FN Thomson Reuters Web of Science™ VR 1.0 PT J AU LITMAN, R TORREY, EF HOMMER, D RADANT, A PICKAR, D WEINBERGER, D AF LITMAN, R TORREY, EF HOMMER, D RADANT, A PICKAR, D WEINBERGER, D TI SMOOTH-PURSUIT EYE TRACKING IN MONOZYGOTIC TWINS DISCORDANT FOR SCHIZOPHRENIA SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH,BETHESDA,MD 20892. NIAAA,BETHESDA,MD 20892. UNIV WASHINGTON,MED CTR,SEATTLE,WA 98105. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 1994 VL 35 IS 9 BP 660 EP 660 DI 10.1016/0006-3223(94)90822-2 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA NJ172 UT WOS:A1994NJ17200164 ER PT J AU ALTEMUS, M CHAVES, S CARMO, A CARTER, S AF ALTEMUS, M CHAVES, S CARMO, A CARTER, S TI PROSPECTIVE-STUDY OF MOOD AND ANXIETY CHANGES DURING PREGNANCY AND POSTPARTUM SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH,CLIN SCI LAB,BETHESDA,MD 20892. UNIV MARYLAND,DEPT ZOOL,COLL PK,MD 20422. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 1994 VL 35 IS 9 BP 661 EP 661 DI 10.1016/0006-3223(94)90825-7 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA NJ172 UT WOS:A1994NJ17200167 ER PT J AU ROSENSTEIN, D ELIN, RJ NIEMELA, JE SCHMIDT, PJ POST, RM RUBINOW, DR AF ROSENSTEIN, D ELIN, RJ NIEMELA, JE SCHMIDT, PJ POST, RM RUBINOW, DR TI MAGNESIUM - MODULATION BY MOOD AND MENSTRUAL-CYCLE SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH,BEHAV ENDOCRINOL SECT,BIOL PSYCHIAT BRANCH,BETHESDA,MD 20892. NIH,CC,DEPT CLIN PATHOL,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 1994 VL 35 IS 9 BP 661 EP 661 DI 10.1016/0006-3223(94)90823-0 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA NJ172 UT WOS:A1994NJ17200165 ER PT J AU SU, TP DANACEAU, MA SCHMIDT, PJ RUBINOW, DR AF SU, TP DANACEAU, MA SCHMIDT, PJ RUBINOW, DR TI EFFECT OF MENSTRUAL-CYCLE PHASE ON BIOCHEMICAL AND BEHAVIORAL-RESPONSE TO M-CPP SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH,EXPTL THERAPEUT BRANCH,BETHESDA,MD 20892. NIH,DEPT NURSING,CTR CLIN,BETHESDA,MD 20892. NIMH,BIOL PSYCHIAT BRANCH,BEHAV ENDOCRINOL SECT,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 1994 VL 35 IS 9 BP 661 EP 661 DI 10.1016/0006-3223(94)90824-9 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA NJ172 UT WOS:A1994NJ17200166 ER PT J AU HITRI, A STAMBUK, M DEUTSCH, SI AF HITRI, A STAMBUK, M DEUTSCH, SI TI EFFECT OF TESTING FREQUENCY ON MK-801 INDUCED POPPING AND ATAXIA IN MICE SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 DVAMC,NIDA RES,WASHINGTON,DC 20422. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 1994 VL 35 IS 9 BP 662 EP 663 DI 10.1016/0006-3223(94)90830-3 PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA NJ172 UT WOS:A1994NJ17200172 ER PT J AU LEIBENLUFT, E FIERO, PL RUBINOW, DR AF LEIBENLUFT, E FIERO, PL RUBINOW, DR TI NEUROENDOCRINE AND CIRCADIAN MODULATION BY THE MENSTRUAL-CYCLE SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH,CLIN PSYCHOBIOL BRANCH,BETHESDA,MD 20892. NIMH,BIOL PSYCHIAT BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 1994 VL 35 IS 9 BP 662 EP 662 DI 10.1016/0006-3223(94)90827-3 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA NJ172 UT WOS:A1994NJ17200169 ER PT J AU SCHMIDT, PJ OLLO, CA RUBINOW, DR AF SCHMIDT, PJ OLLO, CA RUBINOW, DR TI NEUROPSYCHIATRIC EFFECTS OF PERIMENOPAUSAL ESTROGEN REPLACEMENT SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH,BIOL PSYCHIAT BRANCH,BETHESDA,MD 20892. NR 0 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 1994 VL 35 IS 9 BP 662 EP 662 DI 10.1016/0006-3223(94)90828-1 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA NJ172 UT WOS:A1994NJ17200170 ER PT J AU WALLACE, W KIRBY, B MERRIL, CR AF WALLACE, W KIRBY, B MERRIL, CR TI PROTECTION OF TAU FROM HYPERPHOSPHORYLATION BY HEAT-SHOCK PROTEINS IN NEURONAL PC12 CELLS SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH,CTR NEUROSCI,BIOCHEM GENET LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 1994 VL 35 IS 9 BP 663 EP 663 DI 10.1016/0006-3223(94)90832-X PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA NJ172 UT WOS:A1994NJ17200174 ER PT J AU SMITH, MA ALTEMUS, M MICHELSON, D POST, RM AF SMITH, MA ALTEMUS, M MICHELSON, D POST, RM TI ANTIDEPRESSANTS AND ECS DECREASE THE EXPRESSION OF NEUROTROPHIN-3 MESSENGER-RNA SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 1994 VL 35 IS 9 BP 670 EP 671 DI 10.1016/0006-3223(94)90859-1 PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA NJ172 UT WOS:A1994NJ17200201 ER PT J AU WALLACE, W LIEBERBURG, I DAVIS, KL FIBER, E GLUCK, R HAROUTUNIAN, V AF WALLACE, W LIEBERBURG, I DAVIS, KL FIBER, E GLUCK, R HAROUTUNIAN, V TI INDUCTION OF APP RESULTS IN ITS SECRETION AND PRODUCTION OF B-AMYLOID IN SUBCORTICALLY LESIONED RATS SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH,CTR NEUROSCI,BETHESDA,MD 20892. CUNY MT SINAI SCH MED,NEW YORK,NY 10029. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 1994 VL 35 IS 9 BP 671 EP 671 DI 10.1016/0006-3223(94)90860-5 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA NJ172 UT WOS:A1994NJ17200202 ER PT J AU GLICK, ID VINAR, O KLEIN, DF POTTER, WZ MONTGOMERY, SA LECRUBIER, Y AF GLICK, ID VINAR, O KLEIN, DF POTTER, WZ MONTGOMERY, SA LECRUBIER, Y TI PROMISING MEDICATIONS NOT AVAILABLE IN THE UNITED-STATES SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 STANFORD UNIV,SCH MED,STANFORD,CA 94305. ACAD SCI CZECH REPUBL,PRAGUE,CZECH REPUBLIC. STATE INST DRUG CONTROL,PRAGUE,CZECH REPUBLIC. NIMH,BETHESDA,MD 20892. ST MARYS HOSP,SCH MED,LONDON,ENGLAND. HOP LA PITIE SALPETRIERE,PARIS,FRANCE. COLUMBIA UNIV,NEW YORK STATE PSYCHIAT INST,NEW YORK,NY 10032. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 1994 VL 35 IS 9 BP 678 EP 678 DI 10.1016/0006-3223(94)90885-0 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA NJ172 UT WOS:A1994NJ17200227 ER PT J AU ANDREASON, PJ HOMMER, D SIROCCO, K WEINGARTNER, H AF ANDREASON, PJ HOMMER, D SIROCCO, K WEINGARTNER, H TI CEREBRAL METABOLIC CORRELATES OF MONITORING THE SOURCE OF REMEMBERED INFORMATION SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIAAA,DICBR,CLIN STUDIES LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 1994 VL 35 IS 9 BP 684 EP 684 DI 10.1016/0006-3223(94)90908-3 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA NJ172 UT WOS:A1994NJ17200250 ER PT J AU OSTREM, JL BERMAN, KF MATTAY, VS VANHORN, JD ESPOSITO, G WEINBERGER, DR AF OSTREM, JL BERMAN, KF MATTAY, VS VANHORN, JD ESPOSITO, G WEINBERGER, DR TI THE NEURAL BASIS OF ABSTRACT REASONING - AN INVESTIGATION OF 2 PROBLEM-SOLVING TASKS WITH PET SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH,INTRAMURAL RES PROGRAM,CLIN BRAIN DISORDERS BRANCH,PET UNIT,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 1994 VL 35 IS 9 BP 686 EP 686 DI 10.1016/0006-3223(94)90915-6 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA NJ172 UT WOS:A1994NJ17200257 ER PT J AU COPPOLA, R WATSKY, E WEINBERGER, DR AF COPPOLA, R WATSKY, E WEINBERGER, DR TI INDIVIDUAL VARIATION OF DOPAMINE D2 RECEPTORS WITH I-123 IBZM SPECT SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH,CLIN BRAIN DISORDERS BRANCH,WASHINGTON,DC 20032. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 1994 VL 35 IS 9 BP 687 EP 687 DI 10.1016/0006-3223(94)90917-2 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA NJ172 UT WOS:A1994NJ17200259 ER PT J AU KIRKBY, BS OSTREM, JL WEINBERGER, DR BERMAN, KF AF KIRKBY, BS OSTREM, JL WEINBERGER, DR BERMAN, KF TI A PET STUDY OF MONOZYGOTIC TWINS DISCORDANT FOR FRONTAL-LOBE INJURY - NEUROPHYSIOLOGICAL AND COGNITIVE SEQUELAE SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH,INTRAMURAL RES PROGRAM,CLIN BRAIN DISORDERS BRANCH,PET UNIT,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 1994 VL 35 IS 9 BP 687 EP 687 DI 10.1016/0006-3223(94)90916-4 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA NJ172 UT WOS:A1994NJ17200258 ER PT J AU SU, TP HSIAO, J MALHOTRA, AK CHUNG, IW HADD, K TUSKAN, J BRENHOLTZ, R WASKY, E LEE, LS GOREY, J COPPOLA, R WEINBERGER, DR PICKAR, D AF SU, TP HSIAO, J MALHOTRA, AK CHUNG, IW HADD, K TUSKAN, J BRENHOLTZ, R WASKY, E LEE, LS GOREY, J COPPOLA, R WEINBERGER, DR PICKAR, D TI THE EFFECTS OF NEUROLEPTIC DOSE ADJUSTMENT ON D2 RECEPTOR OCCUPANCY AND SCHIZOPHRENIC SYMPTOMATOLOGY, A STUDY USING IBZM SPECT SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH,EXPTL THERAPEUT BRANCH,CLIN BRAIN DISORDERS BRANCH,BETHESDA,MD. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 1994 VL 35 IS 9 BP 689 EP 689 DI 10.1016/0006-3223(94)90925-3 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA NJ172 UT WOS:A1994NJ17200267 ER PT J AU ROSSE, RB ALIM, TN VOCCI, FJ HESS, AL JOHRI, SK DEUTSCH, SI AF ROSSE, RB ALIM, TN VOCCI, FJ HESS, AL JOHRI, SK DEUTSCH, SI TI GREATER INCREASES IN COCAINE CUE-INDUCED CRAVING AND PUPILLARY SIZE IN COCAINE ADDICTS ENDORSING COCAINE-INDUCED PARANOIA SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIDA,DEPT VET AFFAIRS MED CTR,RES UNIT,WASHINGTON,DC 20122. NR 0 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 1994 VL 35 IS 9 BP 693 EP 693 DI 10.1016/0006-3223(94)90939-3 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA NJ172 UT WOS:A1994NJ17200281 ER PT J AU ROSSE, RB SATEL, SL ALIM, TN ISSAC, A HESS, A DEUTSCH, SI AF ROSSE, RB SATEL, SL ALIM, TN ISSAC, A HESS, A DEUTSCH, SI TI PREDICTORS OF COCAINE-INDUCED PARANOIA SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIDA,DEPT VET AFFAIRS MED CTR,PSYCHIAT SERV,VA RES UNIT,WASHINGTON,DC 20122. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 1994 VL 35 IS 9 BP 694 EP 694 DI 10.1016/0006-3223(94)90941-5 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA NJ172 UT WOS:A1994NJ17200283 ER PT J AU BITLER, DA GEORGE, DT LINNOILA, M AF BITLER, DA GEORGE, DT LINNOILA, M TI CHARACTERIZATION OF INDIVIDUALS WHO INITIATE DOMESTIC VIOLENCE SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIAAA,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 1994 VL 35 IS 9 BP 697 EP 698 DI 10.1016/0006-3223(94)90952-0 PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA NJ172 UT WOS:A1994NJ17200296 ER PT J AU BITLER, DA GEORGE, DT LINNOILA, M AF BITLER, DA GEORGE, DT LINNOILA, M TI CHARACTERIZATION OF INDIVIDUALS WHO INITIATE DOMESTIC VIOLENCE SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIAAA,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 1994 VL 35 IS 9 BP 697 EP 697 DI 10.1016/0006-3223(94)90952-0 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA NJ172 UT WOS:A1994NJ17200294 ER PT J AU BREIER, A MALHOTRA, AK SU, TP HO, D HSIAO, JK PICKAR, D AF BREIER, A MALHOTRA, AK SU, TP HO, D HSIAO, JK PICKAR, D TI NEUROANATOMICAL LOCALIZATION OF KETAMINE-INDUCED PSYCHOSIS IN SCHIZOPHRENIC-PATIENTS AND CONTROLS SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH,EXPTL THERAPEUT BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 1994 VL 35 IS 9 BP 704 EP 704 DI 10.1016/0006-3223(94)90977-6 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA NJ172 UT WOS:A1994NJ17200319 ER PT J AU LIPSKA, BK WEINBERGER, DR AF LIPSKA, BK WEINBERGER, DR TI GENETIC-DIFFERENCES IN BEHAVIORAL-RESPONSE TO NEONATAL HIPPOCAMPAL DAMAGE IN RATS SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH,ST ELIZABETHS HOSP,CTR NEUROSCI,CLIN BRAIN DISORDERS BRANCH,WASHINGTON,DC 20032. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 1994 VL 35 IS 9 BP 706 EP 706 DI 10.1016/0006-3223(94)90986-5 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA NJ172 UT WOS:A1994NJ17200328 ER PT J AU CADET, JL GENDRON, T KAHLER, L HENNINGFLELD, J ROTHMAN, RB AF CADET, JL GENDRON, T KAHLER, L HENNINGFLELD, J ROTHMAN, RB TI CHRONIC COCAINE ABUSE IS ASSOCIATED WITH PERIPHERAL-NERVE DAMAGE SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIDA,ARC,MOLEC NEUROPSYCHIAT SECT,BALTIMORE,MD 21224. NIDA,ARC,CLIN PSYCHOPHARMACOL SECT,BALTIMORE,MD 21224. NIDA,ARC,BIOL DRUG DEPENDENCE SECT,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 1994 VL 35 IS 9 BP 707 EP 708 DI 10.1016/0006-3223(94)90990-3 PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA NJ172 UT WOS:A1994NJ17200332 ER PT J AU SWERDLOW, N LIPSKA, B WEINBERGER, D BRAFF, D JASKIW, G GEYER, M AF SWERDLOW, N LIPSKA, B WEINBERGER, D BRAFF, D JASKIW, G GEYER, M TI STARTLE GATING AFTER FRONTAL-CORTEX OR HIPPOCAMPAL-LESIONS IN ADULT-RATS SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 UNIV CALIF SAN DIEGO,DEPT PSYCHIAT,LA JOLLA,CA 92093. NIMH,ST ELIZABETHS HOSP,CTR NEUROSCI,WASHINGTON,DC 20032. UNIV CLEVELAND HOSP,DEPT PSYCHIAT,CLEVELAND,OH 44106. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 1994 VL 35 IS 9 BP 707 EP 707 DI 10.1016/0006-3223(94)90987-3 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA NJ172 UT WOS:A1994NJ17200329 ER PT J AU HITRI, A WYATT, RJ AF HITRI, A WYATT, RJ TI ARE THE REGIONAL DIFFERENCES IN [H-3] GBR-12935 BINDING CLINICALLY RELEVANT SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 VET ADM MED CTR,NIDA,WASHINGTON,DC 20422. NIMH,NEUROPSYCHIAT BRANCH,WASHINGTON,DC 20422. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 1994 VL 35 IS 9 BP 709 EP 709 DI 10.1016/0006-3223(94)90994-6 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA NJ172 UT WOS:A1994NJ17200336 ER PT J AU GIEDD, JN CASTELLANOS, FX KOZUCH, P CASEY, BJ KAYSEN, D KING, AC HAMBURGER, SD RAPOPORT, JL AF GIEDD, JN CASTELLANOS, FX KOZUCH, P CASEY, BJ KAYSEN, D KING, AC HAMBURGER, SD RAPOPORT, JL TI QUANTITATIVE MAGNETIC-RESONANCE-IMAGING OF HUMAN BRAIN-DEVELOPMENT - AGES 4-18 SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH,CHILD PSYCHIAT BRANCH,BETHESDA,MD 20851. 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 INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 1994 VL 35 IS 9 BP 713 EP 713 DI 10.1016/0006-3223(94)91008-1 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA NJ172 UT WOS:A1994NJ17200350 ER PT J AU MURRAY, AM HYDE, TM KNABLE, MB BIGELOW, LB HERMAN, MM KLEINMAN, JE AF MURRAY, AM HYDE, TM KNABLE, MB BIGELOW, LB HERMAN, MM KLEINMAN, JE TI QUANTITATIVE AUTORADIOGRAPHY OF DOPAMINE D4 RECEPTORS IN POSTMORTEM BRAINS FROM SCHIZOPHRENIC-PATIENTS SO BIOLOGICAL PSYCHIATRY 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 INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 1994 VL 35 IS 9 BP 716 EP 716 DI 10.1016/0006-3223(94)91020-0 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA NJ172 UT WOS:A1994NJ17200362 ER PT J AU KULYNYCH, JJ VLADAR, K JONES, DW WEINBERGER, DR AF KULYNYCH, JJ VLADAR, K JONES, DW WEINBERGER, DR TI VOLUME OF THE SUPERIOR TEMPORAL GYRUS IN PATIENTS WITH SCHIZOPHRENIA AND NORMAL CONTROLS - AN INVESTIGATION UTILIZING 3-DIMENSIONAL MRI SURFACE-RENDERING MORPHOMETRY SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract RP KULYNYCH, JJ (reprint author), NIMH,NEUROSCI CTR ST ELIZABETHS,IRP,CLIN BRAIN DISORDERS BRANCH,WASHINGTON,DC 20032, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 1994 VL 35 IS 9 BP 722 EP 722 DI 10.1016/0006-3223(94)91041-3 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA NJ172 UT WOS:A1994NJ17200383 ER PT J AU CASTELLANOS, FX GIEDD, JN ECKBURG, P MARSH, WL KOZUCH, P KING, AC HAMBURGER, SD RITCHIE, GF RAPOPORT, JL AF CASTELLANOS, FX GIEDD, JN ECKBURG, P MARSH, WL KOZUCH, P KING, AC HAMBURGER, SD RITCHIE, GF RAPOPORT, JL TI QUANTITATIVE MORPHOLOGY OF THE CAUDATE-NUCLEUS IN ADHD SO BIOLOGICAL PSYCHIATRY 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 2 Z9 2 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 1994 VL 35 IS 9 BP 725 EP 725 DI 10.1016/0006-3223(94)91052-9 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA NJ172 UT WOS:A1994NJ17200394 ER PT J AU GOODMAN, CB EMILIEN, B CADET, JL YANG, HYT LEE, CH ROTHMAN, RB AF GOODMAN, CB EMILIEN, B CADET, JL YANG, HYT LEE, CH ROTHMAN, RB TI CHRONIC ICV INFUSION WITH MONOCLONAL ANTI-NPFF IGG UP-REGULATES MU-OPIOID BINDING-SITES IN RAT-BRAIN - AN AUTORADIOGRAPHIC STUDY SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIDA,ADDICT RES CTR,CPS,BALTIMORE,MD 21224. NIDA,ADDICT RES CTR,MNS,BALTIMORE,MD 21224. NIMH,ST ELIZABETHS HOSP,CTR NEUROSCI,LBG,WASHINGTON,DC 20032. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 1994 VL 35 IS 9 BP 727 EP 727 DI 10.1016/0006-3223(94)91059-6 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA NJ172 UT WOS:A1994NJ17200401 ER PT J AU MCCARTHY, MF KENDRICK, KA ROSSE, RB WYATT, RJ DEUTSCH, SI AF MCCARTHY, MF KENDRICK, KA ROSSE, RB WYATT, RJ DEUTSCH, SI TI A FUNCTIONAL ASSESSMENT OF DISABILITY SCALE FOR TARDIVE-DYSKINESIA SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 DEPT VET AFFAIRS MED CTR,DEPT PSYCHIAT,WASHINGTON,DC 20422. GEORGETOWN UNIV,SCH MED,DEPT PSYCHIAT,WASHINGTON,DC 20007. NIMH,CTR NEUROSCI,NEUROPSYCHIAT BRANCH,WASHINGTON,DC 20032. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 1994 VL 35 IS 9 BP 731 EP 731 DI 10.1016/0006-3223(94)91075-8 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA NJ172 UT WOS:A1994NJ17200417 ER PT J AU BOJA, JW LADENHEIM, BN EPSTEIN, CJ CADET, JL AF BOJA, JW LADENHEIM, BN EPSTEIN, CJ CADET, JL TI REDUCED DOPAMINE UPTAKE SITES IN HOMOZYGOUS CU/ZN SUPEROXIDE-DISMUTASE TRANSGENIC MICE SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIDA,ADDICT RES CTR,BALTIMORE,MD 21224. UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA 94143. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 1994 VL 35 IS 9 BP 732 EP 732 DI 10.1016/0006-3223(94)91080-4 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA NJ172 UT WOS:A1994NJ17200422 ER PT J AU LICINIO, J WONG, ML AF LICINIO, J WONG, ML TI LOCALIZATION OF INTERLEUKIN-1 TYPE-I RECEPTOR MESSENGER-RNA IN RAT-BRAIN SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH,CLIN NEUROENDOCRINOL BRANCH,INTRAMURAL RES PROGRAM,BETHESDA,MD 20892. RI Licinio, Julio/L-4244-2013 OI Licinio, Julio/0000-0001-6905-5884 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 1994 VL 35 IS 9 BP 732 EP 732 DI 10.1016/0006-3223(94)91078-2 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA NJ172 UT WOS:A1994NJ17200420 ER PT J AU WONG, ML LICINIO, J AF WONG, ML LICINIO, J TI DISTRIBUTION OF STEM-CELL FACTOR MESSENGER-RNA IN ADULT-RAT BRAIN SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH,CLIN NEUROENDOCRINOL BRANCH,INTRAMURAL RES PROGRAM,BETHESDA,MD 20892. RI Licinio, Julio/L-4244-2013 OI Licinio, Julio/0000-0001-6905-5884 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 1994 VL 35 IS 9 BP 732 EP 732 DI 10.1016/0006-3223(94)91079-0 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA NJ172 UT WOS:A1994NJ17200421 ER PT J AU HITRI, A WYATT, RJ AF HITRI, A WYATT, RJ TI PHARMACOLOGICAL RESPONSIVENESS OF [H-3] GBR-12935 BINDING-SITES IN THE PREFRONTAL CORTEX OF COCAINE USING HUMANS AND RATS SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 DVAMC,NIDA RES,WASHINGTON,DC 20422. NIMH,NEUROPSYCHIAT BRANCH,WASHINGTON,DC 20422. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 1994 VL 35 IS 9 BP 733 EP 734 DI 10.1016/0006-3223(94)91084-7 PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA NJ172 UT WOS:A1994NJ17200426 ER PT J AU KLING, MA DEBELLIS, MD LISTWAK, SJ GERACIOTI, TD OROURKE, DK KALOGERAS, KT OLDFIELD, EH CHROUSOS, GP GOLD, PW AF KLING, MA DEBELLIS, MD LISTWAK, SJ GERACIOTI, TD OROURKE, DK KALOGERAS, KT OLDFIELD, EH CHROUSOS, GP GOLD, PW TI OXYTOCIN SHOWS A DIURNAL RHYTHM IN CSF OF HEALTHY-VOLUNTEERS SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH,BETHESDA,MD 20892. UNIV PITTSBURGH,PITTSBURGH,PA 15213. UNIV CINCINNATI,CINCINNATI,OH 45220. NINCDS,BETHESDA,MD 20892. NICHHD,BETHESDA,MD 20892. RI Kling, Mitchel/F-4152-2010 OI Kling, Mitchel/0000-0002-2232-1409 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 1994 VL 35 IS 9 BP 734 EP 734 DI 10.1016/0006-3223(94)91086-3 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA NJ172 UT WOS:A1994NJ17200428 ER PT J AU LILLRANK, SM OJA, SS SARANSAARI, P AF LILLRANK, SM OJA, SS SARANSAARI, P TI [3H]-GABA AND [3H]-FLUNITRAZEPAM BINDING ARE DIFFERENTLY AFFECTED BY HANDLING STRESS AND PHENCYCLIDINE SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH,ST ELIZABETHS HOSP,CTR NEUROSCI,WASHINGTON,DC 20032. UNIV TAMPERE,DEPT BIOMED SCI,SF-33101 TAMPERE,FINLAND. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 1994 VL 35 IS 9 BP 734 EP 735 DI 10.1016/0006-3223(94)91088-X PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA NJ172 UT WOS:A1994NJ17200430 ER PT J AU NOGA, JT HYDE, TM HERMAN, M BIGELOW, LL WEINBERGER, DR KLEINMAN, JE AF NOGA, JT HYDE, TM HERMAN, M BIGELOW, LL WEINBERGER, DR KLEINMAN, JE TI GLUTAMATE-RECEPTOR AUTORADIOGRAPHY OF POSTMORTEM BASAL GANGLIA IN SCHIZOPHRENIA SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH,DIRP,CLIN BRAIN DISORDERS BRANCH,WASHINGTON,DC 20032. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 1994 VL 35 IS 9 BP 735 EP 735 DI 10.1016/0006-3223(94)91089-8 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA NJ172 UT WOS:A1994NJ17200431 ER PT J AU GEORGE, DT BITLER, DA LINNOILA, M AF GEORGE, DT BITLER, DA LINNOILA, M TI REACTION TO SODIUM LACTATE INFUSION IN PERPETRATORS OF DOMESTIC VIOLENCE SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIAAA,BETHESDA,MD 20892. NR 0 TC 7 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 1994 VL 35 IS 9 BP 737 EP 737 DI 10.1016/0006-3223(94)91096-0 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA NJ172 UT WOS:A1994NJ17200438 ER PT J AU GADDE, KM UHDE, TW AF GADDE, KM UHDE, TW TI PANIC DISORDER - GROWTH-HORMONE AND IGF RESPONSES TO EXERCISE SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 1994 VL 35 IS 9 BP 738 EP 738 DI 10.1016/0006-3223(94)91100-2 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA NJ172 UT WOS:A1994NJ17200442 ER PT J AU GREENBERG, BD BENJAMIN, J MURPHY, DL AF GREENBERG, BD BENJAMIN, J MURPHY, DL TI BIPHASIC EFFECTS OF METERGOLINE IN FLUOXETINE-TREATED OCD PATIENTS SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH,CLIN SCI LAB,CLIN NEUROPHARMACOL SECT,BETHESDA,MD 20892. NR 0 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 1994 VL 35 IS 9 BP 738 EP 738 DI 10.1016/0006-3223(94)91102-9 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA NJ172 UT WOS:A1994NJ17200444 ER PT J AU SU, TP BREIER, A MALHOTRA, AK LITMAN, RE HSIAO, JK PICKAR, D AF SU, TP BREIER, A MALHOTRA, AK LITMAN, RE HSIAO, JK PICKAR, D TI CLOZAPINE TREATMENT IN PATIENTS WITH CHRONIC-SCHIZOPHRENIA - EFFICACY AND PREDICTORS OF RESPONSE SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 1994 VL 35 IS 9 BP 745 EP 745 DI 10.1016/0006-3223(94)91128-2 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA NJ172 UT WOS:A1994NJ17200470 ER PT J AU MIALHE, E MILLER, LH AF MIALHE, E MILLER, LH TI BIOLISTIC TECHNIQUES FOR TRANSFECTION OF MOSQUITO EMBRYOS (ANOPHELES-GAMBIAE) SO BIOTECHNIQUES LA English DT Article ID TRANSPOSABLE ELEMENT; GENETIC-TRANSFORMATION; DNA; INTEGRATION; DROSOPHILA; RECOMBINATION; EXPRESSION AB To compensate for the extremely low rates of transformation by DNA microinjection into mosquito embryos of Anopheles gambiae, biolistic techniques were evaluated for introduction of DNA into large numbers of mosquito embryos. Biolistic experiments were first performed with a commercially available instrument intended for this purpose, according to the recommended procedure. The amount of DNA delivered was measured by the expression of luciferase under the control of the Drosophila heat shock protein (hsp) 70 promoter Despite attempts to optimize biolistic parameters, the level of luciferase activity was low and highly variable. Two other methods of biolistic delivery of DNA-coated particles in aqueous suspension were then evaluated. One method used the gas explosion of the commercially available instrument (mentioned above) to drive an aqueous suspension of DNA-coated particles at high pressure. This method reproducibly increased the level of expression about 100-fold without greatly reducing embryo viability. Another method, which was recently described for plant transfection, uses lower pressure to deliver the aqueous suspension of DNA-coated particles. The level of expression of luciferase and the survival of embryos were equivalent to that obtained with the instrument modified for aqueous delivery of particles. Thus, both aqueous methods offer the advantages of reproducibly delivering more DNA to the embryos. Moreover these methods could be suitable for delivering DNA mixed with proteins, such as restriction endonucleases and integrases, that may be destroyed by ethanol precipitation used in the standard PDS-1000/He method. C1 NIAID,MALARIA RES LAB,BETHESDA,MD 20892. NR 17 TC 20 Z9 20 U1 0 U2 1 PU EATON PUBLISHING CO PI NATICK PA 154 E. CENTRAL ST, NATICK, MA 01760 SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD MAY PY 1994 VL 16 IS 5 BP 924 EP & PG 0 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NK216 UT WOS:A1994NK21600035 PM 8068349 ER PT J AU REN, K RUDA, MA AF REN, K RUDA, MA TI A COMPARATIVE-STUDY OF THE CALCIUM-BINDING PROTEINS CALBINDIN-D28K, CALRETININ, CALMODULIN AND PARVALBUMIN IN THE RAT SPINAL-CORD SO BRAIN RESEARCH REVIEWS LA English DT Review DE IMMUNOCYTOCHEMISTRY; SUPERFICIAL DORSAL HORN; DORSAL GRAY COMMISSURE; DORSAL COLUMN; VENTRAL HORN; GANGLIONECTOMY ID NITRIC-OXIDE SYNTHASE; DORSAL-ROOT GANGLIA; NEURONAL NADPH DIAPHORASE; IMMUNOHISTOCHEMICAL LOCALIZATION; HIPPOCAMPAL-NEURONS; NERVOUS-SYSTEM; MESSENGER-RNA; BRAIN-STEM; CYTOARCHITECTONIC ORGANIZATION; HORSERADISH-PEROXIDASE AB Comparison of the immunocytochemical localizations revealed distinct patterns of differential distribution and overlapping of calbindin-D28K (CB-D28K), calretinin (CR), calmodulin (CM) and parvalbumin (PV) in the rat spinal cord. In some areas, one of the four calcium-binding proteins (CBPs) appears to be predominant, for example, CB-D28K in lamina I and ependymal cells, PV at the inner part of laminae II, CR in laminae V and VI and CM in motoneurons of lamina IX. In other regions of the spinal cord, more than one CBPs was abundant. CB-D28K and CR were similarly distributed in lamina II and the lateral spinal and cervical nucleus; CM and PV were similarly abundant in the ventromedial dorsal horn, internal basilar and central cervical nucleus; CR and PV were similarly heterogeneous in the gracile fasciculus from caudal to rostral spinal cord. In the sacral dorsal gray commissure, the distribution patterns of CR and PV were clearly complementary. The unilateral ganglionectomies resulted substantial reduction of CBP-like immunoreactivity (CBP-LI) in the dorsal columns and a reduction of CM- and PV-LI in the ventromedial dorsal horn. In the motor system, only CM labeled large motoneurons in lamina IX and CB-D28K lightly stained pyramidal tract. The apparent absence of CM-LI in the superficial dorsal horn is contradictory to the presence of a CM-dependent nitric oxide synthase in that region. These data indicate that most CBP-LI in the dorsal column pathway had primary afferent origin, while the superficial dorsal horn exhibited intrinsic CBP immunoreactivity. The differential and selective localizations of CBPs in the spinal cord suggest a role for these proteins in spinal nociceptive processing, visceral regulation and dorsal column sensory pathways. RP REN, K (reprint author), NIDR,NEUROBIOL & ANESTHESIOL BRANCH,BLDG 49,ROOM 1A11,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 79 TC 131 Z9 136 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0173 J9 BRAIN RES REV JI Brain Res. Rev. PD MAY PY 1994 VL 19 IS 2 BP 163 EP 179 DI 10.1016/0165-0173(94)90010-8 PG 17 WC Neurosciences SC Neurosciences & Neurology GA NL984 UT WOS:A1994NL98400001 PM 8061685 ER PT J AU QI, CF LISCIA, DS NORMANNO, N MERLO, G JOHNSON, GR GULLICK, WJ CIARDIELLO, F SAEKI, T BRANDT, R KIM, N KENNEY, N SALOMON, DS AF QI, CF LISCIA, DS NORMANNO, N MERLO, G JOHNSON, GR GULLICK, WJ CIARDIELLO, F SAEKI, T BRANDT, R KIM, N KENNEY, N SALOMON, DS TI EXPRESSION OF TRANSFORMING GROWTH-FACTOR-ALPHA, AMPHIREGULIN AND CRIPTO-1 IN HUMAN BREAST CARCINOMAS SO BRITISH JOURNAL OF CANCER LA English DT Article ID MESSENGER RIBONUCLEIC-ACID; MAMMARY EPITHELIAL-CELLS; P53 TUMOR SUPPRESSOR; FACTOR RECEPTOR; TGF-ALPHA; GASTROINTESTINAL CARCINOMAS; COLORECTAL TUMORS; CANCER; GENE; PROTEIN AB The expression of three epidermal growth factor (EGF)-related peptides, transforming growth factor alpha (TGF-alpha), amphiregulin (AR) and cripto-1 (CR-1), was examined by immunocytochemistry (ICC) in 68 primary infiltrating ductal (IDCs) and infiltrating lobular breast carcinomas (ILCs), and in 23 adjacent non-involved human mammary tissue samples. Within the 68 IDC and ILC specimens, 54 (79%) expressed immunoreactive TGF-alpha, 52 (77%) expressed AR and 56 (82%) expressed CR-1. Cytoplasmic staining was observed with all of the antibodies, and this staining could be eliminated by preabsorption of the antibodies with the appropriate peptide immunogen. Cytoplasmic staining with all of the antibodies was confined to the carcinoma cells, since no specific immunoreactivity could be detected in the surrounding stromal or endothelial cells. In addition to cytoplasmic reactivity, the AR antibody also exhibited nuclear staining in a number of the carcinoma specimens. No significant correlations were found between the percentage of carcinoma cells that were positive for TGF-alpha, AR or CR-1 and oestrogen receptor status, axillary lymph node involvement, histological grade, tumour size, proliferative index, loss of heterozygosity on chromosome 17p or overall patient survival. However, a highly significant inverse correlation was observed between the average percentage of carcinoma cells that expressed AR in individual tumours and the presence of a point-mutated p53 gene. Likewise, a significantly higher percentage of tumour cells in the ILC group expressed AR as compared with the average percentage of tumour cells that expressed AR in the IDC group. Of the 23 adjacent, non-involved breast tissue samples, CR-1 could be detected by ICC in only three (13%), while TGF-alpha was found in six (26%) and AR in ten (43%) of the non-involved breast tissues. These data demonstrate that breast carcinomas express multiple EGF-related peptides and show that the differential expression of CR-1 in malignant breast epithelial cells may serve as a potential tumour marker for breast cancer. C1 NCI,TUMOR IMMUNOL & BIOL LAB,TUMOR GROWTH FACTOR SECT,DIV CANC BIOL DIAG & CTR,BETHESDA,MD 20892. US FDA,DIV CYTOKINE BIOL,BETHESDA,MD 20892. HAMMERSMITH HOSP,IMPERIAL CANC RES FUND,MOLEC ONCOL LAB,LONDON W12 0HS,ENGLAND. UNIV NAPLES,FAC MED & CHIRURG 2,CATTEDRA ONCOL MED,I-80131 NAPLES,ITALY. NATL SHIKOKU CANC CTR HOSP,MATSUYAMA,EHIME,JAPAN. OSPED SAN GIOVANNI VECCHIO,SERV ANAT PATOL,USL 1,I-10123 TURIN,ITALY. OI Ciardiello, Fortunato/0000-0002-3369-4841 NR 60 TC 104 Z9 106 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD MAY PY 1994 VL 69 IS 5 BP 903 EP 910 DI 10.1038/bjc.1994.174 PG 8 WC Oncology SC Oncology GA NJ831 UT WOS:A1994NJ83100018 PM 8180021 ER PT J AU BIRKETT, DJ REES, D ANDERSSON, T GONZALEZ, FJ MINERS, JO VERONESE, ME AF BIRKETT, DJ REES, D ANDERSSON, T GONZALEZ, FJ MINERS, JO VERONESE, ME TI IN-VITRO PROGUANIL ACTIVATION TO CYCLOGUANIL BY HUMAN LIVER-MICROSOMES IS MEDIATED BY CYP3A ISOFORMS AS WELL AS BY S-MEPHENYTOIN HYDROXYLASE SO BRITISH JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article DE PROGUANIL; CYCLOGUANIL; HUMAN MICROSOMAL METABOLISM; CYP ISOFORMS ID ACTIVE METABOLITE CYCLOGUANIL; POLYMORPHISM; VARIABILITY; PHARMACOKINETICS; DEFICIENCY; OXIDATION; CLONING AB 1 The activation of proguanil to cycloguanil by human liver microsomes was studied to define the cytochrome P450 (CYP) isoforms involved in this reaction. 2 Apparent K-m values for proguanil ranged from 35 mu M to 183 mu M with microsomes from four human livers. 3 There was a 6.3-fold range of activity with microsomes from seventeen human livers. Rates of proguanil activation correlated significantly with CYP3A activities (benzo[a]pyrene metabolism, caffeine 8-oxidation and omeprazole sulphone formation) and CYP3A immunoreactive content. There was also a highly significant correlation with rates of hydroxyomeprazole formation. Correlations with activities selective for CYP1A2, CYP2C9/10 and CYP2E1, and with immunoreactive CYP1A2 content were not significant. 4 Proguanil activation was inhibited by R,S-mephenytoin, troleandomycin and by inhibitory anti-CYP3A antiserum and anti-CYP2C IgG and was activated by alpha naphthoflavone, Inhibitors selective for CYP1A2, CYP2E1, CYP2A6 or CYP2C9/10 had little or no effect on proguanil activation. The extents of inhibition by R,S-mephenytoin, troleandomycin and the two antibodies varied with the immunoreactive CYP3A content of the microsomes used. 5 It is concluded that proguanil activation to cycloguanil by human liver microsomes is mediated both by S-mephenytoin hydroxylase and isoforms of the CYP3A subfamily. This has implications for the use of proguanil as an in vivo probe for the S-mephenytoin poor metaboliser phenotype. C1 ASTRA HASSLE AB,S-43183 MOLNDAL,SWEDEN. NCI,MOLEC CARCINOGENESIS LAB,BETHESDA,MD 20892. RP BIRKETT, DJ (reprint author), FLINDERS UNIV S AUSTRALIA,MED CTR,DEPT CLIN PHARMACOL,BEDFORD PK,SA 5042,AUSTRALIA. NR 27 TC 64 Z9 64 U1 1 U2 2 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0306-5251 J9 BRIT J CLIN PHARMACO JI Br. J. Clin. Pharmacol. PD MAY PY 1994 VL 37 IS 5 BP 413 EP 420 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA NK539 UT WOS:A1994NK53900003 PM 8054246 ER PT J AU BOUZAS, EA MASTORAKOS, G AF BOUZAS, EA MASTORAKOS, G TI CENTRAL SEROUS RETINOPATHY IN SYSTEMIC LUPUS-ERYTHEMATOSUS - A MANIFESTATION OF THE DISEASE OR OF ITS TREATMENT SO BRITISH JOURNAL OF OPHTHALMOLOGY LA English DT Letter C1 NICHHD,DEV ENDOCRINOL BRANCH,BETHESDA,MD 20892. RP BOUZAS, EA (reprint author), RED CROSS HOSP,DEPT OPHTHALMOL,ERYTHROU STAVROU ST,ATHENS,GREECE. NR 2 TC 10 Z9 10 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 0007-1161 J9 BRIT J OPHTHALMOL JI Br. J. Ophthalmol. PD MAY PY 1994 VL 78 IS 5 BP 420 EP 421 DI 10.1136/bjo.78.5.420-b PG 2 WC Ophthalmology SC Ophthalmology GA NN640 UT WOS:A1994NN64000032 PM 8025087 ER PT J AU FONG, DS RAIZMAN, MB AF FONG, DS RAIZMAN, MB TI SPONTANEOUS HYPHEMA ASSOCIATED WITH ANTERIOR UVEITIS - REPLY SO BRITISH JOURNAL OF OPHTHALMOLOGY LA English DT Letter C1 NEW ENGLAND EYE CTR,BOSTON,MA 02111. RP FONG, DS (reprint author), NEI,DIV BIOMETRY & EPIDEMIOL,CLIN TRIALS BRANCH,BLDG 31,ROOM 6A52,BETHESDA,MD 20892, USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 0007-1161 J9 BRIT J OPHTHALMOL JI Br. J. Ophthalmol. PD MAY PY 1994 VL 78 IS 5 BP 420 EP 420 PG 1 WC Ophthalmology SC Ophthalmology GA NN640 UT WOS:A1994NN64000031 ER PT J AU HAYES, RB POTTERN, LM SWANSON, GM LIFF, JM SCHOENBERG, JB GREENBERG, RS SCHWARTZ, AG BROWN, LM SILVERMAN, DT HOOVER, RN AF HAYES, RB POTTERN, LM SWANSON, GM LIFF, JM SCHOENBERG, JB GREENBERG, RS SCHWARTZ, AG BROWN, LM SILVERMAN, DT HOOVER, RN TI TOBACCO USE AND PROSTATE-CANCER IN BLACKS AND WHITES IN THE UNITED-STATES SO CANCER CAUSES & CONTROL LA English DT Article DE CASE-CONTROL; NEOPLASMS; PROSTATE; RACE; TOBACCO; UNITED-STATES AB Prostate cancer occurs more frequently in Blacks than Whites in the United States. A population-based case-control study which investigated the association between tobacco use and prostate cancer risk was carried out among 981 pathologically confirmed cases (479 Blacks, 502 Whites) of prostate cancer, diagnosed between 1 August 1986 and 30 April 1989, and 1,315 controls (594 Blacks, 721 Whites). Study subjects, aged 40 to 79 years, resided in Atlanta (GA), Detroit (MI), and 10 counties in New Jersey, geographic areas covered by three, population-based, cancer registries. No excesses in risk for prostate cancer were seen for former cigarette smokers, in Blacks (odds ratio [OR] = 1.1, 95 percent confidence interval [CI] = 0.7-1.5) and in Whites (OR = 1.2, CI = 0.9-1.6), or for current cigarette smokers, in Blacks (OR = 1.0, CI = 0.7-1.4) and in Whites (OR = 1.2, CI = 0.8-1.7). Increases in risk were noted for smokers of 40 or more cigarettes per day, among former (OR = 1.4, CI = 1.0-1.5) and current (OR = 1.5, CI = 1.0-2.4) smokers. Duration of cigarette use and cumulative amount of cigarette use (pack-years) were not associated with prostate cancer risk for Blacks or Whites. By age, only the youngest subjects, aged 40 to 59 years, showed excess risk associated with current (OR = 1.5, CI = 1.0-2.3) and former (OR = 1.7, CI = 1.1-2.6) use of cigarettes, but there were no consistent patterns in this group according to amount or duration of smoking. Risks also were not elevated for former or current users of pipes, cigars, or chewing tobacco, but the risk associated with current snuff use was OR = 5.5 (CI = 1.2-26.2). This subgroup finding may have been due to chance. The results of the present study may be consistent with a small excess risk for prostate cancer associated with tobacco use, but the lack of consistent findings in population subgroups and the lack of a clear dose-response relationship argue more strongly that no causal association exists. The data do not indicate that the Black-White difference in prostate cancer risk is related to tobacco use. RP HAYES, RB (reprint author), NCI,PROGRAM EPIDEMIOL & BIOSTAT,EPN 418,BETHESDA,MD 20892, USA. FU NCI NIH HHS [N01-CP-51089, N01-CN-0522, N01-CP-51090] NR 0 TC 27 Z9 27 U1 0 U2 2 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD MAY PY 1994 VL 5 IS 3 BP 221 EP 226 DI 10.1007/BF01830240 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA NP381 UT WOS:A1994NP38100003 PM 8061169 ER PT J AU COCCO, P PALLI, D BUIATTI, E CIPRIANI, F DECARLI, A MANCA, P WARD, MH BLOT, WJ FRAUMENI, JF AF COCCO, P PALLI, D BUIATTI, E CIPRIANI, F DECARLI, A MANCA, P WARD, MH BLOT, WJ FRAUMENI, JF TI OCCUPATIONAL EXPOSURES AS RISK-FACTORS FOR GASTRIC-CANCER IN ITALY SO CANCER CAUSES & CONTROL LA English DT Article DE DIET; FARMING; GASTRIC CANCER; MALES; OCCUPATION