expressed recombinant alpha 1(IV) and alpha 2(IV) mouse collagen chains in Chinese hamster ovary (CHO) cells. An expression vector containing the full, length cDNA for the mouse alpha 1(IV) chain was stably transfected into CHO cells and a cell line, A222, which expressed recombinant alpha 1(IV) chains was selected. These A222 cells were then infected with a retroviral expression vector containing the mouse alpha 2(IV) chain and a cell line, A222-A2, stably expressing both recombinant alpha 1(IV) and alpha 2(IV) chains was obtained, Immunoprecipitation of A222 cell lysates revealed a high level of alpha 1(IV) chain monomer, which was unable to form a homotrimer. Analysis of A222-A2 cell lysates revealed the presence of both monomeric alpha 2(IV) and alpha 1(IV) chains as well as a higher molecular weight collagen IV species. Second dimensional SDS-PAGE analysis demonstrated that the high molecular weight species was a heterotrimer consisting of two alpha 1(IV) and one alpha 2(IV) chain. This heterotrimer collagen IV species was pepsin-resistant indicating the formation of a stable triple-helical structure. Pulse-chase experiments sheaved that the monomer alpha 1(IV) chain was secreted, but at a much slower rate than the heterotrimer. Together these results demonstrate that the alpha 1(IV) chain is not capable of forming homotrimers and suggest that the coexpression with the alpha 2(IV) chain is necessary to form a triple helical structure. (C) 1997 Academic Press. C1 NIDR,CRANIOFACIAL DEV BIOL & REGENERAT BRANCH,NIH,BETHESDA,MD 20892. RI Burbelo, Peter/B-1027-2009 NR 32 TC 16 Z9 17 U1 1 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD FEB 3 PY 1997 VL 231 IS 1 BP 178 EP 182 DI 10.1006/bbrc.1997.6069 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA WH355 UT WOS:A1997WH35500038 PM 9070244 ER PT J AU Gajewski, K Kim, Y Lee, YM Olson, EN Schulz, RA AF Gajewski, K Kim, Y Lee, YM Olson, EN Schulz, RA TI D-mef2 is a target for Tinman activation during Drosophila heart development SO EMBO JOURNAL LA English DT Article DE cardiogenic factors; D-mef2; heart; tinman; transcriptional enhancer ID HOMEOBOX-CONTAINING GENE; TRANSCRIPTION FACTOR; MESODERM; MEF2; DNA; EMBRYOGENESIS; HOMEODOMAIN; EXPRESSION; PROTEIN; EMBRYOS AB The NK-type homeobox gene tinman and the MADS box gene D-mef2 encode transcription factors required for the development and differentiation of the Drosophila heart, and closely related genes regulate cardiogenesis in vertebrates. Genetic analyses indicate that tinman and D-mef2 act at early and late steps, respectively, in the cardiogenic lineage. However, it is unknown whether regulatory interactions exist between these developmental control genes, We show that D-mef2 expression in the developing Drosophila heart requires a novel upstream enhancer containing two Tinman binding sites, both of which are essential for enhancer function in cardiac muscle cells. Transcriptional activity of this cardiac enhancer is dependent on tinman function, and ectopic Tinman expression activates the enhancer outside the cardiac lineage, These results define the only known in vivo target for transcriptional activation by Tinman and demonstrate that D-mef2 lies directly downstream of tinman in the genetic cascade controlling heart formation in Drosophila. C1 UNIV TEXAS,MD ANDERSON CANC CTR,DEPT BIOCHEM & MOL BIOL,HOUSTON,TX 77030. NHLBI,MOL CARDIOL LAB,NIH,BETHESDA,MD 20892. UNIV TEXAS,SW MED CTR,HAMON CTR BASIC CANC RES,DEPT MOL BIOL & ONCOL,DALLAS,TX 75235. FU NCI NIH HHS [CA16672]; NICHD NIH HHS [T32 HD 07324] NR 45 TC 114 Z9 116 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD FEB 3 PY 1997 VL 16 IS 3 BP 515 EP 522 DI 10.1093/emboj/16.3.515 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA WH236 UT WOS:A1997WH23600008 PM 9034334 ER PT J AU Benkirane, M Neuveut, C Chun, RF Smith, SM Samuel, CE Gatignol, A Jeang, KT AF Benkirane, M Neuveut, C Chun, RF Smith, SM Samuel, CE Gatignol, A Jeang, KT TI Oncogenic potential of TAR RNA binding protein TRBP and its regulatory interaction with RNA-dependent protein kinase PKR SO EMBO JOURNAL LA English DT Article DE interferon; regulation; RNA binding protein; translation; transformation ID IMMUNODEFICIENCY-VIRUS TYPE-1; INITIATION FACTOR-II; 58,000-DALTON CELLULAR INHIBITOR; TRANSLATIONAL CONTROL MECHANISM; INTERFERON ACTION; MALIGNANT TRANSFORMATION; P68 KINASE; IN-VIVO; TRANSCRIPTION FACTOR; INFECTED CELLS AB TAR RNA binding protein (TRBP) belongs to an RNA binding protein family that includes the double-stranded RNA-activated protein kinase (PKR), Drosophila Staufen and Xenopus xlrbpa. One member of this family, PKR, is a serine/threonine kinase which has anti-viral and anti-proliferative effects, In this study we show that TRBP is a cellular down-regulator of PKR function, Assaying expression from an infectious HIV-1 molecular clone, we found that PKR inhibited viral protein synthesis and that over-expression of TRBP effectively countered this inhibition. In intracellular and in cell-free assays we show that TRBP directly inhibits PKR autophosphorylation through an RNA binding-independent pathway. Biologically, TRBP serves a growth-promoting role; cells that overexpress TRBP exhibit transformed phenotypes. Our results demonstrate the oncogenic potential of TRBP and are consistent with the notion that intracellular PKR function contributes physiologically towards regulating cellular proliferation. C1 NIAID,MOL VIROL SECT,MOL MICROBIOL LAB,NIH,BETHESDA,MD 20892. UNIV CALIF SANTA BARBARA,DEPT MOL CELLULAR & DEV BIOL,SANTA BARBARA,CA 93106. INST COCHIN GENET MOL,F-75014 PARIS,FRANCE. RI Jeang, Kuan-Teh/A-2424-2008; Chun, Rene/A-9415-2010 OI Chun, Rene/0000-0002-0190-0807 FU NIAID NIH HHS [AI-20611] NR 74 TC 155 Z9 162 U1 1 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD FEB 3 PY 1997 VL 16 IS 3 BP 611 EP 624 DI 10.1093/emboj/16.3.611 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA WH236 UT WOS:A1997WH23600017 PM 9034343 ER PT J AU vanMeerwijk, JPM Marguerat, S Lees, RK Germain, RN Fowlkes, BJ MacDonald, HR AF vanMeerwijk, JPM Marguerat, S Lees, RK Germain, RN Fowlkes, BJ MacDonald, HR TI Quantitative impact of thymic clonal deletion on the T cell repertoire SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID II-DEFICIENT MICE; RECEPTOR TRANSGENIC MICE; BONE-MARROW CHIMERAS; POSITIVE SELECTION; MHC CLASS; NEGATIVE SELECTION; HEMATOPOIETIC-CELLS; SELF-TOLERANCE; THYMOCYTE SUBPOPULATIONS; SEQUENTIAL APPEARANCE AB Interactions between major histocompatibility complex (MHC) molecules expressed on stromal cells and antigen-specific receptors on T cells shape the repertoire of mature T lymphocytes emerging from the thymus. Some thymocytes with appropriate receptors are stimulated to undergo differentiation to the fully mature state (positive selection), whereas others with strongly autoreactive receptors are triggered to undergo programmed cell death before completing this differentiation process (negative selection). The quantitative impact of negative selection on the potentially available repertoire is currently unknown. To address this issue, we have constructed radiation bone marrow chimeras in which MHC molecules are present on radioresistant thymic epithelial cells (to allow positive selection) but absent from radiosensitive hematopoietic elements responsible for negative selection. In such chimeras, the number of mature thymocytes was increased by twofold as compared with appropriate control chimeras. This increase in steady-state numbers of mature thymocytes was not related to proliferation, increased retention, or recirculation and was accompanied by a similar two- to threefold increase in the de novo rate of generation of mature cells. Taken together, our data indicate that half to two-thirds of the thymocytes able to undergo positive selection die before full maturation due to negative selection. C1 UNIV LAUSANNE,LUDWIG INST CANC RES,LAUSANNE BRANCH,CH-1066 EPALINGES,SWITZERLAND. NIH,LYMPHOCYTE BIOL SECT,IMMUNOL LAB,BETHESDA,MD 20892. NIAID,CELLULAR & MOL IMMUNOL LAB,NIH,BETHESDA,MD 20892. RI van Meerwijk, Joost/K-1345-2014 NR 62 TC 143 Z9 145 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD FEB 3 PY 1997 VL 185 IS 3 BP 377 EP 383 DI 10.1084/jem.185.3.377 PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA WG599 UT WOS:A1997WG59900002 PM 9053438 ER PT J AU Zhong, GM Romagnoli, P Germain, RN AF Zhong, GM Romagnoli, P Germain, RN TI Related leucine-based cytoplasmic targeting signals in invariant chain and major histocompatibility complex class II molecules control endocytic presentation of distinct determinants in a single protein SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID MHC CLASS-II; HLA-DR MOLECULES; ANTIGEN-PRESENTATION; B-CELLS; RESTRICTED PRESENTATION; ENDOSOMAL COMPARTMENTS; RAPID INTERNALIZATION; ENDOPLASMIC-RETICULUM; PEPTIDE BINDING; BETA DIMERS AB Leucine-based signals in the cytoplasmic tail of invariant chain (Ii) control targeting of newly synthesized major histocompatibility complex class II molecules to the endocytic pathway for acquisition of antigenic peptides Some protein determinants, however, do not require Ii for effective class II presentation, although endocytic processing is still necessary. Here we demonstrate that a dileucine-based signal in the cytoplasmic tail of the class II beta chain is critical for this Ii-independent presentation. Elimination or mutation of this signal reduces the rate of re-entry of mature surface class II molecules into the endocytic pathway. Antigen presentation controlled by this signal does not require newly synthesized class II molecules and appears to involve determinants requiring only limited proteolysis for exposure, whereas the opposite is true for Ii-dependent determinants. This demonstrates chat related leucine-based trafficking signals in Ii and class II control the functional presentation of protein determinants with distinct processing requirements, suggesting that the peptide binding sites of newly synthesized versus mature class II molecules are made available for antigen binding in distinct endocytic compartments under the control of these homologous cytoplasmic signals. This permits capture of protein fragments produced optimally under distinct conditions of pH and proteolytic activity. C1 NIAID,LYMPHOCYTE BIOL SECT,IMMUNOL LAB,NIH,BETHESDA,MD 20892. RI Romagnoli, Paola/K-2237-2014 NR 63 TC 109 Z9 109 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD FEB 3 PY 1997 VL 185 IS 3 BP 429 EP 438 DI 10.1084/jem.185.3.429 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA WG599 UT WOS:A1997WG59900007 PM 9053443 ER PT J AU Bloom, MB PerryLalley, D Robbins, PF Li, Y ElGamil, M Rosenberg, SA Yang, JC AF Bloom, MB PerryLalley, D Robbins, PF Li, Y ElGamil, M Rosenberg, SA Yang, JC TI Identification of tyrosinase-related protein 2 as a tumor rejection antigen for the B16 melanoma SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID CYTOLYTIC T-LYMPHOCYTES; INFILTRATING LYMPHOCYTES; GENE; PEPTIDE; EPITOPES; CODES; CELLS AB Recently, major advances have been made in the identification of antigens from human melanoma which are recognized by T cells. In spite of this, little is known about the optimal ways to use these antigens to treat patients with cancer. Progress in this area is likely to require accurate preclinical animal models, but the availability of such models has lagged behind developments in human tumor immunology. Whereas many of the identified human melanoma antigens are normal tissue differentiation proteins, analogous murine tumor antigens have not yet been identified. In this paper we identify a normal tissue differentiation antigen, tyrosinase-related protein 2 (TRP-2), expressed by the murine B16 melanoma which was found by screening a cDNA library from B16 with tumor-reactive cytotoxic T lymphocytes (CTL). A peptide conforming to the predicted MHC class I H2-K-b binding motif, TRP-2(181-188), Was identified as the major reactive epitope within TRP-2 recognized by these anti-Bib CTLs. By site-directed mutagenesis, it was shown that alteration of this epitope eliminated recognition of TRP-2. It was further demonstrated that a CTL line raised from splenocytes by repeated stimulation in vitro with this peptide could recognize B16 tumor and was therapeutic against 3-d-old established pulmonary metastases. The use of TRP-2 in a preclinical model of tumor immunotherapy may be helpful in suggesting optimal vaccination strategies for cancer therapy in patients. C1 NCI,SURG BRANCH,NIH,BETHESDA,MD 20892. NR 24 TC 285 Z9 288 U1 0 U2 8 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD FEB 3 PY 1997 VL 185 IS 3 BP 453 EP 459 DI 10.1084/jem.185.3.453 PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA WG599 UT WOS:A1997WG59900009 PM 9053445 ER PT J AU Strey, HH Parsegian, VA Podgornik, R AF Strey, HH Parsegian, VA Podgornik, R TI Equation of state for DNA liquid crystals: Fluctuation enhanced electrostatic double layer repulsion SO PHYSICAL REVIEW LETTERS LA English DT Article ID NEMATIC PHASES; CHAINS AB We have measured the equation of state for DNA solutions at different ionic strengths covering 5 orders of magnitude in DNA osmotic pressure. At high osmotic pressures the equation of state is independent of the ionic strength and is dominated by exponentially decaying hydration repulsion. At lower pressures the equation of state is dominated by screened electrostatics. We also found a fluctuation-enhanced repulsion with a decay length of 4 times the. Debye screening length. We present arguments that the form of the fluctuation part of the osmotic pressure is due to the coupling between bending fluctuations and the compressibility of the nematic array normal to the average director. C1 NIDDKD,NIH,STRUCT BIOL LAB,DIV COMP RES & TECHNOL,BETHESDA,MD 20892. RP Strey, HH (reprint author), NIDDKD,NIH,DIROD,BLDG 12A-2041,12 S DR MSC 5626,BETHESDA,MD 20892, USA. RI Strey, Helmut/B-5456-2009; Podgornik, Rudolf/C-6209-2008 OI Podgornik, Rudolf/0000-0002-3855-4637 NR 13 TC 98 Z9 103 U1 0 U2 15 PU AMERICAN PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 0031-9007 J9 PHYS REV LETT JI Phys. Rev. Lett. PD FEB 3 PY 1997 VL 78 IS 5 BP 895 EP 898 DI 10.1103/PhysRevLett.78.895 PG 4 WC Physics, Multidisciplinary SC Physics GA WG702 UT WOS:A1997WG70200036 ER PT J AU Russ, P Ezzitouni, A Marquez, VE AF Russ, P Ezzitouni, A Marquez, VE TI Hydroxyl- versus amide-directed cyclopropanation from the allylic position in 1-nydroxy-4-N-acyl-cyclopentenes under modified Simmons-Smith conditions SO TETRAHEDRON LETTERS LA English DT Article ID CARBOCYCLIC THYMIDINE; ANALOGS; ACID AB In a functionalized cyclopentene having allylic OH and NH-acyl groups on opposite faces of the ring, the diastereoselective delivery of the incoming methylene group in the diethylzinc version of the Simmons-Smith reaction was completely directed by the NH group. The diastereoselectivity of the reaction can be reversed by complete protection of the amide. (C) 1997, Elsevier Science Ltd. C1 NCI,MED CHEM LAB,DIV BASIC SCI,NIH,BETHESDA,MD 20892. NR 10 TC 12 Z9 12 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0040-4039 J9 TETRAHEDRON LETT JI Tetrahedron Lett. PD FEB 3 PY 1997 VL 38 IS 5 BP 723 EP 726 DI 10.1016/S0040-4039(96)02425-2 PG 4 WC Chemistry, Organic SC Chemistry GA WF320 UT WOS:A1997WF32000008 ER PT J AU Mekonnen, B Ziffer, H AF Mekonnen, B Ziffer, H TI A new route to N-substituted 11-azaartemisinins SO TETRAHEDRON LETTERS LA English DT Article ID ARTEMISININ; QINGHAOSU AB A series of N-substituted 11-azaartemisinins were prepared in high yield by Michael additions to the amide nitrogen in 2a. The presence of substituents on the unsaturated system of the Michael acceptor markedly decreased the yield of the reaction. (C) 1997, Elsevier Science Ltd. C1 NIDDK,CHEM PHYS LAB,NIH,BETHESDA,MD 20892. NIMH,CLIN SCI LAB,NIH,BETHESDA,MD 20892. NR 6 TC 26 Z9 27 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0040-4039 J9 TETRAHEDRON LETT JI Tetrahedron Lett. PD FEB 3 PY 1997 VL 38 IS 5 BP 731 EP 734 DI 10.1016/S0040-4039(96)02417-3 PG 4 WC Chemistry, Organic SC Chemistry GA WF320 UT WOS:A1997WF32000010 ER PT J AU Gampel, J AF Gampel, J TI Death rates in treated and untreated heroin addicts SO ACTA PSYCHIATRICA SCANDINAVICA LA English DT Letter RP Gampel, J (reprint author), NIDA,NIH,ROCKVILLE,MD 20852, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0001-690X J9 ACTA PSYCHIAT SCAND JI Acta Psychiatr. Scand. PD FEB PY 1997 VL 95 IS 2 BP 166 EP 166 DI 10.1111/j.1600-0447.1997.tb00392.x PG 1 WC Psychiatry SC Psychiatry GA WL520 UT WOS:A1997WL52000016 PM 9065684 ER PT J AU OConnor, FC Mayuga, R Arrington, CT Fleg, JL AF OConnor, FC Mayuga, R Arrington, CT Fleg, JL TI Do echocardiographic changes explain the age-associated increase in exercise-induced supraventricular arrhythmias? SO AGING-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE aging; echocardiography; exercise; supraventricular arrhythmias ID APPARENT HEART-DISEASE; CARDIAC-ARRHYTHMIAS; POPULATION AB Although exercise-induced supraventricular arrhythmias (EISVA) increase with advancing age, it is unclear whether age-associated changes in cardiac structure or function play a major role in this increase. To address this question, we examined the relationship between M-mode echocardiographic variables and EISVA occurring during maximal treadmill exercise in 366 healthy volunteers aged 20 to 90 years from the Baltimore Longitudinal Study of Aging. Simple (i.e,, isolated) EISVA were detected in 69 subjects (19%), and complex EISVA (i.e., comprising >10% of beats in any minute or occurring in runs) in another 29 subjects (8%). Univariate predictors of any EISVA, whether simple or complex, were older age (p<0.0001), male gender (p<0.05), greater left atrial size (p<0.01), left ventricular mass index (1<0.0001), interventricular septal thickness (p<0.001), isovolumic relaxation time (p<0.01), atrial filling fraction (p<0.01), reduced mitral E-F closure slope (p<0.001), peak E velocity (p<0.02), and peak E/A ratio ((p<0.0001). Lesser exercise duration (p<0.01), lower maximal heart rate (p<0.0001), and higher peak systolic and diastolic blood pressures (p<0.001) were also associated with EISVA. However, by multiple logistic regression analysis, age (p<0.0001) was the only independent predictor of any EISVA. Univariate predictors of complex EISVA were greater age (p<0.0001), atrial filling fraction (p<0.001), diastolic blood pressure (p<0.05), lesser mitral E-F slope (p<0.004), exercise duration (p<0.005) and maximal heart rate ((p<0.01). However, only age (p<0.0001) independently predicted complex EISVA. Thus, in healthy volunteers undergoing maximal treadmill exercise, EISVA are associated with greater left ventricular wall thickness, reduced early diastolic performance, diminished exercise capacity and elevated exercise blood pressure, However, none of these variables are independent predictors of EISVA over and above the powerful effect of age, (C) 1997, Editrice Kurtis. C1 NIA,CTR GERONTOL RES,CARDIOVASC SCI LAB,NIH,BALTIMORE,MD 21224. NR 21 TC 3 Z9 3 U1 0 U2 0 PU EDITRICE KURTIS S R L PI MILANO PA VIA LUIGI ZOJA, 30-20153 MILANO, ITALY SN 0394-9532 J9 AGING-CLIN EXP RES JI Aging-Clin. Exp. Res. PD FEB-APR PY 1997 VL 9 IS 1-2 BP 120 EP 126 PG 7 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA WT411 UT WOS:A1997WT41100016 PM 9177595 ER PT J AU Hanna, EZ Chou, SP Grant, BF AF Hanna, EZ Chou, SP Grant, BF TI The relationship between drinking and heart disease morbidity in the United States: Results from the National Health Interview Survey SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE heart disease; alcohol consumption; risk factors; protection ID DENSITY-LIPOPROTEIN CHOLESTEROL; MODERATE ALCOHOL-CONSUMPTION; CIGARETTE-SMOKING; MORTALITY; WOMEN; MEN; ASSOCIATION; WHITE; BLACK AB This study, based on data drawn from the responses of 18,323 males and 25,440 females to the 1988 National Health interview Survey, a nationally representative, multistage probability sample of the United States, attempts to define more precisely the level of drinking at which the relationship between heart disease and alcohol consumption is a protective one. Its attempt at precision derives from (1) using drinking categories that represent various points within the range of moderate drinking (1-6 drinks) defined in the literature as protective; (2) adjusting for underreporting that commonly occurs in population surveys by using consumption at time of heaviest drinking; and (3) controlling for age, body mass, smoking, former drinker, and former smoker status, duration of drinking, and sociodemographic factors. It also examines whether the relationship derived from these levels conforms to the U-shaped curve that demonstrates the protective effect of moderate drinking when abstainers are not used as the reference group. Relative to infrequent drinkers (less than 1 drink per day), men report more heart disease at the level of more than five drinks per day. However, black men also report more heart disease, relative to infrequent drinkers, at the greater than two drinks per day level; and women report more heart disease at the level of more than two drinks per day at the time of their heaviest drinking. Former drinkers of both genders, considered as an independent variable in the regression analysis, were more likely to report having heart disease. Abstainers, light drinkers, and infrequent drinkers were not significantly different in their reports of heart disease. Our results are consistent with studies that suggest protection from heart disease occurs only at lower levels of drinking. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA. RP Hanna, EZ (reprint author), NIAAA,DIV BIOMETRY & EPIDEMIOL,6000 EXECUT BLVD,BETHESDA,MD 20892, USA. NR 39 TC 27 Z9 29 U1 3 U2 5 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD FEB PY 1997 VL 21 IS 1 BP 111 EP 118 PG 8 WC Substance Abuse SC Substance Abuse GA WH416 UT WOS:A1997WH41600017 PM 9046382 ER PT J AU Welch, LW Cunningham, AT Eckardt, MJ Martin, PR AF Welch, LW Cunningham, AT Eckardt, MJ Martin, PR TI Fine motor speed deficits in alcoholic Korsakoff's syndrome SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article; Proceedings Paper CT RSA Annual Scientific Meeting CY JUN, 1995 CL STEAMBOAT SPRINGS, CO SP Nat Inst Alcohol Abuse DE neuropsychology; alcoholism; motor performance; Korsakoff's syndrome ID POSITRON EMISSION TOMOGRAPHY; NEUROPSYCHOLOGICAL DEFICITS; DETOXIFIED ALCOHOLICS; CORTEX AB Forty-two alcoholic Korsakoff's syndrome (KS) patients (12 in study I, 30 in study II) averaged slower tapping speeds than 35 alcoholic controls on the Halstead-Reitan manual finger tapping task. KS subjects also tapped slower than 26 normal volunteers in study II. Inverse relationships were found between finger-tapping speed dominant hand and verbal word fluency in one sample, and tapping speed and time to completion on Trail Making Part B and Tactual Performance Test in the other. The most powerful demographic predictors of tapping speed among age, education, length of abstinence, and affective state were age and education. Tapping speed was associated with cognitive tasks measuring frontal systems function (i.e., verbal fluency and Trail Making Part B) in KS subjects. There was no relationship between fine motor performance and general memory scores in the KS subjects. Decreased tapping speed for KS patients was postulated to result from compromised fine motor task initiation and persistence rather than mere slowing, as in Parkinson's disease. These findings suggest disruption of frontocerebellar systems that influence motor generation and set maintenance not previously explored in KS. C1 NIAAA,NATL INST HLTH,ROCKVILLE,MD 20852. VANDERBILT UNIV,MED CTR,SCH MED,ADULT NEUROPSYCHOL SERV,DEPT PSYCHIAT,DIV ALCOHOL & SUBST ABUSE,NASHVILLE,TN 37232. RI Martin, Peter/A-7738-2008 FU NIAAA NIH HHS [1R01AA08492] NR 36 TC 12 Z9 12 U1 1 U2 4 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD FEB PY 1997 VL 21 IS 1 BP 134 EP 139 PG 6 WC Substance Abuse SC Substance Abuse GA WH416 UT WOS:A1997WH41600021 PM 9046386 ER PT J AU Pawlosky, RJ Denkins, Y Ward, G Salem, N AF Pawlosky, RJ Denkins, Y Ward, G Salem, N TI Retinal and brain accretion of long-chain polyunsaturated fatty acids in developing felines: The effects of corn oil-based maternal diets SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE domestic felines; corn oil-based diets; n-3 fatty acids; pregnancy and lactation; docosahexaenoic acid; arachidonic acid; electroretinogram; brain; retina ID DOCOSAHEXAENOIC ACID; DEFICIENCY; METABOLISM; PREGNANCY; INFANTS; BIRTH; CAT; RAT AB A study was carried out in domestic felines to determine whether corn oil-based maternal diets are an adequate source of essential fatty acids to support normal accumulation of long-chain polyunsaturated fatty acids in the brains and retinas of offspring and whether these diets have any subsequent effect on visual function. Female domestic felines were acclimated to one of six different defined diets 1 mo before mating and maintained on the diets throughout pregnancy and lactation. Four diets contained only corn and hydrogenated coconut oils as their source of fat in ratios of 1:9, 3:7, 6:4, and 9:1, respectively. Two reference diets also contained the long-chain polyunsaturated fatty acids arachidonate (20:4n-6) and docosahexaenoate (22:6n-3). When the offspring were 8 wk old, electroretinograms were obtained and the a- and b-wave implicit times were determined. The results showed that animals raised in litters in which the maternal diets were devoid of 20:4n-6 and 22:6n-3 had an increase in a- and b-wave implicit times compared with the controls. In the rod outer segments and brains of these animals, there were lower amounts of 22:6n-3 and higher amounts of long-chain n-6 polyunsaturated fatty acids compared with control animals. These findings showed that although corn oil-based diets were capable of maintaining 20:4n-6 concentrations in the developing brain and retina, only those diets containing 22:6n-3 could support a high accumulation of docosahexaenoic acid in these tissues. Moreover, low amounts of 22:5n-6 in the brains of animals in all of the coin oil-diet groups suggested that young felines have a low biosynthetic capacity to produce this fatty acid or 22:6n-3. These findings suggest that in juvenile felines, maintenance of 22:6n-3 status in the nervous system is important for optimal retinal function. C1 NIAAA,DIV INTRAMURAL CLIN & BIOL RES,LAB MEMBRANE BIOCHEM & BIOPHYS,ROCKVILLE,MD 20852. NR 40 TC 57 Z9 58 U1 1 U2 2 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-2310, BETHESDA, MD 20814-3998 SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD FEB PY 1997 VL 65 IS 2 BP 465 EP 472 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA WF053 UT WOS:A1997WF05300010 PM 9022532 ER PT J AU Cutler, JA Follmann, D Allender, PS AF Cutler, JA Follmann, D Allender, PS TI Randomized trials of sodium reduction: An overview SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article; Proceedings Paper CT Conference on Dietary Sodium and Health CY DEC 15-16, 1994 CL ARLINGTON, VA SP Amer Acad Pediatr, Amer Coll Nutr, Amer Dietet Assoc, Amer Heart Assoc, Amer Soc Nutr Sci, Amer Soc Clin Nutr, Amer Soc Hyperten, Nat Kidney Found DE sodium reduction; blood pressure; clinical trials; meta-analysis ID BLOOD-PRESSURE RESPONSE; LEFT-VENTRICULAR MASS; HIGH-POTASSIUM DIET; LOW-SALT DIET; MILD HYPERTENSION; DOUBLE-BLIND; CLINICAL-TRIALS; HEART-DISEASE; RESTRICTION; SUPPLEMENTATION AB We updated a previously published overview of randomized clinical trials testing the effects of reducing sodium intake. We excluded trials that had confounded designs, enrolled preadolescent study populations, tested intakes outside the usual range for the US population, or reported neither systolic nor diastolic blood pressure. Thirty-two trials with outcome data for 2635 subjects were included. Two reviewers abstracted information independently and differences were reconciled. Pooled blood pressure differences between treated and control groups were highly significant for all trials combined and for trials in hypertensive and normotensive subjects pooled separately. The effects on blood pressure of lowering sodium in hypertensive and normotensive subjects, respectively (each trial weighted according to sample size), were -4.8/-2.5 and -1.9/-1.1 mm Hg (systolic/diastolic). Median differences in sodium excretion between sodium-reduction and control groups in these subgroups were -77 and -76 mmol/24 h, respectively. Weighted linear-regression analyses across the trials showed dose responses, which were more consistent for trials in normotensive subjects. These associations were, per 100 mmol Na/24 h, -5.8/-2.5 and -2.3/-1.4 mm Hg in hypertensive and normotensive subjects, respectively. There is no evidence that sodium reduction as achieved in these trials presents any safety hazards. The blood pressure reduction that would result from a substantial lowering of dietary sodium in the US population could reduce cardiovascular morbidity and mortality. C1 NHLBI, DIV EPIDEMIOL & CLIN APPLICAT, NIH, BETHESDA, MD 20892 USA. NR 52 TC 163 Z9 165 U1 1 U2 1 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9165 EI 1938-3207 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD FEB PY 1997 VL 65 IS 2 SU S BP 643 EP 651 PG 9 WC Nutrition & Dietetics SC Nutrition & Dietetics GA WF760 UT WOS:A1997WF76000010 ER PT J AU Whelton, PK Kumanyika, SK Cook, NR Cutler, JA Borhani, NO Hennekens, CH Kuller, LH Langford, H Jones, DW Satterfield, S Lasser, NL Cohen, JD AF Whelton, PK Kumanyika, SK Cook, NR Cutler, JA Borhani, NO Hennekens, CH Kuller, LH Langford, H Jones, DW Satterfield, S Lasser, NL Cohen, JD TI Efficacy of nonpharmacologic interventions in adults with high-normal blood pressure: Results from phase 1 of the trials of hypertension prevention SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article; Proceedings Paper CT Conference on Dietary Sodium and Health CY DEC 15-16, 1994 CL ARLINGTON, VA SP Amer Acad Pediatr, Amer Coll Nutr, Amer Dietet Assoc, Amer Heart Assoc, Amer Soc Nutr Sci, Amer Soc Clin Nutr, Amer Soc Hyperten, Nat Kidney Found DE prevention; high blood pressure; sodium; epidemiology; nutrition; body weight ID MILD HYPERTENSION; UNITED-STATES; HEART-DISEASE; SODIUM-INTAKE; DIETARY; REDUCTION; RISK; SALT; POPULATIONS; NEED AB Phase I of the Trials of Hypertension Prevention was conducted in 2182 adults, aged 35-54 y, with diastolic blood pressure of 80-89 mm Hg to test the feasibility and blood pressure-lowering effects of seven nonpharmacologic interventions (weight loss, sodium reduction, stress management, and supplementation with calcium, magnesium, potassium, and fish oil). At 6 and 18 mo, weight loss and sodium reduction were well-tolerated and produced significant declines in systolic and diastolic blood pressures (-2.9/-2.4 and -2.1/-1.2 mm Hg for weightless and sodium reduction, respectively, at 18 mo). None of the other interventions lowered blood pressure significantly at either the 6- or 18-mo follow-up visits. These results suggest that both weight loss and sodium reduction provide an effective means to prevent hypertension. The long-term effects of both of these interventions are being tested in phase 2 of the trial. C1 JOHNS HOPKINS UNIV, SCH HYG & PUBL HLTH, WELCH CTR PREVENT EPIDEMIOL & CLIN RES, BALTIMORE, MD USA. SCH MED, BALTIMORE, MD USA. PENN STATE UNIV, COLL MED, HERSHEY, PA USA. BRIGHAM & WOMENS HOSP, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, BOSTON, MA USA. SCH PUBL HLTH, BOSTON, MA USA. NHLBI, DIV EPIDEMIOL & CLIN APPLICAT, BETHESDA, MD 20892 USA. UNIV NEVADA, SCH MED, RENO, NV 89557 USA. UNIV PITTSBURGH, PITTSBURGH, PA 15260 USA. UNIV MISSISSIPPI, JACKSON, MS 39216 USA. UNIV TENNESSEE, MEMPHIS, TN USA. UNIV MED & DENT NEW JERSEY, NEW JERSEY MED SCH, NEWARK, NJ 07103 USA. ST LOUIS UNIV, SCH MED, ST LOUIS, MO USA. NR 51 TC 12 Z9 12 U1 0 U2 0 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9165 EI 1938-3207 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD FEB PY 1997 VL 65 IS 2 SU S BP 652 EP 660 PG 9 WC Nutrition & Dietetics SC Nutrition & Dietetics GA WF760 UT WOS:A1997WF76000011 ER PT J AU Cullen, M Noble, J Erlich, H Thorpe, K Beck, S Klitz, W Trowsdale, J Carrington, M AF Cullen, M Noble, J Erlich, H Thorpe, K Beck, S Klitz, W Trowsdale, J Carrington, M TI Characterization of recombination in the HLA class II region SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; E-BETA GENE; MEIOTIC RECOMBINATION; MOLECULAR CHARACTERIZATION; LINKAGE DISEQUILIBRIUM; HOT-SPOT; HOMOLOGOUS RECOMBINATION; OLIGONUCLEOTIDE PROBES; MOUSE H-2-COMPLEX; CEPH FAMILIES AB Studies of linkage disequilibrium across the HLA class II region have been useful in predicting where recombination is most likely to occur. The strong associations between genes within the 85-kb region from DQB1 to DRB1 are consistent with low frequency of recombination in this segment of DNA. Conversely, a lack of association between alleles of TAP1 and TAP2 (similar to 15 kb) has been observed, suggesting that recombination occurs here with relatively high frequency. Much of the HLA class II region has now been sequenced, providing the tools to undertake detailed analysis of recombination. Twenty-seven families containing one or two recombinant chromosomes within the 500-kb interval between the DPB1 and DRB1 genes were used to determine patterns of recombination across this region. SSCP analysis and microsatellite typing yielded identification of 127 novel polymorphic markers distributed throughout the class II region, allowing refinement of the site of crossover in 30 class II recombinant chromosomes. The three regions where recombination was observed most frequently are as follows: the 45-kb interval between HLA-DNA and RING3 (11 cases), the 50-kb interval between DQB3 and DQB1 (6 cases), and an 8.8-kb segment of the TAP2 gene (3 cases). Six of the 10 remaining recombinants await further characterization, pending identification of additional informative markers, while four recombinants were localized to other intervals (outliers). Analysis of association between markers flanking HLA-DNA to RING3 (45 kb), as well as TAP1 to TAP2 (15 kb), by use of independent CEPH haplotypes indicated little or no linkage disequilibrium, supporting the familial recombination data. A notable sequence motif located within a region associated with increased rates of recombination consisted of a (TGGA)(12) tandem repeat within the TAP2 gene. C1 NCI,FREDERICK CANC RES & DEV CTR,SAIC FREDERICK,INTRAMURAL RES SUPPORT PROGRAM,FREDERICK,MD 21702. ROCHE MOL SYST,DEPT HUMAN GENET,ALAMEDA,CA. SANGER CTR,HINXTON,ENGLAND. UNIV CALIF BERKELEY,DEPT INTEGRAT BIOL,BERKELEY,CA. IMPERIAL CANC RES FUND,HUMAN IMMUNOGENET LAB,LONDON WC2A 3PX,ENGLAND. FU NIGMS NIH HHS [GM35326]; Wellcome Trust NR 74 TC 103 Z9 108 U1 0 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD FEB PY 1997 VL 60 IS 2 BP 397 EP 407 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA WE931 UT WOS:A1997WE93100019 PM 9012413 ER PT J AU Yoshikawa, T Sanders, AR DeteraWadleigh, SD AF Yoshikawa, T Sanders, AR DeteraWadleigh, SD TI Contamination of sequence databases with adaptor sequences SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Letter ID DISEASE; SPERM RP Yoshikawa, T (reprint author), NIMH,CLIN NEUROGENET BRANCH,NIH,UNIT GENE MAPPING & EXPRESS,BLDG 10,ROOM 3N218,BETHESDA,MD 20892, USA. NR 20 TC 3 Z9 3 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD FEB PY 1997 VL 60 IS 2 BP 463 EP 466 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA WE931 UT WOS:A1997WE93100028 PM 9012422 ER PT J AU Leclerc, A Luce, D Demers, PA Boffetta, P Kogevinas, M Belli, S BolmAudorff, U Brinton, LA Colin, D Comba, P Gerin, M Hardell, L Hayes, RB Magnani, C Merler, E Morcet, JF PrestonMartin, S Vaughan, TL Zheng, W AF Leclerc, A Luce, D Demers, PA Boffetta, P Kogevinas, M Belli, S BolmAudorff, U Brinton, LA Colin, D Comba, P Gerin, M Hardell, L Hayes, RB Magnani, C Merler, E Morcet, JF PrestonMartin, S Vaughan, TL Zheng, W TI Sinonasal cancer and occupation. Results from the reanalysis of twelve case-control studies SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE case-control; sinonasal cancer; occupational exposures; leather; wood ID WOOD DUST EXPOSURE; PARA-NASAL SINUSES; PARANASAL SINUSES; CAVITY; FORMALDEHYDE; NOSE; MORTALITY; INDUSTRY; TEXTILE; PHARYNX AB A pooled reanalysis of twelve case-control studies on sinonasal cancer and occupation from seven countries was conducted in order to study associations with occupations other than wood- and leather-related occupations. The pooled data set included a total of 930 cases (680 men and 250 women) and 3,136 controls (2,349 men and 787 women). All the studies included a detailed occupational history for cases and controls. Each job was coded using the same classifications for occupation and industry. Two approaches were used in the analysis: systematic analysis of occupations; a priori analysis using a preestablished list of occupations and industries. The results confirmed associations observed in several studies not included in this analysis. For agricultural workers, significant excesses were observed for squamous cell carcinoma among women (OR=1.69) and men (OR=3.72 for ten years or more of employment as mt orchard worker), and adenocarcinomas among men (OR=2.98 for ten years or more of employment). Associations with textile occupations were observed for adenocarcinoma among women (OR=2.60) and squamous cell carcinoma among men (OR=5.09 for fiber prepares, 3.01 for bleachers). Elevated risks for both histologic types were observed among men employed in food manufacturing (OR=3.25, adenocarcinoma), or as food preserved (OR=13.9, squamous cell carcinoma), and among men employed as cooks (OR=1.99, squamous cell carcinonza). A positive association with squamous cell carcinoma was observed for male transport equipment operators (OR=1.21), and also with adenocarcinoma for male motor-vehicle drivers (OR=2.50). A number of other associations were observed in the systematic analysis. (C) l997 Wiley-Liss,lnc. C1 UNIV BRITISH COLUMBIA, VANCOUVER, BC V5Z 1M9, CANADA. INT AGCY RES CANC, F-69372 LYON, FRANCE. IST SUPER SANITA, I-00161 ROME, ITALY. HESSEN MINIST WOMEN WORK & SOCIAL WELF, WIESBADEN, GERMANY. NCI, BETHESDA, MD 20892 USA. UNIV MONTREAL, MONTREAL, PQ, CANADA. UNIV UMEA HOSP, S-90185 UMEA, SWEDEN. CANC EPIDEMIOL UNIT, TURIN, ITALY. USL, CSPO, FLORENCE, ITALY. UNIV CALIF LOS ANGELES, SCH MED, LOS ANGELES, CA USA. FRED HUTCHINSON CANC RES CTR, SEATTLE, WA 98104 USA. UNIV MINNESOTA, MINNEAPOLIS, MN 55455 USA. RP Leclerc, A (reprint author), HMSM, INSERM UNIT 88, 14 RUE VAL DOSNE, F-94410 ST MAURICE, FRANCE. RI Brinton, Louise/G-7486-2015; LUCE, Daniele/J-9125-2015; Kogevinas, Manolis/C-3918-2017; OI Brinton, Louise/0000-0003-3853-8562; Luce, Daniele/0000-0002-1708-4584 NR 32 TC 25 Z9 25 U1 2 U2 7 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD FEB PY 1997 VL 31 IS 2 BP 153 EP 165 PG 13 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA WF879 UT WOS:A1997WF87900004 PM 9028431 ER PT J AU Yu, ML Guo, YLL Hsu, CC Rogan, WJ AF Yu, ML Guo, YLL Hsu, CC Rogan, WJ TI Increased mortality from chronic liver disease and cirrhosis 13 years after the Taiwan ''yucheng'' (''oil disease'') incident SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE polychlorobiphenyl compounds; PCDFs; mortality; SMR; rice oil ID CAPACITOR MANUFACTURING WORKERS; POLYCHLORINATED-BIPHENYLS; CANCER MORTALITY; EXPOSURE AB In 1979, a mass poisoning involving some 2,000 persons occurred in central Taiwan from cooking oil contaminated by polychlorinated biphenyls (PCBs) and their hear-degraded byproducts, including polychlorinated dibenzofurans (PCDFs). The responsible health department register-ed cases for clinical purposes between 1979 and 1983. The exposed persons are referred to as the ''yucheng''(oil disease) cohort. PCBs and PCDFs are toxic chemicals widely dispersed in the environment and in human tissue, which persist long after exposure. The consequences of exposure to these agents are not well understood. We traced the cohort through December 31, 1991, and compared overall and cause-specific mortality of 1,837 ''yucheng'' subjects with age, gender and calendar time-specific mortality rates for the Taiwan general population. Eighty-three deaths were identified from 23,404 observed person-years. Evert though the overall standardized mortality ratio (SMR) was O.8 (95% confidence interval (Cl) 0.7-1.0), there was a substantial elevation in the mortality rate for chronic liver disease and cirrhosis (10 deaths, SMR = 2.7, 95% Cl = 1.3-4.9). Mortality from malignant neoplasms and other causes was not significantly different from that of the Taiwan population. PCB/PCDF exposure appears to promote the development of severe liver disease, perhaps in combination with known risk factors such as infection with hepatitis B virus. Further follow-up of this young cohort is necessary to see if the consequences include hepatic cancer. (C) 1997 Wiley-Liss, Inc. C1 NATL CHENG KUNG UNIV,COLL MED,DEPT ENVIRONM & OCCUPAT HLTH,TAINAN 70428,TAIWAN. NATL CHENG KUNG UNIV,COLL MED,DEPT PUBL HLTH,TAINAN 70428,TAIWAN. TAINAN CITY HOSP,DEPT PSYCHIAT,TAINAN,TAIWAN. NIEHS,OFF CLIN RES,RES TRIANGLE PK,NC 27709. RI Rogan, Walter/I-6034-2012; OI Rogan, Walter/0000-0002-9302-0160; GUO, Yue Leon/0000-0002-8530-4809 NR 18 TC 28 Z9 30 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD FEB PY 1997 VL 31 IS 2 BP 172 EP 175 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA WF879 UT WOS:A1997WF87900006 PM 9028433 ER PT J AU Tarone, RE Alavanja, MCR Zahm, SH Lubin, JH Sandler, DP McMaster, SB Rothman, N Blair, A AF Tarone, RE Alavanja, MCR Zahm, SH Lubin, JH Sandler, DP McMaster, SB Rothman, N Blair, A TI The agricultural health study: Factors affecting completion and return of self-administered questionnaires in a large prospective cohort study of pesticide applicators SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE epidemiologic methods; prospective cohort study; occupational exposure; selection bias (epidemiology); cancer ID NONRESPONSE BIAS; CARDIOVASCULAR-DISEASE; RISK-FACTORS; MAIL SURVEY; FOLLOW-UP; CANCER; MORTALITY; RESPONDENTS; MINNESOTA; LYMPHOMA AB Response rates were examined in a prospective epidemiologic study of individuals, mostly farmers, from Iowa and North Carolina seeking a pesticide applicator license during the period from 1994 through 1996. in the first year of enrollment 16,535 farmers (representing 77% of eligible farmers applicators) enrolled in the study by completing a 17-page questionnaire administered at a pesticide training session; 47% of the enrolled farmers completed and returned a much longer take-home questionnaire. The characteristics of farmers who completed only the enrollment questionnaire were quite similar to those of farmers who also completed and returned the take-home questionnaire. The most notable difference was the increased age of responders. Thus, the study population might have slightly higher cumulative farm exposures and slightly lower current farm exposures than the base population of all farmer applicators. The lack of evidence for substantial selection bias is reassuring for the Agricultural Health Study, and provides a measure of reassurance for other studies depending an the voluntary completion of self-administered questionnaires. (C) l997 Wiley-Liss, Inc. C1 NIEHS,RES TRIANGLE PK,NC 27709. US EPA,RES TRIANGLE PK,NC 27711. RP Tarone, RE (reprint author), NCI,EPIDEMIOL & BIOSTAT PROGRAM,EPN 403,BETHESDA,MD 20892, USA. RI Zahm, Shelia/B-5025-2015; OI Sandler, Dale/0000-0002-6776-0018 NR 32 TC 75 Z9 75 U1 1 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD FEB PY 1997 VL 31 IS 2 BP 233 EP 242 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA WF879 UT WOS:A1997WF87900013 PM 9028440 ER PT J AU Spong, CY Ghidini, A Sherer, DM Pezzullo, JC Ossandon, M Eglinton, GS AF Spong, CY Ghidini, A Sherer, DM Pezzullo, JC Ossandon, M Eglinton, GS TI Angiogenin: A marker for preterm delivery in midtrimester amniotic fluid SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE preterm delivery; angiogenin; amniotic fluid ID FETAL GROWTH-RETARDATION; INFECTION; LABOR; BIRTH; GENE AB OBJECTIVE: Neovascularization is a response of tissue to ischemic damage. Placental ischemia is thought to underlie a significant portion of preterm deliveries. Our objective was to evaluate whether angiogenin, a potent inducer of neovascularization, is increased in midtrimester amniotic fluid of patients destined to be delivered preterm. STUDY DESIGN: We designed a case-control study of singleton gestations undergoing midtrimester amniocentesis for standard genetic indications. Inclusion criteria were (1) pregnancy outcome information available, (2) gestational age at amniocentesis 15 to 20 weeks, (3) no evidence of fetal structural or chromosomal anomalies, and (4) absence of conditions associated with preterm delivery. Amniotic fluid angiogenin levels were measured by immunoassay and normalized by natural log transformation for statistical analysis. RESULTS: Eleven patients with preterm deliveries were matched with 33 controls. Amniotic fluid angiogenin levels were significantly higher in patients with preterm deliveries compared with controls (median 30.1 ng/ml [range 13.6 to 71.0 ng/ml] vs 17.8 ng/ml [7.8 to 43.3 ng/ml], p = 0.002). Demographic data were not significantly different. The association between angiogenin levels and preterm delivery persisted after small-for-gestational-age neonates were excluded (p = 0.02). Receiver-operator characteristic curve analysis showed that an angiogenin level of 31.0 ng/ml was the optimal cutoff point for prediction of preterm delivery (sensitivity 45.5%, specificity 91.0%, p = 0.03, odds ratio 6.0). CONCLUSIONS: Midtrimester amniotic fluid angiogenin levels are elevated in patients with preterm delivery. This supports the theory that preexisting intrauterine ischemia and inflammation are important risk factors for preterm delivery and may be already present in the early midtrimester. C1 GEORGETOWN UNIV,MED CTR,DEPT OBSTET & GYNECOL,PERINATAL RES FACIL,WASHINGTON,DC 20057. RP Spong, CY (reprint author), GEORGETOWN UNIV,MED CTR,NICHHD,PERINATAL RES BRANCH,WASHINGTON,DC 20057, USA. FU NICHD NIH HHS [N01-HD-3-3198] NR 20 TC 43 Z9 43 U1 1 U2 2 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD FEB PY 1997 VL 176 IS 2 BP 415 EP 418 DI 10.1016/S0002-9378(97)70508-8 PG 4 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA WJ937 UT WOS:A1997WJ93700027 PM 9065191 ER PT J AU Svinarich, DM Wolf, NA Gomez, R Gonik, B Romero, R AF Svinarich, DM Wolf, NA Gomez, R Gonik, B Romero, R TI Detection of human defensin 5 in reproductive tissues SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE infection; reproductive tract; defensins; RACE polymerase chain reaction ID HUMAN AMNIOTIC-FLUID; ANTIMICROBIAL PEPTIDE; SMALL-INTESTINE; GENE; DNA; CLONING; SYSTEM; CELLS AB OBJECTIVES: This study was undertaken to determine whether tissue-specific defensins are expressed within female reproductive tissues. STUDY DESIGN: Messenger ribonucleic acid from amnion, chorion, endometrium, endocervix, myometrium, placenta, small intestine, peripheral blood lymphocytes, and cervical, endometrial, and trophoblast cell lines was reverse transcribed with a 3'-RACE adapter. 