AB Occupational associations with gastric cancer were investigated in a multicenter case-control study in Italy involving interviews with 640 histologically confirmed male cases and 959 controls, randomly selected from the resident populations of the study areas. From information on the three jobs each person held the longest, risks were evaluated according to employment in 35 occupations (ever or 21+ years) and to estimated exposure (ever or 21+ years) to six chemicals using a job-exposure matrix. All risk estimates were adjusted by personal, demographic, and dietary variables identified as gastric-cancer risk factors in previous analyses. The only significantly increased risk was observed for sailors, seamen, and allied groups (ever employed: odds ratio [OR] = 2.9; 95 percent confidence interval [CI] = 1.1-8.0; 21+ years: OR = 3.1, CI = 0.8-13). Nonsignificant increases after 21+ years of employment were observed for forestry workers, miners, and janitors and cleaners. Crude ORs were elevated significantly among farmers, but adjusting for demographic and lifestyle factors largely eliminated the association: a nonsignificant 30 percent excess risk remained for farm laborers, but there was no rise in risk among long-term farm laborers and no excess among farm owners. Application of the job-exposure matrix revealed excess risks of borderline significance associated with potential exposure to mineral dusts and nitrogen oxides. For subjects with 21+ years of potential exposure, nonsignificantly increased risks were related to mineral dusts, asbestos, fertilizers, and nitrosamines. Although possibly incomplete occupational histories and use of broad occupational codes likely resulted in some exposure misclassification, the results of this study indicate that occupation in general is not a strong risk factor for gastric cancer. The findings, however, are consistent with previous reports suggesting that certain occupational exposures may influence gastric cancer risk. C1 NCI,BIOSTAT BRANCH,EPN 431,BETHESDA,MD 20892. RI Decarli, Adriano/C-3129-2017; OI Decarli, Adriano/0000-0003-1451-8292; PALLI, Domenico/0000-0002-5558-2437 NR 0 TC 32 Z9 33 U1 1 U2 2 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD MAY PY 1994 VL 5 IS 3 BP 241 EP 248 DI 10.1007/BF01830243 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA NP381 UT WOS:A1994NP38100006 PM 8061172 ER PT J AU CHOW, WH MCLAUGHLIN, JK MENCK, HR MACK, TM AF CHOW, WH MCLAUGHLIN, JK MENCK, HR MACK, TM TI RISK-FACTORS FOR EXTRAHEPATIC BILE-DUCT CANCERS - LOS-ANGELES-COUNTY, CALIFORNIA (USA) SO CANCER CAUSES & CONTROL LA English DT Article DE ALCOHOL; BODY MASS INDEX; EXTRAHEPATIC BILE DUCT CANCERS; RISK FACTORS; TOBACCO SMOKING; USA AB Extrahepatic bile duct (EBD) cancers are rare and their risk factors are poorly understood. Except for a history of gallbladder diseases, evidence for other potential risk factors, such as excess body weight and use of tobacco and alcohol, is scant. A case-control study was conducted to examine risk factors for EBD cancers, including ampulla of Vater tumors, among Los Angeles County (California, USA) residents. Included were 105 histologically confirmed cases diagnosed between 1 March 1985 and 31 October 1989, aged 30 to 84 years, and 255 population-based controls frequency-matched to cases by gender and age in five-year groups. Cases and controls were interviewed about their demographic background and potential risk factors, including tobacco, alcohol, and beverage consumption, diet, medical history, and reproductive factors among women. For deceased cases, their next-of-kin were interviewed. Risk of cancers of both subsites of extrahepatic duct and ampulla of Vater increased with smoking of cigars/pipes or cigarettes. For both men and women, risks increased twofold or more among those who smoked cigarettes for 50 or more pack-years. While a history of gallbladder diseases substantially increased the risk of cancers of both subsites, excess body mass index was associated only with cancer of extrahepatic duct subsite (odds ratio [OR] = 4.0, 95 percent confidence interval [CI] = 1.1-14.2 among men and OR = 2.7; CI = 0.8-9.4 among women in the highest quartile relative to those in the lowest quartile). Alcohol drinkers had lower risks compared with nondrinkers, but no consistent trend was observed with amount consumed. No consistent patterns of risks were found for coffee, tea, diet, occupation, or reproductive factors. These results suggest that lifestyle-related factors, such as use of tobacco and excess body weight, play a role in EBD cancer risk. RP CHOW, WH (reprint author), NCI,DIV CANC ETIOL,EPIDEMIOL & BIOSTAT PROGRAM,EPN 415,BETHESDA,MD 20892, USA. NR 0 TC 44 Z9 47 U1 2 U2 2 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD MAY PY 1994 VL 5 IS 3 BP 267 EP 272 DI 10.1007/BF01830247 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA NP381 UT WOS:A1994NP38100010 PM 8061176 ER PT J AU VOLPE, DA DU, DL GRIESHABER, CK MURPHY, MJ AF VOLPE, DA DU, DL GRIESHABER, CK MURPHY, MJ TI IN-VITRO CHARACTERIZATION OF THE MYELOTOXICITY OF CYCLOPENTENYL CYTOSINE SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE CYCLOPENTENYL CYTOSINE; CPE-C; MYELOTOXICITY; IN VITRO; HUMAN; MURINE ID HUMAN-BONE-MARROW; CONDITIONED MEDIUM; PROGENITOR CELLS; COLONY FORMATION; CFU-E; CYTIDINE; INVITRO; TRIPHOSPHATE; ARABINOSIDE; ANTITUMOR AB We studied the toxicity of a new experimental anticancer drug, cyclopentenyl cytosine (CPE-C), to human and murine hematopoietic progenitor cells in vitro. Due to CPE-C's in vivo myelotoxicity, it was important to characterize its potential adverse effects on human marrow cells during preclinical development of the drug. Marrow cells were exposed to CPE-C for either 1 h prior to addition in clonal assays or continuously during their culture period. The inhibitory effects of CPE-C on myeloid (CFU-gm) and erythroid (CFU-e, BFU-e) colony formation were concentration- and time-dependent, with continuous CPE-C exposure being significantly more inhibitory than l-h exposure. The results of both exposure experiments were combined to investigate colony inhibition as a function of overall drug exposure (concentration x time, AUC) and data analyzed by the nonlinear Emax equation. Human and murine CFU-gm had similar AUC-response curves and IAUC(70) values (i.e., AUC at 70% colony inhibition) of 40.8 and 41.9 mu Mh, respectively. In contrast, murine CFU-e and BFU-e were more sensitive to CPE-C, having lower IAUC(70) values (both, 21.1 mu Mh) than human CFU-e and BFU-e (107.8 and 33.0 mu Mh, respectively). This difference was most prominent with the late erythroid progenitor, CFU-e, in that the human cells were 5 times more resistant to inhibition by CPE-C. CPE-C was myelotoxic in vitro to human and murine marrow cells and toxicity correlated with overall drug exposure. C1 HIPPLE CANC RES CTR,DAYTON,OH 45439. NCI,BETHESDA,MD 20892. FU NCI NIH HHS [N44-CM-77831] NR 30 TC 10 Z9 10 U1 0 U2 1 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 MAY PY 1994 VL 34 IS 2 BP 103 EP 108 PG 6 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA NM002 UT WOS:A1994NM00200003 PM 8194161 ER PT J AU COLE, DJ TAUBENBERGER, JK POCKAJ, BA YANNELLI, JR CARTER, C CARRASQUILLO, J LEITMAN, S STEINBERG, SM ROSENBERG, SA YANG, YC AF COLE, DJ TAUBENBERGER, JK POCKAJ, BA YANNELLI, JR CARTER, C CARRASQUILLO, J LEITMAN, S STEINBERG, SM ROSENBERG, SA YANG, YC TI HISTOPATHOLOGICAL ANALYSIS OF METASTATIC MELANOMA DEPOSITS IN PATIENTS RECEIVING ADOPTIVE IMMUNOTHERAPY WITH TUMOR-INFILTRATING LYMPHOCYTES SO CANCER IMMUNOLOGY IMMUNOTHERAPY LA English DT Article DE TIL; MELANOMA; HISTOPATHOLOGY; IMAGING; LYMPHOCYTIC INFILTRATE ID INVIVO ANTITUMOR-ACTIVITY; AUTOLOGOUS TUMOR; INTERLEUKIN-2; CANCER; EXPRESSION; HUMANS; CELLS AB Tumor-infiltrating lymphocytes (TIL) from a wide range of human and murine tumors can be expanded in vitro using interleukin-2 (IL-2). These TIL are cytolytic T lymphocytes with in vivo and in vitro antitumor activity in mice and in humans. TIL from human melanoma can recognize autologous tumor in an MHC-restricted fashion, localize in vivo after In-111 labeling, and mediate regression of large metastatic deposits. Although studied extensively in vitro, less is known in vivo about TIL activity associated with tumor regression. This study was undertaken, in association with a study of TIL localization, to investigate mechanisms of TIL action by evaluating histopathological changes that occur at the tumor site during TIL administration. A total of 106 pre- and post-treatment pathological specimens from 25 patients enrolled in phase II TIL treatment and In-111-TIL. imaging protocols were examined blindly by a single pathologist. Histological subtype, lymphocytic infiltration, melanin content, vascularity, and necrosis were documented for each tumor specimen. Average baseline and post-treatment parameters were compared. Any significant changes were evaluated for correlation with clinical response and In-111-TIL localization to tumor. Melanin content and vascularity of the tumor did not change as a result of therapy or correlate with either response or TIL localization. However, both increased lymphocytic infiltration and tumor necrosis were present after TIL administration (P = 0.044 and 0.032 respectively). Furthermore, increases in lymphocytic infiltration correlated with tumor imaging using In-111-TIL, and with the percentage of In-111-labeled injectate present per gram of tumor specimen (P = 0.036 and 0.0041 respectively). This suggests that TIL either account for the increased lymphocytes directly, or localize to tumor and recruit endogenous lymphocytes. We were unable to demonstrate any pretreatment histopathological predictors of response or variables that significantly correlated with subsequent clinical response, although peak and average values of necrosis were higher in responding patients compared to non-responding patients. C1 NCI,DEPT PATHOL,BETHESDA,MD 20892. NCI,DEPT TRANSFUS MED,DIV CANC TREATMENT,BETHESDA,MD 20892. NCI,DEPT NUCL MED,DIV CANC TREATMENT,BETHESDA,MD 20892. NCI,BIOSTAT & DATA MANAGEMENT SECT,DIV CANC TREATMENT,BETHESDA,MD 20892. RP COLE, DJ (reprint author), NCI,SURG BRANCH,DIV CANC TREATMENT,BLDG 10,ROOM 2B42,BETHESDA,MD 20892, USA. RI Carrasquillo, Jorge/E-7120-2010; OI Carrasquillo, Jorge/0000-0002-8513-5734 NR 24 TC 24 Z9 24 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0340-7004 J9 CANCER IMMUNOL IMMUN JI Cancer Immunol. Immunother. PD MAY PY 1994 VL 38 IS 5 BP 299 EP 303 DI 10.1007/BF01525507 PG 5 WC Oncology; Immunology SC Oncology; Immunology GA NH428 UT WOS:A1994NH42800003 PM 8162611 ER PT J AU AFSHARI, CA BARRETT, JC AF AFSHARI, CA BARRETT, JC TI DISRUPTION OF G(0)-G(1) ARREST IN QUIESCENT AND SENESCENT CELLS TREATED WITH PHOSPHATASE INHIBITORS SO CANCER RESEARCH LA English DT Note ID SMALL-T-ANTIGEN; HUMAN-DIPLOID FIBROBLASTS; STIMULATE DNA-SYNTHESIS; PROTEIN PHOSPHATASE-2A; OKADAIC ACID; SIMIAN VIRUS-40; SIGNAL TRANSDUCTION; MAP KINASES; PHOSPHORYLATION; EXPRESSION AB The majority of signal transduction studies have focused on events induced by mitogen stimulation. However, little is known about the negative control signals that cause or maintain growth arrest and must be overcome for mitogenesis to occur. We investigated the possible role of protein phosphatases in this negative regulatory process. Treatment of quiescent hamster and human fibroblasts with low doses of the phosphatase inhibitors sodium o-vanadate or okadaic acid allowed 30-40% of cells to progress from G(0)-G(1) arrest to S phase. This was accompanied by phosphorylation of the retinoblastoma and MAP-kinase proteins, as well as induction of the cdc2 protein. Furthermore, we observed that protein phosphatase inhibitor treatment could override the block to DNA synthesis in senescent cells, which are normally nonresponsive to mitogens. These data suggest that protein phosphatases may play a role in the negative regulation of cell growth and maintenance of growth arrest. C1 NIEHS,MOLEC CARCINOGENESIS LAB,RES TRIANGLE PK,NC 27709. UNIV N CAROLINA,CURRICULUM TOXICOL,CHAPEL HILL,NC 27599. NR 42 TC 36 Z9 38 U1 0 U2 3 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 MAY 1 PY 1994 VL 54 IS 9 BP 2317 EP 2321 PG 5 WC Oncology SC Oncology GA NH256 UT WOS:A1994NH25600009 PM 8162573 ER PT J AU KUZMIN, I STACKHOUSE, T LATIF, F DUH, FM GEIL, L GNARRA, J YAO, M ORCUTT, ML LI, H TORY, K LEPASLIER, D CHUMAKOV, I COHEN, D CHINAULT, AC LINEHAN, WM LERMAN, MI ZBAR, B AF KUZMIN, I STACKHOUSE, T LATIF, F DUH, FM GEIL, L GNARRA, J YAO, M ORCUTT, ML LI, H TORY, K LEPASLIER, D CHUMAKOV, I COHEN, D CHINAULT, AC LINEHAN, WM LERMAN, MI ZBAR, B TI ONE-MEGABASE YEAST ARTIFICIAL CHROMOSOME AND 400-KILOBASE COSMID-PHAGE CONTIGS CONTAINING THE VON HIPPEL-LINDAU TUMOR-SUPPRESSOR AND CA2+-TRANSPORTING ADENOSINE-TRIPHOSPHATASE ISOFORM-2 GENES SO CANCER RESEARCH LA English DT Article ID PLASMA-MEMBRANE; DISEASE; LOCALIZATION; FRAGMENTS; CLONING; REGION; PUMP AB We have isolated and ordered yeast artificial chromosomes (YACs) and cosmids surrounding the von Hippel-Lindau (VHL) tumor suppressor and plasma membrane Ca2+-transporting ATPase isoform 2 (PMCA-2) genes on chromosome 3p25-26. The YAC contig consists of six YACs and covers a region of 1 megabase. A cosmid-phage contig around VHL and PMCA-2 genes (400 kilobases) was established and integrated into the YAC map. Using these clones, we generated an EcoRI map of the 400-kilobase region. PMCA-2 and VHL complementary DNA were positioned entirely within the cosmid-phage contig as well as two polymorphic markers (D3S601 and D3S1317). This physical map of the cloned region will allow a detailed analysis of both the PMCA-2 and VHL genes. Some of the genomic clones may be useful for isolation of the full-length VHL complementary DNA. C1 NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,FREDERICK,MD 21702. NCI,SURG BRANCH,BETHESDA,MD 20892. CTR ETUD POLYMORPHISME HUMAIN,F-75010 PARIS,FRANCE. BAYLOR COLL MED,INST MOLEC GENET,HOUSTON,TX 77030. RP KUZMIN, I (reprint author), NCI,FREDERICK CANC RES & DEV CTR,IMMUNOBIOL LAB,BOX B,FREDERICK,MD 21702, USA. NR 23 TC 22 Z9 22 U1 0 U2 5 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 MAY 1 PY 1994 VL 54 IS 9 BP 2486 EP 2491 PG 6 WC Oncology SC Oncology GA NH256 UT WOS:A1994NH25600037 PM 8162598 ER PT J AU EBINA, M STEINBERG, SM MULSHINE, JL LINNOILA, RI AF EBINA, M STEINBERG, SM MULSHINE, JL LINNOILA, RI TI RELATIONSHIP OF P53 OVEREXPRESSION AND UP-REGULATION OF PROLIFERATING CELL NUCLEAR ANTIGEN WITH THE CLINICAL COURSE OF NONSMALL CELL LUNG-CANCER SO CANCER RESEARCH LA English DT Article ID TUMOR SUPPRESSOR GENE; DNA POLYMERASE-DELTA; PROGNOSTIC FACTOR; MONOCLONAL-ANTIBODIES; PARAFFIN SECTIONS; AUXILIARY PROTEIN; FLOW-CYTOMETRY; EXPRESSION; MUTATIONS; CARCINOMA AB p53 is known to play a central role in the control of cell proliferation and carcinogenesis. In non-small cell lung cancer, however, the clinicopathological studies of p53 have yielded conflicting results. In the current study, me examined 123 non-small cell lung cancers with detailed clinical information, 71 primary and 52 metastatic tumors, using formalin-fixed and paraffin-embedded surgical specimens to show the clinicopathological correlation of the immunohistochemical (DO-7) overexpression of p53. Nuclear specific p53 overexpression appeared in 48 (39%; any number of tumor cells positive) of 123 tumors (35% of primary and 44% of metastatic tumors). The distribution and intensity of staining mere variable. Ninety-eight % of all tumors also expressed nuclear immunoreactivity for proliferating cell nuclear antigen (PCNA; PC 10) to a varying degree. In a univariate analysis, both p53 (>10% of tumor cells positive; n = 11) and PCNA (>50% of tumor cells positive; n = 32) mere associated with shorter survival in the curative intent group (stages I, II, and IIIA) of 63 patients. In a multivariate analysis including all clinicopathological variables, the overexpression of p53 (but not PCNA) was found to be an independent prognostic factor (P-2 = 0.0011) in the curative intent group. No correlation was detected between the immunoreactivities and patient characteristics, such as age, gender, or smoking. Double immunohistochemistry of both p53 and PCNA revealed a distinct pattern, whereas its clinicopathological correlation remained elusive. We conclude that p53 overexpression in non-small cell lung cancer (but not PCNA) is independently associated with a shortened survival and may be of prognostic significance in selected patients with earlier stage cancer. C1 NCI,BIOMARKERS & PREVENT RES BRANCH,EXPTL PATHOL SECT,ROCKVILLE,MD 20850. NCI,BIOSTAT & DATA MANAGEMENT SECT,ROCKVILLE,MD 20850. NR 52 TC 147 Z9 152 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 MAY 1 PY 1994 VL 54 IS 9 BP 2496 EP 2503 PG 8 WC Oncology SC Oncology GA NH256 UT WOS:A1994NH25600039 PM 7909277 ER PT J AU EDWARDS, RJ MURRAY, BP MURRAY, S SCHULZ, T NEUBERT, D GANT, TW THORGEIRSSON, SS BOOBIS, AR DAVIES, DS AF EDWARDS, RJ MURRAY, BP MURRAY, S SCHULZ, T NEUBERT, D GANT, TW THORGEIRSSON, SS BOOBIS, AR DAVIES, DS TI CONTRIBUTION OF CYP1A1, AND CYP1A2 TO THE ACTIVATION OF HETEROCYCLIC AMINES IN MONKEYS AND HUMAN SO CARCINOGENESIS LA English DT Article ID RAT HEPATIC CYTOCHROME-P-450C; ETHOXYRESORUFIN O-DEETHYLASE; HUMAN-LIVER-MICROSOMES; METABOLIC-ACTIVATION; MUTAGENIC ACTIVATION; ANTIPEPTIDE ANTIBODY; AROMATIC-AMINES; SURFACE REGION; ACID SEQUENCE; IDENTIFICATION AB The activation of heterocyclic amines to mutagenic products by hepatic microsomal fractions from cynomolgus monkey, marmoset monkey and man,vas compared with the respective levels of cytochrome P450 enzymes CYP1A1 and CYP1A2. The rate of activation of 2-amino-3,8-dimethylimidazo[4,5-f] quinoxaline (MeIQx), 2-amino-3-methylimidazo[4,5-f] quinoline (IQ) and 2-amino-1-methyl-6-phenylimidazo[4,5-b] pyridine (PhIP) to mutagens by hepatic microsomal fraction from cynomolgus monkey was very low. This was associated with a lack of constitutive expression of CYP1A1 and CYP1A2. In contrast, human hepatic microsomal fraction readily activates these heterocyclic amines and this is associated with constitutive expression of CYP1A2. Treatment of cynomolgus monkey with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) causes a very modest induction of CYP1A2, and a small increase in the activation of MeIQx and IQ. However, there was marked induction of CYP1A1 which was accompanied by > 10-fold increases in PhIP activation and 7-ethoxyresorufin O-deethylase (EROD), 7-methoxyresorufin O-demethylase (MROD) and aryl hydrocarbon hydroxylase activities. Following treatment of cynomolgus monkey with 3-methylcholanthrene, induction of CYP1A1, but not CYP1A2, was evident. In untreated marmoset monkey the activations of MeIQx and PhIP, as well as phenacetin O-deethylase, EROD, MROD and aryl hydrocarbon hydroxylase activities, are similar to those in man, although the activations of IQ and coumarin 7-hydroxylase activity are lower than in man. The presence of constitutive CYP1A2, and the absence of CYP1A1, in the liver of this species correspond to the situation in man. Treatment of marmoset monkey with TCDD results in increased CYP1A2 levels (4-fold), accompanied by proportional increases in the activation of MeIQx and IQ and phenacetin O-deethylase, EROD and MROD activities. The activation of PhIP is increased disproportionately, by 8-fold, most likely due to the activity of CYP1A1 which is also induced by TCDD in this species. Overall, the hepatic metabolism of heterocyclic amines by CYP1A enzymes in the untreated marmoset monkey resembles that in human more closely than that in the cynomolgus monkey. Therefore, marmoset monkey may be a more suitable model than the cynomolgus monkey for carcinogenicity studies involving MeIQx and PhIP, but not IQ. C1 FREE UNIV BERLIN,INST TOXIKOL & EMBRYOPHARMAKOL,W-1000 BERLIN,GERMANY. NCI,EXPTL CARCINOGENESIS LAB,BETHESDA,MD 20892. RP EDWARDS, RJ (reprint author), ROYAL POSTGRAD MED SCH,DEPT CLIN PHARMACOL,DU CANE RD,LONDON W12 0NN,ENGLAND. OI Boobis, Alan/0000-0003-3371-386X NR 53 TC 127 Z9 129 U1 0 U2 2 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD MAY PY 1994 VL 15 IS 5 BP 829 EP 836 DI 10.1093/carcin/15.5.829 PG 8 WC Oncology SC Oncology GA NP072 UT WOS:A1994NP07200008 PM 8200083 ER PT J AU GRAFSTROM, RC DYPBUKT, JM SUNDQVIST, K ATZORI, L NIELSEN, I CURREN, RD HARRIS, CC AF GRAFSTROM, RC DYPBUKT, JM SUNDQVIST, K ATZORI, L NIELSEN, I CURREN, RD HARRIS, CC TI PATHOBIOLOGICAL EFFECTS OF ACETALDEHYDE IN CULTURED HUMAN EPITHELIAL-CELLS AND FIBROBLASTS SO CARCINOGENESIS LA English DT Article ID HUMAN BRONCHIAL FIBROBLASTS; CARCINOGENESIS; INVITRO; FORMALDEHYDE; DNA; MUTAGENICITY; ACROLEIN; TOXICITY; THIOLS; SERUM AB The ability of acetaldehyde, a respiratory carcinogen present in tobacco smoke and automotive emissions, to affect cell viability, thiol status and intracellular Ca2+ levels and to cause DNA damage and mutations has been studied using cultured human cells. Within a concentration range of 3-100 mM, a Ih exposure to acetaldehyde decreases colony survival and inhibits uptake of the vital dye neutral red in bronchial epithelial cells. Acetaldehyde also causes both DNA interstrand cross-links and DNA protein cross-links whereas no DNA single strand breaks are detected. The cellular content of glutathione is also decreased by acetaldehyde, albeit, without concomitant changes in the glutathione redox status or in the content of protein thiols. Transient or sustained increases in cytosolic Ca2+ occur within minutes following exposure of cells to acetaldehyde. Moreover, acetaldehyde significantly decreases the activity of the DNA repair enzyme O-6-methylguanine-DNA methyltransferase. Finally, a 5 h exposure to acetaldehyde causes significant levels of 6-thioguanine resistance mutations in an established mutagenesis model involving skin fibroblasts. The results indicate that mM concentrations of acetaldehyde cause a wide range of cytopathic effects associated with multistep carcinogenesis. The fact that acetaldehyde, in relation to its cytotoxicity, causes comparatively higher genotoxicity and inhibits DNA repair more readily than other major aldehydes in tobacco smoke and automotive emissions is discussed. C1 UNIV TROMSO,INST MED BIOL,N-9001 TROMSO,NORWAY. MICROBIOL ASSOCIATES INC,ROCKVILLE,MD 20850. NCI,HUMAN CARCINOGENESIS LAB,BETHESDA,MD 20892. RP GRAFSTROM, RC (reprint author), KAROLINSKA INST,INST ENVIRONM MED,DIV TOXICOL,S-17177 STOCKHOLM,SWEDEN. RI Grafstrom, Roland/N-7217-2016 NR 29 TC 53 Z9 56 U1 0 U2 2 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD MAY PY 1994 VL 15 IS 5 BP 985 EP 990 DI 10.1093/carcin/15.5.985 PG 6 WC Oncology SC Oncology GA NP072 UT WOS:A1994NP07200030 PM 8200105 ER PT J AU DONG, ZG CMARIK, JL WENDEL, EJ COLBURN, NH AF DONG, ZG CMARIK, JL WENDEL, EJ COLBURN, NH TI DIFFERENTIAL TRANSFORMATION EFFICIENCY BUT NOT AP-1 INDUCTION UNDER ANCHORAGE-DEPENDENT AND ANCHORAGE-INDEPENDENT CONDITIONS SO CARCINOGENESIS LA English DT Article ID JB6 CELLS; EPIDERMAL-CELLS; C-JUN; PROMOTION; RESISTANT; GROWTH; EXPRESSION; CARCINOGENESIS; STROMELYSIN; MECHANISMS AB The JB6 mouse epidermal cell system has been extensively used as an in vitro model for the study of tumor promotion. The present study aimed to assess the relevance of monolayer measurements to the process of transformation, which is induced more efficiently under anchorage-independent (AI) conditions. Although it would be ideal to use identical conditions for studying tumor promoter-induced transformation and biochemical and molecular events that may cause the process, it is not feasible in the case of soft agar conditions because cells cannot be readily recovered. In the present report, we used liquid medium over agar as an AI condition that permited efficient recovery of cells. Responses to tumor promoter have been compared with those in monolayer and semisolid agar. Results indicate that 12-O-tetradecanoyl-phorbol-13-acetate (TPA) induced similar magnitude concentration-dependent transformation of JB6 cells under both of the AI conditions, namely soft agar and over-agar. Under anchorage-dependent (AD) conditions of exposure to TPA, the transformation efficiency was much lower than that seen under AT conditions. Mechanical detachment of monolayer cells after 5-10 days TPA exposure enriched the transformed phenotype. Activator protein 1 transcriptional activity measured at 12 h was induced equally under AD and AI conditions, and thus is not an early limiting event that could explain the lower transformation efficiency seen under AD conditions. To summarize, the over-agar and monolayer assays described in this study can be considered valid for the study of early biochemical and molecular events relevant to the promotion of transformation measured in soft agar. C1 NCI,FREDERICK CANC RES & DEV CTR,VIRAL CARCINOGENESIS LAB,CELL BIOL SECT,FREDERICK,MD 21702. RP DONG, ZG (reprint author), NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702, USA. NR 29 TC 28 Z9 28 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD MAY PY 1994 VL 15 IS 5 BP 1001 EP 1004 DI 10.1093/carcin/15.5.1001 PG 4 WC Oncology SC Oncology GA NP072 UT WOS:A1994NP07200033 PM 8200060 ER PT J AU PEREIRA, MA BARNES, LH RASSMAN, VL KELLOFF, GV STEELE, VE AF PEREIRA, MA BARNES, LH RASSMAN, VL KELLOFF, GV STEELE, VE TI USE OF AZOXYMETHANE-INDUCED FOCI OF ABERRANT CRYPTS IN RAT COLON TO IDENTIFY POTENTIAL CANCER CHEMOPREVENTIVE AGENTS SO CARCINOGENESIS LA English DT Article ID NONSTEROIDAL ANTIINFLAMMATORY DRUG; PUTATIVE PRENEOPLASTIC LESIONS; MALE F344 RATS; FUMARIC-ACID; INTESTINAL CARCINOGENESIS; ORNITHINE DECARBOXYLASE; HEXOSAMINIDASE ACTIVITY; MURINE COLON; DIETARY-FAT; INHIBITION AB Foci of aberrant and/or hexosaminidase-negative crypts in rat colon are putative precancerous lesions that have been proposed as biomarkers for short-term bioassays for chemical carcinogens and chemopreventive agents. The ability of a substance to reduce the yield of azoxymethane (AOM)-induced foci in the colon of male Fischer 344 rats, was evaluated as a screening assay for chemopreventive agents. Twenty-eight test agents were administered continuously in the diet from the start of the experiments until the animals were killed 35 days later. AOM was s.c. administered either as 15 mg/kg body wt on days 7 and 14 or as 30 mg/kg body wt on day 7 of the experiment. Foci of aberrant crypts were evaluated in whole mounts of methylene blue-stained colons. AOM induced twice as many foci when administered between 8.40 and 11.00 a.m. than between 2.45 and 5.55 p.m. Calcium salts of carbonate, chloride and glucarate decreased the yield of AOM-induced foci while the acidic salts of lactate and phosphate did not inhibit the formation of foci. Dimethyl-fumarate, fumaric acid, genistein, piroxicam, simethicone, sodium suramin and sulindac reduced the yield of AOM-induced foci of aberrant crypts, with genistein being the most potent. Only piroxicam of this group has previously been shown to inhibit colon cancer, while the rest have yet to be evaluated. Ibuprofen did not inhibit the formation of foci, although it has been reported to inhibit AOM-induced colon cancer in rats. Piroxicam and sulindac appeared to reduce preferentially hexosaminidase-negative foci of aberrant crypts, compared with those of apparently normal morphology. The AOM-induced foci of aberrant crypts assay appears suitable for screening chemicals for chemopreventive action. C1 NCI,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20856. ENVIRONM HLTH RES & TESTING INC,LEXINGTON,KY 40503. FU NCI NIH HHS [N01-CN-25495-01, N01-CN-85096-01] NR 51 TC 192 Z9 201 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD MAY PY 1994 VL 15 IS 5 BP 1049 EP 1054 DI 10.1093/carcin/15.5.1049 PG 6 WC Oncology SC Oncology GA NP072 UT WOS:A1994NP07200040 PM 8200067 ER PT J AU DEVEREUX, TR WHITE, CM SILLS, RC BUCHER, JR MARONPOT, RR ANDERSON, MW AF DEVEREUX, TR WHITE, CM SILLS, RC BUCHER, JR MARONPOT, RR ANDERSON, MW TI LOW-FREQUENCY OF H-RAS MUTATIONS IN HEPATOCELLULAR ADENOMAS AND CARCINOMAS AND IN HEPATOBLASTOMAS FROM B6C3F1 MICE EXPOSED TO OXAZEPAM IN THE DIET SO CARCINOGENESIS LA English DT Note ID MOUSE-LIVER TUMORS; INDUCED LUNG-TUMORS; PROTOONCOGENE ACTIVATION; N-NITROSODIETHYLAMINE; DNA; CARCINOGENESIS; POLYMERASE; ONCOGENES; RESISTANT; RATS AB Oxazepam has been the subject of recent toxicological and carcinogenesis studies because it is a commonly prescribed tranquilizer and has been shown to cause tumors in rodents. In this study, male and female B6C3F1 mice received 0, 125, 2500 or 5000 p.p.m. oxazepam in the diet for up to 2 years. Hepatocellular adenomas and carcinomas, as well as hepatoblastomas, which developed in these mice, were examined for the presence of activated ras proto-oncogenes. DNA was isolated from 20 or more tumors from each exposure group and analyzed by oligonucleotide hybridization, single-stranded conformation polymorphism analysis and direct sequencing of PCR-amplified H-ras gene fragments for codon 61 mutations. Thirteen of 37 (35%) hepatocellular adenomas and carcinomas from the 125 p.p.m. exposure group had mutations in codon 61, while mutations were detected in only 2 of 25 or 8% of the liver tumors from the 2500 p.p.m. exposure group and none of the 22 tumors from the 5000 p.p.m. group. This compares to 63% of 126 historical control liver tumors and 55% of 20 liver tumors from unexposed B6C3F1 mice in this study. In addition, 12 hepatoblastomas from the two high dose groups were examined for H-ras mutations at codon 61, but none were detected. No tumor DNAs from any of the exposure groups tested had mutations in codons 12, 13 or 117 of the H-ras gene or codons 12 or 13 of the K-ras gene, the other known hotspots for ras activation in mouse liver tumors. These results, together with those from the National Toxicology Program study showing no evidence of cytotoxicity or genotoxicity by oxazepam, suggest that oxazepam preferentially promotes cells that have activating lesions other than ras. C1 NIEHS,ENVIRONM TOXICOL PROGRAM,RES TRIANGLE PK,NC 27709. RP DEVEREUX, TR (reprint author), NIEHS,ENVIRONM CARCINOGENESIS PROGRAM,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 29 TC 30 Z9 30 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD MAY PY 1994 VL 15 IS 5 BP 1083 EP 1087 DI 10.1093/carcin/15.5.1083 PG 5 WC Oncology SC Oncology GA NP072 UT WOS:A1994NP07200046 PM 8200073 ER PT J AU JAIMOVICH, E ROJAS, E AF JAIMOVICH, E ROJAS, E TI INTRACELLULAR CA2+ TRANSIENTS INDUCED BY HIGH EXTERNAL K+ AND TETRACAINE IN CULTURED RAT MYOTUBES SO CELL CALCIUM LA English DT Article ID FROG SKELETAL-MUSCLE; SARCOPLASMIC-RETICULUM; CHARGE MOVEMENT; LOCAL-ANESTHETICS; MUSCULAR DYSGENESIS; TRANSVERSE TUBULES; CALCIUM TRANSIENTS; MODEL SYSTEM; FIBERS; SIGNALS AB Cultured myotubes from rat neonatal skeletal muscle were used to measure intracellular Ca2+ concentration ([Ca2+](i)) and membrane potentials (Vm) using the Indo-1 microfluorimetry method and the nystatin perforated membrane patch technique, respectively. Sudden increases in external [K+](o) from 5 mM to either 22, 42 or 84 mM elicited transient elevations in [Ca2+](i) from a resting level of 106.2 +/- 10.3 nM (n=41) to peak values of 297, 409 and 454 nM, respectively. V-m changes induced by elevated [K+](o) followed the Nernst equation for [K+](o). The complex Ca2+ release response induced by elevated [K+](o) can be described by a minimal model involving two components with different kinetics. This analysis revealed that the extent of the Ca2+ release by the fast component bears a sigmoidal relationship with V-m (midpoint at -47.5 mV and an effective valence of 4). Furthermore, while the fast transitory component was rather insensitive to [Ca2+](o) and nifedipine, the slow component was profoundly inhibited by the dihydropyridine (10 mu M) both in normal and in a Ca2+ deficient medium. Tetracaine (0.05 to 2 mM), a blocker of the charge movement associated with excitation-contraction (E-C) coupling, elicited a fast elevation in [Ca2+](i) followed by a rise at a constant rate to levels as high as 1-2 mu M, and the changes in [Ca2+](i) were readily reversible. Simultaneous measurements of V-m and [Ca2+](i) suggest that the fast component is coupled to the rapid depolarization of the membrane induced by the anesthetic. We concluded that tetracaine triggers the release of Ca2+ from internal stores by at least two different mechanisms, one of which is associated with the depolarizing effects of the drug. C1 NIDDKD,CELL BIOL & GENET LAB,BETHESDA,MD 20892. UNIV CHILE,FAC MED,DEPT FISIOL & BIOFIS,SANTIAGO 7,CHILE. CTR ESTUDIOS CIENT SANTIAGO,SANTIAGO,CHILE. NR 29 TC 37 Z9 38 U1 0 U2 2 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH, MIDLOTHIAN, SCOTLAND EH1 3AF SN 0143-4160 J9 CELL CALCIUM JI Cell Calcium PD MAY PY 1994 VL 15 IS 5 BP 356 EP 368 DI 10.1016/0143-4160(94)90011-6 PG 13 WC Cell Biology SC Cell Biology GA NM235 UT WOS:A1994NM23500003 PM 8033194 ER PT J AU HU, ZY FUJIO, K MARSDEN, ER THORGEIRSSON, SS EVARTS, RP AF HU, ZY FUJIO, K MARSDEN, ER THORGEIRSSON, SS EVARTS, RP TI HEPATIC REGENERATION IN VITAMIN-A-DEFICIENT RATS - CHANGES IN THE EXPRESSION OF TRANSFORMING GROWTH-FACTOR-ALPHA EPIDERMAL GROWTH-FACTOR RECEPTOR AND RETINOIC ACID RECEPTOR-ALPHA AND RECEPTOR-BETA SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID LIVER-REGENERATION; GENE-EXPRESSION; THYROID-HORMONE; DIFFERENTIATION; REGULATOR; MECHANISM; PROMOTER; CELLS; IDENTIFICATION; TRANSCRIPTION AB We have studied the effect of vitamin A deficiency on the expression of transforming growth factor alpha (TGF-alpha), hepatocyte growth factor, acidic fibroblast growth factor, and TCF-beta 1 after partial hepatectomy of vitamin A-supplemented and vitamin A-deficient rats. In addition, the expressions of epidermal growth factor receptor and retinoic acid receptors alpha (RAR alpha) and beta (RAR beta) were studied. Partial hepatectomy was performed on the animals from the vitamin A-supplemented and -deficient groups at the age of 10 weeks when the weights of the animals on the deficient diet had reached a plateau, Two animals from each group were sacrificed before the operation and also 12, 24, 48, and 72 h and 5 days after the operation. Partial hepatectomy of the vitamin A-deficient rats leads to a focal necrosis of liver followed by a rapid restoration of liver mass. Expression of the TGF-alpha and epidermal growth factor receptor was highly elevated in the livers of deficient animals after partial hepatectomy. In the vitamin A-supplemented animals, the level of epidermal growth factor receptor was downregulated following partial hepatectomy. Proliferation of oval cells in vitamin A-deficient livers following partial hepatectomy and subsequent increase in 2.1-kilobase alpha-fetoprotein mRNA was observed, suggesting an activation of the stem cell compartment Another unexpected result was an inverse relationship between RAR beta and RAR alpha expression, the latter becoming the major species after partial hepatectomy in animals on the vitamin A-deficient regimen. The level and time course of TGF-alpha expression following partial hepatectomy was different in vitamin A-deficient animals from those supplemented with vitamin A, whereas no significant difference in the expression patterns of hepatocyte growth factor, acidic fibroblast growth factor, or TGF-beta 1 was observed between vitamin A-supplemented and -deficient animals. C1 NCI,EXPTL CARCINOGENESIS LAB,BETHESDA,MD 20892. NR 47 TC 17 Z9 17 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1044-9523 J9 CELL GROWTH DIFFER JI Cell Growth Differ. PD MAY PY 1994 VL 5 IS 5 BP 503 EP 508 PG 6 WC Cell Biology SC Cell Biology GA NK211 UT WOS:A1994NK21100005 PM 7519440 ER PT J AU SAKAI, Y NELSON, KG SNEDEKER, S BOSSERT, NL WALKER, MP MCLACHLAN, J DIAUGUSTINE, RP AF SAKAI, Y NELSON, KG SNEDEKER, S BOSSERT, NL WALKER, MP MCLACHLAN, J DIAUGUSTINE, RP TI EXPRESSION OF EPIDERMAL GROWTH-FACTOR IN SUPRABASAL CELLS OF STRATIFIED SQUAMOUS EPITHELIA - IMPLICATIONS FOR A ROLE IN DIFFERENTIATION SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID RECEPTOR DISTRIBUTION; FACTOR PRECURSOR; DROSOPHILA DEVELOPMENT; HUMAN KERATINOCYTES; CALCIUM REGULATION; FACTOR BINDING; GENE-PRODUCT; FACTOR-ALPHA; MOUSE; EGF AB There is a disparity in the fact that epidermal growth factor (EGF) can stimulate proliferation of a wide variety of cells in vitro, yet sites of synthesis for this polypeptide in vivo are generally associated with nonproliferative or differentiated cell populations. Unlike other known mitogenic members of the EGF family of ligands, EGF derives from a large (M(r) similar to 130,000) protein that contains multiple EGF-like domains; some of these domains contain putative Ca2+-binding sites. In the present study, the mouse vaginal epithelium was used as a prototype tissue to investigate expression of the EGF precursor by stratified squamous epithelia. Stratification and cornification in this tissue are estrogen dependent. In the fully differentiated epithelium, EGF precursor transcripts were detected by in situ hybridization in suprabasal cells; labeling was not observed in the proliferative basal cell compartment. Amplified transcripts of predicted size were detected in the vaginal organ by the reverse transcription-polymerase chain reaction and Northern hybridization of polyadenylated RNA. Antisera to mature EGF or to the COOH-terminal (cytoplasmic) domain of the precursor localized reactivity exclusively to cells of the granular layer. The staining with the precursor antiserum was localized along cell borders, which supports that this protein is translocated to the cell membrane following synthesis, a known property for precursors of EGF-like ligands. EGF expression was not apparent in the atrophic vaginal epithelium of castrates, which did not present a granular layer. Other stratified squamous epithelia in organs such as skin, esophagus, and tongue also revealed EGF/EGF precursor immunoreactivity in the granular layer. Our findings indicate that EGF precursor expression by stratified squamous epithelia occurs as a late event in the program of epithelial differentiation. Along with the proclivity of EGF to be synthesized by mature, nonproliferative cells in glandular tissues, these results suggest that EGF/EGF precursor does not provide a mitogenic stimulus within the microenvironment of most normal differentiated cells in vivo. Alternatively, the EGF precursor might contribute to the differentiated phenotype as a multifunctional protein that can both sequester and regulate Ca2+ influx in selected cell populations. C1 NIEHS,REPROD & DEV TOXICOL LAB,RES TRIANGLE PK,NC 27709. NIEHS,BIOCHEM RISK ANAL LAB,RES TRIANGLE PK,NC 27709. DUKE UNIV,MED CTR,DEPT OBSTET & GYNECOL,DURHAM,NC 27710. NR 43 TC 37 Z9 37 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1044-9523 J9 CELL GROWTH DIFFER JI Cell Growth Differ. PD MAY PY 1994 VL 5 IS 5 BP 527 EP 535 PG 9 WC Cell Biology SC Cell Biology GA NK211 UT WOS:A1994NK21100008 PM 8049159 ER PT J AU ISHIDA, Y CHUSED, TM MURAKAMI, S ABE, R AF ISHIDA, Y CHUSED, TM MURAKAMI, S ABE, R TI ANTIGEN-SPECIFIC CELL CONJUGATE FORMATION AND LONG-LASTING CALCIUM RESPONSES IN RECOGNITION OF MLS CELLULAR SUPERANTIGEN BY CLONED MURINE T-LYMPHOCYTES SO CELLULAR IMMUNOLOGY LA English DT Article ID MONOCLONAL-ANTIBODY GK1.5; SIGNAL TRANSDUCTION; PHYSICAL ASSOCIATION; IMMATURE THYMOCYTES; NEGATIVE SELECTION; TYROSINE KINASE; SELF-TOLERANCE; EARLY STEPS; RECEPTOR; ACTIVATION AB T lymphocyte recognition of cell-associated minor lymphocyte stimulation (Mls) superantigen was studied by simultaneous flow cytometric measurement of T cell free ionized intracellular calcium ([Ca2+](i)) with the fluorescent probe indo-1 and T cell binding to antigen-presenting cells stained with a long-chained, membrane-fixed cyanine dye. Cloned T cell-B lymphocyte antigen-presenting cell conjugate formation and increased T cell [Ca2+](i) were antigen specific and tightly linked in four Mis-reactive T cell clones. The T cell-antigen-presenting cell conjugates were extremely stable and, like T cell [Ca2+](i) elevation, were maintained for more than 2 hr. Three ligand-receptor pairs, (i)T cell receptor/antigen + class II, (ii) CD4/class II, and (iii) LFA-1/ICAM-1, were obligatory participants in T cell recognition of cell-bound superantigen since monoclonal antibodies to any of them blocked formation of cell conjugates. Despite previous reports, Mis recognition occurred by the conventional T cell recognition pathway with easily detected phosphoinositide hydrolysis. B cell activation greatly enhances their recognition by Mls-specific T cells. (C) 1994 Academic Press, Inc. C1 NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892. USN,MED RES INST,IMMUNE CELL BIOL PROGRAM,BETHESDA,MD 20814. RP ISHIDA, Y (reprint author), NIAID,IMMUNOL LAB,ROCKVILLE,MD 20852, USA. NR 64 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 MAY PY 1994 VL 155 IS 2 BP 414 EP 427 DI 10.1006/cimm.1994.1134 PG 14 WC Cell Biology; Immunology SC Cell Biology; Immunology GA NL799 UT WOS:A1994NL79900014 PM 7910116 ER PT J AU BARTH, TM STANFIELD, BB AF BARTH, TM STANFIELD, BB TI HOMOTOPIC, BUT NOT HETEROTOPIC, FETAL CORTICAL TRANSPLANTS CAN RESULT IN FUNCTIONAL SPARING FOLLOWING NEONATAL DAMAGE TO THE FRONTAL-CORTEX IN RATS SO CEREBRAL CORTEX LA English DT Article ID BILATERAL CUTANEOUS STIMULATION; CENTRAL-NERVOUS-SYSTEM; SENSORIMOTOR CORTEX; OCCIPITAL CORTEX; CEREBRAL-CORTEX; NEWBORN RATS; MOTOR CORTEX; ADULT-RATS; LESIONS; RECOVERY AB Experiments involving the heterotopic transplantation of neocortex during development have indicated that the efferent connections maintained by the transplant as well as other organizational features are appropriate to the transplant's regional locale within the host cortex, rather than to its site of origin within the donor cortex, These findings would seem to be consistent with the idea that developing cortical neurons lack any rigid regional specification. To examine this further, we made lesions in the rostral cortex of newborn rats and placed pieces of either rostral or occipital fetal cortex into the lesion site. Additional cases with similar lesions, but with no transplants, were also prepared, When the animals matured, behavioral testing was done to identify any residual deficits. Compared with lesioned animals that had received no transplants, animals with homotopic transplants show a substantial sparing in certain forelimb placing and somatosensory tasks. In marked contrast, animals with heterotopic transplants did not show any sparing. Indeed, when placing reactions were elicited by vibrissal stimulation (vibrissae --> forelimb placing; extinction-placing) the animals with heterotopic transplants showed a greater impairment than the lesioned animals that received no transplants. These results indicate that while homotopic fetal cortical transplants may help ameliorate behavioral deficits that normally follow neonatal lesions of the rostral cortex, heterotopic transplants do not, and may in fact exacerbate the deficits, despite the fact that such heterotopic transplants have been shown to maintain projections that seemingly are appropriate to their locale, These findings indicate that at a stage when fetal cortical neurons retain the potential to extend axons to targets appropriate for a variety of cortical regions, their capacity for complete functional integration into heterotopic cortical regions may already be restricted. This may imply that a progressive determination of regional cortical attributes occurs during normal fetal development. C1 NIMH, CTR ANIM, NEUROPHYSIOL LAB, POOLESVILLE, MD 20837 USA. RP TEXAS CHRISTIAN UNIV, DEPT PSYCHOL, FT WORTH, TX 76129 USA. NR 54 TC 25 Z9 25 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 EI 1460-2199 J9 CEREB CORTEX JI Cereb. Cortex PD MAY-JUN PY 1994 VL 4 IS 3 BP 271 EP 278 DI 10.1093/cercor/4.3.271 PG 8 WC Neurosciences SC Neurosciences & Neurology GA NP188 UT WOS:A1994NP18800005 PM 8075532 ER PT J AU KASPRZAK, KS ZASTAWNY, TH NORTH, SL RIGGS, CW DIWAN, BA RICE, JM DIZDAROGLU, M AF KASPRZAK, KS ZASTAWNY, TH NORTH, SL RIGGS, CW DIWAN, BA RICE, JM DIZDAROGLU, M TI OXIDATIVE DNA-BASE DAMAGE IN RENAL, HEPATIC, AND PULMONARY CHROMATIN OF RATS AFTER INTRAPERITONEAL INJECTION OF COBALT(II) ACETATE SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID MAMMALIAN CHROMATIN; HYDROGEN-PEROXIDE; FREE-RADICALS; CHELATORS; EXCRETION; METAL; CARCINOGENICITY; RADIATION; CO(II); KIDNEY AB DNA base damage was studied in renal, hepatic, and pulmonary chromatin of male and female F344/NCr rats that had been given either 50 or 100 mu mol of Co(II) acetate/kg body wt in a single ip dose and killed 2 or 10 days later. Control rats received 200 mu mol of sodium acetate/kg body wt. Chromatin was isolated from organs and analyzed by gas chromatography/mass spectrometry with selected ion monitoring. The following II products derived from purine and pyrimidine bases in DNA were quantified: 5-hydroxy-5-methylhydantoin, 5-hydroxyhydantoin, 5-(hydroxymethyl)uracil (5-OHMe-Ura), 5-hydroxycytosine (5-OH-Cyt), thymine glycol, 5,6-dihydroxycytosine, 4,6-diamino-5-formamido-pyrimidine (FapyAde),2,6-diamino-4-hydroxy-5-formamidopyrimidine (FapyGua), 7,8-dihyaro-8-oxoadenine,2-oxoadenine, and 7,8-dihydro-8-oxoguanine. The response was organ-specific. Eight of the DNA base products in renal chromatin of Co(II)-treated rats (mostly 5-OH-Cyt and other pyrimidine products), five in hepatic chromatin (mostly FapyGua and other purine products), and two in pulmonary chromatin (5-OHMe-Ura > FapyAde) were increased by 30% to more than 200% over control levels with increasing Co(II) dose. The renal and hepatic, but not pulmonary, DNA base damage tended to increase with time. No significant differences in response were found between male and female rats. The bases determined were typical products of hydroxyl radical attack on DNA, suggesting a role for this radical in the mechanism(s) of DNA damage caused by Co(II) in vivo. Some of these bases have been shown previously to be promutagenic. The present results imply involvement of oxidative DNA base damage in Co(II)-induced genotoxic and carcinogenic effects. C1 NCI,FREDERICK CANC RES & DEV CTR,DYNCORP,PROGRAM RESOURCES INC,BIOL CARCINOGENESIS DEV PRO,FREDERICK,MD 21702. NIST,CHEM SCI & TECHNOL LAB,GAITHERSBURG,MD 20899. RP KASPRZAK, KS (reprint author), NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,BLDG 538,ROOM 205,FREDERICK,MD 21702, USA. NR 40 TC 40 Z9 41 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD MAY-JUN PY 1994 VL 7 IS 3 BP 329 EP 335 DI 10.1021/tx00039a009 PG 7 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA NL680 UT WOS:A1994NL68000009 PM 8075364 ER PT J AU SZELIGA, J LEE, HM HARVEY, RG PAGE, JE ROSS, HL ROUTLEDGE, MN HILTON, BD DIPPLE, A AF SZELIGA, J LEE, HM HARVEY, RG PAGE, JE ROSS, HL ROUTLEDGE, MN HILTON, BD DIPPLE, A TI REACTION WITH DNA AND MUTAGENIC SPECIFICITY OF SYN-BENZO[G]CHRYSENE 11,12-DIHYDRODIOL 13,14-EPOXIDE SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID BENZOPHENANTHRENE DIHYDRODIOL EPOXIDES; REGION 3,4-DIOL 1,2-EPOXIDES; ESCHERICHIA-COLI; DIOL-EPOXIDES; FJORD-REGION; 1,2-DIHYDRODIOL 3,4-EPOXIDE; MAMMALIAN-CELLS; SHUTTLE VECTOR; SUPF GENE; ADDUCTS AB The spectroscopic characterization of purine deoxyribonucleoside adducts derived from the fjord-region syn-benzo[g] chrysene 11,12-dihydrodiol 13,14-epoxide and the mutagenic specificity of the latter compound for the supF gene in the pSP189 shuttle vector are described. This dihydrodiol epoxide preferentially forms adducts with deoxyadenosine residues in DNA and is preferentially opened trans in reactions with DNA or with deoxyribonucleotides. In common with other fjord-region syn-dihydrodiol epoxides, the most frequently observed mutational changes were A --> T and G --> T changes. This hydrocarbon dihydrodiol epoxide is structurally similar to syn-benzo[c] phenanthrene 3,4-dihydrodiol 1,2-epoxide but has an additional benzene ring annelated distant from the reaction center. As anticipated, there were some common features in the chemistry and mutagenicities of these two compounds, but there were also substantive differences which indicate factors of importance in controlling reactions of these kinds of compounds with DNA. C1 NCI,FREDERICK CANC RES & DEV CTR,DYNCORP INC,PRI,CHEM SYNTH & ANAL LAB,ABL,BASIC RES PROGRAM,C,FREDERICK,MD 21701. UNIV CHICAGO,BEN MAY INST,CHICAGO,IL 60637. FU NCI NIH HHS [N01-CO-74102, N01-CO-74101]; NIEHS NIH HHS [ES-04732] NR 38 TC 53 Z9 55 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD MAY-JUN PY 1994 VL 7 IS 3 BP 420 EP 427 DI 10.1021/tx00039a021 PG 8 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA NL680 UT WOS:A1994NL68000021 PM 8075375 ER PT J AU KOHNO, S AF KOHNO, S TI OFLOXACIN AND PULMONARY TUBERCULOSIS - REPLY SO CHEST LA English DT Letter C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 SN 0012-3692 J9 CHEST JI Chest PD MAY PY 1994 VL 105 IS 5 BP 1624 EP 1624 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA NL392 UT WOS:A1994NL39200092 ER PT J AU LENFANT, C AF LENFANT, C TI THE NHLBI PLANNING PROCESS - A STREAMLINED APPROACH SO CIRCULATION LA English DT Editorial Material RP LENFANT, C (reprint author), NHLBI,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 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 MAY PY 1994 VL 89 IS 5 BP 1921 EP 1921 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA NL675 UT WOS:A1994NL67500001 ER PT J AU BANAI, S JAKLITSCH, MT SHOU, M LAZAROUS, DF SCHEINOWITZ, M BIRO, S EPSTEIN, SE UNGER, EF AF BANAI, S JAKLITSCH, MT SHOU, M LAZAROUS, DF SCHEINOWITZ, M BIRO, S EPSTEIN, SE UNGER, EF TI ANGIOGENIC-INDUCED ENHANCEMENT OF COLLATERAL BLOOD-FLOW TO ISCHEMIC MYOCARDIUM BY VASCULAR ENDOTHELIAL GROWTH-FACTOR IN DOGS SO CIRCULATION LA English DT Article DE CIRCULATION, CORONARY; GROWTH FACTOR, VASCULAR ENDOTHELIAL; ENDOTHELIUM; ANGIOGENESIS ID CORONARY-ARTERY; PERMEABILITY FACTOR; PORCINE HEART; DNA-SYNTHESIS; MITOGEN; CELLS; ANASTOMOSES; EXPRESSION; MODEL AB Background Vascular endothelial growth factor (VEGF) is an endothelial cell-specific mitogen that is angiogenic in vitro and in vivo. It has been hypothesized that VEGF plays a role in myocardial collateral formation; however, the effects of VEGF on collateral flow to ischemic myocardium are unknown. Methods and Results We studied the effect of VEGF on collateral blood flow in dogs subjected to gradual occlusion of the left circumflex coronary artery (LCx). Beginning 10 days after placement of an LCx-constricting device, VEGF 45 mu g (n=9) or saline (n=12) was administered daily via an indwelling catheter in the distal LCx, at a point just beyond the occlusion. Treatment was maintained for 28 days. Collateral blood flow was determined with microspheres 7 days before treatment, immediately before treatment (day 0), and 7, 14, 21, and 28 days into the treatment period. Collateral blood flow was quantified during chromonar-induced maximal vasodilation and expressed as a collateral zone/normal zone (CZ/NZ) ratio. Treatment with VEGF was associated with a 40% increase in collateral blood flow (final CZ/NZ blood flow ratios of 0.49+/-0.06 and 0.35+/-0.02 in the VEGF-treated and control groups, respectively, P=.0037) as well as an 89% increase in the numerical density of intramyocardial distribution vessels (>20 mu m diameter) in the CZ (6.6+/-1.4 versus 3.5+/-0.7 vessels/ mm(2) in VEGF-treated and control dogs, respectively, P<.05). Conclusions We conclude that intracoronary VEGF enhances the development of small coronary arteries supplying ischemic myocardium, resulting in marked augmentation of maximal collateral blood flow delivery. These results demonstrate the feasibility of pharmacological enhancement of collateral growth and suggest a new therapeutic approach for the treatment of myocardial ischemia. C1 NHLBI,CARDIOL BRANCH,BETHESDA,MD 20892. NR 30 TC 496 Z9 546 U1 3 U2 12 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY PY 1994 VL 89 IS 5 BP 2183 EP 2189 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA NL675 UT WOS:A1994NL67500035 PM 7514110 ER PT J AU SHAH, AM SPURGEON, HA SOLLOTT, SJ TALO, A LAKATTA, EG AF SHAH, AM SPURGEON, HA SOLLOTT, SJ TALO, A LAKATTA, EG TI 8-BROMO-CGMP REDUCES THE MYOFILAMENT RESPONSE TO CA2+ IN INTACT CARDIAC MYOCYTES SO CIRCULATION RESEARCH LA English DT Article DE CGMP; CARDIAC CONTRACTION; DIASTOLIC TONE; MYOFILAMENTS; RELAXATION ID DEPENDENT PROTEIN-KINASE; CYCLIC-GMP; NITRIC-OXIDE; SARCOPLASMIC-RETICULUM; CONTRACTILE PROTEINS; TWITCH RELAXATION; FROG VENTRICLE; SKINNED CELLS; CYTOSOLIC PH; MUSCLE AB The role of cGMP in myocardial contraction is not established. Recent reports suggest that nitric oxide, released by endothelial cells or within myocytes, modifies myocardial contraction by raising cGMP. We studied the effects of 8-bromo-cGMP (8bcGMP, 50 mu mol/L) on contraction (cell shortening) and simultaneous intracellular Ca2+ transients (indo 1 fluorescence ratio) in intact adult rat ventricular myocytes (0.5 Hz and 25 degrees C). 8bcGMP reduced myocyte twitch amplitude and time to peak shortening (-19.6+/-4.2% and -17.6+/-1.3%, respectively) and increased steady-state diastolic cell length (+0.6+/-0.1 mu m, mean+/-SEM, n=8; all P<.05) but had no effect on shortening velocity, systolic or diastolic fluorescence ratio, or time to peak fluorescence ratio (all P=NS). In 7 of 13 myocytes, this negative inotropic effect was preceded by a transient positive inotropic effect, with small increases in twitch amplitude, shortening velocity, and cytosolic Ca2+ transient. Analysis of 8bcGMP effects on both the dynamic and steady-state relation between cell shortening and intracellular Ca2+ (during twitch contraction and tetanic contraction, respectively) indicated reduction in the myofilament response to Ca2+ in all cases. These 8bcGMP effects were inhibited by KT5823 (1 mu mol/L), an inhibitor of cGMP-dependent protein kinase, or by the presence of isoproterenol (3 nmol/L). 8bcGMP had no effect on cytosolic pH in cells (n=4) loaded with the fluorescent probe carboxyseminaphthorhodafluor-1. These data indicate that cGMP may modulate myocardial relaxation and diastolic tone by reducing the relative myofilament response to Ca2+, probably via cGMP-dependent protein kinase. C1 NIA, GERONTOL RES CTR, CARDIOVASC SCI LAB, BALTIMORE, MD 21224 USA. RP SHAH, AM (reprint author), UNIV WALES COLL MED, DEPT CARDIOL, HEATH PK, CARDIFF CF4 4XN, S GLAM, WALES. OI Shah, Ajay/0000-0002-6547-0631 NR 60 TC 306 Z9 307 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7330 J9 CIRC RES JI Circ.Res. PD MAY PY 1994 VL 74 IS 5 BP 970 EP 978 PG 9 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA NG968 UT WOS:A1994NG96800023 PM 8156644 ER PT J AU STEARN, BF POLIS, MA AF STEARN, BF POLIS, MA TI PROPHYLAXIS OF OPPORTUNISTIC INFECTIONS IN PERSONS WITH HIV-INFECTION SO CLEVELAND CLINIC JOURNAL OF MEDICINE LA English DT Review DE OPPORTUNISTIC INFECTIONS; HIV INFECTIONS AB BACKGROUND Morbidity and mortality associated with human immunodeficiency virus infection and the acquired immunodeficiency syndrome is most often related to associated opportunistic infections. OBJECTIVE To review the prophylaxis of common opportunistic infections in patients with human immunodeficiency virus. SUMMARY Prophylactic treatment for Pneumocystis carinii pneumonia should begin when the CD4 count falls below 200 cells per muL. Recommended treatment consists of trimethoprim 160 mg and sulfamethoxazole 800 mg daily, but other regimens have been successfully used. This regimen appears to also prevent the development of toxoplasmic encephalitis. Fluconazole 100 mg once or twice weekly can prevent oral and esophageal candidiasis, but its efficacy against life-threatening fungal infections is unproved. Rifabutin 300 mg daily can delay the development of disseminated Mycobacterium avium complex infection. Daily therapy with 300 mg of isoniazid for at least 9 months is recommended for persons at risk for tuberculosis. CONCLUSIONS Prevention of opportunistic infections can prolong the lives of persons infected with human immunodeficiency virus. Effective regimens are available for preventing some of these infections, and studies are in progress to establish optimum regimens for others. C1 NIH,DEPT HLTH & HUMAN SERV,DEPT INTRAMURAL AIDS PROGRAM,BETHESDA,MD 20892. OI Polis, Michael/0000-0002-9151-2268 NR 0 TC 4 Z9 4 U1 1 U2 1 PU CLEVELAND CLINIC PI CLEVELAND PA 9500 EUCLID AVE, CLEVELAND, OH 44106 SN 0891-1150 J9 CLEV CLIN J MED JI Clevel. Clin. J. Med. PD MAY-JUN PY 1994 VL 61 IS 3 BP 187 EP 194 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA NL128 UT WOS:A1994NL12800005 PM 7913002 ER PT J AU COOPER, AM MELBY, PC KARP, CL NEVA, F SACKS, DL AF COOPER, AM MELBY, PC KARP, CL NEVA, F SACKS, DL TI T-CELL RESPONSES TO INFECTED AUTOLOGOUS MONOCYTES IN PATIENTS WITH CUTANEOUS AND MUCOCUTANEOUS LEISHMANIASIS SO CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY LA English DT Article ID MUCOSAL LEISHMANIASIS; PERIPHERAL-BLOOD; INTERFERON-GAMMA; ANTIGENS; IMMUNITY; DONOVANI; LESIONS; RESPONSIVENESS; LYMPHOCYTES; CLONES AB Although there is strong evidence that the control and resolution of human leishmanial infections depend primarily on activation of parasite-infected macrophages mediated by lymphokines derived from T cells, less is known about the nature of the responding cell type(s) which is protective or the antigen(s) (Ag[s]) that elicits these cells to respond. Studies using preparations of whole soluble Ag (''dead Ag'') show that patients respond to a wide range of leishmanial Ags. The objective of the present study was to characterize the response of T cells from patients with healing or healed cutaneous or mucosal infections to Ag expressed by or derived from actively infected autologous monocytes (''live Ag''). Unfractionated T cells proliferated and produced gamma interferon in response to both live and dead Ags. Depletion of CD4(+) T cells resulted in the loss of proliferative and gamma interferon responses to both live and dead Ags. The effect of CD8 depletion, although variable and not limited to the cells stimulated by infected monocytes, was clear for some patients. Expansion of T cells specific for live Ags by using amastigote-infected cells followed by restimulation with fast-protein liquid chromatography-fractionated soluble Ags revealed that a diversity of Ags ore associated with infected monocytes. There may, however, be quantitative differences in the expression of certain Ags since prestimulation with live Ag induced higher responses to restimulation in mucocutaneous leishmaniasis patients than in localized cutaneous leishmaniasis patients. Prestimulation with dead Ag induced similar secondary responses in both patient groups. C1 NIAID,PARASIT DIS LAB,BETHESDA,MD 20892. UNIV TEXAS,HLTH SCI CTR,DEPT MED,DIV INFECT DIS,SAN ANTONIO,TX 78229. OI Cooper, Andrea/0000-0001-6050-3863 NR 21 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 1071-412X J9 CLIN DIAGN LAB IMMUN JI Clin. Diagn. Lab. Immunol. PD MAY PY 1994 VL 1 IS 3 BP 304 EP 309 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA PT564 UT WOS:A1994PT56400009 PM 7496967 ER PT J AU HUESTIS, MA MITCHELL, JM CONE, EJ AF HUESTIS, MA MITCHELL, JM CONE, EJ TI LOWERING THE FEDERALLY MANDATED CANNABINOID IMMUNOASSAY CUTOFF INCREASES TRUE-POSITIVE RESULTS SO CLINICAL CHEMISTRY LA English DT Article DE DRUGS OF ABUSE; MARIJUANA; GAS CHROMATOGRAPHY; MASS SPECTROMETRY; INTERMETHOD COMPARISON; URINE SCREENING ID CHROMATOGRAPHY-MASS-SPECTROMETRY; GAS-CHROMATOGRAPHY; URINE; DELTA-9-TETRAHYDROCANNABINOL; CONFIRMATION; METABOLITES; THRESHOLD; ASSAY; ACID; EMIT AB Proposed changes to the Health and Human Services Guidelines for forensic urine drug testing will lower the required cannabinoid immunoassay cutoff concentration from 100 to 50 mu g/L. We investigated the effect of this change on the sensitivity, specificity, and efficiency of eight cannabinoid immunoassays: Syva Emit(R) d.a.u.(TM) 100; Syva Emit II 100; Syva Emit d.a.u. 50; Syva Emit II 50; Roche Abuscreen(R) Online(TM); Roche Abuscreen radioimmunoassay; Diagnostic Reagents(R); and Abbott ADx(R). All specimens also were assayed by gas chromatography/mass spectrometry. Lowering the cutoff concentration from 100 to 50 mu g/L increased efficiencies and sensitivities for all immunoassays, with minor decreases in specificity (1.0-2.6%). There was a 23.2-53.6% increase in the number of true-positive specimens identified. Thus, lowering the cannabinoid immunoassay cutoff concentration from 100 to 50 mu g/L resulted in detection of a substantial number of additional true-positive specimens, with an accompanying small increase in unconfirmed positive results. C1 NIDA,ADDICT RES CTR,CHEM & DRUG METAB SECT,BALTIMORE,MD 21224. USN,DRUG SCREENING LAB,NAVAL AIR STN,JACKSONVILLE,FL 32212. NR 17 TC 20 Z9 22 U1 1 U2 2 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 MAY PY 1994 VL 40 IS 5 BP 729 EP 733 PG 5 WC Medical Laboratory Technology SC Medical Laboratory Technology GA NK828 UT WOS:A1994NK82800009 PM 8174244 ER PT J AU THOMPSON, EW TORRI, J SABOL, M SOMMERS, CL BYERS, S VALVERIUS, EM MARTIN, GR LIPPMAN, ME STAMPFER, MR DICKSON, RB AF THOMPSON, EW TORRI, J SABOL, M SOMMERS, CL BYERS, S VALVERIUS, EM MARTIN, GR LIPPMAN, ME STAMPFER, MR DICKSON, RB TI ONCOGENE-INDUCED BASEMENT-MEMBRANE INVASIVENESS IN HUMAN MAMMARY EPITHELIAL-CELLS SO CLINICAL & EXPERIMENTAL METASTASIS LA English DT Article DE BASEMENT MEMBRANE; HUMAN BREAST CANCER; INVASION; ONCOGENE; UVOMORULIN; VIMENTIN ID BREAST-CANCER CELLS; IV COLLAGENASE; METASTATIC PROPERTIES; EXTRACELLULAR-MATRIX; ADHESION MECHANISMS; KERATIN EXPRESSION; ESTROGEN-RECEPTOR; LAMININ RECEPTOR; TUMOR INVASION; VIMENTIN AB Expression of the intermediate filament protein vimentin, and loss of the cellular adhesion protein uvomorulin (E-cadherin) have been associated with increased invasiveness of established human breast cancer cell lines in vitro and in vivo. In the current study, we have further examined these relationships in oncogenically transformed human mammary epithelial cells. A normal human mammary epithelial strain, termed 184, was previously immortalized with benzo[a]pyrene, and two distinct sublines were derived (A1N4 and 184B5). These sublines were infected with retroviral vectors containing a single or two oncogenes of the nuclear, cytoplasmic, and plasma membrane-associated type (v-ras(H), v-ras(Ki), v-mos, SV40T and c-myc). All infectants have been previously shown to exhibit some aspects of phenotypic transformation. In the current study, cellular invasiveness was determined in vitro using Matrigel, a reconstituted basement membrane extract. Lineage-specific differences were observed with respect to low constitutive invasiveness and invasive changes after infection with ras, despite similar ras-induced transformation of each line. Major effects on cellular invasiveness were observed after infection of the cells with two different oncogenes (v-ras(H) + SV40T and v-ras(H) + v-mos). In contrast, the effects of single oncogenes were only modest or negligible. All oncogenic infectants demonstrated increased attachment to laminin, but altered secretion of the 72 kDa and 92 kDa gelatinases was not associated with any aspect of malignant progression. Each of the two highly invasive double oncogene transformants were vimentin-positive and uvomorulin-negative, a phenotype indicative of the epithelial-mesenchymal transition (EMT) previously associated with invasiveness of established human breast cancer cell lines, Weakly invasive untransformed mammary epithelial cells in this study were positive for both vimentin and uvomorulin, suggesting that uvomorulin may over-ride the otherwise vimentin-associated invasiveness. C1 GEORGETOWN UNIV,MED CTR,VINCENT T LOMBARDI CANC RES CTR,WASHINGTON,DC 20007. NIDR,BETHESDA,MD. UNIV CALIF BERKELEY,LAWRENCE BERKELEY LAB,BERKELEY,CA. RP THOMPSON, EW (reprint author), GEORGETOWN UNIV,MED CTR,DEPT CELL BIOL,3800 RESERVOIR RD NW,WASHINGTON,DC 20007, USA. RI Thompson, Erik/A-1425-2009 OI Thompson, Erik/0000-0002-9723-4924 FU NCI NIH HHS [CA-24844, UO1-CA51908] NR 69 TC 57 Z9 60 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0262-0898 J9 CLIN EXP METASTAS JI Clin. Exp. Metastasis PD MAY PY 1994 VL 12 IS 3 BP 181 EP 194 DI 10.1007/BF01753886 PG 14 WC Oncology SC Oncology GA NQ407 UT WOS:A1994NQ40700001 PM 8194193 ER PT J AU NARIAI, T DEGEORGE, JJ GREIG, NH GENKA, S RAPOPORT, SI PURDON, AD AF NARIAI, T DEGEORGE, JJ GREIG, NH GENKA, S RAPOPORT, SI PURDON, AD TI DIFFERENCES IN RATES OF INCORPORATION OF INTRAVENOUSLY INJECTED RADIOLABELED FATTY-ACIDS INTO PHOSPHOLIPIDS OF INTRACEREBRALLY IMPLANTED TUMOR AND BRAIN IN AWAKE RATS SO CLINICAL & EXPERIMENTAL METASTASIS LA English DT Article DE ARACHIDONIC ACID; BRAIN; CARCINOSARCOMA; DOCOSAHEXAENOIC ACID; FATTY ACIDS; INCORPORATION; IN VIVO IMAGING; LIPID; METABOLISM; PALMITIC ACID; PHOSPHOLIPID; TUMORS; TURNOVER ID UNANESTHETIZED RATS; LIPID-COMPOSITION; ARACHIDONIC-ACID; CELLS; METABOLISM; PALMITATE; INVIVO; DIFFERENTIATION; HYDROLYSIS; ASTROCYTES AB This study investigates the incorporation of three intravenously administered radiolabeled fatty acids, [9,10-H-3]palmitate (H-3-PAM), [1-C-14]arachidonate (C-14-ACH) and [1-C-14]docosahexaenoate (C-14-DHA), into lipids of intracerebrally implanted tumor and contralateral brain cortex in awake rats. A suspension of Walker 256 carcinosarcoma cells (1 x 10(6) cells) was implanted into the right cerebral hemisphere of an 8- to 9-week-old Fischer-344 rat. Seven days later, the awake rat was infused intravenously for 5 min with 3H-PAM (6.4 mCi/kg), C-14-ACH (170 mu Ci/kg) or C-14-DHA (100 mu Ci/kg). Twenty min after the start of infusion, the rat was killed and intracranial tumor mass and brain cortex were removed for lipids analysis. Each radiolabel was incorporated more into tumor than into brain cortex. Ratios of net incorporation rate coefficients (k*) into tumor as compared with brain were 4.5, 3.4 and 1.7 for H-3-PAM, C-14-ACH and C-14-DHA, respectively. Lipid radioactivity comprised more than 80% of total tumor or brain radioactivity for each probe. Phospholipids contained 58%, 89% and 68% of tumor lipid radioactivity, and 58%, 82% and 74% of brain lipid radioactivity, for H-3-PAM, C-14-ACH and C-14-DHA, respectively. Incorporation coefficients (k*(i)) for a phospholipid class (i)-choline phosphoglycerides (PC), inositol monophosphoglycerides (PI), ethanolamine phosphoglycerides (PE), serine phosphoglycerides (PS), and sphingomyelin (SM)-were greater in tumor than in brain for each fatty acid probe, except that values for k*(PE) and k*(PS) using C-14-DHA were equivalent. Differences in k*(i) between tumor and brain were largest for SM and PC and the change in k*(PC) accounted for 65-90% of the increase in the net phospholipid incorporation rate for each probe. Differences in k*(PI), k*(PE) and k*(PS) were smaller than those in k*(PC) and k*(SM), and varied with the probe. Differences in k*(i) were related to differences in tumor and brain phospholipid composition and metabolism. The results indicate that suitably radiolabeled fatty acids may be used to image and characterize metabolism of lipid compartments of a brain tumor in vivo using positron emission tomography. C1 NIA,NEUROSCI LAB,BETHESDA,MD 20892. NR 44 TC 26 Z9 26 U1 0 U2 2 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0262-0898 J9 CLIN EXP METASTAS JI Clin. Exp. Metastasis PD MAY PY 1994 VL 12 IS 3 BP 213 EP 225 DI 10.1007/BF01753889 PG 13 WC Oncology SC Oncology GA NQ407 UT WOS:A1994NQ40700004 PM 8194196 ER PT J AU BARILE, MF KAPATAISZOUMBOS, K SNOY, P GRABOWSKI, MW SNELLER, M MILLER, L CHANDLER, DKF AF BARILE, MF KAPATAISZOUMBOS, K SNOY, P GRABOWSKI, MW SNELLER, M MILLER, L CHANDLER, DKF TI EXPERIMENTALLY-INDUCED SEPTIC ARTHRITIS IN CHIMPANZEES INFECTED WITH MYCOPLASMA-HOMINIS, MYCOPLASMA-PNEUMONIAE, AND UREAPLASMA-UREALYTICUM SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID IMMUNE-COMPLEXES; INFLAMMATORY POLYARTHRITIS; RHEUMATOID-ARTHRITIS; URETHRAL INFECTION; SYRIAN-HAMSTERS; SYNOVIAL-FLUID; HYPOGAMMAGLOBULINEMIA; PATIENT; PATHOGENICITY; GENITALIUM AB Mycoplasma hominis was isolated in pure culture from septic synovial aspirates from an individual (patient A) during 16 different bouts of exacerbation over a 70-month period of observation. Two isolates, 10(7) and also 10(6) color-changing units (CCU) of the 1620 isolate and 5 X 10(4) CCU of the 1628 isolate, caused inflammation in chimpanzees inoculated intraarticularly. Inflammation was also induced with 10(7) CCU of the 2010B isolate, serovar VII of Ureaplasma urealyticum, recovered from an agammaglobulinemic individual (patient B) with septic polyarthritis and with 3 X 10(6) CCU of the PI-1428 isolate of Mycoplasma pneumoniae. Inflammation persisted for up to 36 days and was self-limiting. The aspirates contained up to 220,000 white blood cells/mm(3) and up to 10(7) CCU/mL. There was good correlation between the severity of inflammation and the numbers of organisms, but antibody was not detected in aspirates during the peak severity of disease. As the numbers of organisms decreased, detectable levels of antibody increased, thus suggesting that antibody may have been bound to antigen. Chimpanzees previously infected with either the 1628 isolate of M. hominis or the 2010B isolate of U. urealyticum were protected on challenge with > 100 times the minimal dose causing arthritis. Chimpanzees showed little or no inflammation when inoculated intraarticularly with 5 X 10(8) CCU of the type strain PG-21 of M. hominis or with the type strain CO of U. urealyticum or when inoculated intravenously with 3 X 10(8) CCU of the arthrogenic 1620 isolate of M. hominis. C1 US FDA,CTR BIOL EVALUAT & RES,MYCOPLASMA LAB,BETHESDA,MD. US FDA,CTR BIOL EVALUAT & RES,PATHOBIOL & PRIMATOL LAB,PRIMATE UNIT,BETHESDA,MD. NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. NR 70 TC 14 Z9 14 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 MAY PY 1994 VL 18 IS 5 BP 694 EP 703 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA NL167 UT WOS:A1994NL16700003 PM 8075258 ER PT J AU WALSH, TJ HIEMENZ, J PIZZO, PA AF WALSH, TJ HIEMENZ, J PIZZO, PA TI EVOLVING RISK-FACTORS FOR INVASIVE FUNGAL-INFECTIONS - ALL NEUTROPENIC PATIENTS ARE NOT THE SAME SO CLINICAL INFECTIOUS DISEASES LA English DT Editorial Material ID COLONY-STIMULATING FACTOR; BONE-MARROW TRANSPLANT; STEM-CELL TRANSPLANTS; PERIPHERAL-BLOOD; AMPHOTERICIN-B; GRANULOCYTOPENIC PATIENTS; EMPIRIC THERAPY; ACUTE-LEUKEMIA; ASPERGILLOSIS; CANCER C1 H LEE MOFFITT CANC CTR & RES INST,TAMPA,FL. RP WALSH, TJ (reprint author), NCI,PEDIAT BRANCH,INFECT DIS SECT,BLDG 10,ROOM 13N-240,BETHESDA,MD 20892, USA. NR 55 TC 77 Z9 78 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 MAY PY 1994 VL 18 IS 5 BP 793 EP 798 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA NL167 UT WOS:A1994NL16700019 PM 8075273 ER PT J AU WALSH, SL PRESTON, KL STITZER, ML CONE, EJ BIGELOW, GE AF WALSH, SL PRESTON, KL STITZER, ML CONE, EJ BIGELOW, GE TI CLINICAL-PHARMACOLOGY OF BUPRENORPHINE - CEILING EFFECTS AT HIGH-DOSES SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID AGENT; ADDICTION; MORPHINE AB Objective: The purpose of this study was to characterize the acute effects of buprenorphine, an opioid partial mu-agonist, across a wide range of doses in comparison to methadone. Method: Healthy adult male volunteers, who had experience with but were not physically dependent on opioids, participated while residing on a closed research unit. Four subjects received buprenorphine (0, 1, 2, 4, 8, 16, and 32 mg sublingually and five subjects received methadone (0, 15, 30, 45, and 60 mg orally) in ascending order at 1-week intervals. Physiologic, subjective, and behavioral measures were monitored for 96 hours after drug administration. Results: Both drugs produced typical opioid agonist effects (positive mood, sedation, respiratory depression, and miosis), some of which persisted for 24 to 48 hours. A plateau was observed for the dose effects of buprenorphine on subjective measures and respiratory depression. Pharmacokinetic data revealed that plasma concentrations of buprenorphine were linearly related to dose, indicating no limits on sublingual absorption in this dose range. Conclusions: This study shows a plateau on buprenorphine effects, consistent with its partial agonist classification, and that single doses of buprenorphine up to 70 times the recommended analgesic dose are well tolerated by nondependent humans. C1 NIDA,ADDICT RES CTR,BALTIMORE,MD. RP WALSH, SL (reprint author), JOHNS HOPKINS UNIV,SCH MED,DEPT PSYCHIAT & BEHAV SCI,5510 NATHAN SHOCK DR,BALTIMORE,MD 21224, USA. RI Preston, Kenzie/J-5830-2013 OI Preston, Kenzie/0000-0003-0603-2479 FU NIDA NIH HHS [DA 006120, DA 06165] NR 24 TC 378 Z9 391 U1 2 U2 11 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 MAY PY 1994 VL 55 IS 5 BP 569 EP 580 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA NM880 UT WOS:A1994NM88000012 PM 8181201 ER PT J AU KEENAN, RM HATSUKAMI, DK PENTEL, PR THOMPSON, TN GRILLO, MA AF KEENAN, RM HATSUKAMI, DK PENTEL, PR THOMPSON, TN GRILLO, MA TI PHARMACODYNAMIC EFFECTS OF COTININE IN ABSTINENT CIGARETTE SMOKERS SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID SQUIRREL-MONKEYS; NICOTINE; METABOLITES; PHARMACOKINETICS; PLASMA; RATS AB The nicotine metabolite cotinine was administered to abstinent cigarette smokers to determine whether it has pharmacologic activity as assessed by various physiologic and subjective measurements. By means of a randomized, double-blind, placebo-controlled counterbalanced-order design, subjects received cotinine base (30 mg) intravenously after 48 hours of abstinence from cigarette smoking. Serum cotinine concentrations increased to levels commonly achieved during daily cigarette smoking, whereas no change in serum nicotine concentration was observed. Cotinine compared with placebo produced subjective differences in self-reported ratings of restlessness, anxiety and tension, insomnia, sedation, and pleasantness. Cotinine had minimal effects on cardiovascular measurements. These findings indicate that cotinine is behaviorally active in the setting of cigarette abstinence at blood concentrations similar to those commonly achieved through daily cigarette smoking. C1 UNIV MINNESOTA,SCH MED,DEPT PSYCHIAT,MINNEAPOLIS,MN 55455. UNIV MINNESOTA,SCH MED,DEPT MED,MINNEAPOLIS,MN 55455. UNIV MINNESOTA,SCH MED,DEPT PHARMACOL,MINNEAPOLIS,MN 55455. RP KEENAN, RM (reprint author), NIDA,ADDICT RES CTR,CLIN PHARMACOL BRANCH,POB 5180,BALTIMORE,MD 21224, USA. NR 29 TC 43 Z9 45 U1 0 U2 2 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 MAY PY 1994 VL 55 IS 5 BP 581 EP 590 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA NM880 UT WOS:A1994NM88000013 PM 8181202 ER PT J AU HENNINGFIELD, JE SINGLETON, EG AF HENNINGFIELD, JE SINGLETON, EG TI MANAGING DRUG-DEPENDENCE - PSYCHOTHERAPY OR PHARMACOTHERAPY SO CNS DRUGS LA English DT Article ID OPIATE ADDICTS; NICOTINE GUM; SMOKING AB Drug dependence involves the repetitive use of substances that produce reinforcing effects in the CNS. Drug dependence disorders can often be more effectively and less expensively treated than the consequences of dependence (e.g. HIV infection, liver cirrhosis, lung