3'-RACE polymerase chain reaction was conducted with an upstream human defensin 5 primer and 3'-RACE adapter primer, Polymerase chain reaction products hybridizing to a human defensin 5 probe were cloned for sequence analysis. Sequence data were compared against a nucleotide sequence database, and secondary structure predictions were made. RESULTS: Chorionic tissue, endocervical tissue, endometrial tissue, and an endometrial cell line all demonstrated a single hybridizing 362 bp polymerase chain reaction product. Sequence analysis of all clones demonstrated near-perfect identity with human defensin 5. CONCLUSIONS: Human endocervix, endometrium, and chorion express defensin 5 at the level of transcription. These findings suggest that a previously unrecognized mechanism of protecting female reproductive tissues against infection, by means of a natural antimicrobial system (defensins), may be present. C1 WAYNE STATE UNIV,SCH MED,DEPT OBSTET & GYNECOL,DETROIT,MI 48201. NICHHD,PERINATOL RES BRANCH,DETROIT,MI. NR 28 TC 83 Z9 86 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD FEB PY 1997 VL 176 IS 2 BP 470 EP 475 DI 10.1016/S0002-9378(97)70517-9 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA WJ937 UT WOS:A1997WJ93700036 PM 9065200 ER PT J AU Reynolds, TH Brozinick, JT Rogers, MA Cushman, SW AF Reynolds, TH Brozinick, JT Rogers, MA Cushman, SW TI Effects of exercise training on glucose transport and cell surface GLUT-4 in isolated rat epitrochlearis muscle SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE swim training; muscle contraction; glycogen ID SKELETAL-MUSCLE; PLASMA-MEMBRANE; PROTEIN-CONTENT; INSULIN; TRANSLOCATION; CONTRACTION; INCREASES; CAPACITY; STIMULATION; EXPRESSION AB The effects of exercise training on maximal glucose transport activity and cell surface GLUT-4 were examined in rat epitrochlearis muscle. Five days of swim training (2 x 3 h/day) produce a significant increase in citrate synthase activity (24.5 +/- 0.6 vs. 20.1 +/- 0.7 mu mol . min(-1) . g(-1)), GLUT-4 content (22.9 +/- 0.8 vs. 17.4 +/- 0.4% GLUT-4 standard), and glycogen levels (54.3 +/- 9.4 vs. 28.6 +/- 9.4 mu mol/g). Maximally, insulin-stimulated glucose transport activity and cell surface GLUT-4 are increased by 55 (1.50 +/- 0.11 vs. 0.97 +/- 0.10 mu mol . ml(-1) . 20 min(-1)) and 48% [12.0 +/- 0.8 vs. 8.1 +/- 0.9 disintegrations . min(-1) (dpm) . mg(-1)], respectively, in exercise-trained epitrochlearis muscles. In contrast, hypoxia-stimulated glucose transport activity and cell surface GLUT-4 are reduced by 38 (0.78 +/- 0.08 vs. 1.25 +/- 0.14 mu mol . ml(-1) . 20 min(-1)) and 40% (5.7 +/- 0.9 vs. 9.4 +/- 1.2 dpm/mg), respectively, in exercise-trained epitrochlearis muscles. These results demonstrate that changes in insulin- and hypoxia-stimulated glucose transport activity after exercise training are fully accounted for by the appearance of cell surface GLUT-4 and support the concept of two intracellular pools of GLUT-4. Finally, we propose that high levels of muscle glycogen with exercise training may contribute to the decrease in hypoxia-stimulated glucose transport activity. C1 UNIV MARYLAND, DEPT KINESIOL, COLLEGE PK, MD 20742 USA. RP Reynolds, TH (reprint author), NIDDKD, EXPT DIABET METAB & NUTR SECT,DIABET BRANCH,NIH, BLDG 10,RM 5N102, 10 CTR DR MSC 1420, BETHESDA, MD 20892 USA. NR 31 TC 28 Z9 28 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD FEB PY 1997 VL 272 IS 2 BP E320 EP E325 PG 6 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA WJ627 UT WOS:A1997WJ62700021 PM 9124341 ER PT J AU Vannucci, SJ Gibbs, EM Simpson, IA AF Vannucci, SJ Gibbs, EM Simpson, IA TI Glucose utilization and glucose transporter proteins GLUT-1 and GLUT-3 in brains of diabetic (db/db) mice SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE cerebral glucose utilization; diabetes; leptin ID RAT-BRAIN; CHRONIC HYPERGLYCEMIA; ENERGY-METABOLISM; GENE-EXPRESSION; IMMATURE RAT; BLOOD-FLOW; BARRIER; MELLITUS AB This study describes the effects of diabetes on brain growth, cerebral glucose utilization (CGU), and the glucose transporter proteins GLUT-1 and GLUT-3 in the genetically diabetic db/db mouse. Mice were studied at 5 and 10 wk of age and compared with age-matched nondiabetic littermates. At 5 wk, db/db mice were not yet hyperglycemic, but their body weights were 27.5% greater than those of their nondiabetic littermates. By 10 wk, db/db mice were both hyperglycemic (blood glucose values of 39.3 +/- 4.3 vs. 12.1 +/- 2.1 mmol/l for db/db and control, respectively) and obese, with a twofold increase in body weight. Significant reductions in brain weight were observed at 5 wk (15% decrease in brain wet wt), and no further brain growth was observed, such that by 10 wk, brains of db/db mice were 25% smaller than those of control mice; brain wet weight-to-dry weight ratios were slightly reduced. Global rates of CGU, as determined with 2-[C-14]deoxyglucose, were significantly reduced in the 10-wk diabetic mice. Levels of brain glucose and brain-to-blood glucose ratios were increased in 5- and 10-wk db/db mice, reflecting adequate glucose delivery to the brain. Blood-brain barrier GLUT-1 levels were unchanged, and mRNA levels were regionally increased. The expression of the neuronal glucose transporter GLUT-S was not reduced to a significant extent in brains of db/db mice. The results of this study indicate that the db/db mouse has markedly decelerated brain growth accompanied by global reductions in glucose metabolism that are not due to reductions in glucose transport capacity. C1 PFIZER INC, DIV CENT RES, DEPT METAB DIS, GROTON, CT 06340 USA. NIDDKD, EXPT DIABET METAB & NUTR SECT, DIABET BRANCH, NIH, BETHESDA, MD 20892 USA. RP Vannucci, SJ (reprint author), PENN STATE UNIV, MILTON S HERSHEY MED CTR, DEPT PEDIAT, HERSHEY, PA 17033 USA. NR 34 TC 70 Z9 71 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD FEB PY 1997 VL 272 IS 2 BP E267 EP E274 PG 8 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA WJ627 UT WOS:A1997WJ62700014 PM 9124334 ER PT J AU Mootha, VK Arai, AE Balaban, RS AF Mootha, VK Arai, AE Balaban, RS TI Maximum oxidative phosphorylation capacity of the mammalian heart SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE canine; swine; adenosine diphosphate; inorganic phosphate; myocardial oxygen consumption; oxidative phosphorylation; mitochondria; cytochrome A; symmorphosis ID ADENINE-NUCLEOTIDE TRANSLOCASE; OXYGEN-CONSUMPTION; BLOOD-FLOW; RAT-HEART; MITOCHONDRIA; RESPIRATION; MUSCLE; METABOLISM; PHOSPHATE; TRANSPORT AB It is difficult to estimate the maximum in vivo aerobic ATP production rate of the intact heart independent of limitations imposed by blood flow, oxygen delivery, and maximum mechanical power. This value is critical for establishing the kinetic parameters that control oxidative phosphorylation, as well as for providing insights into the limits of myocardial performance. In this study, the maximum ADP-P-i-driven heart mitochondrial respiratory rate (MVo(2mito)) was determined with saturating levels of oxygen, substrates, and cofactors at 37 degrees C. These rates were normalized to cytochrome alpha(1) alpha(3) (cytochrome oxidase; Cyt alpha) content. To extrapolate this rate to the intact heart, the Cyt alpha content of the myocardium (nmol Cyt alpha/g wet wt myocardium) was determined in the same hearts. The maximum ADP-P-i-driven mitochondrial respiratory rates were 676 +/- 31 and 665 +/- 65 nmol O-2 . min(-1). nmol Cyt alpha(-1) in the dog and pig, respectively. The Cyt alpha content in the two species was 43.6 +/- 2.4 and 36.6 +/- 3.1 nmol Cyt alpha/g wet wt, respectively. With these values, the MVo(2mito) was calculated to be 29.5 (dog) and 24.3 (pig) mu mol O-2 . min(-1). g wet wt myocardium(-1). Comparison with in vivo studies shows that the exercising heart can utilize 80-90% of its maximum oxidative capacity, implying there is little aerobic ATP production reserve in the mammalian heart. C1 NHLBI, Cardiac Energet Lab, NIH, Bethesda, MD 20892 USA. RP Balaban, RS (reprint author), NHLBI, Cardiac Energet Lab, NIH, Bldg 10,Rm B1D-161,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Balaban, Robert/A-7459-2009 OI Balaban, Robert/0000-0003-4086-0948 NR 35 TC 85 Z9 85 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD FEB PY 1997 VL 272 IS 2 BP H769 EP H775 PG 7 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA WJ809 UT WOS:A1997WJ80900024 PM 9124437 ER PT J AU Xiao, RP Pepe, S Spurgeon, HA Capogrossi, MC Lakatta, EG AF Xiao, RP Pepe, S Spurgeon, HA Capogrossi, MC Lakatta, EG TI Opioid peptide receptor stimulation reverses beta-adrenergic effects in rat heart cells SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE beta-adrenergic stimulation; cardiac myocytes; intracellular calcium; calcium current; contraction ID ADENYLATE-CYCLASE; CARDIAC MYOCYTES; PROTEIN-PHOSPHORYLATION; ENKEPHALIN PEPTIDES; MEDIATED INHIBITION; MESSENGER-RNA; CA2+; MODULATION; RELEASE; CALCIUM AB Opioid peptide receptor (OPR) agonists are co-released with the beta-adrenergic receptor (beta-AR) agonist norepinephrine (NE) from nerve terminals in the heart during sympathetic stimulation. Whereas recent studies indicate that OPR and beta-AR coexist on the surface of cardiac myocytes, whether significant "cross talk" occurs between OPR and beta-AR signaling cascades within heart cells is unknown. In the present study we demonstrate a marked effect of delta-OPR stimulation to modulate beta-adrenergic responses in single isolated rat ventricular myocytes. Nanomolar concentrations (10(-8) M) of the OPR agonist leucine enkephalin (LE), a naturally occurring delta-opioid peptide, inhibited NE-induced increases in sarcolemmal L-type Ca2+ current, cytosolic Ca2+ transient, and contraction. The antiadrenergic effect of LE was pertussis toxin sensitive and abolished by naloxone, an opioid receptor antagonist. In contrast, LE was unable to inhibit the positive inotropic effects induced by equipotent concentrations of 8-(4 chlorophenylthio)adenosine 3',5'-cyclic monophosphate, a cell-permeant adenosine 3',5'-cyclic monophosphate analog, or by the non-receptor-induced increase in contraction by elevated bathing Ca2+ concentration. These results indicate that an interaction of the OPR and beta-AR systems occurs proximal to activation of the adenosine 3',5'-cyclic monophosphate-dependent protein kinase of the beta-AR intracellular signaling pathway. This modulation of beta-adrenergic effects by OPR activation at the myocyte level may have important implications in the regulation of cardiac Ca2+ metabolism and contractility, particularly during the myocardial response to stress. C1 NIA, Gerontol Res Ctr, Cardiovasc Sci Lab, Baltimore, MD 21224 USA. RP Xiao, RP (reprint author), NIA, Gerontol Res Ctr, Cardiovasc Sci Lab, 4940 Eastern Ave, Baltimore, MD 21224 USA. NR 39 TC 54 Z9 59 U1 0 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD FEB PY 1997 VL 272 IS 2 BP H797 EP H805 PG 9 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA WJ809 UT WOS:A1997WJ80900028 PM 9124441 ER PT J AU Ebina, M Hoyt, RF McNelly, NAF Sorokin, SP Linnoila, RI AF Ebina, M Hoyt, RF McNelly, NAF Sorokin, SP Linnoila, RI TI Effects of hydrogen and bicarbonate ions on endocrine cells in fetal rat lung organ cultures SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Article DE pulmonary endocrine cell; calcitonin gene-related peptide; pH ID GENE-RELATED PEPTIDE; NEURO-EPITHELIAL BODIES; CAROTID-BODY CELLS; NEUROEPITHELIAL BODIES; INTRACELLULAR PH; CALCIUM CHANNELS; NEONATAL RAT; SUBSTANCE-P; CALCITONIN; IMMUNOREACTIVITY AB Concentrations of H+ and HCO3, rise in fluid lining hypercapnic airways. Effects of these ions on pulmonary endocrine cells were studied in 119 fetal rat lung organ cultures by semiquantitative staining for calcitonin gene-related peptide (CGRP)-like immunoreactive material. Intracellular CGRP was determined in cultures under ''no-release'' baseline conditions and after incubation in control or test media. After exposure to HCO3--free medium at pH 7.4 (incubation control), CGRP fell moderately from no-release levels. Bombesin (1 ng/ml) promoted further significant loss of peptide, which was dependent on extracellular Ca2+ and inhibited by somatostatin and [D-Arg(1),D-Pro(2),D-Trp(7,9) ,Leu(11)] substance P, a bombesin receptor antagonist. CGRP staining of explants incubated with 24 mM HCO, maintained no-release levels at and above pH 7.1 but decreased significantly at pH 6.8. The drop was blocked by somatostatin or exclusion of HCO3, and was not augmented by bombesin or 48 mM HCO,. Results suggest that pulmonary endocrine cells may respond to hypercapnia by releasing bioactive peptides like CGRP, thus stimulating afferent nerves and altering patterns of ventilation and perfusion. C1 BOSTON UNIV, SCH MED, DEPT ANAT & NEUROBIOL, LAB PULM CELL BIOL, BOSTON, MA 02118 USA. NCI, NATL INST HLTH, DIV CLIN SCI, BIOMARKERS & PREVENT RES BRANCH, ROCKVILLE, MD 20850 USA. FU NHLBI NIH HHS [HL-19379] NR 42 TC 4 Z9 4 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1040-0605 J9 AM J PHYSIOL-LUNG C JI Am. J. Physiol.-Lung Cell. Mol. Physiol. PD FEB PY 1997 VL 272 IS 2 BP L178 EP L186 PG 9 WC Physiology; Respiratory System SC Physiology; Respiratory System GA WJ524 UT WOS:A1997WJ52400002 PM 9124367 ER PT J AU Alexander, GE Furey, ML Grady, CL Pietrini, P Brady, DR Mentis, MJ Schapiro, MB AF Alexander, GE Furey, ML Grady, CL Pietrini, P Brady, DR Mentis, MJ Schapiro, MB TI Association of premorbid intellectual function with cerebral metabolism in Alzheimer's disease: Implications for the cognitive reserve hypothesis SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article; Proceedings Paper CT 24th Annual Meeting of the Society-for-Neuroscience CY NOV 13-18, 1994 CL MIAMI BEACH, FL SP Soc Neurosci ID GLUCOSE-UTILIZATION; BLOOD-FLOW; DEMENTIA; EDUCATION; PREVALENCE; ATTENTION; OCCUPATION; TOMOGRAPHY; DIAGNOSIS; CORTEX AB Objective: Clinical heterogeneity in Alzheimer's disease has been widely observed. One factor that may influence the expression of dementia in Alzheimer's disease is premorbid intellectual ability. It has been hypothesized that premorbid ability, as measured by educational experience, reflects a cognitive reserve that can affect the clinical expression of Alzheimer's disease. The authors investigated the relation between estimates of premorbid intellectual function and cerebral glucose metabolism in patients with Alzheimer's disease to test the effect of differing levels of premorbid ability on neurophysiological dysfunction. Method: In a resting state with eyes closed and ears occluded, 46 patients with Alzheimer's disease were evaluated with positron emission tomography and [F-18]-2-fluoro-2-deoxy-D-glucose to determine cerebral metabolism. Premorbid intellectual ability was assessed by a demographics-based IQ estimate and performance on a measure of word-reading ability. Results: After the authors controlled for demographic characteristics and dementia severity, both estimates of premorbid intellectual ability were inversely correlated with cerebral metabolism in the prefrontal, premotor, and left superior parietal association regions. In addition, the performance-based estimate (i.e., reading ability) was inversely correlated with metabolism in the anterior cingulate, paracentral, right orbitofrontal, and left thalamic regions, after demographic and clinical variables were controlled for. Conclusions: The results suggest that higher levels of premorbid ability are associated with greater pathophysiological effects of Alzheimer's disease among patients of similar dementia severity levels. These findings provide support for a cognitive reserve that can alter the clinical expression of dementia and influence the neurophysiological heterogeneity observed in Alzheimer's disease. RP Alexander, GE (reprint author), NIA,NEUROSCI LAB,BLDG 10,9000 ROCKVILLE PIKE,RM 6C414,BETHESDA,MD 20892, USA. RI Furey, Maura/H-5273-2013 NR 51 TC 193 Z9 195 U1 3 U2 13 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD FEB PY 1997 VL 154 IS 2 BP 165 EP 172 PG 8 WC Psychiatry SC Psychiatry GA WF150 UT WOS:A1997WF15000005 PM 9016263 ER PT J AU Mitchell, PB Manji, HK Chen, G Jolkovsky, L SmithJackson, E Denicoff, K Schmidt, M Potter, WZ AF Mitchell, PB Manji, HK Chen, G Jolkovsky, L SmithJackson, E Denicoff, K Schmidt, M Potter, WZ TI High levels of G(s)alpha in platelets of euthymic patients with biopolar affective disorder SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID BIPOLAR AFFECTIVE-DISORDER; CONGESTIVE-HEART-FAILURE; G-PROTEINS; ADRENERGIC-RECEPTORS; SIGNAL TRANSDUCTION; ADENYLATE-CYCLASE; RAT CORTEX; LITHIUM; BINDING; EXERCISE AB Objective: Previous investigations have suggested the involvement of signal-transducing guanine-nucleotide-binding proteins (G proteins) both in the mechanism of action of lithium and in the pathophysiology of bipolar affective disorder. To determine whether such G protein abnormalities are a trait phenomenon, the authors investigated the levels of G protein ex subunits in platelets and lymphocytes of euthymic patients with bipolar affective disorder. Method: Selective antibodies were used to quantitate levels of G protein a subunits regulating adenylylcyclase activity (G(s) alpha-both 45- and 52-kDa forms-and G(i1-2)alpha) and those regulating phosphoinositide turnover (G(q/11)alpha) in both platelets and lymphocytes of 44 euthymic patients with bipolar affective disorder and 27 matched comparison subjects. Results: Levels of both G(s) alpha 45 and G(s) alpha 52 were higher in the platelets of the euthymic bipolar patients (both bipolar I and bipolar II) than in those of the comparison subjects. Conclusions: These findings are consistent with previous reports of high G(s) alpha levels in bipolar affective disorder and, furthermore, suggest that such levels may be a trait abnormality for this condition. C1 NIMH,EXPT THERAPEUT BRANCH,BETHESDA,MD 20892. NIMH,BIOL PSYCHIAT BRANCH,BETHESDA,MD 20892. UNIV NEW S WALES,SCH PSYCHIAT,FAC MED,SYDNEY,NSW,AUSTRALIA. RI Schmidt, Mark/I-5052-2016; Chen, Guang/A-2570-2017; OI Schmidt, Mark/0000-0003-3417-8977; Mitchell, Philip/0000-0002-7954-5235 NR 33 TC 45 Z9 49 U1 0 U2 2 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD FEB PY 1997 VL 154 IS 2 BP 218 EP 223 PG 6 WC Psychiatry SC Psychiatry GA WF150 UT WOS:A1997WF15000013 PM 9016271 ER PT J AU Marangell, LB Ketter, TA George, MS Pazzaglia, PJ Callahan, AM Parekh, P Andreason, PJ Horwitz, B Herscovitch, P Post, RM AF Marangell, LB Ketter, TA George, MS Pazzaglia, PJ Callahan, AM Parekh, P Andreason, PJ Horwitz, B Herscovitch, P Post, RM TI Inverse relationship of peripheral thyrotropin-stimulating hormone levels to brain activity in mood disorders SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article; Proceedings Paper CT 147th Annual Meeting of the American-Psychiatric-Association CY MAY 21-26, 1994 CL PHILADELPHIA, PA SP Amer Psychiat Assoc, NIMH, Dept Vet Affairs, Cooperat Studies Program, Med Res Serv ID POSITRON EMISSION TOMOGRAPHY; CEREBRAL BLOOD-FLOW; SLEEP-DEPRIVATION; AFFECTIVE-ILLNESS; GLUCOSE-METABOLISM; NEUROENDOCRINOLOGICAL INVESTIGATIONS; ENDOGENOUS-DEPRESSION; MAJOR DEPRESSION; THYROID-FUNCTION; PROLACTIN AB Objective: The authors' goal was to investigate relationships between peripheral thyroid hormone levels and cerebral blood flow (CBF) and cerebral glucose metabolism in affectively ill patients. Method: Medication-free inpatients with major depression or bipolar disorder were studied with oxygen-15 water and positron emission tomography (PET) to measure CBF (N=19) or with [F-18]fluorodeoxyglucose and PET to measure cerebral glucose metabolism (N=29). Linear regression was used to correlate global CBF and cerebral glucose metabolism with serum thyrotropin-stimulating hormone (TSH), triiodothyronine (T-3), thyroxine (T-4), and free T-4 concentrations. Statistical parametric mapping was used to correlate regional CBF and cerebral glucose metabolism with these thyroid indexes. Post hoc t tests were used to further explore the relationships between serum TSH and global CBF and cerebral glucose metabolism. Results: Serum TSH was inversely related to both global and regional CBF and cerebral glucose metabolism. These relationships persisted in the cerebral glucose metabolism analysis and to a lesser extent, in the CBF analysis after severity of depression had been controlled for. In contrast, no significant relationships were observed between T-3, T-4, or free T-4 and global or regional CBF and cerebral glucose metabolism. Conclusions: These data suggest that peripheral TSH (putatively the best marker of thyroid status) is inversely related to global and regional CBF and cerebral glucose metabolism. These findings indicate relationships between thyroid and cerebral activity that could provide mechanistic hypotheses for thyroid contributions to primary and secondary mood disorders and the psychotropic effects of thyroid axis manipulations. C1 NIH,BETHESDA,MD 20892. NR 52 TC 47 Z9 51 U1 0 U2 0 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD FEB PY 1997 VL 154 IS 2 BP 224 EP 230 PG 7 WC Psychiatry SC Psychiatry GA WF150 UT WOS:A1997WF15000014 PM 9016272 ER PT J AU Read, JS Troendle, JF Klebanoff, MA AF Read, JS Troendle, JF Klebanoff, MA TI Infectious disease mortality among infants in the United States, 1983 through 1987 SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID POSTNEONATAL MORTALITY; BIRTH-WEIGHT; RISK; DEATHS; POPULATION; CHILDREN; TRENDS; AGE AB Objectives. The purpose of this study was to determine the relative importance of infectious disease as a cause of infant mortality in the United States and to identify characteristics at birth associated with subsequent infectious disease mortality. Methods. Birth and infant death certificate data from the National Center for Health Statistics (NCHS) 1983 through 1987 Linked Birth/ Infant Death Data Sets were analyzed. Results. Infection was the underlying cause of death for over 16 000 infants, representing the fourth leading cause of mortality in this cohort. Almost 90% of infectious disease deaths during infancy were due to noncongenital infections, and the majority of these deaths occurred during the postneonatal period. Low birthweight, preterm birth, and male gender were independently associated with postneonatal mortality due to noncongenital infection. Conclusions. NCHS should revise its classification system for causes of infant mortality to incorporate an ''infectious Diseases'' category. Future research should be directed toward clarifying the low birthweight-infectious disease mortality relationship and determining the degree to which infection-related infant deaths might be prevented by existing vaccines or improved access to health care. RP Read, JS (reprint author), NICHHD,DIV EPIDEMIOL STAT & PREVENT RES,NIH,6100 EXECUT BLVD,ROOM 4B11F,BETHESDA,MD 20892, USA. NR 33 TC 25 Z9 26 U1 0 U2 1 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD FEB PY 1997 VL 87 IS 2 BP 192 EP 198 DI 10.2105/AJPH.87.2.192 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA WN493 UT WOS:A1997WN49300012 PM 9103096 ER PT J AU Susser, E Valencia, E Conover, S Felix, A Tsai, WY Wyatt, RJ AF Susser, E Valencia, E Conover, S Felix, A Tsai, WY Wyatt, RJ TI Preventing recurrent homelessness among mentally ill men: A ''critical time'' intervention after discharge from a shelter SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID ASSERTIVE COMMUNITY TREATMENT; HOSPITAL TREATMENT; TREATMENT PROGRAM; RISK-FACTORS; COST; DIAGNOSIS; ILLNESS; MODEL; CARE AB Objectives. This study examined a strategy to prevent homelessness among individuals with severe mental illness by providing a bridge between institutional and community care. Methods. Ninety-six men with severe mental illness who were entering community housing from a shelter institution were randomized to receive 9 months of a ''critical time'' intervention plus usual services or usual services only. The primary analysis compared the mean number of homeless nights for the two groups during the 18-month follow-up period, To elucidate time trends, survival curves were used. Results. Over the 18-month follow-up period, the average number of homeless nights was 30 for the critical time intervention group and 91 for the usual services group, Survival curves showed that after the 9-month period of active intervention, the difference between the two groups did not diminish. Conclusions. Strategies that focus on a critical time of transition may contribute to the prevention of recurrent homelessness among individuals with mental illness, even after the period of active intervention. C1 COLUMBIA UNIV,NEW YORK STATE PSYCHIAT INST,SCH PUBL HLTH,NEW YORK,NY 10032. PRESBYTERIAN HOSP PSYCHIAT SERV,NEW YORK,NY. NEW YORK ACAD MED,CTR URBAN EPIDEMIOL STUDIES,NEW YORK,NY. NIMH,NEUROPSYCHIAT BRANCH,BETHESDA,MD 20892. RP Susser, E (reprint author), COLUMBIA UNIV,NEW YORK STATE PSYCHIAT INST,SCH MED,722 W 168TH ST,BOX 24,NEW YORK,NY 10032, USA. FU NIMH NIH HHS [5-R18-MH48041] NR 47 TC 156 Z9 161 U1 2 U2 12 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD FEB PY 1997 VL 87 IS 2 BP 256 EP 262 DI 10.2105/AJPH.87.2.256 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA WN493 UT WOS:A1997WN49300022 PM 9103106 ER PT J AU Nebeling, LC Forman, MR Graubard, BI Snyder, RA AF Nebeling, LC Forman, MR Graubard, BI Snyder, RA TI The impact of lifestyle characteristics on carotenoid intake in the United States: The 1987 National Health Interview Survey SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID FOOD FREQUENCY QUESTIONNAIRE; CANCER PREVENTION; DIET; VEGETABLES; SMOKERS; SMOKING; ALCOHOL C1 INFORMAT MANAGEMENT SERV INC,SILVER SPRING,MD. RP Nebeling, LC (reprint author), NCI,DIV CANC PREVENT & CONTROL,EPN,SUITE 211,6130 EXECUT BLVD,MSC 7326,BETHESDA,MD 20892, USA. NR 21 TC 26 Z9 26 U1 0 U2 2 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD FEB PY 1997 VL 87 IS 2 BP 268 EP 271 DI 10.2105/AJPH.87.2.268 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA WN493 UT WOS:A1997WN49300024 PM 9103108 ER PT J AU Kiang, J Szu, SSC Wang, LX Tang, M Lee, YC AF Kiang, J Szu, SSC Wang, LX Tang, M Lee, YC TI Determination of 2-keto-3-deoxyoctulosonic acid (KDO) with high-performance anion-exchange chromatography (HPAEC): Survey of stability of KDO and optimal hydrolytic conditions SO ANALYTICAL BIOCHEMISTRY LA English DT Article ID PULSED AMPEROMETRIC DETECTION; OLIGOSACCHARIDES AB A new method for 2-keto-3-deoxy-octulosonic acid (KDO) determination using high-performance anion-exchange chromatography was developed. KDO is well separated from Neu5Ac, and the response was linear from 20 pmol to 5 nmol. The method was used to examine the stability of KDO under various hydrolytic conditions and to survey optimal hydrolytic conditions for release of KDO. (C) 1997 Academic Press. C1 JOHNS HOPKINS UNIV,DEPT BIOL,BALTIMORE,MD 21218. NICHHD,NIH,BETHESDA,MD 20892. NR 15 TC 14 Z9 14 U1 0 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD FEB 1 PY 1997 VL 245 IS 1 BP 97 EP 101 DI 10.1006/abio.1996.9951 PG 5 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA WE924 UT WOS:A1997WE92400013 PM 9025974 ER PT J AU Linder, CY Elkahloun, AG Bittner, M Trent, JM Meltzer, PS AF Linder, CY Elkahloun, AG Bittner, M Trent, JM Meltzer, PS TI Restriction mapping of recombinant cosmid clones using lambda terminase and field inversion gel electrophoresis SO ANALYTICAL BIOCHEMISTRY LA English DT Article ID DNA-MOLECULES; VECTOR; FRAGMENTS RP Linder, CY (reprint author), NCI,NATL CTR HUMAN GENOME RES,CANC GENET LAB,BETHESDA,MD 20892, USA. NR 14 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD FEB 1 PY 1997 VL 245 IS 1 BP 105 EP 107 DI 10.1006/abio.1996.9956 PG 3 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA WE924 UT WOS:A1997WE92400015 PM 9025976 ER PT J AU Njoku, DB Pohl, LR Martin, JL AF Njoku, DB Pohl, LR Martin, JL TI Compound A toxicity in Wistar rats: Role of thiols SO ANESTHESIA AND ANALGESIA LA English DT Meeting Abstract C1 JOHNS HOPKINS MED INST,DEPT ANES,BALTIMORE,MD 21287. NIH,MOL & CELLULAR TOXICOL SECT,BETHESDA,MD 20892. NR 4 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD FEB PY 1997 VL 84 SU 2 BP S530 EP S530 PG 1 WC Anesthesiology SC Anesthesiology GA WF780 UT WOS:A1997WF78000529 ER PT J AU Berman, CM Rasmussen, KLR Suomi, SJ AF Berman, CM Rasmussen, KLR Suomi, SJ TI Group size, infant development and social networks in free-ranging rhesus monkeys SO ANIMAL BEHAVIOUR LA English DT Article ID MACACA-MULATTA; VERVET MONKEYS; CAYO-SANTIAGO; PROXIMITY; MACAQUES; MATRICES AB The hypothesis that demographic processes are important in determining social structure among non-human primates through their effects on the development of individual social relationships was tested. Changes in maternal behaviour, infants' social milieux and infants' social networks were examined as a function of changes in group size and composition among free-ranging rhesus monkeys, Macaca mulatta, on Cayo Santiago, Puerto Rico. Data were analysed for 10 group-years collected between 1974 and 1990 representing a single social group during periods of rapid expansion and fissioning, two daughter groups following fissioning and an unrelated group that did not undergo fissioning. As group size expanded, infants found themselves near (<5 m) larger numbers of group members and smaller proportions of close kin. Mothers spent more time near their infants and sought more proximity with them. Infants developed social networks that were more highly kin biased. When the groups fissioned, these trends reversed. Significant correlations were found between group size, mother-infant interaction and infant social networks across all group-years. Individual variation in the degree to which infant social networks were kin biased was related both directly to the infant's social milieu and indirectly to its relationship with its mother. Given the long-term nature of the mother's influence on social networks, these results suggest that demographic influences on developmental processes can lead to progressive changes in social structure in the absence of resource scarcity. (C) 1997 The Association for the Study of Animal Behaviour. C1 NICHHD,COMPARAT ETHOL LAB,POOLESVILLE,MD 20837. RP Berman, CM (reprint author), SUNY BUFFALO,DEPT ANTHROPOL,BUFFALO,NY 14260, USA. NR 47 TC 47 Z9 49 U1 1 U2 29 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0003-3472 J9 ANIM BEHAV JI Anim. Behav. PD FEB PY 1997 VL 53 BP 405 EP 421 DI 10.1006/anbe.1996.0321 PN 2 PG 17 WC Behavioral Sciences; Zoology SC Behavioral Sciences; Zoology GA WP960 UT WOS:A1997WP96000018 ER PT J AU Pajak, A Williams, OD Broda, G Baczynska, E Rywik, S Davis, CE Kawalec, E Chodkowska, E Irving, S Manolio, T AF Pajak, A Williams, OD Broda, G Baczynska, E Rywik, S Davis, CE Kawalec, E Chodkowska, E Irving, S Manolio, T TI Changes over time in blood lipids and their correlates in Polish rural and urban populations: The Poland United States Collaborative Study in Cardiopulmonary Disease Epidemiology SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE lipids; correlates; nutrition; POL-MONICA Project; Poland; United States; cardiovascular disease; epidemiology ID CORONARY HEART-DISEASE; CARDIOVASCULAR EPIDEMIOLOGY; RISK-FACTORS; CHOLESTEROL; THERAPY; WOMEN; MEN AB PURPOSE: The purpose of this manuscript is to examine changes in blood lipid levels and related factors between 1983 and 1987 in two selected Polish populations, to evaluate these changes and their association with other coronary heart disease (CHD) risk factors, and to examine the nutrient intake changes for consistency with observed lipid changes. METHODS: Men and women, aged 35-64 were screened from Warsaw and rural Tamobrzeg province, Poland-the Pol-MONICA screening sites. An independent random sample of 5132 screened in 1983-84 and a second independent random sample of 2596 screened in 1987-88 were compared. A 25% cohort of the 1983-84 sample was also rescreened in 1987-88 (n = 1236) and 24-hour dietary recall information on this cohort was used to evaluate nutrient intake changes and their relationship to the lipid changes. RESULTS: For the random samples, the total cholesterol increased by 5.1 mg/dL (rural) and by 7.9 mg/dL (urban) for women; there were no significant changes among men. Low-density lipoprotein cholesterol (LDL-C) increased for all site and gender subgroups by 5.4-8.7 mg/dL. Among rural men and women, high-density lipoprotein cholesterol (HDL-C) decreased by 3.4 and 3.3 mg/dL, respectively, whereas it increased by 3.3 mg/dL among urban women and did not change among urban men. Total triglycerides (TG) increased by 9.5 mg/dL for rural men, with no significant change for rural women. For urban men and women, TG decreased by 29.5 and 21.8 mg/dL respectively. In the cohort, changes in dietary intake (decreases in energy from fat, Keys index and increases in the polyunsaturated to saturated fats ratio) were related to a decrease in TC at both sites and to a decrease or smaller increase in LDL-C for rural men. CONCLUSIONS: The observed changes were generally unfavorable, with a decrease in the proportion of persons with desirable lipid levels. At both sites nutritional changes were favorable, including a drop in total energy intake. Less pronounced were changes in percentages of total energy from fats, where the only significant decrease was for rural women; however, improvements in dietary fat composition and declines in cholesterol consumption were found. These favorable changes in diet were not strong enough or were not in effect long enough to counter the unfavorable changes in blood lipids. (C) 1997 by Elsevier Science Inc. C1 JAGIELLONIAN UNIV,SCH PUBL HLTH,UNIT CLIN EPIDEMIOL & POPULAT STUDIES,POL MONICA KRAKOW PROJECT,KRAKOW,POLAND. UNIV ALABAMA,SCH PUBL HLTH,DEPT BIOSTAT,BIRMINGHAM,AL 35294. CARDINAL WYSZYNSKI NATL INST CARDIOL,DEPT EPIDEMIOL & PREVENT CARDIOVASC DIS,WARSAW,POLAND. UNIV N CAROLINA,SCH PUBL HLTH,DEPT BIOSTAT,CHAPEL HILL,NC. NHLBI,BETHESDA,MD 20892. FU NHLBI NIH HHS [N01-HV-1-2243, N01-HV-0-8112, N01-HV-5-9224] NR 25 TC 5 Z9 5 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 1047-2797 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD FEB PY 1997 VL 7 IS 2 BP 115 EP 124 DI 10.1016/S1047-2797(96)00125-1 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA WQ521 UT WOS:A1997WQ52100006 PM 9099399 ER PT J AU Shaten, BJ Kuller, LH Kjelsberg, MO Stamler, J Ockene, JK Cutler, JA Cohen, JD AF Shaten, BJ Kuller, LH Kjelsberg, MO Stamler, J Ockene, JK Cutler, JA Cohen, JD TI Lung cancer mortality after 16 years in MRFIT participants in intervention and usual care groups SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE lung cancer; mortality; intervention studies; smoking cessation; clinical trials ID MALE BRITISH DOCTORS; TRIAL; SMOKING; HEALTH; DEATH AB PURPOSE: The Multiple Risk Factor Intervention Trial (MRFIT), a randomized clinical trial for the primary prevention of coronary heart disease, enrolled 12,866 men (including 8194 cigarette smokers) aged 35-57 years at 22 clinical centers across the United States. Participants were randomized either to special intervention (SI), which included an intensive smoking cessation program, or to usual care (UC). After 16 years of follow-up, lung cancer mortality rates were higher in the SI than in the UC group. Since rates of smoking cessation in SI were higher than those for UC for the 6 years of the trial, and since risk of lung cancer mortality is known to decline with smoking cessation, these results were unexpected. The purpose of the present study was to investigate hypotheses that could explain the higher observed lung cancer mortality rates in the SI as compared with the UC group. METHODS: Analytic methods were employed to determine whether SI and UC participants differed either in baseline characteristics or in characteristics that changed during the trial and to determine whether these differences could explain the higher rates of lung cancer mortality among SI as compared to UC participants. Rates of mortality from coronary heart (CHD) were examined to explore the possibility that prevention of CHD death may have contributed to greater mortality due to lung cancer in the SI group. RESULTS: From randomization through December 1990, 135 SI and II? UC participants died from lung cancer. The relative difference between the SI and U groups adjusted for age and number of cigarettes smoked per day, was 1.17 (95% CI:0.92-1.51). The greatest difference between the SI and UC groups in lung cancer mortality rates occurred among the heaviest smokers at baseline who did not achieve sustained smoking cessation by year 2. In this group the rates of death from CHD were approximately the same among the SI and UC subjects. No differences in baseline characteristics were found between SI and UC smokers who did not achieve sustained cessation by year 2, and there were no differences;in follow-up characteristics between the two study groups that could explain the difference in lung cancer mortality. CONCLUSIONS: None of the hypotheses proposed to explain the unexpected higher rates of lung cancer mortality among SI as compared with UC subjects were sustained by the data. Thus we conclude that the difference observed is due to chance, and that a longer period of sustained smoking cessation plus follow-up is necessary to detect a reduction in lung cancer mortality as a result of smoking cessation intervention in a randomized clinical trial. (C) 1997 by Elsevier Science Inc. C1 UNIV PITTSBURGH,GRAD SCH PUBL HLTH,PITTSBURGH,PA. NORTHWESTERN UNIV,DEPT PREVENT MED,SCH MED,CHICAGO,IL 60611. UNIV MASSACHUSETTS,MED CTR,DEPT MED,DIV PREVENT & BEHAV MED,WORCESTER,MA. NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,BETHESDA,MD 20892. ST LOUIS UNIV,MED CTR,ST LOUIS,MO. RP Shaten, BJ (reprint author), UNIV MINNESOTA,SCH PUBL HLTH,COORDINATING CTR BIOMET RES,SUITE 200,2221 UNIV AVE SE,MINNEAPOLIS,MN 55414, USA. FU NHLBI NIH HHS [R01 HL43232] NR 19 TC 22 Z9 23 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 1047-2797 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD FEB PY 1997 VL 7 IS 2 BP 125 EP 136 DI 10.1016/S1047-2797(96)00123-8 PG 12 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA WQ521 UT WOS:A1997WQ52100007 PM 9099400 ER PT J AU DeRijk, R Sternberg, EM AF DeRijk, R Sternberg, EM TI Corticosteroid resistance and disease SO ANNALS OF MEDICINE LA English DT Article DE glucocorticoid receptor; glucocorticoids; pathology; resistance ID CORTICOTROPIN-RELEASING HORMONE; GLUCOCORTICOID RECEPTOR; BIOCHEMICAL MANIFESTATIONS; DEPRESSION; STRESS; NEUROBIOLOGY; AFFINITY; THERAPY; BINDING; ASTHMA AB Both the unpredictability of side-effects and efficacy of glucocorticoid treatment can be problematic during clinical treatment. Here we discuss the evidence that exists for the hypothesis that individual glucocorticoid sensitivity underlies this problem. We suggest that glucocorticoid sensitivity is actually much more dynamic and common than previously thought. It is postulated that acquired tissue-specific glucocorticoid resistance could play a role in the origin and pathogenesis of depression, autoimmune disorders and AIDS. Moreover, recent genetic research has shown mutations in the glucocorticoid receptor (on) gene and GR protein which are suggested to play a role in the pathogenesis of leukaemia, hereditary glucocorticoid resistance and Nelson's syndrome. These findings indicate that variations in the on and in glucocorticoid resistance play a central role in a wide variety of diseases. C1 NIMH, CLIN NEUROENDOCRINOL BRANCH, BETHESDA, MD 20892 USA. LEIDEN UNIV, LEIDEN AMSTERDAM CTR DRUG RES, SYLVIUS LABS, DIV MED PHARMACOL, LEIDEN, NETHERLANDS. NR 27 TC 33 Z9 34 U1 1 U2 1 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 0785-3890 EI 1365-2060 J9 ANN MED JI Ann. Med. PD FEB PY 1997 VL 29 IS 1 BP 79 EP 82 DI 10.3109/07853899708998746 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA WM093 UT WOS:A1997WM09300010 PM 9073327 ER PT J AU Chen, R Gerloff, C Hallett, M Cohen, LG AF Chen, R Gerloff, C Hallett, M Cohen, LG TI Involvement of the ipsilateral motor cortex in finger movements of different complexities SO ANNALS OF NEUROLOGY LA English DT Article; Proceedings Paper CT 31st Meeting of the Canadian-Congress-of-Neurological-Sciences CY JUN 27, 1996 CL ONTARIO, CANADA SP Canadian Congress Neurol Sci ID TRANSCRANIAL MAGNETIC STIMULATION; LEFT-HEMISPHERE DAMAGE; BRAIN-STIMULATION; RECOVERY; STROKE; LESIONS; ARM; REORGANIZATION; PERFORMANCE; INFARCTION AB Functional imaging and behavioral studies suggest involvement of the ipsilateral hemisphere in hand movements, particularly of the left hand. If this is so, transient disturbance of the motor cortex (M1) with repetitive transcranial magnetic stimulation (rTMS) may affect ipsilateral motor sequences, and the effects may differ on the two sides. We studied 15 right-handed subjects who played a simple and a complex piano sequence for 8 seconds each. Two seconds after the beginning of each sequence, rTMS was delivered to the ipsilateral or contralateral M1, or directed away from the head (control trial). Ipsilateral M1 stimulation on either side induced timing errors in both sequences, and with the complex sequence induced more timing errors in the left hand than in the right hand. Errors of the right hand with both sequences occurred in the stimulation period only, but errors of the left hand with the complex sequence occurred in both the stimulation and poststimulation periods. We conclude that the ipsilateral M1 is involved in fine finger movements. The left hemisphere plays a greater role in timing ipsilateral complex sequences than the right hemisphere and may be more involved in the processing of complex motor programs. C1 NINCDS,HUMAN CORTICAL PHYSIOL UNIT,HUMAN MOTOR CONTROL SECT,MED NEUROL BRANCH,NIH,BETHESDA,MD 20892. RI Chen, Robert/B-3899-2009 OI Chen, Robert/0000-0002-8371-8629 NR 38 TC 230 Z9 232 U1 0 U2 6 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD FEB PY 1997 VL 41 IS 2 BP 247 EP 254 DI 10.1002/ana.410410216 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA WH852 UT WOS:A1997WH85200015 PM 9029074 ER PT J AU Marietta, J Walters, KS Burgess, R Ni, L Fukushima, K Moore, KC Hejtmancik, JF Smith, RJH AF Marietta, J Walters, KS Burgess, R Ni, L Fukushima, K Moore, KC Hejtmancik, JF Smith, RJH TI Usher's syndrome type IC: Clinical studies and fine-mapping the disease locus SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article DE