cancer). Systematic psychotherapy or behavioural intervention is the most widely studied and used treatment for drug dependence. Medications can be used to treat aspects of drug dependence by reducing withdrawal symptoms, blocking the addicting effects of the drugs, and by protracting episodes of remission. We conclude that insofar as a critical therapeutic goal is a change of behaviour, some form of behavioural intervention is the cornerstone of all therapies for drug dependence, and that a comprehensive drug dependence treatment programme should include the option to administer medications as indicated. Additionally, the most cost-effective approaches to treating drug dependence in large populations may be those that integrate psychotherapeutic and medication-based approaches as per the needs of the individual patients. RP HENNINGFIELD, JE (reprint author), NIDA,ADDICT RES CTR,CLIN PHARMACOL BRANCH,POB 5180,BALTIMORE,MD 21224, USA. OI Singleton, Edward G./0000-0003-3442-877X NR 31 TC 2 Z9 2 U1 0 U2 0 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND SN 1172-7047 J9 CNS DRUGS JI CNS Drugs PD MAY PY 1994 VL 1 IS 5 BP 317 EP 322 DI 10.2165/00023210-199401050-00001 PG 6 WC Clinical Neurology; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA NM199 UT WOS:A1994NM19900001 ER PT J AU OSWALD, IP WYNN, TA SHER, A JAMES, SL AF OSWALD, IP WYNN, TA SHER, A JAMES, SL TI NO AS AN EFFECTOR MOLECULE OF PARASITE KILLING - MODULATION OF ITS SYNTHESIS BY CYTOKINES SO COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-PHARMACOLOGY TOXICOLOGY & ENDOCRINOLOGY LA English DT Review DE NO; PARASITE KILLING; CYTOKINES ID TUMOR-NECROSIS-FACTOR; NITRIC-OXIDE SYNTHASE; GROWTH-FACTOR-BETA; GAMMA-ACTIVATED MACROPHAGES; L-ARGININE; IFN-GAMMA; FACTOR-ALPHA; SCHISTOSOMA-MANSONI; RIBONUCLEOTIDE REDUCTASE; PERITONEAL-MACROPHAGES AB It has recently been appreciated that NO, a molecule previously known to play a physiologic role in blood pressure regulation, is a major effector molecule of macrophage cytotoxicity against a variety of microbial targets, including protozoan and helminth parasites. NO production by macrophages is arginine dependent and catalyzed by a cytokine-inducible form of the NO synthase. This activity is positively controlled by several up-regulatory stimuli (including IFN-gamma, TNF-alpha, IL-2) and negatively controlled by others (principally IL-10, IL-4, TGF-beta). Other cell types, such as endothelial cells and hepatocytes, display a similar capacity for NO production in response to cytokine stimulation. In murine models of leishmaniasis and schistosomiasis, in vivo NO synthesis correlates with protective immunity against infection. The effector molecule that plays a similar role in cell-mediated immunity in man has not yet been identified. RP OSWALD, IP (reprint author), NIAID,PARASIT DIS LAB,BLDG 4,ROOM 126,BETHESDA,MD 20892, USA. RI Wynn, Thomas/C-2797-2011; OSWALD, Isabelle/A-8497-2013; OI OSWALD, Isabelle/0000-0001-9918-277X NR 55 TC 83 Z9 85 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0742-8413 J9 COMP BIOCHEM PHYS C JI Comp. Biochem. Physiol. C-Pharmacol. Toxicol. Endocrinol. PD MAY PY 1994 VL 108 IS 1 BP 11 EP 18 DI 10.1016/1367-8280(94)90083-3 PG 8 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Toxicology; Zoology SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Toxicology; Zoology GA NQ394 UT WOS:A1994NQ39400002 PM 7520338 ER PT J AU CALVO, JC AF CALVO, JC TI DATALOAD - A USER-FRIENDLY PROGRAM TO PREPARE BINDING DATA FOR THE LIGAND SOFTWARE SO COMPUTERS IN BIOLOGY AND MEDICINE LA English DT Article DE LIGAND; BINDING; COMPUTER; DATA ANALYSIS; SOFTWARE ID DRUG-RECEPTOR INTERACTIONS; QUANTITATIVE-ANALYSIS; SYSTEMS; BRAIN AB This paper presents a program for the preparation of binding data to be used with the LIGAND software. This program will analyze saturation and competition/displacement binding data, and prepare all the necessary files that provide the input values for the final processing by the LIGAND package. Features include choices of different units for specific activity of the labeled tracer, and screen editing of the data, and results are provided as an average of replicates or as individual points. The program creates a graphic file to observe the raw data as a B/T vs T graph, prior to the analysis with the LIGAND program. The program saves all the information in a session file. Calculation of the bound/free values for the raw data is also provided. C1 NIDR,BONE RES BRANCH,PROTEOGLYCAN CHEM SECT,BETHESDA,MD 20892. NR 8 TC 1 Z9 1 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0010-4825 J9 COMPUT BIOL MED JI Comput. Biol. Med. PD MAY PY 1994 VL 24 IS 3 BP 205 EP 210 DI 10.1016/0010-4825(94)90016-7 PG 6 WC Biology; Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Computer Science; Engineering; Mathematical & Computational Biology GA NX223 UT WOS:A1994NX22300005 PM 7924265 ER PT J AU WEST, SG AF WEST, SG TI PERSONALITY AND SOCIAL-PSYCHOLOGY - TOWARDS A SYNTHESIS - KRAHE,B SO CONTEMPORARY PSYCHOLOGY LA English DT Book Review RP WEST, SG (reprint author), ARIZONA STATE UNIV,NIMH,INTERVENT RES CTR,TEMPE,AZ 85287, USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 0010-7549 J9 CONTEMP PSYCHOL JI Comtemp. Psychol. PD MAY PY 1994 VL 39 IS 5 BP 486 EP 487 PG 2 WC Psychology, Multidisciplinary SC Psychology GA NL999 UT WOS:A1994NL99900030 ER PT J AU NEWLIN, DB AF NEWLIN, DB TI THE NEUROBIOLOGY OF DRUG AND ALCOHOL ADDICTION - KALIVAS,PW, SAMSON,HH SO CONTEMPORARY PSYCHOLOGY LA English DT Book Review RP NEWLIN, DB (reprint author), NIDA,ADDICT RES CTR,BALTIMORE,MD 21224, USA. NR 2 TC 4 Z9 4 U1 0 U2 0 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 0010-7549 J9 CONTEMP PSYCHOL JI Comtemp. Psychol. PD MAY PY 1994 VL 39 IS 5 BP 511 EP 512 PG 2 WC Psychology, Multidisciplinary SC Psychology GA NL999 UT WOS:A1994NL99900050 ER PT J AU HARTMANN, C RECIPON, H JUBIER, MF VALON, C DELCHERBESIN, E HENRY, Y DEBUYSER, J LEJEUNE, B RODE, A AF HARTMANN, C RECIPON, H JUBIER, MF VALON, C DELCHERBESIN, E HENRY, Y DEBUYSER, J LEJEUNE, B RODE, A TI MITOCHONDRIAL-DNA VARIABILITY DETECTED IN A SINGLE WHEAT REGENERANT INVOLVES A RARE RECOMBINATION EVENT ACROSS A SHORT REPEAT SO CURRENT GENETICS LA English DT Article DE RECIPROCAL RECOMBINATION; MITOCHONDRIAL GENOME; CHONDRIOME VARIABILITY; TRITICUM AESTIVUM ID SOMATIC TISSUE-CULTURES; LARGE-SCALE DELETIONS; GENOME ORGANIZATION; HOMOLOGOUS RECOMBINATION; SOMACLONAL VARIATION; SEQUENCE-ANALYSIS; IMMATURE EMBRYOS; ANTHER CULTURE; PLASTID DNA; MAIZE AB The mitochondrial genome of the selfed progeny of a plant regenerated from long-term somatic tissue culture displays specific structural rearrangements characterized by the appearance of novel restriction fragments. A mitochondrial DNA library was constructed from this selfed progeny in the SalI site of cosmid pHC79 and the novel fragments were subsequently studied. They were shown to arise from reciprocal recombination events involving DNA sequences present in the parental plant. The regions of recombination were sequenced and the nucleotide sequences were aligned with those of the presumptive parental fragments. We characterized an imperfect short repeated DNA sequence, 242 bp long, within which a 7-bp DNA repeat could act as a region of recombination. The use of PCR technology allowed us to show that these fragments were present in both parental plants and tissue cultures as low-abundance sequence arrangements. C1 UNIV PARIS 11,CNRS,URA 1128,BIOL MOLEC VEGETALE LAB,F-91405 ORSAY,FRANCE. NIH,NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,BETHESDA,MD 20892. CNRS,INST SCI VEGETALES,F-91198 GIF SUR YVETTE,FRANCE. RI HENRY, Yves/B-8941-2008 NR 45 TC 34 Z9 34 U1 0 U2 2 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0172-8083 J9 CURR GENET JI Curr. Genet. PD MAY PY 1994 VL 25 IS 5 BP 456 EP 464 DI 10.1007/BF00351786 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA NH458 UT WOS:A1994NH45800011 PM 8082192 ER PT J AU LAND, KC GURALNIK, JM BLAZER, DG AF LAND, KC GURALNIK, JM BLAZER, DG TI ESTIMATING INCREMENT-DECREMENT LIFE-TABLES WITH MULTIPLE COVARIATES FROM PANEL-DATA - THE CASE OF ACTIVE LIFE EXPECTANCY SO DEMOGRAPHY LA English DT Article ID UNITED-STATES; POPULATION; MORTALITY; HETEROGENEITY; SELECTION; DYNAMICS AB A fundamental limitation of current multistate life table methodology-evident in recent estimates of active life expectancy for the elderly-is the inability to estimate tables from data on small longitudinal panels in the presence of multiple covariates (such as sex, race, and socioeconomic status). This paper presents an approach to such an estimation based on an isomorphism between the structure of the stochastic model underlying a conventional specification of the increment-decrement life table and that of Markov panel regression models for simple state spaces. We argue that Markov panel regression procedures can be used to provide smoothed or graduated group-specific estimates of transition probabilities that are more stable across short age intervals than those computed directly from sample data. We then join these estimates with increment-decrement life table methods to compute group-specific total, active, and dependent life expectancy estimates. To illustrate the methods, we describe an empirical application to the estimation of such life expectancies specific to sex, race, and education (years of school completed) for a longitudinal panel of elderly persons. We find that education extends both total life expectancy and active life expectancy. Education thus may serve as a powerful social protective mechanism delaying the onset of health problems at older ages. C1 DUKE UNIV,CTR DEMOG STUDIES,DURHAM,NC 27708. DUKE UNIV,CTR AGING & HUMAN DEV,DURHAM,NC 27708. NIA,EPIDEMIOL DEMOG & BIOMETRY PROGRAM,BETHESDA,MD 20892. DUKE UNIV,MED CTR,OFF MED EDUC,DURHAM,NC 27710. RP LAND, KC (reprint author), DUKE UNIV,DEPT SOCIOL,DURHAM,NC 27708, USA. FU NIA NIH HHS [NIA NO2-AG-1-2102] NR 55 TC 66 Z9 66 U1 0 U2 1 PU POPULATION ASSN AMER PI WASHINGTON PA 1722 N ST NW, WASHINGTON, DC 20036 SN 0070-3370 J9 DEMOGRAPHY JI Demography PD MAY PY 1994 VL 31 IS 2 BP 297 EP 319 DI 10.2307/2061887 PG 23 WC Demography SC Demography GA NV479 UT WOS:A1994NV47900008 PM 7926190 ER PT J AU SALINAS, PC FLETCHER, C COPELAND, NG JENKINS, NA NUSSE, R AF SALINAS, PC FLETCHER, C COPELAND, NG JENKINS, NA NUSSE, R TI MAINTENANCE OF WNT-3 EXPRESSION IN PURKINJE-CELLS OF THE MOUSE CEREBELLUM DEPENDS ON INTERACTIONS WITH GRANULE CELLS SO DEVELOPMENT LA English DT Article DE PURKINJE CELLS; GRANULE CELLS; WEAVER; WNT GENES; EN-2; MEANDER TAIL; MOUSE DEVELOPMENT ID POSTNATAL-DEVELOPMENT; REGIONAL DIFFERENCES; INT-1 PROTOONCOGENE; MOLECULAR LAYER; GENE-EXPRESSION; MESSENGER-RNAS; WEAVER; MICE; RAT; PHENOTYPE AB Wnt genes encode secreted proteins implicated in cell fate changes during development. To define specific cell populations in which Wnt genes act, we have examined Wnt expression in the cerebellum. This part of the brain has a relatively simple structure and contains well-characterized cell populations. We found that Wnt-3 is expressed during development of the cerebellum and that expression is restricted to the Purkinje cell layer in the adult. Wnt-3 expression in Purkinje cells increases postnatally as granule cells start to make contacts with Purkinje cells. To investigate whether interactions with granule cells influence Wnt-3 expression in Purkinje cells, we examined gene expression in several mouse mutants, using the expression of En-2 to follow the fate of granule cells. In the weaver mutant, in which granule cells fail to migrate and subsequently die in the external granular layer, Wnt-3 expression was normal at postnatal day 15 (P15). At that time, some granule cells are still present in the external granular layer. At P28, however, when granule cells could no longer be detected, Wnt-3 expression was almost absent. In the meander tail mutant, in which the anterior cerebellar lobes lack granule cells, Wnt-3 expression was only detected in the normal posterior lobes. Since En genes are implicated in cell-cell interactions mediated by Wnt genes, we examined En-2/En-2 mutant mice, finding normal Wnt-3 expression, indicating that the effect of granule cells on the maintenance of Wnt-3 is not mediated by En-2. Our results show that Wnt-3 expression in Purkinje cells is modulated by their presynaptic granule cells at the time of neuronal maturation. C1 STANFORD UNIV,DEPT DEV BIOL,STANFORD,CA 94305. STANFORD UNIV,HOWARD HUGHES MED INST,STANFORD,CA 94305. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. FU PHS HHS [N01-C0-74101] NR 39 TC 47 Z9 47 U1 0 U2 1 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0950-1991 J9 DEVELOPMENT JI Development PD MAY PY 1994 VL 120 IS 5 BP 1277 EP 1286 PG 10 WC Developmental Biology SC Developmental Biology GA NM702 UT WOS:A1994NM70200022 PM 8026336 ER PT J AU UCHIDA, N SHIMAMURA, K MIYATANI, S COPELAND, NG GILBERT, DJ JENKINS, NA TAKEICHI, M AF UCHIDA, N SHIMAMURA, K MIYATANI, S COPELAND, NG GILBERT, DJ JENKINS, NA TAKEICHI, M TI MOUSE ALPHA-N-CATENIN - 2 ISOFORMS, SPECIFIC EXPRESSION IN THE NERVOUS-SYSTEM, AND CHROMOSOMAL LOCALIZATION OF THE GENE SO DEVELOPMENTAL BIOLOGY LA English DT Article ID CADHERIN-ASSOCIATED PROTEIN; CELL-ADHESION; HOMOLOG; ORGANIZATION; PLAKOGLOBIN; VINCULIN; CDNA AB We isolated cDNAs encoding mouse homologues of chicken alpha N-catenin, a protein associated with the cadherin cell adhesion molecules, and identified two isoforms of this protein. One isoform (alpha N-catenin I) was identical to the chicken alpha N-catenin that had previously been identified, and the other (alpha N-catenin II) differed in having a 48-amino acid insertion in its C-terminal region. The ratio of the two isoforms changed during development; the isoform II was more abundant than the other in earlier embryonic stages, whereas isoform I was predominant in the adult stage. Immunostaining and in situ hybridization analyses revealed that the mouse alpha N-catenin was expressed almost exclusively in the nervous system. During embryogenesis, alpha N-catenin was first detected in nerve fibers of cranial and dorsal root ganglia and also in early neurons in the neural tube, including motor neurons. Thereafter, the expression of this protein occurred in various regions of the nervous system. Neurons, in general, strongly expressed alpha N-catenin, especially in their axonal fibers. On the other hand, the expression in glial cells varied with the region. For example, the ependymal layers of the neural tube generally expressed low levels of alpha N-catenin except at the inner limiting membrane facing the central canal, whereas the floor and roof plate exhibited strong expression of this protein at various portions of the central nervous system. The choroid plexus was devoid of alpha N-catenin. In the alpha N-catenin-negative regions, another subtype of alpha-catenin, alpha E-catenin, was expressed. Concerning nonneural tissues, alpha N-catenin was expressed only in some local mesenchymal cell clusters and the lens fibers. These results suggest that alpha N-catenin plays specific roles in neural cell-cell interactions. We also localized the mouse alpha N-catenin gene to chromosome 6. (C) 1994 Academic Press, Inc. C1 NCI,FREDERICK CANC RES & DEV CTR,MAMMALIAN GENET LAB,ABL,BASIC RES PROGRAM,FREDERICK,MD 21702. RP UCHIDA, N (reprint author), KYOTO UNIV,FAC SCI,DEPT BIOPHYS,SAKYO KU,KYOTO 60601,JAPAN. RI Takeichi, Masatoshi/G-5903-2012; OI Takeichi, Masatoshi/0000-0002-9931-3378; Uchida, Naoshige/0000-0002-5755-9409 FU NCI NIH HHS [N01-CO-74101] NR 22 TC 58 Z9 59 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 0012-1606 J9 DEV BIOL JI Dev. Biol. PD MAY PY 1994 VL 163 IS 1 BP 75 EP 85 DI 10.1006/dbio.1994.1124 PG 11 WC Developmental Biology SC Developmental Biology GA NL724 UT WOS:A1994NL72400007 PM 8174789 ER PT J AU XU, H FEDEROFF, H MARAGOS, J PARADA, LF KESSLER, JA AF XU, H FEDEROFF, H MARAGOS, J PARADA, LF KESSLER, JA TI VIRAL TRANSDUCTION OF TRKA INTO CULTURED NODOSE AND SPINAL MOTOR-NEURONS CONVEYS NGF RESPONSIVENESS SO DEVELOPMENTAL BIOLOGY LA English DT Article ID NERVE GROWTH-FACTOR; TYROSINE KINASE RECEPTOR; HERPES-SIMPLEX VIRUS; NEUROTROPHIC FACTOR; SENSORY NEURONS; BETA-GALACTOSIDASE; PROTEIN-KINASE; MESSENGER-RNA; FACTOR FAMILY; CELL-DEATH AB The trkA gene encodes the tyrosine kinase receptor that transduces the NGF signal. We have used a defective herpes simplex virus-1 (HSV-1) vector containing a full-length rat trkA sequence (pHSVtrkA) to express NGF receptors in primary cultures of neonatal nodose neurons and embryonic spinal motor neurons which are normally unresponsive to NGF. Transduction of rat neonatal nodose ganglion neurons and spinal motor neurons with pHSVtrkA resulted in expression of functional NGF receptors. Stimulation of these receptors by NGF resulted in the survival and the morphologic and biochemical differentiation of these neurons. These observations indicate that nodose and spinal motor neurons can express the downstream signal transduction apparatus necessary to mediate the survival and differentiating effects mediated by ligand binding to trkA and that transduction with pHSVtrkA can effectively convert NGF nonresponsive neurons into responsive ones. (C) 1994 Academic Press, Inc. C1 YESHIVA UNIV ALBERT EINSTEIN COLL MED,DEPT NEUROL,BRONX,NY 10461. YESHIVA UNIV ALBERT EINSTEIN COLL MED,DEPT NEUROSCI,BRONX,NY 10461. YESHIVA UNIV ALBERT EINSTEIN COLL MED,DEPT MED,BRONX,NY 10461. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,MOLEC EMBRYOL SECT,FREDERICK,MD 21702. RI Parada, luis/B-9400-2014 FU NCI NIH HHS [N01-CO-74101]; NINDS NIH HHS [NS20778, NS20013] NR 47 TC 36 Z9 36 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 0012-1606 J9 DEV BIOL JI Dev. Biol. PD MAY PY 1994 VL 163 IS 1 BP 152 EP 161 DI 10.1006/dbio.1994.1131 PG 10 WC Developmental Biology SC Developmental Biology GA NL724 UT WOS:A1994NL72400014 PM 8174770 ER PT J AU MACKINNONLEWIS, C VOLLING, BL LAMB, ME DECHMAN, K RABINER, D CURTNER, ME AF MACKINNONLEWIS, C VOLLING, BL LAMB, ME DECHMAN, K RABINER, D CURTNER, ME TI A CROSS-CONTEXTUAL ANALYSIS OF BOYS SOCIAL COMPETENCE - FROM FAMILY TO SCHOOL SO DEVELOPMENTAL PSYCHOLOGY LA English DT Article ID PEER RELATIONS; CHILDREN; CHILDHOOD; BEHAVIOR; INFORMATION AB This study examined the extent to which the hostile attributions and coercive behaviors of mothers and sons were associated with indexes of aggression, acceptance by peers, and teacher-rated social competence in the peer group. Ss were 104 married and divorced mothers and their sons (7 to 9 years old). Mothers' and sons' hostile attributions were significantly related to the coerciveness of their interactions, but only mothers' attributions related to reports of the children's aggression in the classroom. Boys who reported many stressful events in their lives behaved coercively with their mothers and were viewed as more aggressive and less socially competent with peers. The relation between stressful life events and the boys' aggression with their peers was mediated, in part, by boys' coerciveness with their mothers. The association between boys' coerciveness with their mothers and social acceptance by peers appeared to be mediated by the aggressiveness of their interactions with their peers. C1 UNIV MICHIGAN,DEPT PSYCHOL,ANN ARBOR,MI 48109. NICHHD,BETHESDA,MD 20892. UNIV ALABAMA,DEPT PSYCHOL,UNIVERSITY,AL 35486. RP MACKINNONLEWIS, C (reprint author), UNIV N CAROLINA,DEPT HUMAN DEV & FAMILY STUDIES,FAMILY RES CTR,GREENSBORO,NC 27412, USA. NR 47 TC 49 Z9 50 U1 1 U2 2 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 0012-1649 J9 DEV PSYCHOL JI Dev. Psychol. PD MAY PY 1994 VL 30 IS 3 BP 325 EP 333 DI 10.1037//0012-1649.30.3.325 PG 9 WC Psychology, Developmental SC Psychology GA NL719 UT WOS:A1994NL71900002 ER PT J AU MODAN, M HARRIS, MI AF MODAN, M HARRIS, MI TI FASTING PLASMA-GLUCOSE IN SCREENING FOR NIDDM IN THE US AND ISRAEL SO DIABETES CARE LA English DT Note ID GLYCOSYLATED HEMOGLOBIN; DIABETES-MELLITUS; TOLERANCE TEST; DIAGNOSIS; POPULATION; HYPERTENSION; INTOLERANCE; PREVALENCE; CRITERIA; OBESITY AB OBJECTIVE- To demonstrate the inadequacy of fasting plasma glucose for screening for NIDDM, even among groups at high risk for diabetes. RESEARCH DESIGN AND METHODS- Representative samples of adults 40-69 years of age in the U.S. (n = 2,035) and Israel (n = 2,316) were selected. Fasting plasma glucose (FPG) was measured and a 2-h oral glucose tolerance test (OGTT) was administered. Subjects with undiagnosed NIDDM were identified using internationally accepted diagnostic criteria (FPG greater than or equal to 7.8 mM or 2-h plasma glucose greater than or equal to 11.1 mM). RESULTS- Only 31-38% of subjects with undiagnosed NIDDM had fasting hyperglycemia (greater than or equal to 7.8 mM), and 36% in the U.S. and 19% in Israel had normoglycemia (<6.1 mM). Postchallenge glucose, diagnostic of diabetes, was associated with all fasting values, including values <5.0 mM. Based on sensitivity, specificity, and positive predictive value, no FPG level provided a satisfactory cutoff point to use in screening for undiagnosed NIDDM. Sensitivity at each FPG cutoff point varied little among groups classified by age, sex, race, blood pressure status, or body mass index (BMI) levels >23, but sensitivity was lower among those with BMI levels <23. CONCLUSIONS- In the clinical setting, FPG is commonly used in screening for NIDDM. However, fasting values greater than or equal to 7.8 mM are highly insensitive for detecting NIDDM. Lower FPG cutoff points that achieve acceptable sensitivity are accompanied by inadequately low specificity, require a high percentage of patients to be retested, and result in a low yield of diabetes among those screened. Clinicians and researchers who seek detection of undiagnosed NIDDM should use the OGTT, because FPG lacks adequate sensitivity and specificity for this purpose. C1 NIDDK,MIH,NATL DIABET DATA GRP,BETHESDA,MD 20892. CHAIM SHEBA MED CTR,DEPT CLIN EPIDEMIOL,IL-52621 TEL HASHOMER,ISRAEL. NR 15 TC 42 Z9 42 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 MAY PY 1994 VL 17 IS 5 BP 436 EP 439 DI 10.2337/diacare.17.5.436 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA NK271 UT WOS:A1994NK27100014 PM 7741837 ER PT J AU HARRIS, MI MODAN, M AF HARRIS, MI MODAN, M TI SCREENING FOR NIDDM - WHY IS THERE NO NATIONAL PROGRAM SO DIABETES CARE LA English DT Article ID CORONARY HEART-DISEASE; DEPENDENT DIABETES-MELLITUS; UNITED-STATES POPULATION; NON-HISPANIC WHITES; CARDIOVASCULAR RISK-FACTORS; IMPAIRED GLUCOSE-TOLERANCE; GLYCOSYLATED HEMOGLOBIN; MEXICAN-AMERICANS; MYOCARDIAL-INFARCTION; PHYSICAL-ACTIVITY C1 CHAIM SHEBA MED CTR,DEPT CLIN EPIDEMIOL,IL-52621 TEL HASHOMER,ISRAEL. RP HARRIS, MI (reprint author), NIDDK,NATL DIABET DATA GRP,WESTWOOD BLDG,ROOM 620,BETHESDA,MD 20892, USA. NR 69 TC 43 Z9 44 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 MAY PY 1994 VL 17 IS 5 BP 440 EP 444 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA NK271 UT WOS:A1994NK27100015 PM 8062613 ER PT J AU KNOWLER, WC AF KNOWLER, WC TI SCREENING FOR NIDDM - OPPORTUNITIES FOR DETECTION, TREATMENT, AND PREVENTION SO DIABETES CARE LA English DT Article ID DEPENDENT DIABETES-MELLITUS; IMPAIRED GLUCOSE-TOLERANCE; GLUCOKINASE GENE; RISK-FACTORS; INSULIN; POPULATION; LINKAGE C1 NIDDKD, PHOENIX, AZ USA. NR 35 TC 50 Z9 54 U1 1 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD MAY PY 1994 VL 17 IS 5 BP 445 EP 450 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA NK271 UT WOS:A1994NK27100016 PM 8062614 ER PT J AU PERI, A COWAN, BD BHARTIYA, D MIELE, L NIEMAN, LK NWAEZE, IO MUKHERJEE, AB AF PERI, A COWAN, BD BHARTIYA, D MIELE, L NIEMAN, LK NWAEZE, IO MUKHERJEE, AB TI EXPRESSION OF CLARA CELL 10-KD GENE IN THE HUMAN ENDOMETRIUM AND ITS RELATIONSHIP TO OVARIAN MENSTRUAL-CYCLE SO DNA AND CELL BIOLOGY LA English DT Article ID RABBIT UTEROGLOBIN GENE; TISSUE-SPECIFIC EXPRESSION; HORMONAL-REGULATION; KDA PROTEIN; PROGESTERONE; LOCALIZATION; REGION; TRANSGLUTAMINASE; ANTIGENICITY; SECRETIONS AB Clara cell 10-kD (cc10-kD) protein has been suggested to be the human counterpart of rabbit uteroglobin (UG). Like UG, this protein is also a potent inhibitor of phospholipase A(2) (PLA(2)) and a substrate of transglutaminase. Although it has been established that UG gene expression in the rabbit endometrium is stimulated by progesterone, the expression of cc10-kD gene in the human endometrium is not clearly understood. The present study was undertaken to determine whether the cc10-kD gene is expressed in the human endometrium and whether its level of expression changes in relation to the ovarian menstrual cycle. Using reverse transcriptase polymerase chain reaction (RT-PCR) and immunofluorescence, we demonstrate that the cc10-kD gene is expressed in different stages of the menstrual cycle and that the highest level of expression is reached during the luteal phase. These results suggest that like rabbit UC, cc10-kD gene expression in the human endometrium may be stimulated by progesterone. Since cc10-kD is a potent inhibitor of PLA(2) activity, this protein may play an important physiological role in regulating eicosanoid levels in the human uterus. C1 NICHHD, HUMAN GENET BRANCH, DEV GENET SECT, BETHESDA, MD 20892 USA. UNIV MISSISSIPPI, MED CTR, DEPT OBSTET & GYNECOL, JACKSON, MS 39216 USA. NICHHD, DEV ENDOCRINOL BRANCH, BETHESDA, MD 20892 USA. NR 46 TC 32 Z9 32 U1 1 U2 1 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 MAY PY 1994 VL 13 IS 5 BP 495 EP 503 DI 10.1089/dna.1994.13.495 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity GA NQ077 UT WOS:A1994NQ07700005 PM 7517678 ER PT J AU LAN, MS LU, J GOTO, Y NOTKINS, AL AF LAN, MS LU, J GOTO, Y NOTKINS, AL TI MOLECULAR-CLONING AND IDENTIFICATION OF A RECEPTOR-TYPE PROTEIN-TYROSINE-PHOSPHATASE, IA-2, FROM HUMAN INSULINOMA SO DNA AND CELL BIOLOGY LA English DT Article ID GLUTAMIC-ACID DECARBOXYLASE; CENTRAL-NERVOUS-SYSTEM; DIABETES-MELLITUS; FAMILY; SEQUENCE; DROSOPHILA; NEURONS; MEMBER; GENES; CELLS AB A novel 3.6-kb cDNA, IA-2, with a 2,937-bp open reading frame was isolated from a human insulinoma subtraction library (ISL-153). The predicted amino acid sequence and in vitro-translated product of IA-2 cDNA revealed a 979-amino-acid protein with a pI value of 7.09 and a molecular mass of 105,847 daltons. The protein sequence is consistent with a signal peptide, an extracellular domain, a transmembrane region, and an intracellular domain. The extracellular domain contains an unusual cysteine-rich region following the signal peptide. The intracellular cytoplasmic domain of IA-2 possesses highly conserved regions similar to the catalytic domains found in members of the protein tyrosine phosphatase (PTP) family. Northern blot analysis showed that IA-2 mRNA was expressed in five of five freshly isolated human insulinomas, rat and mouse insulinoma cell lines, and enriched normal mouse islets. It also was found in normal human brain, pituitary, pancreas, and brain tumor cell lines, but not in a variety of other normal or tumor tissues. Based on the sequence and expression data, it appears that IA-2 is a new member of the receptor-type PTP family that is expressed in islet and brain tissues. RP LAN, MS (reprint author), NIDR,ORAL MED LAB,BLDG 30,ROOM 121,BETHESDA,MD 20892, USA. NR 40 TC 285 Z9 290 U1 1 U2 5 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 MAY PY 1994 VL 13 IS 5 BP 505 EP 514 DI 10.1089/dna.1994.13.505 PG 10 WC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity GA NQ077 UT WOS:A1994NQ07700006 PM 8024693 ER PT J AU KAVSAN, VM GREBENJUK, VA KOVAL, AP SKOROKHOD, AS ROBERTS, CT LEROITH, D AF KAVSAN, VM GREBENJUK, VA KOVAL, AP SKOROKHOD, AS ROBERTS, CT LEROITH, D TI ISOLATION OF A 2ND NONALLELIC INSULIN-LIKE GROWTH-FACTOR-I GENE FROM THE SALMON GENOME SO DNA AND CELL BIOLOGY LA English DT Article ID NUCLEOTIDE-SEQUENCE; CHUM SALMON; DNA FRAGMENTS; EXPRESSION; HORMONE; RNA AB We have characterized a second nonallelic insulin-like growth factor-I (IGF-I) gene in the chum salmon (Oncorhynchus keta) genome. This gene, IGF-I.2, differs from the previously described chum salmon ICE-I gene, IGF-I.1, in the E peptide-coding portion of exon 3; specifically, the IGF-I.2 gene lacks one codon present in the ICE-I gene and contains two potential splice donor sites at the 3' end of exon 3 rather than the single, more distal site present in the ICF-I.1 gene. The expression of these two ICE-I genes could give rise to as many as six ICE-I mRNA species, each of which would encode a unique E-peptide moiety of the ICE-I prohormone. Thus, the presence of multiple, distinct IGF genes adds an additional level of complexity to IGF-I gene expression and IGF-I biosynthesis in salmon. C1 NIDDK,DIABET BRANCH,BETHESDA,MD 20892. UKRAINIAN ACAD SCI,INST MOLEC BIOL & GENET,KIEV 252627,UKRAINE. NR 22 TC 29 Z9 31 U1 0 U2 1 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 MAY PY 1994 VL 13 IS 5 BP 555 EP 559 DI 10.1089/dna.1994.13.555 PG 5 WC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity GA NQ077 UT WOS:A1994NQ07700012 PM 8024699 ER PT J AU NEWMAN, RA FUENTES, A COVEY, JM BENVENUTO, JA AF NEWMAN, RA FUENTES, A COVEY, JM BENVENUTO, JA TI PRECLINICAL PHARMACOLOGY OF THE NATURAL MARINE PRODUCT DOLASTATIN-10 (NSC-376128) SO DRUG METABOLISM AND DISPOSITION LA English DT Article ID ANTINEOPLASTIC AGENTS; CYCLOSPORINE; TUBULIN; BINDING AB The preclinical pharmacology and pharmacokinetics of the natural marine product dolastatin 10 were investigated. Pharmacokinetics of [H-3]dolastatin 10 were determined in CD2F1 mice after intravenous, subcutaneous, and intraperitoneal routes of administration. After intravenous injection (0.24 mg/kg), plasma drug concentration declined rapidly and was cleared from plasma with a half-life of 5.6 hr. After a subcutaneous dose of 0.32 mg/kg, dolastatin 10 concentrations slowly rose to a maximum of 11 ng/ml and then declined with an elimination half-life of 3.7 hr. Most of the radioactivity in plasma was found to be from drug-derived radiolabeled products and not from parent compound. Urinary excretion of dolastatin 10 was <2% of the administered dose, irrespective of the route of administration. In vitro, dolastatin 10 was stable in mouse plasma for at least 24 hr at 37 degrees C. The drug was also highly protein-bound (>81%) in human, dog, and mouse plasmas. Dolastatin 10 underwent rapid conversion to more polar products after incubation with whole liver homogenate or the S9 fraction from rat liver. One of these metabolites was identified by mass spectrometry as a dihydroxy derivative of dolastatin 10. C1 NCI,PHARMACOL BRANCH,BETHESDA,MD 20892. RP NEWMAN, RA (reprint author), UNIV TEXAS,MD ANDERSON CANC CTR,DEPT CLIN INVEST,BOX 52,1515 HOLCOMBE BLVD,HOUSTON,TX 77030, USA. FU NCI NIH HHS [NCI CA-16672, N01-CM-27712] NR 8 TC 21 Z9 21 U1 0 U2 2 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0090-9556 J9 DRUG METAB DISPOS JI Drug Metab. Dispos. PD MAY-JUN PY 1994 VL 22 IS 3 BP 428 EP 432 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA NL978 UT WOS:A1994NL97800014 PM 8070319 ER PT J AU ADLER, WH NAGEL, JE AF ADLER, WH NAGEL, JE TI ACQUIRED-IMMUNODEFICIENCY-SYNDROME IN THE ELDERLY SO DRUGS & AGING LA English DT Review ID IMMUNE-DEFICIENCY-SYNDROME; SAN-FRANCISCO; AIDS; HIV; VIRUS; AGE; TRANSMISSION; TRANSFUSION; INFECTION; PEOPLE AB Recent data from the US show that since 1990 the number of paediatric patients with AIDS is decreasing while the number of patients with AIDS over age 50 years is increasing. To date, little attention has been given to understanding AIDS risk-taking behaviours, clinical presentations, and therapeutic needs of middle-aged and older HIV-infected individuals. Older HIV-infected individuals deteriorate more rapidly than younger patients due to an accelerated loss of CD3+ helper T cells. Despite recognised age-related physiological differences between young and elderly individuals, scant information about drug optimisation for the treatment of AIDS in older individuals is available. More data need to be collected about this group of AIDS patients, and appropriate treatment strategies designed for their special needs. RP ADLER, WH (reprint author), NIA,GERONTOL RES CTR,CLIN IMMUNOL SECT,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. NR 44 TC 30 Z9 30 U1 0 U2 0 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND SN 1170-229X J9 DRUG AGING JI Drugs Aging PD MAY PY 1994 VL 4 IS 5 BP 410 EP 416 DI 10.2165/00002512-199404050-00006 PG 7 WC Geriatrics & Gerontology; Pharmacology & Pharmacy SC Geriatrics & Gerontology; Pharmacology & Pharmacy GA NL014 UT WOS:A1994NL01400006 PM 8043943 ER PT J AU HE, CY MERRICK, BA WITCHER, LL PATTERSON, RM DALUGE, DR SELKIRK, JK AF HE, CY MERRICK, BA WITCHER, LL PATTERSON, RM DALUGE, DR SELKIRK, JK TI PHENOTYPIC CHANGE AND ALTERED PROTEIN EXPRESSION IN X-RAY AND METHYLCHOLANTHRENE-TRANSFORMED C3H10T1/2 FIBROBLASTS SO ELECTROPHORESIS LA English DT Article ID 2-DIMENSIONAL GEL-ELECTROPHORESIS; CHEMICAL CARCINOGENESIS; DIMENSIONAL ELECTROPHORESIS; SEQUENTIAL-ANALYSIS; CELLS; ONCOGENES; CANCER; PROMOTION; CYCLIN; GENE AB The morphology, growth properties and cellular protein patterns from parent and two transformed C3H10T1/2 cell lines were analyzed to associate the phenotypic and protein differences with cell transformation. Transformed 10T1/2 cells were obtained by colony isolation after exposure of parent 10T1/2 cells to methylcholanthrene (MCA-1 cell line) or X-ray irradiation (XR-III cell line). Compared to parent 10T1/2 and MCA-1 cells, XR-III cells were much smaller in size and exhibited the highest growth rate, greatest cell saturation density, increased plating efficiency and greater expression of proliferating cell nuclear antigen. MCA-1 cells showed intermediate characteristics between parent and XR-III cells. Among the three cell lines, only XR-III cells showed anchorage-independent growth in soft agar. When [S-35]methionine-labeled whole cell lysate proteins were separated by two-dimensional polyacrylamide gel electrophoresis, computer comparison algorithms revealed a 97% similarity in protein profiles among almost 800 proteins detected from each cell line. However, comparison of proteins patterns of the transformed cell lines to that of parent 10T1/2 cells showed that 30 and 20 proteins were induced or repressed in XR-III cells and MCA-1 cells, respectively. Similarly, 81 and 24 proteins showed significant quantitative changes (threefold or greater) in XR-III and MCA-1 cells, respectively, as compared with parent 10T1/2 cell proteins. The anchorage-independent growth and increased proliferation properties of XR-III cells suggest a later stage of transformation compared to MCA-1 cells. Overall, these data suggest that gradational morphologic and phenotypic aberrancy in MCA-1 and XR-III cell lines from parent cells is accompanied by an increased diversity in protein expression in a limited set of proteins, some of which may play important roles in the multistep transformation process. C1 NIEHS,DIV INTRAMURAL RES,MOLEC CARCINOGENESIS LAB,RES TRIANGLE PK,NC 27709. NR 40 TC 4 Z9 4 U1 0 U2 0 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0173-0835 J9 ELECTROPHORESIS JI Electrophoresis PD MAY PY 1994 VL 15 IS 5 BP 726 EP 734 DI 10.1002/elps.11501501100 PG 9 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA NU199 UT WOS:A1994NU19900026 PM 7925252 ER PT J AU MERRICK, BA PATTERSON, RM WITCHER, LL HE, CY SELKIRK, JK AF MERRICK, BA PATTERSON, RM WITCHER, LL HE, CY SELKIRK, JK TI SEPARATION AND SEQUENCING OF FAMILIAR AND NOVEL MURINE PROTEINS USING PREPARATIVE 2-DIMENSIONAL GEL-ELECTROPHORESIS SO ELECTROPHORESIS LA English DT Article ID MOUSE EMBRYO CELLS; MEMBRANE; IDENTIFICATION; PHOSPHORYLATION; TRANSFORMATION; CLONING; MEMBER; FIBROBLASTS; HOMOLOG; BRAIN AB Strategies are needed for rapid protein isolation in order to identify disease-related proteins and facilitate the design of oligonucleotides for further molecular inquiry. In our laboratory, C3H10T1/2 murine fibroblasts have been found to express a variety of proteins in various subcellular fractions which are relevant to experimental transformation and carcinogenesis. Preparative two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) procedures were developed to identify major cytoplasmic proteins by electroblotting and microsequencing. Isoelectric focusing tube gels were enlarged to 6 mm ID to accommodate larger protein loads at 0.5 to 2 mg protein. Separated proteins were electrotransferred from 6 mm thick slab gels onto 0.22 mu polyvinylidene difluoride membranes. Nearly 100 prominent blotted proteins were stained with Coomassie Brilliant Blue between pI 4.5-7.0 and 18-106 kDa and, of these, 27 prominent and well-resolved proteins were selected for sequencing. Sequences of 14 to 24 amino acid residues in length were obtained from 11 proteins which were identified from computerized databases. Some of these identified proteins had structural or enzymatic functions while others had only recently been discovered, including a newly reported Hsp 70 class member and a novel calcium-binding protein, reticulocalbin. The new heat shock protein has a molecular mass of 75 kDa and has been designated as Grp75, PBP74, CSA or p66(mot-1) in mice and humans with purported roles in transformation and antigen processing. Reticulocalbin is an endoplasmic reticular protein which contains six domains of the EF-hand motif associated with high-affinity calcium-binding proteins. It may be involved in protein transport and luminal protein processing. In addition, sequences of 5 to 11 residues in length were also obtained from six other unidentified proteins. Thus, we have found that preparative 2-D PAGE serves as a powerful one-step purification method for protein isolation and characterization from an important in vitro murine model for the study of carcinogenesis. RP MERRICK, BA (reprint author), NIEHS,MOLEC CARCINOGENESIS LAB,POB 12233,D4-03,RES TRIANGLE PK,NC 27709, USA. NR 50 TC 8 Z9 24 U1 0 U2 0 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0173-0835 J9 ELECTROPHORESIS JI Electrophoresis PD MAY PY 1994 VL 15 IS 5 BP 735 EP 745 DI 10.1002/elps.11501501101 PG 11 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA NU199 UT WOS:A1994NU19900027 PM 7523108 ER PT J AU MUKHOPADHYAY, G SOZHAMANNAN, S CHATTORAJ, DK AF MUKHOPADHYAY, G SOZHAMANNAN, S CHATTORAJ, DK TI RELAXATION OF REPLICATION CONTROL IN CHAPERONE-INDEPENDENT INITIATOR MUTANTS OF PLASMID P1 SO EMBO JOURNAL LA English DT Article DE ACTION AT A DISTANCE; DNA-PROTEIN INTERACTIONS; DNA REPLICATION; HEAT SHOCK PROTEINS; PROTEIN FOLDING ID HEAT-SHOCK PROTEINS; LAMBDA-DNA-REPLICATION; NEGATIVE CONTROL; LAC REPRESSOR; BINDING; ORIGIN; REPA; GRPE; DIMERIZATION; MONOMERIZATION AB Escherichia coli chaperones DnaJ, DnaK and GrpE increase P1 plasmid initiator binding to the origin by promoting initiator folding. The binding allows initiation and also promotes pairing of origins which is believed to control initiation frequency. Chaperone-independent DNA binding mutants are often defective in replication control. We show here that these mutants have increased rates of association for DNA binding and defects in origin pairing. The increases in association rates were found to be due either to increased protein folding into active forms or to increases in the association rate constant, k(on). Since the dissociation rate constants for DNA release with these mutants are not changed, it is unlikely that the DNA binding domain is affected. The pairing domain may thus control replication and modulate DNA binding. The role of the pairing domain in DNA binding can be significant in vivo as the selection for chaperone-independent binding favors pairing-defective mutants. C1 NCI, BIOCHEM LAB, BETHESDA, MD 20892 USA. NR 40 TC 27 Z9 27 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0261-4189 EI 1460-2075 J9 EMBO J JI Embo J. PD MAY 1 PY 1994 VL 13 IS 9 BP 2089 EP 2096 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA NK166 UT WOS:A1994NK16600009 PM 7910558 ER PT J AU DARWICHE, N CELLI, G DE LUCA, LM AF DARWICHE, N CELLI, G DE LUCA, LM TI SPECIFICITY OF RETINOID RECEPTOR GENE-EXPRESSION IN MOUSE CERVICAL EPITHELIA SO ENDOCRINOLOGY LA English DT Article ID ACID-BINDING PROTEIN; VITAMIN-A; INTRAEPITHELIAL NEOPLASIA; THYROID-HORMONE; X-RECEPTOR; BETA; DIFFERENTIATION; GAMMA; SKIN; EMBRYOGENESIS AB Retinoids are powerful regulators of epithelial differentiation and are essential for its maintenance. Because retinoids are necessary for cervical epithelial differentiation, they have been used as chemopreventive agents of cervical dysplasia and neoplasia. We were interested in determining whether different cervical epithelial phenotypes express specific retinoid receptors. The cervical epithelium contains the two phenotypes, stratified squamous and simple columnar, which join at the squamocolumnar junction. In addition, the simple columnar epithelium undergoes squamous metaplasia in response to vitamin A deficiency. Therefore, the cervical epithelium is suitable to study the expression pattern of the retinoid receptors in the three phenotypes, simple columnar, stratified squamous, and squamous metaplastic, simultaneously. The distribution pattern of the major retinoic acid receptor (RAR) isoforms (alpha 1, alpha 2, beta 2, beta 3, gamma 1, and gamma 2) and retinoid-X receptors (RXR alpha, -beta, and -gamma) was studied by in situ hybridization. At the tissue level, RAR alpha (1 and 2) and RXR (alpha and beta) transcripts and, to a lesser extent, RAR gamma (1 and 2) transcripts were associated with the cervical stratified squamous subjunctional epithelium. The simple columnar epithelium, which is highly responsive to vitamin A status, expressed high levels of RAR alpha (1 and 2), RAR beta (2 and 3), and RXR (alpha and beta) transcripts. Only RAR beta (2 and 3) and RXR (alpha and beta) transcripts were downmodulated by the condition of vitamin A deficiency and expressed less in squamous metaplastic foci than the simple columnar epithelium. RXR gamma was undetectable in all three cervical epithelia. At the cellular level, basal and suprabasal expression was found for RARs, and preferential localization of RXRs was seen in basal cells. RXRs are auxiliary proteins for a variety of other nuclear receptors with which they form heterodimers, including RARs. The fact that RXRs are mainly localized in basal and columnar cells of the cervix suggests the need for the regulation and diversity generated by potential heterodimeric interactions in these rapidly proliferating cells in vivo. The unique pattern of expression and localization of the RARs and RXRs in different cervical epithelial tissues and cell types supports the hypothesis that they perform specific functions in cervical epithelial differentiation. This is in contrast to the major isoforms of each RAR, which have similar patterns of expression in the different cervical epithelial phenotypes and cell types, suggesting a redundancy in function. C1 NCI, CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB, DIFFERENTIAT CONTROL SECT, BETHESDA, MD 20892 USA. OI Darwiche, Nadine/0000-0002-1862-5426 NR 49 TC 41 Z9 41 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 MAY PY 1994 VL 134 IS 5 BP 2018 EP 2025 DI 10.1210/en.134.5.2018 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA NG467 UT WOS:A1994NG46700006 PM 8156902 ER PT J AU RALL, DP AF RALL, DP TI REGARDING BIAS - REPLY SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Letter ID MESOTHELIOMA RP RALL, DP (reprint author), NIEHS,BETHESDA,MD, USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU NATL INST ENVIRON HEALTH SCI PI RES TRIANGLE PK PA PO BOX 12233, RES TRIANGLE PK, NC 27709 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD MAY PY 1994 VL 102 IS 5 BP 426 EP 426 PG 1 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA NU651 UT WOS:A1994NU65100005 ER PT J AU CAMPBELL, MK FEUER, EJ WUN, LM AF CAMPBELL, MK FEUER, EJ WUN, LM TI COHORT SPECIFIC RISKS OF DEVELOPING BREAST-CANCER TO AGE-85 IN CONNECTICUT SO EPIDEMIOLOGY LA English DT Article DE BREAST NEOPLASMS; INCIDENCE; LIFE TABLE; COHORT; TIME TRENDS AB Previous estimates of the lifetime risk of developing breast cancer have used cross-sectional estimates of incidence. Cross sectional rates, however, yield a biased picture of cohort risks when rates are unstable, as breast cancer trends have been. We developed cohort life tables for Connecticut women born from 1888-1892 to 1948-1952 to generate more specific estimates of breast cancer risk to age 85. Multiple decrement life tables were produced for each birth cohort. We included as cases only the first reports of breast cancer in women with no earlier malignancy. Our results indicate that widely circulated lifetime risks of 1 in 9 may be inflated slightly owing to changing incidence. We estimate that of those women 40-44 years old in 1992, 1 woman in 10 will develop breast cancer by age 85. For women born between 1928 and 1932, 1 in 13 will be diagnosed with breast cancer by age 85. The results are insensitive to mortality trends in the past. Errors in the estimates are more likely to arise from changes in incidence and mortality in the future. RP CAMPBELL, MK (reprint author), NCI,DIV CANC PREVENT & CONTROL,EXECUT PLAZA N,ROOM 313,BETHESDA,MD 20892, USA. NR 0 TC 11 Z9 11 U1 0 U2 3 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD MAY PY 1994 VL 5 IS 3 BP 290 EP 296 DI 10.1097/00001648-199405000-00006 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA NJ910 UT WOS:A1994NJ91000006 PM 8038242 ER PT J AU DEVINSKY, O RONSAVILLE, D COX, C WITT, E FEDIO, P THEODORE, WH AF DEVINSKY, O RONSAVILLE, D COX, C WITT, E FEDIO, P THEODORE, WH TI INTERICTAL AGGRESSION IN EPILEPSY - THE BUSS-DURKEE HOSTILITY INVENTORY SO EPILEPSIA LA English DT Article DE SEIZURES; EPILEPSY; AGGRESSION; BEHAVIOR; TEMPORAL LOBE; PSYCHOMETRICS ID TEMPORAL-LOBE EPILEPSY; PSYCHOMOTOR EPILEPSY; EPILEPTOGENIC LESION; AFFECTIVE-DISORDER; SCHIZOPHRENIA; PSYCHOSIS; ABNORMALITIES; LATERALITY; BEHAVIOR AB Adult patients with left, right, or bilateral temporal lobe epilepsy or absence epilepsy, and normal controls completed the Buss-Durkee Hostility Inventory (BDHI), a standardized questionnaire of aggressive tendencies. Patients with left temporal lobe seizure foci scores higher on the Suspicion scale than did other patients or controls (p < 0.05). Factor analysis scale scores identified three factors: hostile feelings, covert aggression, and overt aggression. The groups differed on their pattern of factor scores (p < 0.01): patients with left temporal lobe epilepsy scored higher than other groups on hostile feelings, normal controls scored higher on Covert aggression, and bitemporal patients scores higher on Overt aggression. Patients with absence seizures did not differ from controls. Lateralization of the seizure focus in patients with temporal lobe epilepsy may alter expression of aggressive behavior. C1 NINCDS,CLIN EPILEPSY SECT,MED NEUROL BRANCH,BETHESDA,MD. NINCDS,NEUROPSYCHOL SECT,MED NEUROL BRANCH,BETHESDA,MD 20892. NR 46 TC 18 Z9 19 U1 1 U2 3 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD MAY-JUN PY 1994 VL 35 IS 3 BP 585 EP 590 DI 10.1111/j.1528-1157.1994.tb02478.x PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA NW291 UT WOS:A1994NW29100015 PM 8026404 ER PT J AU TALARWILLIAMS, C SNELLER, MC AF TALARWILLIAMS, C SNELLER, MC TI COMPLICATIONS OF CORTICOSTEROID-THERAPY SO EUROPEAN ARCHIVES OF OTO-RHINO-LARYNGOLOGY LA English DT Review DE AUTOIMMUNE AND INFLAMMATORY DISEASE; CORTICOSTEROID THERAPY; COMPLICATIONS ID GLUCOCORTICOID-INDUCED OSTEOPOROSIS; BONE LOSS; MANAGEMENT; MECHANISMS AB The biochemistry and pharmacology of corticosteroids are reviewed as related to their clinical use, inclusive of head and neck disease. Complications and their management are discussed, as is a dosage regimen considered useful for most patients. Alternate-day corticosteroid therapy is stressed, especially in the long-term management of autoimmune and inflammatory disorders. C1 NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. NR 28 TC 12 Z9 12 U1 0 U2 0 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 MAY PY 1994 VL 251 IS 3 BP 131 EP 136 PG 6 WC Otorhinolaryngology SC Otorhinolaryngology GA NR209 UT WOS:A1994NR20900001 PM 8080631 ER PT J AU WONG, P TAILLEFER, D LAKINS, J PINEAULT, J CHADER, G TENNISWOOD, M AF WONG, P TAILLEFER, D LAKINS, J PINEAULT, J CHADER, G TENNISWOOD, M TI MOLECULAR CHARACTERIZATION OF HUMAN TRPM-2/CLUSTERIN, A GENE ASSOCIATED WITH SPERM MATURATION, APOPTOSIS AND NEURODEGENERATION SO EUROPEAN JOURNAL OF BIOCHEMISTRY LA English DT Article ID PROGRAMMED CELL-DEATH; RETE TESTIS FLUID; SULFATED GLYCOPROTEIN-2; MESSENGER-RNA; HUMAN HOMOLOG; RAT SERTOLI; EXPRESSION; CLUSTERIN; SP-40,40; PROTEIN AB The TRPM-2/clusterin gene and its cognate protein has been characterized in a number of species. Although the functional role, or roles, of the TRPM-2/clusterin protein remains to be firmly established, the gene has been implicated in a variety of physiological processes, including sperm maturation, lipid transport, membrane remodelling and inhibition of the complement cascade. TRPM-2/clusterin is induced de novo during the regression of the prostate and other hormone-dependent tissues after hormone ablation, and is over-expressed in several human neurodegenerative diseases including Alzheimer's disease, epilepsy and retinitis pigmentosa. We describe the genomic structure of the human TRPM-2/clusterin gene which is organized into nine exons, ranging in size from 47 bp (exon I) to 412 bp (exon V), spanning a region of 16580 bp. Comparison with sequences registered in the databases shows that it has extensive similarity to the human protein designated as SP-40,40 or complement-lysis inhibitor (CLI), a protein that appears to block the membrane-attack complex of complement. However, the cDNA sequences reported for SP-40,40 and CLI diverge significantly in the 5' untranslated region of the mRNA (coded for by exon I), raising the possibility that the TRPM-2/clusterin gene is present in the human genome as a small multi-gene family or that there are several alternate exon I sequences in the TRPM-2 gene. Southern analysis and fluorescent in situ hybridization suggest that the clusterin gene is a single-copy gene, and that, if alternative exon I sequences are present in the genome, they Lie outside of the lambda 2 clones that have been characterized. Analysis of the promoter region of the human TRPM-2/clusterin gene shows many similarities to the rat TRPM-2/clusterin promoter including a putative control region containing several potential regulatory elements that may regulate the complex tissue-specific control C1 UNIV OTTAWA,DEPT BIOCHEM,OTTAWA,ON,CANADA. NEI,RETINAL CELL & MOLEC BIOL LAB,BETHESDA,MD 20892. NR 46 TC 116 Z9 121 U1 1 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 MAY 1 PY 1994 VL 221 IS 3 BP 917 EP 925 DI 10.1111/j.1432-1033.1994.tb18807.x PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NK281 UT WOS:A1994NK28100004 PM 8181474 ER PT J AU JUST, I WOLLENBERG, P MOSS, J AKTORIES, K AF JUST, I WOLLENBERG, P MOSS, J AKTORIES, K TI CYSTEINE-SPECIFIC ADP-RIBOSYLATION OF ACTIN SO EUROPEAN JOURNAL OF BIOCHEMISTRY LA English DT Article ID PERFRINGENS IOTA TOXIN; BOTULINUM C2 TOXIN; GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE; CLOSTRIDIUM-SPIROFORME; CHROMAFFIN CELLS; SKELETAL-MUSCLE; BINARY TOXIN; RIBOSYLTRANSFERASE; INHIBITION; FILAMENTS AB Incubation of lysate from human polymorphonucleated neutrophils and human platelets with [P-32]NAD resulted in the labeling of a 42-kDa protein. Phosphodiesterase (Crotalus durissus) released 5'-AMP from the radiolabeled protein. The 42-kDa protein was identified as actin by binding to DNAse-I, two-dimensional gel electrophoresis and partial proteolysis. The rate of ADP-ribosylation was greater with [P-32]ADP-ribose than with [P-32]NAD, indicating a non-enzymic modification. ADP-ribose also modified actin in the actin-DNAse-I complex, but denatured actin was not modified by ADP-ribose. Only cytoplasmic beta/gamma-actin isoforms were non-enzymically ADP-ribosylated but not muscle alpha-actin. The acceptor amino acid was identified as a cysteine residue whereas the bacterial ADP-ribosyltransferase C. perfingens iota toxin catalyzes incorporation of ADP-ribose to Arg177 of actin. Alkylation of cysteine residues of actin with N-ethylmaleimide prevented subsequent non-enzymic ADP-ribosylation but not the toxin catalyzed modification. Non-enzymically ADP-ribosylated actin was further modified by C. pefingens iota toxin. The F-actin stabilizing mycotoxin phalloidin blocked the non-enzymic ADP-ribosylation and, conversely, ADP-ribosylation inhibited the phalloidin-induced polymerization of ADP-ribosylated actin. The data indicate that cytoplasmic actin is non-enzymically ADP-ribosylated by ADP-ribose at a cysteine residue to inhibit actin polymerization. C1 NHLBI, CELLULAR METAB LAB, BETHESDA, MD 20892 USA. RP UNIV SAARLAND, INST PHARMAKOL & TOXIKOL, D-66421 HOMBURG, GERMANY. NR 55 TC 34 Z9 34 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0014-2956 J9 EUR J BIOCHEM JI Eur. J. Biochem. PD MAY 1 PY 1994 VL 221 IS 3 BP 1047 EP 1054 DI 10.1111/j.1432-1033.1994.tb18823.x PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NK281 UT WOS:A1994NK28100020 PM 8181461 ER PT J AU WAUBEN, MHM KOZHICH, A JOOSTEN, I SCHLIEF, A BOOG, CJP VANEDEN, W AF WAUBEN, MHM KOZHICH, A JOOSTEN, I SCHLIEF, A BOOG, CJP VANEDEN, W TI INHIBITION OF ENTIRE MYELIN BASIC PROTEIN-INDUCED EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS IN LEWIS RATS BY MAJOR HISTOCOMPATIBILITY COMPLEX CLASS II-BINDING COMPETITOR PEPTIDES SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; COMPETITOR PEPTIDE; MAJOR HISTOCOMPATIBILITY COMPLEX CLASS II ID T-CELL ACTIVATION; ANTIGEN PRESENTATION; DETERMINANTS; INVIVO; IA; LINES; EAE; RECOGNITION; SELECTION; RECEPTORS AB Previous studies have shown that major histocompatibility complex (MHC) blockade by competitor peptides with high MHC class IT binding affinity can prevent peptide-induced experimental autoimmune encephalomyelitis (EAE). However, none of these studies addressed the question whether this approach could also be used to prevent EAE induced with a multivalent antigen. In this report we show the effect of competitor peptides co-immunized during EAE induction with entire guinea pig myelin basic protein (MBP) in Lewis rats. As MHC class II binding competitor peptides we used one nonimmunogenic disease-nonrelated peptide, and two immunogenic peptides, one EAE-related and one non-EAE-related. The respective efficacy of these three competitor peptides to inhibit MBP-induced proliferation of an encephalitogenic T cell line in vitro correlated with their respective MHC binding affinity. Co-immunization of the competitor peptides during disease induction with entire MBP resulted in a competitor concentration-dependent inhibition of clinical signs of EAE. These results demonstrate that, although polyclonal T cell responses to MBP were not completely inhibited, co-administration of immunogenic or nonimmunogenic either EAE-related or non-EAE-related MHC class II binding competitor peptides can inhibit the development of EAE induced with entire MBP. C1 NEI,IMMUNOL LAB,BETHESDA,MD 20892. RP WAUBEN, MHM (reprint author), UNIV UTRECHT,FAC VET MED,INST INFECT DIS & IMMUNOL,POB 80165,3508 TD UTRECHT,NETHERLANDS. RI Joosten, Irma/D-2374-2010; Joosten, Irma/N-4418-2013 OI Joosten, Irma/0000-0003-2950-4977 NR 38 TC 7 Z9 7 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 MAY PY 1994 VL 24 IS 5 BP 1053 EP 1060 DI 10.1002/eji.1830240507 PG 8 WC Immunology SC Immunology GA NL649 UT WOS:A1994NL64900006 PM 7514128 ER PT J AU HORGAN, KJ TANAKA, Y LUCE, GEG VANSEVENTER, GA NUTMAN, TB SHAW, S AF HORGAN, KJ TANAKA, Y LUCE, GEG VANSEVENTER, GA NUTMAN, TB SHAW, S TI CD45RB EXPRESSION DEFINES 2 INTERCONVERTIBLE SUBSETS OF HUMAN CD4(+) T-CELLS WITH MEMORY FUNCTION SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Note DE CD45; MEMORY CELLS ID LEUKOCYTE COMMON ANTIGEN; LYMPHOCYTES-T; IFN-GAMMA; CD4+; MURINE; CLONES; ISOFORMS; INVIVO; NAIVE AB Reciprocal expression of CD45RA and CD45RO in human CD4(+) T cells defines populations understood to be naive cells (CD45RA(+)CD45RO(-)) and memory cells (CD45RA(-)CD45RO(+)). We investigate two subsets of CD45RA(-)CD45RO(+) CD4(+) human T cells which differ by fourfold in their expression of the CD45RB isoform; one is CD45RB(bright) and the other is CD45RB(intermediate). In contrast, CD45RA(+) naive cells are all CD45RB(bright). Both subsets of CD45RA(-) cells proliferate in response to recall antigens so we designate them MEM 1 (CD45RO(+)RB(bright)) and MEM 2 (CD45RO(+)RB(intermediate)). CD45RA and CD45RB expression are regulated independently during bt vitro activation of naive cells. When MEM 1 cells are activated they tend to down-regulate CD45RB expression, whereas activated MEM 2 cells tend to up-regulate CD45RB expression. Thus, in contrast to the stability of the CD45RA(-)CD45RO(+) phenotype, the MEM 1 and MEM 2 phenotypes are labile and may interconvert. MEM 1 and MEM 2 cells produced comparable amounts of interleukin(IL)-2, IL-4, and IL-5 though MEM 1 cells produced slightly more interferon(IFN)-gamma (mean 1.7-fold more). MEM 1 cells consistently proliferated more (mean 2.3-fold more) than MEM 2 cells early during in vitro activation. Thus, differential expression of CD45RB within CD45RA(-) cells defines two subsets that have similar properties except for somewhast greater IFN-gamma production and proliferative responses by MEM 1 cells. Variability in CD45RB expression may represent a mechanism for fine-tuning the responsiveness of memory cells in vivo. C1 NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892. NIAID,PARASIT DIS LAB,BETHESDA,MD 20892. NR 20 TC 27 Z9 27 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 MAY PY 1994 VL 24 IS 5 BP 1240 EP 1243 DI 10.1002/eji.1830240536 PG 4 WC Immunology SC Immunology GA NL649 UT WOS:A1994NL64900035 PM 7910140 ER PT J AU ISAACS, KR JACOBOWITZ, DM AF ISAACS, KR JACOBOWITZ, DM TI MAPPING OF THE COLOCALIZATION OF CALRETININ AND TYROSINE-HYDROXYLASE IN THE RAT SUBSTANTIA-NIGRA AND VENTRAL TEGMENTAL AREA SO EXPERIMENTAL BRAIN RESEARCH LA English DT Article DE FLUORESCENCE IMMUNOHISTOCHEMISTRY; CALCIUM-BINDING PROTEIN; DOPAMINE; NEUROPROTECTION; RAT ID CALCIUM-BINDING PROTEIN; MPTP-INDUCED PARKINSONISM; IMMUNOHISTOCHEMICAL LOCALIZATION; DOPAMINERGIC-NEURONS; BRAIN; CALBINDIN; DISEASE; SYSTEMS; MESENCEPHALON; DESTRUCTION AB The distribution of calretinin (CR), a calcium binding protein, was compared with that of tyrosine hydroxylase (TH), the rate-limiting enzyme in the synthesis of dopamine, throughout the rostrocaudal extent of the rat subsantia nigra (SN) and ventral tegmental area (VTA). After mapping the cells using double-labelling immunofluorescence, it was possible to distinguish three distinct cell types: cells immunoreactive for CR only, cells immunoreactive for TH only, and cells in which the two proteins were colocalized (CR+TH). Colocalized cells in rat brain sections comprised approximately 40-55% of the fluorescent labelled cells in the SN compacta, 30-40% in the VTA, and 55-80% in the SN lateralis. Colocalized cells in the SN reticulata were infrequent except in the more caudal sections where a majority of the TH-immunoreactive cells also contained CR. The percentage of CR cells that contained TH was approximately 80% in the SN compacta and averaged 65% in the VTA. Overall, the percentage of TH-immunoreactive cells which also contained CR was approximately 50% in the SN compacta and 45% in the VTA. These data reveal a significant degree of colocalization of CR in dopamine-producing cells of the SN and VTA and suggest the need for studies concerning the fate of these individual cell types following experimental manipulations. RP ISAACS, KR (reprint author), NIMH,CLIN SCI LAB,BLDG 10,ROOM 3D-48,BETHESDA,MD 20892, USA. NR 40 TC 41 Z9 41 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0014-4819 J9 EXP BRAIN RES JI Exp. Brain Res. PD MAY PY 1994 VL 99 IS 1 BP 34 EP 42 PG 9 WC Neurosciences SC Neurosciences & Neurology GA NP589 UT WOS:A1994NP58900005 PM 7925794 ER PT J AU CARTER, CA DOHERTY, MM RUSNAK, DW NETTESHEIM, P FERRIOLA, PC AF CARTER, CA DOHERTY, MM RUSNAK, DW NETTESHEIM, P FERRIOLA, PC TI ALTERATIONS IN THE LOCALIZATION OF F-ACTIN, FIBRONECTIN, AND THROMBOSPONDIN OCCUR PRIOR TO NEOPLASTIC TRANSFORMATION IN RAT TRACHEAL EPITHELIAL-CELLS SO EXPERIMENTAL CELL RESEARCH LA English DT Article ID HUMAN SQUAMOUS CARCINOMA; MELANOMA-CELLS; FOCAL CONTACTS; ORGANIZATION; ATTACHMENT; EXPRESSION; ADHESION; MICROFILAMENT; PROGRESSION; METASTASIS AB Structural glycoproteins and cytoskeletal proteins play a major role in the regulation of cellular organization and function. Changes in the structure and function of these proteins are involved in the cascade of events which lead to neoplastic transformation. We evaluated RNA levels, protein localization, and organization of selected proteins in an in vitro model system of respiratory carcinogenesis to examine alterations in cell architecture. Localization of fibronectin (Fn), thrombospondin (Tsp), and F-actin was examined in (1) primary rat tracheal epithelial (RTE) cells; (2) spontaneously immortalized nonneoplastic cells (SPOC-1); and (3) neoplastic cells (EGV5T) derived from tumors arising following transplantation of an N-methyl-N-'nitro-N-nitrosoguanidine-transformed RTE cell line into nude mice. Proteins were stained with fluorescein-labeled antibodies or phalloidin compound and analysis was performed with a confocal laser scanning microscope. Primary RTE cells display organized F-actin stress fibers, perinuclear Fn and Tsp, and pericellular Fn in fibrillar arrays. In larger colonies, Tsp occurs between cells and occasionally in fibrillar arrays. SPOC-1 cells, unlike primary RTE cells and neoplastic EGV5T cells, seldom form junctions and exhibit few cell surface extensions. F-actin stress fibers are reduced in these immortalized cells. F-actin in SPOC-1 cells occurs in the perinuclear region, scattered diffusely throughout the cell and in punctate adhesions. Fn and Tsp are localized to the perinuclear region with Fn staining more intensely. EGV5T neoplastic cells also display a dramatic loss of stress fibers and F-actin is concentrated mainly near the cell periphery. Perinuclear staining of Fn and Tsp occurs in some cells within the colony. Levels of Tsp RNA and Fn RNA and protein are significantly reduced in both cell lines compared to primary RTE cells. We conclude that structural protein disruptions are early events in the transformation of these respiratory epithelial cells. (C) 1994 Academic Press, Inc. C1 NIEHS,RES TRIANGLE PK,NC 27709. NR 52 TC 18 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 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD MAY PY 1994 VL 212 IS 1 BP 141 EP 150 DI 10.1006/excr.1994.1128 PG 10 WC Oncology; Cell Biology SC Oncology; Cell Biology GA NL213 UT WOS:A1994NL21300018 PM 8174636 ER PT J AU SHERMAN, S AF SHERMAN, S TI PROCEEDINGS OF A CONFERENCE ON MENOPAUSE - CURRENT KNOWLEDGE AND RECOMMENDATIONS FOR RESEARCH - PREFACE SO EXPERIMENTAL GERONTOLOGY LA English DT Editorial Material RP SHERMAN, S (reprint author), NIA,GERIATR PORGRAM,ENDOCRINE & MUSCULOSKELETAL BRANCH,GATEWAY BLDG,SUITE 3E327,BETHESDA,MD 20816, USA. 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 0531-5565 J9 EXP GERONTOL JI Exp. Gerontol. PD MAY-AUG PY 1994 VL 29 IS 3-4 BP 233 EP 235 DI 10.1016/0531-5565(94)90001-9 PG 3 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA NT200 UT WOS:A1994NT20000001 ER PT J AU BELLINO, FL AF BELLINO, FL TI BIOLOGY OF THE OVARY AND THE NEUROENDOCRINE SYSTEM IN MENOPAUSE - INTRODUCTION SO EXPERIMENTAL GERONTOLOGY LA English DT Editorial Material RP BELLINO, FL (reprint author), NIA,BIOL AGING PROGRAM,GATEWAY BLDG,SUITE 2C231,BETHESDA,MD 20892, USA. 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 0531-5565 J9 EXP GERONTOL JI Exp. Gerontol. PD MAY-AUG PY 1994 VL 29 IS 3-4 BP 253 EP 254 DI 10.1016/0531-5565(94)90004-3 PG 2 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA NT200 UT WOS:A1994NT20000004 ER PT J AU ORY, MG AF ORY, MG TI SOCIOCULTURAL AND BIOBEHAVIORAL PERSPECTIVES IN MENOPAUSAL RESEARCH - INTRODUCTION SO EXPERIMENTAL GERONTOLOGY LA English DT Editorial Material RP ORY, MG (reprint author), NIA,BEHAV & SOCIAL RES PROGRAM,GATEWAY BLDG,SUITE 533,BETHESDA,MD 20892, USA. 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 0531-5565 J9 EXP GERONTOL JI Exp. Gerontol. PD MAY-AUG PY 1994 VL 29 IS 3-4 BP 305 EP 306 DI 10.1016/0531-5565(94)90010-8 PG 2 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA NT200 UT WOS:A1994NT20000010 ER PT J AU WEISS, S AF WEISS, S TI SESSION-IV - MANAGEMENT AND HEALTH-CARE IMPLICATIONS OF MENOPAUSE - INTRODUCTION SO EXPERIMENTAL GERONTOLOGY LA English DT Editorial Material C1 NATL INST NURSING RES,BETHESDA,MD 20892. 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 0531-5565 J9 EXP GERONTOL JI Exp. Gerontol. PD MAY-AUG PY 1994 VL 29 IS 3-4 BP 445 EP 445 DI 10.1016/0531-5565(94)90024-8 PG 1 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA NT200 UT WOS:A1994NT20000024 ER PT J AU MONJAN, AA BELLINO, FL ORY, MG SHERMAN, S WEISS, S AF MONJAN, AA BELLINO, FL ORY, MG SHERMAN, S WEISS, S TI SESSION-VI - RESEARCH DIRECTIONS - RESEARCH RECOMMENDATIONS SO EXPERIMENTAL GERONTOLOGY LA English DT Article; Proceedings Paper CT Conference on Menopause: Current Knowledge and Recommendation for Research CY MAR, 1993 CL BETHESDA, MD SP NIH, NINR, OFF RES WOMENS HLTH, N AMER MENOPAUSE SOC C1 NATL INST NURSING RES,BETHESDA,MD 20892. RP MONJAN, AA (reprint author), NIA,GATEWAY BLDG,7201 WISCONSIN AVE,BETHESDA,MD 20892, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0531-5565 J9 EXP GERONTOL JI Exp. Gerontol. PD MAY-AUG PY 1994 VL 29 IS 3-4 BP 525 EP 528 DI 10.1016/0531-5565(94)90033-7 PG 4 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA NT200 UT WOS:A1994NT20000033 PM 7925770 ER PT J AU TOURAY, MG SEELEY, DC MILLER, LH AF TOURAY, MG SEELEY, DC MILLER, LH TI PLASMODIUM-GALLINACEUM - DIFFERENTIAL LYSIS OF 2 DEVELOPMENTAL STAGES OF MALARIA SPOROZOITES BY THE ALTERNATIVE PATHWAY OF COMPLEMENT SO EXPERIMENTAL PARASITOLOGY LA English DT Article DE PLASMODIUM GALLINACEUM; OOCYST SPOROZOITES; SALIVARY GLAND SPOROZOITES; MOSQUITO VECTOR; AEDES AEGYPTI; ALTERNATIVE PATHWAY OF COMPLEMENT; DEVELOPMENTAL REGULATION; SPOROZOITE LYSIS ID TRYPANOSOMA-CRUZI; AEDES-AEGYPTI; PROMASTIGOTES; BINDING; INFECTIVITY; EVASION; GROWTH; SALIVA; HOST AB During sporogonic development of Plasmodium gallinaceum in the mosquito vector, two developmentally distinct sporozoite stages can be isolated. Sporozoites obtained from oocysts in abdomens of mosquitoes 10 days after an infective blood meal are poorly infectious to the vertebrate host (chicken); days later, sporozoites isolated from mosquito salivary glands are highly infectious. In a first step toward understanding the physiologic basis of this developmentally regulated infectivity to the vertebrate host, we determined the relative resistance of the two sporozoite stages to lysis by the complement system of the vertebrate host. Whereas 86% of oocyst sporozoites were lysed when incubated in fresh chicken serum in vitro, only 24% of salivary gland sporozoites were lysed under identical incubation conditions. Preincubation of oocyst sporozoites in a homogenate of female Aedes aegypti salivary glands did not diminish their susceptibility to lysis by serum, indicating that lysis was mediated by the interaction of serum factors with parasite-specific molecules. The lytic activity of fresh chicken serum was abrogated by incubating for 45 min at 56 degrees C or chelating with EDTA. Fresh chicken serum specifically depleted of Ca2+, by chelating with EGTA in the presence of Mg2+, retained its ability to lyse oocyst sporozoites. The lysis of salivary gland sporozoites mediated by chicken antisporozoite serum is abrogated by EGTA, indicating that the antibody-dependent complement pathway in chicken serum is blocked by EGTA. Because oocyst sporozoite lysis by serum was heat sensitive and Mg2+ dependent, but Ca2+ independent, we conclude that lysis was mediated by the alternative pathway of complement. One factor in the development from noninfectious oocyst sporozoites to infectious salivary gland sporozoites is the ability to resist lysis by the alternative pathway of complement. (C) 1994 Academic Press,Inc. RP TOURAY, MG (reprint author), NIAID,MALARIA RES LAB,BLDG 4,ROOM 126,BETHESDA,MD 20892, USA. NR 19 TC 5 Z9 7 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 0014-4894 J9 EXP PARASITOL JI Exp. Parasitol. PD MAY PY 1994 VL 78 IS 3 BP 294 EP 301 DI 10.1006/expr.1994.1031 PG 8 WC Parasitology SC Parasitology GA NK870 UT WOS:A1994NK87000006 PM 8162961 ER PT J AU FRIED, M GWADZ, RW KASLOW, DC AF FRIED, M GWADZ, RW KASLOW, DC TI IDENTIFICATION OF 2 CYSTEINE-RICH, LIPOPHILIC PROTEINS ON THE SURFACE OF PLASMODIUM-KNOWLESI OOKINETES - PKS20 AND PKS24 SO EXPERIMENTAL PARASITOLOGY LA English DT Note ID TRANSMISSION-BLOCKING IMMUNITY; PHASE-SEPARATION; VIVAX MALARIA; SEXUAL STAGES; TRITON X-114; ANTIGENS; GALLINACEUM; FALCIPARUM; ANTIBODIES; FAMILY RP FRIED, M (reprint author), NIAID,MOLEC VACCINE SECT,MALARIA RES LAB,BETHESDA,MD 20892, USA. NR 26 TC 6 Z9 6 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 0014-4894 J9 EXP PARASITOL JI Exp. Parasitol. PD MAY PY 1994 VL 78 IS 3 BP 326 EP 330 DI 10.1006/expr.1994.1034 PG 5 WC Parasitology SC Parasitology GA NK870 UT WOS:A1994NK87000009 PM 7909295 ER PT J AU PENNYPACKER, KR HONG, JS MCMILLIAN, MK AF PENNYPACKER, KR HONG, JS MCMILLIAN, MK TI PHARMACOLOGICAL REGULATION OF AP-1 TRANSCRIPTION FACTOR DNA-BINDING ACTIVITY SO FASEB JOURNAL LA English DT Article DE FOS-RELATED ANTIGEN; C-JUN; CNS; CAMP RESPONSIVE ELEMENT BINDING PROTEIN; ADRENAL GLAND; DOPAMINE; KAINATE; NICOTINE ID TYROSINE-HYDROXYLASE GENE; C-FOS EXPRESSION; PROTEIN-KINASE-C; RAT STRIATUM; DIFFERENTIAL EXPRESSION; JUN; BRAIN; ACTIVATION; INDUCTION; SEIZURE AB The AP-1 transcription factor family consists of two groups of proteins, fos-related antigens (fra) and jun proteins. These transcription factors are usually expressed at low basal levels but they can be dramatically induced in a variety of cell types by many different stimuli, in which the quantity of AP-1 transcription factor and the DNA binding activity also rise. The quantity and DNA binding activity of transcription factors are not always at low levels. For example, early in brain development a high basal expression of AP-1. DNA binding activity exists. Similarly, adult rat adrenal gland contains high levels of AP-1 DNA binding activity whose regulation appears to be through post-translational modification (i.e., phosphorylation). Thus, AP-1 DNA binding activity is modulated in a developmental and tissue-specific manner. RP PENNYPACKER, KR (reprint author), NIEHS,MOLEC & INTEGRAT NEUROSCI LAB,RES TRIANGLE PK,NC 27709, USA. RI Pennypacker, Keith/I-5092-2012 NR 43 TC 65 Z9 67 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAY PY 1994 VL 8 IS 8 BP 475 EP 478 PG 4 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA NM364 UT WOS:A1994NM36400003 PM 8181665 ER PT J AU HANEY, AF NEWBOLD, RR DOTY, E AF HANEY, AF NEWBOLD, RR DOTY, E TI AN ELICITED INTRAPERITONEAL INFLAMMATORY RESPONSE HAS NO EFFECT ON THE ESTABLISHMENT OF PREGNANCY IN THE MOUSE SO FERTILITY AND STERILITY LA English DT Article DE INTRAPERITONEAL INFLAMMATION; REPRODUCTION; ACTIVATED LEUKOCYTES; MICE ID ENDOMETRIOSIS-ASSOCIATED SUBFERTILITY; TUMOR-NECROSIS-FACTOR; SPERM MOTILITY INVITRO; PERITONEAL-FLUID; ACTIVATED LYMPHOCYTES; INVIVO MODEL; FACTOR-ALPHA; MACROPHAGES; INFERTILITY; IMMUNOMODULATION AB Objective: To determine the impact of intraperitoneal inflammation on reproduction in the mouse. Design: The effect of an elicited sterile intraperitoneal inflammatory exudate and the passive intraperitoneal transfer of activated syngeneic leukocytes on mating efficiency and uterine implantations was evaluated in mice. Setting: Research laboratory. Interventions: Intraperitoneal injection of thioglycolate was used to elicit large numbers of activated peritoneal macrophages (mean 24.4 X 10(6) leukocytes/animal) in female CD-1 mice. The impact of this intraperitoneal exudate on mating efficiency and number of uterine horn implantations after gonadotropin-stimulated ovulation was determined. In separate experiments, the ovarian bursa present in this species was opened surgically to provide direct access of peritoneal constituents to the genital tract and the experiments repeated. Identical endpoints were evaluated in a third group of experiments using C3H/HEN syngeneic mice after passive transfer of 2, 5, and 10 X 10(6) similarly activated syngeneic peritoneal leukocytes. Results: Neither the elicitation of a peritoneal inflammatory exudate nor the passive transfer of up to 10 X 10(6) activated syngeneic peritoneal macrophages reduced the mating efficiency or the number of uterine implantations. Furthermore, surgically opening the ovarian bursa did not alter these results, although it was associated with anatomic distortion and lowered the number of implantations in all groups. Conclusions: We could not confirm the previously published reports suggesting a profound adverse impact of intraperitoneal inflammation on reproduction in mice, even when providing direct continuity between the peritoneal cavity and the genital tract. Consequently, the usefulness of this model needs to be re-evaluated before considering it an adequate paradigm for evaluating potential mechanisms of infertility in women. C1 NIEHS,RES TRIANGLE PK,NC 27709. RP HANEY, AF (reprint author), DUKE UNIV,MED CTR,BOX 2971,DURHAM,NC 27710, USA. NR 25 TC 7 Z9 7 U1 0 U2 0 PU AMER SOC REPRODUCTIVE MEDICINE PI BIRMINGHAM PA 1209 MONTGOMERY HIGHWAY, BIRMINGHAM, AL 35216-2809 SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD MAY PY 1994 VL 61 IS 5 BP 956 EP 962 PG 7 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA NJ202 UT WOS:A1994NJ20200026 PM 8174736 ER PT J AU ALEXANDER, D AF ALEXANDER, D TI ITS TIME TO GET ON WITH IT SO FETAL DIAGNOSIS AND THERAPY LA English DT Editorial Material RP ALEXANDER, D (reprint author), NICHHD,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-3837 J9 FETAL DIAGN THER JI Fetal Diagn. Ther. PD MAY-JUN PY 1994 VL 9 IS 3 BP 139 EP 141 PG 3 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA NQ665 UT WOS:A1994NQ66500001 PM 8060507 ER PT J AU CARMASSI, F DENEGRI, F MORALE, M PUCCETTI, R SONG, KY CHUNG, SI AF CARMASSI, F DENEGRI, F MORALE, M PUCCETTI, R SONG, KY CHUNG, SI TI ASSESSMENT OF COAGULATION AND FIBRINOLYSIS IN SYNOVIAL-FLUID OF RHEUMATOID-ARTHRITIS PATIENTS SO FIBRINOLYSIS LA English DT Article ID PLASMINOGEN-ACTIVATOR; LEUKOCYTE ELASTASE; ALPHA-2-PLASMIN INHIBITOR; LATENT COLLAGENASE; BLOOD-COAGULATION; ENDOTHELIAL-CELLS; FIBRINOGEN; PROTEASES; THROMBIN; TISSUE AB In order to understand the mechanism of fibrin deposition in the synovia during the progression of rheumatoid arthritis (RA), activities of coagulation factors, fibrinolytic enzymes, and corresponding inhibitors were measured in synovial fluid of 12 RA