compound cilia; linkage disequilibrium; Usher's syndrome type IC ID SYNDROME TYPE-II; RETINITIS-PIGMENTOSA; NASAL-MUCOSA; CILIA; GENE; ULTRASTRUCTURE; LOCALIZATION; LINKAGE; CHROMOSOME-11; ABNORMALITIES AB Usher's syndrome type I is a heterogeneous group of diseases characterized by severe to profound sensorineural hearing loss, absent vestibular function, and progressive pigmentary retinopathy. Other identifying clinical features have not been documented. In this study, we examined olfactory acuity, plasma levels of polyunsaturated fatty acids and sarcosine, and cilia ultrastructure in a homogeneous cohort of patients with Usher's syndrome type IC. The normal age-dependent decline in olfactory acuity was observed, and normal plasma levels of polyunsaturated fatty acids and sarcosine were found. However, the incidence of compound cilia in biopsies from the inferior turbinate was significantly higher than that reported in control populations. By reconstructing haplotypes in affected persons, D11S902 and D11S1310 were identified as flanking markers over an interval that contains a candidate gene, KCNC1. No mutations in the coding sequence of this gene could be demonstrated in affected persons. C1 UNIV IOWA,DEPT OTOLARYNGOL,MOL OTOLARYNGOL RES LABS,IOWA CITY,IA 52242. UNIV IOWA,CENT ELECT MICROSCOPY RES FACIL,IOWA CITY,IA 52242. NEI,NIH,BETHESDA,MD 20892. FU NIDCD NIH HHS [R01-DC02046] NR 32 TC 12 Z9 12 U1 0 U2 2 PU ANNALS PUBL CO PI ST LOUIS PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 SN 0003-4894 J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD FEB PY 1997 VL 106 IS 2 BP 123 EP 128 PG 6 WC Otorhinolaryngology SC Otorhinolaryngology GA WH405 UT WOS:A1997WH40500006 PM 9041816 ER PT J AU Neamati, N Mazumder, A Zhao, H Sunder, S Burke, TR Schultz, RJ Pommier, Y AF Neamati, N Mazumder, A Zhao, H Sunder, S Burke, TR Schultz, RJ Pommier, Y TI Diarylsulfones, a novel class of human immunodeficiency virus type 1 integrase inhibitors SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID HIV-1 INTEGRASE; IN-VITRO AB A majority of reported human immunodeficiency virus type 1 integrase (HIV-1 IN) inhibitors are polyhydroxylated aromatic compounds containing two phenyl rings separated by aliphatic or aromatic linkers. Most inhibitors possessing a catechol moiety exhibit considerable toxicity in cellular assays. In an effort to identify nonhydroxylated analogs, a series of aromatic sulfones were tested for their ability to inhibit the 3' processing and strand transfer steps that are necessary for HIV replication. Several aromatic sulfones have preciously been shown to have moderate activity against HIV-1 reverse transcriptase in cellular assays; however, their inhibitory potencies against IN have not been explored. In the present study, the inhibitory effect of a series of sulfones and sulfonamides against IN was determined. Among 52 diaryl sulfones tested, 4 were determined to be highly potent (50% inhibitory concentration [IC50], 0.8 to 10 mu g/ml), 5 had good potencies (IC50, 11 to 50 mu g/ml), 10 showed moderate potencies (IC50, 51 to 100 mu g/ml), and 33 were inactive (IC50, > 100 mu g/ml) against IN. All of the active compounds exhibited similar potencies against HIV-2 IN. Sulfa drugs, used extensively in treating Pneumocystis carinii pneumonia, a leading cause of morbidity and mortality in AIDS patients, were also examined. Among 19 sulfonamides tested, sulfasalazine (IC50, 50 mu g/ml) was the most potent. We conclude that potent inhibitors of IN can be designed based on the results presented in this study. C1 NCI,DIV BASIC SCI,MOL PHARMACOL LAB,BETHESDA,MD 20892. NCI,DIV BASIC SCI,MED CHEM LAB,BETHESDA,MD 20892. NCI,DIV CANC BIOL DIAG & CTR,DEV THERAPEUT PROGRAM,DRUG SYNTHESIS & CHEM BRANCH,BETHESDA,MD 20892. RI Burke, Terrence/N-2601-2014 NR 30 TC 87 Z9 88 U1 2 U2 7 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD FEB PY 1997 VL 41 IS 2 BP 385 EP 393 PG 9 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA WG303 UT WOS:A1997WG30300026 PM 9021196 ER PT J AU Rice, WG Baker, DC Schaeffer, CA Graham, L Bu, M Terpening, S Clanton, D Schultz, R Bader, JP Buckheit, RW Field, L Singh, PK Turpin, JA AF Rice, WG Baker, DC Schaeffer, CA Graham, L Bu, M Terpening, S Clanton, D Schultz, R Bader, JP Buckheit, RW Field, L Singh, PK Turpin, JA TI Inhibition of multiple phases of human immunodeficiency virus type 1 replication by a dithiane compound that attacks the conserved zinc fingers of retroviral nucleocapsid proteins SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID ACID-BINDING-PROTEINS; REVERSE-TRANSCRIPTASE; STRAND TRANSFER; OXATHIIN CARBOXANILIDE; RATIONAL DESIGN; HIV-1 PROTEASE; GAG PROTEINS; IN-VITRO; 3'-AZIDO-3'-DEOXYTHYMIDINE; RNA AB The human immunodeficiency virus type 1 (HIV-1) nucleocapsid p7 protein contains two retrovirus-type zinc finger domains that are required for multiple phases of viral replication. Chelating residues (three Cys residues and one His residue) of the domains are absolutely conserved among all strains of HIV-1 and other retroviruses, and mutations in these residues result in noninfectious virions. These properties establish the zinc finger domains as logical targets for antiviral chemotherapy. Selected dithiobis benzamide (R-SS-R) compounds were previously found to inhibit HIV-1 replication by mediating an electrophilic attack on the zinc fingers. Unfortunately, reaction of these disulfide-based benzamides with reducing agents yields two monomeric structures (two R-SH structures) that can dissociate and no longer react with the zinc fingers, suggesting that in vivo reduction would inactivate the compounds. Through an extensive drug discovery program of the National Cancer Institute, a nondissociable tethered dithiane compound (1,2-dithiane-4,5-diol, 1,1-dioxide, fis; NSC 624151) has been identified. This compound specifically attacks the retroviral zinc fingers, but not other antiviral targets. The lead compound demonstrated broad antiretroviral activity, ranging from field isolates and drug-resistant strains of HIV-1 to HIV-2 and simian immunodeficiency virus. The compound directly inactivated HIV-1 virions and blocked production of infectious virus from cells harboring integrated proviral DNA. NSC 624151 provides a scaffold from which medicinal chemists can develop novel compounds for the therapeutic treatment of HIV infection. C1 NCI,FREDERICK CANC RES & DEV CTR,SAIC FREDERICK,ANTI AIDS VIRUS DRUG SCREEN LAB,FREDERICK,MD 21702. FREDERICK RES CTR,SO RES INST,VIROL RES GRP,FREDERICK,MD. UNIV TENNESSEE,DEPT CHEM,KNOXVILLE,TN 37996. NCI,DIV CANC TREATMENT DIAGNOS & CTR,DEV THERAPEUT PROGRAM,BETHESDA,MD 20892. VANDERBILT UNIV,DEPT CHEM,NASHVILLE,TN. RP Rice, WG (reprint author), NCI,FREDERICK CANC RES & DEV CTR,SAIC FREDERICK,LAB ANTIVIRAL DRUG MECH,DEV THERAPEUT PROGRAM,FREDERICK,MD 21702, USA. NR 53 TC 75 Z9 76 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD FEB PY 1997 VL 41 IS 2 BP 419 EP 426 PG 8 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA WG303 UT WOS:A1997WG30300031 PM 9021201 ER PT J AU DeLucca, AJ Bland, JM Jacks, TJ Grimm, C Cleveland, TE Walsh, TJ AF DeLucca, AJ Bland, JM Jacks, TJ Grimm, C Cleveland, TE Walsh, TJ TI Fungicidal activity of Cecropin A SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID BROTH MICRODILUTION METHOD; ANTIFUNGAL SUSCEPTIBILITY; INVASIVE ASPERGILLOSIS; FUSARIUM INFECTIONS; FILAMENTOUS FUNGI; EPIDEMIOLOGY; DIAGNOSIS; AGENTS; AIDS AB Cecropin A (CA) fungicidal properties were explored. Nongerminated and germinated Aspergillus spp. and Fusarium spp. conidia were treated with CA. CA achieved complete lethality at less than or equal to 25 mu M (99 mu g/ml) for germinating, but not nongerminating, conidia of Aspergillus spp. CA achieved total lethality for nongerminated and germinating conidia of Fusarium spp at 1.5 mu M (6 mu g/ml). MIC and minimal lethal concentration assays in buffered RPMI medium gave similar results. C1 NCI,PEDIAT BRANCH,IMMUNOCOMPROMISED HOST SECT,NIH,BETHESDA,MD 20892. RP DeLucca, AJ (reprint author), USDA ARS,SO REG RES CTR,1100 ROBERT E LEE BLVD,NEW ORLEANS,LA 70124, USA. NR 36 TC 67 Z9 78 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD FEB PY 1997 VL 41 IS 2 BP 481 EP 483 PG 3 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA WG303 UT WOS:A1997WG30300044 PM 9021214 ER PT J AU Lang, L Eckelman, WC AF Lang, L Eckelman, WC TI Labeling proteins at high specific activity using N-succinimidyl 4-[F-18](fluoromethyl) benzoate SO APPLIED RADIATION AND ISOTOPES LA English DT Article ID ERYTHROPOIETIN RECEPTOR; INTERLEUKIN-2 RECEPTOR; TRANSFERRIN RECEPTOR; CELLS; BINDING; GA-67 AB High effective specific activity N-succinimidyl 4-[F-18](fluoromethyl)benzoate was prepared using a reversed phase HPLC procedure. Reversed phase HPLC removed several additional impurities not removed by normal phase HPLC, thereby increasing the effective specific activity. Small amount (<100 mu g) of sensitive proteins such as erythropoietin can be labeled with this reagent in high yield without aggregation. Copyright (C) 1997 Published by Elsevier Science Ltd RP Lang, L (reprint author), NIH,POSITRON EMISS TOMOG DEPT,WARREN GRANT MAGNUSON CLIN CTR,BLDG 10,ROOM 1C-497,BETHESDA,MD 20892, USA. NR 16 TC 38 Z9 41 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0969-8043 J9 APPL RADIAT ISOTOPES JI Appl. Radiat. Isot. PD FEB PY 1997 VL 48 IS 2 BP 169 EP 173 DI 10.1016/S0969-8043(96)00151-0 PG 5 WC Chemistry, Inorganic & Nuclear; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Chemistry; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA WF439 UT WOS:A1997WF43900003 PM 9219343 ER PT J AU DiGiovanna, JJ Eaglstein, WH AF DiGiovanna, JJ Eaglstein, WH TI Report of the workshop on training clinical researchers in arthritis and musculoskeletal and skin diseases - Comment SO ARCHIVES OF DERMATOLOGY LA English DT Letter RP DiGiovanna, JJ (reprint author), NIAMSD,DERMATOL CLIN RES UNIT,NIH,BLDG 10,ROOM 9N228,100 CTR DR,MSC 1820,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD FEB PY 1997 VL 133 IS 2 BP 241 EP 242 DI 10.1001/archderm.133.2.241 PG 2 WC Dermatology SC Dermatology GA WH067 UT WOS:A1997WH06700020 PM 9041844 ER PT J AU Neumeister, A PraschakRieder, N Hesselmann, B Rao, ML Gluck, J Kasper, S AF Neumeister, A PraschakRieder, N Hesselmann, B Rao, ML Gluck, J Kasper, S TI Effects of tryptophan depletion on drug-free patients with seasonal affective disorder during a stable response to bright light therapy SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID SEROTONIN FUNCTION; SUMMER DEPRESSION; WINTER DEPRESSION; PLASMA TRYPTOPHAN; CIRCADIAN PHASE; PHOTOTHERAPY; ANTIDEPRESSANT; MOOD; CHLOROPHENYLPIPERAZINE; MELATONIN AB Background: A dysfunction of the serotonin system may play a major role in the pathogenesis of seasonal affective disorder. Bright light therapy has been shown to be effective in the treatment of winter depression in patients with seasonal affective disorder. Light therapy-induced remission from depression may be associated with changes in brain serotonin function. Methods: After at least 2 weeks of clinical remission, 12 drug-free patients who had had depression with seasonal affective disorder underwent tryptophan depletion in a double-blind, placebo-controlled, balanced crossover design study. Results: Short-term tryptophan depletion induced a significant decrease in plasma free and total tryptophan levels (P<.001 for both, repeated measures analysis of variance), with peak effects occurring 5 hours after ingestion of a tryptophan-free amino acid drink. It emerged that tryptophan depletion leads to a transient depressive relapse, which was most pronounced on the day after the tryptophan-depletion testing. No clinically relevant mood changes were observed in the control testing. Conclusions: The maintenance of light therapy-induced remission from depression in patients with seasonal mood cycles seems to depend on the functional integrity of the brain serotonin system. Our results suggest that the serotonin system might be involved in the mechanism of action of light therapy. C1 UNIV VIENNA,DEPT GEN PSYCHIAT,VIENNA,AUSTRIA. UNIV BONN,D-5300 BONN,GERMANY. RP Neumeister, A (reprint author), NIMH,CLIN PSYCHOBIOL BRANCH,9000 ROCKVILLE PIKE,BLDG 10,ROOM 4S-239,BETHESDA,MD 20892, USA. OI Gluck, Judith/0000-0001-8923-9306 NR 57 TC 102 Z9 102 U1 1 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD FEB PY 1997 VL 54 IS 2 BP 133 EP 138 PG 6 WC Psychiatry SC Psychiatry GA WG141 UT WOS:A1997WG14100006 PM 9040281 ER PT J AU Gold, JM Carpenter, C Randolph, C Goldberg, TE Weinberger, DR AF Gold, JM Carpenter, C Randolph, C Goldberg, TE Weinberger, DR TI Auditory working memory and Wisconsin Card Sorting Test performance in schizophrenia SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID FRONTAL-LOBE DAMAGE; PREFRONTAL CORTEX; DEFICITS AB Background: Impaired Wisconsin Card Sorting Test (WCST) performance has been one critical piece of evidence suggesting frontal lobe dysfunction in schizophrenia. However, the specific cognitive processes underlying impaired performance have not been identified. Impaired WCST performance in schizophrenia might in part reflect a fundamental working memory deficit. Method: We examined the performance of 30 normal subjects and 36 patients with schizophrenia on a neuropsychological battery including a novel measure of working memory-letter-number (IN) span. Results: Patients with schizophrenia were impaired on LN span performance, which was also highly correlated with WCST performance (r=0.74). Between-group WCST differences were eliminated when we covaried LN span. Regression analyses suggested that LN span performance predicted the WCST category achieved score, whereas measures of set shifting, verbal fluency, and attention were predictive of perseveration. Conclusion: Working memory may be a critical determinant of one aspect of WCST performance in schizophrenia. C1 NIMH,INTRAMURAL RES PROGRAM,CLIN & RES SERV BRANCH,WASHINGTON,DC 20032. NIMH,INTRAMURAL RES PROGRAM,CLIN BRAIN DISORDERS BRANCH,WASHINGTON,DC 20032. NORTHWESTERN UNIV,SCH MED,DEPT PSYCHIAT,CHICAGO,IL 60611. RP Gold, JM (reprint author), UNIV MARYLAND,MARYLAND PSYCHIAT RES CTR,POB 21247,CATONSVILLE,MD 21228, USA. NR 39 TC 495 Z9 501 U1 5 U2 27 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD FEB PY 1997 VL 54 IS 2 BP 159 EP 165 PG 7 WC Psychiatry SC Psychiatry GA WG141 UT WOS:A1997WG14100009 PM 9040284 ER PT J AU Schaefer, JR Scharnagl, H Baumstark, MW Schweer, H Zech, LA Seyberth, H Winkler, K Steinmetz, A Marz, W AF Schaefer, JR Scharnagl, H Baumstark, MW Schweer, H Zech, LA Seyberth, H Winkler, K Steinmetz, A Marz, W TI Homozygous familial defective apolipoprotein B-100 - Enhanced removal of apolipoprotein E-containing VLDLs and decreased production of LDLs SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE hypercholesterolemia; apolipoprotein B-100; atherosclerosis; genetic disease; stable-isotope tracer kinetics ID LOW-DENSITY-LIPOPROTEIN; PRIMARY HYPERCHOLESTEROLEMIA; STABLE-ISOTOPE; A-I; RECEPTOR; ATHEROSCLEROSIS; METABOLISM; CATABOLISM; MUTATION; PATIENT AB Familial defective apolipoprotein B-100 (FDB) is a frequently inherited disorder of lipoprotein metabolism. The glutamine-for-arginine substitution at position 3500 of apolipoprotein (apo) B-100 leads to defective binding of apo B-100 to the low density lipoprotein (LDL) receptor and accumulation of LDL in the plasma. We recently identified a patient homozygous for this mutation. His LDL cholesterol and apo B concentrations were approximately twice normal, whereas his apo E plasma level was low. Using a stable-isotope labeling technique ([H-2(3)]leucine-primed constant infusion), we studied lipoprotein turnover in vivo in the fasting state in this patient and three clinically healthy, normolipidemic individuals not carrying the FDB mutation. The residence time of LDL apo B-100 was prolonged 3.6-fold in the FDB homozygote (8.3 vs 2.3 days). The production rate of LDL ape B-100 was decreased (7.4 vs 15 mg per kg per day). In FDB the residence time of very low density lipoprotein (VLDL) ape B-100 was longer (2.6 vs 1.3 hours), whereas the residence time of VLDL apo E was shorter (2.6 vs 4.5 hours) than normal. These data show that the in vivo metabolism of apo B-100-containing lipoproteins in FDB is different from that in familial hypercholesterolemia, in which LDL receptors are defective. In both conditions the residence times of LDL apo B-100 appear to be increased to approximately the same degree. This contrasts with the LDL ape B-100 synthetic rate, which is increased in familial hypercholesterolemia and decreased in FDB. The decreased production of LDL apo B-100 in FDB may originate from enhanced removal of apo E-containing LDL precursors by LDL receptors, which may be upregulated in response to the decreased flux of LDL-derived cholesterol into hepatocytes. C1 UNIV FREIBURG,DEPT MED,DIV CLIN CHEM,D-79106 FREIBURG,GERMANY. UNIV FREIBURG,DEPT MED,DIV SPORTS MED,D-79106 FREIBURG,GERMANY. UNIV MARBURG,DEPT MED,DIV CARDIOL,D-35032 MARBURG,GERMANY. NHLBI,MOL DIS BRANCH,NATL INST HLTH,BETHESDA,MD 20892. RI Schweer, Horst/C-6240-2008; Baumstark, Manfred/F-8432-2012 OI Baumstark, Manfred/0000-0002-5442-1586 NR 47 TC 44 Z9 45 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD FEB PY 1997 VL 17 IS 2 BP 348 EP 353 PG 6 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA WK394 UT WOS:A1997WK39400017 PM 9081691 ER PT J AU Dugi, KA Feuerstein, LM Hill, S Shih, J SantamarinaFojo, S Brewer, HB Hoeg, JM AF Dugi, KA Feuerstein, LM Hill, S Shih, J SantamarinaFojo, S Brewer, HB Hoeg, JM TI Lipoprotein lipase correlates positively and hepatic lipase inversely with calcific atherosclerosis in homozygous familial hypercholesterolemia SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article; Proceedings Paper CT 67th Scientific Session of the American-Heart-Association CY NOV 14-17, 1994 CL DALLAS, TX SP Amer Heart Assoc DE atherosclerosis; coronary disease; macrophages; computed tomography x-ray; xanthomatosis ID LOW-DENSITY-LIPOPROTEIN; TRIGLYCERIDE-RICH LIPOPROTEINS; ULTRAFAST COMPUTED-TOMOGRAPHY; SUBENDOTHELIAL CELL-MATRIX; RECEPTOR-RELATED PROTEIN; CORONARY-ARTERY DISEASE; SMOOTH-MUSCLE CELLS; ELECTRON-BEAM CT; TRANSGENIC MICE; PLASMA-LIPOPROTEINS AB Homozygous familial hypercholesterolemia (FH) is a rare genetic disorder that leads to premature atherosclerosis due to a defective LDL receptor. There is, however, a large degree of phenotypic heterogeneity at the level of atherosclerosis even in patients with identical mutations of the LDL receptor protein. Lipoprotein lipase (LPL) and hepatic lipase (HL) are crucial enzymes in lipoprotein metabolism, and both have been proposed as having proatherogenic as well as antiatherogenic effects. To evaluate a potential role for these enzymes in the severity of atherosclerosis, we correlated postheparin LPL mass and activity as well as HL activity with the volume of total calcific atherosclerosis (heart and thoracic aorta), coronary artery calcific atherosclerosis, and Achilles tendon width as measured by computed tomography in 15 FH homozygotes. LPL dimer and total mass were positively correlated with all three parameters (r=.65 to .87, P<.01) as was LPL activity (r=.52 to .63, P<.05). HL activity was negatively correlated with total and coronary artery calcified lesion volume (r=-.55 to .57, P<.05). In a multiple regression model of the coronary artery lesion volume, LPL dimer mass and HL activity together accounted for 84% of the variability (r=.92, P<.0001). In a multiple regression model of the total calcified lesion volume, HL activity, total cholesterol, age, and LPL dimer mass to ether accounted for 85% of the variability (r=.92, P=.0005). These data demonstrate a significant correlation of LPL mass and activity with the extent of calcific atherosclerosis in homozygous FH. It is not clear whether LPL is the cause or consequence of the observed correlation, but if the association between LPL and coronary artery lesions is also present in patients with other genetic dyslipoproteinemias, LPL could constitute a new risk factor for cardiovascular disease. C1 NHLBI,MOL DIS BRANCH,NATL INST HLTH,BETHESDA,MD 20892. NHLBI,OFF BIOSTAT RES,NATL INST HLTH,BETHESDA,MD 20892. NATL INST HLTH,DEPT RADIOL,WARREN G MAGNUSON CLIN CTR,BETHESDA,MD. NR 87 TC 34 Z9 34 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD FEB PY 1997 VL 17 IS 2 BP 354 EP 364 PG 11 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA WK394 UT WOS:A1997WK39400018 PM 9081692 ER PT J AU Branigan Pardo, J AF Branigan Pardo, J TI Comparison of synovial tissue and synovial fluid as the source of nucleic acids for detection of Chlamydia trachomatis by polymerase chain reaction (vol 39, pg 1740, 1996) SO ARTHRITIS AND RHEUMATISM LA English DT Correction, Addition C1 NIAMS,ARTHRIT & RHEUMATISM BRANCH,NIH,BETHESDA,MD. NR 1 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD FEB PY 1997 VL 40 IS 2 BP 387 EP 387 PG 1 WC Rheumatology SC Rheumatology GA WH408 UT WOS:A1997WH40800024 ER PT J AU JohnsonThompson, MC Jay, JM AF JohnsonThompson, MC Jay, JM TI Ethnic diversity in ASM: The early history of African-American microbiologists SO ASM NEWS LA English DT Article C1 NIEHS,NIH,RES TRIANGLE PK,NC 27709. UNIV NEVADA,LAS VEGAS,NV 89154. NR 6 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0044-7897 J9 ASM NEWS JI ASM News PD FEB PY 1997 VL 63 IS 2 BP 77 EP 82 PG 6 WC Microbiology SC Microbiology GA WH376 UT WOS:A1997WH37600015 ER PT J AU Logue, SE Paylor, R Wehner, JM AF Logue, SE Paylor, R Wehner, JM TI Hippocampal lesions cause learning deficits in inbred mice in the Morris water maze and conditioned-fear task SO BEHAVIORAL NEUROSCIENCE LA English DT Article ID PROTEIN-KINASE-C; MUTANT MICE; PLACE NAVIGATION; GENETIC-ANALYSIS; DBA/2 MICE; RATS; REPRESENTATION; PERFORMANCE; BEHAVIOR; STRAINS AB This study examined the effect of hippocampal lesions on acquisition of the Morris water maze and conditioned-fear task in inbred mice. C57BL/6J, DBA/2J, and B6D2F1 hybrid mice were given hippocampal lesions or sham surgery and then tested. The lesioned C57BL/6J and B6D2F1 mice failed to learn the Morris task relative to sham-operated controls, and no DBA group learned the task. In the contextual component of conditioned fear, lesions decreased freezing in all strains. But the lesions only affected freezing to the conditioned stimulus in the DBA/2J and B6D2F1 strains. These data demonstrate that C57BL/6J and B6D2F1 mice use the hippocampus to solve the Morris water maze and conditioned-fear task, and the DBA mice use the hippocampus, to some degree, in the conditioned-fear task. C1 UNIV COLORADO,INST BEHAV GENET,BOULDER,CO 80309. NIMH,SECT BEHAV NEUROPHARMACOL,BETHESDA,MD 20892. UNIV COLORADO,SCH PHARM,BOULDER,CO 80309. FU NICHD NIH HHS [5T32HD-07289]; NIMH NIH HHS [MH-48663] NR 37 TC 279 Z9 282 U1 2 U2 13 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 0735-7044 J9 BEHAV NEUROSCI JI Behav. Neurosci. PD FEB PY 1997 VL 111 IS 1 BP 104 EP 113 DI 10.1037/0735-7044.111.1.104 PG 10 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA WK480 UT WOS:A1997WK48000009 PM 9109628 ER PT J AU Domachowske, JB AF Domachowske, JB TI The role of nitric oxide in the regulation of cellular iron metabolism SO BIOCHEMICAL AND MOLECULAR MEDICINE LA English DT Review ID TUMOR-NECROSIS-FACTOR; RECEPTOR MESSENGER-RNA; INCREASED FERRITIN SYNTHESIS; TRANSFERRIN RECEPTOR; TRANSLATIONAL REGULATION; RESPONSIVE ELEMENTS; HUMAN HEPATOCYTES; INTERFERON-GAMMA; CHRONIC DISEASE; FACTOR-ALPHA AB Eukaryotic cellular iron homeostasis becomes impaired during inflammation, manifesting itself most dramatically as the anemia of chronic disease. This alteration in cellular iron metabolism is the result of a complex network of events, acting at the transciptional and translational levels to alter the expression of proteins involved in the uptake, storage, and utilization of iron. With the discovery of nitric oxide (NO), its role in host defense, and its interactions with a number of different iron-containing proteins, investigators have begun unravelling the connection between iron metabolism and NO. Following a brief discussion of normal cellular iron metabolism, this review focuses on alterations in iron homeostasis observed during inflammation with an emphasis on the role of NO. A working model involving NO in the pathogenesis of the anemia of chronic disease is proposed. (C) 1997 Academic Press. RP Domachowske, JB (reprint author), NIAID,HOST DEF LAB,NIH,BLDG 10,ROOM 11N112,BETHESDA,MD 20892, USA. NR 56 TC 30 Z9 32 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 1077-3150 J9 BIOCHEM MOL MED JI Biochem. Mol. Med. PD FEB PY 1997 VL 60 IS 1 BP 1 EP 7 DI 10.1006/bmme.1996.2557 PG 7 WC Biochemistry & Molecular Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Research & Experimental Medicine GA WN211 UT WOS:A1997WN21100001 PM 9066977 ER PT J AU Chen, D Guo, JR Miki, T Tachibana, M Gahl, WA AF Chen, D Guo, JR Miki, T Tachibana, M Gahl, WA TI Molecular cloning and characterization of rab27a and rab27b, novel human rab proteins shared by melanocytes and platelets SO BIOCHEMICAL AND MOLECULAR MEDICINE LA English DT Article ID GTP-BINDING PROTEIN; IDENTIFICATION; ORGANELLES; PURIFICATION; DEFICIENT; MEMBRANES; GTPASES; C25KG AB Rabs are prenylated, membrane-bound proteins involved in vesicular fusion and trafficking. We isolated the complete cDNAs of two rab isoforms, rab27a and rab27b, from human melanoma cells and melanocytes. Rab27a is the human homolog of a rat megakaryocyte rab called ram p25. Rab27b corresponds to a small GTP-binding protein, c25KG, which was previously purified from platelets but whose cDNA had not been cloned. Sequence comparisons with known rabs indicate that rab27a and rab27b comprise a melanocyte/platelet subfamily within the rab family. In addition, rab27a was expressed in a large variety of cell and tissue types, excluding brain, and rab27b manifested itself primarily in testis. Bacterially expressed and purified rab27a and rab27b exhibited GTP-binding activity and can now be used for antibody production and studies of the substrate specificities of geranylgeranyl transferase. In addition, the expression of rab27a and rab27b in both melanocytes and platelets makes them candidates for involvement in mouse and human disorders characterized by the combination of pigment dilution and a platelet storage pool defect. (C) 1997 Academic Press. C1 NCI,DIV BASIC SCI,NATL INST HLTH,BETHESDA,MD 20892. NIDOCD,DIV INTRAMURAL RES,NATL INST HLTH,BETHESDA,MD 20892. RP Chen, D (reprint author), NICHHD,SECT HUMAN BIOCHEM GENET,HERITABLE DISORDERS BRANCH,NATL INST HLTH,BETHESDA,MD 20892, USA. NR 32 TC 85 Z9 88 U1 0 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 1077-3150 J9 BIOCHEM MOL MED JI Biochem. Mol. Med. PD FEB PY 1997 VL 60 IS 1 BP 27 EP 37 DI 10.1006/bmme.1996.2559 PG 11 WC Biochemistry & Molecular Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Research & Experimental Medicine GA WN211 UT WOS:A1997WN21100003 PM 9066979 ER PT J AU Cabib, E Drgon, T Drgonova, J Ford, RA Kollar, R AF Cabib, E Drgon, T Drgonova, J Ford, RA Kollar, R TI The yeast cell wall, a dynamic structure engaged in growth and morphogenesis SO BIOCHEMICAL SOCIETY TRANSACTIONS LA English DT Article; Proceedings Paper CT 659th Meeting of the London-Biochemical-Society CY SEP 04-06, 1996 CL UNIVERSITY OF LONDON, LONDON, ENGLAND SP London Biochem Soc HO UNIVERSITY OF LONDON ID GTP-BINDING PROTEIN; SACCHAROMYCES-CEREVISIAE; CHITIN SYNTHESIS; BETA-(1->3)GLUCAN SYNTHETASE; SYNTHASE; ENZYME; CYTOSKELETON; SEPARATION; ACTIN RP Cabib, E (reprint author), NIDDK,BIOCHEM & METAB LAB,BETHESDA,MD 20892, USA. RI Drgonova, Jana/B-2903-2008; OI Drgonova, Jana/0000-0002-4623-8466 NR 30 TC 50 Z9 52 U1 3 U2 7 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON, ENGLAND W1N 3AJ SN 0300-5127 J9 BIOCHEM SOC T JI Biochem. Soc. Trans. PD FEB PY 1997 VL 25 IS 1 BP 200 EP 204 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WK473 UT WOS:A1997WK47300042 PM 9056871 ER PT J AU Gonzalez, FJ AF Gonzalez, FJ TI Recent update on the PPAR alpha-null mouse SO BIOCHIMIE LA English DT Article; Proceedings Paper CT French-Society-of-Biochemistry-and-Molecular-Biology/Study-Group-on-Meta bolic-Regulation Meeting CY SEP, 1996 CL DIJON, FRANCE SP French Soc Biochem & Molec Biol, Study Grp Metab Regulat DE peroxisome proliferation; PPAR alpha; non-genotoxic carcinogens; inflammatory response; gene expression ID PROLIFERATOR-ACTIVATED RECEPTOR; PEROXISOME PROLIFERATORS; PHENYLACETATE; DEHYDROEPIANDROSTERONE; CANCER; CELLS; GENE; RAT; DIFFERENTIATION; INHIBITION AB Short-term treatment of rats and mice with peroxisome proliferators (PP) results in an increase in liver peroxisome number, marked hepatomegaly and induction of several genes encoding peroxisomal and other microsomal and mitochondrial enzymes involved in fatty acid metabolism. Chronic treatment of rodents with PP results in hepatocellular carcinoma. Species differences in PP responses have been found. For example, PP such as clofibrate and gemfibrozil, are highly effective lipid and cholesterol lowering drugs in humans but do not cause peroxisome proliferation and there is no evidence for increased liver cancers in patients receiving these drugs. A receptor, designated PP-activated receptor alpha (PPAR alpha) is capable of trans activating reporter genes containing a PP response (PPRE), but requires the presence of both PP, 9-cis retinoic acid and another receptor called RXR alpha. However, PP may not directly bind to PPAR alpha but probably indirectly disturb cellular metabolism to liberate an endogenous ligand. Subsequent to the first identification of a PPAR alpha, other members of this receptor family were found and designated PPAR alpha, PPAR beta (also called NUC1 and PPAR delta) and PPAR gamma. The alpha form is most abundant in liver and kidney, sites of peroxisome proliferation while the other two receptors are not significantly expressed in these tissues. On the basis of tissue-specific localization and spectrum of target gene activation, the physiological function of PPAR alpha and PPAR gamma appear to be related to fatty acid metabolism and regulation of adipogenesis, respectively. To gain insight into the function of PPAR alpha and its role in the peroxisome proliferator response and hepatocellular carcinogenesis, gene targeting was used to develop a PPAR alpha-deficient mouse. These animals are resistant to the pleiotropic effects of PP and no induction of any known target gene has been found. Recent studies on the phenotypes of these mice have led to an understanding of the mechanism of action of PP. They have also provided a useful model to establish the physiological role of PPAR alpha in fatty acid homeostasis and inflammation. RP Gonzalez, FJ (reprint author), NCI,LAB METAB,DIV BASIC SCI,NIH,BLDG 37,ROOM 3E-24,BETHESDA,MD 20892, USA. NR 34 TC 83 Z9 83 U1 0 U2 2 PU EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS PA 141 RUE JAVEL, 75747 PARIS, FRANCE SN 0300-9084 J9 BIOCHIMIE JI Biochimie PD FEB-MAR PY 1997 VL 79 IS 2-3 BP 139 EP 144 DI 10.1016/S0300-9084(97)81506-4 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XG388 UT WOS:A1997XG38800012 PM 9209711 ER PT J AU Bryant, SD Balboni, G Guerrini, R Salvadori, S Tomatis, R Lazarus, LH AF Bryant, SD Balboni, G Guerrini, R Salvadori, S Tomatis, R Lazarus, LH TI Opioid diketopiperazines: Refinement of the delta opioid antagonist pharmacophore SO BIOLOGICAL CHEMISTRY LA English DT Article DE diketopiperazine; Monte Carlo; opioid peptide; antagonist; pharmacophore ID TETRAPEPTIDE TYR-COH JOM-13; RECEPTOR PHARMACOPHORE; CONFORMATIONS; BINDING; ANALOGS; MODELS; MU; REPLACEMENTS; DIPEPTIDES; PEPTIDES AB Bioactive models for a delta opioid receptor antagonist are proposed based on the structurally rigid, diketopiperazine containing cycle 2',6'-dimethyl-L-tyrosyl (Dmt)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (Tie), Monte Carlo conformational analysis of c(Dmt-Tic) generated three low energy clusters (I-III) of conformers. The lowest energy conformer representing cluster I superimposed best with the X-ray crystal structures of c(Tyr-Tic), an inactive diketopiperazine with similar framework as c(Dmt-Tic), with H-Tyr-Tic-NH2, a dipeptide of moderate delta opioid affinity and lacking bioactivity, and with H-Tyr-Tic-Phe-Phe-OH (TIPP), a selective and potent delta opioid receptor antagonist. Clusters I and II superimposed best with three different overlays of naltrindole, a potent delta opiate antagonist, and with two other H-Tyr-Tic-NH delta opioid antagonist pharmacophores proposed by Temussi et al, (1994) and Wilkes and Schiller (1995), The 3-dimensional topography of these two clusters of c(Dmt-Tic) conformations may represent bioactive models for interaction of an antagonist at delta opioid receptors. Cluster I conformers exhibited gauche(-) (- 64 degrees) and gauche(+) (53 degrees) orientations of the side chains Dmt and Tie, respectively, while cluster II contained trans (179 degrees) and gauche(+) (62 degrees) orientations of those side-chains. Aromatic ring distances were 5.4 Angstrom for cluster I conformations and 8.2 Angstrom for cluster II structures. Orientation about the peptide bond N-C' was cis (- 5 degrees and 3 degrees) for both clusters, respectively, These structural features may provide optimal alignment of the physicochemical moieties important for delta opioid receptor interaction, such as the hydrophobic methyl groups of Dmt, hydrogen bonding of the dimethyltyrosine hydroxyl group within the receptor pocket and cation-pi interactions involving the aromatic rings of Dmt and Tie, as profiled by the three point attachment hypothesis. C1 NIEHS, LCBRA, RES TRIANGLE PK, NC 27709 USA. UNIV FERRARA, DEPT PHARMACEUT SCI, I-44100 FERRARA, ITALY. UNIV FERRARA, CTR BIOTECHNOL, I-44100 FERRARA, ITALY. OI Guerrini, Remo/0000-0002-7619-0918 NR 48 TC 32 Z9 32 U1 0 U2 0 PU WALTER DE GRUYTER & CO PI BERLIN PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY SN 1431-6730 J9 BIOL CHEM JI Biol. Chem. PD FEB PY 1997 VL 378 IS 2 BP 107 EP 114 DI 10.1515/bchm.1997.378.2.107 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WR669 UT WOS:A1997WR66900007 PM 9088539 ER PT J AU Callahan, AM Frye, MA Marangell, LB George, MS Ketter, TA LHerrou, T Post, RM AF Callahan, AM Frye, MA Marangell, LB George, MS Ketter, TA LHerrou, T Post, RM TI Comparative antidepressant effects of intravenous and intrathecal thyrotropin-releasing hormone: Confounding effects of tolerance and implications for therapeutics SO BIOLOGICAL PSYCHIATRY LA English DT Article DE thyrotropin-releasing hormone; depression; bipolar disorder; tolerance; intravenous administration; intrathecal administration ID AMYOTROPHIC LATERAL SCLEROSIS; ENDOGENOUS-DEPRESSION; PSYCHIATRIC-PATIENTS; CEREBROSPINAL-FLUID; TRH; BRAIN; CHOLECYSTOKININ; RAT; SPASTICITY; INHIBITION AB A significant amount of preclinical and human data indicate that thyrotropin-releasing hormone (TRH) has antidepressant effects. Although early studies showing these effects using intravenous TRH were not consistently replicated, it has been suggested that this could be explained by its poor blood-brain barrier penetration, For this reason we compared the antidepressant effect of intrathecal and intravenous TRH administered in a double-blind design to 2 treatment-refractory patients with bipolar II disorder. Each experienced a robust antidepressant response by both routes; subsequent open trials of intravenous TRH also were effective until apparent tolerance developed. Intrathecal TRH was readministered and both subjects again experienced robust antidepressant responses. These preliminary data suggest a differential mechanism of tolerance to the two routes of administration and raise the possibility that a subgroup of patients may be responsive to the antidepressant effects of TRH independent of its route of administration. (C) 1997 Society of Biological Psychiatry. C1 NIMH, BIOL PSYCHIAT BRANCH, NIH, BETHESDA, MD 20892 USA. MT SINAI MED CTR, NEW YORK, NY 10029 USA. BAYLOR COLL MED, HOUSTON, TX 77030 USA. MED UNIV S CAROLINA, CHARLESTON, SC 29425 USA. STANFORD UNIV, SCH MED, STANFORD, CA 94305 USA. ELECT VILLAGE SYST, GREENBELT, MD USA. VET ADM MED CTR, BRONX, NY 10468 USA. NR 50 TC 49 Z9 49 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD FEB 1 PY 1997 VL 41 IS 3 BP 264 EP 272 DI 10.1016/S0006-3223(97)00372-7 PG 9 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA WF218 UT WOS:A1997WF21800003 PM 9024949 ER PT J AU Murphy, DGM Mentis, MJ Pietrini, P Grady, C Daly, E Haxby, JV DeLaGranja, M Allen, G Largay, K White, BJ Powell, CM Horwitz, B Rapoport, SI Schapiro, MB AF Murphy, DGM Mentis, MJ Pietrini, P Grady, C Daly, E Haxby, JV DeLaGranja, M Allen, G Largay, K White, BJ Powell, CM Horwitz, B Rapoport, SI Schapiro, MB TI A PET study of Turner's syndrome: Effects of sex steroids and the X chromosome on brain SO BIOLOGICAL PSYCHIATRY LA English DT Article DE Turner's syndrome; X chromosome; sex steroids; brain ageing; brain development; positron emission tomography ID CEREBRAL GLUCOSE-UTILIZATION; CERCOPITHECUS-AETHIOPS-SABAEUS; POSITRON EMISSION TOMOGRAPHY; ALZHEIMERS-DISEASE; HEMISPHERIC-SPECIALIZATION; METABOLIC ASYMMETRIES; AFFILIATIVE BEHAVIOR; COGNITIVE FUNCTION; 49,XXXXY SYNDROME; SCHIZOPHRENIA AB Women with Turner's syndrome (TS) allow us to study the neurobiological associates of cognitive and behavioral abnormalities because they lack one/part of one X chromosome, and endogenous estrogen. We studied 13 healthy controls (mean age +/- SD, 28 +/- 6 years) and 16 TS subjects (mean age +/- SD, 26 +/- 6 years). We measured cognitive abilities using neuropsychological tests, and cerebral metabolic rates for glucose with positron emission tomography. Compared to controls, TS subjects had significant absolute hypermetabolism in most brain areas; however, normalized metabolism was significantly lower in TS subjects than controls in the insula and association neocortices bilaterally, and there were significant differences in functional metabolic associations of brain region pairs originating in occipital cortex bilaterally, and within the right hemisphere. There were significant correlations between right-left cognitive and metabolic asymmetries in the TS group. Also, within TS a preliminary analysis demonstrated ''X chromosome dosage'' effects in language ability and left temporal metabolism, asymmetry of right-left test scores, and parietal metabolism. We hypothesize that within TS: i) generalized brain hypermetabolism reflects global abnormalities in neuron packing; ii) neuronal abnormalities occur in association neocortex that differ in nature or extent from whole brain and are associated with significant differences in normalized metabolism; iii) cognitive deficits are related to brain metabolic abnormalities; and iv) social-behavioral problems may be related to abnormalities of brain metabolism. Moreover, in human brain the X chromosome involved in development of the association neocortices. (C) 1997 Society of Biological Psychiatry. C1 NIA, NEUROSCI LAB, NIH, BETHESDA, MD 20892 USA. NIDDK, BIOL CHEM LAB, NIH, CYTOGENET UNIT, BETHESDA, MD USA. NIH, MED GENET PROGRAM, BETHESDA, MD 20892 USA. RP Murphy, DGM (reprint author), INST PSYCHIAT, DEPT PSYCHOL MED, SECT MENTAL IMPAIRMENT, DECRESPIGNY PK RD, LONDON SE5 8AF, ENGLAND. RI daly, eileen/B-6716-2011; OI Daly, Eileen/0000-0003-3625-3467 NR 88 TC 55 Z9 56 U1 1 U2 4 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 FEB 1 PY 1997 VL 41 IS 3 BP 285 EP 298 DI 10.1016/S0006-3223(95)00660-5 PG 14 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA WF218 UT WOS:A1997WF21800005 PM 9024951 ER PT J AU Wolkowitz, OM Reus, VI Roberts, E Manfredi, F Chan, T Raum, WJ Ormiston, S Johnson, R Canick, J Brizendine, L Weingartner, H AF Wolkowitz, OM Reus, VI Roberts, E Manfredi, F Chan, T Raum, WJ Ormiston, S Johnson, R Canick, J Brizendine, L Weingartner, H TI Dehydroepiandrosterone (DHEA) treatment of depression SO BIOLOGICAL PSYCHIATRY LA English DT Article DE DHEA; DHEA-S; cortisol; depression; memory ID ANTIGLUCOCORTICOID STRATEGIES; SULFATE; MEN; MEMORY; WOMEN; STEROIDS; HORMONES; PATTERN; DISEASE; MICE AB Dehydroepiandrosterone (DHEA) and its sulfate, DHEA-S, are plentiful adrenal steroid hormones that decrease with aging and may have significant neuropsychiatric effects. In this study, six middle-aged and elderly patients with major depression and low basal plasma DHEA and/or DHEA-S levels were openly administered DHEA (30-90 mg/d X 4 weeks) in doses sufficient to achieve circulating plasma levels observed in younger healthy individuals. Depression ratings, as well as aspects of memory performance significantly improved. One treatment-resistant patient received extended treatment with DHEA for 6 months; her depression ratings improved 48-72% and her semantic memory performance improved 63%. These measures returned to baseline after treatment ended. In both studies, improvements in depression ratings and memory performance were directly related to increases in plasma levels of DHEA and DHEA-S and to increases in their ratios with plasma cortisol levels. These preliminary data suggest DHEA may have antidepressant and promemory effects and should encourage double-blind trials in depressed patients. (C) 1997 Society of Biological Psychiatry. C1 CITY HOPE NATL MED CTR, BECKMAN RES INST, DUARTE, CA 91010 USA. CITY HOPE NATL MED CTR, DEPT NEUROBIOCHEM, DUARTE, CA 91010 USA. UNIV CALIF LOS ANGELES, SCH MED, DEPT INTERNAL MED, LOS ANGELES, CA USA. UNIV CALIF LOS ANGELES, SCH MED, DEPT ENDOCRINOL, LOS ANGELES, CA USA. NIAAA, BETHESDA, MD USA. UNIV CALIF SAN FRANCISCO, SCH MED, CTR NEUROBIOL & PSYCHIAT, SAN FRANCISCO, CA 94143 USA. RP Wolkowitz, OM (reprint author), UNIV CALIF SAN FRANCISCO, SCH MED, DEPT PSYCHIAT, 401 PARNASSUS AVE, BOX F-0984, SAN FRANCISCO, CA 94143 USA. RI reus, victor/I-7923-2015 OI reus, victor/0000-0002-8193-5697 NR 55 TC 233 Z9 240 U1 2 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD FEB 1 PY 1997 VL 41 IS 3 BP 311 EP 318 DI 10.1016/S0006-3223(96)00043-1 PG 8 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA WF218 UT WOS:A1997WF21800008 PM 9024954 ER PT J AU Wine, RN Ku, WW Li, LH Chapin, RE AF Wine, RN Ku, WW Li, LH Chapin, RE TI Cyclophilin A is present in rat germ cells and is associated with spermatocyte apoptosis SO BIOLOGY OF REPRODUCTION LA English DT Article ID GLYCOL MONOMETHYL ETHER; BINDING-PROTEIN; IDENTIFICATION; THYMOCYTES; IMMUNOPHILINS; PURIFICATION; ISOMERASES; TOXICITY; NUCLEASE AB Recent investigations in our laboratory revealed divalent cation-dependent endonuclease activity in testes from 2-methoxyethanol-treated rats, which was able to cleave substrate DNA into a pattern of DNA fragmentation consisting of similar to 180-200 base pairs. Further studies were undertaken to characterize the active nuclease. F344 rats were treated with 2-methoxyethanol, a glycol ether that causes the death of pachytene spermatocytes in juvenile and adult rats. The active nuclease was found in nuclear extract from treated animals, but not controls. A radioactive gel nuclease assay, which detects degradation and loss of P-32-labeled DNA from a DNA-containing polyacrylamide gel, localized the nuclease activity to a band of approximate to 18 kDa. This activity was dependent on calcium and was inhibited by both zinc and aurintricarboxylic acid. Amino acid sequence data showed that this protein was identical to cyclophilin A. Immunohistochemistry using antibodies against cyclophilin A found specific staining in pachytene spermatocytes, spermatids, interstitial cells, and Sertoli cell nuclei. Cyclophilin A staining was present in both control and 2-methoxyethanol-treated rat testes in a stage-dependent manner, with pachytene spermatocytes in stage-VIII-XIV seminiferous tubules most heavily stained. These data demonstrate that rat testis germ cells contain relatively high levels of cyclophilin A whose nuclease activity is associated with spermatocyte apoptosis induced by 2-methoxyethanol. RP Wine, RN (reprint author), NIEHS,REPROD TOXICOL GRP,NATL TOXICOL PROGRAM,POB 12233,MD D2-06,RES TRIANGLE PK,NC 27709, USA. OI Chapin, Robert/0000-0002-5997-1261 NR 29 TC 15 Z9 15 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PD FEB PY 1997 VL 56 IS 2 BP 439 EP 446 DI 10.1095/biolreprod56.2.439 PG 8 WC Reproductive Biology SC Reproductive Biology GA WF236 UT WOS:A1997WF23600019 PM 9116144 ER PT J AU Henry, ER AF Henry, ER TI The use of matrix methods in the modeling of spectroscopic data sets SO BIOPHYSICAL JOURNAL LA English DT Article ID LEAST-SQUARES; GLOBAL ANALYSIS; ALGORITHMS; PROTEIN AB We describe a general approach to the model-based analysis of sets of spectroscopic data that is built upon the techniques of matrix analysis. A model hypothesis may often be expressed by writing a matrix of measured spectra as the product of a matrix of spectra of individual molecular species and a matrix of corresponding species