patients. Almost all of the synovial fluid (SF) fibrinogen molecules were found to be fragmented and some portions of the molecule that were slightly affected were found to be in a complex with albumin molecules. Immunohistochemical analysis showed deposits of insoluble fibrin in synovial membranes and pannus, in levels related to the progression of disease. Coagulation factor VII, VIII, X, XII, and XIII activities in SF were found to be 30 to 50% of plasma levels but factors II and V activities were less than 25% of plasma levels. Protein C and antithrombin III activities in SF were 30% of plasma levels. However, the two orders of magnitude, higher level of thrombin-antithrombin HI (TAT) complex in SF than in plasma, suggests a steady activation of coagulation cascade in synovia. The observed increased levels of fibrinogen, TAT complexes, B beta 15-42 peptide and plasminogen activator inhibitor-1 (PAI-1) in plasma are consistent with the systemic inflammatory state of RA patients. Although a 30% decrease in plasma levels of alpha(2)-plasmin inhibitor activity, acid a 2-fold higher level of PAI-1 activity in SF were found, the presence of D-dimer and B beta 15-92 peptide in SF suggests an active participation of plasmin in the fibrino(geno)lysis. In addition, elevated levels of elastase-alpha(1)-proteinase inhibitor complexes and of thrombin-increasable fibrinopeptide A in SF suggest the participation of leukocyte elastase in fibrin(ogen)olysis as well. C1 CHOONG AHUNG UNIV,DEPT PATHOL,SEOUL,SOUTH KOREA. NIDR,CELLULAR DEV & ONCOL LAB,BETHESDA,MD 20892. RP CARMASSI, F (reprint author), UNIV PISA,MED CLIN 2,VIA ROMA 67,I-56126 PISA,ITALY. OI Carmassi, Franco/0000-0003-2244-4430 NR 68 TC 5 Z9 5 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH, MIDLOTHIAN, SCOTLAND EH1 3AF SN 0268-9499 J9 FIBRINOLYSIS JI Fibrinolysis PD MAY PY 1994 VL 8 IS 3 BP 162 EP 171 DI 10.1016/S0268-9499(05)80014-1 PG 10 WC Hematology SC Hematology GA NM551 UT WOS:A1994NM55100004 ER PT J AU HEINDEL, JJ CHAPIN, RE GULATI, DK GEORGE, JD PRICE, CJ MARR, MC MYERS, CB BARNES, LH FAIL, PA GRIZZLE, TB SCHWETZ, BA YANG, RSH AF HEINDEL, JJ CHAPIN, RE GULATI, DK GEORGE, JD PRICE, CJ MARR, MC MYERS, CB BARNES, LH FAIL, PA GRIZZLE, TB SCHWETZ, BA YANG, RSH TI ASSESSMENT OF THE REPRODUCTIVE AND DEVELOPMENTAL TOXICITY OF PESTICIDE/FERTILIZER MIXTURES BASED ON CONFIRMED PESTICIDE CONTAMINATION IN CALIFORNIA AND IOWA GROUNDWATER SO FUNDAMENTAL AND APPLIED TOXICOLOGY LA English DT Article ID ZERO DOSE CONTROL; CHEMICAL-MIXTURE; ETHYLENE DIBROMIDE; B6C3F1 MICE; TOXICOLOGY; WORKERS; ALDICARB; AREAS AB Pesticides and fertilizers, as used in modern agriculture, contribute to the overall low-level contamination of groundwater sources. In order to determine the potential of pesticide and fertilizer mixtures to produce reproductive or developmental toxicity at concentrations up to 100X the median level found in groundwater, we prepared and studied two mixtures of pesticides and a fertilizer (ammonium nitrate). One mixture containing aldicarb, atrazine, dibromochloropropane, 1,2-dichloropropane, ethylene dibromide, and simazine plus ammonium nitrate was considered to be a representative of groundwater contamination in California (CAL). The other, containing alachlor, atrazine, cyanazine, metolachlor, metribuzin, and ammonium nitrate, simulated groundwater contamination in Iowa (IOWA). Each mixture was administered in the drinking water of either Swiss CD-I mice during a Reproductive Assessment by Continuous Breeding study or pregnant Sprague-Dawley rats (gd 6-20) at three dose levels (1X, 10X, and 100X) where Ix was the median concentration of each pesticide component as determined in the groundwater surveys in California or Iowa. Unlike conventional toxicology studies, the purpose of this study was to evaluate the health effects of realistic human concentrations. Thus, the testing concentrations are probably well below the maximally tolerated dose. Propylene glycol was used as the solubilizer for the pesticides in drinking water formulations in both studies. In the reproductive study, neither mixture caused any clinical signs of toxicity, changes in food or water consumption, or body weight in either F, or F, mice at doses up to 100X the median groundwater concentrations. There were no treatment-related effects on fertility or any measures of reproductive performance of either the F, or the F, generation mice exposed to either CAL or IOWA at up to 100X. Similarly, measures of spermatogenesis, epididymal sperm concentration, percentage motile sperm, percentage abnormal sperm, and testicular and epididymal histology were normal. In the developmental study, CAL- or IOWA-exposed females did not exhibit any significant treatment-related clinical signs of toxicity. No adverse effects of CAL or IOWA were observed for measures of embryo/fetal toxicity, including resorptions per litter, live litter size, or fetal body weight. CAL or IOWA did not cause an increased incidence of fetal malformations or variations. In summary, administration of these pesticide/fertilizer mixtures at levels up to 100-fold greater than the median concentrations in groundwater supplies in California or Iowa did not cause any detectable reproductive (mice), general, or developmental toxicity (rats). (C) 1994 Society of Toxicology. C1 ENVIRONM HLTH RES & TESTING INC, LEXINGTON, KY 40503 USA. RES TRIANGLE INST, RES TRIANGLE PK, NC 27709 USA. RP HEINDEL, JJ (reprint author), NIEHS, NATL TOXICOL PROGRAM, POB 12233, MD E1-02, RES TRIANGLE PK, NC 27709 USA. OI Chapin, Robert/0000-0002-5997-1261 FU NIEHS NIH HHS [N01-ES 65141, N01-ES-65142, NTP/NIEHS N01-ES-95255] NR 77 TC 28 Z9 29 U1 1 U2 19 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0272-0590 J9 FUND APPL TOXICOL JI Fundam. Appl. Toxicol. PD MAY PY 1994 VL 22 IS 4 BP 605 EP 621 DI 10.1006/faat.1994.1067 PG 17 WC Toxicology SC Toxicology GA NL761 UT WOS:A1994NL76100013 PM 8056207 ER PT J AU CHANG, HK GENDELMAN, R LISZIEWICZ, J GALLO, RC ENSOLI, B AF CHANG, HK GENDELMAN, R LISZIEWICZ, J GALLO, RC ENSOLI, B TI BLOCK OF HIV-1 INFECTION BY A COMBINATION OF ANTISENSE TAT RNA AND TAR DECOYS - A STRATEGY FOR CONTROL OF HIV-1 SO GENE THERAPY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; TRANS-ACTIVATOR GENE; LONG TERMINAL REPEAT; TRANSFORMING GROWTH FACTOR-BETA-1; RETROVIRUSES HTLV-III; TUMOR NECROSIS FACTOR; HUMAN T-CELLS; KAPOSIS-SARCOMA; TYPE-1 REPLICATION; AIDS THERAPY AB The tat gene product (Tat) of HIV-1 is an early regulatory protein necessary for viral gene expression and replication. Tat may also play a role as an extracellular protein in both HIV-1 replication and AIDS-associated disorders such as Kaposi's sarcoma. Thus, Tat represents a good target for a gene therapy against AIDS. Here we show that when vectors expressing antisense tat RNA are transiently transfected into CD4(+) cells, they block about 70% of HIV-1 replication and inhibit the rescue of Tat-defective HIV-1 proviruses by inhibition of Tat protein expression and consequent lack of transcriptional activation of the HIV-promoter, However, antisense tal vectors cannot block the activity of extracellular Tat protein. Another tat inhibitory construct (poly-Tat-activation response; TAR) previously suggested to inhibit HIV-1 transactivation by sequestering the Tat protein, inhibited the activity of extracellular Tat, but like antisense tat RNA did not completely block Viral gene expression and replication. These results suggested that one mode of inhibition is not sufficient to block Tat function. However, when the antisense tat and the poly-TAR constructs were combined HIV-1 gene expression was completely blocked (94-98%), suggesting that a combination of inhibitory genes blocking Tat by sequential steps may be a better approach for AIDS gene therapy. C1 NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. NR 78 TC 37 Z9 38 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0969-7128 J9 GENE THER JI Gene Ther. PD MAY PY 1994 VL 1 IS 3 BP 208 EP 216 PG 9 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA PT947 UT WOS:A1994PT94700009 PM 7584083 ER PT J AU SMITH, SA DICIOCCIO, RA STRUEWING, JP EASTON, DF GALLION, HH ALBERTSEN, H MAZOYER, S JOHANSSON, B STEICHENGERSDORF, E STRATTON, M FORD, D MARSHALL, G WHITE, RL PIVER, MS PONDER, BAJ AF SMITH, SA DICIOCCIO, RA STRUEWING, JP EASTON, DF GALLION, HH ALBERTSEN, H MAZOYER, S JOHANSSON, B STEICHENGERSDORF, E STRATTON, M FORD, D MARSHALL, G WHITE, RL PIVER, MS PONDER, BAJ TI LOCALIZATION OF THE BREAST-OVARIAN CANCER SUSCEPTIBILITY GENE (BRCAI) ON 17Q12-21 TO AN INTERVAL OF LESS-THAN-OR-EQUAL-TO-ICM SO GENES CHROMOSOMES & CANCER LA English DT Note ID FAMILIAL BREAST; LINKAGE AB A breast-ovarian cancer susceptibility gene, BRCA1, which is responsible for disease in approximately 45% of breast cancer families and most families that contain breast and ovarian cancer, has been assigned by genetic linkage to 17q12-21. Here, we report the analysis of three marker-disease recombinants in families that contain breast and ovarian cancer, two of which strongly suggest a location for BRCA1 telomeric to D17S702, a microsatellite polymorphism, and a third which suggests a location centromeric to EDH17B, the gene encoding estradiol-17B dehydrogenase. If the interpretation of these recombinants is correct, the results localise BRCA1 to an interval of less than or equal to 1cM. (C) 1994 Wiley-Liss, Inc. C1 ROSWELL PK CANC INST,DEPT GYNECOL ONCOL,BUFFALO,NY 14263. NIH,GENET EPIDEMIOL BRANCH,BETHESDA,MD 20892. INST CANC RES,EPIDEMIOL SECT,SUTTON SM2 5NG,SURREY,ENGLAND. INST CANC RES,MOLEC CARCINOGENESIS SECT,SUTTON SM2 5NG,SURREY,ENGLAND. UNIV UTAH,SALT LAKE CITY,UT 84112. HOWARD HUGHES MED INST,ECCLES INST HUMAN GENET,SALT LAKE CITY,UT 84112. RP SMITH, SA (reprint author), UNIV CAMBRIDGE,DEPT PATHOL,CRC,HUMAN CANC GENET RES GRP,TENNIS COURT RD,CAMBRIDGE CB2 1QP,ENGLAND. RI Struewing, Jeffery/C-3221-2008; Struewing, Jeffery/I-7502-2013 OI Struewing, Jeffery/0000-0002-4848-3334 NR 16 TC 18 Z9 18 U1 0 U2 5 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD MAY PY 1994 VL 10 IS 1 BP 71 EP 76 DI 10.1002/gcc.2870100112 PG 6 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA NH438 UT WOS:A1994NH43800011 PM 7519878 ER PT J AU BRANNAN, CI PERKINS, AS VOGEL, KS RATNER, N NORDLUND, ML REID, SW BUCHBERG, AM JENKINS, NA PARADA, LF COPELAND, NG AF BRANNAN, CI PERKINS, AS VOGEL, KS RATNER, N NORDLUND, ML REID, SW BUCHBERG, AM JENKINS, NA PARADA, LF COPELAND, NG TI TARGETED DISRUPTION OF THE NEUROFIBROMATOSIS TYPE-1 GENE LEADS TO DEVELOPMENTAL ABNORMALITIES IN HEART AND VARIOUS NEURAL CREST-DERIVED TISSUES SO GENES & DEVELOPMENT LA English DT Article DE NEUROFIBROMATOSIS; NF1; RAS; ES CELLS; TRANSGENIC MICE ID CELLS; RAS; PROTEIN; DIFFERENTIATION; PRODUCT; LOCUS; GAP; SEQUENCES; ENCODES; EMBRYO AB The neurofibromatosis (NF1) gene shows significant homology to mammalian GAP and is an important regulator of the ras signal transduction pathway. To study the function of NF1 in normal development and to try and develop a mouse model of NF1 disease, we have used gene targeting in ES cells to generate mice carrying a null mutation at the mouse Nf1 locus. Although heterozygous mutant mice, aged up to 10 months, have not exhibited any obvious abnormalities, homozygous mutant embryos die in utero. Embryonic death is likely attributable to a severe malformation of the heart. Interestingly, mutant embryos also display hyperplasia of neural crest-derived sympathetic ganglia. These results identify new roles for NF1 in development and indicate that some of the abnormal growth phenomena observed in NE1 patients can be recapitulated in neurofibromin-deficient mice. C1 YALE UNIV,SCH MED,DEPT PATHOL,NEW HAVEN,CT 06437. UNIV CINCINNATI,COLL MED,DEPT ANAT & CELL BIOL,CINCINNATI,OH 45267. RP BRANNAN, CI (reprint author), NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702, USA. RI Parada, luis/B-9400-2014; OI Buchberg, Arthur/0000-0002-0543-5631 FU NCI NIH HHS [N01-CO-74101]; NINDS NIH HHS [NS28840] NR 44 TC 419 Z9 425 U1 0 U2 1 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 0890-9369 J9 GENE DEV JI Genes Dev. PD MAY 1 PY 1994 VL 8 IS 9 BP 1019 EP 1029 DI 10.1101/gad.8.9.1019 PG 11 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA NJ947 UT WOS:A1994NJ94700003 PM 7926784 ER PT J AU LINCOLN, AJ WILLIAMS, SC JOHNSON, PF AF LINCOLN, AJ WILLIAMS, SC JOHNSON, PF TI A REVISED SEQUENCE OF THE RAT C/EBP GENE SO GENES & DEVELOPMENT LA English DT Note ID TRANSCRIPTION FACTOR; EXPRESSION; FAMILY C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. RI Johnson, Peter/A-1940-2012 OI Johnson, Peter/0000-0002-4145-4725 FU NCI NIH HHS [N01-CO-74101] NR 7 TC 13 Z9 14 U1 0 U2 0 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 0890-9369 J9 GENE DEV JI Genes Dev. PD MAY 1 PY 1994 VL 8 IS 9 BP 1131 EP 1132 DI 10.1101/gad.8.9.1131 PG 2 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA NJ947 UT WOS:A1994NJ94700011 PM 7926792 ER PT J AU KOUPRINA, N ELDAROV, M MOYZIS, R RESNICK, M LARIONOV, V AF KOUPRINA, N ELDAROV, M MOYZIS, R RESNICK, M LARIONOV, V TI A MODEL SYSTEM TO ASSESS THE INTEGRITY OF MAMMALIAN YACS DURING TRANSFORMATION AND PROPAGATION IN YEAST SO GENOMICS LA English DT Article ID ARTIFICIAL CHROMOSOME LIBRARY; SEQUENCE-TAGGED SITES; CARRYING HUMAN DNA; SACCHAROMYCES-CEREVISIAE; HUMAN GENOME; MITOTIC RECOMBINATION; GENETIC-CONTROL; X-CHROMOSOME; CONSTRUCTION; CLONES AB Yeast artificial chromosomes (YACs) containing mammalian DNA potentially can undergo deletions during transformation and propagation, possibly due to interactions between repeat DNAs. To study factors involved in such rearrangements, we developed a genetic system that can signal physical changes. An Alu-HIS3-Alu cassette has been targeted to a mitotically stable YAC containing a 360-kb DNA insert of human chromosome 2. Five YACs with the cassette integrated at different positions were examined for loss of the internal HIS3 marker during transformation into yeast and subsequent growth. The average frequency of the internal marker loss in mitotically growing cells was approximately 1.0 x 10(-4). Physical analysis of His(-) YACs retaining both telomeric markers demonstrated that loss of the marker was due to deletions (20-90 kb). These results contrast with those obtained with YACs following transformation. Nearly 33% of the retransformed YACs lacked the internal HIS3 marker. The transformation-associated loss was also due to deletions varying from 80 to 260 kb. Similar results were obtained following retransformation with the parent human YAC and another mitotically stable YAC containing a 390-kb insert of mouse DNA The high level of transformation-associated deletions in the human YACs was reduced over 10-fold when the host was a recombination-deficient strain deleted for the RAD52 gene. The level of internal human YAC instability during mitotic growth was also significantly decreased in the rad52 mutant strain compared to that in the isogenic Rad(+) strain. However, retransformation of the rad52 mutant with a YAC-containing mouse DNA yielded comparable levels of alterations to those observed for the wildtype strain. Thus, there must be additional genetic factors involved in transformation-associated deletions in YACs. We propose that these YACs and strains can be useful tools for investigating YAC integrity. During the course of these studies a unique category of deletions was identified in mitotically propagated YACs that result from recombination between identical sequences in the telomeric region and the HIS3 cassette. In addition to the known YAC ''fragmentation'' method, this may provide a means for generating internal deletions as well as an alternative method for mapping. (C) 1994 Academic Press, Inc. C1 NIEHS,MOLEC GENET LAB,RES TRIANGLE PK,NC 27709. RUSSIAN ACAD SCI,INST CYTOL,ST PETERSBURG 194064,RUSSIA. CTR BIOENGN,MOSCOW 117984,RUSSIA. LOS ALAMOS NATL LAB,CTR HUMAN GENOME STUDIES,LOS ALAMOS,NM 87545. FU NHGRI NIH HHS [1-YO2-HG-60021-01] NR 68 TC 42 Z9 43 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD MAY 1 PY 1994 VL 21 IS 1 BP 7 EP 17 DI 10.1006/geno.1994.1218 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA NL712 UT WOS:A1994NL71200002 PM 8088818 ER PT J AU MALLO, M STEINGRIMSSON, E COPELAND, NG JENKINS, NA GRIDLEY, T AF MALLO, M STEINGRIMSSON, E COPELAND, NG JENKINS, NA GRIDLEY, T TI GENOMIC ORGANIZATION, ALTERNATIVE POLYADENYLATION, AND CHROMOSOMAL LOCALIZATION OF GRG, A MOUSE GENE-RELATED TO THE GROUCHO TRANSCRIPT OF THE DROSOPHILA ENHANCER OF SPLIT COMPLEX SO GENOMICS LA English DT Article ID 3' UNTRANSLATED REGION; LOOP-HELIX PROTEINS; MESSENGER-RNA; SHOWS HOMOLOGY; BETA-SUBUNIT; LINKAGE MAP; DNA-BINDING; LOCUS; NEUROGENESIS; MELANOGASTER AB The Grg gene encodes a 197-amino-acid protein homologous to the amino-terminal domain of the product of the groucho gene of the Drosophila Enhancer of split complex. We describe here the genomic organization of the mouse Grg gene. It spans approximately 7 kb on chromosome 10 and consists of seven exons. The 3' region of the Grg gene contains two functional polyadenylation sites that give rise to two transcripts that are differentially expressed among adult mouse tissues. The promoter region is very GC rich and lacks TATA box and ''initiator'' sequences. Primer extension analysis and ribonuclease protection assays show that Grg has a major transcription start site situated downstream of putative binding moths for the transcription factors Sp1, E2A, and PuF. (C) 1994 Academic Press, Inc. C1 ROCHE INST MOLEC BIOL,ROCHE RES CTR,NUTLEY,NJ 07110. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. RI Mallo, Moises/D-5907-2016 OI Mallo, Moises/0000-0002-9744-0912 FU NCI NIH HHS [N01-CO-74101] NR 50 TC 16 Z9 16 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD MAY 1 PY 1994 VL 21 IS 1 BP 194 EP 201 DI 10.1006/geno.1994.1242 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA NL712 UT WOS:A1994NL71200026 PM 7916324 ER PT J AU HESS, EJ COLLINS, KA COPELAND, NG JENKINS, NA WILSON, MC AF HESS, EJ COLLINS, KA COPELAND, NG JENKINS, NA WILSON, MC TI DELETION MAP OF THE COLOBOMA (CM) LOCUS ON MOUSE CHROMOSOME-2 SO GENOMICS LA English DT Note ID INSITU HYBRIDIZATION; GENE; SNAP-25; PROTEIN; LOCALIZATION; SEQUENCE; LINKAGE; MUTANT AB The extent of the semidominant coloboma (Cm) mutation on mouse Chromosome 2 was determined by deletion mapping using interspecific hybrid mice. The Cm deletion mutation results in ophthalmic dysmorphology and behavioral deficits, including profound hyperactivity, and has been shown to encompass the gene Snap. In addition to Snap, the gene encoding phospholipase C beta-1 (Plcb-1), which maps 0.60 +/- 0.60 cM proximal to Snap, and simple sequence repeat (SSR) loci D2Mit19, D2Mit46, D2Mit28, and D2Mit136 were shown to be deleted at the Cm locus. In contrast, analysis of other closely linked SSRs and genes either proximal (Bmp-2a) or distal (Nec-1) to Snap, as well as a complementation test with the closely linked mutation lethal milk (lm), indicates that these gene sequences are unaffected by the Cm mutation. These data demonstrate that the Cm deletion represents a contiguous gene defect encompassing 1.1 to 2.2 cM that may be probed for genes, both in the mouse and in the syntenic region of human Chr 20, that independently affect elements of neurological behavior and eye development. (C) 1994 Academic Press, Inc. C1 Scripps Res Inst, DEPT NEUROPHARMACOL, LA JOLLA, CA 92037 USA. NCI, FREDERICK CANC RES FACIL,MAMMALIAN GENET LAB,BRI, BASIC RES PROGRAM, FREDERICK, MD 21701 USA. FU NIMH NIH HHS [MH48989]; PHS HHS [N10-C0-74101] NR 25 TC 50 Z9 50 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD MAY 1 PY 1994 VL 21 IS 1 BP 257 EP 261 DI 10.1006/geno.1994.1254 PG 5 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA NL712 UT WOS:A1994NL71200038 PM 7916325 ER PT J AU FIEBER, LA SCHMALE, MC AF FIEBER, LA SCHMALE, MC TI DIFFERENCES IN A K-CURRENT IN SCHWANN-CELLS FROM NORMAL AND NEUROFIBROMATOSIS-INFECTED DAMSELFISH SO GLIA LA English DT Article DE TUMOR; PATCH CLAMP; DENERVATION ID VOLTAGE-DEPENDENT CALCIUM; RABBIT SCIATIC-NERVES; POTASSIUM CHANNELS; BICOLOR DAMSELFISH; POMACENTRUS-PARTITUS; VONRECKLINGHAUSEN NEUROFIBROMATOSIS; SODIUM CURRENTS; ADULT-RABBITS; ION CHANNELS; TYPE-1 AB Patch clamp techniques were used to study whole cell ionic currents in Schwann cells (SC) from a tropical marine fish, the bicolor damselfish, Pomacentrus partitus. The bicolor damselfish is affected by a disease termed damselfish neurofibromatosis (DNF), being developed as an animal model of neurofibromatosis-type 1 (NF1) in humans. NF1 affects SC, fibroblasts, and perineurial cells. The sole depolarization-activated ionic current present in cultured SC from normal fish peripheral nerve and from neurofibromas of fish with induced or spontaneously occurring DNF was an inactivating K+ current (K current), with a strong dependence on the Nernst potential for K+ This K current activated at depolarizations to -40 mV and above and inactivated during a maintained test pulse (0.2-1 s), but inactivation was significantly greater in tumored SC. Both currents were inhibited by 4-aminopyridine (K-d similar to 1 mM) and by dendrotoxin (15 mu M) but were insensitive to extracellular tetraethyammonium (less than or equal to 150 mM), indicating that the whole cell currents were similar pharmacologically. The currents could be distinguished on the basis of their sensitivity to depolarized holding potential, with normal cells less sensitive. Half-inactivation of the current was -32 mV in normal cells and -38 mV in tumored cells. Inactivation curves constructed from the average normalized current for many SC were significantly different in normal and tumored cells. When the depolarized holding potential was maintained between test depolarizations, greater voltage-dependent inactivation in tumored cells was apparent. Normal cells maintained an average of 36% of peak current at a holding voltage of -40 mV, while in tumored cells this average was 12%, a significant difference. (C) 1994 Wiley-Liss, Inc. RP FIEBER, LA (reprint author), UNIV MIAMI,ROSENSTIEL SCH MARINE & ATMOSPHER SCI,NIEHS,CTR MARINE & FRESHWATER BIOMED SCI,MBF,MIAMI,FL 33149, USA. OI Fieber, Lynne/0000-0002-7717-2260 FU NIEHS NIH HHS [P30ES05705]; NINDS NIH HHS [NS21997] NR 41 TC 8 Z9 8 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0894-1491 J9 GLIA JI Glia PD MAY PY 1994 VL 11 IS 1 BP 64 EP 72 DI 10.1002/glia.440110109 PG 9 WC Neurosciences SC Neurosciences & Neurology GA NH644 UT WOS:A1994NH64400007 PM 8070896 ER PT J AU ANDERSON, BJ LI, XC ALCANTARA, AA ISAACS, KR BLACK, JE GREENOUGH, WT AF ANDERSON, BJ LI, XC ALCANTARA, AA ISAACS, KR BLACK, JE GREENOUGH, WT TI GLIAL HYPERTROPHY IS ASSOCIATED WITH SYNAPTOGENESIS FOLLOWING MOTOR-SKILL LEARNING, BUT NOT WITH ANGIOGENESIS FOLLOWING EXERCISE SO GLIA LA English DT Article DE ASTROCYTE; BERGMANN GLIA; MORPHOLOGY; PLASTICITY; LEARNING ID VISUAL-CORTEX SYNAPSES; RAT-BRAIN; CEREBELLAR CORTEX; PATHOLOGICAL RESEARCH; ADRENERGIC-RECEPTORS; ASTROCYTE PROCESSES; SYNAPTIC DENSITY; NUMBER; CELLS; LOCALIZATION AB Rats reared from weaning in a complex environment have an increase in 1) glial surface area, 2) capillary volume, and 3) the number of synapses, per neuron. In that paradigm it has not been possible to determine whether the glial increase more closely correlates with the increase in synaptic numbers or with angiogenesis. More recently we have found that rats that exercised had an increase in the density of capillaries without an increase in the synaptic numbers, whereas rats that learned new motor skills had a greater number of synapses per neuron without an increase in the density of capillaries. Those findings provided the opportunity to investigate whether changes in glial volume in the cerebellum correspond to changes in the number of synapses or in capillary volume. Glial area fraction estimates were obtained using point counts on electron micrographs from the previous studies. The skill learning group had a greater volume of molecular layer per Purkinje cell, and also a greater volume of glia per Purkinje cell, than rats in either an inactive group or rats in two exercise groups. No significant differences were found in glial volume per synapse and glial volume per capillary across groups, although there was a tendency for glial volume per capillary to be lower in the exercise groups. The data indicate that glial volume correlates with synaptic numbers and not with capillary density. (C) 1994 Wiley-Liss, Inc. C1 UNIV ILLINOIS,BECKMAN INST,CTR NEUROBIOL LEARNING & MEMORY,URBANA,IL 61801. INDIANA UNIV,PROGRAM NEURAL SCI,BLOOMINGTON,IN 47405. INDIANA UNIV,CTR INTEGRAT STUDY ANIM BEHAV,BLOOMINGTON,IN 47405. UNIV ILLINOIS,DEPT PHYSIOL,URBANA,IL 61801. YALE UNIV,SCH MED,NEUROANAT SECT,NEW HAVEN,CT 06510. NIMH,CLIN SCI LAB,BETHESDA,MD 20892. UNIV UTAH,DEPT PSYCHIAT,SALT LAKE CITY,UT 84132. UNIV ILLINOIS,DEPT PSYCHOL,URBANA,IL 61801. UNIV ILLINOIS,DEPT CELL & STRUCT BIOL,URBANA,IL 61801. UNIV ILLINOIS,NEUROSCI PROGRAM,URBANA,IL 61801. FU NIA NIH HHS [AG10154]; NICHD NIH HHS [HD-07333]; NIMH NIH HHS [MH18412] NR 40 TC 109 Z9 113 U1 4 U2 8 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0894-1491 J9 GLIA JI Glia PD MAY PY 1994 VL 11 IS 1 BP 73 EP 80 DI 10.1002/glia.440110110 PG 8 WC Neurosciences SC Neurosciences & Neurology GA NH644 UT WOS:A1994NH64400008 PM 7520887 ER PT J AU SIMMONDS, P ALBERTI, A ALTER, HJ BONINO, F BRADLEY, DW BRECHOT, C BROUWER, JT CHAN, SW CHAYAMA, K CHEN, DS CHOO, QL COLOMBO, M CUYPERS, HTM DATE, T DUSHEIKO, GM ESTEBAN, JI FAY, O HADZIYANNIS, SJ HAN, J HATZAKIS, A HOLMES, EC HOTTA, H HOUGHTON, M IRVINE, B KOHARA, M KOLBERG, JA KUO, G LAU, JYN LELIE, PN MAERTENS, G MCOMISH, F MIYAMURA, T MIZOKAMI, M NOMOTO, A PRINCE, AM REESINK, HW RICE, C ROGGENDORF, M SCHALM, SW SHIKATA, T SHIMOTOHNO, K STUYVER, L TREPO, C WEINER, A YAP, PL URDEA, MS AF SIMMONDS, P ALBERTI, A ALTER, HJ BONINO, F BRADLEY, DW BRECHOT, C BROUWER, JT CHAN, SW CHAYAMA, K CHEN, DS CHOO, QL COLOMBO, M CUYPERS, HTM DATE, T DUSHEIKO, GM ESTEBAN, JI FAY, O HADZIYANNIS, SJ HAN, J HATZAKIS, A HOLMES, EC HOTTA, H HOUGHTON, M IRVINE, B KOHARA, M KOLBERG, JA KUO, G LAU, JYN LELIE, PN MAERTENS, G MCOMISH, F MIYAMURA, T MIZOKAMI, M NOMOTO, A PRINCE, AM REESINK, HW RICE, C ROGGENDORF, M SCHALM, SW SHIKATA, T SHIMOTOHNO, K STUYVER, L TREPO, C WEINER, A YAP, PL URDEA, MS TI A PROPOSED SYSTEM FOR THE NOMENCLATURE OF HEPATITIS-C VIRAL GENOTYPES SO HEPATOLOGY LA English DT Letter ID NON-B HEPATITIS; VIRUS GENOME; MOLECULAR-CLONING; NON-A; SEQUENCE; ORGANIZATION; DISTINCT; CARRIER; JAPAN; RNA C1 UNIV PADUA,IST MED CLIN,MED CLIN 2,I-35123 PADUA,ITALY. NIH,WARREN G MAGNUSON CLIN CTR,DEPT TRANSFUS MED,IMMUNOL SECT,BETHESDA,MD 20892. OSPED MOLINETTE,DEPT GASTROENTEROL LAB,I-10126 TURIN,ITALY. CTR DIS CONTROL,CTR INFECT DIS,DIV VIRAL DIS,HEPATITIS BRANCH,ATLANTA,GA 30333. UNIV PARIS 05,INSERM,U370,F-75730 PARIS 15,FRANCE. UNIV ROTTERDAM HOSP,HOSP DIJKZIGT,3015 GD ROTTERDAM,NETHERLANDS. TORANOMON GEN HOSP,DEPT GASTROENTEROL,TOKYO,JAPAN. NATL TAIWAN UNIV HOSP,HEPATITIS RES CTR,TAIPEI,TAIWAN. CHIRON CORP,NON A NON B RES,EMERYVILLE,CA 94608. UNIV MILAN,IST MED INTERNA,CATTEDRA MED INTERNA 1,I-20122 MILAN,ITALY. NETHERLANDS RED CROSS,BLOOD TRANSFUS SERV,CENT LAB,CLB,DEPT DEV RES,1066 CX AMSTERDAM,NETHERLANDS. KANAZAWA MED UNIV,DEPT BIOCHEM,UCHINADA,ISHIKAWA 92002,JAPAN. UNIV LONDON,ROYAL FREE HOSP,SCH MED,DEPT MED,LONDON NW3 2PF,ENGLAND. AUTONOMOUS UNIV BARCELONA,GEN HOSP,DEPT MED INTERNA,SERV HEPATOL,LIVER RES UNIT,E-08035 BARCELONA,SPAIN. UNIV NACL ROSARIO,CTR TECNOL SALUD PUBL,FAC CIENCIAS BIOQUIM & FARMACEUT,RA-2000 ROSARIO,ARGENTINA. HIPPOKRATON GEN HOSP,GR-11527 ATHENS,GREECE. UNIV ATHENS,SCH MED,DEPT HYG & EPIDEMIOL,NATL RETROVIRUS REFERENCE CTR,GR-11527 ATHENS,GREECE. UNIV OXFORD,DEPT ZOOL,OXFORD OX1 3PS,ENGLAND. KOBE UNIV,SCH MED,DEPT MICROBIOL,KOBE 650,JAPAN. CHIRON CORP,NUCLE ACID SYST,EMERYVILLE,CA 94608. CHIRON CORP,MOLEC BIOL,EMERYVILLE,CA. UNIV FLORIDA,DEPT MED,HEPATOBILIARY DIS SECT,GAINESVILLE,FL 32610. NETHERLANDS RED CROSS,BLOOD TRANSFUS SERV,CENT LAB,CLB,DIV DIAGNOST,DEPT VIRUS SEROL,AMSTERDAM,NETHERLANDS. INNOGENET NV SA,B-9052 ZWIJNAARDE GHENT,BELGIUM. ROYAL INFIRM,SCOTLAND & SE SCOTLAND BLOOD TRANSFUS SERV,EDINBURGH EH3 9HB,MIDLOTHIAN,SCOTLAND. NATL INST HLTH,DEPT VIROL 2,TOKYO 162,JAPAN. NAGOYA CITY UNIV,SCH MED,DEPT INTERNAL MED 2,NAGOYA,AICHI 467,JAPAN. UNIV TOKYO,INST MED SCI,DEPT MICROBIOL,TOKYO 108,JAPAN. NEW YORK BLOOD CTR,LINDSLEY F KIMBALL RES INST,VIROL & PARASITOL LAB,NEW YORK,NY 10021. NETHERLANDS RED CROSS,BLOOD BANK,1066 CX AMSTERDAM,NETHERLANDS. WASHINGTON UNIV,MED CTR,SCH MED,DEPT MOLEC MICROBIOL,ST LOUIS,MO 63110. UNIV ESSEN GESAMTHSCH KLINIKUM,ROBERT KOCH HAUS INST VIROL,WHO,W-4300 ESSEN 1,GERMANY. NATL CANC CTR,RES INST,DIV VIROL,TOKYO 104,JAPAN. INSERM,U271,HEPATITIS AIDS & HUMAN RETROVIRUS RES UNIT,F-69424 LYON 03,FRANCE. TOKYO METROPOLITAN INST MED SCI,DEPT MICROBIOL,TOKYO 113,JAPAN. CHIRON CORP,IMMUNOCHEM,EMERYVILLE,CA 94608. NIHON UNIV,SCH MED,DEPT PATHOL,TOKYO,JAPAN. RP SIMMONDS, P (reprint author), UNIV EDINBURGH,SCH MED,DEPT MED MICROBIOL,EDINBURGH EH8 9AG,MIDLOTHIAN,SCOTLAND. OI Bonino, Ferruccio/0000-0001-9942-0328; CHEN, DING-SHINN/0000-0001-7791-6154 NR 21 TC 953 Z9 979 U1 2 U2 19 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD MAY PY 1994 VL 19 IS 5 BP 1321 EP 1324 DI 10.1016/0270-9139(94)90887-7 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA NJ328 UT WOS:A1994NJ32800034 PM 8175159 ER PT J AU BURKE, JD BURKE, KC RAE, DS AF BURKE, JD BURKE, KC RAE, DS TI INCREASED RATES OF DRUG-ABUSE AND DEPENDENCE AFTER ONSET OF MOOD OR ANXIETY DISORDERS IN ADOLESCENCE SO HOSPITAL AND COMMUNITY PSYCHIATRY LA English DT Article; Proceedings Paper CT American-Psychiatric-Association Annual Meeting CY MAY 02-09, 1992 CL WASHINGTON, DC SP AMER PSYCHIAT ASSOC ID DIAGNOSTIC INTERVIEW SCHEDULE; CATCHMENT-AREA SITES; PSYCHIATRIC-DISORDERS; MAJOR DEPRESSION; MENTAL-DISORDERS; SUBSTANCE ABUSE; COMMUNITY POPULATIONS; LIFETIME PREVALENCE; UNITED-STATES; CO-OCCURRENCE AB Objectives: The aim of the study was to examine the relationship of prevalence and age at onset of drug abuse and dependence to mood and anxiety disorders, using epidemiologic data. methods: Life-table analyses using data collected on 20,745 respondents in the National Institute of Mental Health's Epidemiologic Catchment Area surveys were used to calculate the hazard rate for developing drug disorders subsequent to adolescent-onset or adult-onset mood and anxietY disorders. Results: For respondents with onset of a mood disorder during adolescence, the peak age for developing drug abuse and dependence occurs between 15 and 19 years; when the mood disorder begins in adulthood, the peak onset for drug disorders is delayed to between 25 and 29 years of age, Similar but less striking results are found for onset of drug abuse and dependence following either panic or obsessive-compulsive disorder. Conclusions. These findings highlight the need for future prospective studies of children and adolescents to date the onset of mental disorders and substance use disorders. If prospective studies can confirm the apparent pattern of substance use disorders occurring subsequent to mental disorders, prevention and treatment strategies for youth at risk should be developed. C1 TEXAS A&M UNIV,HLTH SCI CTR,TEMPLE,TX. SCOTT & WHITE HOSP & CLIN,DEPT PSYCHIAT,TEMPLE,TX. NIMH,DIV EPIDEMIOL SERV & RES,ROCKVILLE,MD 20857. RI Burke, Jack/I-4440-2012 OI Burke, Jack/0000-0001-5868-1695 NR 42 TC 44 Z9 45 U1 7 U2 7 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0022-1597 J9 HOSP COMMUNITY PSYCH PD MAY PY 1994 VL 45 IS 5 BP 451 EP 455 PG 5 WC Public, Environmental & Occupational Health; Psychiatry SC Public, Environmental & Occupational Health; Psychiatry GA NJ221 UT WOS:A1994NJ22100006 PM 8045539 ER PT J AU BARRON, KS ROBINSON, MA AF BARRON, KS ROBINSON, MA TI THE HUMAN T-CELL RECEPTOR VARIABLE GENE SEGMENT TCRBV6S1 HAS 2 NULL ALLELES SO HUMAN IMMUNOLOGY LA English DT Article ID V-BETA-GENE; DNA AB The extent of polymorphism in TCRBV6S1 was examined by screening 203 individuals of diverse ethnic backgrounds by using SSCP. Three alleles were detected, including two that were described previously (TCRBV6S1*1 and *2P). The third allele (TCRBV6S1*3P), identified in these studies, is a pseudogene because, similar to allele *2P, it contains a substitution of a highly conserved cysteine residue near CDR3. Among a panel of 126 Caucasian donors, alleles *1, *2P, and *3P were observed to have frequencies of 0.72, 0.12, and 0.16, respectively. The extent of this survey suggests that it is unlikely for there to be additional common variants of TCRBV6S1. The approach used here enables rapid typing for polymorphism in a TCRBV gene that results in an allelically determined hole in the TCR repertoire. C1 NIAID,IMMUNOGENET LAB,ROCKVILLE,MD 20852. NR 9 TC 18 Z9 18 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PD MAY PY 1994 VL 40 IS 1 BP 17 EP 19 DI 10.1016/0198-8859(94)90016-7 PG 3 WC Immunology SC Immunology GA NP352 UT WOS:A1994NP35200003 PM 8045788 ER PT J AU RAVNIKGLAVAC, M GLAVAC, D DEAN, M AF RAVNIKGLAVAC, M GLAVAC, D DEAN, M TI SENSITIVITY OF SINGLE-STRAND CONFORMATION POLYMORPHISM AND HETERODUPLEX METHOD FOR MUTATION DETECTION IN THE CYSTIC-FIBROSIS GENE SO HUMAN MOLECULAR GENETICS LA English DT Article ID REGULATOR CFTR GENE; GRADIENT GEL-ELECTROPHORESIS; POLYMERASE CHAIN-REACTION; NUCLEOTIDE-BINDING FOLD; POINT MUTATIONS; FRAMESHIFT MUTATION; BASE SUBSTITUTIONS; DNA-SEQUENCE; IDENTIFICATION; POPULATION AB The gene responsible for cystic fibrosis (CF) contains 27 coding exons and more than 300 independent mutations have been identified. An efficient and optimized strategy is required to identify additional mutations and/or to screen patient samples for the presence of known mutations. We have tested several different conditions for performing single-stranded conformation polymorphism (SSCP) analysis in order to determine the efficiency of the method and to identify the optimum conditions for mutation detection. Each exon and corresponding exon boundaries were amplified. A panel of 134 known CF mutations were used to test the efficiency of detection of mutations. The SSCP conditions were varied by altering the percentage and cross-linking of the acrylamide, employing MDE (an acrylamide substitute), and by adding sucrose and glycerol. The presence of heteroduplexes could be detected on most gels and in same cases contributed to the ability to distinguish certain mutations. Each analysis condition detected 75-98% of the mutations, and all of the mutations could be detected by at least one condition. Therefore, an optimized SSCP analysis can be used to efficiently screen for mutations in a large gene. C1 NCI,FREDERICK CANC RES & DEV CTR,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. RI Dean, Michael/G-8172-2012 OI Dean, Michael/0000-0003-2234-0631 NR 55 TC 164 Z9 166 U1 0 U2 2 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD MAY PY 1994 VL 3 IS 5 BP 801 EP 807 DI 10.1093/hmg/3.5.801 PG 7 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA NM099 UT WOS:A1994NM09900016 PM 7521710 ER PT J AU MAEKAWA, M SUDO, K KANNO, T TAKAYASU, S LI, SSL KITAJIMA, M MATSUURA, Y AF MAEKAWA, M SUDO, K KANNO, T TAKAYASU, S LI, SSL KITAJIMA, M MATSUURA, Y TI A NOVEL DELETION MUTATION OF LACTATE-DEHYDROGENASE A(M) GENE IN THE 5TH FAMILY WITH THE ENZYME DEFICIENCY SO HUMAN MOLECULAR GENETICS LA English DT Article ID M-SUBUNIT DEFICIENCY; A ISOZYME C1 JIKEI UNIV, DAISAN HOSP, SCH MED, DEPT LAB MED, TOKYO 201, JAPAN. MED COLL OITA, DEPT DERMATOL, OITA 87956, JAPAN. NIEHS, GENET LAB, RES TRIANGLE PK, NC 27709 USA. FUJITSU LTD, MINATO KU, TOKYO 105, JAPAN. RP MAEKAWA, M (reprint author), HAMAMATSU UNIV SCH MED, DEPT LAB MED, HANDA CHO 3600, HAMAMATSU, SHIZUOKA 43131, JAPAN. NR 10 TC 8 Z9 8 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD MAY PY 1994 VL 3 IS 5 BP 825 EP 826 DI 10.1093/hmg/3.5.825 PG 2 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA NM099 UT WOS:A1994NM09900022 PM 8081370 ER PT J AU LI, H SCHMIDT, L WEI, MH HUSTAD, T LERMAN, MI ZBAR, B TORY, K AF LI, H SCHMIDT, L WEI, MH HUSTAD, T LERMAN, MI ZBAR, B TORY, K TI 14 NEW POLYMORPHIC DINUCLEOTIDE REPEATS ON HUMAN-CHROMOSOME-3 - D3S1432, D3S1433, D3S1434, D3S1483, D3S1484, D3S1485, D3S1486, D3S1487, D3S1488, D3S1489, D3S1490, D3S1496, D3S1497 AND D3S1498 SO HUMAN MOLECULAR GENETICS LA English DT Note ID LINKAGE MAP C1 NCI,FREDERICK CANC RES & DEV CTR,IMMUNOBIOL LAB,FREDERICK,MD 21702. RP LI, H (reprint author), NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702, USA. NR 5 TC 0 Z9 0 U1 0 U2 3 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD MAY PY 1994 VL 3 IS 5 BP 837 EP 837 DI 10.1093/hmg/3.5.837 PG 1 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA NM099 UT WOS:A1994NM09900027 PM 8081375 ER PT J AU IYONAGA, K TAKEYA, M SAITA, N SAKAMOTO, O YOSHIMURA, T ANDO, M TAKAHASHI, K AF IYONAGA, K TAKEYA, M SAITA, N SAKAMOTO, O YOSHIMURA, T ANDO, M TAKAHASHI, K TI MONOCYTE CHEMOATTRACTANT PROTEIN-1 IN IDIOPATHIC PULMONARY FIBROSIS AND OTHER INTERSTITIAL LUNG-DISEASES SO HUMAN PATHOLOGY LA English DT Article DE MCP-1; MONOCLONAL ANTIBODY; IMMUNOHISTOCHEMISTRY; METAPLASTIC EPITHELIAL CELLS; NORTHERN BLOT ANALYSIS ID ALVEOLAR EPITHELIAL-CELLS; BLOOD MONONUCLEAR LEUKOCYTES; AMINO-ACID ANALYSIS; INTRAALVEOLAR FIBROSIS; MONOCLONAL-ANTIBODIES; GROWTH-FACTOR; EXPRESSION; METAPLASIA; MACROPHAGES; INJURY C1 KUMAMOTO UNIV,SCH MED,DEPT PATHOL 2,KUMAMOTO 860,JAPAN. KUMAMOTO UNIV,SCH MED,DEPT INTERNAL MED 1,KUMAMOTO 860,JAPAN. NCI,IMMUNOBIOL LAB,IMMUNOPATHOL SECT,FREDERICK,MD 21701. NR 46 TC 77 Z9 80 