populations as a function of experimental conditions. The modeling procedure then requires the simultaneous determination of a set of species spectra and a set of model parameters (from which the populations are derived), such that this product yields an optimal description of the measured spectra. This procedure may be implemented as an optimization problem in the space of the (possibly nonlinear) model parameters alone, coupled with the efficient solution of a corollary linear optimization problem using matrix decomposition methods to obtain a set of species spectra corresponding to any set of model parameters. Known species spectra, as well as other information and assumptions about spectral shapes, may be incorporated into this general framework, using parametrized analytical functional forms and basis-set techniques. The method by which assumed relationships between global features (e.g., peak positions) of different species spectra may be enforced in the modeling without otherwise specifying the shapes of the spectra will be shown. We also consider the effect of measurement errors on this approach and suggest extensions of the matrix-based least-squares procedures applicable to situations in which measurement errors may not be assumed to be normally distributed. A generalized analysis procedure is introduced for cases in which the species spectra vary with experimental conditions. RP Henry, ER (reprint author), NIH,CHEM PHYS LAB,BLDG 5,ROOM 110,BETHESDA,MD 20892, USA. RI Henry, Eric/J-3414-2013 OI Henry, Eric/0000-0002-5648-8696 NR 20 TC 47 Z9 48 U1 2 U2 13 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1997 VL 72 IS 2 BP 652 EP 673 PN 1 PG 22 WC Biophysics SC Biophysics GA WD509 UT WOS:A1997WD50900013 PM 9017194 ER PT J AU Kukuljan, M Vergara, L Stojilkovic, SS AF Kukuljan, M Vergara, L Stojilkovic, SS TI Modulation of the kinetics of inositol 1,4,5-trisphosphate-induced [Ca2+](i) oscillations by calcium entry in pituitary gonadotrophs SO BIOPHYSICAL JOURNAL LA English DT Article ID INTRACELLULAR CALCIUM; CA2+ OSCILLATIONS; ENDOPLASMIC-RETICULUM; RAT GONADOTROPES; XENOPUS-OOCYTES; RELEASE; TRISPHOSPHATE; MECHANISM; FEEDBACK; INFLUX AB Inositol 1,4,5-trisphosphate (InsP(3)) binds to its receptor channels and causes liberation of Ca2+ from intracellular stores, frequently in an oscillatory manner. In addition to InsP(3), the activation and inactivation properties of these intracellular channels are controlled by Ca2+. We studied the influence of Ca2+ entry on the kinetics of InsP(3)-triggered oscillations in cytosolic calcium ([Ca2+](i)) in gonadotrophs stimulated with gonadotropin-releasing hormone, an agonist that activates InsP(3) production. The natural expression of voltage-gated Ca2+ channels (VGCC) in these cells was employed to manipulate Ca2+ entry by voltage clamping the cells at different membrane potentials (V-m). Under physiological conditions, the frequency of the GnRH-induced oscillations increased with time, while the amplitude decreased, until both reached stable values. However, in cells with V-m held at -50 mV or lower, both parameters progressively decreased until the signal was abolished. These effects were reverted by a depolarization of the membrane positive to -45 mV in both agonist- and InsP(3)-stimulated gonadotrophs. Depolarization also led to an increase in the fraction of time during which the [Ca2+](i) remained elevated; this effect originated from both an increase in the mean duration of spikes and a decrease in the interval between spikes. The frequency and amplitude of spiking depended on the activity of VGCC, but displayed different temporal courses and voltage relationships. The depolarization-driven recovery of the frequency was instantaneous, whereas the recovery of the amplitude of spiking was more gradual. The midpoints of the V-m sensitivity curve for amplitude and duration of spiking (-15 mV) were close to the value observed for L-type Ca2+ current and for depolarization-induced increase in [Ca2+](i), whereas this parameter was much lower (-35 mV) for interval between spikes and frequency of oscillations. These observations are compatible with at least two distinct effects of Ca2+ entry on the sustained [Ca2+](i) oscillations. Calcium influx facilitates its liberation from intracellular stores by a direct and instantaneous action on the release mechanism. It also magnifies the Ca2+ signal and decreases the frequency because of its gradual effect on the reloading of intracellular stores. C1 NICHHD,ENDOCRINOL & REPROD RES BRANCH,UCS,NIH,BETHESDA,MD 20892. NIDDK,CELL BIOL & GENET LAB,BETHESDA,MD 20892. UNIV CHILE,FAC MED,DEPT PHYSIOL & BIOPHYS,SANTIAGO,CHILE. NR 31 TC 16 Z9 16 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1997 VL 72 IS 2 BP 698 EP 707 PN 1 PG 10 WC Biophysics SC Biophysics GA WD509 UT WOS:A1997WD50900016 PM 9017197 ER PT J AU Xie, L Li, WX Barnett, VA Schoenberg, M AF Xie, L Li, WX Barnett, VA Schoenberg, M TI Graphical evaluation of alkylation of myosin's SH1 and SH2: The N-phenylmaleimide reaction SO BIOPHYSICAL JOURNAL LA English DT Article ID WEAKLY-BINDING CROSSBRIDGES; SKINNED RABBIT PSOAS; SULFHYDRYL MODIFICATION; SKELETAL-MUSCLE; FIBERS; HEADS AB Previous assertions about the effect of alkylation of SH1 and SH2 on the myosin high-salt calcium and EDTA ATPases have been summarized, and a simple procedure for obtaining the fractional labeling of SH1 and SH2 after treatment of myosin with alkylating agents has been derived. A simple graphical procedure for illustrating the degree of preference of a particular alkylating agent for SH1 over SH2 has also been developed. The procedures we developed were validated by applying them to two previously studied compounds, 4-(2-iodoacetamido)-TEMPO and 2,4-dinitrofluorobenzine, and then were used to determine a procedure for maximizing the extent of labeling of SH1 alone by N-phenylmaleimide, a compound not previously studied in this manner. It was found that similar to 80% of the SH1 sites could be alkylated without significant alkylation of SH2. C1 NIAMSD,PHYS BIOL LAB,NIH,BETHESDA,MD 20892. UNIV MINNESOTA,SCH MED,DEPT PHYSIOL,MINNEAPOLIS,MN 55455. NR 20 TC 9 Z9 9 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1997 VL 72 IS 2 BP 858 EP 865 PN 1 PG 8 WC Biophysics SC Biophysics GA WD509 UT WOS:A1997WD50900030 PM 9017211 ER PT J AU Podgornik, R Parsegian, VA AF Podgornik, R Parsegian, VA TI On a possible microscopic mechanism underlying the vapor pressure paradox SO BIOPHYSICAL JOURNAL LA English DT Article ID X-RAY; HYDRATION FORCES; FLUID MEMBRANES; FILMS; FLUCTUATIONS; BILAYERS AB We investigate the free energy and the profile of the displacement field in a stack of sterically interacting smectic multilayers bounded by surfaces under tension. We show that this tension can lead to a significant change in the multilayer free energy. It creates an additional long-range attraction (a pseudo-Casimir attraction) of the van der Waals type and leads to a perturbation in the spatial profile of the displacement field fluctuations. This perturbation can extend to macroscopic distances into the multilayer, away from the perturbing surfaces. The lowering of the free energy of the layers varies explicitly as an inverse power of the thickness of the stack, but also depends implicitly on the bare interactions between the smectic layers. One may regard this lowered energy as being due to a kind of mechanical van der Waals force. We investigate in detail the characteristics and magnitude of the free energy as well as the fluctuations in the displacement field for some typical situations of underlying interlamellar interactions. C1 NIH, STRUCT BIOL LAB, DIV COMP RES & TECHNOL, BETHESDA, MD 20892 USA. RI Podgornik, Rudolf/C-6209-2008 OI Podgornik, Rudolf/0000-0002-3855-4637 NR 21 TC 40 Z9 41 U1 0 U2 4 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1997 VL 72 IS 2 BP 942 EP 952 PN 1 PG 11 WC Biophysics SC Biophysics GA WD509 UT WOS:A1997WD50900038 PM 9017219 ER PT J AU Abugo, OO Macdonald, VW Rudolph, AS Hess, JR Balagopalakrishna, C Rifkind, JM AF Abugo, OO Macdonald, VW Rudolph, AS Hess, JR Balagopalakrishna, C Rifkind, JM TI Measurements of free and encapsulated hemoglobin oxidation by EPR spectroscopy. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 WALTER REED ARMY INST RES,BLOOD RES DETACHMENT,WASHINGTON,DC. USN,RES LAB,CTR BIOMOL SCI & ENGN,WASHINGTON,DC 20375. NIA,NATL INST HLTH,CTR GERONTOL RES,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1997 VL 72 IS 2 BP MAMF2 EP MAMF2 PN 2 PG 1 WC Biophysics SC Biophysics GA WE747 UT WOS:A1997WE74700044 ER PT J AU Barnett, SM Levin, IW AF Barnett, SM Levin, IW TI Protein and lipid structural characteristics associated with disruption of the purple membrane crystalline array: An infrared spectroscopy study SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIDDK,NIH,CHEM PHYS LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1997 VL 72 IS 2 BP MAMJ1 EP MAMJ1 PN 2 PG 1 WC Biophysics SC Biophysics GA WE747 UT WOS:A1997WE74700074 ER PT J AU Barnoy, S McPhie, P Lee, G Eidelman, O Pollard, HB AF Barnoy, S McPhie, P Lee, G Eidelman, O Pollard, HB TI Selective interactions in the intervening segment of the NBF-1 domain of CFTR. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 UNIFORMED SERV UNIV HLTH SCI,DEPT ANAT & CELL BIOL,BETHESDA,MD 20814. NIDDK,CELL BIOL & GENET LAB,NIH,BETHESDA,MD 20892. NIDDK,LBP,NIH,BETHESDA,MD 20892. NR 3 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1997 VL 72 IS 2 BP MP312 EP MP312 PN 2 PG 1 WC Biophysics SC Biophysics GA WE747 UT WOS:A1997WE74700444 ER PT J AU Chen, YD AF Chen, YD TI Theoretical formalism for single kinesin motility SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIDDK,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1997 VL 72 IS 2 BP MP201 EP MP201 PN 2 PG 1 WC Biophysics SC Biophysics GA WE747 UT WOS:A1997WE74700333 ER PT J AU Choi, Y Williamson, LC Neale, EA Copeland, TD Takahashi, M McEnery, MW AF Choi, Y Williamson, LC Neale, EA Copeland, TD Takahashi, M McEnery, MW TI Expression of Na/K-ATPase alpha subunit isoforms during neuronal differentiation and maturation. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 CASE WESTERN RESERVE UNIV,SCH MED,DEPT PHYSIOL & BIOPHYS,CLEVELAND,OH 44106. NCI,FREDERICK CANC RES & DEV CTR,DEV NEUROBIOL LAB,NIH,ABL BAS RES PROGRAM,FREDERICK,MD 21702. MITSUBISHI KASEI INST LIFE SCI,TOKYO,JAPAN. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1997 VL 72 IS 2 BP MPMF7 EP MPMF7 PN 2 PG 1 WC Biophysics SC Biophysics GA WE747 UT WOS:A1997WE74700132 ER PT J AU Dai, R Robinson, RC Friedman, FK AF Dai, R Robinson, RC Friedman, FK TI Cytochrome P450 recognition sites for NADPH cytochrome P450 reductase and substrates. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NCI,NIH,BETHESDA,MD 20892. RI Friedman, Fred/D-4208-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1997 VL 72 IS 2 BP MP290 EP MP290 PN 2 PG 1 WC Biophysics SC Biophysics GA WE747 UT WOS:A1997WE74700424 ER PT J AU Durell, SR Guy, HR AF Durell, SR Guy, HR TI Structural models of Shaker K+ channels in closed, open, and inactivated conformations SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NCI,LMMB,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1997 VL 72 IS 2 BP MPO24 EP MPO24 PN 2 PG 1 WC Biophysics SC Biophysics GA WE747 UT WOS:A1997WE74700157 ER PT J AU Frisbie, SM Chalovich, JM Yu, LC AF Frisbie, SM Chalovich, JM Yu, LC TI Cross-bridges are in weak-binding states in the presence of high concentrations of AMP-PNP in skinned rabbit psoas muscle. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. E CAROLINA UNIV,SCH MED,GREENVILLE,NC 27858. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1997 VL 72 IS 2 BP MPMA3 EP MPMA3 PN 2 PG 1 WC Biophysics SC Biophysics GA WE747 UT WOS:A1997WE74700085 ER PT J AU Frolov, VA Leikina, E Bronk, P Chernomordik, L Zimmerberg, J AF Frolov, VA Leikina, E Bronk, P Chernomordik, L Zimmerberg, J TI Wild-type HA induces hemifusion between cell membranes. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NICHHD,NIH,LTPB,BETHESDA,MD 20892. RUSSIAN ACAD SCI,AN FRUMKIN ELECTROCHEM INST,MOSCOW,RUSSIA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1997 VL 72 IS 2 BP MAMI3 EP MAMI3 PN 2 PG 1 WC Biophysics SC Biophysics GA WE747 UT WOS:A1997WE74700069 ER PT J AU Gibrat, JF Madej, T Spouge, JL Bryant, SH AF Gibrat, JF Madej, T Spouge, JL Bryant, SH TI The vast protein structure comparison method SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,NIH,BETHESDA,MD 20894. NR 0 TC 9 Z9 9 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1997 VL 72 IS 2 BP MP298 EP MP298 PN 2 PG 1 WC Biophysics SC Biophysics GA WE747 UT WOS:A1997WE74700431 ER PT J AU Gruschus, JM Tsao, DHH Wang, LH Nirenberg, M Ferretti, JA AF Gruschus, JM Tsao, DHH Wang, LH Nirenberg, M Ferretti, JA TI Characterization of water at the water-mediated invariant asparagine 51 DNA contact of the vnd/NK-2 homeodomain by NMR SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NHLBI,BIOPHYS CHEM LAB,NIH,BETHESDA,MD 20892. NHLBI,LAB BIOCHEM GENET,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 1 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1997 VL 72 IS 2 BP MP430 EP MP430 PN 2 PG 1 WC Biophysics SC Biophysics GA WE747 UT WOS:A1997WE74700565 ER PT J AU Hao, Y Durell, SR Guy, HR AF Hao, Y Durell, SR Guy, HR TI Structural models of homologous ion channel families: HERG, AKT1, Kir, TWIK, and cyclic nucleotide-gated channels SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NCI,LMMB,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1997 VL 72 IS 2 BP MPO25 EP MPO25 PN 2 PG 1 WC Biophysics SC Biophysics GA WE747 UT WOS:A1997WE74700159 ER PT J AU Henry, ER Jones, CM Hofrichter, J Eaton, WA AF Henry, ER Jones, CM Hofrichter, J Eaton, WA TI A two-state allosteric model can explain hemoglobin kinetics. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIDDK,CHEM PHYS LAB,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 1 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1997 VL 72 IS 2 BP MP341 EP MP341 PN 2 PG 1 WC Biophysics SC Biophysics GA WE747 UT WOS:A1997WE74700476 ER PT J AU Holte, LL Gawrisch, K AF Holte, LL Gawrisch, K TI Solid state mas NMR measurements on the docosahexaenoic chain in bilayers. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIAAA,NIH,ROCKVILLE,MD 20852. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1997 VL 72 IS 2 BP MP246 EP MP246 PN 2 PG 1 WC Biophysics SC Biophysics GA WE747 UT WOS:A1997WE74700379 ER PT J AU Kane, DJ Fendler, K Grell, E Bamberg, E Taniguchi, K Froelich, JP Clarke, RJ AF Kane, DJ Fendler, K Grell, E Bamberg, E Taniguchi, K Froelich, JP Clarke, RJ TI Kinetic investigations of conformational changes of the Na+,K+-ATPase. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 MAX PLANCK INST BIOPHYS,D-6000 FRANKFURT,GERMANY. HOKKAIDO UNIV,SAPPORO,HOKKAIDO 060,JAPAN. NIA,NIH,BALTIMORE,MD 21224. RI Clarke, Ronald/L-5259-2016 OI Clarke, Ronald/0000-0002-0950-8017 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1997 VL 72 IS 2 BP MPMF6 EP MPMF6 PN 2 PG 1 WC Biophysics SC Biophysics GA WE747 UT WOS:A1997WE74700134 ER PT J AU Kidder, LH Lewis, EN Huang, C Levin, IW AF Kidder, LH Lewis, EN Huang, C Levin, IW TI The exploration of lipid domain formation using classical and imaging vibrational spectroscopic methods SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIDDK,CHEM PHYS LAB,NIH,BETHESDA,MD 20892. UNIV VIRGINIA,SCH MED,DEPT BIOCHEM,CHARLOTTESVILLE,VA 22908. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1997 VL 72 IS 2 BP MP270 EP MP270 PN 2 PG 1 WC Biophysics SC Biophysics GA WE747 UT WOS:A1997WE74700403 ER PT J AU Kloczkowski, A Jernigan, RL AF Kloczkowski, A Jernigan, RL TI New methods to enumerate conformations of compact proteins SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NCI,MATH BIOL LAB,NIH,BETHESDA,MD 20892. RI Jernigan, Robert/A-5421-2012; Kloczkowski, Andrzej/B-9868-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1997 VL 72 IS 2 BP MP458 EP MP458 PN 2 PG 1 WC Biophysics SC Biophysics GA WE747 UT WOS:A1997WE74700591 ER PT J AU Koenig, BW Holte, LL Strey, H Gawrisch, K AF Koenig, BW Holte, LL Strey, H Gawrisch, K TI Response of phospholipid membranes to lateral pressure - Effect of polyunsaturated acyl chains SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIAAA,LMBB,NIH,BETHESDA,MD 20892. NIH,LSB,DCRT,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1997 VL 72 IS 2 BP MP278 EP MP278 PN 2 PG 1 WC Biophysics SC Biophysics GA WE747 UT WOS:A1997WE74700410 ER PT J AU Le, SY Maizel, JV AF Le, SY Maizel, JV TI Structure, function, and evolution of the virus internal ribosome entry sites. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NCI,LMMB,DBS,NIH,FREDERICK,MD 21702. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1997 VL 72 IS 2 BP MAMD3 EP MAMD3 PN 2 PG 1 WC Biophysics SC Biophysics GA WE747 UT WOS:A1997WE74700028 ER PT J AU Lee, SP Xiao, J Knutson, JR Lewis, MS Han, MK AF Lee, SP Xiao, J Knutson, JR Lewis, MS Han, MK TI Zn2+ promotes the self-association of HIV-1 integrase in vitro. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 GEORGETOWN UNIV,MED CTR,DEPT BIOCHEM & MOL BIOL,WASHINGTON,DC 20007. NHLBI,CELL BIOL LAB,BIOMED ENGN & INSTRUMENTAT PROGRAM,NIH,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1997 VL 72 IS 2 BP MP297 EP MP297 PN 2 PG 1 WC Biophysics SC Biophysics GA WE747 UT WOS:A1997WE74700433 ER PT J AU Lewis, EN Kidder, LH Pentchev, P Levin, IW Lester, DS AF Lewis, EN Kidder, LH Pentchev, P Levin, IW Lester, DS TI Infrared spectroscopic imaging studies of brain tissue derived from the mutant Niemann Pick C mouse SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIDDK,PHYS CHEM LAB,NIH,BETHESDA,MD 20892. NINCDS,DEV & METAB NEUROL BRANCH,NIH,BETHESDA,MD 20892. US FDA,CTR DRUG EVALUAT & RES,LAUREL,MD 20708. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1997 VL 72 IS 2 BP MPME5 EP MPME5 PN 2 PG 1 WC Biophysics SC Biophysics GA WE747 UT WOS:A1997WE74700121 ER PT J AU Mozzarelli, A Rivetti, C Rossi, GL Eaton, WA Henry, ER AF Mozzarelli, A Rivetti, C Rossi, GL Eaton, WA Henry, ER TI The oxygen affinity of hemoglobin crystals is not altered by allosteric effectors. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 UNIV PARMA,INST BIOCHEM SCI,I-43100 PARMA,ITALY. NIDDK,CHEM PHYS LAB,NIH,BETHESDA,MD 20892. RI Mozzarelli, Andrea/C-3615-2014 OI Mozzarelli, Andrea/0000-0003-3762-0062 NR 0 TC 0 Z9 0 U1 0 U2 2 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1997 VL 72 IS 2 BP MP344 EP MP344 PN 2 PG 1 WC Biophysics SC Biophysics GA WE747 UT WOS:A1997WE74700478 ER PT J AU Nirmala, R Rifkind, J AF Nirmala, R Rifkind, J TI Role of distal histidine in propagating structural information in hemoglobin SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIA,CELLULAR & MOL BIOL LAB,MOL DYNAM SECT,NIH,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1997 VL 72 IS 2 BP MP339 EP MP339 PN 2 PG 1 WC Biophysics SC Biophysics GA WE747 UT WOS:A1997WE74700475 ER PT J AU Rostovtseva, TK Liu, TT Colombini, M Bezrukov, SM AF Rostovtseva, TK Liu, TT Colombini, M Bezrukov, SM TI Probing the VDAC channel by examining the pH dependence of its selectivity and the open-channel current noise SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIH,LSB,DCRT,BETHESDA,MD 20982. UNIV MARYLAND,DEPT ZOOL,COLLEGE PK,MD 20742. RI Colombini, Marco/A-1540-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1997 VL 72 IS 2 BP MPO67 EP MPO67 PN 2 PG 1 WC Biophysics SC Biophysics GA WE747 UT WOS:A1997WE74700201 ER PT J AU Sanna, MT Razynska, A Karavitis, M Koley, AP Friedman, FK Russu, IM Brinigar, WS Fronticelli, C AF Sanna, MT Razynska, A Karavitis, M Koley, AP Friedman, FK Russu, IM Brinigar, WS Fronticelli, C TI Expression and characterization of human hemoglobin with alpha-globin produced in Escherichia coli. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 UNIV MARYLAND,COLLEGE PK,MD 20742. NCI,BETHESDA,MD 20892. TEMPLE UNIV,PHILADELPHIA,PA 19122. WESLEYAN UNIV,MIDDLETOWN,CT 06459. RI Friedman, Fred/D-4208-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1997 VL 72 IS 2 BP MP350 EP MP350 PN 2 PG 1 WC Biophysics SC Biophysics GA WE747 UT WOS:A1997WE74700484 ER PT J AU Sidorova, NY Rau, DC AF Sidorova, NY Rau, DC TI Correlating DNA-protein binding energies and water release. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIH,LSB,DCRT,BETHESDA,MD 20892. NIDDK,ODIR,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1997 VL 72 IS 2 BP MP428 EP MP428 PN 2 PG 1 WC Biophysics SC Biophysics GA WE747 UT WOS:A1997WE74700564 ER PT J AU Steinbach, PJ Brooks, BR AF Steinbach, PJ Brooks, BR TI Dynamics of myoglobin in solution simulated at multiple temperatures SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIH,DCRT,BETHESDA,MD 20892. NR 1 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1997 VL 72 IS 2 BP MP468 EP MP468 PN 2 PG 1 WC Biophysics SC Biophysics GA WE747 UT WOS:A1997WE74700604 ER PT J AU Urbaneja, MA CasasFinet, JR Fisher, RJ Rein, A Bladen, S Fivash, RJ Gorelick, RJ Kane, BP Arthur, LO Henderson, LE AF Urbaneja, MA CasasFinet, JR Fisher, RJ Rein, A Bladen, S Fivash, RJ Gorelick, RJ Kane, BP Arthur, LO Henderson, LE TI HIV-1 nucleocapsid (NC) protein p7 exhibits specific nucleic acid binding. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 SAIC,AVP,FREDERICK,MD 21702. SAIC,PCI,FREDERICK,MD 21702. NCI,DMS,FCRDC,FREDERICK,MD 21702. NCI,ABL,BRP,FCRDC,FREDERICK,MD 21702. RI Fisher, Robert/B-1431-2009 NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1997 VL 72 IS 2 BP MP426 EP MP426 PN 2 PG 1 WC Biophysics SC Biophysics GA WE747 UT WOS:A1997WE74700560 ER PT J AU Xie, L Li, WX Schoenberg, M AF Xie, L Li, WX Schoenberg, M TI Myosin subfragment-1 modified with NPM or pPDM does not hydrolyze ATP but will bind strongly to F-actin if ATP concentration is sufficiently low SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIAMS,LPB,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1997 VL 72 IS 2 BP MP162 EP MP162 PN 2 PG 1 WC Biophysics SC Biophysics GA WE747 UT WOS:A1997WE74700296 ER PT J AU Xie, L Li, WX Barnett, VA Schoenberg, M AF Xie, L Li, WX Barnett, VA Schoenberg, M TI Simple graphical procedure for quantifying alkylation of myosin's SH1 and SH2 SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIAMS,LPB,NIH,BETHESDA,MD 20892. UNIV MINNESOTA,SCH MED,DEPT PHYSIOL,MINNEAPOLIS,MN 55455. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1997 VL 72 IS 2 BP MP160 EP MP160 PN 2 PG 1 WC Biophysics SC Biophysics GA WE747 UT WOS:A1997WE74700292 ER PT J AU Xu, S Yu, LC Schoenberg, M AF Xu, S Yu, LC Schoenberg, M TI NPM-reacted myosin crossbridges can bind strongly to actin. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIAMS,LPB,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1997 VL 72 IS 2 BP MP161 EP MP161 PN 2 PG 1 WC Biophysics SC Biophysics GA WE747 UT WOS:A1997WE74700295 ER PT J AU Yarmola, E Calabrese, PP Chrambach, A Weiss, GH AF Yarmola, E Calabrese, PP Chrambach, A Weiss, GH TI Experimental evidence of a non-diffusional nature of band spreading in gel electrophoresis. Corroboration of an alternative model of band spreading SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NICHHD,SMA,LTPB,NIH,BETHESDA,MD 20892. RAS,LBP,IMB,MOSCOW 117984,RUSSIA. NIH,PSL,DCRT,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1997 VL 72 IS 2 BP MP443 EP MP443 PN 2 PG 1 WC Biophysics SC Biophysics GA WE747 UT WOS:A1997WE74700577 ER PT J AU Zhang, FL Lucke, C Baier, LJ Sacchettini, JC Hamilton, JA AF Zhang, FL Lucke, C Baier, LJ Sacchettini, JC Hamilton, JA TI Comparison of T54 allele with normal A54 allele of human intestinal fatty acid binding protein. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 BOSTON UNIV,SCH MED,DEPT BIOPHYS,BOSTON,MA 02118. NIDDK,PHOENIX EPIDEMIOL & CLIN RES BRANCH,NIH,PHOENIX,AZ 85016. TEXAS A&M UNIV,DEPT BIOCHEM & BIOPHYS,COLLEGE STN,TX 77845. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1997 VL 72 IS 2 BP MP294 EP MP294 PN 2 PG 1 WC Biophysics SC Biophysics GA WE747 UT WOS:A1997WE74700426 ER PT J AU Aguilella, V Rostovtseva, TK Vodyanoy, I Bezrukov, SM Parsegian, VA AF Aguilella, V Rostovtseva, TK Vodyanoy, I Bezrukov, SM Parsegian, VA TI Gramicidin A channel as a sensor of membrane lipid titration. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIH,LSB,DCRT,BETHESDA,MD 20982. UNIV JAUME 1,CASTELLO DE PLANA,SPAIN. RI Aguilella, Vicente/B-7592-2008 OI Aguilella, Vicente/0000-0002-2420-2649 NR 0 TC 1 Z9 1 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1997 VL 72 IS 2 BP TH275 EP TH275 PN 2 PG 1 WC Biophysics SC Biophysics GA WE747 UT WOS:A1997WE74702253 ER PT J AU Alarcon, JM Rojas, E delaFuente, M AF Alarcon, JM Rojas, E delaFuente, M TI Alzheimer's disease amyloid beta-protein evokes Na+ entry across the membrane of unilamellar phosphatidylserine (PS) but not phosphatidylcholine (PC) liposomes. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 UNIV CHILE,DEPT PHYSIOL BIOPHYS,FAC MED,SANTIAGO,CHILE. NIDDK,LCBG,NIH,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1997 VL 72 IS 2 BP TH299 EP TH299 PN 2 PG 1 WC Biophysics SC Biophysics GA WE747 UT WOS:A1997WE74702277 ER PT J AU Arispe, N Ma, J Pollard, H AF Arispe, N Ma, J Pollard, H TI Xanthine drug activation of CFTR channels expressed in HEK293 cells. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 CASE WESTERN RESERVE UNIV,DEPT PHYSIOL & BIOPHYS,CLEVELAND,OH 44106. UNIFORMED SERV UNIV HLTH SCI,DEPT ANAT & CELL BIOL,BETHESDA,MD 20814. NIDDK,CELL BIOL & GENET LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1997 VL 72 IS 2 BP TUAM9 EP TUAM9 PN 2 PG 1 WC Biophysics SC Biophysics GA WE747 UT WOS:A1997WE74700648 ER PT J AU Barnett, SM Dracheva, S Bose, S Hendler, RW Levin, IW AF Barnett, SM Dracheva, S Bose, S Hendler, RW Levin, IW TI Protein and lipid structural characteristics associated with the recovery of normal bacteriorhodopsin photocycle behavior in triton-treated purple membrane SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIDDK,CHEM PHYS LAB,BETHESDA,MD 20892. NHLBI,CELL BIOL LAB,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1997 VL 72 IS 2 BP TU393 EP TU393 PN 2 PG 1 WC Biophysics SC Biophysics GA WE747 UT WOS:A1997WE74701177 ER PT J AU Begg, CM Williamson, LC Neale, EA Vance, CL Copeland, TD McEnery, MW AF Begg, CM Williamson, LC Neale, EA Vance, CL Copeland, TD McEnery, MW TI Changes in the level and pattern of expression of voltage-dependent calcium channel beta subunits during neuronal differentiation and maturation. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 CASE WESTERN RESERVE UNIV,SCH MED,DEPT PHYSIOL & BIOPHYS,CLEVELAND,OH 44106. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. NICHHD,DEV NEUROBIOL LAB,NIH,FREDERICK,MD 21702. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1997 VL 72 IS 2 BP TUP59 EP TUP59 PN 2 PG 1 WC Biophysics SC Biophysics GA WE747 UT WOS:A1997WE74700845 ER PT J AU Bose, S Mukhopadhyay, AK Dracheva, S Hendler, RW AF Bose, S Mukhopadhyay, AK Dracheva, S Hendler, RW TI The role of salt in reconstituting photocycle behavior to triton-damaged purple membranes by addition of native lipids SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NHLBI,CELL BIOL LAB,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1997 VL 72 IS 2 BP TU394 EP TU394 PN 2 PG 1 WC Biophysics SC Biophysics GA WE747 UT WOS:A1997WE74701180 ER PT J AU CasasFinet, JR Urbaneja, MA McGrath, G Gorelick, RJ Bosche, WJ Kane, BP Arthur, IO Henderson, LE Copeland, T Lee, BM DeGuzman, RN Summers, MF AF CasasFinet, JR Urbaneja, MA McGrath, G Gorelick, RJ Bosche, WJ Kane, BP Arthur, IO Henderson, LE Copeland, T Lee, BM DeGuzman, RN Summers, MF TI Conformational heterogeneity in HIV-1 nucleocapsid protein p7 SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 AVP,SAIC,FREDERICK,MD. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. UNIV MARYLAND,HOWARD HUGHES MED INST,BALTIMORE,MD 21201. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1997 VL 72 IS 2 BP TUPM2 EP TUPM2 PN 2 PG 1 WC Biophysics SC Biophysics GA WE747 UT WOS:A1997WE74700754 ER PT J AU Chik, JK Chi, SL Rau, D Leikin, S Parsegian, VA AF Chik, JK Chi, SL Rau, D Leikin, S Parsegian, VA TI The effect of osmotic pressure and Hofmeister salts on the heat aggregation of hydroxypropylcellulose and poly-L-proline SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIH,DCRT,LSB,BETHESDA,MD 20892. NIDDK,ODIR,NIH,BETHESDA,MD 20892. PRINCETON UNIV,PRINCETON,NJ 08544. NR 0 TC 0 Z9 0 U1 1 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1997 VL 72 IS 2 BP TH396 EP TH396 PN 2 PG 1 WC Biophysics SC Biophysics GA WE747 UT WOS:A1997WE74702372 ER PT J AU Colson, AO Perlman, JH Jain, R Cohen, LA Osman, R Gershengorn, MC AF Colson, AO Perlman, JH Jain, R Cohen, LA Osman, R Gershengorn, MC TI Sequential binding of the thyrotropin-releasing hormone (TRH) to the TRH receptors: A model for small ligand binding to G protein coupled receptors. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 CUNY MT SINAI SCH MED,NEW YORK,NY 10029. CORNELL UNIV MED COLL,NEW YORK,NY 10021. NIDDK,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1997 VL 72 IS 2 BP TUAM3 EP TUAM3 PN 2 PG 1 WC Biophysics SC Biophysics GA WE747 UT WOS:A1997WE74700691 ER PT J AU Davenport, L Knutson, JR Sackett, DL AF Davenport, L Knutson, JR Sackett, DL TI High pressure induces a stable molten globule state in tubulin. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NCI,NIH,BETHESDA,MD 20892. NHLBI,NIH,BETHESDA,MD 20892. CUNY BROOKLYN COLL,BROOKLYN,NY 11210. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1997 VL 72 IS 2 BP TH253 EP TH253 PN 2 PG 1 WC Biophysics SC Biophysics GA WE747 UT WOS:A1997WE74702230 ER PT J AU Dimitriadis, EK AF Dimitriadis, EK TI Non-isodesmic indefinite association of anthrax truncated protective antigen SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NCI,BEIP,NCRR,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1997 VL 72 IS 2 BP TU456 EP TU456 PN 2 PG 1 WC Biophysics SC Biophysics GA WE747 UT WOS:A1997WE74701240 ER PT J AU Dubois, M Zemb, T Fuller, N Rand, RP Parsegian, VA AF Dubois, M Zemb, T Fuller, N Rand, RP Parsegian, VA TI Equation of state of a charged-bilayer system: The measured entropy of the lamellar-lamellar transition in DDAB SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 CEA SACLAY,SCM,F-91191 GIF SUR YVETTE,FRANCE. BROCK UNIV,ST CATHARINES,ON L2S 3A1,CANADA. NIH,BETHESDA,MD 20892. RI ZEMB, Thomas/E-5958-2010 NR 0 TC 1 Z9 1 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1997 VL 72 IS 2 BP TH329 EP TH329 PN 2 PG 1 WC Biophysics SC Biophysics GA WE747 UT WOS:A1997WE74702304 ER PT J AU Durell, SR Wallqvist, A AF Durell, SR Wallqvist, A TI Solvation thermodynamics of hydrophilic and hydrophobic groups studied by molecular dynamics simulation. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NCI,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1997 VL 72 IS 2 BP TH400 EP TH400 PN 2 PG 1 WC Biophysics SC Biophysics GA WE747 UT WOS:A1997WE74702377 ER PT J AU Ehrenstein, D Iwasa, KH AF Ehrenstein, D Iwasa, KH TI Current noise power spectrum of the membrane motor of the cochlear outer hair cell. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIDCD,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1997 VL 72 IS 2 BP TH119 EP TH119 PN 2 PG 1 WC Biophysics SC Biophysics GA WE747 UT WOS:A1997WE74702092 ER PT J AU Gawrisch, K Yau, WM Wimley, WC White, SH AF Gawrisch, K Yau, WM Wimley, WC White, SH TI Location of tryptophan sidechains in membranes studied with H-1 MAS NMR SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIH,ROCKVILLE,MD 20852. UNIV CALIF IRVINE,IRVINE,CA 92717. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1997 VL 72 IS 2 BP TU319 EP TU319 PN 2 PG 1 WC Biophysics SC Biophysics GA WE747 UT WOS:A1997WE74701105 ER PT J AU Hawkins, ME Schulte, TW Balis, FM AF Hawkins, ME Schulte, TW Balis, FM TI A hybridization probe containing a fluorescent guanosine analog with increased fluorescence intensity upon formation of a hairpin. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NCI,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1997 VL 72 IS 2 BP TU371 EP TU371 PN 2 PG 1 WC Biophysics SC Biophysics GA WE747 UT WOS:A1997WE74701157 ER PT J AU Hogue, C AF Hogue, C TI Database of experimentally interesting proteins for fluorescence studies. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIH,NCBL,NATL LIB MED,BETHESDA,MD 20894. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1997 VL 72 IS 2 BP THAM4 EP THAM4 PN 2 PG 1 WC Biophysics SC Biophysics GA WE747 UT WOS:A1997WE74701963 ER PT J AU Huster, D Barry, JA Gawrisch, K AF Huster, D Barry, JA Gawrisch, K TI Lateral lipid organization in polyunsaturated membranes SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIAAA,METAB & MOL BIOL LAB,NIH,ROCKVILLE,MD 20852. UNIV LEIPZIG,INST MED PHYS & BIOPHYS,D-04103 LEIPZIG,GERMANY. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1997 VL 72 IS 2 BP TH305 EP TH305 PN 2 PG 1 WC Biophysics SC Biophysics GA WE747 UT WOS:A1997WE74702281 ER PT J AU Janczewski, AM Spurgeon, HA Lakatta, EG AF Janczewski, AM Spurgeon, HA Lakatta, EG TI Sarcoplasmic reticulum directly buffers calcium influx via the sarcolemmal sodium-calcium exchanger and rapidly modulates its impact on calcium release in cardiac myocytes. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIA,GERONTOL RES CTR,CARDIOVASC SCI LAB,NIH,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1997 VL 72 IS 2 BP TU138 EP TU138 PN 2 PG 1 WC Biophysics SC Biophysics GA WE747 UT WOS:A1997WE74700925 ER PT J AU Johnson, BD Zheng, W Kauser, K Freay, AD Korach, KS Scheuer, T Catterall, WA Rubanyi, GM AF Johnson, BD Zheng, W Kauser, K Freay, AD Korach, KS Scheuer, T Catterall, WA Rubanyi, GM TI Estrogen receptor disruption increases expression of the cardiac L-type calcium channel in a transgenic mouse SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 UNIV WASHINGTON,DEPT PHARMACOL,SEATTLE,WA 98195. BERLEX BIOSCI,RICHMOND,CA 94804. NIEHS,RES TRIANGLE PK,NC 27709. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1997 VL 72 IS 2 BP THP65 EP THP65 PN 2 PG 1 WC Biophysics SC Biophysics GA WE747 UT WOS:A1997WE74702039 ER PT J AU Kovbasnjuk, O Leader, JP Spring, KR AF Kovbasnjuk, O Leader, JP Spring, KR TI Fluid flows across MDCK cell tight junctions (TJ). SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NHLBI,LKEM,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1997 VL 72 IS 2 BP TH381 EP TH381 PN 2 PG 1 WC Biophysics SC Biophysics GA WE747 UT WOS:A1997WE74702359 ER PT J AU Kriegler, S Yakel, JL AF Kriegler, S Yakel, JL TI Activation of PKC by phorbol esters inhibits the current and alters the permeability ratio in expressed kainate receptors. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIEHS,LAB SIGNAL TRANSDUCT,RES TRIANGLE PK,NC 27709. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1997 VL 72 IS 2 BP TH123 EP TH123 PN 2 PG 1 WC Biophysics SC Biophysics GA WE747 UT WOS:A1997WE74702097 ER PT J AU Kuznetsova, N Chi, SL Leikin, S AF Kuznetsova, N Chi, SL Leikin, S TI Effect of alcohols, polyols and sugars on protein self-assembly. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 RUSSIAN ACAD SCI,VA ENGELHARDT MOL BIOL INST,MOSCOW,RUSSIA. PRINCETON UNIV,PRINCETON,NJ 08544. NIH,LSB,DCRT,BETHESDA,MD 20892. NIDDK,ODIR,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 1 U2 2 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1997 VL 72 IS 2 BP TH397 EP TH397 PN 2 PG 1 WC Biophysics SC Biophysics GA WE747 UT WOS:A1997WE74702373 ER PT J AU Luo, G Herrera, AH Horowits, R AF Luo, G Herrera, AH Horowits, R TI Identification of N-RAP and its actin binding domains. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIAMS,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1997 VL 72 IS 2 BP TH235 EP TH235 PN 2 PG 1 WC Biophysics SC Biophysics GA WE747 UT WOS:A1997WE74702212 ER PT J AU Minetti, CASA Blake, MS Tai, JY Remeta, DP AF Minetti, CASA Blake, MS Tai, JY Remeta, DP TI Characterization of native and recombinant forms of Por A and Por B gene products from Neisseria meningitidis. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 N AMER VACCINE INC,BELTSVILLE,MD 20705. NHLBI,NIH,BETHESDA,MD 20892. RI Minetti, Conceicao/B-5077-2009 OI Minetti, Conceicao/0000-0002-9682-2898 NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1997 VL 72 IS 2 BP THAM4 EP THAM4 PN 2 PG 1 WC Biophysics SC Biophysics GA WE747 UT WOS:A1997WE74701917 ER PT J AU Mirotznik, RR Stanley, EF AF Mirotznik, RR Stanley, EF TI Botulinum toxin Cl selectively cleaves syntaxin the the calyx nerve terminal of the chick ciliary ganglion SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NINCDS,SYNAPT MECH SECT,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1997 VL 72 IS 2 BP TH115 EP TH115 PN 2 PG 1 WC Biophysics SC Biophysics GA WE747 UT WOS:A1997WE74702090 ER PT J AU Paquette, T Clay, JR Ogbaghebriel, A Sasyniuk, BI Shrier, A AF Paquette, T Clay, JR Ogbaghebriel, A Sasyniuk, BI Shrier, A TI Effect of divalent cations on the E-4031 sensitive repolarization current, I-Kr, in rabbit ventricular myocytes SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 MCGILL UNIV,DEPT PHYSIOL,MONTREAL,PQ H3G 1Y6,CANADA. MCGILL UNIV,DEPT PHARMACOL,MONTREAL,PQ H3G 1Y6,CANADA. NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1997 VL 72 IS 2 BP TUP16 EP TUP16 PN 2 PG 1 WC Biophysics SC Biophysics GA WE747 UT WOS:A1997WE74700801 ER PT J AU Parsegian, VA Podgornik, R AF Parsegian, VA Podgornik, R TI Closing in on the vapor pressure paradox. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. RI Podgornik, Rudolf/C-6209-2008 OI Podgornik, Rudolf/0000-0002-3855-4637 NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1997 VL 72 IS 2 BP TH330 EP TH330 PN 2 PG 1 WC Biophysics SC Biophysics GA WE747 UT WOS:A1997WE74702307 ER PT J AU Sharma, P Huang, XL Barchi, JJ Pant, HC AF Sharma, P Huang, XL Barchi, JJ Pant, HC TI Structural basis of neurofilament phosphorylation by cyclin dependent kinase-5 SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NINCDS,NEUROCHEM LAB,NIH,BETHESDA,MD 20892. NCI,DIV BASIC SCI,NIH,BETHESDA,MD 20814. RI Barchi Jr., Joseph/N-3784-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1997 VL 72 IS 2 BP TH262 EP TH262 PN 2 PG 1 WC Biophysics SC Biophysics GA WE747 UT WOS:A1997WE74702238 ER PT J AU Singh, Y Leppla, SH Dimitriadis, K Lewis, MS AF Singh, Y Leppla, SH Dimitriadis, K Lewis, MS TI Association of anthrax protective antigen and lethal factor: A thermodynamic analysis SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIDR,LME,BETHESDA,MD 20892. NIH,BEIP,NCRR,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1997 VL 72 IS 2 BP TU457 EP TU457 PN 2 PG 1 WC Biophysics SC Biophysics GA WE747 UT WOS:A1997WE74701241 ER PT J AU Stanley, EF Mirotznik, RR AF Stanley, EF Mirotznik, RR TI Botulinum toxin C1 eliminates modulation of presynaptic calcium channels by GTP gamma S: Implication of syntaxin involvement in the G-protein modulation pathway. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NINCDS,SYNAPT MECHANISMS SECT,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1997 VL 72 IS 2 BP TUAM2 EP TUAM2 PN 2 PG 1 WC Biophysics SC Biophysics GA WE747 UT WOS:A1997WE74700666 ER PT J AU Suciu, DJ Begg, CM Vance, CL Zimmermann, LK Copeland, TD McEnery, MW AF Suciu, DJ Begg, CM Vance, CL Zimmermann, LK Copeland, TD McEnery, MW TI Subcellular distribution of calcium channel alpha1 and beta subunits during rat brain ontogeny. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 CASE WESTERN RESERVE UNIV,SCH MED,DEPT PHYSIOL & BIOPHYS,CLEVELAND,OH 44106. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1997 VL 72 IS 2 BP TUP58 EP TUP58 PN 2 PG 1 WC Biophysics SC Biophysics GA WE747 UT WOS:A1997WE74700842 ER PT J AU Walczak, WJ Xiao, JM Kopetz, ES Lease, K Grau, H Lee, SP Han, MK Knutson, JR AF Walczak, WJ Xiao, JM Kopetz, ES Lease, K Grau, H Lee, SP Han, MK Knutson, JR TI ''Golden ruler'': Very long-range resonance energy transfer to surface plasmon acceptors. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NHLBI,CELL BIOL LAB,NIH,BETHESDA,MD 20892. GEORGETOWN UNIV,MED CTR,DEPT BIOCHEM & MOL BIOL,WASHINGTON,DC 20007. NR 0 TC 0 Z9 0 U1 1 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1997 VL 72 IS 2 BP TU367 EP TU367 PN 2 PG 1 WC Biophysics SC Biophysics GA WE747 UT WOS:A1997WE74701152 ER PT J AU Xiao, RP Avdonin, P Akliter, SA Zhou, YY Ziman, B Cheng, H Lefkowitz, RJ Koch, WJ Lakatta, EG AF Xiao, RP Avdonin, P Akliter, SA Zhou, YY Ziman, B Cheng, H Lefkowitz, RJ Koch, WJ Lakatta, EG TI Dual coupling of beta(2)-adrenergic receptor to G(i) as well as to G(s) in cardiac myocytes SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIA,GERONTOL RES CTR,CARDIOVASC SCI LAB,BALTIMORE,MD 21224. DUKE UNIV,MED CTR,DEPT SURG,DURHAM,NC 27710. DUKE UNIV,MED CTR,DEPT MED,DURHAM,NC 27710. DUKE UNIV,MED CTR,HOWARD HUGHES MED INST,DURHAM,NC 27710. NR 0 TC 0 Z9 0 U1 1 U2 2 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1997 VL 72 IS 2 BP TUAM2 EP TUAM2 PN 2 PG 1 WC Biophysics SC Biophysics GA WE747 UT WOS:A1997WE74700693 ER PT J AU Xu, ASL Chu, CK London, RE AF Xu, ASL Chu, CK London, RE TI The facilitated and non-facilitated membrane transport of D- and L-2'-fluoro-5-methyl arbinofuranosyluracil in human erythrocytes: A F-19 NMR study. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIEHS,STRUCT BIOL LAB,RES TRIANGLE PK,NC 27709. UNIV GEORGIA,COLL PHARM,DEPT MED CHEM,ATHENS,GA 30602. NR 0 TC 0 Z9 0 U1 1 U2 2 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1997 VL 72 IS 2 BP TU343 EP TU343 PN 2 PG 1 WC Biophysics SC Biophysics GA WE747 UT WOS:A1997WE74701128 ER PT J AU Zhou, YY Lakatta, EG Xiao, RP AF Zhou, YY Lakatta, EG Xiao, RP TI Blockade of beta(2)-adrenergic positive inotropic effect by inhibitory cAMP analog Rp-CPT-cAMP in cardiomyocytes SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIA,GERONTOL RES CTR,CARDIOVASC SCI LAB,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 U1 1 U2 2 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1997 VL 72 IS 2 BP TUAM4 EP TUAM4 PN 2 PG 1 WC Biophysics SC Biophysics GA WE747 UT WOS:A1997WE74700694 ER PT J AU Bezrukov, SM Pustovoit, MA Vodyanoy, I AF Bezrukov, SM Pustovoit, MA Vodyanoy, I TI Stochastic resonance in non-dynamical systems without response thresholds SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIH,LSB,DCRT,BETHESDA,MD 20892. ST PETERSBURG NUCL PHYS INST,ST PETERSBURG,RUSSIA. OFF NAVAL RES,LONDON,ENGLAND. RI Pustovoit, Mark/B-5249-2008 NR 0 TC 0 Z9 0 U1 0 U2 2 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1997 VL 72 IS 2 BP WP102 EP WP102 PN 2 PG 1 WC Biophysics SC Biophysics GA WE747 UT WOS:A1997WE74701515 ER PT J AU Bose, S Hendler, RW Shrager, RI Chan, SI Smith, PD AF Bose, S Hendler, RW Shrager, RI Chan, SI Smith, PD TI Evidence for a branched sequence of electron transfer in the reduction of O-2 by cytochrome aa(3) SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract ID OXIDASE C1 NHLBI,LCB,NIH,BETHESDA,MD 20892. NIH,LAS,DCRT,BETHESDA,MD 20892. NIH,BEIP,NCRR,BETHESDA,MD 20892. CALTECH,LCP,PASADENA,CA 91125. NR 2 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1997 VL 72 IS 2 BP WP395 EP WP395 PN 2 PG 1 WC Biophysics SC Biophysics GA WE747 UT WOS:A1997WE74701804 ER PT J AU Chan, CK Eaton, WA Hofrichter, J AF Chan, CK Eaton, WA Hofrichter, J TI Submillisecond processes in protein folding studied by ultrarapid mixing and continuous flow SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIDDK,NIH,CHEM PHYS LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 1 U2 2 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1997 VL 72 IS 2 BP WP383 EP WP383 PN 2 PG 1 WC Biophysics SC Biophysics GA WE747 UT WOS:A1997WE74701792 ER PT J AU Chanturiya, AN Zimmerberg, J Chernomordik, LV AF Chanturiya, AN Zimmerberg, J Chernomordik, LV TI Alcohols promote hemifusion of liposomes to planar lipid bilayers. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIH,LCMB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1997 VL 72 IS 2 BP WP307 EP WP307 PN 2 PG 1 WC Biophysics SC Biophysics GA WE747 UT WOS:A1997WE74701716 ER PT J AU Chizmadzhev, YA Kumenko, DA Chernomordik, L Zimmerberg, J Cohen, FS AF Chizmadzhev, YA Kumenko, DA Chernomordik, L Zimmerberg, J Cohen, FS TI Growth of fusion pores connecting membranes of different tensions. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 RUSSIAN ACAD SCI,AN FRUMKIN ELECTROCHEM INST,MOSCOW 117071,RUSSIA. NICHHD,LTPB,NIH,BETHESDA,MD 20892. RUSH MED COLL,DEPT PHYSIOL & MOL BIOPHYS,CHICAGO,IL 60612. RI Chizmadzhev, Yuri/L-1984-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1997 VL 72 IS 2 BP WP306 EP WP306 PN 2 PG 1 WC Biophysics SC Biophysics GA WE747 UT WOS:A1997WE74701718 ER PT J AU Iwasa, KH Adachi, M AF Iwasa, KH Adachi, M TI Force generation in the cochlear outer hair cell under voltage clamp. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIDCD,BIOPHYS SECT,LCB,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1997 VL 72 IS 2 BP WAMJ5 EP WAMJ5 PN 2 PG 1 WC Biophysics SC Biophysics GA WE747 UT WOS:A1997WE74701340 ER PT J AU Kasianowicz, JJ Bezrukov, SM AF Kasianowicz, JJ Bezrukov, SM TI pH sensitivity of PEG-induced effects on S-aureus alpha-hemolysin single channel current SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NATL INST STAND & TECHNOL,BOULDER,CO 80303. NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1997 VL 72 IS 2 BP WP101 EP WP101 PN 2 PG 1 WC Biophysics SC Biophysics GA WE747 UT WOS:A1997WE74701512 ER PT J AU Kinard, TA Satin, LS deVries, G Sherman, A AF Kinard, TA Satin, LS deVries, G Sherman, A TI Titrating K-ATP conductances into single insulin-secreting cells via dynamic clamping. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,DEPT PHARMACOL & TOXICOL,RICHMOND,VA 23298. NIDDK,MATH RES BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1997 VL 72 IS 2 BP WPOS6 EP WPOS6 PN 2 PG 1 WC Biophysics SC Biophysics GA WE747 UT WOS:A1997WE74701418 ER PT J AU Kornyshev, AA Leikin, S AF Kornyshev, AA Leikin, S TI Theory of interaction between helical biomolecules. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 FORSCHUNGSZENTRUM JULICH, FORSCHUNGSZENTRUM, INST ENERGIEVERFAHRENSTECH, JULICH, GERMANY. LSB, DCRT, BETHESDA, MD 20892 USA. NIDDK, ODIR, NIH, BETHESDA, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1997 VL 72 IS 2 BP WAMK8 EP WAMK8 PG 1 WC Biophysics SC Biophysics GA WE747 UT WOS:A1997WE74701353 ER PT J AU Leikina, EA Frolov, V Zimmerberg, J Chernomordik, LV AF Leikina, EA Frolov, V Zimmerberg, J Chernomordik, LV TI Law temperature-arrested stage of influenza hemagglutinin mediated cell-cell fusion is subsequent to the lipid-sensitive fusion stage but prior to lipid mixing and fusion pore formation. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NICHHD,LTPB,NIH,BETHESDA,MD 20892. AN FRUMKIN ELECTROCHEM INST,MOSCOW 117071,RUSSIA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1997 VL 72 IS 2 BP WP296 EP WP296 PN 2 PG 1 WC Biophysics SC Biophysics GA WE747 UT WOS:A1997WE74701707 ER PT J AU Mitchell, DC Litman, BJ AF Mitchell, DC Litman, BJ TI Phospholipid acyl chain unsaturation determines cholesterol effects on rhodopsin photoactivation SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIAAA,NIH,ROCKVILLE,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1997 VL 72 IS 2 BP WP352 EP WP352 PN 2 PG 1 WC Biophysics SC Biophysics GA WE747 UT WOS:A1997WE74701764 ER PT J AU Niebylski, CD Litman, BJ AF Niebylski, CD Litman, BJ TI Lateral phase heterogeneity in dipolyunsaturated and disaturated phospholipid bilayers monitored with novel pyrene-labeled phospholipids. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIAAA,LMBB,NIH,SECT FLUORESCENCE STUDIES,ROCKVILLE,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1997 VL 72 IS 2 BP WP323 EP WP323 PN 2 PG 1 WC Biophysics SC Biophysics GA WE747 UT WOS:A1997WE74701735 ER PT J AU Plonsky, I Leikina, E Oomens, AGP Blissard, GW Zimmerberg, J Chernomordik, L AF Plonsky, I Leikina, E Oomens, AGP Blissard, GW Zimmerberg, J Chernomordik, L TI The target membrane influences the pH-dependence and kinetics of viral fusion. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NICHHD,NIH,BETHESDA,MD 20892. CORNELL UNIV,BOYCE THOMPSON INST,ITHACA,NY 14853. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1997 VL 72 IS 2 BP WP295 EP WP295 PN 2 PG 1 WC Biophysics SC Biophysics GA WE747 UT WOS:A1997WE74701705 ER PT J AU Simpson, PB Russell, JT AF Simpson, PB Russell, JT TI Multiple cellular specialization define wave propagation sites with elevated Ca2+ release kinetics in oligodendrocytes. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NICHHD,LCMN,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1997 VL 72 IS 2 BP WP257 EP WP257 PN 2 PG 1 WC Biophysics SC Biophysics GA WE747 UT WOS:A1997WE74701668 ER PT J AU Strey, HH Podgornik, R Rau, DC Yu, L Parsegian, VA AF Strey, HH Podgornik, R Rau, DC Yu, L Parsegian, VA TI Chirality, structure and free energy of DNA liquid crystals. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 EXXON RES & ENGN CO,FLORHAM PK,NJ 07932. NIAMS,LCP,NIDDK,OD,DCRT,LSB,NIH,BETHESDA,MD 20892. RI Podgornik, Rudolf/C-6209-2008 OI Podgornik, Rudolf/0000-0002-3855-4637 NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1997 VL 72 IS 2 BP WP413 EP WP413 PN 2 PG 1 WC Biophysics SC Biophysics GA WE747 UT WOS:A1997WE74701824 ER PT J AU Thompson, PA Eaton, A Hofrichter, J AF Thompson, PA Eaton, A Hofrichter, J TI Laser temperature jump studies of the helix-coil transition of an alanine-based peptide SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIDDK,NIH,CHEM PHYS LAB,BETHESDA,MD 20892. NR 0 TC 3 Z9 3 U1 1 U2 2 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1997 VL 72 IS 2 BP WP377 EP WP377 PN 2 PG 1 WC Biophysics SC Biophysics GA WE747 UT WOS:A1997WE74701786 ER PT J AU Vogel, SS Radko, SP Chrambach, A Chestkov, VV AF Vogel, SS Radko, SP Chrambach, A Chestkov, VV TI Reconstitution of calcium triggered exocytosis in vitro using 'reserve' granules. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIH,SMS,NINDS,BETHESDA,MD 20892. RAMS,MGC,MOSCOW,RUSSIA. RI Vogel, Steven/A-3585-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1997 VL 72 IS 2 BP WAME4 EP WAME4 PN 2 PG 1 WC Biophysics SC Biophysics GA WE747 UT WOS:A1997WE74701298 ER PT J AU Yu, JH Simplaceanu, V Tjandra, NL Cottam, PF Lukin, JA Ho, C AF Yu, JH Simplaceanu, V Tjandra, NL Cottam, PF Lukin, JA Ho, C TI H-1, C-13, N-15 NMR assignments and secondary structure of the 25 KD glutamine-binding protein from Escherichia coli SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 CARNEGIE MELLON UNIV,DEPT BIOL SCI,PITTSBURGH,PA 15217. NIH,PHYS CHEM LAB,NNDDK,BETHESDA,MD 20892. RI Ho, Chien/O-6112-2016 OI Ho, Chien/0000-0002-4094-9232 NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1997 VL 72 IS 2 BP WP442 EP WP442 PN 2 PG 1 WC Biophysics SC Biophysics GA WE747 UT WOS:A1997WE74701853 ER PT J AU Zhang, JQ Horowits, R AF Zhang, JQ Horowits, R TI Interaction between expressed nebulin fragments and actin. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIAMS,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1997 VL 72 IS 2 BP WPMA8 EP WPMA8 PN 2 PG 1 WC Biophysics SC Biophysics GA WE747 UT WOS:A1997WE74701362 ER PT J AU Selvaggi, TA Walker, RE Fleisher, TA AF Selvaggi, TA Walker, RE Fleisher, TA TI Development of antibodies to fetal calf serum with arthus-like reactions in human immunodeficiency virus-infected patients given syngeneic lymphocyte infusions SO BLOOD LA English DT Article ID BOVINE SERUM; ADOPTIVE IMMUNOTHERAPY; MARROW TRANSPLANTATION; HIV INFECTION; BONE-MARROW; CELLS; GENERATION; THERAPY; INVITRO; CANCER AB In an attempt to restore immune competence to 12 human immunodeficiency virus-1 (HIV-1)-infected patients, lymphocytes from their HIV-1-uninfected identical twin siblings were cultured in medium supplemented with 5% fetal calf serum (FCS), anti-CD3 antibody, and interleukin-2 (100 IU/mL for 10 days and then infused into the patients. After multiple infusions, at 6- to 8-week intervals, half of the patients developed arthus-like reactions within 4 to 12 hours of infusion consisting of fever >39 degrees C, hypotension, rigors, arthralgias, myalgias, headache, and/or malaise. Preinfusion and postinfusion serum samples were evaluated for the presence of antibodies to FCS using double immunodiffusion. All preinfusion serum samples were negative by this method while 8 of the 12 patients developed antibodies to a single component of FCS after two or more infusions of lymphocytes cultured in FCS-supplemented medium. Prick skin testing to standardized beef extract was negative in all patients. There was a correlation between initial CD4 level and the development of antibodies to FCS (median initial CD4 count in FCS antibody positive patients = 362.0/mu L v median initial CD4 count of nonresponders = 135.0/mu L). There was no correlation with response to recall antigens in delayed-type hypersensitivity testing. We conclude that selected patients were sensitized to a single component of FCS carried on donor lymphocytes, despite thorough washing of the cells before infusion. The development of antibodies to FCS indicates that immune complex formation could have occurred after the cell infusions, resulting in the arthus-like reactions. These observations suggest that the therapeutic use of human lymphocytes cultured in FCS may expose the recipient to immunogenic substances with possible clinical sequelae. C1 NIH,WARREN GRANT MAGNUSON CLIN CTR,SERV IMMUNOL,CLIN PATHOL,BETHESDA,MD 20892. NIAID,IMMUNOREGULAT LAB,NIH,BETHESDA,MD 20892. NR 20 TC 159 Z9 164 U1 0 U2 4 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD FEB 1 PY 1997 VL 89 IS 3 BP 776 EP 779 PG 4 WC Hematology SC Hematology GA WG073 UT WOS:A1997WG07300004 PM 9028307 ER PT J AU Barlogie, B Jagannath, S Vesole, DH Naucke, S Cheson, B Mattox, S Bracy, D Salmon, S Jacobson, J Crowley, J Tricot, G AF Barlogie, B Jagannath, S Vesole, DH Naucke, S Cheson, B Mattox, S Bracy, D Salmon, S Jacobson, J Crowley, J Tricot, G TI Superiority of tandem autologous transplantation over standard therapy for previously untreated multiple myeloma SO BLOOD LA English DT Article ID BONE-MARROW TRANSPLANTATION; SOUTHWEST-ONCOLOGY-GROUP; MAINTENANCE THERAPY; CELL LEUKEMIA; CHEMOTHERAPY; MELPHALAN; REMISSION AB Virtually no progress has been made during more than 2 decades of clinical trials for multiple myeloma (MM) involving standard therapy (ST). Recent studies suggest that dose intensification requiring hematopoietic stem cell support results in higher complete response (CR) rates and extended disease control. ''Total Therapy'' (TT) consisting of non-cross-resistant induction regimens, followed by a double autotransplant (AT) procedure, was administered to 123 untreated patients with symptomatic MM. Upon hematologic recovery, interferon (IFN) maintenance (3 million units [MU]/m(2) subcutaneously thrice weekly) was given until disease recurrence/progression. Results were compared with the outcome of untreated patients receiving ST according to Southwest Oncology Group (SWOG) trials. One hundred sixteen pair mates were selected from both TT and among 1,123 patients to match for the major prognostic features. TT induced CR in 40% of all 123 patients (intent-to-treat). By 12 months, 7% had died, including 4% from treatment-related complications. With a median follow-up of 31 months, median durations of event-free survival (EFS) and overall survival (OS) are 49 and 62+ months, respectively. Abnormalities of chromosomes 11q and 13 were associated with inferior outcome, whereas CR within 6 months after induction was a favorable prognostic feature for both EFS and OS. In comparison to ST, TT induced higher PR rates (85% v 52%, P < .0001) (CR rates not available on SWOG trials) and extended EFS (49 v 22 months, P = .0001) and OS (62+ v 48 months, P = .01). Compared to ST, dose intensification with double AT markedly augments tumor cytoreduction, effecting not only higher CR rates but also significantly extending EFS and OS in previously untreated patients with MM. (C) 1997 by The American Society of Hematology. C1 UNIV ARKANSAS MED SCI HOSP,ARKANSAS CANC RES CTR,LITTLE ROCK,AR 72205. NCI,BETHESDA,MD 20892. ARIZONA CANC CTR,TUCSON,AZ. FRED HUTCHINSON CANC RES CTR,SEATTLE,WA 98104. RP Barlogie, B (reprint author), UNIV ARKANSAS MED SCI HOSP,DIV HEMATOL ONCOL,LITTLE ROCK,AR 72205, USA. FU NCI NIH HHS [CA38926, CA55819, CA59340] NR 20 TC 424 Z9 434 U1 0 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD FEB 1 PY 1997 VL 89 IS 3 BP 789 EP 793 PG 5 WC Hematology SC Hematology GA WG073 UT WOS:A1997WG07300006 PM 9028309 ER PT J AU Selleri, C Sato, T DelVecchio, L Luciano, L Barrett, AJ Rotoli, B Young, NS Maciejewski, JP AF Selleri, C Sato, T DelVecchio, L Luciano, L Barrett, AJ Rotoli, B Young, NS Maciejewski, JP TI Involvement of Fas-mediated apoptosis in the inhibitory effects of interferon-alpha in chronic myelogenous leukemia SO BLOOD LA English DT Article ID CHRONIC MYELOID-LEUKEMIA; HEMATOPOIETIC PROGENITOR CELLS; NECROSIS-FACTOR-ALPHA; MARROW STROMAL CELLS; BCR-ABL; SURFACE ANTIGEN; HOST DISEASE; IN-VITRO; EXPRESSION; CYTOTOXICITY AB Interferon-alpha (IFN-alpha) is an established treatment for chronic myelogenous leukemia (CML) in chronic phase, but the mechanism of its antileukemic activity is not clear. One possible mechanism of action might include the induction of apoptosis, and especially Fas-mediated cell killing may play an important role in the elimination of malignant cells. We investigated Fas receptor (Fas-R) expression and the consequences of Fas-R triggering in CML patients. Using two-color flow cytometry, we found a significantly higher number of Fas-R-expressing CD34(+) cells in the bone marrow (BM) of CML patients compared with normal subjects. We have previously shown that IFN-gamma induces Fas-R expression on CD34(+) cells; in this study, we investigated whether IFN-alpha induces Fas-R expression on CML progenitor cells. Dose-dependent induction of Fas-R expression was observed after IFN-alpha stimulation of CD34(+) cells from CML BM. In methylcellulose culture, IFN-alpha alone at a therapeutic concentration showed only marginal antiproliferative effects on both normal and CML BM progenitors. In contrast, a Fas-R agonist, the anti-CD95 monoclonal antibody CH11. inhibited colony formation from normal progenitors, and the inhibition was even stronger on CML progenitors. When CML BM cells were cultured in the presence of IFN-alpha, Fas-R-mediated inhibition of colony growth was potentiated in a dose-dependent fashion, consistent with IFN-alpha induction of Fas-R expression. This functional effect did not require the presence of accessory cells, since similar results were obtained with purified CD34(+) cells. In suspension cultures, we demonstrated that suppression of CML hematopoiesis by IFN-alpha and Fas-R agonist was exerted through Fas-R-mediated induction of apoptosis. Our findings suggest that the Fas-R/Fas-ligand system might be involved in the immunologic regulation of CML progenitor growth and that its effect can be amplified by IFN-alpha. (C) 1997 by The American Society of Hematology. C1 UNIV NAPLES FEDERICO II,SCH MED,DIV HEMATOL,NAPLES,ITALY. CARDARELLI HOSP,SERV IMMUNOHEMATOL,NAPLES,ITALY. NHLBI,HEMATOL BRANCH,BETHESDA,MD 20892. NR 60 TC 123 Z9 128 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD FEB 1 PY 1997 VL 89 IS 3 BP 957 EP 964 PG 8 WC Hematology SC Hematology GA WG073 UT WOS:A1997WG07300024 PM 9028327 ER PT J AU Krenacs, L Wellmann, A Sorbara, L Himmelmann, AW Bagdi, E Jaffe, ES Raffeld, M AF Krenacs, L Wellmann, A Sorbara, L Himmelmann, AW Bagdi, E Jaffe, ES Raffeld, M TI Cytotoxic cell antigen expression in anaplastic large cell lymphomas of T- and null-cell type and Hodgkin's disease: Evidence for distinct cellular origin SO BLOOD LA English DT Article ID LARGE GRANULAR LYMPHOCYTES; POLYMERASE CHAIN-REACTION; PORE-FORMING PROTEIN; NATURAL-KILLER-CELL; KI-1 LYMPHOMA; TARGET-CELLS; MEDIATED CYTOTOXICITY; CYTOLYTIC LYMPHOCYTES; GENE REARRANGEMENTS; DNA FRAGMENTATION AB Anaplastic large cell lymphoma (ALCL) is composed of large, frequently bizarre, cells of T- or null-cell phenotype that show a preferential sinusoidal growth pattern and consistent CD30 positivity. Whether these tumors represent a single entity or several, and what the exact cell origin, is controversial. Recently, granzyme B, a cytotoxic granule component, was reported in a small percentage of ALCL, suggesting that some cases may originate from cytotoxic lymphocytes. To further investigate this possibility, we performed an immunohistochemical study of 33 ALCLs of T- and null-cell type, using monoclonal antibodies to cytotoxic cell-associated antigens, including CD8, CD56, CD57, and the cytotoxic granular proteins perforin and TIA-1. In addition, CD4 expression was also evaluated. ALCL cases included 27 classical systemic forms and variants, 3 primary cutaneous (PC) forms, and 3 acquired immunodeficiency syndrome-associated forms. Cytotoxic antigen expression was also studied in 51 cases of Hodgkin's disease (HD) and 17 large B-cell lymphomas (LBCLs) with anaplastic cytomorphology and/or CD30 positivity. We found that 76% of ALCLs, representing all subtypes except the PC forms, expressed either TIA-1, perforin, or both proteins. Expression of TIA-1 and perforin were highly correlated (P < .001). On the basis of their immunophenotypic profiles, several subtypes of cytotoxic antigen positive and negative ALCL could be recognized. Fifty-five percent of ALCLs (18 of 33) displayed an immunophenotypic profile consistent with cytotoxic T cells. Six cases expressed cytotoxic granular proteins in the absence of lineage specific markers, and one case expressed both T-cell- and natural killer cell-like markers. These 7 cases (21%) were placed into a phenotypic category of cytotoxic lymphocytes of unspecified subtype. Twenty-four percent (8 cases) of ALCLs were cytotoxic granule protein negative. All but one of these displayed a T-cell phenotype. Cytotoxic granule protein expression did not correlate with the presence of the NPM-ALK fusion transcript. Only 10% of the 51 HD cases were found to be TIA-1(+), and none expressed perforin. Cytotoxic antigen expression was absent in LBCL. The expression of cytotoxic granule proteins in the majority of ALCL implies a cytotoxic lymphocyte phenotype and suggests that most cases originate from lymphocytes with cytotoxic potential. Furthermore, the demonstration of cytotoxic cell related proteins may be a useful addition to the current panel of antibodies used to distinguish ALCL, HD, and anaplastic LBCL. This is a US government work. There are no restrictions on its use. C1 NCI,HEMATOPATHOL SECT,PATHOL LAB,NIH,BETHESDA,MD 20892. NIAID,IMMUNOREGULAT HUMAN LYMPHOCYTE FUNCT UNIT,IMMUNOREGULAT LAB,NIH,BETHESDA,MD 20892. ALBERT SZENT GYORGYI MED UNIV,DEPT PATHOL,H-6701 SZEGED,HUNGARY. RI Krenacs, Laszlo/L-8063-2014 OI Krenacs, Laszlo/0000-0001-6541-3031 NR 60 TC 137 Z9 141 U1 1 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD FEB 1 PY 1997 VL 89 IS 3 BP 980 EP 989 PG 10 WC Hematology SC Hematology GA WG073 UT WOS:A1997WG07300027 PM 9028330 ER PT J AU Gianni, M Terao, M Fortino, I LiCalzi, M Viggiano, V Barbui, T Rambaldi, A Garattini, E AF Gianni, M Terao, M Fortino, I LiCalzi, M Viggiano, V Barbui, T Rambaldi, A Garattini, E TI Stat1 is induced and activated by all-trans retinoic acid in acute promyelocytic leukemia cells SO BLOOD LA English DT Article ID LEUKOCYTE ALKALINE-PHOSPHATASE; INTERFERON REGULATORY FACTOR; COLONY-STIMULATING FACTOR; RECEPTOR-ALPHA GENE; TRANSCRIPTION FACTOR; DIFFERENTIATION THERAPY; FUNCTIONAL-ANALYSIS; GAMMA-INTERFERONS; NUCLEAR FACTORS; IFN-ALPHA AB Treatment of freshly isolated acute promyelocytic leukemia (APL) cells and the myelogenous leukemia cell lines, NB4, HL-60, and U937, with all-trans retinoic acid (ATRA) results in a remarkable elevation in the amounts of Stat1 alpha and Stat2 proteins. Stat1 alpha protein levels are augmented by ATRA as a consequence of elevated amounts of the corresponding transcripts. The retinoid increases the levels of nuclear complexes that are capable of binding to interferon (IFN)-regulated consensus sequences and contain Stat1 and/or Stat2 proteins, and causes a rapid and long-lasting elevation in Stat1 alpha tyrosine phosphorylation. Transient transfection experiments show that ATRA enhances the transactivating properties of Stat1 alpha observed on an appropriate reporter gene, in the presence of the RAR alpha retinoic acid receptor, but not in the presence of the PML-RAR protein. Treatment of NB4 cells with ATRA is associated with a remarkable upregulation of the two IFN-responsive genes IFN-responsive factor 1 and 2'-5' oligoadenylate synthetase, as well as with an augmentation in the levels of IFN alpha secretion. Our data show that ATRA is capable of modulating the amounts and the state of activation of some of the components of the IFN intracellular signaling pathways. They also suggest that the retinoid can bypass IFN/IFN-receptor interactions and induce the expression of IFN-regulated genes. (C) 1997 by The American Society of Hematology. C1 IST RIC FARMACOL MARIO NEGRI,MOL BIOL UNIT,CTR DANIELA & CATULLO BORGOMAAINERIO,I-20157 MILAN,ITALY. OSPED RIUNITI BERGAMO,DIV HEMATOL,I-24100 BERGAMO,ITALY. FREDERICK CANC RES & DEV CTR,EXPT IMMUNOL LAB,FREDERICK,MD. NR 41 TC 100 Z9 102 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD FEB 1 PY 1997 VL 89 IS 3 BP 1001 EP 1012 PG 12 WC Hematology SC Hematology GA WG073 UT WOS:A1997WG07300029 PM 9028332 ER PT J AU Bartley, AJ Jones, DW Weinberger, DR AF Bartley, AJ Jones, DW Weinberger, DR TI Genetic variability of human brain size and cortical gyral patterns SO BRAIN LA English DT Article DE genetics; twins; human brain size; cortical anatomy; gyral patterns ID MONOZYGOTIC TWINS; CEREBRAL-CORTEX; SCHIZOPHRENIA; GYRIFICATION; EVOLUTION; IMAGES AB The development of the primate brain is determined by an interaction of genetic programmes and environmental events. We examined quantitatively the contribution of each of these factors to adult human brain hemisphere volume and global cortical gyral patterns by comparing 3-0 MRI renderings of brains of 10 pairs of monozygotic (MZ) and nine pairs of same-sex dizygotic (DZ) twins. Brain volume was highly correlated in MZ pairs [unbiased intraclass correlation coefficient, ICC(U) = 0.95, P < 0.00001], but not in DZ pairs [ICC(U) = 0.35, P = 0.09]. Structural equation modelling indicated a 94% heritability of brain volume. Gyral patterns appeared visually more similar in MZ than in DZ pairs. This was confirmed statistically by a cross-correlation analysis of rendered images of lateral and mesial cortical surfaces. MZ twins exhibited significantly greater similarity than did DZ twins in comparisons of gyral patterns; DZ twins were not more alike than unrelated pairings. Ipsilateral hemispheres were significantly more alike than contralateral hemispheres within MZ pairs, but not within DZ pairs. Contralateral hemispheres within an individual were more alike than contralateral hemispheres between twins in the DZ pairs, but not in the MZ pairs. Heritability for gyral-sulcal patterns, as reflected in the cross-correlation data, was low and ill defined. These results indicate that human cerebral size is determined almost entirely by genetic factors and that overall cortical gyral patterns, though significantly affected by genes, are determined primarily by nongenetic factors. C1 NIMH, ST ELIZABETHS HOSP,CTR NEUROSCI, CLIN BRAIN DISORDERS BRANCH,INTRAMURA RES PROGRAM, WASHINGTON, DC 20032 USA. NR 53 TC 222 Z9 222 U1 1 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD FEB PY 1997 VL 120 BP 257 EP 269 DI 10.1093/brain/120.2.257 PN 2 PG 13 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA WN553 UT WOS:A1997WN55300004 PM 9117373 ER PT J AU Fedio, P August, A Patronas, N Sato, S Kufta, C AF Fedio, P August, A Patronas, N Sato, S Kufta, C TI Semantic, phonological, and perceptual changes following left and right intracarotid injection (Wada) with a low amytal dosage SO BRAIN AND COGNITION LA English DT Article ID RIGHT-HEMISPHERE; LEXICAL ACCESS; DUAL-ROUTE; MEMORY; RECOGNITION; IMPAIRMENT; COLOR AB Intracarotid injection of a low dosage of amobarbital (75 mg, 5% solution) was studied in 30 temporal lobectomy candidates while naming achromatic, incongruously, and congruously colored pictorial objects and reading real, nonsense, and embedded words. Semantic errors and phonological alexia followed the left injection, while the right injection induced visuoperceptual errors. When the contralateral hemisphere was anesthetized, the left brain formulated supraordinate categories for words and objects, while the right brain applied concrete labels. The basic language proficiency of patients influenced recovery and outcome; left temporal patients who were interictally anemic performed especially poorly after both injections. Codifying phonological and perceptual changes during the intracarotid amobarbital procedure can improve interpretations about language laterality and organization. (C) 1997 Academic Press. C1 NINCDS,DEPT NEURORADIOL,BETHESDA,MD 20892. NINCDS,DEPT ELECTROENCEPHALOG,BETHESDA,MD 20892. NINCDS,DEPT NEUROL SURG,BETHESDA,MD 20892. NIH,CTR CLIN,BETHESDA,MD 20892. RP Fedio, P (reprint author), NINCDS,DEPT NEUROPSYCHOL,NIH,BLDG 10,RM 5D-49,BETHESDA,MD 20892, USA. NR 49 TC 20 Z9 20 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0278-2626 J9 BRAIN COGNITION JI Brain Cogn. PD FEB PY 1997 VL 33 IS 1 BP 98 EP 117 DI 10.1006/brcg.1997.0886 PG 20 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA WM100 UT WOS:A1997WM10000009 PM 9056278 ER PT J AU Zhang, L Oz, M Stewart, RR Peoples, RW Weight, FF AF Zhang, L Oz, M Stewart, RR Peoples, RW Weight, FF TI Volatile general anaesthetic actions on recombinant nACh(alpha 7), 5-HT3 and chimeric nACh(alpha 7)-5-HT3 receptors expressed in Xenopus oocytes SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Article DE anaesthetics; receptors; ion channels; molecular chimera; acetylcholine receptor; 5-hydroxytryptamine receptor ID ANESTHETICS; BINDING AB The effect of halothane and isoflurane was studied on the function of recombinant neurotransmitter receptors expressed in Xenopus oocytes. Both anaesthetics inhibited nicotinic acetylcholine type alpha 7 (nACh(alpha 7)) receptor-mediated responses, potentiated 5-hydroxytryptamine type 3 (5-HT3) receptor-mediated responses at low agonist concentrations, and inhibited the function of a chimeric receptor (with the N-terminal domain from the nACh(alpha 7) receptor and the transmembrane and C-terminal domains from the 5-HT3 receptor) in a manner similar to that of the nACh(alpha 7) receptor. Since the N-terminal domain of the chimeric receptor was from the nAC(alpha 7) receptor, the observations suggest that the inhibition involves the N-terminal domain of the receptor. RP Zhang, L (reprint author), NIAAA,MOL & CELLULAR NEUROBIOL LAB,NIH,12501 WASHINGTON AVE,BETHESDA,MD 20892, USA. RI Oz, Murat/E-2148-2012 NR 10 TC 50 Z9 51 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0007-1188 J9 BRIT J PHARMACOL JI Br. J. Pharmacol. PD FEB PY 1997 VL 120 IS 3 BP 353 EP 355 DI 10.1038/sj.bjp.0700934 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA WE383 UT WOS:A1997WE38300001 PM 9031735 ER PT J AU Kurpad, SN Dolan, ME McLendon, RE Archer, GE Moschel, RC Pegg, AE Bigner, DD Friedman, HS AF Kurpad, SN Dolan, ME McLendon, RE Archer, GE Moschel, RC Pegg, AE Bigner, DD Friedman, HS TI Intraarterial O-6-benzylguanine enables the specific therapy of nitrosourea-resistant intracranial human glioma xenografts in athymic rats with 1,3-bis(2-chloroethyl)-1-nitrosourea SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE BCNU; chemotherapy; drug resistance; gliomas; O-6-benzylguanine ID HUMAN-TUMOR-CELLS; O-6-ALKYLGUANINE-DNA ALKYLTRANSFERASE ACTIVITY; BRAIN-TUMORS; PHASE-I; O6-METHYLGUANINE-DNA METHYLTRANSFERASE; CHLOROETHYLNITROSOUREA CYTOTOXICITY; ALKYLATING-AGENTS; O6-BENZYLGUANINE; SENSITIVITY; DNA AB The prognosis for patients with malignant gliomas continues to be dismal. The high degree of resistance of gliomas to nitrosourea-based chemotherapy is one major factor in poor treatment outcome. The identification of O-6-alkylguanine-DNA alkyltransferase (AGAT) as a major determinant of nitrosourea resistance has resulted in the development of several agents to inactivate this repair protein and counteract tumor cell resistance. However, a major problem in preclinical trials has been the marked nitrosourea dose limitations imposed by the prior administration of AGAT-depleting agents. We investigated the AGAT depletion and selective enhancement of BCNU activity of intraarterial (i.a.) O-6-benzylguanine (O(6)BG) in the human malignant glioma xenograft D-456 MG growing intracranially (i.c.) in athymic rats. Whereas i.a. O(6)BG at 2.5 mg/kg produced 100% inhibition of D-456 MG AGAT i.c. activity 8 h after administration, intraperitoneal (i.p.) O(6)BG at this dose produced only 40% inhibition, requiring-dose escalation to 10 mg/kg to produce 100% AGAT depletion. Prior administration of i.p. O(6)BG (10 mg/kg) and i.a. O(6)BG (2.5 mg/kg) limited maximum tolerated intravenous (i.v.) BCNU doses (37.5 mg/kg when given alone) to 6.25 and 25 mg/kg, respectively. Higher doses of BCNU alone or in combination with O(6)BG produced histopathologic evidence of cerebral and hepatic toxicity. Therapy experiments revealed a significantly improved median survival for rats treated with O(6)BG i.a. (2.5 mg/kg) plus BCNU i.v. (25 mg/kg, days 61 and 59 in duplicate experiments) compared with saline (day 21, P = 0.001), O(6)BG i.a. or i.p. (days 22 and 23, P = 0.001), BCNU i.v. (37.5 mg/kg, day 29, P = 0.001), and O(6)BG i.p. (10 mg/kg) plus BCNU i.v. (6.25 mg/kg, day 37, P < 0.001). Therefore, O(6)BG i.a., by virtue of rapid AGAT depletion and selective uptake into i.c. tumors, offers significant potential for regional chemomodulation of AGAT-mediated nitrosourea resistance in malignant human gliomas with concomitant reduction of systemic toxicity. C1 DUKE UNIV,MED CTR,DEPT PATHOL,DURHAM,NC 27710. CASE WESTERN RESERVE UNIV,DEPT NEUROL SURG,CLEVELAND,OH 44106. UNIV CHICAGO,HEMATOL ONCOL SECT,CHICAGO,IL 60637. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. PENN STATE UNIV,MILTON S HERSHEY MED CTR,DEPT CELLULAR & MOL PHYSIOL,HERSHEY,PA 17033. DUKE UNIV,MED CTR,PREUSS LAB BRAIN TUMOR RES,DURHAM,NC 27710. DUKE UNIV,MED CTR,DEPT PEDIAT,DURHAM,NC 27710. FU NCI NIH HHS [CA 11898]; NINDS NIH HHS [NS 20023, NS 30245] NR 49 TC 24 Z9 24 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD FEB PY 1997 VL 39 IS 4 BP 307 EP 316 DI 10.1007/s002800050577 PG 10 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA WE056 UT WOS:A1997WE05600005 PM 9025771 ER PT J AU Sun, EC Fears, TR Goedert, JJ AF Sun, EC Fears, TR Goedert, JJ TI Epidemiology of squamous cell conjunctival cancer SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID HUMAN PAPILLOMAVIRUS DNA; POLYMERASE CHAIN-REACTION; CERVICAL-CANCER; SKIN-CANCER; CARCINOMA; INFECTION; RISK; SUNLIGHT; MELANOMA; TYPE-16 AB The etiology of squamous cell carcinoma of the conjunctiva (SCCC) is not well known, A possible role of UVB radiation is suggested by an excess of SCCC in tropical countries and by the association between squamous cell skin cancer and exposure to UVB, Human papillomavirus type 16 also may be involved, given that it has been detected in benign and malignant conjunctival lesions and is the primary etiological agent involved in carcinoma of the anogenital tract. To examine the relationship between UVB exposure and SCCC, population-based age-adjusted incidence rates of SCCC and of conjunctival melanoma and squamous cell cancer of the eyelid were plotted against the WE insolation of each registry site. Incidence data were examined further for patterns of second primary cancers among people with SCCC, SCCC was rare in the United States, with an incidence rate of 0.03 per 100,000 persons, although the rate was approximately 5-fold higher among males and whites, Regression analysis suggested a link between UVB exposure and SCCC rates (beta = 2.25; r = 0.58) that was as strong as that for squamous cell carcinoma of the eyelid (beta = 2.73; r = 0.62) and much stronger than for conjunctival melanoma (beta = 0.28; r = 0.02). Risk of a second malignancy after SCCC was not increased overall (20 observed and 14.1 expected), although a significant excess of salivary gland cancer (4 observed and 0.03 expected) and a borderline excess of lung cancer (6 observed and 2.4 expected) were noted, These observations suggest that UV radiation likely contributes to SCCC development. Additional research is needed to define the other exposures and host susceptibility that likely interact with UV-related genetic damage in the multifactorial development of this rare neoplasm. C1 NCI,DIV CANC EPIDEMIOL & GENET,ROCKVILLE,MD 20852. NR 37 TC 64 Z9 69 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD FEB PY 1997 VL 6 IS 2 BP 73 EP 77 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA WG445 UT WOS:A1997WG44500001 PM 9037556 ER PT J AU Dawsey, SM Shen, Q Nieberg, RK Liu, SF English, SA Cao, J Zhou, B Wang, GQ Lewin, KJ Liu, FS Roth, MJ Taylor, PR AF Dawsey, SM Shen, Q Nieberg, RK Liu, SF English, SA Cao, J Zhou, B Wang, GQ Lewin, KJ Liu, FS Roth, MJ Taylor, PR TI Studies of esophageal balloon cytology in Linxian, China SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID VITAMIN MINERAL SUPPLEMENTATION; NUTRITION INTERVENTION TRIALS; DISEASE-SPECIFIC MORTALITY; SQUAMOUS-CELL CARCINOMA; SUBSEQUENT RISK; GENERAL-POPULATION; CANCER INCIDENCE; BRUSH CYTOLOGY; DYSPLASIA AB Esophageal cancer is the second leading cause of cancer death in China. Esophageal cancer has a very poor prognosis, principally because most tumors are asymptomatic until they are unresectable. Esophageal balloon cytology is an early detection method developed by Chinese scientists to identify resectable early cancers and precursor lesions, Previous studies have reported high sensitivities for detecting esophageal cancer in symptomatic patients, The current report describes several studies evaluating this diagnostic technique in asymptomatic individuals, A comparison of Chinese and U.S. cytological diagnoses of the same esophageal samples showed that the Chinese categories of precancerous neoplasia were more inclusive than the corresponding U.S. categories, Comparisons of both Chinese and U.S. cytological diagnoses with concurrent histological findings showed low (14-36%) sensitivities for the cytological detection of biopsy-proven cancers. Prospective follow-up studies of several screened cohorts showed a consistent progression of risk for developing esophageal cancer with increasing severity of initial cytological diagnosis, These preliminary studies suggest that esophageal balloon cytology is a useful technique that can benefit from additional research to improve its optimal performance. C1 HENAN MED UNIV,ZHENGZHOU,PEOPLES R CHINA. UNIV CALIF LOS ANGELES,LOS ANGELES,CA 90024. CHINESE ACAD MED SCI,INST CANC,BEIJING 100021,PEOPLES R CHINA. RP Dawsey, SM (reprint author), NCI,CANC PREVENT STUDIES BRANCH,EXECUT PLAZA N,ROOM 211,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 39 TC 25 Z9 26 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD FEB PY 1997 VL 6 IS 2 BP 121 EP 130 PG 10 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA WG445 UT WOS:A1997WG44500008 PM 9037563 ER PT J AU Hukku, B Thraves, P Dritschilo, A Rhim, JS AF Hukku, B Thraves, P Dritschilo, A Rhim, JS TI Chromosomal changes observed in immortalized human keratinocytes transformed by ionizing radiation SO CANCER GENETICS AND CYTOGENETICS LA English DT Article ID SQUAMOUS-CELL CARCINOMA; HUMAN EPIDERMAL-KERATINOCYTES; HUMAN-DIPLOID CELLS; NEOPLASTIC TRANSFORMATION; GENE; ABNORMALITIES; IDENTIFICATION; REGION; LINES; HEAD AB Human epithelial cancer cells were induced by concerted action of DNA tumor virus and X-ray radiation. Treatment of nontumorigenic early passage AD12-SV40 immortalized epithelial cells (RHEK-1) at passage 23 with radiation, resulted in further changes in their growth properties. One day old cultures of these RHEK-1 cells were irradiated with graded doses of X-rays (0, 2, 4, 6, and 8 Gy i.e. RHEK-1, RHEK-1/200R, RHEK-1/400R, RHEK-1/600R, and RHEK-1/800R). Morphologic alterations, the ability to grow in soft agar, and to form rapidly-growing squamous cell carcinomas in nude mice were concomitantly acquired properties of the radiation transformed cell lines RHEK-1/200R and RHEK-1/400R. On the basis of commonality in having addition of some extra material in chromosome 11 in the region between q14/q22 in all tumorigenic cell lines RHEK-1/200R and RHEK-1/400R, and deletion of the same region in nontumorigenic irradiated cell lines-RHEK-1/600R and RHEK-1/800R, it is deduced this region may have some important oncogene/s or other gene/s that play an important role in tumorigenesis. When compared to squamous cell carcinoma data, the duplication observed in the present study is also observed in 28 to 38% of head and neck and also in 25% of cases of untreated malignant lesions of oral squamous cell carcinoma. Thus, this study shows the correlation between in vitro induced squamous cell carcinoma to in vivo tumors. (C) Elsevier Science Inc., 1997. C1 WAYNE STATE UNIV,SCH MED,DETROIT,MI 48201. GEORGETOWN UNIV,SCH MED,DEPT RADIAT MED,VINCENT T LOMBARDI CANC RES CTR,WASHINGTON,DC. NCI,MOL ONCOL LAB,FREDERICK,MD. RP Hukku, B (reprint author), CHILDRENS HOSP MICHIGAN,DEPT PEDIAT,CELL CULTURE LAB,3901 BEAUBIEN BLVD,DETROIT,MI 48201, USA. FU NCI NIH HHS [CA52954, N0I-CP33063, CA52945] NR 60 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0165-4608 J9 CANCER GENET CYTOGEN JI Cancer Genet. Cytogenet. PD FEB PY 1997 VL 93 IS 2 BP 125 EP 139 DI 10.1016/S0165-4608(96)00210-5 PG 15 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA WN739 UT WOS:A1997WN73900004 PM 9078297 ER PT J AU Peters, KF Hadley, DW AF Peters, KF Hadley, DW TI The human genome project SO CANCER NURSING LA English DT Article ID GENE; BREAST RP Peters, KF (reprint author), JOHNS HOPKINS UNIV,NIH,NATL CTR HUMAN GENOME RES,MED GENET BRANCH,GENET COUNSELING GRAD PROGRAM,BETHESDA,MD, USA. NR 9 TC 5 Z9 5 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0162-220X J9 CANCER NURS JI Cancer Nurs. PD FEB PY 1997 VL 20 IS 1 BP 62 EP 75 DI 10.1097/00002820-199702000-00008 PG 14 WC Oncology; Nursing SC Oncology; Nursing GA WG326 UT WOS:A1997WG32600008 PM 9033151 ER PT J AU Agarwal, R Coffing, SL Baird, WM Kiselyov, AS Harvey, RG Dipple, A AF Agarwal, R Coffing, SL Baird, WM Kiselyov, AS Harvey, RG Dipple, A TI Metabolic activation of benzo[g]chrysene in the human mammary carcinoma cell line MCF-7 SO CANCER RESEARCH LA English DT Article ID REGION DIOL-EPOXIDES; POLYCYCLIC AROMATIC-HYDROCARBONS; FEMALE CD RATS; FJORD-REGION; DNA-ADDUCTS; 11,12-DIHYDRODIOL 13,14-EPOXIDE; DIHYDRODIOL EPOXIDE; MAMMALIAN-CELLS; MOUSE EPIDERMIS; BENZOPHENANTHRENE AB Benzo[g]chrysene (BgC) is an environmental pollutant, and recent studies have demonstrated that anti-BgC-11,12-dihydrodiol 13,14-epoxide (anti-BgCDE) is a potent mammary carcinogen in rats. To determine whether BgC can be metabolically activated to anti-BgCDE in human cells, the human mammary carcinoma cell line MCF-7 was treated with BgC and with the racemic trans-3,4- and 11,12 dihydrodiols. The DNA adducts formed in these experiments were examined using P-32-postlabeling, and specific adducts were identified through comparisons with adducts obtained by the reaction of the racemic syn- and anti-BgCDEs with calf thymus DNA and with purine deoxyribonucleoside-3'-phosphates in vitro. It was found that BgC is metabolically activated in MCF-7 cells to form major DNA adducts through both the syn- and anti-11,12-dihydrodiol 13,14-epoxide metabolites. BgC is therefore a potential environmental risk to humans. The major BgC-DNA adducts formed from both the dihydrodiol-epoxide diastereomers were deoxyadenosine adducts. Thus, BgC has DNA-binding properties that are very similar to those of the potent mammary carcinogens 7,12-dimethylbenz[a]anthracene and dibenzo[a,l]pyrene. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. PURDUE UNIV,CTR CANC,W LAFAYETTE,IN 47907. BEN MAY INST,CHICAGO,IL 60637. NR 41 TC 27 Z9 29 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD FEB 1 PY 1997 VL 57 IS 3 BP 415 EP 419 PG 5 WC Oncology SC Oncology GA WF517 UT WOS:A1997WF51700016 PM 9012467 ER PT J AU Reddy, BS Wang, CX Samaha, H Lubet, R Steele, VE Kelloff, GJ Rao, CV AF Reddy, BS Wang, CX Samaha, H Lubet, R Steele, VE Kelloff, GJ Rao, CV TI Chemoprevention of colon carcinogenesis by dietary perillyl alcohol SO CANCER RESEARCH LA English DT Article ID CELL-DEATH; COLORECTAL-CANCER; D-LIMONENE; BILE-SALT; APOPTOSIS; INDUCTION; TUMOR; INHIBITION; DIFFERENTIATION; DEOXYCHOLATE AB Epidemiological studies suggest that consumption of diets containing fruits and vegetables, major sources of phytochemicals and micronutrients, may reduce the risk of developing cancer of the colon, Several phytochemicals and micronutrients present in fruits and vegetables are known to exert cancer-chemopreventive effects in several organs, including the colon, Monoterpenes such as d-limonene and perillyl alcohol derived from orange peels and lavender, respectively, have been shown to possess chemopreventive properties against mammary, liver, and/or lung carcinogenesis, The present study was designed to investigate the efficacy of dietary 40 and 80% maximum tolerated dose (MTD) levels of perillyl alcohol on azoxymethane (AOM)-induced colon carcinogenesis, The effect of this agent on the process of apoptosis in colon tumors was also investigated, Prior to the efficacy study, the MTD of perillyl alcohol was determined in male F344 rats in a 6-week subchronic toxicity study and found to be a 2.5-g/kg diet when added to the AIN-76A diet. At 5 weeks of age, groups of male F344 rats were fed control (AIN-76A) diet or diets containing 1 and 2 g perillyl alcohol/kg diet, representing 40 and 80% MTD levels, respectively, At 7 weeks of age, all animals except those in the vehicle-treated groups were given two weekly s.c. injections of AOM (15 mg/kg body weight/week), All animals were continued on their respective dietary regimen for 52 weeks after AOM treatment and then sacrificed. Colon tumors were evaluated histopathologically using routine procedures, Perillyl alcohol at the 1-g/kg level significantly inhibited the incidence (percentage of animals with tumors) and multiplicity (tumors/animals) of invasive adenocarcinomas of the colon, whereas perillyl alcohol at 2 g/kg diet inhibited the incidence of total adenocarcinomas of the colon and small intestine as compared to the control diet. Our studies also indicate that the colon tumors of animals fed perillyl alcohol exhibited increased apoptosis as compared to those fed the control diet, These results demonstrate the potential chemopreventive activity of perillyl alcohol against colon carcinogenesis, The chemopreventive activity of perillyl alcohol is mediated through the tumor cell loss by apoptosis. C1 AMER HLTH FDN, DIV PATHOL & TOXICOL, VALHALLA, NY 10595 USA. NCI, CHEMOPREVENT BRANCH, DIV CANC CONTROL & PREVENT, BETHESDA, MD 20892 USA. RP AMER HLTH FDN, DIV NUTR CARCINOGENESIS, 1 DANA RD, VALHALLA, NY 10595 USA. RI Chinthalapally, Rao/B-3633-2010 FU NCI NIH HHS [N01CN-25450-01, CA17613] NR 38 TC 121 Z9 124 U1 0 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD FEB 1 PY 1997 VL 57 IS 3 BP 420 EP 425 PG 6 WC Oncology SC Oncology GA WF517 UT WOS:A1997WF51700017 PM 9012468 ER PT J AU Greenblatt, MS Feitelson, MA Zhu, M Bennett, WP Welsh, JA Jones, R Borkowski, A Harris, CC AF Greenblatt, MS Feitelson, MA Zhu, M Bennett, WP Welsh, JA Jones, R Borkowski, A Harris, CC TI Integrity of p53 in hepatitis B X antigen-positive and -negative hepatocellular carcinomas SO CANCER RESEARCH LA English DT Article ID TUMOR-SUPPRESSOR GENE; VIRUS-DNA INTEGRATION; HEPATOMA-CELL LINE; LIVER-CANCER; HBX GENE; TRANSCRIPTIONAL ACTIVITY; CARRIER PATIENTS; TRANSGENIC MICE; SURFACE-ANTIGEN; PROTEIN AB Inactivation of the tumor suppressor p53 seems to be important to the pathogenesis of hepatocellular carcinoma (HCC) associated with chronic hepatitis B virus infection, Although this inactivation may be due to mutations in the p53 gene, recent evidence suggests that the hepatitis B virus-encoded X antigen (HBxAg) binds to and inactivates wild-type p53, Hence, experiments were designed to test the hypothesis that there is a low frequency of p53 mutations in HBxAg-positive HCC, HBxAg and p53 were assayed by immunohistochemistry (IHC) in HCC and nontumor liver from 16 Chinese patients, half of whom were hepatitis B surface antigen carriers, HBxAg was detectable in tumor and/or nontumor cells from all patients by IHC; six of these samples also had detectable p53, To determine whether p53 detection by MC, and hence stabilization, is associated with mutation, sequencing of p53 exons 5-8 was performed with each patient sample, Wild-type sequences were found in 13 of 16 KBxAg-positive cases (81%), Hence, HBxAg is a common marker of HCC that correlates with the persistence of wild-type p53 among both carriers and noncarriers, The low frequency of p53 mutations in HCC in these patients implies that p53 inactivation may occur predominantly by complex formation with HBxAg. C1 NCI,NIH,HUMAN CARCINOGENESIS LAB,BETHESDA,MD 20892. UNIV MARYLAND,DEPT PATHOL,BALTIMORE,MD 21201. THOMAS JEFFERSON UNIV,DEPT PATHOL ANAT & CELL BIOL,PHILADELPHIA,PA 19107. FOURTH MIL MED UNIV,DEPT PATHOL,XIAN 710032,PEOPLES R CHINA. FU NCI NIH HHS [CA 48656, CA 66971] NR 66 TC 47 Z9 50 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD FEB 1 PY 1997 VL 57 IS 3 BP 426 EP 432 PG 7 WC Oncology SC Oncology GA WF517 UT WOS:A1997WF51700018 PM 9012469 ER PT J AU Preston, GA Barrett, JC Biermann, JA Murphy, E AF Preston, GA Barrett, JC Biermann, JA Murphy, E TI Effects of alterations in calcium homeostasis on apoptosis during neoplastic progression SO CANCER RESEARCH LA English DT Article ID ANCHORAGE-INDEPENDENT GROWTH; TUMOR-SUPPRESSOR GENE; HAMSTER EMBRYO CELLS; HUMAN HEPATOMA-CELLS; INTRACELLULAR CALCIUM; DNA FRAGMENTATION; PHOSPHATASE INHIBITORS; CA2+-ATPASE INHIBITOR; HUMAN-NEUTROPHILS; STORE DEPLETION AB Our previous studies showed that early, stage I preneoplastic cells (sup(+)I) are highly susceptible to apoptosis, whereas the later, stage II preneoplastic cells (sup(-)II) are relatively resistant. To examine possible mechanisms that might explain these differences in the regulation of apoptosis, Ca2+ homeostasis was analyzed and comparisons were made between these two Syrian hamster embryo cell lines, The Ca2+ indicator, fura-2, and fluorescent microscopy were used to measure intracellular free calcium concentrations, [Ca2+](i), The results indicated that the [Ca2+](i) level in logarithmically growing sup(+)I cells (similar to 100 nM) was considerably lower than that observed in sup(-)II cells (similar to 260 nM), Serum removal resulted in a reduction of [Ca2+](i) in the sup(+)I cells (similar to 82 nM), whereas the [Ca2+](i) level in sup(-)II cells did not change, Endoplasmic reticulum (ER) calcium levels were determined by measuring thapsigargin-releasable Ca2+. Reduced ER calcium was consistently observed in cells induced to undergo apoptosis, Specifically, thapsigargin-releasable Ca2+ was greatly reduced in sup(+)I cells (45 nM) as compared to sup(-)II cells (190 nM) after 4 h in low serum, When sup(-)II cells were placed under conditions that resulted in apoptosis (thapsigargin or okadaic acid), decreased ER calcium was observed, To determine whether reduced ER calcium had a causative effect in apoptosis, ER calcium levels were exogenously increased in sup(+)I cells by raising extracellular Ca2+ to 3 mM; ER calcium levels were maintained, and apoptosis was blocked, Studies were performed to determined whether the decrease in ER calcium could be attributed to reduced Ca2+ influx at the plasma membrane, To measure directly whether Ca2+ entry was decreased in sup(+)I cells in 0.2% serum, Mn2+ uptake was used to monitor Ca2+ influx, The data show that in low serum, the rate of thapsigargin-induced Mn2+ entry in sup(+)I cells was approximately 50% lower than that of sup(-)II cells, demonstrating that capacitative entry is reduced in sup(+)I cells, In further support of this hypothesis, thapsigargin-treated sup(+)I cells (0.2% serum) showed decreased Ca2+ entry upon raising extracellular Ca2+ from 0 to 2 mM. We report the novel finding that early preneoplastic cells, which exhibit a high propensity to undergo apoptosis, have decreased calcium entry at the plasma membrane, resulting in decreased ER calcium pools, This study provides new insight into mechanisms that can be involved in the regulation/dysregulation of apoptosis during neoplastic progression, Furthermore, the data imply that preneoplastic cells, which have developed a mechanism to maintain ER calcium, would be less susceptible to apoptosis and would thus have an increased potential for becoming transformed. C1 NIEHS,LAB MOL BIOPHYS,NIH,RES TRIANGLE PK,NC 27709. RP Preston, GA (reprint author), NIEHS,MOL CARCINOGENESIS LAB,NIH,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 47 TC 49 Z9 49 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD FEB 1 PY 1997 VL 57 IS 3 BP 537 EP 542 PG 6 WC Oncology SC Oncology GA WF517 UT WOS:A1997WF51700036 PM 9012487 ER PT J AU Kasprzak, KS Jaruga, P Zastawny, TH North, SL Riggs, CW Olinski, R Dizdaroglu, M AF Kasprzak, KS Jaruga, P Zastawny, TH North, SL Riggs, CW Olinski, R Dizdaroglu, M TI Oxidative DNA base damage and its repair in kidneys and livers of nickel(II)-treated male F344 rats SO CARCINOGENESIS LA English DT Article ID ESCHERICHIA-COLI; GAS-CHROMATOGRAPHY; LIPID-PEROXIDATION; IONIZING-RADIATION; MASS-SPECTROMETRY; CHROMATIN; NICKEL; SITE; CARCINOGENESIS; MUTAGENESIS AB DNA base damage was assayed using gas chromatography/ mass spectrometry with selected ion monitoring (GC/MS-SIM) in renal and hepatic chromatin of male F344 rats up to 14 days after a single i.p. injection of 90 mu mol Ni(II) acetate/kg body wt. Ten different damaged bases were quantified, No damage was found in either organ 12 h after Ni(II) treatment. The damage became significant only from day 1, with magnitude and persistence depending on the organ and base, In livers, levels of five DNA base products were significantly elevated over those in control rats, They were: 8-oxoguanine (by 46% at day 1 postinjection); 2,6-diamino-4-hydroxy-5-formamidopyrimidine (by 107% at day 1); 5-(hydroxymethyl)uracil (by 94% at day 1); 5,6-dihydroxyuracil (by 128% at day 1); and 5-hydroxyhydantoin (by 39% in terms of the overall adjusted means for days 1-14 post-injection). The elevation was highest at day 1 post-injection followed by a decrease at later days, except for 5-hydroxyhydantoin. In kidneys, the levels of only three damaged bases, 8-oxoguanine, 5-hydroxyhydantoin and 5,6-dihydroxyuracil were increased significantly (by 31, 73 and 60%, respectively) and one base, 8-oxoadenine, was increased by 26%, just below significance, all in terms of overall adjusted means for days 1-14 post-injection. Hence, unlike those in the liver, the renal increases persisted for 14 days, The results reveal a tissue specific response to Ni(II)-mediated oxidative DNA base damage with apparently faster DNA repair in liver than in kidney, the main target of NL(II) carcinogenicity. C1 NATL INST STAND & TECHNOL,CHEM SCI & TECHNOL LAB,GAITHERSBURG,MD 20899. DATA MANAGEMENT SERV INC,FCRDC,FREDERICK,MD 21702. L RYDYGIER MED SCH,DEPT CLIN BIOCHEM,BYDGOSZCZ,POLAND. RP Kasprzak, KS (reprint author), NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21702, USA. RI Olinski, Ryszard/E-9607-2014; Jaruga, Pawel/M-4378-2015 NR 34 TC 55 Z9 55 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD FEB PY 1997 VL 18 IS 2 BP 271 EP 277 DI 10.1093/carcin/18.2.271 PG 7 WC Oncology SC Oncology GA WK667 UT WOS:A1997WK66700006 PM 9054618 ER PT J AU Hemminki, K Dickey, C Karlsson, S Bell, D Hsu, YZ Tsai, WY Mooney, LA Savela, K Perera, FP AF Hemminki, K Dickey, C Karlsson, S Bell, D Hsu, YZ Tsai, WY Mooney, LA Savela, K Perera, FP TI Aromatic DNA adducts in foundry workers in relation to exposure, life style and CYP1A1 and glutathione transferase M1 genotype SO CARCINOGENESIS LA English DT Article ID WHITE BLOOD-CELLS; DEOXYRIBONUCLEIC-ACID; GENETIC-POLYMORPHISM; CANCER RISK; HYDROCARBONS; 1-HYDROXYPYRENE; LUNG; SUSCEPTIBILITY; HPRT; BUS AB Levels of aromatic DNA adducts in foundry workers and controls were followed at four annual samplings. During this time exposure to polycyclic aromatic hydrocarbons (PAH) decreased and the level of DNA adducts decreased accordingly, In the total group exposure was related to the level of adducts, Adduct levels correlated with urinary 1-hydroxypyrene (LOGU1OH), air benzo[alpha]pyrene, weekly working hours and daily cigarette consumption, In a multivariate model 1-hydroxypyrene had a consistent effect, Neither glutathione transferase M1 (GSTM1) nor cytochrome P450 1A1 (CYP1A1) genotypes had clear effects, Yet the individuals lacking GSTM1 had a stronger effect of LOGU1OH and some effect by other sources of PAH, such as charcoal broiled food, although all these variables were not significant in the multivariate model, The rare individuals with a CYP1A1 polymorphism MspI containing an amino acid change at isoleucine had an increased level of adducts, The results showed that the postlabelling method used was able to detect an increase in aromatic DNA adducts in leukocytes when exposure to benzo[alpha]pyrene in air was similar to 5 ng/m(3), At such low levels smoking and charcoal broiled food may be important contributors to adducts. C1 COLUMBIA UNIV,DIV ENVIRONM SCI,NEW YORK,NY 10032. NIEHS,RES TRIANGLE PK,NC 27709. INST OCCUPAT HLTH,SF-00250 HELSINKI,FINLAND. RP Hemminki, K (reprint author), KAROLINSKA INST,NOVUM,DEPT BIOSCI,S-14157 HUDDINGE,SWEDEN. OI Mooney, LaVerne A./0000-0003-1120-356X FU PHS HHS [1-PO1-E505249] NR 31 TC 68 Z9 70 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD FEB PY 1997 VL 18 IS 2 BP 345 EP 350 DI 10.1093/carcin/18.2.345 PG 6 WC Oncology SC Oncology GA WK667 UT WOS:A1997WK66700015 PM 9054627 ER PT J AU Tarasova, NI Wank, SA Hudson, EA Romanov, VI Czerwinski, G Resau, JH Michejda, CJ AF Tarasova, NI Wank, SA Hudson, EA Romanov, VI Czerwinski, G Resau, JH Michejda, CJ TI Endocytosis of gastrin in cancer cells expressing gastrin/CCK-B receptor SO CELL AND TISSUE RESEARCH LA English DT Article DE cholecystokinin receptor; fluorescent microscopy; confocal microscopy; gastrointestinal hormones; gastrin; drug delivery; cancer cells ID HUMAN-COLON-CANCER; CHOLECYSTOKININ RECEPTOR; CCK-B; GROWTH; INTERNALIZATION; PEPTIDE; STIMULATION; PROGLUMIDE; CARCINOMA; PATHWAYS AB Endocytosis of gastrin was studied in a number of gastrin-receptor-expressing cell lines by confocal laser scanning microscopy (CLSM) with the aid of a biologically active fluorescent derivative, rhodamine green heptagastrin. Rapid clustering (within 4-7 min) and internalization of fluorescent ligand upon binding at room temperature and 37 degrees C were observed in the rat pancreatic acinar carcinoma cell line AR42J, human gastric carcinomas AGS-P and SIIA, human colon carcinomas HCT116 and HT29, and in NIH/3T3 cells transfected with human and rat gastrin/cholecystokinin-B receptor cDNA. Internalization was inhibited by hypertonic medium. Fluorescent heptagastrin and transferrin colocalized in the same endocytic vesicles at different stages of internalization suggesting that endocytosis occurred predominantly through a clathrin-dependent mechanism. At 37 degrees C partial colocalization with the lysosomal marker neutral red was detected by CLSM, implying that internalized gastrin accumulated in the lysosomes, Immunoelectron microscopy studies with antibodies against gastrin revealed the presence of the internalized hormone in multivesicular vesicles and endosomes. Almost no hormone was detected in lysosomes with the antibodies to gastrin, suggesting that the degradation of the peptide is rapid in those vesicles, Continuous accumulation of fluorescent label was observed by CLSM in the presence of the protein synthesis inhibitor cycloheximide, suggesting that the gastrin receptor is recycled back to the cell membrane after hormone delivery to intracellular compartments, An estimated average recycling time for the receptor molecules was I h in NIH/3T3 cells. C1 NIDDKD,DIGEST DIS BRANCH,NIH,BETHESDA,MD 20892. NCI,MATH BIOL LAB,MEMBRANE STRUCT SECT,BETHESDA,MD 20892. RP Tarasova, NI (reprint author), NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MOL ASPECTS DRUG DESIGN SECT,POB B,FREDERICK,MD 21702, USA. NR 32 TC 31 Z9 32 U1 0 U2 5 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0302-766X J9 CELL TISSUE RES JI Cell Tissue Res. PD FEB PY 1997 VL 287 IS 2 BP 325 EP 333 DI 10.1007/s004410050757 PG 9 WC Cell Biology SC Cell Biology GA WG167 UT WOS:A1997WG16700009 PM 8995203 ER PT J AU Ligeti, L Mayevsky, A Ruttner, Z Kovach, AGB McLaughlin, AC AF Ligeti, L Mayevsky, A Ruttner, Z Kovach, AGB McLaughlin, AC TI Can the indo-1 fluorescence approach measure brain intracellular calcium in vivo? A multiparametric study of cerebrocortical anoxia and ischemia SO CELL CALCIUM LA English DT Article ID CYTOSOLIC FREE CALCIUM; NADH REDOX STATE; SPREADING DEPRESSION; CEREBRAL-ISCHEMIA; CAT CORTEX; INVIVO MEASUREMENT; REPERFUSION; DAMAGE; RATS; HOMEOSTASIS AB Indo-1 fluorescence was used to monitor intracellular calcium levels in the cat brain in vivo, using the approach proposed by Uematsu et al. [Uematsu D., Greenberg J.H., Reivich M., Karp A. In vivo measurement of cytosolic free calcium during cerebral ischemia and reperfusion. Ann Neurol 1988; 24: 420-428]. In addition, extracellular calcium and potassium levels, NADH redox state, electrocorticogram (ECoG), DC potential and relative cerebral blood flow were monitored simultaneously. Changes in the Indo-1 fluorescence ratio F-400/F-506 were monitored during anoxia, reversible ischemia and irreversible ischemia. Although these perturbations resulted in the expected changes in extracellular calcium and potassium levels, NADH redox state, ECoG and other physiological parameters, they did not result in significant increases in the F-400/F-506 ratio. The apparent insensitivity of the in vivo Indo-1 approach is due to the difficulty in obtaining accurate fluorescence signals from Indo-1 in the brain. Two reasons for this difficulty appear to be problems in loading Indo-1 into the brain, and problems in correcting Indo-1 fluorescence signals for changes in NADH fluorescence and changes in absorption of intrinsic chromophores. Under the conditions of our in vivo cat experiments, Indo-1 fluorescence is not a viable approach for measuring changes in cerebral intracellular calcium levels. C1 NIMH,NIH,BETHESDA,MD 20892. NIAAA,NIH,ROCKVILLE,MD 20852. SEMMELWEIS UNIV MED,DEPT PHYSIOL 2,H-1085 BUDAPEST,HUNGARY. BAR ILAN UNIV,DEPT LIFE SCI,RAMAT GAN,ISRAEL. UNIV PENN,CEREBROVASC RES CTR,PHILADELPHIA,PA 19104. NR 39 TC 3 Z9 3 U1 0 U2 1 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0143-4160 J9 CELL CALCIUM JI Cell Calcium PD FEB PY 1997 VL 21 IS 2 BP 115 EP 124 DI 10.1016/S0143-4160(97)90035-X PG 10 WC Cell Biology SC Cell Biology GA WL182 UT WOS:A1997WL18200003 PM 9132294 ER PT J AU Cidlowski, JA AF Cidlowski, JA TI DATELINE Shanghai - First International Symposium on Programmed Cell Death, Shanghai, China, September 8-12, 1996 SO CELL DEATH AND DIFFERENTIATION LA English DT Editorial Material RP Cidlowski, JA (reprint author), NATL INST ENVIRONM HLTH SCI,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 1350-9047 J9 CELL DEATH DIFFER JI Cell Death Differ. PD FEB PY 1997 VL 4 IS 2 BP 168 EP 168 DI 10.1038/sj.cdd.4400227 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA WE588 UT WOS:A1997WE58800009 PM 16465224 ER PT J AU Shirabe, S Fang, WH Schwartz, JP AF Shirabe, S Fang, WH Schwartz, JP TI Altered intermediate filament expression in human neuroblastoma cells transformed by a growth-promoting agent derived from schizophrenic CSF SO CELLULAR AND MOLECULAR NEUROBIOLOGY LA English DT Article DE vimentin; neurofilament; SK-N-SH(EP); neuroblastoma; immunohistochemistry; Western blot; schizophrenia ID NEUROFILAMENT PROTEINS; NERVOUS-SYSTEM; VIMENTIN; FIBROBLASTS; PHOSPHORYLATION; CULTURE; DISEASE; VIRUS; TUMOR; ACID AB I, Transformed (TR) cell lines showed faster doubling times and higher cell densities at confluence, as well as altered morphology, changing from flat epitheloid to smaller round or bipolar shapes, Since such morphological changes are suggestive of alterations in intermediate filaments, we have analyzed the expression of both vimentin and neurofilament, 2, Immunohistochemical analysis of vimentin showed a redistribution from a cytoplasmic network to a perinuclear accumulation in TR cell lines, 3. Western blot analysis demonstrated that the vimentin content was decreased 60-90%, The content of the 70-kD neurofilament protein was also decreased in TR cells, but its intracellular distribution was indistinguishable from that in the control eel lines. C1 NINCDS,MOL GENET SECT,CLIN NEUROSCI BRANCH,NIH,BETHESDA,MD 20892. NR 28 TC 5 Z9 5 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0272-4340 J9 CELL MOL NEUROBIOL JI Cell. Mol. Neurobiol. PD FEB PY 1997 VL 17 IS 1 BP 1 EP 11 DI 10.1023/A:1026320919282 PG 11 WC Cell Biology; Neurosciences SC Cell Biology; Neurosciences & Neurology GA WF903 UT WOS:A1997WF90300001 PM 9118201 ER PT J AU Rebois, RV Warner, DR Basi, NS AF Rebois, RV Warner, DR Basi, NS TI Does subunit dissociation necessarily accompany the activation of all heterotrimeric G proteins! SO CELLULAR SIGNALLING LA English DT Review DE heterotrimeric G proteins; activation; subunit dissociation ID BETA-GAMMA-SUBUNITS; NUCLEOTIDE-BINDING PROTEINS; ADENYLATE-CYCLASE SYSTEM; TURKEY ERYTHROCYTE-MEMBRANES; BOVINE CEREBRAL-CORTEX; AMINO-TERMINAL REGION; MUSCARINIC K+ CHANNEL; REGULATORY COMPONENT; ALPHA-SUBUNIT; ADP-RIBOSYLATION AB Heterotrimeric (alpha beta gamma) G proteins mediate a variety of signal transduction events in virtually every cell of every eukaryotic organism. The predominant hypothesis is that dissociation of the alpha-subunit from the G beta gamma-subunit complex necessarily accompanies the activation of these proteins, and that the alpha-subunit is primarily responsible for regulating the response of effector molecules. However, there is increasing evidence that both the alpha-subunit and the beta gamma-subunit complex function in regulating effector activity. Furthermore, data for some G proteins suggest that they function as activated heterotrimers rather than as dissociated subunits. (C) 1997 Elsevier Science Inc. RP Rebois, RV (reprint author), NINCDS, CELLULAR & MOL NEUROBIOL LAB, NIH, BLDG 49, RM 2A28, BETHESDA, MD 20892 USA. NR 154 TC 57 Z9 57 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0898-6568 J9 CELL SIGNAL JI Cell. Signal. PD FEB PY 1997 VL 9 IS 2 BP 141 EP 151 DI 10.1016/S0898-6568(96)00133-7 PG 11 WC Cell Biology SC Cell Biology GA WT132 UT WOS:A1997WT13200003 PM 9113413 ER PT J AU McElvaney, NG Stoller, JK Buist, AS Prakash, UBS Brantly, ML Schluchter, MD Crystal, RD AF McElvaney, NG Stoller, JK Buist, AS Prakash, UBS Brantly, ML Schluchter, MD Crystal, RD TI Baseline characteristics of enrollees in the national heart, lung and blood institute registry of alpha(1)-antitrypsin deficiency SO CHEST LA English DT Article DE alpha(1)-antitrypsin; augmentation therapy; COPD; emphysema; registries ID ALPHA-1-ANTITRYPSIN DEFICIENCY; AUGMENTATION THERAPY; EMPHYSEMA; GENE; PROTEASE; STRATEGIES; ELASTASES; DISEASE; VALUES AB Objective: alpha(1)-Antitrypsin (alpha(1)-AT) deficiency is a hereditary disorder characterized by a high risk for the development of emphysema at an early age. In 1988, the National Heart, Lung and Blood Institute, National Institutes of Health, initiated a registry of individuals with alpha(1)-AT deficiency to help define the natural history and clinical course of this disorder. This article describes demographic and clinical characteristics of subjects enrolled in the Registry at baseline. Design: Prospective longitudinal natural history study. Setting: Thirty-seven clinical centers in the United States (36 centers) and Canada (one center). Patients: There were 1,129 subjects 18 years or older with severe deficiency of alpha(1)-AT, defined as having serum alpha(1)-AT levels less than or equal to 11 mu mol/L confirmed by a Central Phenotyping Laboratory, or a ZZ or ZNull genotype identified by genomic DNA analysis. Results: Most enrollees were symptomatic white subjects in their fourth to sixth decade, with a ZZ phenotype, a history of having smoked cigarettes, and pulmonary function tests demonstrating a pattern consistent with emphysema. Interestingly, only a small percentage were current smokers on enrollment, suggesting that this population is amenable to smoking cessation. A subgroup of individuals in the Registry with relatively normal lung function were younger, more likely to have never smoked and more likely to have come to medical attention owing to a family history of alpha(1)-AT deficiency rather than symptomatic involvement. Conclusions: These results emphasize the need for increased awareness and early detection of alpha(1)-AT deficiency. In this endeavor, dissemination of the information contained in the Registry to health-care professionals and the general population, along with initiation of appropriate preventative measures before significant lung damage has occurred, could have considerable benefits for individuals with this condition. C1 NHLBI,PULM CRIT CARE MED BRANCH,NIH,BETHESDA,MD 20892. OREGON HLTH SCI UNIV,DEPT PHYSIOL,PORTLAND,OR 97201. MAYO CLIN,DIV PULM & CRIT CARE & INTERNAL MED,ROCHESTER,MN. CLEVELAND CLIN FDN,DEPT BIOSTAT & EPIDEMIOL,CLEVELAND,OH 44195. NEW YORK HOSP,CORNELL MED CTR,DIV PULM & CRIT CARE MED,NEW YORK,NY 10021. RP McElvaney, NG (reprint author), CLEVELAND CLIN FDN,ALPHA ANTITRYPSIN DEFICIENCY REGISTRY,DEPT BIOSTAT,CLEVELAND,OH 44195, USA. RI McElvaney, Noel/A-6809-2010 FU NHLBI NIH HHS [N01-HR-86036] NR 31 TC 109 Z9 115 U1 0 U2 1 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 SN 0012-3692 J9 CHEST JI Chest PD FEB PY 1997 VL 111 IS 2 BP 394 EP 403 DI 10.1378/chest.111.2.394 PG 10 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA WH304 UT WOS:A1997WH30400029 PM 9041988 ER PT J AU Nagel, DE Putnam, FW Noll, JG Trickett, PK AF Nagel, DE Putnam, FW Noll, JG Trickett, PK TI Disclosure patterns of sexual abuse and psychological functioning at a 1-year follow-up SO CHILD ABUSE & NEGLECT LA English DT Article DE child sexual abuse; disclosure; psychological functioning; 1-year follow-up ID CHILDREN; DEPRESSION; CHILDHOOD AB This study describes the disclosure processes of a sample of 68 sexually abused girls, with a focus on the manner in which abuse was revealed-on purpose, accidentally, or resulting from a precipitating event. This categorization is a more descriptive conceptualization of the disclosure process than has been proposed or assessed in previous studies. The circumstances surrounding disclosure are found to be related to long term psychological functioning. Children who disclosed accidentally were younger, experienced abuse for shorter durations, and received the most therapy. At follow-up, children who purposely disclosed had greater anxiety and greater difficulties coping. Discussion focuses on ways in which identifying and encouraging the least traumatic methods of disclosure would contribute to better outcomes for victims of sexual abuse. C1 UNIV SO CALIF,DEPT PSYCHOL,LOS ANGELES,CA 90089. RP Nagel, DE (reprint author), NIMH,UNIT DEV TRAUMATOL,15 N DR MSC 2668,BLDG 15K,BETHESDA,MD 20892, USA. NR 31 TC 33 Z9 33 U1 1 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0145-2134 J9 CHILD ABUSE NEGLECT JI Child Abuse Negl. PD FEB PY 1997 VL 21 IS 2 BP 137 EP 147 DI 10.1016/S0145-2134(96)00139-1 PG 11 WC Family Studies; Psychology, Social; Social Work SC Family Studies; Psychology; Social Work GA WG471 UT WOS:A1997WG47100003 PM 9056093 ER PT J AU Goldstein, DS Holmes, C Stuhlmuller, JE Lenders, JWM Kopin, IJ AF Goldstein, DS Holmes, C Stuhlmuller, JE Lenders, JWM Kopin, IJ TI 6-[F-18]fluorodopamine positron emission tomographic scanning in the assessment of cardiac sympathoneural function SO CLINICAL AUTONOMIC RESEARCH LA English DT Article DE fluorodopamine; sympathetic; trimethaphan; desipramine; tyramine ID SYMPATHETIC-NERVE ACTIVITY; NEURONAL UPTAKE; PLASMA DIHYDROXYPHENYLGLYCOL; NOREPINEPHRINE RELEASE; HUMAN-HEART; INNERVATION; 6-FLUORODOPAMINE; DESIPRAMINE; RATS; NEUROTRANSMITTERS AB Thoracic positron emission tomographic (PET) scanning after injection of 6-[F-18]fluorodopamine ([F-18]-6F-DA) visualizes cardiac sympathetic innervation We tested whether changes in curves relating myocardial [F-18]-6F-DA-derived radioactivity with time (time-activity curves, TACs) can reflect changes in important aspects of cardiac sympathetic function. Thoracic PET scans were obtained after intravenous administration of [F-18]-6F-DA or the perfusion imaging agent [N-13]ammonia into normal volunteers. Ganglion blockade with trimethaphan (TRI) was used to decrease sympathoneural traffic, desipramine (DMI) to block neuronal uptake of catecholamines, and tyramine (TYR) to displace vesicular amines. After [F-18]-6F-DA administration, myocardial concentrations of [F-18]-6F-DA-derived radioactivity declined bi-exponentially from the peak value. TRI increased the y-intercept (y(o)) value for the early phase (p = 0.01), and DMI decreased the y(o) for the late phase (p = 0.01). The TRI effect did not result from increased arterial [F-18]-6F-DA concentrations or from increased myocardial perfusion. TYR infusion, begun 90 min after [F-18]-6F-DA administration, accelerated the decline of myocardial radioactivity by 2.6-fold (p = 0.003). Alterations in post-ganglionic sympathoneural traffic, neuronal catecholamine uptake, and vesicular turnover of monoamines produce distinct changes in myocardial TACs after [F-18]-6F-DA injection. [F-18]-6F-DA PET scanning may therefore enable assessments of effects of stressors, drugs, and neurocardiological disorders on specific aspects of cardiac sympathoneural function. C1 NINCDS,CLIN NEUROSCI BRANCH,NIH,BETHESDA,MD 20892. NR 36 TC 37 Z9 37 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0959-9851 J9 CLIN AUTON RES JI Clin. Auton. Res. PD FEB PY 1997 VL 7 IS 1 BP 17 EP 29 DI 10.1007/BF02267622 PG 13 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA WL849 UT WOS:A1997WL84900004 PM 9074825 ER PT J AU Higgins, JJ Ide, SE Oghalai, JS Polymeropoulos, MH AF Higgins, JJ Ide, SE Oghalai, JS Polymeropoulos, MH TI Lack of mutations in the biotin-binding region of the pyruvate carboxylase (PC) gene in a family with partial PC deficiency SO CLINICAL BIOCHEMISTRY LA English DT Article C1 NIH,GENE MAPPING UNIT,LAB GENET DIS RES,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. RP Higgins, JJ (reprint author), NINCDS,CLIN NEUROGENET UNIT,MED NEUROL BRANCH,NIH,BLDG 10,ROOM 5N234,BETHESDA,MD 20892, USA. NR 9 TC 4 Z9 4 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0009-9120 J9 CLIN BIOCHEM JI Clin. Biochem. PD FEB PY 1997 VL 30 IS 1 BP 79 EP 81 DI 10.1016/S0009-9120(96)00125-7 PG 3 WC Medical Laboratory Technology SC Medical Laboratory Technology GA WK389 UT WOS:A1997WK38900014 PM 9056115 ER PT J AU Husain, SR Obiri, NI Gill, P Zheng, T Pastan, I Debinski, W Puri, RK AF Husain, SR Obiri, NI Gill, P Zheng, T Pastan, I Debinski, W Puri, RK TI Receptor for interleukin 13 on AIDS-associated Kaposi's sarcoma cells serves as a new target for a potent Pseudomonas exotoxin-based chimeric toxin protein SO CLINICAL CANCER RESEARCH LA English DT Article ID GROWTH-FACTOR; CYTOKINES; EXPRESSION; PATHOGENESIS; MACROPHAGES; AUTOCRINE; PARACRINE; HIV-1 AB AIDS-associated Kaposi's sarcoma (AIDS-KS), the most common malignant complication of human immunodeficiency virus infection, is characterized by neoplastic proliferation of mesenchymal cells, AIDS-KS cells release and respond to an array of cytokines through specific plasma membrane receptors, Specific targeting of potent cytotoxic agents to cell surface receptors/antigens on Kaposi's sarcoma cells may provide effective therapy for this malignancy, We have identified a new target in the form of an interleukin 13 (IL-13) receptor that is overexpressed in the five AIDS-KS cell lines examined. Radio-labeled IL-13 cross-linked to a single protein of about M-r 70,000 in AIDS KS cells, We utilized a chimeric cytotoxic protein composed of IL-13 and a truncated Pseudomonas exotoxin (IL13-PE38QQR), which was found to be specifically and highly cytotoxic to AIDS-KS cells, as determined by protein synthesis inhibition and clonogenic assays, IL13-PE38QQR demonstrated significant antitumor activity in a human epidermoid carcinoma xenograft model. Normal human umbilical vein-derived endothelial, lymphoid, and bone marrow precursor cells expressed low levels of IL-13 receptors, and IL-13 toxin was not cytotoxic to them. Thus, IL-13 receptor on AIDS-KS cells may represent a novel plasma membrane protein(s) that could be utilized to target therapeutic agents. C1 NIH, LAB MOL TUMOR BIOL,DIV CELLULAR & GENE THERAPIES, CTR BIOL EVALUAT & RES,FOOD & DRUG ADM, BETHESDA, MD 20892 USA. UNIV SO CALIF, SCH MED, LOS ANGELES, CA 90033 USA. NCI, MOL BIOL LAB, DIV BASIC SCI, BETHESDA, MD 20892 USA. PENN STATE UNIV, COLL MED, DIV NEUROSURG, HERSHEY, PA 17033 USA. PENN STATE UNIV, MILTON S HERSHEY MED CTR, HERSHEY, PA 17033 USA. NR 26 TC 76 Z9 78 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD FEB PY 1997 VL 3 IS 2 BP 151 EP 156 PG 6 WC Oncology SC Oncology GA WY366 UT WOS:A1997WY36600002 PM 9815666 ER PT J AU Drees, M Dengler, WA Roth, T Labonte, H Mayo, J Malspeis, L Grever, M Sausville, EA Fiebig, HH AF Drees, M Dengler, WA Roth, T Labonte, H Mayo, J Malspeis, L Grever, M Sausville, EA Fiebig, HH TI Flavopiridol (L86-8275): Selective antitumor activity in vitro and activity in vivo for prostate carcinoma cells SO CLINICAL CANCER RESEARCH LA English DT Article ID HUMAN-TUMOR XENOGRAFTS; KINASE-ACTIVITY; CLONOGENIC-ASSAY; PROTEIN-KINASES; INHIBITION; FLAVONOIDS; PHOSPHORYLATION; PROGRESSION; GENISTEIN; GROWTH AB We have selected a panel of human tumor xenografts for in vitro and in vivo studies that allows an indication of selectivity of action of novel chemotherapeutic agents, We report here the antitumor activity of the flavone flavopiridol (previously designated L86-8275), which has been selected for further studies based in part on its behavior in the anticancer drug screening system of the United States National Cancer Institute, Eighteen human tumor and five cell line-derived xenografts established by serial passage in nude mice in our laboratory were used as tumor models for irt vitro investigations using a modified double-layer soft agar assay. In vivo investigations were completed in nude mice bearing advanced-stage s.c. growing prostate cancer xenografts, Antitumor activity in vitro (test/control less than or equal to 30%) of flavopiridol was observed at the very low concentration of 0.1 ng/ml in three of four prostatic xenografts and in one melanoma xenograft. Overall, in 14 of 23 (61%) tumor xenografts, drug treatment resulted in a IC70 of <10 ng/ml, demonstrating the high antiproliferative potential of flavopiridol, Toxicity to in vitro bone marrow cultures was evident only at 100 ng/ml, indicating potential high selectivity for susceptible tumor cells, Comparison of tumor cells with bone marrow samples tested showed clear prostate carcinoma and moderate melanoma selectivity, In vivo studies of flavopiridol confirmed antitumor activity in both prostate cancer xenografts investigated. At the maximal tolerated dose of 10 mg/kg/day administered p.o. on days 1-4 and 7-11, flavopiridol effected tumor regression in PRXF1337 and tumor stasis lasting for 4 weeks in PRXF1369. We conclude that flavopiridol shows strong prostate- and moderate melanoma-specific antitumor activity in vitro. The prostate antitumor activity is also reflected by the two in vivo models studied. Initial clinical efforts with flavopiridol might consider early evaluation in patients with prostate carcinoma. C1 UNIV FREIBURG,DEPT INTERNAL MED,D-79106 FREIBURG,GERMANY. NCI,BIOL TESTING BRANCH,BETHESDA,MD 20892. NCI,LAB PHARMACEUT CHEM,BETHESDA,MD 20892. NCI,DEV THERAPEUT PROGRAM,BETHESDA,MD 20892. NR 46 TC 113 Z9 116 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD FEB PY 1997 VL 3 IS 2 BP 273 EP 279 PG 7 WC Oncology SC Oncology GA WY366 UT WOS:A1997WY36600019 PM 9815683 ER PT J AU Hristova, EN Rehak, NN Cecco, S Ruddel, M Herion, D Eckardt, M Linnoila, M Elin, RJ AF Hristova, EN Rehak, NN Cecco, S Ruddel, M Herion, D Eckardt, M Linnoila, M Elin, RJ TI Serum ionized magnesium in chronic alcoholism: Is it really decreased? SO CLINICAL CHEMISTRY LA English DT Article; Proceedings Paper CT AACC/CSCC Annual Meeting CY JUL, 1996 CL CHICAGO, IL DE ion-selective electrodes; electrolytes; ethanol; variation, source of ID CALCIUM; PLASMA AB Chronic alcoholism is associated with a marked deficit in total magnesium (tMg). However, little is known about the status of the physiologically active form, ionized magnesium (iMg). We assessed serum iMg (measured with two ion-selective electrodes, AVL 988-4 and NOVA CRT) and tMg concentrations in chronic alcoholics at admission (n = 31) and after abstinence (n = 13) and compared these results with those for a control group (n = 40). At admission, the tMg and NOVA iMg concentrations in alcoholics (0.78 +/- 0.020 and 0.38 +/- 0.016 mmol/L, respectively) were significantly less (P < 0.001) than in the controls (0.85 +/- 0.008 and 0.50 +/- 0.006 mmol/L). The AVL iMg results, however, did,not differ significantly between the two groups: 0.53 +/- 0.013 vs 0.56 +/- 0.006 mmol/L, respectively (P > 0.05). The mean iMg between the two analyzers differed significantly in both groups (P < 0.001). After 3 weeks of abstinence, the alcoholics showed a significant increase in tMg (P < 0.001) and in both NOVA and AVL iMg values (P < 0.01 for each). tMg concentrations were positively correlated with the AVL iMg values in both alcoholics and controls but correlated positively with the NOVA iMg results only in the controls. Thus, the altered status of iMg is instrument-dependent, and the usefulness of the measurement in alcoholics is yet to be determined. C1 NIAAA,NIH,BETHESDA,MD 20892. RP Hristova, EN (reprint author), NIH,WARREN GRANT MAGNUSON CLIN CTR,DEPT CLIN PATHOL,CLIN CHEM SERV,BLDG 10,RM 2C-407,10 CTR DR,BETHESDA,MD 20892, USA. NR 16 TC 17 Z9 19 U1 0 U2 1 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD FEB PY 1997 VL 43 IS 2 BP 394 EP 399 PG 6 WC Medical Laboratory Technology SC Medical Laboratory Technology GA WF913 UT WOS:A1997WF91300022 PM 9023146 ER PT J AU Gonzalez, CE Couriel, DR Walsh, TJ AF Gonzalez, CE Couriel, DR Walsh, TJ TI Disseminated zygomycosis in a neutropenic patient: Successful treatment with amphotericin B lipid complex and granulocyte colony-stimulating factor SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID INVASIVE FUNGAL-INFECTIONS; DISSEMINATED MUCORMYCOSIS; ASPERGILLUS-FUMIGATUS; RHIZOMUCOR-PUSILLUS; CUTANEOUS LESIONS; RHIZOPUS-ORYZAE; CANCER-PATIENTS; LEUKEMIA; INVITRO; HYPHAE AB Disseminated zygomycosis in persistently neutropenic patients has been almost uniformly fatal despite aggressive surgical and medical management. We describe a neutropenic patient with disseminated zygomycosis that involved the lungs and kidneys and was successfully treated with amphotericin B lipid complex and granulocyte colony-stimulating factor, followed by suppressive therapy with amphotericin B for 1 pear. This approach preserved the patient's renal function and restored systemic host defenses. The single pulmonary lesion was resected, but no resection of renal tissue was attempted because of the bilateral extension of the renal lesions. After a 1-year period of followup without antifungal therapy, the patient's condition remains stable, and there has been no relapse of the infection. C1 NCI,PEDIAT BRANCH,INFECT DIS SECT,BETHESDA,MD 20892. NHLBI,BETHESDA,MD 20892. NR 37 TC 96 Z9 99 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD FEB PY 1997 VL 24 IS 2 BP 192 EP 196 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA WH302 UT WOS:A1997WH30200018 PM 9114146 ER PT J AU Burns, DN Tuomala, R Chang, BH Hershow, R Minkoff, H Rodriguez, E Zorrilla, C Hammill, H Regan, J AF Burns, DN Tuomala, R Chang, BH Hershow, R Minkoff, H Rodriguez, E Zorrilla, C Hammill, H Regan, J TI Vaginal colonization or infection with Candida albicans in human immunodeficiency virus-infected women during pregnancy and during the postpartum period SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID CELL-MEDIATED-IMMUNITY; HIV-SEROPOSITIVE WOMEN; CD4 PERCENTAGE; TRANSMISSION; DEFINITION; FREQUENCY; COUNTS; CYCLE; LIFE; AIDS AB We evaluated the relationship between immunologic status and vaginal colonization or infection with Candida albicans for 605 women enrolled in a multicenter, prospective cohort study of mother-to-infant transmission of human immunodeficiency virus type 1 (HIV-1), A low CD4(+) lymphocyte level (<14% vs. greater than or equal to 14%, which corresponds to an absolute count of similar to 200 x 10(6)/L) was associated with a two- to fivefold increased likelihood of vaginal colonization (odds ratio [OR], 2.28; 95% confidence interval [CI], 1.01-5.19) and vaginal candidiasis (OR, 3.08; 95% CI, 1.21-7.71) during pregnancy and during the postpartum period (OR, 2.98; 95% CI, 1.51-5.88 and OR, 5.45; 95% CI, 1.73-16.6, respectively), These associations persisted in multivariate logistic regression analyses, No associations with CD8(+) lymphocyte levels or CD8(+) CD38(+) or other lymphocyte subset levels were found after adjustment for CD4(+) cell level and other covariates, However, postpartum (but not antepartum) antibiotic use and pregnancy were also associated with vaginal colonization and candidiasis (P less than or equal to.001 for each), Vaginal candidiasis was not associated with an increased risk of mother-to-infant transmission of HIV-1; however, a related, more inclusive variable, clinical vaginitis or vaginosis of any etiology at the last antepartum visit, was associated with mother-to-infant transmission (OR, 1.92; 95% CI, 1.07-3.43), These findings emphasize the complex, multifactorial nature of vaginal candidiasis and highlight the need for safe and effective treatment and prevention strategies for women with advanced HIV infection. C1 NIAID,DIV AIDS,NIH,BETHESDA,MD 20892. BRIGHAM & WOMENS HOSP,DEPT OBSTET & GYNECOL,BOSTON,MA 02115. NEW ENGLAND RES INST INC,WATERTOWN,MA 02172. UNIV ILLINOIS,SCH PUBL HLTH,DIV EPIDEMIOL & BIOSTAT,CHICAGO,IL. SUNY HLTH SCI CTR,DEPT OBSTET & GYNECOL,BROOKLYN,NY. COLUMBIA UNIV COLL PHYS & SURG,DEPT PEDIAT,NEW YORK,NY 10032. UNIV PUERTO RICO,SCH MED,DEPT OBSTET & GYNECOL,SAN JUAN,PR 00936. BAYLOR COLL MED,DEPT OBSTET & GYNECOL,HOUSTON,TX 77030. RP Burns, DN (reprint author), NICHHD,PEDIAT ADOLESCENT & MATERNAL AIDS BRANCH,6100 EXECUT BLVD,ROOM 4B11,BETHESDA,MD 20892, USA. FU NIAID NIH HHS [AI-34840, AI-34842, AI-34841] NR 50 TC 25 Z9 27 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD FEB PY 1997 VL 24 IS 2 BP 201 EP 210 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA WH302 UT WOS:A1997WH30200020 PM 9114148 ER PT J AU Bonilla, HF Chenoweth, CE Tully, JG Blythe, LK Robertson, JA Ognenovski, VM Kauffman, CA AF Bonilla, HF Chenoweth, CE Tully, JG Blythe, LK Robertson, JA Ognenovski, VM Kauffman, CA TI Mycoplasma felis septic arthritis in a patient with hypogammaglobulinemia SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID INFLAMMATORY POLYARTHRITIS; PNEUMONIAE; INFECTION; HOMINIS; IMMUNODEFICIENCY; PLEURITIS; HORSES; CATS AB We describe the first documented case of Mycoplasma felis infection in a woman who had common variable immunodeficiency and who presented with septic arthritis of the left hip and right knee. M. felis was isolated from both joints. She had been exposed to cats before the diagnosis of M. felis septic arthritis was made, Both of the patient's joints were surgically debrided, and she was treated with doxycycline for several months. In spite of initial improvement, destruction of her hip was noted, Subsequently, she underwent hip arthroplasty; histopathological examination of the bone at the time of surgery showed chronic osteomyelitis, and doxycycline therapy was continued. C1 VET ADM MED CTR,ANN ARBOR,MI 48105. UNIV MICHIGAN,SCH MED,DIV INFECT DIS,DEPT INTERNAL MED,ANN ARBOR,MI. UNIV MICHIGAN,SCH MED,DIV RHEUMATOL,DEPT INTERNAL MED,ANN ARBOR,MI. UNIV MICHIGAN,CTR MED,DEPT PATHOL,CLIN MICROBIOL LAB,ANN ARBOR,MI 48109. NIAID,MOL MICROBIOL LAB,NIH,FREDERICK,MD. UNIV ALBERTA,DEPT MED MICROBIOL & IMMUNOL,EDMONTON,AB,CANADA. NR 47 TC 23 Z9 24 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD FEB PY 1997 VL 24 IS 2 BP 222 EP 225 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA WH302 UT WOS:A1997WH30200023 PM 9114151 ER PT J AU Rex, JH Pfaller, MA Galgiani, JN Bartlett, MS EspinelIngroff, A Ghannoum, MA Lancaster, M Odds, FC Rinaldi, MG Walsh, TJ Barry, AL AF Rex, JH Pfaller, MA Galgiani, JN Bartlett, MS EspinelIngroff, A Ghannoum, MA Lancaster, M Odds, FC Rinaldi, MG Walsh, TJ Barry, AL TI Development of interpretive breakpoints for antifungal susceptibility testing: Conceptual framework and analysis of in vitro in vivo correlation data for fluconazole, itraconazole, and Candida infections SO CLINICAL INFECTIOUS DISEASES LA English DT Review ID SERUM BACTERICIDAL ACTIVITIES; HUMAN-IMMUNODEFICIENCY-VIRUS; QUALITY-CONTROL GUIDELINES; BROTH MACRODILUTION METHOD; AMPHOTERICIN-B; RESISTANT CANDIDA; NATIONAL-COMMITTEE; PROTEIN-BINDING; PHARMACOKINETIC PROPERTIES; MULTICENTER EVALUATION AB The availability of reproducible antifungal susceptibility testing methods now permits analysis of data correlating susceptibility in vitro with outcome in vivo in order to define interpretive breakpoints. In this paper, we have examined the conceptual framework underlying interpretation of antimicrobial susceptibility testing results and then used these ideas to drive analysis of data packages developed by the respective manufacturers that correlate fluconazole and itraconazole MICs with outcome of candidal infections, Tentative fluconazole interpretive breakpoints for MICs determined by the National Committee for Clinical Laboratory Standards' M27-T broth macrodilution methodology are proposed: isolates for which MICs are less than or equal to 8 mu g/mL are susceptible to fluconazole, whereas those for which MICs are greater than or equal to 64 mu g/mL appear resistant, Isolates for which the MIC of fluconazole is 16-32 mu g/mL are considered susceptible dependent upon dose (S-DD), on the basis of data indicating clinical response when >100 mg of fluconazole per day is given, These breakpoints do not, however, apply to Candida krusei, as it is considered inherently resistant to fluconazole, Tentative interpretive MIC breakpoints for itraconazole apply only to mucosal candidal infections and are as follows: susceptible, less than or equal to 0.125 mu g/mL; S-DD, 0.25-0.5 mu g/mL; and resistant, greater than or equal to 1.0 mu g/mL. These tentative breakpoints are now open for public commentary. C1 UNIV TEXAS,SCH MED,DEPT INTERNAL MED,DIV INFECT DIS,CTR STUDY EMERGING & REEMERGING PATHOGENS,HOUSTON,TX. UNIV IOWA,COLL MED,DEPT PATHOL,IOWA CITY,IA 52242. VET AFFAIRS MED CTR,TUCSON,AZ. UNIV ARIZONA,COLL MED,TUCSON,AZ. INDIANA UNIV,MED CTR,DEPT PATHOL,INDIANAPOLIS,IN. VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,DIV INFECT DIS,RICHMOND,VA 23298. UNIV HOSP CLEVELAND,CTR MED MYCOL,DEPT DERMATOL,CLEVELAND,OH 44106. CASE WESTERN RESERVE UNIV,SCH MED,CLEVELAND,OH. ACCUMED INT INC,WESTLAKE,OH. JANSSEN RES FDN,B-2340 BEERSE,BELGIUM. UNIV TEXAS,HLTH SCI CTR,AUDIE L MURPHY MEM VET HOSP,LAB SERV,SAN ANTONIO,TX. NCI,INFECT DIS SECT,PEDIAT BRANCH,BETHESDA,MD 20892. INST CLIN MICROBIOL,TUALATIN,OR. NR 123 TC 646 Z9 667 U1 2 U2 15 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD FEB PY 1997 VL 24 IS 2 BP 235 EP 247 PG 13 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA WH302 UT WOS:A1997WH30200026 PM 9114154 ER PT J AU Park, MK Khan, J Stock, F Lucey, DR AF Park, MK Khan, J Stock, F Lucey, DR TI Successful treatment of Stomatococcus mucilaginosus meningitis with intravenous vancomycin and intravenous ceftriaxone SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID INFECTIONS; CHILDREN; LEUKEMIA C1 NCI,CLIN MICROBIOL SECT,NIH,BETHESDA,MD 20892. NCI,EXPT IMMUNOL BRANCH,NIH,BETHESDA,MD 20892. RP Park, MK (reprint author), NIAID,PEDIAT BRANCH,NIH,BLDG 10,ROOM 11N228,MSC-1888,BETHESDA,MD 20892, USA. NR 8 TC 8 Z9 8 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD FEB PY 1997 VL 24 IS 2 BP 278 EP 278 PG 1 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA WH302 UT WOS:A1997WH30200041 PM 9114169 ER PT J AU DeVry, J Fritze, J Post, RM AF DeVry, J Fritze, J Post, RM TI The management of coexisting depression in patients with dementia: Potential of calcium channel antagonists SO CLINICAL NEUROPHARMACOLOGY LA English DT Review DE calcium channel antagonists; nimodipine; depression; dementia ID CEREBROSPINAL-FLUID SOMATOSTATIN; BEHAVIORAL DESPAIR TEST; ALZHEIMERS-DISEASE; CSF SOMATOSTATIN; INTRACELLULAR CALCIUM; AFFECTIVE-DISORDERS; NUCLEUS-ACCUMBENS; RATS; NIMODIPINE; NIFEDIPINE AB Depression frequently coexists with dementia, although in many cases the depression is not recognized clinically. Depression represents a major additional burden in dementia, not only for the patients but also for families, caregivers, and, economically, society as a whole. However, depression in patients with dementia does respond to treatment, and appropriate therapy can significantly improve the well-being of these patients. Depression in patients with dementia is currently treated with a variety of standard antidepressive agents (tricyclic antidepressants, selective serotonin reuptake inhibitors, monoamine oxidase inhibitors), but none is free from significant side effects. Moreover, the use of these drugs is often complicated by a number of age-related factors or effects on the cholinergic neurotransmitter system, Consequently, an antidementia treatment with concomitant antidepressive properties and an acceptable benefit/risk ratio would represent an attractive therapeutic option. The pathogenesis of depression in patients with dementia is not well understood, but may be related to increased intracellular calcium ions in the CNS, the so-called ''calcium hypothesis.'' This hypothesis may explain why some calcium antagonists exert psychotropic effects, including putative antidepressant activity. Animal models and clinical data provide support for the use of calcium channel antagonists for the treatment of depression, with the potential for good tolerability. The latter aspect is especially important for elderly patients with dementia. Although antidepressive effects have been seen with a number of calcium channel antagonists, the dihydropyridine derivative nimodipine shows particular potential for clinical use, perhaps because nimodipine is one of the most lipophilic of these drugs and therefore achieves high concentrations in the CNS, and because of the unique biochemical properties of the dihydropyridine compounds compared with other L-type calcium channel blockers. Nimodipine also increases somatostatin levels in CSF, one of the cardinal biochemical deficits in Alzheimer's disease. Data obtained incidentally from the use of nimodipine in the treatment of elderly demented patients clearly demonstrate significant antidepressant activity by the drug in this patient group. Formal clinical evaluation is therefore recommended to establish more clearly the therapeutic benefits offered by nimodipine in patients who suffer from both dementia and depression. C1 UNIV FRANKFURT KLINIKUM,D-6000 FRANKFURT,GERMANY. NIMH,BETHESDA,MD 20892. RP DeVry, J (reprint author), TROPONWERKE GMBH & CO KG,INST NEUROBIOL,NEURATHER RING 1,D-51063 COLOGNE,GERMANY. NR 88 TC 17 Z9 17 U1 1 U2 3 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0362-5664 J9 CLIN NEUROPHARMACOL JI Clin. Neuropharmacol. PD FEB PY 1997 VL 20 IS 1 BP 22 EP 35 PG 14 WC Clinical Neurology; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA WL140 UT WOS:A1997WL14000003 PM 9037570 ER PT J AU Bauer, KS Kohn, EC Reed, E Sarosy, GA Lush, RM Simmons, BR Davis, PA Figg, WD AF Bauer, KS Kohn, EC Reed, E Sarosy, GA Lush, RM Simmons, BR Davis, PA Figg, WD TI Pharmacokinetics (PK) of micronized carboxy amido-triazole (CAI) in cancer patients (PTS) SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 NCI,CLIN PHARMACOL BRANCH,BETHESDA,MD 20892. RI Figg Sr, William/M-2411-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 1997 VL 61 IS 2 BP PI35 EP PI35 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA WJ684 UT WOS:A1997WJ68400035 ER PT J AU DePetrillo, PB AF DePetrillo, PB TI Ethanol inhibits calcium-stimulated protease activity. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 NIAAA,NIH,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 1997 VL 61 IS 2 BP PI102 EP PI102 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA WJ684 UT WOS:A1997WJ68400212 ER PT J AU Dionne, RA McCullagh, L AF Dionne, RA McCullagh, L TI Analgesic efficacy of the S(+) isomer of ibuprofen in comparison to racemic ibuprofen. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 NIDR,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 1997 VL 61 IS 2 BP PIII5 EP PIII5 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA WJ684 UT WOS:A1997WJ68400232 ER PT J AU Freed, CR Breeze, RE Leehey, MA Schneck, SA OBrien, CF Thompson, LL Ramig, LO McRae, CA Mazziotta, JC Miletich, RS Eidelberg, D AF Freed, CR Breeze, RE Leehey, MA Schneck, SA OBrien, CF Thompson, LL Ramig, LO McRae, CA Mazziotta, JC Miletich, RS Eidelberg, D TI Fetal neurotransplantation for Parkinsons disease: Results after eight years. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 UNIV COLORADO,SCH MED,DENVER,CO. UNIV CALIF LOS ANGELES,MED CTR,LOS ANGELES,CA 90024. NIH,BETHESDA,MD 20892. N SHORE UNIV HOSP,MANHASSET,NY. RI Eidelberg, David/F-5214-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 1997 VL 61 IS 2 BP PII42 EP PII42 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA WJ684 UT WOS:A1997WJ68400153 ER PT J AU Gordon, SM Dionne, RA AF Gordon, SM Dionne, RA TI Oral surgery as a model of central hyperalgesia. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 NIDR,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 1997 VL 61 IS 2 BP PII11 EP PII11 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA WJ684 UT WOS:A1997WJ68400238 ER PT J AU Holtzman, JL Zhou, LX Pihlstrom, B Hardwick, JP Park, SS Wrighton, SA AF Holtzman, JL Zhou, LX Pihlstrom, B Hardwick, JP Park, SS Wrighton, SA TI Phenytoin metabolism by gingiva from normal humans SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 UNIV MINNESOTA,DEPT MED & PHARMACOL,MINNEAPOLIS,MN 55455. UNIV MINNESOTA,SCH DENTIST,MINNEAPOLIS,MN 55455. VET ADM MED CTR,MINNEAPOLIS,MN. NE OHIO UNIV,COLL MED,ROOTSTOWN,OH 44272. NCI,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21701. ELI LILLY & CO,INDIANAPOLIS,IN 46285. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 1997 VL 61 IS 2 BP PI11 EP PI11 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA WJ684 UT WOS:A1997WJ68400011 ER PT J AU Lieberman, R Boone, C Crowell, J Hawk, E Malone, W Steele, V Lubet, R Sigman, C Kelloff, G AF Lieberman, R Boone, C Crowell, J Hawk, E Malone, W Steele, V Lubet, R Sigman, C Kelloff, G TI Surrogate endpoint biomarker (SEB) guided drug development: A practical strategy for chemoprevention (CP) of preinvasive cancer (PRECA) SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 NCI,CHEMOPREVENT RES PROGRAM,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 1 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 1997 VL 61 IS 2 BP PII1 EP PII1 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA WJ684 UT WOS:A1997WJ68400113 ER PT J AU Lush, RM Stinson, S Senderowicz, AM Hill, K Feuer, J Headlee, D Figg, W Sausville, E AF Lush, RM Stinson, S Senderowicz, AM Hill, K Feuer, J Headlee, D Figg, W Sausville, E TI Flavopiridol (NSC649890) pharmacokinetics suggest enterohepatic circulation SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 NCI,CLIN PHARMACOL BRANCH,BETHESDA,MD 20892. NCI,DEV THERAPEUT PROGRAM,BETHESDA,MD 20892. RI Figg Sr, William/M-2411-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 1997 VL 61 IS 2 BP PI34 EP PI34 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA WJ684 UT WOS:A1997WJ68400034 ER PT J AU Preston, KL Silverman, K Goldberger, BA Cone, EJ AF Preston, KL Silverman, K Goldberger, BA Cone, EJ TI Criteria for identifying new cocaine use: Presence of cocaine in urine. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 NIDA,ADDICT RES CTR,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,BALTIMORE,MD. UNIV FLORIDA,GAINESVILLE,FL. RI Preston, Kenzie/J-5830-2013 OI Preston, Kenzie/0000-0003-0603-2479 NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 1997 VL 61 IS 2 BP PI104 EP PI104 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA WJ684 UT WOS:A1997WJ68400214 ER PT J AU Shoaf, SE AF Shoaf, SE TI Pharmacokinetic modeling of alcohol following IV infusion or oral ingestion with food. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 NIAAA,DICBR,LCS,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 1997 VL 61 IS 2 BP PI109 EP PI109 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA WJ684 UT WOS:A1997WJ68400219 ER PT J AU Kingman, A Selwitz, RH AF Kingman, A Selwitz, RH TI Proposed methods for improving the efficiency of the DMFS index in assessing initiation and progression of dental caries SO COMMUNITY DENTISTRY AND ORAL EPIDEMIOLOGY LA English DT Article DE caries initiation; caries progression; dental caries; DMF index; epidemiology ID CLINICAL-TRIAL; DENTIFRICES; MANAGEMENT; DIAGNOSIS AB Recent changes in the epidemiology of dental caries and advances in the development of new diagnostic measurement techniques have stimulated interest in improved methods of assessing changes in dental caries status. Traditional methods for assessing change focus primarily on the development of new lesions at the cavitation level and incorporate incomplete information on the progression of existing cavitated lesions. A methodology to expand the clinical recording of dental caries in clinical studies to include 1) both non-cavitated and cavitated lesions and 2) the surface area affected for restorations is suggested. New indices are proposed to estimate changes in the number of new lesions, the progression of existing carious lesions, and the total change in caries status for a subject. It is anticipated that the new indices will produce more efficient methods of assessing change in caries status in longitudinal clinical studies, The degree of improvement can be estimated directly Improvements in efficiency may reduce the duration or number of subjects required in caries clinical trials. RP Kingman, A (reprint author), NIDR,DIV INTRAMURAL RES,BETHESDA,MD 20892, USA. NR 37 TC 16 Z9 18 U1 0 U2 3 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 FEB PY 1997 VL 25 IS 1 BP 60 EP 68 DI 10.1111/j.1600-0528.1997.tb00900.x PG 9 WC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health SC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health GA WN576 UT WOS:A1997WN57600007 PM 9088693 ER PT J AU Vidal, A Figueroa, MP Eberwein, ME Kreda, S Barrantes, FJ AF Vidal, A Figueroa, MP Eberwein, ME Kreda, S Barrantes, FJ TI Co-distribution of tropomyosin and alpha-actinin with actin in Psammobatis extenta electrocytes brings out their similarity with muscle fiber cytoplasm SO COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY A-PHYSIOLOGY LA English DT Article DE electric organ; muscle fibers; actin; actin-binding proteins; Rajidae ID TORPEDO-MARMORATA ELECTROCYTE; ACETYLCHOLINE-RECEPTOR; ELECTRIC ORGAN; POSTSYNAPTIC MEMBRANES; MONOCLONAL-ANTIBODIES; PROTEIN; CYTOSKELETON; LOCALIZATION; ULTRASTRUCTURE; TISSUE AB Electric organs of Psammobatis extenta (Rajiformes) electric fish derive from myoblasts of the caudal region (16). Here we study the presence of muscle proteins, actin and the actin-binding proteins, alpha-actinin and tropomyosin, in the electrocytes by means of biochemical approaches, scanning electron microscopy and immunocytochemical methods. NBD-phallacidin is employed to detect the filamentous form of actin (F-actin). Immunoblots of actin and alpha-actinin from P. extenta skeletal and smooth muscle show that the electric organ forms of actin and alpha-actinin correspond to muscle types. Scanning electron microscopy shows that P. extenta electrocytes are highly polarized cells, semicircular in shape, with an anterior, concave innervated face and a posterior, convex, non-innervated face. The immunofluorescence patterns of alpha-actinin and tropomyosin distribution are similar to those of actin, in that these epitopes appear to occur throughout the entire electrocyte cytoplasm. F-actin, as revealed by NBD-phallacidin fluorescence, was also found throughout the cytoplasm. This is the first time that evidence is presented to demonstrate the existence of muscle actin in this weak electric fish species electrocyte. The close evolutionary connection to that of muscle cells is discussed. Copyright (C) 1996 Elsevier Science Inc. C1 UNIV NACL SUR,INST INVEST BIOQUIM,CONICET,RA-8000 BAHIA BLANCA,ARGENTINA. NIEHS,CELLULAR & MOL PHARMACOL LAB,RES TRIANGLE PK,NC 27709. NR 31 TC 4 Z9 4 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0300-9629 J9 COMP BIOCHEM PHYS A JI Comp. Biochem. Physiol. A-Physiol. PD FEB PY 1997 VL 116 IS 2 BP 113 EP 118 DI 10.1016/S0300-9629(96)00160-0 PG 6 WC Biochemistry & Molecular Biology; Physiology; Zoology SC Biochemistry & Molecular Biology; Physiology; Zoology GA WA046 UT WOS:A1997WA04600005 PM 9011031 ER PT J AU Currey, KM Shapiro, BA AF Currey, KM Shapiro, BA TI Secondary structure computer prediction of the poliovirus 5' non-coding region is improved by a genetic algorithm SO COMPUTER APPLICATIONS IN THE BIOSCIENCES LA English DT Article ID NONCODING REGION; 5'-UNTRANSLATED REGION; 5'-NONCODING REGION; MULTIPLE SITES; CELL-PROTEINS; RNA; TRANSLATION; NEUROVIRULENCE; SEQUENCE; DOMAINS AB Comparison of the secondary structure of the 5' non-coding region of poliovirus 3 RNA derived from the genetic algorithm with the model of Skinner et al. (J. Mel. Biol., 207, 379-392, 1989) demonstrates many of the confirmed structural elements. The genetic algorithm (Shapiro and Navetta, J. Supercomput., 8, 195-201, 1994) generates a population of all possible stems, then mixes, combines, and recombines these stems in multiple iterations on a massively parallel computer ultimately selecting a most fit structure based on its energy. The secondary structure of the region containing the determinants of neurovirulence was better predicted using the genetic algorithm, whereas the dynamic programing algorithm (Zuker, Science, 244, 48-52, 1989) required phylogenetic comparative sequence analysis to arrive at the con ect conclusion. In addition, artificial mutations were introduced throughout this region of the genome and although rearrangements in structure may occur, many structures persisted, suggesting that the given structures thus selected may have evolved to withstand isolated mutations. The genetic algorithm-derived structure for the 5' non-coding region compares favorably with the biological data and functions previously described, and contains all of the 'persistent' structures, suggesting also that the persistence factor may be an aid to validating structures. C1 NCI,FREDERICK CANC RES & DEV CTR,MATH BIOL LAB,DIV BASIC SCI,FREDERICK,MD 21702. RP Currey, KM (reprint author), UNIV MARYLAND,MED CTR,DEPT PEDIAT,SIDS INST,22 S GREENE ST,BALTIMORE,MD 21201, USA. NR 38 TC 18 Z9 19 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0266-7061 J9 COMPUT APPL BIOSCI JI Comput. Appl. Biosci. PD FEB PY 1997 VL 13 IS 1 BP 1 EP 12 PG 12 WC Computer Science, Interdisciplinary Applications SC Computer Science GA WP556 UT WOS:A1997WP55600001 PM 9088703 ER PT J AU Chao, KM Zhang, JH Ostell, J Miller, W AF Chao, KM Zhang, JH Ostell, J Miller, W TI A tool for aligning very similar DNA sequences SO COMPUTER APPLICATIONS IN THE BIOSCIENCES LA English DT Article ID ALGORITHM AB Results: We have produced a computer program, named sim3, that solves the following computational problem. Two DNA sequences are given, where the shorter sequence is very similar to some contiguous region of the longer sequence. Sim3 determines such a similar region of the longer sequence, and then computes an optimal set of single-nucleotide changes (i.e., insertions, deletions or substitutions) that will convert the shorter sequence to that region. Thus, the alignment scoring scheme is designed to model sequencing errors, rather than evolutionary processes. The program can align a 100 kb sequence to a I megabase sequence in a few seconds on a workstation, provided that there are very few differences between the shorter sequence and some region in the longer sequence. The program has been used to assemble sequence data for the Genomes Division at the National Center for Biotechnology Information. Availability: A version of sim3 for UNIX machines can be obtained by anonymous ftp from ncbi. nlm. nih, gov, in the pub/sim3 directory. Contact: For portable versions for Macs and PCs, contact zjing@sunset. nlm. nih. gov. C1 PENN STATE UNIV, DEPT COMP SCI & ENGN, UNIVERSITY PK, PA 16802 USA. PROVIDENCE UNIV, DEPT COMP SCI & INFORMAT MANAGEMENT, TAICHUNG 43309, TAIWAN. NIH, NATL CTR BIOTECHNOL INFORMAT, NATL LIB MED, BETHESDA, MD 20892 USA. OI CHAO, KUN-MA0/0000-0003-2837-1279 FU NLM NIH HHS [R01 LM05110] NR 17 TC 19 Z9 20 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0266-7061 J9 COMPUT APPL BIOSCI JI Comput. Appl. Biosci. PD FEB PY 1997 VL 13 IS 1 BP 75 EP 80 PG 6 WC Computer Science, Interdisciplinary Applications SC Computer Science GA WP556 UT WOS:A1997WP55600010 PM 9088712 ER PT J AU Velarde, CA Short, BL Rivera, O Seale, W Howard, R Kolobow, T AF Velarde, CA Short, BL Rivera, O Seale, W Howard, R Kolobow, T TI Reduced airway resistance and work of breathing during mechanical ventilation with an ultra-thin, two-stage polyurethane endotracheal tube (the Kolobow tube) SO CRITICAL CARE MEDICINE LA English DT Article DE mechanical ventilation; neonate; airway resistance; work of breathing; respiratory mechanics; respiratory function test; intubation; endotracheal ID INSPIRATORY WORK; IMPOSED WORK; PRESSURE SUPPORT; DEMAND-FLOW; SYSTEMS AB Objectives: To compare dynamic pulmonary function studies using the ultrathin walled Kolobow endotracheal tube, with conventional endotracheal tubes of similar external diameter on rabbits during mechanical ventilation. To test the hypothesis that the increased internal diameter of the Kolobow tube will result in decreased airway resistance and work of breathing. Design: Controlled animal study. Setting: Institutional animal research facility. Subjects: Adult female Dutch Belted rabbits (n = 6), weighing 1.4 to 1.6 kg. Interventions: The animals were initially intubated with a conventional endotracheal tube (2.5-mm internal diameter; 3.6-mm outer diameter); they were paralyzed and placed on a mechanical ventitator. Ventilatory settings were adjusted to obtain standard arterial blood gases: pH of 7.35 to 7.45; Pace, of 35 to 40 torr (4.7 to 5.3 kPa), and Pao(2) of 90 to 100 torr (12.0 to 13.3 kPa). After the stabilization period, pulmonary function tests (PFTs) were measured (period 1), the conventional endotracheal tube was replaced with a Kolobow tube, and PFTs were measured again and recorded (period 2). While continuously monitoring tidal volume, the peak inspiratory pressure was decreased to match the tidal volume measured during ventilation with the conventional endotracheal tube. Once the desired tidal volume was reached, PFTs were recorded (period 3). Flows were unchanged during the experiment and the length of the endotracheal tubes was the same for both the conventional and the Kolobow tube. Measurements and Main Results: Mean values of the airway resistance and work of breathing from periods 1 and 3 were compared using the Student's t-test. There was a 59% decrease in total airway resistance (p = .001) and 45% decrease in the work of breathing (p = .0006). Conclusions: The use of the ultrathin walled Kolobow endotracheal tube resulted in significant decreases in airway resistance and work of breathing, which has the potential for improving the ventilatory mechanics in very small premature newborns. C1 GEORGE WASHINGTON UNIV,CHILDRENS NATL MED CTR,SCH MED & HLTH SCI,DIV NEONATOL,DEPT PEDIAT,WASHINGTON,DC. NHLBI,CELL BIOL LAB,NIH,BETHESDA,MD 20892. NR 19 TC 2 Z9 2 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD FEB PY 1997 VL 25 IS 2 BP 276 EP 279 DI 10.1097/00003246-199702000-00014 PG 4 WC Critical Care Medicine SC General & Internal Medicine GA WJ268 UT WOS:A1997WJ26800015 PM 9034264 ER PT J AU Hesselgesser, J HalksMiller, M DelVecchio, V Peiper, SC Hoxie, J Kolson, DL Taub, D Horuk, R AF Hesselgesser, J HalksMiller, M DelVecchio, V Peiper, SC Hoxie, J Kolson, DL Taub, D Horuk, R TI CD4-independent association between HIV-1 gp120 and CXCR4: Functional chemokine receptors are expressed in human neurons SO CURRENT BIOLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; HUMAN CELL-LINE; NEUROLOGIC MANIFESTATIONS; NTERA-2 CELLS; T-CELLS; INTERLEUKIN-8; DIFFERENTIATION; INFECTION; CYTOKINES AB Background: Chemokines are a family of proteins that chemoattract and activate immune cells by interacting with specific receptors on the surface of their targets. We have shown previously that chemokine receptors including the interleukin-8 receptor B (CXCR2) and the Duffy blood group antigen are expressed on subsets of neurons in Various regions of the adult central nervous system. Results: Using a combination of immunohistochemical staining and receptor-binding studies, we show that hNT cells, which are differentiated human neurons derived from the cell line NTera 2, express functional chemokine receptors of the C-X-C and C-C types. These chemokine receptors include CXCR2, CXCR4, CCR1 and CCR5. We demonstrate high-affinity binding of both types of chemokines to hNT neurons and dose-dependent chemotactic responses to these chemokines in differentiated, but not undifferentiated, NTera 2 cells, In addition, we show that the envelope glycoprotein from the T-cell-tropic human immunodeficiency virus 1 (HIV-1) strain IIIB is a CD4-independent, dose-dependent inhibitor of the binding of stromal cell-derived factor 1 to its receptor, CXCR4. Conclusions: These data support the recent findings that members of the chemokine receptor family, including CCR5 and LESTR/Fusin (CXCR4), function as coreceptors in combination with CD4 for HIV-1 invasion. This is the first report of functional expression of chemokine receptors on human neurons. Furthermore, our studies provide evidence for the direct, CD4-independent association of the viral envelope protein of the HIV-1 strain IIIB with the chemokine receptor CXCR4. C1 BERLEX BIOSCI, DEPT PHARMACOL, RICHMOND, CA 94804 USA. UNIV LOUISVILLE, JAMES GRAHAM BROWN CANC CTR, DEPT PATHOL, HENRY VOGT CANC RES INST, LOUISVILLE, KY 40292 USA. UNIV LOUISVILLE, JAMES GRAHAM BROWN CANC CTR, DEPT MED, HENRY VOGT CANC RES INST, LOUISVILLE, KY 40292 USA. UNIV PENN, MED CTR, DEPT MED, PHILADELPHIA, PA 19104 USA. UNIV PENN, MED CTR, DEPT MICROBIOL, PHILADELPHIA, PA 19104 USA. UNIV PENN, MED CTR, DEPT NEUROL, PHILADELPHIA, PA 19104 USA. NCI, CLIN SERV PROGRAM, SAIC FREDERICK, FREDERICK, MD 21702 USA. RP Hesselgesser, J (reprint author), BERLEX BIOSCI, DEPT IMMUNOL, 15049 SAN PABLO AVE, RICHMOND, CA 94804 USA. NR 47 TC 254 Z9 258 U1 0 U2 3 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD FEB 1 PY 1997 VL 7 IS 2 BP 112 EP 121 DI 10.1016/S0960-9822(06)00055-8 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA WH226 UT WOS:A1997WH22600024 PM 9024623 ER PT J AU Wade, PA Wolffe, AP AF Wade, PA Wolffe, AP TI Chromatin: Histone acetyltransferases in control SO CURRENT BIOLOGY LA English DT Article ID YEAST; DNA AB Several transcriptional regulators have been found to act as enzymes that acetylate histones. The targeted past-translational modification of histones within regulatory nucleoprotein complexes provides an attractive mechanism for controlling transcription within a chromatin environment. RP Wade, PA (reprint author), NICHHD,MOL EMBRYOL LAB,NIH,BLDG 18T,ROOM 106,BETHESDA,MD 20892, USA. NR 13 TC 49 Z9 49 U1 0 U2 2 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD FEB 1 PY 1997 VL 7 IS 2 BP R82 EP R84 DI 10.1016/S0960-9822(06)00042-X PG 3 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA WH226 UT WOS:A1997WH22600011 PM 9081669 ER PT J AU Minton, AP AF Minton, AP TI Influence of excluded volume upon macromolecular structure and associations in 'crowded' media SO CURRENT OPINION IN BIOTECHNOLOGY LA English DT Article ID BOVINE SERUM-ALBUMIN; SELF-ASSOCIATION; CYTOSKELETAL ELEMENTS; INDUCED ORGANIZATION; PROTEIN SOLUTIONS; THERMODYNAMIC NONIDEALITY; CONCENTRATED PROTEIN; ESCHERICHIA-COLI; FILAMENT BUNDLES; OSMOTIC-STRESS AB Results of experimental studies published since the last major review of excluded volume effects in biopolymer solutions in 1993 add to our appreciation of the scope and magnitude of such effects. Recent theoretical studies have improved incrementally our ability to understand and model excluded volume effects in simple model systems. RP Minton, AP (reprint author), NIDDKD,BIOCHEM PHARMACOL LAB,NIH,BLDG 8,ROOM 226,BETHESDA,MD 20892, USA. NR 44 TC 137 Z9 139 U1 0 U2 14 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0958-1669 J9 CURR OPIN BIOTECH JI Curr. Opin. Biotechnol. PD FEB PY 1997 VL 8 IS 1 BP 65 EP 69 DI 10.1016/S0958-1669(97)80159-0 PG 5 WC Biochemical Research Methods; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA WF599 UT WOS:A1997WF59900010 PM 9013656 ER PT J AU Recipon, H Makalowski, W AF Recipon, H Makalowski, W TI The biologist and the World Wide Web: An overview of the search engines technology, current status and future perspectives SO CURRENT OPINION IN BIOTECHNOLOGY LA English DT Article RP Recipon, H (reprint author), NIH,NATL CTR BIOTECHNOL INFORMAT,BLDG 38A,ROOM 8N-805,BETHESDA,MD 20894, USA. RI Makalowski, Wojciech/I-2843-2016 NR 2 TC 6 Z9 7 U1 1 U2 1 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0958-1669 J9 CURR OPIN BIOTECH JI Curr. Opin. Biotechnol. PD FEB PY 1997 VL 8 IS 1 BP 115 EP 118 DI 10.1016/S0958-1669(97)80166-8 PG 4 WC Biochemical Research Methods; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA WF599 UT WOS:A1997WF59900017 PM 9013663 ER PT J AU Makalowski, W Recipon, H AF Makalowski, W Recipon, H TI Web alert - Analytical biotechnology SO CURRENT OPINION IN BIOTECHNOLOGY LA English DT Article RP Makalowski, W (reprint author), NIH,NATL CTR BIOTECHNOL INFORMAT,BLDG 38A,ROOM 8N-805,BETHESDA,MD 20894, USA. RI Makalowski, Wojciech/I-2843-2016 NR 0 TC 0 Z9 0 U1 1 U2 1 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0958-1669 J9 CURR OPIN BIOTECH JI Curr. Opin. Biotechnol. PD FEB PY 1997 VL 8 IS 1 BP 119 EP 119 DI 10.1016/S0958-1669(97)80167-X PG 1 WC Biochemical Research Methods; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA WF599 UT WOS:A1997WF59900018 PM 9013662 ER PT J AU Yamada, KM Geiger, B AF Yamada, KM Geiger, B TI Molecular interactions in cell adhesion complexes SO CURRENT OPINION IN CELL BIOLOGY LA English DT Article ID PROTEIN-TYROSINE KINASE; EPIDERMAL GROWTH-FACTOR; CYTOPLASMIC DOMAIN; SIGNAL-TRANSDUCTION; EXTRACELLULAR-MATRIX; INTEGRIN BETA(1C); FACTOR RECEPTOR; C-SRC; SUBUNIT; PHOSPHORYLATION AB Cell adhesions consist of multimolecular protein complexes of transmembrane adhesion receptors anchoring intracellular cytoskeletal structural proteins and signal transduction molecules. Recent advances reveal that components of cell adhesion complexes display multiple interactions and functions, which cooperate to mediate both cell adhesion and signaling. Cell-matrix and cell-cell adhesions can serve as both recipients and generators of signaling information, using hierarchical and synergistic molecular interactions regulated by aggregation, conformational changes, phosphorylation, and tension. C1 WEIZMANN INST SCI,DEPT MOL CELL BIOL,IL-76100 REHOVOT,ISRAEL. RP Yamada, KM (reprint author), NIDR,CRANIOFAC DEV BIOL & REGENERAT BRANCH,NIH,BLDG 30,ROOM 421,30 CONVENT DR,MSC 4370,BETHESDA,MD 20892, USA. OI Yamada, Kenneth/0000-0003-1512-6805 NR 69 TC 444 Z9 460 U1 0 U2 17 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0955-0674 J9 CURR OPIN CELL BIOL JI Curr. Opin. Cell Biol. PD FEB PY 1997 VL 9 IS 1 BP 76 EP 85 DI 10.1016/S0955-0674(97)80155-X PG 10 WC Cell Biology SC Cell Biology GA WF597 UT WOS:A1997WF59700012 PM 9013677 ER PT J AU SchartonKersten, TM Sher, A AF SchartonKersten, TM Sher, A TI Role of natural killer cells in innate resistance to protozoan infections SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID CRYPTOSPORIDIUM-PARVUM INFECTION; NECROSIS-FACTOR-ALPHA; COMBINED IMMUNODEFICIENCY MICE; INTERFERON-GAMMA-PRODUCTION; LEISHMANIA-MAJOR INFECTION; GROWTH-FACTOR-BETA; TOXOPLASMA-GONDII; IFN-GAMMA; NK-CELLS; GLYCOSYLPHOSPHATIDYLINOSITOL TOXIN AB Natural killer cells are now recognized as major effectors of innate resistance to protozoan parasites. The principal mechanism by which they control the growth of these pathogens is indirect, involving cytokine production rather than cytolytic activity. Recent studies have identified a series of positive and negative signals provided by cytokines and cellular interactions which regulate protozoa-induced natural killer cell function. RP SchartonKersten, TM (reprint author), NIAID,IMMUNOBIOL SECT,PARASIT DIS LAB,9000 ROCKVILLE PIKE,BLDG 4,ROOM 126,BETHESDA,MD 20892, USA. NR 86 TC 83 Z9 84 U1 0 U2 1 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD FEB PY 1997 VL 9 IS 1 BP 44 EP 51 DI 10.1016/S0952-7915(97)80157-4 PG 8 WC Immunology SC Immunology GA WL184 UT WOS:A1997WL18400007 PM 9039777 ER PT J AU Ramsden, DA vanGent, DC Gellert, M AF Ramsden, DA vanGent, DC Gellert, M TI Specificity in V(D)J recombination: New lessons from biochemistry and genetics SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID DEPENDENT PROTEIN-KINASE; BROKEN DNA-MOLECULES; MOUSE THYMOCYTES; STRAND TRANSFER; IMMUNE-SYSTEM; MECHANISM; SIGNAL; RAG-1; REARRANGEMENT; RESOLUTION AB Recent in vitro work on V(D)J recombination has helped to clarify its mechanism. The first stage of the reaction, which can be reproduced with the purified RAG1 and RAG2 proteins, is a site-specific cleavage that generates the same broken DNA species found in vivo. The cleavage reaction is closely related to known types of transpositional recombination, such as that of HIV integrase. All the site specificity of V(D)J recombination, including the 12/23 rule, is determined by the RAG proteins. The later steps largely overlap with the repair of radiation-induced DNA double-strand breaks, as indicated by the identity of several newly characterized factors involved in repair. These developments open the way for a thorough biochemical study of V(D)J recombination. C1 ERASMUS UNIV ROTTERDAM,DEPT CELL BIOL & GENET,NL-3000 DR ROTTERDAM,NETHERLANDS. RP Ramsden, DA (reprint author), NIDDKD,MOL BIOL LAB,NIH,BLDG 5,BETHESDA,MD 20892, USA. NR 42 TC 29 Z9 30 U1 1 U2 1 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD FEB PY 1997 VL 9 IS 1 BP 114 EP 120 DI 10.1016/S0952-7915(97)80167-7 PG 7 WC Immunology SC Immunology GA WL184 UT WOS:A1997WL18400017 PM 9039786 ER PT J AU Dobson, CM Ptitsyn, OB AF Dobson, CM Ptitsyn, OB TI Folding and binding from theory to therapy - Editorial overview SO CURRENT OPINION IN STRUCTURAL BIOLOGY LA English DT Editorial Material C1 NCI,MATH BIOL LAB,NIH,BETHESDA,MD 20892. RUSSIAN ACAD SCI,INST PROT RES,PUSHCHINO 142292,RUSSIA. RP Dobson, CM (reprint author), UNIV OXFORD,OXFORD CTR MOL SCI,NEW CHEM LAB,S PARKS RD,OXFORD OX 3XT,ENGLAND. NR 0 TC 14 Z9 14 U1 0 U2 2 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0959-440X J9 CURR OPIN STRUC BIOL JI Curr. Opin. Struct. Biol. PD FEB PY 1997 VL 7 IS 1 BP 1 EP 2 DI 10.1016/S0959-440X(97)80001-2 PG 2 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA WK090 UT WOS:A1997WK09000001 PM 9032069 ER PT J AU Eaton, WA Munoz, V Thompson, PA Chan, CK Hofrichter, J AF Eaton, WA Munoz, V Thompson, PA Chan, CK Hofrichter, J TI Submillisecond kinetics of protein folding SO CURRENT OPINION IN STRUCTURAL BIOLOGY LA English DT Article ID 2-STATE TRANSITION; DOMAIN; PRINCIPLES; ENERGY; BUNDLE; EVENTS; ACID AB New experimental methods permit observation of protein folding and unfolding on the previously inaccessible nanosecond-microsecond timescale. These studies are beginning to establish times for the elementary motions in protein folding - secondary structure and loop formation, local hydrophobic collapse, and global collapse to the compact denatured state. They permit an estimate of about one microsecond for the shortest time in which a protein can possibly fold. RP Eaton, WA (reprint author), NIDDKD,CHEM PHYS LAB,NIH,BLDG 5,BETHESDA,MD 20892, USA. NR 49 TC 181 Z9 182 U1 0 U2 7 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0959-440X J9 CURR OPIN STRUC BIOL JI Curr. Opin. Struct. Biol. PD FEB PY 1997 VL 7 IS 1 BP 10 EP 14 DI 10.1016/S0959-440X(97)80003-6 PG 5 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA WK090 UT WOS:A1997WK09000003 PM 9032067 ER PT J AU Rice, PA AF Rice, PA TI Making DNA do a U-turn: IHF and related proteins SO CURRENT OPINION IN STRUCTURAL BIOLOGY LA English DT Article ID INTEGRATION HOST FACTOR; ESCHERICHIA-COLI; HU PROTEIN; BINDING PROTEIN; CRYSTAL-STRUCTURE; ADENINE TRACT; MINOR-GROOVE; TF1; COMPLEXES; SITES AB IHF and HU belong to a family of proteins that introduce sharp bends into DNA and act as accessory factors in a variety of cellular processes in prokaryotes. In addition to the crystal structure of IHF bound to DNA, the past year has seen a number of advances in the understanding of the interactions of these proteins with DNA in solution. RP Rice, PA (reprint author), NIDDKD,MOL BIOL LAB,NIH,BLDG 5,ROOM 237,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 61 TC 77 Z9 77 U1 2 U2 4 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0959-440X J9 CURR OPIN STRUC BIOL JI Curr. Opin. Struct. Biol. PD FEB PY 1997 VL 7 IS 1 BP 86 EP 93 DI 10.1016/S0959-440X(97)80011-5 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA WK090 UT WOS:A1997WK09000011 PM 9032059 ER PT J AU Lin, JJ Maeda, R Ong, RC Kim, JB Lee, LM Kung, HF Maeno, M AF Lin, JJ Maeda, R Ong, RC Kim, JB Lee, LM Kung, HF Maeno, M TI XBMP-1B (Xtld), a Xenopus homolog of dorso-ventral polarity gene in Drosophila, modifies tissue phenotypes of ventral explants SO DEVELOPMENT GROWTH & DIFFERENTIATION LA English DT Article DE bone morphogenetic protein-1; dorso-ventral axis; tolloid; Xenopus ID BONE MORPHOGENETIC PROTEIN-1; ANIMAL POLE TISSUE; SEA-URCHIN; MESODERM; EXPRESSION; EMBRYO; SIGNALS; BMP-1; DIFFERENTIATION; PROTEASE AB Previously we have isolated a Xenopus cDNA homolog of bone morphogenetic protein-1 (XBMP-1A). In the present report we describe a new cDNA clone called XBMP-1B (or Xtld) from a Xenopus embryonic library. Sequence analysis indicates that these two clones share an identical N-terminal sequence, including a region of metalloprotease domain, three copies of a repeat first found in complement proteins C1r/s and an epidermal growth factor (EGF)-like sequence. XBMP-1B protein has an additional copy of an EGF-like sequence followed by two copies of complement 1 r/s repeat in the C-terminus. The overall protein structure predicted from the XBMP-1B sequence reveals that it encodes a protein homologous to Drosophila tolloid. Three XBMP-1 transcripts (2.9, 5.2 and 6.6 kb) were detected by northern blot analysis. However, the 2.9 kb transcript hybridized specifically with XBMP-1A and the 5.2 and 6.6 kb transcripts hybridized with XBMP-1B. In Drosophila, a major function of tolloid is to augment the activity of the decapentaplegic gene product, a close relative of tumor growth factor (TGF)-beta superfamily members, BMP-2/4. Although XBMP-1 and XBMP-4 are detected in various adult tissues of Xenopus, the expression pattern of these two genes was not tightly correlated. In the embryo, the expression of XBMP-1 increased gradually from the morula to the swimming tadpole stages. Injection of XBMP-1B RNA into the ventral blastomeres at the 4-cell stage caused an elongation of the ventral marginal zone explants and converted globin-positive blood cells to mesenchymal and muscle tissues at later stages. It was shown that XBMP-1A was less active and a 1A mutant lacking the signal sequence was inactive. Further studies revealed that injection of XBMP-1B RNA into the ventral marginal zone induced up-regulation of dorsal marginal zone markers, such as goosecoid and chordin, at the gastrulation stage. These data indicate that XBMP-1 may have a role in determining dorso-ventral patterning in Xenopus, but in a different way from the dpp/tolloid system demonstrated in Drosophila. C1 NIIGATA UNIV,FAC SCI,DEPT BIOL,NIIGATA 95021,JAPAN. NCI,FREDERICK CANC RES & DEV CTR,DEPT BASIC SCI,LAB BIOCHEM PHYSIOL,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,RECOMBINANT DNA LAB,SAIC,FREDERICK,MD 21702. NR 30 TC 22 Z9 23 U1 0 U2 0 PU BLACKWELL SCIENCE PI CARLTON PA 54 UNIVERSITY ST, P O BOX 378, CARLTON VICTORIA 3053, AUSTRALIA SN 0012-1592 J9 DEV GROWTH DIFFER JI Dev. Growth Diff. PD FEB PY 1997 VL 39 IS 1 BP 43 EP 51 PG 9 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA WX471 UT WOS:A1997WX47100006 PM 9079034 ER PT J AU Sheng, HZ Bertuzzi, S Chiang, C Shawlot, W Taira, M Dawid, I Westphal, H AF Sheng, HZ Bertuzzi, S Chiang, C Shawlot, W Taira, M Dawid, I Westphal, H TI Expression of murine Lhx5 suggests a role in specifying the forebrain SO DEVELOPMENTAL DYNAMICS LA English DT Article DE Lhx5; forebrain; LIM; homeobox ID SPATIALLY RESTRICTED EXPRESSION; LIM DOMAIN; MOUSE DEVELOPMENT; HOMEOBOX GENES; 2 MEMBERS; FAMILY; PATTERNS; PROTEIN; CNS; HOMEODOMAIN AB A LIM homeobox gene, Lim5, is known to be expressed in the forebrain of Xenopus and zebrafish (Toyama et al. [1995] Dev. Biol. 170:583-593). Results from developmental and comparative studies of its mouse ortholog, Lhx5, indicate that this gene may play important roles in forebrain development. Lhx5 expression is detected in the most anterior portion of the neural tube at the headfold stage, overlapping partially with Otx2 expression domain, After neural tube closure, Lhx5 is expressed as a transverse stripe, covering most of the diencephalic primordium. This expression recedes to restricted areas as Dlx gene expression occurs; By midgestation, both genes, Lhx5 and Dlx5, are expressed in the diencephalon and ventral telencephalon in an alternating complementary pattern. It may be that Dlx inhibits Lhx5, and this may represent a step of early regionalization of the forebrain. Lhx5 is also expressed in midbrain, hindbrain, and spinal cord, overlapping extensively with Lhx1 starting from day E10.5 of gestation. The early, persistent, and dynamic expression of Lhx5 suggests a regulatory function in forebrain formation. (C) 1997 Wiley-Liss, Inc. C1 NICHHD,LAB MAMMALIAN GENES & DEV,NIH,BETHESDA,MD 20892. NICHHD,GENET MOL LAB,NIH,BETHESDA,MD 20892. UNIV TEXAS,MD ANDERSON CANC CTR,DEPT MOL GENET,HOUSTON,TX 77030. NR 42 TC 62 Z9 64 U1 1 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD FEB PY 1997 VL 208 IS 2 BP 266 EP 277 DI 10.1002/(SICI)1097-0177(199702)208:2<266::AID-AJA13>3.0.CO;2-1 PG 12 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA WF520 UT WOS:A1997WF52000013 PM 9022063 ER PT J AU Eastman, RC Cowie, CC Harris, MI AF Eastman, RC Cowie, CC Harris, MI TI Undiagnosed diabetes or impaired glucose tolerance and cardiovascular risk SO DIABETES CARE LA English DT Editorial Material ID DISEASE; ONSET RP Eastman, RC (reprint author), NIDDKD,DIV DIABET ENDOCRINOL & METAB DIS,NIH,BETHESDA,MD 20892, USA. NR 14 TC 39 Z9 39 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD FEB PY 1997 VL 20 IS 2 BP 127 EP 128 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA WC851 UT WOS:A1997WC85100001 PM 9118758 ER PT J AU Cowie, CC Harris, MI AF Cowie, CC Harris, MI TI Ambulatory medical care for non-Hispanic whites, African-Americans, and Mexican-Americans with NIDDM in the US SO DIABETES CARE LA English DT Article ID DEPENDENT DIABETES-MELLITUS; RENAL-DISEASE; RACE; ACCESS AB OBJECTIVE - To assess whether medical care for diabetes is different among non-Hispanic whites, African-Americans, and Mexican-Americans with NIDDM. RESEARCH DESIGN END METHODS - A questionnaire was administered to a representative U.S. sample of 2,170 noninstitutionalized adults with NIDDM. Information was obtained on physician visits, hyperglycemic therapy, monitoring of glycemic control, screening for and monitoring of complications, and diabetes education. RESULTS - About 90% of subjects had a regular diabetes physician, and the physician visit rate was similar by race (median of four visits per year). African-Americans were more likely to be treated with insulin (51.9%) than non-Hispanic whites (35.9%, P < 0.0001) and Mexican-Americans (46.2%). Among insulin-treated subjects, African-Americans were less likely to use multiple daily insulin injections (35.1 vs. 53.8% of non-Hispanic whites [P < 0.0001] and 50.5% of Mexican-Americans [P = 0.027]) and were less likely to self-monitor their blood glucose at least once per day (14.0 vs. 29.8% of non-Hispanic whites [P < 0.0001] and 29.0% of Mexican-Americans). The rates of visits to specialists for diabetes complications, physician testing of blood glucose, and screening For hypertension, retinopathy, and foot problems were not substantially different among the three race/ethnic groups. A higher proportion of African-Americans (43.3%) than non-Hispanic whites (31.5%, P < 0.0001) and Mexican-Americans (25.6%, P = 0.001) had received patient education; however, the median number of hours of instruction was lower for African-Americans. CONCLUSIONS - The frequency of diabetes care is similar among non-Hispanic whites, African-Americans, and Mexican-Americans. The major differences relate to methods of glycemic control and patient education. C1 SOCIAL & SCI SYST,BETHESDA,MD. RP Cowie, CC (reprint author), NIDDKD,NIH,NATCHER BLDG,RM 5AN24A,45 CTR DR,BETHESDA,MD 20892, USA. FU NIDDK NIH HHS [N01-DK-1-2282] NR 23 TC 56 Z9 56 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD FEB PY 1997 VL 20 IS 2 BP 142 EP 147 DI 10.2337/diacare.20.2.142 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA WC851 UT WOS:A1997WC85100004 PM 9118761 ER PT J AU Hansen, AJ Lee, YH Gonzalez, FJ Mackenzie, PI AF Hansen, AJ Lee, YH Gonzalez, FJ Mackenzie, PI TI HNF1 alpha activates the rat UDP glucuronosyltransferase UGT2B1 gene promoter SO DNA AND CELL BIOLOGY LA English DT Article ID ALBUMIN GENE; HEPATOMA-CELLS; BINDING-PROTEINS; LIVER; TRANSCRIPTION; EXPRESSION; HNF-1; HOMEOPROTEIN AB The rat UDP glucuronosyltransferase UGT2B1 is expressed mainly in the liver where it glucuronidates steroids and environmental toxins and carcinogens. A region between -42 and -55 bp upstream from the UGT2B1 gene transcription start site was previously identified as sharing sequence similarity with the hepatocyte nuclear factor 1 (HNF1) consensus binding site. In this study, the importance of this region in the regulation of the UGT2B1 gene was confirmed by functional and DNA binding assays. A minimal UGT2B1 gene promoter containing the putative HNF1 binding site was fused to the CAT reporter gene and transfected into HepG2 cells, Only low levels of CAT activity were detected, This activity was increased 50-fold when an HNF1 alpha expression vector was co-transfected with the UGT2B1 promoter CAT construct but was not altered when a HNF1 beta expression vector was used. A UGT2B1 promoter construct with the HNF1-like region deleted was not activated by either co-transfected HNF1 expression vector. DNase 1 footprinting and gel-shift analysis demonstrated that nuclear proteins present in both HepG2 cells and rat liver bind to the HNF1-like element. The presence of HNF1 alpha in these nuclear proteins that bind to the HNF1-like element was confirmed by supershift analysis with antisera to HNF1 alpha. Specific binding of nuclear proteins to the HNF1-like dement was not seen in extracts from three cell lines derived from nonhepatic tissues. These data strongly suggest that the liver-enriched factor HNF1 alpha binds to, and activates, the UGT2B1 gene promoter. C1 FLINDERS MED CTR,DEPT CLIN PHARMACOL,BEDFORD PK,SA 5042,AUSTRALIA. NCI,NIH,BETHESDA,MD 20891. NR 34 TC 23 Z9 23 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1044-5498 J9 DNA CELL BIOL JI DNA Cell Biol. PD FEB PY 1997 VL 16 IS 2 BP 207 EP 214 DI 10.1089/dna.1997.16.207 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity GA WL018 UT WOS:A1997WL01800010 PM 9052741 ER PT J AU Gerloff, C Toro, C Uenishi, N Cohen, LG Leocani, L Hallett, M AF Gerloff, C Toro, C Uenishi, N Cohen, LG Leocani, L Hallett, M TI Steady-state movement-related cortical potentials: A new approach to assessing cortical activity associated with fast repetitive finger movements SO ELECTROENCEPHALOGRAPHY AND CLINICAL NEUROPHYSIOLOGY LA English DT Article DE movement-related cortical potentials; topographic mapping; sensorimotor cortex; finger movements; cortical physiology; nyquist value; Bereitschaftspotential ID HUMAN MOTOR CORTEX; MAGNETIC-FIELD; TOPOGRAPHY; ARM AB Traditionally, studies of movement-related cortical potentials have focused on the preparation of single self-paced movements performed slowly. We studied MRCPs elicited by metronome-paced, fast repetitive finger movements (2/s) with 28-channel(10 normal subjects) and 122-channel (two subjects) EEG. EMG-locked averaging of 500 ms time windows (300 ms before to 200 ms after each EMG onset) produced a distinct pattern of phasic MRCPs (steady-state MRCPs). The main components were a pre-movement peak (pre-MP), 57 ms before EMG onset, and a post-movement peak (post-MP), 93 ms after EMG onset. From timing information and topographic mapping results, we propose that the pre-MF is largely generated by a tangential source in the anterior bank of the central sulcus and reflects precentral motor processing, whereas the post-MP is generated in the posterior bank of the central sulcus and represents post-central feedback processing. Steady-state MRCPs require actual recording times of less than 10 min, and show excellent intersession reproducibility. These characteristics may make them convenient for studying sensorimotor cortex activity experimentally and clinically. (C) 1997 Elsevier Science Ireland Ltd. RP Gerloff, C (reprint author), NINCDS,HUMAN MOTOR CONTROL SECT,MED NEUROL BRANCH,NIH,BLDG 10,ROOM 5N226,10 CTR DR MSC 1428,BETHESDA,MD 20892, USA. NR 24 TC 53 Z9 53 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0013-4694 J9 ELECTROEN CLIN NEURO JI Electroencephalogr. Clin. Neurophysiol. PD FEB PY 1997 VL 102 IS 2 BP 106 EP 113 DI 10.1016/S0921-884X(96)96039-7 PG 8 WC Engineering, Biomedical; Clinical Neurology SC Engineering; Neurosciences & Neurology GA WJ735 UT WOS:A1997WJ73500005 PM 9060861 ER PT J AU HernandezSanchez, C Wood, TL LeRoith, D AF HernandezSanchez, C Wood, TL LeRoith, D TI Developmental and tissue-specific sulfonylurea receptor gene expression SO ENDOCRINOLOGY LA English DT Article ID SENSITIVE POTASSIUM CHANNEL; K+ CHANNELS; BINDING-SITES; ANTIDIABETIC SULFONYLUREAS; GLIBENCLAMIDE BINDING; INSULIN-SECRETION; H-3 GLIBENCLAMIDE; PANCREATIC-ISLETS; MOUSE ISLETS; GLUCOSE AB We have studied the developmental regulation of mouse sulfonylurea receptor (SUR) gene expression throughout several embryonic stages as well as in the adult mouse. To this end we used a 229-bp mouse complementary DNA corresponding to the 3'-end of the SUR gene for in situ hybridization and solution hybridization/ribonuclease protection assays. We found that the SUR gene was expressed as early as embryonic day 12 in the developing pancreas, heart, and central nervous system. These tissues maintained significant levels of SUR messenger RNA (mRNA) throughout development. In addition, SUR mRNA was detected in the submandibular gland, anterior duodenum, dorsal root ganglia, lens, retina, and vibrissae by late developmental stages. SUR mRNA is widely distributed in adult mouse tissues, with the exception of the liver. In the adult pancreas, the SUR gene was expressed exclusively in endocrine tissue. Although significant levels of SUR mRNA were broadly seen throughout the brain, neurons of the cerebellum, hippocampus, and thalamus had especially high levels of SUR mRNA. These findings support the idea that the SUR has important functions in many other tissues in addition to the islets of the pancreas. C1 PENN STATE UNIV, COLL MED, DEPT ANAT & NEUROSCI, HERSHEY, PA 17033 USA. RP HernandezSanchez, C (reprint author), NIDDKD, SECT MOL & CELLULAR PHYSIOL,DIABET BRANCH,NIH, ROOM 8S235A, BLDG 10, BETHESDA, MD 20892 USA. RI Hernandez Sanchez, Catalina/N-1737-2014 OI Hernandez Sanchez, Catalina/0000-0002-0846-5019 NR 39 TC 19 Z9 20 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 FEB PY 1997 VL 138 IS 2 BP 705 EP 711 DI 10.1210/en.138.2.705 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA WC646 UT WOS:A1997WC64600027 PM 9003005 ER PT J AU Oldenburg, NBE EvansStorms, RB Cidlowski, JA AF Oldenburg, NBE EvansStorms, RB Cidlowski, JA TI In vivo resistance to glucocorticoid-induced apoptosis in rat thymocytes with normal steroid receptor function in vitro SO ENDOCRINOLOGY LA English DT Article ID T-CELL RECEPTOR; INTERNUCLEOSOMAL FRAGMENTATION; ANTIPEPTIDE ANTIBODIES; DEOXYRIBONUCLEIC-ACID; DNA FRAGMENTATION; EPITHELIAL-CELLS; IL-2 PROTECTS; MOUSE THYMUS; BONE-MARROW; DEATH AB Previous studies have shown that although the majority of rat thymic lymphocytes are sensitive to glucocorticoid-induced apoptosis in vivo, a small population of mature thymic lymphocytes remains even after high dose steroid administration. Here, we describe experiments that were performed to understand the molecular basis of the resistance of these cells to glucocorticoid-induced apoptosis. Adrenalectomized rats were treated for 72 h with a bolus dose (5 mg/kg body weight) of dexamethasone to produce a population of thymocytes that survived glucocorticoid administration. Reinjection of these animals with equivalent doses of dexamethasone failed to induce further thymic regression or apoptosis in these cells. Glucocorticoid receptor number and receptor binding affinity for dexamethasone were similar in control and resistant thymocytes. Western blot analysis using epitope-purified antiglucocorticoid receptor antibodies confirmed this observation. To delineate the mechanism of resistance, we evaluated whether cells resistant to dexamethasone in. vivo showed any response to this glucocorticoid in vitro. The ability of glucocorticoid to inhibit [H-3]lysine incorporation into protein in cells treated with dexamethasone in vitro was equivalent to control cells, indicating that glucocorticoid receptor function was normal in both populations. To evaluate whether in vivo glucocorticoid-resistant thymocytes retain any capacity to undergo apoptosis, in vitro studies were performed on these cells using the calcium ionophore A23187 to induce programmed cell death. Cleavage of chromatin into 30- to 60-kilobase fragments or oligonucleosomal fragments characteristic of apoptosis was observed in both sensitive and resistant thymocytes treated in vitro with A23187. Cells resistant to glucocorticoid in vivo unexpectedly exhibited internucleosomal cleavage of chromatin and apoptosis in response to dexamethasone in vitro. We examined the levels of the apoptosis suppressor Bcl-2 in thymocytes isolated from control and 72 h dexamethasone-treated rats to determine whether increased expression of this protein could explain the resistance to glucocorticoid-induced apoptosis that we observed. Both glucocorticoid-sensitive and -resistant thymocytes expressed similar levels of Bcl-2. Together, these data indicate that resistance to glucocorticoid in vivo is not due to alteration of the glucocorticoid receptor or to expression of Bcl-2, but rather to some endogenous thymic factor and/or cell-to-cell contact that probably alters glucocorticoid receptor signaling. C1 NIEHS, NIH, CELLULAR & MOL PHARMACOL LAB, RES TRIANGLE PK, NC 27709 USA. NR 53 TC 19 Z9 23 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 FEB PY 1997 VL 138 IS 2 BP 810 EP 818 DI 10.1210/en.138.2.810 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA WC646 UT WOS:A1997WC64600041 PM 9003019 ER PT J AU Usdin, TB AF Usdin, TB TI Evidence for a parathyroid hormone-2 receptor selective ligand in the hypothalamus SO ENDOCRINOLOGY LA English DT Article ID PEPTIDE AB The PTH2 receptor is expressed in several brain nuclei but we have been unable to detect mRNA encoding PTH, which is the only known ligand for the PTH2 receptor, in the brain. We now have evidence for a PTH2 receptor selective ligand in an acid-acetone extract made from bovine hypothalamus. The partially purified extract activates the PTH2 receptor more effectively than it activates the PTH/PTHrP receptor, while PTH activates these two receptors at similar concentration. The activity appears immunologically distinct from PTH and its effect is potently antagonized by [D-Trp(12)]bPTH(7-34). These data provide evidence for a biologically active peptide, which may be related to PTH, and which is a potential new neurotransmitter or hormone. RP Usdin, TB (reprint author), NIMH, BLDG 36, RM 3A17, 36 CONVENT DR, BETHESDA, MD 20892 USA. NR 10 TC 56 Z9 56 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 FEB PY 1997 VL 138 IS 2 BP 831 EP 834 DI 10.1210/en.138.2.831 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA WC646 UT WOS:A1997WC64600044 PM 9003022 ER PT J AU Neill, JD Duck, LW Sellers, JC Musgrove, LC Scheschonka, A Druey, KM Kehrl, JH AF Neill, JD Duck, LW Sellers, JC Musgrove, LC Scheschonka, A Druey, KM Kehrl, JH TI Potential role for a regulator of G protein signaling (RGS3) in gonadotropin-releasing hormone (GnRH) stimulated desensitization SO ENDOCRINOLOGY LA English DT Article ID RECEPTORS; RESPONSES; CELLS AB The cellular and molecular mechanisms of gonadotrope desensitization are unknown but transduction of the GnRH signal is known to involve sequentially the GnRH receptor, Gq alpha protein, phospllolipase C beta-1, inositol-1,4,5-trisphosphate (IP3), and intracellular Ca+2 release. Here, we report the results of studies of a new family of proteins known as regulators of G protein signaling (RGS) that recently have been implicated in desensitization of several ligand induced processes. Using DNA-mediated transfection, we coexpressed the GnRH receptor and RGS1, 2, 3, or 4 in COS-1 cells. Control cells and those expressing RGS1, 2; and 4 produced five fold increases in IP3 levels during the 30 sec after treatment with GnRH. In contrast, RGS3 expression suppressed by 75% the GnRH-induced IP3 responses. RGS3 was shown to bind Gq alpha protein in a model in vitro system: recombinant RGS3-glutathione-S-transferase (GST) fusion protein bound five-fold more S-35-met labeled Gq alpha protein than did with GST alone, suggesting that the mechanism of RGS3 action is attenuation of Gq alpha protein activation of phospholipase C. RGS3 mRNA and protein were observed to be expressed endogenously in the gonadotropic alpha T3-1 cell line. These results suggest a potential role for RGS3 in modulating the LH secretory responsiveness of the pituitary gonadotrope to GnRH. C1 UNIV ALABAMA, SCH DENT, BIRMINGHAM, AL 35294 USA. NIAID, IMMUNOREGULAT LAB, NIH, BETHESDA, MD 20892 USA. RP Neill, JD (reprint author), UNIV ALABAMA, SCH MED, DEPT PHYSIOL & BIOPHYS, BIRMINGHAM, AL 35294 USA. OI Kehrl, John/0000-0002-6526-159X NR 18 TC 85 Z9 86 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 FEB PY 1997 VL 138 IS 2 BP 843 EP 846 DI 10.1210/en.138.2.843 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA WC646 UT WOS:A1997WC64600047 PM 9003025 ER PT J AU Chen, NY Chen, WY Striker, LJ Striker, GE Kopchick, JJ AF Chen, NY Chen, WY Striker, LJ Striker, GE Kopchick, JJ TI Co-expression of bovine growth hormone (GH) and human GH antagonist genes in transgenic mice SO ENDOCRINOLOGY LA English DT Article ID ANALOG AB Bovine growth hormone (bGH) transgenic (Tg) mice have been shown to possess enhanced growth phenotypes and exhibit severe glomerulosclerosis. One amino acid substitution in GH, i.e. G119R in bGH or G120R in human (h) GH, results in GH antagonists (GHAs). GHA-Tg mice exhibit dwarf phenotypes and normal kidneys. In order to investigate the possibility of GHAs as pharmaceutical agents for the treatment of human diseases with excessive GH levels, we cross bred mice that express bGH with those that express hGHA. Double positive Tg mice were identified that express both genes although at different levels. Kidney histological studies revealed that the double positive Tg mice with high GHA/GH expression ratios possessed normal or near normal kidneys, whereas those with low GHA/GH ratios exhibited glomerulosclerosis similar to GH-Tg mice. Thus, co-expression of GH and GHA genes in vivo results in animal phenotypes and kidney histopathologies which are a reflection of the relative expression levels of each gene. C1 OHIO UNIV, EDISON BIOTECHNOL INST, CELLULAR & MOL BIOL GRP, ATHENS, OH 45701 USA. OHIO UNIV, DEPT SCI BIOL, ATHENS, OH 45701 USA. NIDDKD, METAB DIS BRANCH, RENAL CELL BIOL SECT, NIH, BETHESDA, MD 20892 USA. NR 11 TC 21 Z9 21 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 FEB PY 1997 VL 138 IS 2 BP 851 EP 854 DI 10.1210/en.138.2.851 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA WC646 UT WOS:A1997WC64600049 PM 9003027 ER PT J AU Cunningham, ML Tindall, KR AF Cunningham, ML Tindall, KR TI Mutagenic carcinogens and noncarcinogens in transgenic mice - Response SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Letter RP Cunningham, ML (reprint author), NIEHS,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 1 TC 1 Z9 1 U1 0 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 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD FEB PY 1997 VL 105 IS 2 BP 163 EP 163 DI 10.2307/3433232 PG 1 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA WU342 UT WOS:A1997WU34200005 ER PT J AU Langford, CA AF Langford, CA TI Complications of cyclophosphamide therapy SO EUROPEAN ARCHIVES OF OTO-RHINO-LARYNGOLOGY LA English DT Review DE cyclophosphamide; toxicity; autoimmune disease; vasculitis; Wegener's granulomatosis ID SYSTEMIC LUPUS-ERYTHEMATOSUS; PNEUMOCYSTIS-CARINII PNEUMONIA; INDUCED HEMORRHAGIC CYSTITIS; INDUCED OVARIAN FAILURE; CYTO-TOXIC DRUGS; RHEUMATOID-ARTHRITIS; WEGENERS GRANULOMATOSIS; PULSE CYCLOPHOSPHAMIDE; HODGKINS-DISEASE; CONTROLLED TRIAL AB Cyclophosphamide is a powerful immunosuppressive agent that is commonly used clinically to treat neoplastic and inflammatory diseases affecting various sites, including the head and neck. The pharmacology of cyclophosphamide is reviewed with an emphasis on its toxicities and strategies for minimizing therapeutic adverse effects. Principles of therapy are discussed and illustrated by the use of cyclophosphamide in the treatment of Wegener's granulomatosis, a form of systemic vasculitis with prominent head and neck manifestations. RP Langford, CA (reprint author), NIAID,IMMUNOREGULAT LAB,IMMUNOL DIS SECT,NIH,BLDG 10,ROOM 11B-13,BETHESDA,MD 20892, USA. NR 64 TC 19 Z9 20 U1 1 U2 5 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0937-4477 J9 EUR ARCH OTO-RHINO-L JI Eur. Arch. Oto-Rhino-Laryn. PD FEB PY 1997 VL 254 IS 2 BP 65 EP 72 DI 10.1007/BF01526181 PG 8 WC Otorhinolaryngology SC Otorhinolaryngology GA WM181 UT WOS:A1997WM18100001 PM 9065658 ER PT J AU Costa, J Ashford, DA Nimtz, M Bento, I Frazao, C Esteves, CL Faro, CJ Kervinen, J Pires, E Verissimo, P Wlodawer, A Carrondo, MA AF Costa, J Ashford, DA Nimtz, M Bento, I Frazao, C Esteves, CL Faro, CJ Kervinen, J Pires, E Verissimo, P Wlodawer, A Carrondo, MA TI The glycosylation of the aspartic proteinases from barley (Hordeum vulgare L) and cardoon (Cynara cardunculus L) SO EUROPEAN JOURNAL OF BIOCHEMISTRY LA English DT Article DE aspartic proteinase; Cynara cardunculus; glycosylation; Hordeum vulgare ID N-LINKED OLIGOSACCHARIDES; CATHEPSIN-D; HUMAN RENIN; SECRETION; ENZYME; PURIFICATION; SPECIFICITY; EXPRESSION; LECTIN; GRAINS AB Plant aspartic proteinases characterised at the molecular level contain one or more consensus N-glycosylation sites [Runeberg-Roos, P., Tormakangas, K. & Ostman, A. (1991) Eur. J. Biochem. 202, 1021-1027; Asakura, T., Watanabe, H., Abe, K. & Arai, S. (1995) Eur. J. Biochem. 232, 77-83; Verissimo, P., Faro, C., Moir, A. J. G., Lin, Y., Tang, J. & Pires, E. (1996) Eur. J. Biochem. 235, 762-768]. We found that the glycosylation sites are occupied for the barley (Hordeum vulgare L.) aspartic proteinase (Asn333) and the cardoon (Cynara cardunculus L.) aspartic proteinase, cardosin A (Asn70 and Asn363). The oligosaccharides from each site were released from peptide pools by enzymatic hydrolysis with peptide-N-glycanase A or by hydrazinolysis and their structures were determined by exoglycosidase sequencing combined with matrix-assisted laser desorption/ionization time of flight mass spectrometry. It was observed that 6% of the oligosaccharides from the first glycosylation site of cardosin A are of the oligomannose type. Modified type glycans with proximal Fuc and without Xyl account for about 82%, 14% and 3% of the total oligosaccharides from the first and the second glycosylation sites of cardosin A and from H. vulgare aspartic proteinase, respectively. Oligosaccharides with Xyl but without proximal Fuc were only detected in the latter proteinase (4%). Glycans with proximal Fuc and Xyl account for 6%, 86% and 92% of the total oligosaccharides from the first and second glycosylation sites of cardosin A and from H. vulgare aspartic proteinase, respectively. C1 INST BIOL EXPT & TECNOL,OEIRAS,PORTUGAL. UNIV YORK,DEPT BIOL,PLANT LAB,PLANT GLYCOPROT RES FACIL,YORK YO1 5DD,N YORKSHIRE,ENGLAND. GESELL BIOTECHNOL FORSCH MBH,DEPT MOL INSTRUMENTAL STRUCT RES,D-3300 BRAUNSCHWEIG,GERMANY. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MACROMOL STRUCT LAB,FREDERICK,MD. UNIV COIMBRA,FAC CIENCIAS & TECNOL,DEPT BIOQUIM,COIMBRA,PORTUGAL. INST SUPER TECN,LISBON,PORTUGAL. RP Costa, J (reprint author), UNIV NOVA LISBOA,INST TECNOL QUIM & BIOL,APART 12,P-2780 OEIRAS,PORTUGAL. RI Costa, Julia/B-7131-2008; Carrondo, Manuel/C-8155-2011; Bento, Isabel/A-5436-2011; OI Costa, Julia/0000-0001-7782-6319; Bento, Isabel/0000-0003-3801-4929; Carrondo, Maria Armenia/0000-0002-1261-1162; Faro, Carlos/0000-0002-0480-8379; Pires, Euclides/0000-0002-5853-0165; Verissimo, Paula/0000-0003-0532-4242; Frazao, Carlos/0000-0002-7725-1671 NR 28 TC 42 Z9 44 U1 0 U2 5 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0014-2956 J9 EUR J BIOCHEM JI Eur. J. Biochem. PD FEB 1 PY 1997 VL 243 IS 3 BP 695 EP 700 DI 10.1111/j.1432-1033.1997.t01-1-00695.x PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WG563 UT WOS:A1997WG56300016 PM 9057834 ER PT J AU Baguley, BC Leteurtre, F Riou, JF Finlay, GJ Pommier, Y AF Baguley, BC Leteurtre, F Riou, JF Finlay, GJ Pommier, Y TI A carbamate analogue of amsacrine with activity against non-cycling cells stimulates topoisomerase II cleavage at DNA sites distinct from those of amsacrine SO EUROPEAN JOURNAL OF CANCER LA English DT Article DE topoisomerase; acridine; intercalation; Lewis lung ID MATRIX-ASSOCIATED REGION; HERPES-SIMPLEX VIRUS; LEUKEMIA-CELLS; RESISTANT; EXPRESSION; BETA; PROTEIN; BINDING; NUCLEI; AGENTS AB AMCA (methyl N-[4-(9-acridinylamino)-2-methoxyphenyl]carbamate hydrochloride), an amsacrine analogue containing a methylcarbamate rather than a methylsulphonamide side chain, contrasts with amsacrine, doxorubicin and etoposide in its relatively high cytotoxicity against non-cycling tumour cells. AMCA bound DNA more tightly than amsacrine, but the DNA base selectivity of binding, as measured by ethidium displacement from poly[dA-dT].[dA-dT] and poly[dG-dC].[dG-dC], was unchanged. AMCA-induced topoisomerase cleavage sites on pBR322, C-MYC and SV40 DNA were investigated using agarose or sequencing gels. DNA fragments were end-labelled, incubated with purified topoisomerase II from different mammalian sources and analysed after treatment with sodium dodecylsulphate/proteinase K. AMCA stimulated the cleavage activity of topoisomerase II, but the DNA sequence selectivity of cleavage was different from that of amsacrine and other topoisomerase inhibitors. It was similar to that of the methoxy derivative of AMCA, indicating that the changed specificity resulted from the carbamate group rather than from the methoxy group. The pattern of DNA cleavage induced by AMCA was similar for topoisomerase II alpha and II beta. (C) 1997 Elsevier Science Ltd. C1 NCI,MOL PHARMACOL LAB,BETHESDA,MD 20892. RHONE POULENC RORER SA,MOL PHARMACOL LAB,F-94403 VITRY SUR SEINE,FRANCE. RP Baguley, BC (reprint author), UNIV AUCKLAND,SCH MED,CANC RES LAB,PRIVATE BAG 92019,AUCKLAND,NEW ZEALAND. NR 40 TC 13 Z9 13 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD FEB PY 1997 VL 33 IS 2 BP 272 EP 279 DI 10.1016/S0959-8049(96)00410-8 PG 8 WC Oncology SC Oncology GA WR852 UT WOS:A1997WR85200024 PM 9135499 ER PT J AU Kimura, S AF Kimura, S TI Role of the thyroid-specific enhancer-binding protein in transcription, development and differentiation SO EUROPEAN JOURNAL OF ENDOCRINOLOGY LA English DT Review ID THYROTROPIN RECEPTOR GENE; TISSUE-SPECIFIC EXPRESSION; EMBRYONIC MOUSE LUNG; FACTOR-I; BRANCHING MORPHOGENESIS; THYROGLOBULIN PROMOTER; TARGETED DISRUPTION; B GENE; N-MYC; DEFINITIVE ENDODERM RP Kimura, S (reprint author), NCI,METAB LAB,NIH,BLDG 37,ROOM 3E-24,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 81 TC 10 Z9 10 U1 0 U2 0 PU SCANDINAVIAN UNIVERSITY PRESS PI OSLO PA PO BOX 2959 TOYEN, JOURNAL DIVISION CUSTOMER SERVICE, N-0608 OSLO, NORWAY SN 0804-4643 J9 EUR J ENDOCRINOL JI Eur. J. Endocrinol. PD FEB PY 1997 VL 136 IS 2 BP 128 EP 136 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA WQ850 UT WOS:A1997WQ85000002 PM 9116904 ER PT J AU Fiorillo, MT Meadows, L DAmato, M Shabanowitz, J Appella, E Sorrentino, R AF Fiorillo, MT Meadows, L DAmato, M Shabanowitz, J Appella, E Sorrentino, R TI Susceptibility to ankylosing spondylitis correlates with the C-terminal residue of peptides presented by various HLA-B27 subtypes SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE ankylosing spondylitis; HLA-B27; peptide elution ID CLASS-I; MONOCLONAL-ANTIBODY; MASS-SPECTROMETRY; MHC; MOLECULES; IDENTIFICATION; DISEASE AB Susceptibility to spondyloarthropaties is strongly associated with some HLA-B27 alleles. Evidence suggests a direct pathogenic role for the B27 molecules which possibly present an arthritogenic peptide to the T cells. If this hypothesis is true, B27 subtypes that differ structurally but are disease-associated ought to be capable of presenting such peptide(s), while non-disease-associated ones would not. We have recently described a B27 subtype, B*2709, and shown its absence in ankylosing spondylitis (AS) patients. Here, we show the elution and sequence of peptides from HLA-B*2709 molecules. Similar to other B27 subtypes, these peptides are mainly nonamers with an Arg at position P2. Comparison of the C-terminal anchors of peptides eluted from B*2702 and B*2705 with those eluted from B*2709 reveals that, while B*2702 and B*2705 have a broader specificity, B*2709 molecules appear to only accept C-terminal hydrophobic residues. A common feature shared by the two caucasoid AS-associated subtypes (B*2702 and B*2705) but different from B*2709, is the presence of a Tyr as peptide C-terminal anchor. The substitution of Val for Tyr at the C terminus in one of the eluted peptides greatly reduces the binding to B*2709 molecules. This finding suggests Tyr as a discriminative amino acid allowed at the C terminus of peptides bound to the AS-associated B27 subtypes, but not to those which are not associated with AS. C1 UNIV ROMA LA SAPIENZA,DIPARTIMENTO BIOL CELULARE & SVILUPPO,I-00185 ROME,ITALY. UNIV VIRGINIA,DEPT CHEM,CHARLOTTESVILLE,VA. UNIV VIRGINIA,DEPT PATHOL,CHARLOTTESVILLE,VA. NCI,CELL BIOL LAB,NIH,BETHESDA,MD 20892. UNIV AQUILA,DEPT EXPT MED,I-67100 LAQUILA,ITALY. CNR,CELL BIOL LAB,ROME,ITALY. RI D'Amato, Mauro/F-2450-2010; Hunt, Donald/I-6936-2012; OI D'Amato, Mauro/0000-0003-2743-5197; Hunt, Donald/0000-0003-2815-6368; Sorrentino, Rosa/0000-0002-9632-2383 FU PHS HHS [AL-33993]; Telethon [E.0410] NR 23 TC 85 Z9 85 U1 0 U2 2 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD FEB PY 1997 VL 27 IS 2 BP 368 EP 373 DI 10.1002/eji.1830270205 PG 6 WC Immunology SC Immunology GA WJ737 UT WOS:A1997WJ73700004 PM 9045906 ER PT J AU Rojo, S Wagtmann, N Long, EO AF Rojo, S Wagtmann, N Long, EO TI Binding of a soluble p70 killer cell inhibitory receptor to HLA-B*5101: Requirement for all three p70 immunoglobulin domains SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE natural killer; HLA-B; inhibitory receptor; soluble receptor ID HLA-B MOLECULES; RECOGNITION; ALLELES; CLONES; NKB1; CLONING; LINE AB Lysis of target cells by natural killer (NK) cells can be prevented by killer cell inhibitory receptors (KIR) specific for major histocompatibility complex class I molecules. Functional studies have identified two distinct p58 KIR, each reactive with a different group of HLA-C allotypes, and distinct p70 KIR specific for some HLA-B or HLA-A allotypes. The NK specificities for each group of HLA-C allotypes have been reproduced by direct binding of recombinant soluble p58 molecules. Here, we show that a soluble p70 KIR binds to HLA-B*5101, but not to HLA-A or HLA-C molecules. Truncated soluble forms of the HLA-B*5101-specific p70 KIR, including one with two immunoglobulin (Ig) domains reactive with a monoclonal antibody that blocks p70 KIR function, did not bind to HLA-B*5101, indicating that all three Ig domains are required for binding. C1 NIAID,IMMUNOGENET LAB,NIH,ROCKVILLE,MD 20852. RI Long, Eric/G-5475-2011 OI Long, Eric/0000-0002-7793-3728 NR 17 TC 52 Z9 53 U1 0 U2 0 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD FEB PY 1997 VL 27 IS 2 BP 568 EP 571 DI 10.1002/eji.1830270231 PG 4 WC Immunology SC Immunology GA WJ737 UT WOS:A1997WJ73700030 PM 9045932 ER PT J AU Glass, M Brotchie, JM Maneuf, YP AF Glass, M Brotchie, JM Maneuf, YP TI Modulation of neurotransmission by cannabinoids in the basal ganglia SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Review ID INSITU HYBRIDIZATION HISTOCHEMISTRY; GAMMA-AMINOBUTYRIC-ACID; RECEPTOR MESSENGER-RNA; RAT-BRAIN; SUBSTANTIA-NIGRA; HUNTINGTONS-DISEASE; MULTIPLE-SCLEROSIS; NEURONAL-ACTIVITY; CALCIUM CURRENTS; GLOBUS-PALLIDUS C1 UNIV MANCHESTER,SCH BIOL SCI,DIV NEUROSCI,MANCHESTER M13 9PT,LANCS,ENGLAND. NIMH,CELL BIOL LAB,BETHESDA,MD 20892. OI Glass, Michelle/0000-0002-5997-6898 NR 68 TC 56 Z9 57 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD FEB PY 1997 VL 9 IS 2 BP 199 EP 203 DI 10.1111/j.1460-9568.1997.tb01390.x PG 5 WC Neurosciences SC Neurosciences & Neurology GA WL973 UT WOS:A1997WL97300001 PM 9058040 ER PT J AU Vogels, R Saunders, RC Orban, GA AF Vogels, R Saunders, RC Orban, GA TI Effects of inferior temporal lesions on two types of orientation discrimination in the macaque monkey SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE identification; macaque; plasticity; temporal comparison; visual cortex ID SHORT-TERM-MEMORY; INFEROTEMPORAL CORTEX; VISUAL MEMORY; PARAHIPPOCAMPAL GYRUS; RECOGNITION MEMORY; RHESUS-MONKEYS; NEURONS; TASKS; STIMULI; PRIMATE AB Rhesus monkeys with transection of the forebrain commissures were trained in two different tasks in which grating orientation was the discriminandum. In the temporal same-different task, the monkeys had to judge whether or not two successively presented gratings differed in orientation. In the identification task, we measured how well the monkey could judge the orientation of the grating. The performance in any task was affected neither by a unilateral anterior temporal cortical area lesion nor by a subsequent posterior temporal cortical area lesion in the same hemisphere resulting in a two-stage inferior temporal (IT) lesion. However, a single stage IT (combined anterior and posterior temporal cortical areas) lesion of the other hemisphere severely disrupted the performance in the temporal same-different task, but only barely increased just noticeable differences in orientation in the identification task. This indicates that the impairment in a temporal comparison task after an IT lesion is not due to a perceptual coding deficit, but is related to the temporal comparison per se. Thus, IT is involved in the temporal comparison of successively presented stimuli. On the other hand, the two IT lesions, each having a different history (single versus two stage) had dramatically different behavioural effects, suggesting an important role for adult brain plasticity in determining the behavioural outcome of a brain lesion. C1 NIH,BETHESDA,MD 20892. RP Vogels, R (reprint author), CATHOLIC UNIV LEUVEN,FAC GENEESKUNDE,NEURO & PSYCHOFYSIOL LAB,CAMPUS GASTHUISBERG,HERESTR,B-3000 LOUVAIN,BELGIUM. NR 48 TC 25 Z9 25 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD FEB PY 1997 VL 9 IS 2 BP 229 EP 245 DI 10.1111/j.1460-9568.1997.tb01394.x PG 17 WC Neurosciences SC Neurosciences & Neurology GA WL973 UT WOS:A1997WL97300005 PM 9058044 ER PT J AU Nakanishi, H Sun, Y Nakamura, RK Mori, K Ito, M Suda, S Namba, H Storch, FI Dang, TP Mendelson, W Mishkin, M Kennedy, C Gillin, JC Smith, CB Sokoloff, L AF Nakanishi, H Sun, Y Nakamura, RK Mori, K Ito, M Suda, S Namba, H Storch, FI Dang, TP Mendelson, W Mishkin, M Kennedy, C Gillin, JC Smith, CB Sokoloff, L TI Positive correlations between cerebral protein synthesis rates and deep sleep in Macaca mulatta SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article; Proceedings Paper CT 25th Annual Meeting of the Society-for-Neuroscience CY NOV 11-16, 1995 CL SAN DIEGO, CA SP Soc Neurosci, USDA, ARS, CSRS, OGPS DE autoradiography; deep sleep; leucine; NREM sleep; rhesus monkey ID EYE-MOVEMENT SLEEP; POSITRON EMISSION TOMOGRAPHY; GLUCOSE-UTILIZATION; REGIONAL RATES; PRECURSOR POOL; SYNTHESIS INVIVO; WAKE CYCLE; DEGRADATION; BRAIN; OSCILLATIONS AB Local rates of cerebral protein synthesis (ICPSleu) were determined with the autoradiographic L-[1-C-14]leucine method in seven awake and seven asleep, adult rhesus monkeys conditioned to sleep in a restraining chair in a darkened, ventilated chamber while EEG., EGG, and EMG were monitored. Prior to the period of measurement all animals slept for 1-4 h. Controls were awakened after at least one period of rapid-eye-movement (REM) sleep. Experimental animals were allowed to remain asleep, and they exhibited non-REM sleep for 71-99% of the experimental period. Statistically significant differences in ICPSleu between control and experimental animals were found in four of the 57 regions of brain examined, but these effects may have occurred by chance. In the sleeping animals, however, correlations between ICPSleu and percent time in deep sleep were positive in all regions and were statistically significant (P less than or equal to 0.05) in 35 of the regions. When time in deep sleep was weighted for the integrated specific activity of leucine in grey matter, positive correlations were statistically significant (P less than or equal to 0.05) in 18 regions in the experimental animals. These results suggest that rates of protein synthesis are increased in many regions of the brain during deep sleep compared with light sleep. C1 NIMH,CEREBRAL METAB LAB,BETHESDA,MD 20892. NIMH,NEUROPSYCHOL LAB,BETHESDA,MD 20892. NIMH,BIOL BRANCH,BETHESDA,MD 20892. NIMH,ADULT PSYCHIAT BRANCH,BETHESDA,MD 20892. SAN DIEGO VET ADM,SAN DIEGO,CA. UNIV CALIF SAN DIEGO,CLEVELAND CLIN FDN,SAN DIEGO,CA 92103. NR 46 TC 81 Z9 83 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD FEB PY 1997 VL 9 IS 2 BP 271 EP 279 DI 10.1111/j.1460-9568.1997.tb01397.x PG 9 WC Neurosciences SC Neurosciences & Neurology GA WL973 UT WOS:A1997WL97300008 PM 9058047 ER PT J AU Safieddine, S Prior, AMS Eybalin, M AF Safieddine, S Prior, AMS Eybalin, M TI Choline acetyltransferase, glutamate decarboxylase, tyrosine hydroxylase, calcitonin gene-related peptide and opioid peptides coexist in lateral efferent neurons of rat and guinea-pig SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE auditory system; coexistence of neurotransmitters; efferent innervations; immunocytochemistry; in situ hybridization ID GAMMA-AMINOBUTYRIC-ACID; PREPROENKEPHALIN MESSENGER-RNA; CENTRAL NERVOUS-SYSTEM; OLIVOCOCHLEAR NEURONS; GABA-LIKE; AMACRINE CELLS; RABBIT RETINA; BRAIN-STEM; IMMUNOCYTOCHEMICAL DETECTION; IMMUNOELECTRON MICROSCOPY AB The lateral efferent (olivocochlear) innervation of the cochlea originates in the brainstem lateral superior olive. It is likely to use acetylcholine, gamma-aminobutyric acid, dopamine and various neuropeptides as neurotransmitters and/or neuromodulators. In order to determine the different coexistence patterns of these molecules in lateral efferent perikarya, we have used double and triple immunofluorescence co-localization techniques to colocalize choline acetyltransferase, glutamate decarboxylase, tyrosine hydroxylase, calcitonin gene-related peptide and enkephalins in single sections of the lateral superior olive. We also used a non-radoactive in situ hybridization technique onto serial sections of this nucleus to confirm the immunofluorescence co-localization data at the mRNA level. Whatever the pair or triplet of primary antibodies tested was, a high ratio of coexistence was observed in the immunofluorescence experiments. In triple co-localization experiments, 90-93% of the choline acetyltransferase-like immunoreactive neurons were also immunoreactive to the two other antigens investigated. The in situ hybridization co-localization data, based on the use of biotin-labelled oligoprobes, qualitatively confirmed these immunofluorescence data. In conclusion, it can be postulated that acetylcholine, gamma-aminobutyric acid, dopamine, calcitonin gene-related peptide, enkephalins and dynorphins (whose coexistence with choline acetyltransferase and enkephalins has been previously described immunocytochemically) coexist in lateral efferent neurons. Based on these results, it is tempting to propose the lateral efferent innervation as a useful model with which the functional implications of the coexistence of neurotransmitters/neuromodulators can be investigated in vivo. C1 INSERM U254,F-34295 MONTPELLIER 5,FRANCE. UNIV MONTPELLIER 1,CHU MONTPELLIER,HOP ST CHARLES,F-34295 MONTPELLIER 5,FRANCE. NIDOCD,NEUROCHEM LAB,NIH,BETHESDA,MD 20892. RI EYBALIN, Michel/A-9895-2011 OI EYBALIN, Michel/0000-0001-9086-1856 NR 60 TC 59 Z9 60 U1 1 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD FEB PY 1997 VL 9 IS 2 BP 356 EP 367 DI 10.1111/j.1460-9568.1997.tb01405.x PG 12 WC Neurosciences SC Neurosciences & Neurology GA WL973 UT WOS:A1997WL97300016 PM 9058055 ER PT J AU Sacco, O Fregonese, B Oddone, M Verna, A Tassara, E Mereu, C Rossi, GA AF Sacco, O Fregonese, B Oddone, M Verna, A Tassara, E Mereu, C Rossi, GA TI Severe endobronchial obstruction in a girl with relapsing polychondritis: Treatment with Nd YAG laser and endobronchial silicon stent SO EUROPEAN RESPIRATORY JOURNAL LA English DT Article DE atelectasis; laser therapy; relapsing polychondritis; silicon stent ID ADOLESCENT; PATHOLOGY; CT AB Relapsing polychondritis (RP) is an uncommon disorder of unknown aetiology characterized by inflammation and destruction of the cartilaginous structures of many organs, including the tracheobronchial tree, When untreated, there is a high mortality rate, usually from respiratory obstructive complications. An 8 year old white girl, with a previous diagnosis of RP, was referred to our department for evaluation of worsening dyspnoea, Bronchoscopy showed localized inflammatory and fibrotic alterations of the mucosa, leading to severe obstruction of the left mainstem bronchus at its origin The condition was successfully treated by endoscopic neodymium yttrium aluminium garnet (Nd YAG) laser. Re-evaluation of the patient, 7 months later, demonstrated branchial stenosis and malacia requiring mechanical dilatation and positioning of an endobronchial silicon stent, which was well-tolerated by the patient. C1 G GASLINI INST CHILDREN,DIV PULM,I-16147 GENOA,ITALY. G GASLINI INST CHILDREN,SERV RADIOL,I-16147 GENOA,ITALY. UNIV GENOA,NATL CANC INST,DEPT ONCOL,ENDOSCOPY RESP CTR,GENOA,ITALY. NR 19 TC 15 Z9 16 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0903-1936 J9 EUR RESPIR J JI Eur. Resp. J. PD FEB PY 1997 VL 10 IS 2 BP 494 EP 496 DI 10.1183/09031936.97.10020494 PG 3 WC Respiratory System SC Respiratory System GA WG332 UT WOS:A1997WG33200038 PM 9042655 ER PT J AU Radzius, A Carriero, NJ Weinhold, LL Gorelick, DA Henningfield, JE AF Radzius, A Carriero, NJ Weinhold, LL Gorelick, DA Henningfield, JE TI Changes in cigarette smoking not observed following repeated cocaine self-administration SO EXPERIMENTAL AND CLINICAL PSYCHOPHARMACOLOGY LA English DT Article AB Acute administration of same psychoactive drugs (e.g., cocaine, heroin, methadone, d-amphetamine) has been found to increase spontaneous cigarette smoking for 1-3 hr, but the effects of chronic drug administration have not been systematically studied. Computerized cigarette dispensers were used to study the effects of multiple daily cocaine administrations on cigarette smoking. Participants were 8 (5 male) cocaine-dependent cigarette smokers who resided on a closed clinical research ward and smoked an average of 16.7 cigarettes per day during the week prior to starting the study. During test sessions on Monday, Wednesday, and Friday of each week, participants could obtain either cocaine (25 mg iv) on 2 days or saline (1 mi iv) on the other day, 3 times per day at 2-hr intervals under double-blind conditions. The number of cigarettes dispensed during study days was analyzed in 2-hr increments. No significant cocaine effect was found. These findings fail to show a change in the number of cigarettes smoked after chronic cocaine self-administration over time intervals longer than 1-3 hr. C1 NIDA,DIV INTRAMURAL RES,TREATMENT BRANCH,BALTIMORE,MD 21224. NIDA,DIV INTRAMURAL RES,CLIN PHARMACOL BRANCH,BALTIMORE,MD 21224. NR 10 TC 5 Z9 5 U1 0 U2 0 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 1064-1297 J9 EXP CLIN PSYCHOPHARM JI Exp. Clin. Psychopharmacol. PD FEB PY 1997 VL 5 IS 1 BP 51 EP 53 DI 10.1037//1064-1297.5.1.51 PG 3 WC Psychology, Biological; Psychology, Clinical; Pharmacology & Pharmacy; Psychiatry SC Psychology; Pharmacology & Pharmacy; Psychiatry GA WM074 UT WOS:A1997WM07400006 PM 9234039 ER PT J AU Li, ZH Cheng, HP Lederer, WJ Froehlich, J Lakatta, EG AF Li, ZH Cheng, HP Lederer, WJ Froehlich, J Lakatta, EG TI Enhanced proliferation and migration and altered cytoskeletal proteins in early passage smooth muscle cells from young and old rat aortic explants SO EXPERIMENTAL AND MOLECULAR PATHOLOGY LA English DT Article ID INTERMEDIATE FILAMENTS; PATHOLOGY; VIMENTIN; DIFFERENTIATION; FEATURES; DESMIN; ACTIN; MEDIA; WALL; ARTERIOSCLEROSIS AB Smooth muscle cell (SMC) proliferation, migration, and cytoskeletal protein expression were studied in cultured cells obtained from the aortic explants of young (6-month) and old (30-month) Fischer 344XNB rats. Second-passage SMC were cultured on coverslips, and cytoskeletal fibers were examined by immunofluorescence microscopy using antibodies specific for smooth muscle myosin, or-smooth muscle actin, vimentin, desmin, and tubulin. The cytoskeletal fiber density was quantified as fluorescence intensity by confocal microscopy. The proliferation of SMC was analyzed from the growth curve of cells grown in culture from 0 to 14 days, and a Boyden chamber assay was used to quantify the SMC migration rate. The diameter of fresh SMC digested enzymatically from old rat aortae was 52.4% larger than that of the cells from young animals (20.0+/-3 mu m vs 13.1 +/- 2 mu m, P < 0.05). In SMC cultured from old animals, the intensities of smooth muscle myosin, a-smooth muscle actin, and vimentin decreased by 59.6, 41.2, and 54.8%, respectively; desmin and tubulin increased by 46.1 and 65.1% (all P < 0.001). Compared to SMC isolated from young rat aortae, the number of SMC cultured (second passage) from the old rat aorta was increased by 48.4, 27.2, and 26.9%, respectively, at Days 3, 7, and 14 in culture (P < 0.05, P < 0.01, and P < 0.001). The migration rate of SMC cultured from old rats was 59.3% higher than that of the cells obtained from young rats. These data show that alterations of the SMC cytoskeleton occur concomitantly with changes in SMC proliferation and migration rate during aging, suggesting that the age-associated changes in cytoskeletal proteins may play a role in remodeling of the aortic wall during aging. (C) 1997 Academic Press. RP Li, ZH (reprint author), NIA,CARDIOVASC SCI LAB,NIH,BALTIMORE,MD 21224, USA. RI Lederer, William/B-1285-2010 NR 43 TC 47 Z9 53 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0014-4800 J9 EXP MOL PATHOL JI Exp. Mol. Pathol. PD FEB PY 1997 VL 64 IS 1 BP 1 EP 11 DI 10.1006/exmp.1997.2204 PG 11 WC Pathology SC Pathology GA XF990 UT WOS:A1997XF99000001 PM 9203504 ER PT J AU Iatropoulos, MJ WilliamS, GM Abdo, KM Kari, FW Hart, RW AF Iatropoulos, MJ WilliamS, GM Abdo, KM Kari, FW Hart, RW TI Mechanistic studies on genotoxicity and carcinogenicity of salicylazosulfapyridine an anti-inflammatory medicine SO EXPERIMENTAL AND TOXICOLOGIC PATHOLOGY LA English DT Article DE genotoxicity; carcinogenicity; salicylazosulfapyridine (SASP); toxicity testing methodology; risk assessment; rodent human extrapolation ID BONE-MARROW ERYTHROCYTES; ULCERATIVE-COLITIS; COLORECTAL-CANCER; MICRONUCLEUS TEST; DEFICIENT RATS; BOWEL-DISEASE; DNA DAMAGE; SULFASALAZINE; INVITRO; METABOLITES AB Salicylazosulfapyridine (SASP), which has been in clinical use for over 50 years, was reported by the National Toxicology Program to increase rat (F344 strain) urinary bladder and mouse (B6C3F(1) hybrid) liver tumors under ad libitum (AL) feeding conditions, while under a feed restriction (FR) regimen, these tumors were not increased. The present investigations were undertaken to assess the implications of these results for the safety of SASP in humans. SASP and its 2 major metabolites, 5-aminosalicylic acid (ASA) and sulfapyridine (SP) were tested for in vivo induction of micronuclei in mouse bone marrow cells with or without prefolic treatment and for in vivo formation of DNA adducts in rat and mouse liver and urinary bladder. None exhibited mutagenicity or DNA reactivity. SASP and SP have induced sister chromatid exchanges and micronuclei (MN) in cultured human lymphocytes in the absence of liver activation enzymes and in B6C3F, mice (but not in rats) MN in bone marrow and peripheral RBC. Treatment with folate reduces the frequency of MN. Perhaps the short (28 days) RBC lifespan in mouse underlies the sensitivity of this species. Thus, SASP without folate supplementation is an aneuploidogen. In a 2-year study in AL fed SASP-treated (high dose 337.5 mg/kg) rats, urinary pH was increased and urinary specific gravity was reduced at 60 weeks. At the end, this SASP group showed urothelial hyperplasia and papillomas in the urinary bladders of male rats primarily. In the FR high dose SASP group, the hyperplasia was reduced from 82 % to 14 %. At the end of 2 years, the incidence of multiorgan leukemia was reduced in both AL and FR high dose SASP groups. Thus, SASP caused intraluminal bladder changes in the rat (especially males) consisting of chronic urothelial stimulation, concretions, hyperplasia which resulted in neoplasia. In the mouse, because of species differences in liver ratios (mouse > rat) and, increasing (3 times higher) liver perfusion in the mouse, compared to the rat, there was hepatocellular toxicity and resulting preneoplasia and neoplasia within 2 years. These findings occurred in all AL SASP groups (flat curve without dose response); but were reduced under FR conditions. In this species, the multiorgan lymphoma incidence was reduced in both AL and FR high dose SASP groups. Thus, SASP and its major metabolites are not genotoxic. Folate deficiency associated with SASP administration is probably responsible for aneuploidy in lymphocytes and erythrocytes. SASP does not induce neoplasia directly in either livers, urinary bladders or other organs. Accordingly, SASP is judged to pose no carcinogenic risk to humans. C1 NIEHS,RES TRIANGLE PK,NC 27709. NATL CTR TOXICOL RES,JEFFERSON,AR 72079. RP Iatropoulos, MJ (reprint author), AMER HLTH FDN,1 DANA RD,VALHALLA,NY 10595, USA. NR 78 TC 8 Z9 9 U1 0 U2 0 PU GUSTAV FISCHER VERLAG PI JENA PA VILLENGANG 2, D-07745 JENA, GERMANY SN 0940-2993 J9 EXP TOXICOL PATHOL JI Exp. Toxicol. Pathol. PD FEB PY 1997 VL 49 IS 1-2 BP 15 EP 28 PG 14 WC Pathology; Toxicology SC Pathology; Toxicology GA WP789 UT WOS:A1997WP78900003 PM 9085070 ER PT J AU Rao, PV Zigler, JS Garland, D AF Rao, PV Zigler, JS Garland, D TI Analysis of small GTP-binding proteins of the lens by GTP overlay assay reveals the presence of unique GTP-binding proteins associated with fiber cells SO EXPERIMENTAL EYE RESEARCH LA English DT Article DE lens; small GTP-binding proteins; Ras superfamily GTPases; differentiation; cytoskeleton; signal-transduction ID ACTIN STRESS FIBERS; EYE LENS; GROWTH-FACTOR; NEUROFIBROMATOSIS TYPE-2; MAMMALIAN-CELLS; CHICKEN LENS; RAS; CRYSTALLINS; IDENTIFICATION; RHO AB Low molecular weight GTP-binding proteins are molecular switches which are thought to play pivotal roles in cell growth, differentiation, cytoskeletal organization and vesicular trafficking. In this study, members of this family of proteins have been identified and characterized in the eye lens, for the first time. [alpha-P-32]GTP blot overlay assays of monkey and human lens water soluble and membranous insoluble fractions revealed the presence of specific GTP-binding proteins in the range of 20-30 kDa (small GTPases) in both fractions, with much higher amounts in the membranous insoluble fraction. In the insoluble fraction, in addition to 20-30 kDa GTPases, there are three distinct GTP-binding proteins, ranging from 33-45 kDa, The small GTPases (20-30 kDa) were present throughout the lens in epithelium, cortex and nucleus, while the 33-45 kDA GTP-binding protein bands were exclusively associated with the cortex and nucleus (fiber cells). Analysis of lens fractions by two-dimensional electrophoresis, immunoprecipitation using monoclonal and sequence specific polyclonal antibodies and C3 exoenzyme mediated ADP-ribosylation demonstrated the presence of Ras, Rap, Rho, Rac, Rab and several other small GTPases. The 33-45 kDa GTP-binding proteins that are associated with lens fiber cells appear to be distinct from the small GTPases and from heterotrimeric GTPases, and were not detected in brain or heart tissue. The presence of different complements of GTP-binding proteins in lens fibers and epithelial cells suggests their involvement in important regulatory functions, possibly related to cell growth, differentiation and organization of the cytoskeleton. (C) 1997 Academic Press Limited. RP Rao, PV (reprint author), NEI,LAB MECHANISMS OCULAR DIS,BLDG6,ROOM 237,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 55 TC 18 Z9 18 U1 0 U2 0 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0014-4835 J9 EXP EYE RES JI Exp. Eye Res. PD FEB PY 1997 VL 64 IS 2 BP 219 EP 227 DI 10.1006/exer.1996.0197 PG 9 WC Ophthalmology SC Ophthalmology GA WL804 UT WOS:A1997WL80400012 PM 9176056 ER PT J AU Brady, JP Duncan, MK Wawrousek, EF Piatigorsky, J AF Brady, JP Duncan, MK Wawrousek, EF Piatigorsky, J TI The transcription factor, kid-1, is highly expressed in both eye and kidney of the mouse SO EXPERIMENTAL EYE RESEARCH LA English DT Letter ID ZINC-FINGERS; KRAB DOMAIN; PROTEIN; CDNA; LENS C1 NEI,MOL & DEV BIOL LAB,BETHESDA,MD 20892. RI Wawrousek, Eric/A-4547-2008 NR 12 TC 7 Z9 9 U1 0 U2 0 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0014-4835 J9 EXP EYE RES JI Exp. Eye Res. PD FEB PY 1997 VL 64 IS 2 BP 287 EP 290 DI 10.1006/exer.1996.0206 PG 4 WC Ophthalmology SC Ophthalmology GA WL804 UT WOS:A1997WL80400020 PM 9176064 ER EF