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD MAY PY 1994 VL 25 IS 5 BP 455 EP 463 DI 10.1016/0046-8177(94)90117-1 PG 9 WC Pathology SC Pathology GA NP557 UT WOS:A1994NP55700005 PM 8200639 ER PT J AU Unser, M AF Unser, Michael TI Fast Gabor-Like Windowed Fourier and Continuous Wavelet Transforms SO IEEE SIGNAL PROCESSING LETTERS LA English DT Article AB Fast algorithms for the evaluation of running windowed Fourier and continuous wavelet transforms are presented. The analysis functions approximate complex-modulated Gaussians as closely as desired and may be optimally localized in time and frequency. The Gabor filtering is performed indirectly by convolving a premodulated signal with a Gaussian-like window and demodulating the output. The window functions are either B-splines dilated by an integer factor m or quasi-Gaussians of arbitrary size generated from the n-fold convolution of a symmetrical exponential. Both approaches result in a recursive implementation with a complexity independent of the window size (O(N)). C1 NIH, Biomed Engn & Instrumentat Program, Natl Ctr Res Resources, Bethesda, MD 20892 USA. RP Unser, M (reprint author), NIH, Biomed Engn & Instrumentat Program, Natl Ctr Res Resources, Bethesda, MD 20892 USA. RI Unser, Michael/A-1550-2008 NR 13 TC 21 Z9 21 U1 2 U2 6 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 1070-9908 J9 IEEE SIGNAL PROC LET JI IEEE Signal Process. Lett. PD MAY PY 1994 VL 1 IS 5 BP 76 EP 79 DI 10.1109/97.294384 PG 4 WC Engineering, Electrical & Electronic SC Engineering GA V04VK UT WOS:000207085700002 ER PT J AU WEI, S CHARMLEY, P ROBINSON, MA CONCANNON, P AF WEI, S CHARMLEY, P ROBINSON, MA CONCANNON, P TI THE EXTENT OF THE HUMAN GERMLINE T-CELL RECEPTOR-V-BETA GENE SEGMENT REPERTOIRE SO IMMUNOGENETICS LA English DT Article ID VARIABLE REGION GENES; ANTIGEN RECEPTOR; ALLELIC VARIATIONS; ALPHA-CHAIN; POLYMORPHISMS; FAMILIES; IDENTIFICATION; ORGANIZATION; DIVERSITY; SEQUENCE AB An assessment of the size of the human TCRBV gene segment repertoire based on the identification of TCRBV gene segments in genomic DNA was undertaken. PCR amplification from cloned and uncloned genomic DNA sources, nucleotide sequencing, Southern blot hybridization, and cosmid cloning were used to identify TCRBV gene segments in multiple unrelated individuals. The key advantages to this approach were: 1) TCRBV gene segments which are expressed only at very low levels in cDNA libraries were still detectable, and 2) it was possible to discriminate between alleles at the same locus vs products of different loci. A total of 63 unique TCRBV gene segments were identified and sequenced. Six of these TCRBV gene segments had not been previously described. Thirty-four cosmid clones containing 51 of the 63 identified TCRBV gene segments were isolated and screened for the presence of additional novel TCRBV subfamily members. These results, obtained by a variety of complementary approaches, indicate that the human TCRBV germline repertoire encodes at least 63 TCRBV gene segments of which 52 are functional. The availability of the majority of these TCRBV gene segments on cosmid clones should facilitate further investigation of germline TCRBV gene segment polymorphism and putative disease associations. C1 VIRGINIA MASON RES CTR,SEATTLE,WA 98101. NIAID,IMMUNOGENET LAB,TWINBROOK FACIL 2,ROCKVILLE,MD 20852. UNIV WASHINGTON,SCH MED,DEPT IMMUNOL,SEATTLE,WA 98195. OI Concannon, Patrick/0000-0002-5801-1859 FU NIDDK NIH HHS [DK41347] NR 42 TC 150 Z9 153 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0093-7711 J9 IMMUNOGENETICS JI Immunogenetics PD MAY PY 1994 VL 40 IS 1 BP 27 EP 36 DI 10.1007/BF00163961 PG 10 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA NN362 UT WOS:A1994NN36200004 PM 8206523 ER PT J AU HARDY, KJ YOUNG, HA LAGOO, AS AF HARDY, KJ YOUNG, HA LAGOO, AS TI MOLECULAR DIAGNOSTICS SO IMMUNOLOGY AND ALLERGY CLINICS OF NORTH AMERICA LA English DT Review ID POLYMERASE CHAIN-REACTION; SEVERE COMBINED IMMUNODEFICIENCY; X-CHROMOSOME INACTIVATION; NUCLEOSIDE PHOSPHORYLASE-DEFICIENCY; FRAGMENT-LENGTH POLYMORPHISM; NUCLEIC-ACID AMPLIFICATION; ADENOSINE-DEAMINASE GENE; RECEPTOR MESSENGER-RNA; HUMAN GENOME PROJECT; EPSTEIN-BARR-VIRUS C1 UNIV MISSISSIPPI,MED CTR,SCH MED,JACKSON,MS 39216. NCI,BETHESDA,MD 20892. RP HARDY, KJ (reprint author), UNIV MISSISSIPPI,MED CTR,2500 N STATE ST,JACKSON,MS 39216, USA. NR 119 TC 3 Z9 3 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0889-8561 J9 IMMUNOL ALLERGY CLIN JI Immunol. Allerg. Clin. North Am. PD MAY PY 1994 VL 14 IS 2 BP 199 EP 223 PG 25 WC Allergy; Immunology SC Allergy; Immunology GA NM501 UT WOS:A1994NM50100002 ER PT J AU FLEISHER, TA AF FLEISHER, TA TI IMMUNOPHENOTYPING OF LYMPHOCYTES BY FLOW-CYTOMETRY SO IMMUNOLOGY AND ALLERGY CLINICS OF NORTH AMERICA LA English DT Article ID T-CELL SUBSETS; PERIPHERAL-BLOOD; IDENTIFICATION; CAUCASIANS; SEPARATION; POPULATION; DISEASE RP FLEISHER, TA (reprint author), NIH,WARREN G MAGNUSON CLIN CTR,BLDG 10,ROOM 2C410,BETHESDA,MD 20892, USA. NR 33 TC 8 Z9 8 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0889-8561 J9 IMMUNOL ALLERGY CLIN JI Immunol. Allerg. Clin. North Am. PD MAY PY 1994 VL 14 IS 2 BP 225 EP 240 PG 16 WC Allergy; Immunology SC Allergy; Immunology GA NM501 UT WOS:A1994NM50100003 ER PT J AU JANIK, JE LONGO, DL AF JANIK, JE LONGO, DL TI LABORATORY CHARACTERIZATION OF MALIGNANCIES OF THE IMMUNE-SYSTEM SO IMMUNOLOGY AND ALLERGY CLINICS OF NORTH AMERICA LA English DT Article ID POLYMERASE CHAIN-REACTION; BONE-MARROW TRANSPLANTATION; COLONY-STIMULATING FACTOR; NON-HODGKINS-LYMPHOMAS; CELL ANTIGEN RECEPTOR; TUMOR-NECROSIS-FACTOR; FOLLICULAR LYMPHOMA; LYMPHOCYTES-T; CHROMOSOMAL TRANSLOCATION; MULTIPLE-MYELOMA RP JANIK, JE (reprint author), NCI,FCRDC,BLDG 576,ROOM 100,FREDERICK,MD 21702, USA. NR 76 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0889-8561 J9 IMMUNOL ALLERGY CLIN JI Immunol. Allerg. Clin. North Am. PD MAY PY 1994 VL 14 IS 2 BP 301 EP 322 PG 22 WC Allergy; Immunology SC Allergy; Immunology GA NM501 UT WOS:A1994NM50100006 ER PT J AU MUROCACHO, CA EMANCIPATOR, SN LAMM, ME AF MUROCACHO, CA EMANCIPATOR, SN LAMM, ME TI IMMUNOHISTOLOGY AND IMMUNOPATHOLOGY SO IMMUNOLOGY AND ALLERGY CLINICS OF NORTH AMERICA LA English DT Review ID EPIDERMOLYSIS-BULLOSA-ACQUISITA; IMMUNE-COMPLEX GLOMERULONEPHRITIS; GLOMERULAR BASEMENT-MEMBRANE; GLUTAMIC-ACID DECARBOXYLASE; WEGENER GRANULOMATOSIS; CELIAC-DISEASE; VII COLLAGEN; DERMATITIS-HERPETIFORMIS; HORSERADISH-PEROXIDASE; CYTOPLASM ANTIBODIES C1 CASE WESTERN RESERVE UNIV,SCH MED,INST PATHOL,2085 ADELBERT RD,ROOM 204,CLEVELAND,OH 44106. NIAID,BETHESDA,MD 20892. NR 125 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0889-8561 J9 IMMUNOL ALLERGY CLIN JI Immunol. Allerg. Clin. North Am. PD MAY PY 1994 VL 14 IS 2 BP 401 EP 423 PG 23 WC Allergy; Immunology SC Allergy; Immunology GA NM501 UT WOS:A1994NM50100012 ER PT J AU VANEWIJK, W SHORES, EW SINGER, A AF VANEWIJK, W SHORES, EW SINGER, A TI CROSSTALK IN THE MOUSE THYMUS SO IMMUNOLOGY TODAY LA English DT Article ID T-CELL DIFFERENTIATION; EPITHELIAL-CELLS; POSITIVE SELECTION; I-A; MICE; MICROENVIRONMENTS; IDENTIFICATION; SUBPOPULATIONS; MEDULLA; GROWTH AB The development of mature T cells within the thymus is dependent upon intact cortical and medullary microenvironments. In turn, thymic microenvironments themselves are dependent on lymphoid cells to maintain their integrity. Here, Willem van Ewijk and colleagues discuss experiments that have established the phenomenon of 'crosstalk' within the mouse thymus and suggest a mechanism whereby lymphoid and stromal cells influence each other in a consecutive manner during T-cell development. C1 NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892. RP VANEWIJK, W (reprint author), ERASMUS UNIV ROTTERDAM,DEPT IMMUNOL,POB 1738,3000 DR ROTTERDAM,NETHERLANDS. NR 33 TC 190 Z9 192 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0167-5699 J9 IMMUNOL TODAY JI Immunol. Today PD MAY PY 1994 VL 15 IS 5 BP 214 EP 217 DI 10.1016/0167-5699(94)90246-1 PG 4 WC Immunology SC Immunology GA NJ948 UT WOS:A1994NJ94800006 PM 8024681 ER PT J AU RAGHAVAN, N FREEDMAN, DO FITZGERALD, PC UNNASCH, TR OTTESEN, EA NUTMAN, TB AF RAGHAVAN, N FREEDMAN, DO FITZGERALD, PC UNNASCH, TR OTTESEN, EA NUTMAN, TB TI CLONING AND CHARACTERIZATION OF A POTENTIALLY PROTECTIVE CHITINASE-LIKE RECOMBINANT ANTIGEN FROM WUCHERERIA-BANCROFTI SO INFECTION AND IMMUNITY LA English DT Article ID BRUGIA-PAHANGI; INFECTIVE LARVAE; SERRATIA-MARCESCENS; ENDEMIC FILARIASIS; IMMUNE-RESPONSES; PACIFIC ISLAND; MALAYI; VACCINATION; PROTEINS; GENE AB While there is no direct evidence demonstrating the existence of protective immunity to Wuchereria bancrofti infection in humans, the presence of individuals, in populations in areas where infection is endemic, with no clinical evidence of past or current infection despite appreciable exposure to the infective larvae, suggests that protective immunity to filarial parasites may occur naturally. Earlier work indicated that such putatively immune individuals generated antibodies to a 43-kDa antigen from larval extracts of the related filarial parasite Brugia malayi that was recognized by only 8% of the infected population. With rabbit antiserum raised against this 43-kDa antigen, this current study identified a recombinant clone, WbN43, with an insert size of 2.3 kb, from a W. bancrofti genomic expression library. The recombinant fusion protein was differentially recognized by the putatively immune individuals but not by the infected patients. The coding sequence (684 bp) from the 5' end had significant sequence similarity to chitinases from Serratia marcescens, Bacillus circulans, Streptomyces plicatus, and B. malayi. Peptide sequencing of the expressed product also defined a chitinase-like sequence. Molecular characterization indicated WbN43 to be a low-copy-number gene, with expression predominantly in infective larvae and microfilariae but not in adult parasites. C1 NIH,PARASIT DIS LAB,BETHESDA,MD 20892. NIH,DIV COMP RES & TECHNOL,BETHESDA,MD 20892. UNIV ALABAMA,DIV GEOG MED,BIRMINGHAM,AL 35205. NR 54 TC 47 Z9 47 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD MAY PY 1994 VL 62 IS 5 BP 1901 EP 1908 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA NH313 UT WOS:A1994NH31300055 PM 8168956 ER PT J AU FLESCH, IEA HESS, JH OSWALD, IP KAUFMANN, SHE AF FLESCH, IEA HESS, JH OSWALD, IP KAUFMANN, SHE TI GROWTH-INHIBITION OF MYCOBACTERIUM-BOVIS BY IFN-GAMMA STIMULATED MACROPHAGES - REGULATION BY ENDOGENOUS TUMOR-NECROSIS-FACTOR-ALPHA AND BY IL-10 SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE CYTOKINE PRODUCTION; INFECTION; INTRACELLULAR BACTERIA; MACROPHAGE ACTIVATION ID LISTERIA-MONOCYTOGENES INFECTION; BONE-MARROW MACROPHAGES; INTERFERON-GAMMA; MURINE MACROPHAGES; INTERLEUKIN-10 IL-10; PERITONEAL-MACROPHAGES; ACTIVATED MACROPHAGES; CYTOKINE PRODUCTION; BCG INFECTION; MOUSE AB Murine bone marrow-derived macrophages (BMM) are able to inhibit the intracellular growth of Mycobacterium bovis and Mycobacterium tuberculosis H37Rv after activation with recombinant (r) IFN and growth inhibition is mediated by reactive nitrogen intermediates (RNI) derived from L-arginine. We now demonstrate that tumor necrosis factor (TNF)-alpha acts as an endogenous cofactor in the induction of mycobacterial growth inhibition. TNF-alpha was produced by BMM stimulated with rIFN-gamma and infected with mycobacteria, and a specific antiserum to TNF-alpha inhibited rIFN-gamma-induced production of RNI as well as growth inhibition of M. bovis. IL-10, a cytokine which suppresses antimycobacterial macrophage functions, was also produced by BMM activated with rIFN-gamma and infected with M. bovis. IFN-gamma-induced production of TNF-alpha and of reactive nitrogen intermediates as well as mycobacterial growth inhibition were inhibited by exogenous IL-10, but only when given prior to IFN-gamma stimulation. We conclude that the outcome of mycobacterial infection is regulated by a coordinate interplay between IFN-gamma, TNF-alpha and IL-10. C1 NIAID,PARASIT DIS LAB,BETHESDA,MD 20814. RP FLESCH, IEA (reprint author), UNIV ULM,DEPT IMMUNOL,ALBERT EINSTEIN ALLEE 111,D-89070 ULM,GERMANY. RI OSWALD, Isabelle/A-8497-2013; Kaufmann, Stefan HE/I-5454-2014 OI Kaufmann, Stefan HE/0000-0001-9866-8268 NR 35 TC 105 Z9 105 U1 0 U2 2 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD MAY PY 1994 VL 6 IS 5 BP 693 EP 700 DI 10.1093/intimm/6.5.693 PG 8 WC Immunology SC Immunology GA NP537 UT WOS:A1994NP53700003 PM 8080840 ER PT J AU CHANG, GC LIU, R PANNIERS, R LI, GC AF CHANG, GC LIU, R PANNIERS, R LI, GC TI RAT FIBROBLASTS TRANSFECTED WITH THE HUMAN 70-KDA HEAT-SHOCK GENE EXHIBIT ALTERED TRANSLATION AND EUKARYOTIC INITIATION FACTOR-2-ALPHA PHOSPHORYLATION FOLLOWING HEAT-SHOCK SO INTERNATIONAL JOURNAL OF HYPERTHERMIA LA English DT Article DE HSP70; GENE EXPRESSION; TRANSLATION; EIF-2-ALPHA PHOSPHORYLATION ID REGULATED EIF-2-ALPHA KINASE; CHINESE-HAMSTER FIBROBLASTS; BINDING-PROTEIN COMPLEX; FACTOR-II; MAMMALIAN-CELLS; HELA-CELLS; RESISTANT VARIANTS; ALPHA-SUBUNIT; MESSENGER-RNA; RECOVERY AB Heat shock inhibits translation in a wide variety of cells. After heating, eukaryotic initiation factor 2-alpha (eIF-2alpha) becomes phosphorylated which prevents the binding of Met-tRNA to the 40s ribosomal subunit inhibiting initiation of translation. Thermotolerant cells demonstrate resistance to inhibition of translation by additional heating suggesting that heat shock proteins may help to maintain translational integrity following thermal stress. Here we have examined the effects of increased intracellular levels of hsp70 protein on translation and eIF-2alpha phosphorylation using rat fibroblasts stably transfected with a cloned human hsp70 gene. We observed a decrease in the rate of translational inhibition following heat shock in both hsp70-transfected and thermotolerant cells. Upon recovery at 37-degrees-C, both hsp70-transfected and thermotolerant cells exhibit a faster rate of translational recovery. Utilizing slab gel isoelectric focusing coupled with immunoblotting we demonstrate that 45-degrees-C heat shock leads to a rapid 4-5-fold increase in eIF-2alpha phosphorylation, with little difference seen between control cells and hsp70-transfected cells. However, dephosphorylation of eIF-2alpha occurs faster in the hsp70-transfected cells. These results suggest that hsp70 may play a role in facilitating the dephosphorylation of eIF-2alpha as well as reversing the inhibition of translation following heat shock. C1 UNIV CALIF SAN FRANCISCO,DEPT RADIAT ONCOL,RADIAT ONCOL RES LAB,SAN FRANCISCO,CA 94143. MEM SLOAN KETTERING CANC CTR,DEPT MED PHYS,NEW YORK,NY 10021. MEM SLOAN KETTERING CANC CTR,DEPT RADIAT ONCOL,NEW YORK,NY 10021. NIH,DIV RES GRANTS,BETHESDA,MD 20892. FU NCI NIH HHS [CA-56909, CA-31397] NR 44 TC 11 Z9 11 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI LONDON PA ONE GUNDPOWDER SQUARE, LONDON, ENGLAND EC4A 3DE SN 0265-6736 J9 INT J HYPERTHER JI Int. J. Hyperthermia PD MAY-JUN PY 1994 VL 10 IS 3 BP 325 EP 337 DI 10.3109/02656739409010276 PG 13 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA NP476 UT WOS:A1994NP47600004 PM 7930798 ER PT J AU THEILE, M HARTMANN, S NAUNDORF, H RUESS, D ELBE, B KRAUSE, H DEPPERT, W BARRETT, JC SCHERNECK, S AF THEILE, M HARTMANN, S NAUNDORF, H RUESS, D ELBE, B KRAUSE, H DEPPERT, W BARRETT, JC SCHERNECK, S TI WILD-TYPE P53 IS NOT INVOLVED IN REVERSION OF THE TUMORIGENIC PHENOTYPE OF BREAST-CANCER CELLS AFTER TRANSFER OF NORMAL CHROMOSOME-17 SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE BREAST CANCER CELLS; HUMAN CHROMOSOME 17; MICROCELL-MEDIATED CHROMOSOME TRANSFER; POLYMORPHIC MICROSATELLITE MARKERS; P53 TUMOR SUPPRESSOR GENE ID TUMOR SUPPRESSION; GENE; GROWTH; LINE; CARCINOMAS; FUSION AB A number of different candidate tumor suppressor genes involved in human breast cancer are presumed to be located on chromosome 17. To verify the relevance of chromosome 17 abnormalities in breast cancer cells, a normal human chromosome 17 was transferred by microcell fusion to R30 tumor cells derived from an infiltrating ductal mammary carcinoma. The tumorigenicity of the microcell hybrids in nude mice was examined. The tumor volume obtained with different clones was reduced by up to 94% of the value corresponding to the parental tumor cells. This effect was accompanied by a reduction of anchorage-independent growth, as well as cell growth rates on plastic plates. These effects were independent of the continued presence of a transferred 17q arm and could not be attributed to the action of the normal p53 gene. The results support the assumption that in addition to p53 a further tumor suppressor gene is located on 17p which is involved in breast cancer. C1 MAX DELBRUCK CTR MOLEK MED,BEREICH TUMOR THERAPIE,D-13122 BERLIN,GERMANY. WITEGA EV,D-13122 BERLIN,GERMANY. HEINE PETTE INST EXPT VIROL & IMMUNOL,TUMOR VIROL ABT,D-20251 HAMBURG,GERMANY. NIEHS,MOLEC CARCINOGENESIS LAB,RES TRIANGLE PK,NC 27709. RP THEILE, M (reprint author), MAX DELBRUCK CTR MOLEK MED,BEREICH TUMOR GENET,ROBERT ROEELE STR 10,D-13122 BERLIN,GERMANY. NR 44 TC 8 Z9 8 U1 0 U2 0 PU PROFESSOR D A SPANDIDOS PI ATHENS PA 1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD MAY PY 1994 VL 4 IS 5 BP 1067 EP 1075 PG 9 WC Oncology SC Oncology GA NF123 UT WOS:A1994NF12300009 PM 21567021 ER PT J AU BIANCO, C TORTORA, G BASOLO, F FIORE, L FONTANINI, G MERLO, G SALOMON, DS BIANCO, AR CIARDIELLO, F AF BIANCO, C TORTORA, G BASOLO, F FIORE, L FONTANINI, G MERLO, G SALOMON, DS BIANCO, AR CIARDIELLO, F TI EFFECTS OF MUTANT P53 GENES ON TRANSFORMATION OF HUMAN MAMMARY EPITHELIAL-CELLS SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE MAMMARY EPITHELIAL CELLS; ONCOGENES; TRANSFORMATION; P53 ID HUMAN BREAST-CANCER; C-HA-RAS; GROWTH-FACTOR RECEPTOR; TUMOR SUPPRESSOR; ESTROGEN-RECEPTOR; EXPRESSION; MUTATIONS; OVEREXPRESSION; C-ERBB-2; PROTEIN AB MCF-10A cells are a spontaneously immortalized, nontransformed human mammary epithelial cell line that contains two normal p53 alleles and produces a normal p53 protein. We have recently shown that overexpression of several genes that are important for normal mammary gland development and for neoplastic transformation, such as transforming growth factor alpha, c-Ha-rns or c-erbB-2, leads to in vitro transformation of these cells (Ciardiello et al: Mol Carcinogen 6: 43-52, 1992). To investigate the neoplastic potential of mutated forms of the p53 gene on MCF-10A cells, we have constructed two expression vector plasmids containing two p53 mutants that were isolated from human primary breast carcinomas. Overexpression of either mutant p53 gene confers on MCF-10A cells the ability to grow in serum-free medium in monolayer culture and to form colonies in semi-solid medium. Furthermore, to determine whether a mutated p53 gene may cooperate with a point mutated c-Ha-ras and/or the normal c-erbB-2 protooncogenes in the transformation of these cells, we generated clones of MCF-10A cells that overexpress a combination of these gene pruducts. Although these cells were able to grow with a higher cloning efficiency in soft agar, none of the cell lines was tumorigenic when injected subcutaneously into immunodeficient mice. C1 UNIV NAPOLI FEDERICO II,FAC MED & CHIRURG,CATTEDRA ONCOL MED,I-80131 NAPLES,ITALY. UNIV PISA,FAC MED & CHIRURG,INST ANAT PATOL,I-56100 PISA,ITALY. FRIEDRICH MIESCHER INST,CH-4002 BASEL,SWITZERLAND. NCI,LTIB,TUMOR GROWTH FACTOR SECT,BETHESDA,MD 20892. RI Fontanini, Gabriella/O-7636-2015 OI Fontanini, Gabriella/0000-0003-1957-2052 NR 31 TC 6 Z9 6 U1 0 U2 1 PU PROFESSOR D A SPANDIDOS PI ATHENS PA 1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD MAY PY 1994 VL 4 IS 5 BP 1077 EP 1082 PG 6 WC Oncology SC Oncology GA NF123 UT WOS:A1994NF12300010 PM 21567022 ER PT J AU SHRAYER, D KONESS, J KOUTTAB, N BOGAARS, H HEARING, VJ MAIZEL, A WANEBO, HJ AF SHRAYER, D KONESS, J KOUTTAB, N BOGAARS, H HEARING, VJ MAIZEL, A WANEBO, HJ TI ANTITUMOR EFFECTS OF POLYVALENT AND MONOVALENT VACCINES COUPLED WITH INTERLEUKIN-2 IN A METASTATIC MELANOMA MODEL SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE MELANOMA; POLYVALENT ANTIGEN; POLYCLONAL ANTIBODY; INTERLEUKIN-2; IMMUNIZATION ID FORMALINIZED EXTRACELLULAR ANTIGENS; ACTIVE-SPECIFIC IMMUNOTHERAPY; PURIFIED GM2 GANGLIOSIDE; MURINE MELANOMA; B-16 MELANOMA; ANTIBODIES; IMMUNIZATION; MICE; FECA; B700 AB We have previously reported that preimmunization of mice with formalinized extracellular antigens (fECA) derived from melanoma cells, in combination with interleukin 2 (IL-2) treatment and surgical resection, decreased subsequent tumor growth and increased survival of mice in a new model for spontaneous metastasis of melanoma. In this study, we have modified the sequence of tumor growth and therapy to more closely mimic the clinical situation. Mice were challenged subcutaneously in the tail with 5 x 10(5) B16 F10 melanoma cells and, by day 21, all of them had developed localized melanoma tumors. The primary tumor-bearing tails of control and experimental animals were then resected distal to the base of the tail, and therapy of the mice was initiated the following day. Groups of mice received different polyvalent and monovalent murine melanoma vaccines (including native or formalin treated extracellular antigens, intact melanoma cells, or purified B700 antigen), with or without concomitant low doses of IL-2. The results demonstrate that the vaccine therapies elicited significant increases in survival of the mice, accompanied by reductions in the size of lymph nodes and in the number of pulmonary metastases. These effects, particularly with the intact melanoma cell vaccine, could be improved even further with concomitant IL-2 treatment. C1 BROWN UNIV,ROGER WILLIAMS MED CTR,DEPT PATHOL,PROVIDENCE,RI 02908. BROWN UNIV,ROGER WILLIAMS MED CTR,DEPT SURG,PROVIDENCE,RI 02908. NCI,CELL BIOL LAB,BETHESDA,MD 20892. NR 20 TC 9 Z9 9 U1 0 U2 0 PU PROFESSOR D A SPANDIDOS PI ATHENS PA 1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD MAY PY 1994 VL 4 IS 5 BP 1121 EP 1127 PG 7 WC Oncology SC Oncology GA NF123 UT WOS:A1994NF12300017 PM 21567029 ER PT J AU DOUEK, PC GANDJBAKHCHE, A LEON, MB BONNER, RF AF DOUEK, PC GANDJBAKHCHE, A LEON, MB BONNER, RF TI FUNCTIONAL-PROPERTIES OF A PROTOTYPE RHEOLYTIC CATHETER FOR PERCUTANEOUS THROMBECTOMY - IN-VITRO INVESTIGATIONS SO INVESTIGATIVE RADIOLOGY LA English DT Article DE CATHETER AND CATHETERIZATION; INTERVENTIONAL PROCEDURES; ASPIRATION THROMBECTOMY; THROMBOLYSIS; THROMBOSIS; EXPERIMENTAL ID FOGARTY BALLOON CATHETER; ASPIRATION; EMBOLECTOMY; DISSOLUTION; OCCLUSIONS; EXPERIENCE; THERAPY; INVITRO; LIMB AB RATIONALE AND OBJECTIVES. The performance of a rheolytic catheter designed to provide rapid fragmentation and evacuation of debris was evaluated. Specifically, fragmentation and evacuation efficiency was investigated in vitro. METHODS. Fragmentation, aspiration, and recanalization of large thrombotic occlusions (8-cm length, 6-mm inner diameter) composed of clot (n = 11) or collagen gels (n = 20) of different stiffness were performed with different jet pressures at rates optimized by visual observation and were recorded on videotape for subsequent analysis. The size and number of the resulting particles in the evacuated fluid and those remaining in the artificial vessel were determined using filtration and laser light scattering techniques. The rate of fragmentation, mean particulate size, and efficiency of evacuation were evaluated as a function of operating parameters and ''clot stiffness.'' RESULTS. Complete fragmentation of fresh thrombus occurred at 11,000 psi by direct action of the 6 radially disposed jets, which created a trapping vortex from which most of the particles (80%) were evacuated by suction. At lower pressure (5,500 psi), fragmentation efficiency was unchanged for fresh thrombus and softer 5% gels. Ninety-five percent of the thrombus was fragmented in very small particles with a mean diameter of 0.8 +/- 0.4 mu m, while 5% of the mass of the fragmented thrombus was in particles >40 mu m. At 11,000 psi, the maximal rate of advancement associated with complete material fragmentation decreased with stiffness. For very stiff gels or heavily cross-linked old thrombus, complete fragmentation and removal of material was not achieved. CONCLUSION. The high-pressure rheolytic catheter rapidly fragmented and evacuated large thrombi much larger than the catheter diameter-features with potential for treating large thrombi, such as acute pulmonary emboli or deep vein thrombi. However, this rapid forceful disruption may damage vessel walls and invariably creates a broad range of particulate sizes, which makes evacuation of almost all of the particulate material imperative to minimize clinically relevant distal embolization. C1 NIH,NATL CTR RES RESOURCES,BIOMED ENGN & INSTRUMENTAT PROGRAM,BETHESDA,MD 20892. NIH,DIV COMP RES & TECHNOL,PHYS SCI LAB,BETHESDA,MD 20892. WASHINGTON HOSP CTR,DIV CARDIOL,WASHINGTON,DC 20010. RI Bonner, Robert/C-6783-2015 NR 21 TC 20 Z9 21 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0020-9996 J9 INVEST RADIOL JI Invest. Radiol. PD MAY PY 1994 VL 29 IS 5 BP 547 EP 552 DI 10.1097/00004424-199405000-00004 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NQ847 UT WOS:A1994NQ84700004 PM 8077094 ER PT J AU FUJIMOTO, Y HAMPTON, LL SNYDERWINE, EG NAGAO, M SUGIMURA, T ADAMSON, RH THORGEIRSSON, SS AF FUJIMOTO, Y HAMPTON, LL SNYDERWINE, EG NAGAO, M SUGIMURA, T ADAMSON, RH THORGEIRSSON, SS TI P53 GENE MUTATION IN HEPATOCELLULAR-CARCINOMA INDUCED BY 2-AMINO-3-METHYLIMIDAZO[4,5-F]QUINOLINE IN NONHUMAN-PRIMATES SO JAPANESE JOURNAL OF CANCER RESEARCH LA English DT Article DE FOOD MUTAGEN; PCR-SSCP; DNA ADDUCT ID BEEF EXTRACT; HETEROCYCLIC AMINES; BROILED SARDINE; FOOD MUTAGEN; DNA ADDUCTS; CARCINOGENICITY; TUMORS; RATS; POLYMORPHISMS; AFLATOXIN-B1 AB 2-Amino-3-methylimidazo[4,5-f]quinoline (IQ) is one of several heterocyclic amines formed during the cooking of proteinaceous foods. IQ is a patent carcinogen in rodent bioassays and causes a high incidence of hepatocellular carcinomas in nonhuman primates. We examined 20 hepatocellular carcinomas (HCCs) from nonhuman primates for mutations of the p53 gene using polymerase chain reaction-single strand conformational polymorphism analysis. Mutations in the p53 gene were detected in 4 of 20 HCCs (20%) with 3 showing G-to-T transversions and one a G-to-A transition. Three of these mutations were observed in codons 175 and 248 that are known mutational hot spots in human cancers. These data indicate that part of the IQ-induced HCCs in nonhuman primates may involve inactivation of the p53 gene and suggest that IQ and possibly other heterocyclic amines may participate in human carcinogenesis by a similar mechanism. C1 NCI,EXPTL CARCINOGENESIS LAB,BETHESDA,MD 20892. NCI,DIV CANC ETIOL,BETHESDA,MD 20892. NATL CANC CTR,RES INST,CHUO KU,TOKYO 104,JAPAN. NR 28 TC 14 Z9 14 U1 0 U2 0 PU JAPANESE CANCER ASSOCIATION PI TOKYO PA EDITORIAL OFFICE 7TH FLOOR, JOHKOH BLDG 2-23-11, KOISHIKAWA, TOKYO 112, JAPAN SN 0910-5050 J9 JPN J CANCER RES JI Jpn. J. Cancer Res. PD MAY PY 1994 VL 85 IS 5 BP 506 EP 509 PG 4 WC Oncology SC Oncology GA NP417 UT WOS:A1994NP41700010 PM 8014109 ER PT J AU ZANCONATO, S MOROMISATO, DY MOROMISATO, MY WOODS, J BRASEL, JA LEROITH, D ROBERTS, CT COOPER, DM AF ZANCONATO, S MOROMISATO, DY MOROMISATO, MY WOODS, J BRASEL, JA LEROITH, D ROBERTS, CT COOPER, DM TI EFFECT OF TRAINING AND GROWTH-HORMONE SUPPRESSION ON INSULIN-LIKE GROWTH-FACTOR-I MESSENGER-RNA IN YOUNG-RATS SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE LIVER; HINDLIMB MUSCLE; INSULIN-LIKE GROWTH FACTOR I PROTEIN LEVEL ID START SITE USAGE; BINDING-PROTEINS; SOMATOMEDIN-C; MUSCLE GROWTH; LEADER EXONS; EXERCISE; GENE; ADAPTATIONS; EXPRESSION; MYOBLASTS AB The growth hormone (GH)-insulin-like growth factor I (IGF-I) axis plays a role in the adaptation to exercise training, but IGF-I gene expression in response to exercise training and GH suppression has not been studied. Twenty female rats underwent a 4-wk treadmill training program begun in the prepubertal period (day 14 of life). In 10 of the training rats, GH production was suppressed by anti-GH-releasing hormone antibodies (GH suppressed). IGF-I mRNA and protein levels were measured in liver and hindlimb skeletal muscle. GH suppression reduced IGF-I mRNA expression in the liver to a much greater extent than in the muscle. In the GH control rats, training induced significant increases in hepatic exon 1-derived IGF-I mRNA (mean increase 30%; P < 0.05) and muscle exon 2-derived mRNA (mean increase 35%; P < 0.05). In the GH-suppressed rats, only muscle exon 1-derived transcripts were significantly increased by training (55%; P < 0.05) and this was associated with a significant increase in muscle IGF-I protein levels (P < 0.05). We speculate that the ana belie response to training may involve both GH-dependent increases in IGF-I mRNA in the liver and GH-independent increases in the muscle. C1 UNIV CALIF LOS ANGELES,HARBOR MED CTR,DEPT PEDIAT,DIV RESP & CRIT CARE,TORRANCE,CA 90509. UNIV CALIF LOS ANGELES,HARBOR MED CTR,DEPT PEDIAT,DIV ENDOCRINOL,TORRANCE,CA 90509. NIDDKD,DIABET BRANCH,MOLEC & CELLULAR PHYSIOL SECT,BETHESDA,MD 20892. FU NCRR NIH HHS [RR-00425]; NHLBI NIH HHS [HL-11907]; NICHD NIH HHS [HD-26939] NR 31 TC 58 Z9 59 U1 0 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD MAY PY 1994 VL 76 IS 5 BP 2204 EP 2209 PG 6 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA NL970 UT WOS:A1994NL97000054 PM 8063688 ER PT J AU MAIER, WE KODAVANTI, PRS HARRY, GJ TILSON, HA AF MAIER, WE KODAVANTI, PRS HARRY, GJ TILSON, HA TI SENSITIVITY OF ADENOSINE TRIPHOSPHATASES IN DIFFERENT BRAIN-REGIONS TO POLYCHLORINATED BIPHENYL CONGENERS SO JOURNAL OF APPLIED TOXICOLOGY LA English DT Article DE POLYCHLORINATED BIPHENYLS; ADENOSINE TRIPHOSPHATASES; MITOCHONDRIA; BRAIN ID RAT-LIVER MITOCHONDRIA; NOREPINEPHRINE CONCENTRATIONS; PCBS; SYNAPTOSOMES; MECHANISM; EXPOSURE; DOPAMINE; MONKEYS; ATPASE; CELLS AB Polychlorinated biphenyl (PCBs) mixtures contain a number of different congeners, some of which have been proposed to be neuroactive. Recent studies have suggested that ortho-substituted PCBs may be neuroactive, while 'dioxin-like' non-ortho-substituted congeners are not. This study compared the in vitro effects of a putative neuroactive ortho-biphenyl (2,2'-dichlorobiphenyl; DCBP) with that of a putative non-neuroactive congener lacking ortho-chlorine substitutions (3,3',4,4',5-pentachlorobiphenyl; PCBP) on Mg2+-ATPase activity in mitochondrial and synaptosomal preparations from striatum, hypothalamus, cerebellum and hippocampus. In these studies, DCBP significantly inhibited oligomycin-sensitive (OS) Mg2+-ATPase activity in all four brain regions in a concentration-dependent manner; PCBP, on the other hand, had no effect on OS Mg2+-ATPase activity in any brain region examined at concentrations up to 100 mu M. The striatum, a dopamine-rich region, was not preferentially sensitive to the effects of DCBP. Furthermore, DCBP did not inhibit synaptosomal Na+/ K+-ATPase activity, suggesting a specificity of action on OS Mg2+-ATPase. These data support previous structure-activity relationships, suggesting that ortho-substituted PCB congeners are neuroactive while non-ortho-substituted congeners are not. Disruption of mitochondrial oxidative energy production may play a role in the neuroactivity of ortho-chlorinated PCBs. C1 US EPA,HLTH EFFECTS RES LAB,DIV NEUROTOXICOL,CELLULAR & MOLEC TOXICOL BRANCH,RES TRIANGLE PK,NC 27711. UNIV N CAROLINA,CURRICULUM TOXICOL,CHAPEL HILL,NC 27599. NIEHS,DIV INTRAMURAL RES,RES TRIANGLE PK,NC 27709. FU NIEHS NIH HHS [NIEHS T32 ES07126] NR 31 TC 37 Z9 37 U1 3 U2 3 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0260-437X J9 J APPL TOXICOL JI J. Appl. Toxicol. PD MAY-JUN PY 1994 VL 14 IS 3 BP 225 EP 229 DI 10.1002/jat.2550140313 PG 5 WC Toxicology SC Toxicology GA NQ006 UT WOS:A1994NQ00600013 PM 8083484 ER PT J AU JENSEN, CG BROWN, S PEDERSEN, S AF JENSEN, CG BROWN, S PEDERSEN, S TI EFFECT OF 4.5S RNA DEPLETION ON ESCHERICHIA-COLI PROTEIN-SYNTHESIS AND SECRETION SO JOURNAL OF BACTERIOLOGY LA English DT Article ID RECOGNITION; RIBONUCLEOPROTEIN; TRANSLATION; INVIVO; GENE AB We examined the synthesis of individual proteins following depletion of 4.5S RNA by using a strain deficient in the induction of heat shock proteins. We found that initially the synthesis of all proteins was equally affected, and the peptide elongation rate was reduced by approximately 10%. For up to 1 generation time after the onset of inhibition of total protein synthesis, the processing of secreted proteins was unaffected. After further depletion of 4.5S RNA, accumulation of precursors of secreted proteins was observed under some growth conditions. C1 UNIV COPENHAGEN,DEPT MOLEC CELL BIOL,DK-1353 COPENHAGEN,DENMARK. NCI,FREDERICK CANC RES & DEV CTR,ABL,BASIC RES PROGRAM,FREDERICK,MD 21702. RI Pedersen, Steen/M-5188-2014; OI Pedersen, Steen/0000-0002-4145-942X; Brown, Stanley/0000-0002-8453-8144 FU NCI NIH HHS [N01-CO-74101] NR 17 TC 20 Z9 21 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD MAY PY 1994 VL 176 IS 9 BP 2502 EP 2506 PG 5 WC Microbiology SC Microbiology GA NJ081 UT WOS:A1994NJ08100004 PM 7513325 ER PT J AU GOVINDARAJ, S EISENSTEIN, E JONES, LH SANDERSLOEHR, J CHISTOSERDOV, AY DAVIDSON, VL EDWARDS, SL AF GOVINDARAJ, S EISENSTEIN, E JONES, LH SANDERSLOEHR, J CHISTOSERDOV, AY DAVIDSON, VL EDWARDS, SL TI AROMATIC AMINE DEHYDROGENASE, A 2ND TRYPTOPHAN TRYPTOPHYLQUINONE ENZYME SO JOURNAL OF BACTERIOLOGY LA English DT Article ID QUINOPROTEIN METHYLAMINE DEHYDROGENASE; METHYLOBACTERIUM-EXTORQUENS AM1; RESONANCE RAMAN-SPECTROSCOPY; PARACOCCUS-DENITRIFICANS; PROSTHETIC GROUP; PSEUDOMONAS AM1; COFACTOR; SUBUNIT; EQUILIBRIUM; RESOLUTION AB Aromatic amine dehydrogenase (AADH) catalyzes the oxidative deamination of aromatic amines including tyramine and dopamine. AADH is structurally similar to methylamine dehydrogenase (MADH) and possesses the same tryptophan tryptophylquinone (TTQ) prosthetic group. AADH exhibits an alpha(2) beta(2) structure with subunit molecular weights of 39,000 and 18,000 and with a quinone covalently attached to each beta subunit. Neither subunit cross-reacted immunologically with antibodies to the corresponding subunits of MADH, and the N-terminal amino acid sequence of the beta subunit of AADH exhibited no homology with the highly conserved beta subunits of MADH. The absorption spectra for the oxidized, semiquinone, and reduced forms of AADH have been characterized, and extinction coefficients for the absorption maxima of each redox form have been determined. These spectra are very similar to those for MADH, indicating the likelihood of a TTQ cofactor. This was verified by the near identity of the vibrational frequencies and intensities in the resonance Raman spectra for the oxidized forms of AADH and MADH. A stable semiquinone of AADH could be observed during a reductive titration with dithionite, whereas titration with tyramine proceeded directly from the oxidized to the reduced form. AADH was very stable against denaturation by heat and exposure to guanidine. The individual subunits could be separated by gel filtration after incubation in guanidine hydrochloride, and partial reconstitution of activity was observed on recombination of the subunits. Steady-state kinetic analysis of AADH yielded a V-max of 17 mu mol/min/mg and K-m for tyramine of 5.4 mu M. Substrate inhibition by tyramine was observed. AADH was irreversibly inhibited by hydrazine, phenylhydrazine, hydroxylamine, semicarbazide, and aminoguanidine. Isonicotinic acid hydrazide (isoniazid) and isonicotinic acid 2-isopropyl hydrazide (iproniazid) were reversible noncompetitive inhibitors of AADH and exhibited K-i values of 8 and 186 mu M, respectively. The similarities and differences between AADH and other amine oxidizing enzymes are also discussed. C1 CTR ADV RES BIOTECHNOL,ROCKVILLE,MD 20850. UNIV MARYLAND,DEPT CHEM,BALTIMORE,MD 21228. UNIV MARYLAND,DEPT BIOCHEM,BALTIMORE,MD 21228. UNIV MISSISSIPPI,MED CTR,DEPT BIOCHEM,JACKSON,MS 39216. OREGON GRAD INST SCI & TECHNOL,DEPT CHEM BIOCHEM & MOLEC BIOL,PORTLAND,OR 97291. CALTECH,WM KECK LABS,PASADENA,CA 91125. NIAMSD,STRUCT BIOL LAB,BETHESDA,MD 20892. FU NIGMS NIH HHS [GM34468, GM41574] NR 39 TC 60 Z9 63 U1 0 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD MAY PY 1994 VL 176 IS 10 BP 2922 EP 2929 PG 8 WC Microbiology SC Microbiology GA NL838 UT WOS:A1994NL83800020 PM 8188594 ER PT J AU SAMUELS, DS MARCONI, RT HUANG, WM GARON, CF AF SAMUELS, DS MARCONI, RT HUANG, WM GARON, CF TI GYRB MUTATIONS IN COUMERMYCIN A(1)-RESISTANT BORRELIA-BURGDORFERI SO JOURNAL OF BACTERIOLOGY LA English DT Note ID LYME-DISEASE AGENT; N-TERMINAL FRAGMENT; GYRASE-B-PROTEIN; DNA GYRASE; LINEAR CHROMOSOME; ESCHERICHIA-COLI; COUMARIN DRUGS; NOVOBIOCIN; TOPOISOMERASES; RESISTANCE AB We have isolated and characterized mutants of Borrelia burgdorferi that are resistant to the antibiotic coumermycinn A(1) which targets the B subunit of DNA gyrase. Mutants had either 100- or 300-fold higher resistance to coumermycin A(1) than wild-type B. burgdorferi. In each case, a single point mutation in the gyrB gene converted Arg-133 to Gly or Ile. Mutations in the homologous Arg residue of Escherichia coli DNA gyrase are also associated with resistance to coumarin antimicrobial agents. C1 UNIV UTAH,MED CTR,DEPT CELLULAR VIRAL & MOLEC BIOL,SALT LAKE CITY,UT 84132. RP SAMUELS, DS (reprint author), NIAID,ROCKY MT LABS,VECTORS & PATHOGENS LAB,HAMILTON,MT 59840, USA. RI Samuels, D Scott/B-7549-2012 OI Samuels, D Scott/0000-0001-8352-7593 FU NIGMS NIH HHS [GM21960] NR 41 TC 53 Z9 54 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD MAY PY 1994 VL 176 IS 10 BP 3072 EP 3075 PG 4 WC Microbiology SC Microbiology GA NL838 UT WOS:A1994NL83800038 PM 8188609 ER PT J AU OSHIRO, S NAKAMURA, Y ISHIGE, R HORI, M NAKAJIMA, H GAHL, WA AF OSHIRO, S NAKAMURA, Y ISHIGE, R HORI, M NAKAJIMA, H GAHL, WA TI REDUCTION SITE OF TRANSFERRIN-DEPENDENT AND TRANSFERRIN-INDEPENDENT IRON IN CULTURED HUMAN FIBROBLASTS SO JOURNAL OF BIOCHEMISTRY LA English DT Article DE RECEPTOR-MEDIATED ENDOCYTOSIS; TRANSFERRIN; TRANSFERRIN RECEPTOR; TRANSFERRIN-DEPENDENT IRON UPTAKE; TRANSFERRIN-INDEPENDENT IRON UPTAKE ID PLASMA-MEMBRANE; DIFERRIC TRANSFERRIN; MECHANISM; RETICULOCYTES; HEPATOCYTES; SYSTEM; REDOX; CELLS AB Mammalian cells internalize iron as diferric transferrin (Fe(2)Tf) iron via receptor-mediated endocytosis (RME) and a redox mechanism under physiological condition and as an iron salt through the Tf-independent iron uptake (Tf-IU) system under morbid conditions. We have previously shown that Tf iron is reduced at the Tf molecule through a redox system on the plasma membrane prior to uptake [Oshiro, S., Nakajima, H., Markello, T., Krasnewich, D., Bernadini, I., and Gahl, W. (1993) J. Biol. Chem. 268, 21586-21591]. In the present study, the reduction site for Tf iron uptake via RME and for Tf-independent iron uptake via the Tf-IU system were examined using specific iron sources and well-characterized ferric or ferrous iron chelators in cultured human fibroblasts. At 4 degrees C for 1 h, although [Fe-55](2)Tf was not internalized into the cells, Fe-55 from [55Fe](2)Tf-Sepharose was taken up. However, under the same conditions, EDTA or dipyridyl removed the radioactive iron as a ferric or ferrous iron-chelator complex from [55Fe](2)Tf bound to the Tf receptor on the cell surface. Moreover, after Fe-55-citrate was loaded into the cells at 4 degrees C for 1 h, Fe-55 was removed from the cell surface by dipyridyl just as observed for [Fe-55](2)Tf-Sepharose. In inhibition experiments, ferric citrate showed a dose-dependent inhibition of the iron uptake of both Tf iron and Tf-independent iron. Conversely, Fe(2)Tf dose-dependently inhibited the uptake of Fe-55-citrate. These results suggest that Tf-independent iron as well as Fe(2)Tf is reduced at the plasma membrane prior to uptake, as the ferric reduction of Fe(2)Tf taken up by the redox mechanism occurs at the same site. C1 DOKKYO UNIV,SCH MED,DEPT INTERNAL MED 3,MIBU,TOCHIGI 32102,JAPAN. SHOWA COLL PHARMACEUT SCI,DEPT BIOCHEM,MACHIDA,TOKYO 194,JAPAN. NICHHD,BETHESDA,MD 20892. RP OSHIRO, S (reprint author), TOKYO MED & DENT UNIV,MED RES INST,DEPT BIOCHEM GENET,BUNKYO KU,1-5-45 YUSHIMA,TOKYO 113,JAPAN. NR 17 TC 13 Z9 13 U1 0 U2 0 PU JAPANESE BIOCHEMICAL SOC PI TOKYO PA ISHIKAWA BLDG-3F 25-16 HONGO-5-CHOME, TOKYO TOKYO 113, JAPAN SN 0021-924X J9 J BIOCHEM-TOKYO JI J. Biochem. (Tokyo) PD MAY PY 1994 VL 115 IS 5 BP 849 EP 852 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NL051 UT WOS:A1994NL05100010 PM 7961596 ER PT J AU HOLDEN, JP GROOD, ES KORVICK, DL CUMMINGS, JF BUTLER, DL BYLSKIAUSTROW, DI AF HOLDEN, JP GROOD, ES KORVICK, DL CUMMINGS, JF BUTLER, DL BYLSKIAUSTROW, DI TI IN-VIVO FORCES IN THE ANTERIOR CRUCIATE LIGAMENT - DIRECT MEASUREMENTS DURING WALKING AND TROTTING IN A QUADRUPED SO JOURNAL OF BIOMECHANICS LA English DT Article ID ACHILLES-TENDON FORCES; STRAIN; INVIVO; INVITRO; JOINT AB In vivo forces in the anterior cruciate ligament (ACL) were measured in three adult goats during quiet standing and during gait (walking or trotting). A modified pressure transducer (MPT) was implanted within the anteromedial band of the ligament to make direct measurements of ACL force. One or two days following implantation, measurements were made of ACL force, knee joint flexion angle, ground reaction forces, and speed of locomotion. MPT calibration was performed in vitro using anteroposterior displacement tests at six flexion angles. The ACL was loaded during quiet standing (30-61 N) and during the stance phase of gait. Peak ACL forces were achieved within the first 40% of stance, with magnitudes ranging from 63 to 124 N during walking and from 102 to 150 N during trotting. The average ACL force during the stance phase ranged from 34 to 68 N while walking and from 46 to 69 N while trotting. The partial correlations between peak ACL force and speed, and between average ACL force and speed, were both statistically different from zero (p < 0.01). ACL forces dropped to zero during the swing phase in all trials. ACL forces were less than 15 N throughout swing in two of the animals, both of which did not extend their knees during gait beyond 20 degrees from full extension. In the animal which did show knee extension beyond 40 degrees (20 degrees from full extension), ACL loading occurred during late swing. The magnitude of the peak ACL force during late swing was significantly correlated with the extent of knee extension in this animal. C1 UNIV CINCINNATI,NOYES GIANNESTRAS BIOMECH LABS,CINCINNATI,OH. RP HOLDEN, JP (reprint author), NIAMSD,BIOMECH LAB,BLDG 10,ROOM 6S-235,BETHESDA,MD 20892, USA. FU NIAMS NIH HHS [AR39703] NR 26 TC 140 Z9 144 U1 4 U2 16 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0021-9290 J9 J BIOMECH JI J. Biomech. PD MAY PY 1994 VL 27 IS 5 BP 517 EP 526 DI 10.1016/0021-9290(94)90063-9 PG 10 WC Biophysics; Engineering, Biomedical SC Biophysics; Engineering GA NL013 UT WOS:A1994NL01300002 PM 8027088 ER PT J AU GRONENBORN, AM CLORE, GM AF GRONENBORN, AM CLORE, GM TI IDENTIFICATION OF N-TERMINAL HELIX CAPPING BOXES BY MEANS OF C-13 CHEMICAL-SHIFTS SO JOURNAL OF BIOMOLECULAR NMR LA English DT Note DE CAPPING BOX; C-13 CHEMICAL SHIFTS; ALPHA-HELIX STOP SIGNALS ID MAGNETIC-RESONANCE SPECTROSCOPY; PANCREATIC TRYPSIN-INHIBITOR; SECONDARY STRUCTURE; NMR-SPECTROSCOPY; ALPHA-HELICES; ASSIGNMENTS; PROTEINS; H-1; N-15; SUBSTITUTION AB We have examined the C-13(alpha) and C-13(beta) chemical shifts of a number of proteins and found that their values at the N-terminal end of a helix provide a good predictor for the presence of a capping box. A capping box consists of a hydrogen-bonded cycle of four amino acids in which the side chain of the N-cap residue forms a hydrogen bond with the backbone amide of the N3 residue, whose side chain in turn may accept a hydrogen bond from the amide of the N-cap residue. The N-cap residue exhibits characteristic values for its backbone torsion angles, with phi and psi clustering around 94 +/- 15 degrees and 167 +/- 5 degrees, respectively. This is manifested by a 1-2 ppm upheld shift of the C-13(alpha) resonance and a 1-4 ppm downfield shift of the C-13(beta) resonance, relative to their random coil values, and is mainly associated with the unusually large value of psi. The residues following the N-cap residue exhibit downfield shifts of 1-3 ppm for the C-13(alpha) resonances and small upfield shifts for the C-13(beta) ones, typical of an alpha-helix. RP GRONENBORN, AM (reprint author), NIDDKD,CHEM PHYS LAB,BLDG 5,BETHESDA,MD 20892, USA. RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 NR 22 TC 72 Z9 72 U1 0 U2 1 PU ESCOM SCI PUBL BV PI LEIDEN PA PO BOX 214, 2300 AE LEIDEN, NETHERLANDS SN 0925-2738 J9 J BIOMOL NMR JI J. Biomol. NMR PD MAY PY 1994 VL 4 IS 3 BP 455 EP 458 PG 4 WC Biochemistry & Molecular Biology; Spectroscopy SC Biochemistry & Molecular Biology; Spectroscopy GA NK935 UT WOS:A1994NK93500010 PM 8019146 ER PT J AU STOJILKOVIC, SS VUKICEVIC, S LUYTEN, FP AF STOJILKOVIC, SS VUKICEVIC, S LUYTEN, FP TI CALCIUM SIGNALING IN ENDOTHELIN-DERIVED AND PLATELET-DERIVED GROWTH FACTOR-STIMULATED CHONDROCYTES SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article ID RABBIT ARTICULAR CHONDROCYTES; PHOSPHOLIPASE-C-GAMMA; PITUITARY GONADOTROPHS; PROTEOGLYCAN SYNTHESIS; EXTRACELLULAR CALCIUM; MONOLAYER-CULTURE; DNA-SYNTHESIS; CELLS; RECEPTOR; MITOGENESIS AB In bovine articular chondrocytes, endothelin (ET) and platelet-derived growth factor (PDGF) receptors mediate agonist-induced increases in inositol phosphate hydrolysis, cytoplasmic calcium concentration ([Ca2+](i)), and mitogenesis. In most cells, ET stimulated nonoscillatory [Ca2+](i) elevations with dose-dependent increases in both spike and plateau amplitudes. However, about 15% of cells showed oscillatory Ca2+ responses with a constant Frequency and variable shape and duration of spiking. ET-1 and ET-2 were more potent than ET-3 in stimulating [Ca2+](i) responses in inhibiting the specific binding of I-125-ET-1 and I-125-ET-3 and in promoting internalization of the receptor-ligand complex, consistent with actions through endothelin ET(A) receptors. Similar nonoscillatory and oscillatory patterns of Ca2+ responses were observed in PDGF-stimulated cells. In cells showing nonoscillatory Ca2+ responses to ET-1, subsequent stimulation with PDGE was frequently followed by the development of an oscillatory Ca2+ response. Nonoscillatory responses to both agonists were only slightly reduced in Ca2+-deficient medium, but the oscillatory responses were critically dependent on Ca2+ entry. Ca2+ spiking was not altered in the presence of the voltage-sensitive Ca2+ channel blocker, nifedipine; also, depolarization of chondrocytes by high K+ did not induce [Ca2+](i) responses, confirming that voltage-sensitive calcium channels are not expressed in these cells. At high agonist concentrations, ET- but not PDGF-stimulated cells underwent rapid desensitization. Activation of ET(A) and PDGF receptors was associated with differential stimulation of thymidine incorporation; ET-1 induced a low-amplitude bell-shaped dose-response curve; PDGF induced a sustained sigmoidal and dose-dependent rise. These data indicate that two distinct types of Ca2+-mobilizing receptors initiate similar patterns of [Ca2+](i) responses but have different capacities to maintain and reinitiate the Ca2+ signaling, as well as to promote mitogenesis. C1 NIDR,BONE RES BRANCH,BETHESDA,MD. RP STOJILKOVIC, SS (reprint author), NICHHD,ENDOCRINOL & REPROD RES BRANCH,BLDG 49,ROOM 6A-36,BETHESDA,MD 20892, USA. NR 40 TC 29 Z9 29 U1 0 U2 2 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD MAY PY 1994 VL 9 IS 5 BP 705 EP 714 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA NF563 UT WOS:A1994NF56300015 PM 8053400 ER PT J AU REDDY, SV TAKAHASHI, S DALLAS, M WILLIAMS, RE NECKERS, L ROODMAN, GD AF REDDY, SV TAKAHASHI, S DALLAS, M WILLIAMS, RE NECKERS, L ROODMAN, GD TI INTERLEUKIN-6 ANTISENSE DEOXYOLIGONUCLEOTIDES INHIBIT BONE-RESORPTION BY GIANT-CELLS FROM HUMAN GIANT-CELL TUMORS OF BONE SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article ID OSTEOBLASTS; IL-6 AB The effects of antisense constructs to IL-6 on the bone-resorbing capacity of purified giant cells from giant cell tumors of bone were examined to further define the role of IL-6 in human osteoclastic bone resorption. In addition, we wanted to determine the utility of antisense constructs to cytokines produced by osteoclasts as probes to identify the molecular events responsible for the bone-resorptive process. Giant cells were cultured on sperm whale dentin for 24 h in the presence of fluoresceinated antisense or scrambled antisense deoxyoligonucleotides complementary to IL-6 mRNA. The giant cells actively incorporated these oligonucleotides, as evidenced by their intense fluorescence. The number of resorptive lacunae formed and the area of the dentin resorbed were significantly decreased in cultures of giant cells treated with antisense IL-6 constructs compared with control cultures treated with scrambled antisense constructs to IL-6 (60 +/- 13 versus 12 +/- 6 lacunae and 1.2 +/- 0.3 versus 0.26 +/- 0.1 x 10(5) mu m(2)). IL-6 levels in conditioned media from giant cell cultures treated with IL-6 antisense constructs were fourfold lower than those in control media obtained from giant cells treated with scrambled antisense constructs to IL-6. These data confirm the capacity of IL-6 antisense oligomers to block IL-6 production by these cells. These observations show that IL-6 plays an important role in the bone-resorptive process of human osteoclasts and suggest that antisense constructs to cytokines produced by bone cells may be useful for determining the molecular events occurring during bone resorption. C1 UNIV TEXAS,HLTH SCI CTR,DEPT MED HEMATOL,SAN ANTONIO,TX. UNIV TEXAS,HLTH SCI CTR,AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX. NIH,BETHESDA,MD. NR 13 TC 53 Z9 53 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD MAY PY 1994 VL 9 IS 5 BP 753 EP 757 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA NF563 UT WOS:A1994NF56300021 PM 8053406 ER PT J AU NICKEL, W HUBER, LA KAHN, RA KIPPER, N BARTHEL, A FASSHAUER, D SOLING, HD AF NICKEL, W HUBER, LA KAHN, RA KIPPER, N BARTHEL, A FASSHAUER, D SOLING, HD TI ADP-RIBOSYLATION FACTOR AND A 14-KD POLYPEPTIDE ARE ASSOCIATED WITH HEPARAN SULFATE-CARRYING POST-TRANS-GOLGI NETWORK SECRETORY VESICLES IN RAT HEPATOCYTES SO JOURNAL OF CELL BIOLOGY LA English DT Article ID GTP-BINDING PROTEIN; PLASMA-MEMBRANE PROTEINS; YPT1 GENE-PRODUCT; SYNAPTIC VESICLES; BREFELDIN-A; ENDOPLASMIC-RETICULUM; GUANINE-NUCLEOTIDE; COATED VESICLES; CELL-SURFACE; MDCK CELLS AB Constitutive secretory vesicles carrying heparan sulfate proteoglycan (HSPG) were identified in isolated rat hepatocytes by pulse-chase experiments with [S-35]sulfate and purified by velocity-controlled sucrose gradient centrifugation followed by equilibrium density centrifugation in Nycodenz. Using this procedure, the vesicles were separated from plasma membranes, Golgi, trans-Golgi network (TGN), ER, endosomes, lysosomes, transcytotic vesicles, and mitochondria. The diameter of these vesicles was similar to 100-200 nm as determined by electron microscopy. A typical coat structure as described for intra-Golgi transport vesicles or clathrin-coated vesicles could not be seen, and the vesicles were not associated with the coat protein beta-COP. Furthermore, the vesicles appear to represent a low density compartment (1.05-1.06 g/ml). Other constitutively secreted proteins (rat serum albumin, apolipoprotein E, and fibrinogen) could not be detected in purified HSPG-carrying vesicles, but banded in the denser fractions of the Nycodenz gradient. Moreover, during pulse-chase labeling with [S-35]methionine, labeled albumin did not appear in the post-TGN vesicle fraction carrying HSPGs. These findings indicate sorting of HSPGs and albumin into different types of constitutive secretory vesicles in hepatocytes. Two proteins were found to be tightly associated with the membranes of the HSPG carrying vesicles: a member of the ADP ribosylation factor family of small guanine nucleotide-binding proteins and an unknown 14-kD peripheral membrane protein (VAPP14). Concerning the secretory pathway, we conclude from these results that ADP ribosylation factor proteins are not only involved in vesicular transport from the ER via the Golgi to the TGN, but also in vesicular transport from the TGN to the plasma membrane. C1 UNIV GOTTINGEN,ZENTRUM INNERE MED,KLIN BIOCHEM ABT,D-37070 GOTTINGEN,GERMANY. EUROPEAN MOLEC BIOL LAB,CELL BIOL PROGRAMME,D-69012 HEIDELBERG,GERMANY. NCI,BIOL CHEM LAB,BETHESDA,MD 20892. RI Fasshauer, Dirk/B-1563-2013 OI Fasshauer, Dirk/0000-0002-1040-4282 NR 56 TC 38 Z9 38 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD MAY PY 1994 VL 125 IS 4 BP 721 EP 732 DI 10.1083/jcb.125.4.721 PG 12 WC Cell Biology SC Cell Biology GA NL319 UT WOS:A1994NL31900002 PM 8188742 ER PT J AU ROSS, SA AHRENS, RA DE LUCA, LM AF ROSS, SA AHRENS, RA DE LUCA, LM TI RETINOIC ACID ENHANCES ADHESIVENESS, LAMININ AND INTEGRIN BETA-1 SYNTHESIS, AND RETINOIC ACID RECEPTOR EXPRESSION IN F9 TERATOCARCINOMA CELLS SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID EMBRYONAL CARCINOMA-CELLS; TRANSFORMED MOUSE FIBROBLASTS; LECTIN-BINDING; CYCLIC-AMP; NEOPLASTIC TRANSFORMATION; EXTRACELLULAR-MATRIX; FLUOROMETRIC ASSAY; PARIETAL ENDODERM; DIBUTYRYL-CAMP; MESSENGER-RNA AB The teratocarcinoma-derived F9 cells respond to retinoic acid (RA) and RA plus dibutyrylcyclic adenosine monophosphate (dcAMP) by differentiating into endoderm cells, which elaborate a laminin and type IV collagen-rich matrix. We found that the induction of differentiation is accompanied by a small but consistent increase in cell adhesiveness to a variety of substrates, including laminin. Therefore we investigated biochemical mechanisms involved in this phenomenon. Endoglycosidase treatment showed that laminin contains complex and hybrid oligosaccharide structures. RA enhanced general biosynthesis of laminin without a specific increase in galactose incorporation: this sugar was mainly in polylactosamine structures in the A chain of laminin and as terminal galactose alpha 1,3 galactose in the B chain. Laminin receptor analysis showed that RA decreased laminin binding protein-37 (LBP-37) but increased the amount of beta 1 integrin, suggesting the involvement of beta 1 integrin in the attachment process. Northern blot analysis showed increased expression of retinoid receptors within hours of RA exposure. These studies demonstrate that RA increases cell to substrate interactions by increasing the biosynthesis of laminin and beta 1 integrin. These effects are most likely subsequent to the RA-induced biosynthesis of the retinoid receptors. (C) 1994 Wiley-Liss, Inc.** C1 NCI, CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB, DIFFERENTIAT CONTROL SECT, BETHESDA, MD 20892 USA. UNIV MARYLAND, NUTR SCI PROGRAM, COLL PK, MD 20742 USA. NR 52 TC 36 Z9 36 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD MAY PY 1994 VL 159 IS 2 BP 263 EP 273 DI 10.1002/jcp.1041590210 PG 11 WC Cell Biology; Physiology SC Cell Biology; Physiology GA NG715 UT WOS:A1994NG71500009 PM 7512975 ER PT J AU BALLOCK, RT HEYDEMANN, A WAKEFIELD, LM FLANDERS, KC ROBERTS, AB SPORN, MB AF BALLOCK, RT HEYDEMANN, A WAKEFIELD, LM FLANDERS, KC ROBERTS, AB SPORN, MB TI INHIBITION OF THE CHONDROCYTE PHENOTYPE BY RETINOIC ACID INVOLVES UP-REGULATION OF METALLOPROTEASE GENES INDEPENDENT OF TGF-BETA SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID PREMATURE EPIPHYSEAL CLOSURE; RAT CARTILAGE PROTEOGLYCAN; EPIDERMAL GROWTH-FACTOR; C-FOS; DIFFERENTIAL PATTERN; BINDING-PROTEINS; TRANSCRIPTION; EXPRESSION; COLLAGEN; RECEPTORS AB Retinoic acid has been identified as a key morphogen governing pattern formation in the developing cartilaginous skeleton. Retinoids have also been implicated in the premature closure of the cartilage growth plate following vitamin A intoxication or administration of retinoids for dermatologic conditions. Previous studies of the mechanism of action of retinoids in non-chondrogenic cells have concluded that retinoic acid is a negative regulater of AP-1 responsive metalloprotease genes. We show that inhibition of expression of the cartilage phenotype by retinoic acid in epiphyseal chondrocytes is associated with positive regulation of AP-1 responsive metalloprotease genes, as well as induction of gene expression for the two components of the transcription factor AP-1, c-fos and c-jun. Despite the similar effects of TGF-beta 1 on expression of cartilage matrix proteins and metalloproteases in this culture system, no appreciable changes in the expression of TGF-beta isoforms were evident in response to retinoic acid treatment. The present investigation demonstrates that regulation of AP-1 responsive genes by retinoic acid can be either positive or negative, depending on the target cell type, and illuminates new mechanisms by which retinoic acid and other retinoids may exert control during development and growth of the limb. (C) 1994 Wiley-Liss, Inc.** RP BALLOCK, RT (reprint author), NCI,CHEMOPREVENT LAB,BLDG 41,ROOM C629,BETHESDA,MD 20892, USA. NR 40 TC 39 Z9 39 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD MAY PY 1994 VL 159 IS 2 BP 340 EP 346 DI 10.1002/jcp.1041590217 PG 7 WC Cell Biology; Physiology SC Cell Biology; Physiology GA NG715 UT WOS:A1994NG71500016 PM 8163572 ER PT J AU KUTTY, RK NAGINENI, CN KUTTY, G HOOKS, JJ CHADER, GJ WIGGERT, B AF KUTTY, RK NAGINENI, CN KUTTY, G HOOKS, JJ CHADER, GJ WIGGERT, B TI INCREASED EXPRESSION OF HEME OXYGENASE-1 IN HUMAN RETINAL-PIGMENT EPITHELIAL-CELLS BY TRANSFORMING GROWTH-FACTOR-BETA SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID MESSENGER-RNA; BILIVERDIN REDUCTASE; RAPID INDUCTION; RAT-LIVER; PURIFICATION; PROTEIN; CDNA; FACTOR-BETA-1; STRESS; DNA AB Antibodies specific for heme oxygenase-1 (HO-1) were produced in rabbits, using the multiple antigen peptide (MAP) technique, and were employed to investigate the ability of transforming growth factor-beta 1 (TGF-beta 1) to induce the HO-1 protein in cultured human retinal pigment epithelial (RPE) cells. Western blot analyses showed that the cytokine induced HO-1 in these cells in a time- and dose-dependent manner. TGF-beta 1 also increased the mRNA for HO-1 in treated cells prior to the increase in HO-1 protein. The induction was effectively blocked by a neutralizing antibody preparation against TGF-beta 1. When tested under similar conditions, other growth factors such as basic fibroblast growth factor-I, platelet-derived growth factor, insulin-like growth factor, transforming growth factor-beta, and epidermal growth factor did not show appreciable induction of HO-1. Lipopolysaccharide, tumor necrosis factor-alpha, and interferon-gamma were also not inducers, although TGF-beta 2 effectively induced HO-1. Heavy metal ions and thiol reagents were also highly potent inducers of HO-1 in human RPE cells. The induction of HO-1 by TGF-beta 1 was also observed in bovine choroid fibroblasts, but not in HELA, HEL or bovine corneal fibroblasts. Our results demonstrate for the first time that HO-1 can be induced by an important cytokine, TGF-beta 1, causing an increase in the expression of both HO-1 message and protein in specific neuroepithelial and fibroblast cells. (C) 1994 Wiley-Liss, Inc.** C1 NEI,IMMUNOL LAB,BETHESDA,MD 20892. RP KUTTY, RK (reprint author), NEI,RETINAL CELL & MOLEC BIOL LAB,BETHESDA,MD 20892, USA. NR 45 TC 91 Z9 92 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD MAY PY 1994 VL 159 IS 2 BP 371 EP 378 PG 8 WC Cell Biology; Physiology SC Cell Biology; Physiology GA NG715 UT WOS:A1994NG71500020 PM 8163576 ER PT J AU TURKHEIMER, F MORESCO, RM LUCIGNANI, G SOKOLOFF, L FAZIO, F SCHMIDT, K AF TURKHEIMER, F MORESCO, RM LUCIGNANI, G SOKOLOFF, L FAZIO, F SCHMIDT, K TI THE USE OF SPECTRAL-ANALYSIS TO DETERMINE REGIONAL CEREBRAL GLUCOSE-UTILIZATION WITH POSITRON EMISSION TOMOGRAPHY AND [F-18] FLUORODEOXYGLUCOSE - THEORY, IMPLEMENTATION, AND OPTIMIZATION PROCEDURES SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE TRACER KINETICS ID BRAIN TRANSFER CONSTANTS; TIME UPTAKE DATA; METABOLIC-RATE; F-18 FLUORODEOXYGLUCOSE; GRAPHICAL EVALUATION; DEOXYGLUCOSE; HUMANS; MODELS AB A method for kinetic analysis of dynamic positron emission tomography (PET) data by linear programming that allows identification of the components of a measured PET signal without predefining a compartmental model has recently been proposed by Cunningham and co-workers. The method identifies a small subset of functions from a large input set of feasible functions that best fits the time course of total radioactivity measured by PET. To investigate in detail the properties of this technique, we applied it to PET studies with [F-18]fluorodeoxyglucose, a tracer with well-characterized kinetic properties. We examined dynamically acquired data over various time intervals in many brain regions and found that the number of components identified by the method is stable and consistent with the presence of kinetic heterogeneity in every region. We optimized the method for determination of regional rates of glucose utilization; calculated rates were found to be somewhat dependent upon the treatment of noise in the measured tissue data and upon the time interval in which the data were collected. The application of a numerical filter to remove noise in the data resulted in values for regional cerebral glucose utilization that were stable with time and consistent with rates determined by the other established techniques. Based on the results of the current study, we expect that the spectral analysis technique will prove to be a highly flexible tool for kinetic analysis of other tracer compounds; it is capable of producing low-variance, time-stable estimates of physiological parameters when optimized for time interval of application, input spectrum of components, and processing of noise in the data. C1 UNIV MILAN,INST H SAN RAFFAELE,CNR,IST NEUROSCI & BIOIMMAGINI,DEPT NUCL MED,MILAN,ITALY. US PHS,NIMH,CEREBRAL METAB LAB,BETHESDA,MD. RI Lucignani, Giovanni/C-6773-2008; Turkheimer, Federico/B-9485-2012 OI Turkheimer, Federico/0000-0002-3766-3815 FU Medical Research Council [MC_U120085814] NR 26 TC 52 Z9 52 U1 0 U2 3 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD MAY PY 1994 VL 14 IS 3 BP 406 EP 422 PG 17 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA NG209 UT WOS:A1994NG20900006 PM 8163583 ER PT J AU HORVATH, I SANDOR, NT RUTTNER, Z MCLAUGHLIN, AC AF HORVATH, I SANDOR, NT RUTTNER, Z MCLAUGHLIN, AC TI ROLE OF NITRIC-OXIDE IN REGULATING CEREBROCORTICAL OXYGEN-CONSUMPTION AND BLOOD-FLOW DURING HYPERCAPNIA SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE CEREBRAL OXYGEN CONSUMPTION; CEREBRAL BLOOD FLOW; HYPERCAPNIA; NITRIC OXIDE; L-NAME ID ARGININE METHYL-ESTER; LONG EVANS RATS; ANESTHETIZED RATS; INHIBITION; BRAIN; STIMULATION; HYPERCARBIA; METABOLISM; INCREASES; INVITRO AB The effect of the nitric oxide (NO) synthase inhibitor N-omega-nitro-L-arginine methyl ester (L-NAME) on the response of cerebrocortical oxygen consumption (CMRO(2)) and blood flow (CBF) to two levels of hypercapnia (P(a)co(2) similar to 60 mm Hg and P(a)co2 similar to 90 mm Hg) was investigated in ketamine-anesthetized rats. CBF was calculated using the Kety-Schmidt approach and CMRO(2) was calculated from the product of CBF and the arteriovenous (superior sagittal sinus) difference for oxygen. L-NAME treatment did not have a significant effect on either CMRO(2) or CBF under normocapnic conditions but inhibited the hypercapnic increase of CMRO(2) and the hypercapnic increase in CBF. These results suggest that NO plays a role in the response of CMRO(2) and CBF during hypercapnia and are consistent with the suggestion that at least part of the increase in CBF observed during hypercapnia is coupled to an increase in CMRO(2). C1 NIAAA,ROCKVILLE,MD 20852. SEMMELWEIS UNIV MED,INST PHYSIOL 2,H-1085 BUDAPEST,HUNGARY. HUNGARIAN ACAD SCI,INST EXPTL MED,BUDAPEST,HUNGARY. NR 47 TC 42 Z9 42 U1 1 U2 3 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD MAY PY 1994 VL 14 IS 3 BP 503 EP 509 PG 7 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA NG209 UT WOS:A1994NG20900016 PM 8163593 ER PT J AU FRIEDMAN, TC GARCIABORREGUERO, D HARDWICK, D AKUETE, CN STAMBUK, MK DORN, LD STARKMAN, MN LOH, YP CHROUSOS, GP AF FRIEDMAN, TC GARCIABORREGUERO, D HARDWICK, D AKUETE, CN STAMBUK, MK DORN, LD STARKMAN, MN LOH, YP CHROUSOS, GP TI DIURNAL RHYTHM OF PLASMA DELTA-SLEEP-INDUCING PEPTIDE IN HUMANS - EVIDENCE FOR POSITIVE CORRELATION WITH BODY-TEMPERATURE AND NEGATIVE CORRELATION WITH RAPID EYE-MOVEMENT AND SLOW-WAVE SLEEP SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID DSIP-LIKE MATERIAL; INTRACEREBROVENTRICULAR INJECTION; RATS; RADIOIMMUNOASSAY; IMMUNOREACTIVITY; CORTISOL; BLOOD; CELLS; CSF AB Since delta-sleep-inducing peptide (DSIP) was isolated in 1977, numerous reports have suggested that this nonapeptide stimulates asleep [slow wave sleep (SWS)]. Although DSIP-like immunoreactivity (DSIP-LI) has been found in the serum of many animals and man, its diurnal rhythm and relation to sleep stages have not been well defined. We hypothesized that circulating levels of this putative sleep hormone would be highest at night and would probably be elevated before or during episodes of SWS. We, therefore, measured plasma DSIP-LI levels every 30 min for 24 h in 12 normal volunteers in whom we obtained simultaneous polygraphic recordings. We found a distinct diurnal rhythm for plasma DSIP-LI levels, with the maximum at 1500 and the minimum at 0100 h. DSIP-LI levels were substantially lower in rapid eye movement sleep (P < 0.005) and somewhat lower in SWS (P < 0.05) compared to awake values. DSIP-LI levels did not rise before, during, or after a significant percentage of episodes of SWS. We found, however, that the diurnal rhythm of DSIP-LI closely followed that of body temperature with a high degree of correlation (r(2) = 0.66; P < 0.0001). We conclude that endogenous elevations of circulating DSIP may be associated with suppression of slow wave and rapid eye movement sleep, and that the circadian rhythm of this peptide is coupled directly or indirectly to that of body temperature. C1 NICHHD, DEV ENDOCRINOL BRANCH, BETHESDA, MD 20892 USA. NIMH, CLIN NEUROENDOCRINOL BRANCH, BETHESDA, MD 20892 USA. NIMH, CLIN PSYCHOBIOL BRANCH, BETHESDA, MD 20892 USA. UNIV MICHIGAN, MED CTR, DEPT PSYCHIAT, ANN ARBOR, MI 48109 USA. RP FRIEDMAN, TC (reprint author), NICHHD, DEV NEUROBIOL LAB, BLDG 10, ROOM 10N262, 9000 ROCKVILLE PIKE, BETHESDA, MD 20892 USA. NR 36 TC 6 Z9 7 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAY PY 1994 VL 78 IS 5 BP 1085 EP 1089 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA NK241 UT WOS:A1994NK24100018 PM 8175965 ER PT J AU WERTHEIMER, E LITVIN, Y EBSTEIN, RP BENNET, ER BARBETTI, F ACCILI, D TAYLOR, SI AF WERTHEIMER, E LITVIN, Y EBSTEIN, RP BENNET, ER BARBETTI, F ACCILI, D TAYLOR, SI TI DELETION OF EXON-3 OF THE INSULIN-RECEPTOR GENE IN A KINDRED WITH A FAMILIAL FORM OF INSULIN-RESISTANCE SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID TYROSINE KINASE DOMAIN; DEPENDENT DIABETES-MELLITUS; HUMAN GLUCOKINASE GENE; NONSENSE MUTATION; MESSENGER-RNA; DECREASED LEVELS; MUTANT ALLELES; POLYMORPHISMS; SUBSTITUTION; PATIENT AB Molecular scanning techniques, such as denaturing gradient gel electrophoresis (DGGE), greatly facilitate screening candidate genes for mutations. We have used DGGE to screen for mutations in the insulin receptor gene in a family in which four of five daughters were affected by type A insulin resistance in association with acanthosis nigricans and hyperandrogenism. DGGE did not detect mutations in any of the 22 exons of the insulin receptor gene. Nevertheless, Southern blot analysis suggested that there was a deletion of exon 3 in the other paternal allele of the insulin receptor gene. Analysis of the father's cDNA confirmed that exon 3 was deleted from mRNA molecules derived from one of his two alleles of the insulin receptor gene. Furthermore, the father was found to be hemizygous for a polymorphic sequence (GAC(Asp) at codon 234) in exon 3 that was not inherited by any of the five daughters. Instead, all five daughters inherited the paternal allele with the deletion mutation. We did not detect mutations in the mother's insulin receptor gene. Furthermore, the clinical syndrome did not segregate with either of the mother's two alleles of the insulin receptor gene. Although the youngest daughter inherited the mutant allele from her father, she was not clinically affected. The explanation for the incomplete penetrance is not known. These results emphasize the importance of specifically searching for deletion mutations when screening candidate genes for mutations. Furthermore, the existence of apparently asymptomatic carriers of mutations in the insulin receptor gene, such as the father in the present study, suggests that the prevalence of mutations in the insulin receptor gene may be higher than would be predicted on the basis of the observed prevalence of patients with extreme insulin resistance. C1 NIDDKD, DIABET BRANCH, BETHESDA, MD 20892 USA. PROGININ CLIN, JERUSALEM, ISRAEL. SARAH HERZOG HOSP, GERIATR RES LAB, JERUSALEM, ISRAEL. OI Ebstein, Richard/0000-0002-3626-541X NR 34 TC 12 Z9 12 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAY PY 1994 VL 78 IS 5 BP 1153 EP 1158 DI 10.1210/jc.78.5.1153 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA NK241 UT WOS:A1994NK24100029 PM 8175972 ER PT J AU BERMAS, BL PETRI, M GOLDMAN, D MITTLEMAN, B MILLER, MW STOCKS, NI VIA, CS SHEARER, GM AF BERMAS, BL PETRI, M GOLDMAN, D MITTLEMAN, B MILLER, MW STOCKS, NI VIA, CS SHEARER, GM TI T-HELPER CELL DYSFUNCTION IN SYSTEMIC LUPUS-ERYTHEMATOSUS (SLE) - RELATION TO DISEASE-ACTIVITY SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Article DE INTERLEUKIN-2; SYSTEMIC LUPUS ERYTHEMATOSUS; LUPUS ACTIVITY INDEX ID INTERLEUKIN-2; RESTRICTION; ACTIVATION; RESPONSES; DECREASE; PATHWAYS; SUBSETS; CLONES AB Patients with systemic lupus erythematosus (SLE) are known to have defects in both humoral and cellular immunity. The significance of defective T cell-mediated immunity and its relationship to disease activity have not been dearly established. We studied in vitro T helper cell (Th) function in 150 SLE Outpatients and correlated Th function with validated measures of disease activity. Interleukin 2 (IL-2) production by peripheral blood mononuclear cells (PBMC) was measured after stimulation with the recall antigens influenza A virus (FLU) and tetanus toroid (TET), irradiated allogeneic peripheral blood mononuclear cells (ALLO), and phytohemagglutinin (PHA). We observed three patterns of Th response: (1) 76 of 150 (50%) of patients responded to the recall antigens FLU and/or TET, ALLO, and PHA; (2) 62 of 150 (42%) of patients did not respond to recall antigens but responded to ALLO and PHA; and (3) 12 of 150 (8%) of patients did not respond to either recall antigens or ALLO antigens. This diminished T cell function was correlated with higher disease activity as measured by four scales of clinical activity, such that individuals who exhibited more in vitro immune dysfunction Presented with significant increases in their clinical activity indicies. The alterations in T cell function could not be accounted for by medication doses alone. Thus, SLE patients have multiple distinct defects at the level of the Th cell which are associated with clinical measures of disease activity. C1 NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,SCH MED,DEPT MED,DIV MOLEC & CLIN RHEUMATOL,BALTIMORE,MD 21205. UNIV MARYLAND,SCH MED,DIV CLIN IMMUNOL & RHEUMATOL,BALTIMORE,MD 21201. VET ADM MED CTR,RES SERV,BALTIMORE,MD 21201. FU NHLBI NIH HHS [HL 47080-01] NR 29 TC 57 Z9 59 U1 0 U2 1 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0271-9142 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD MAY PY 1994 VL 14 IS 3 BP 169 EP 177 DI 10.1007/BF01533366 PG 9 WC Immunology SC Immunology GA NP532 UT WOS:A1994NP53200003 PM 7929693 ER PT J AU LEI, KJ PAN, CJ SHELLY, LL LIU, JL CHOU, JY AF LEI, KJ PAN, CJ SHELLY, LL LIU, JL CHOU, JY TI IDENTIFICATION OF MUTATIONS IN THE GENE FOR GLUCOSE-6-PHOSPHATASE, THE ENZYME-DEFICIENT IN GLYCOGEN-STORAGE-DISEASE TYPE 1A SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE INBORN ERROR OF METABOLISM; GENETIC MUTATION; ENDOPLASMIC RETICULUM AND/OR RETENTION SIGNAL ID MICROSOMAL GLUCOSE-6-PHOSPHATASE; TRANSMEMBRANE PROTEINS; ENDOPLASMIC-RETICULUM; METHYLATION; RETENTION; SYSTEM AB Glycogen storage disease (GSD) type la is an autosomal recessive inborn error of metabolism caused by a deficiency in microsomal glucose-6-phosphatase (G6Pase), the key enzyme in glucose homeostasis. Southern blot hybridization analysis using a panel of human-hamster hybrids showed that human G6Pase is a single-copy gene located on chromosome 17. To correlate specific defects with clinical manifestations of this disorder, we identified mutations in the G6Pase gene of GSD type 1a patients. In the G6Pase gene of a compound heterozygous patient (LLP), two mutations in exon 2 of one allele and exon 5 of the other allele were identified. The exon 2 mutation converts an arginine at codon 83 to a cysteine (R83C). This mutation, previously identified by us in another GSD type 1a patient, was shown to have no detectable phosphohydrolase activity. The exon 5 mutation in the G6Pase gene of LLP converts a glutamine codon at 347 to a stop (Q347SP). This Q347SP mutation was also detected in all exon 5 subclones (five for each patient) of two homozygous patients, KB and CB, siblings of the same parents. The predicted Q347SP mutant G6Pase is a truncated protein of 346 amino acids, 11 amino acids shorter than the wild type G6Pase of 357 residues. Site-directed mutagenesis and transient expression assays demonstrated that G6Pase-Q347SP was devoid of G6Pase activity. G6Pase is an endoplasmic reticulum (ER) membrane-associated protein containing an ER retention signal, two lysines (KK), located at residues 354 and 355. We showed that the G6Pase-K355SP mutant containing a lysine-355 to stop codon mutation is enzymatically active. Our data demonstrate that the ER protein retention signal in human G6Pase is not essential for activity. However, residues 347-354 may be required for optimal G6Pase catalysis. C1 NICHHD,HUMAN GENET BRANCH,BETHESDA,MD 20892. NR 20 TC 82 Z9 84 U1 1 U2 1 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 MAY PY 1994 VL 93 IS 5 BP 1994 EP 1999 DI 10.1172/JCI117192 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA NJ960 UT WOS:A1994NJ96000018 PM 8182131 ER PT J AU KARALIS, K MASTORAKOS, G CHROUSOS, GP TOLIS, G AF KARALIS, K MASTORAKOS, G CHROUSOS, GP TOLIS, G TI SOMATOSTATIN ANALOGS SUPPRESS THE INFLAMMATORY REACTION IN-VIVO SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE SOMATOSTATIN; INFLAMMATION; TUMOR NECROSIS FACTOR-ALPHA; SUBSTANCE P; CORTICOTROPIN-RELEASING HORMONE ID TUMOR-NECROSIS-FACTOR; CORTICOTROPIN-RELEASING HORMONE; SUBSTANCE-P; SMS 201-995; NEUROPEPTIDES; SECRETION; RECEPTORS; NEURONS; ADRENOCORTICOTROPIN; LYMPHOCYTES AB Somatostatin (Sms) and its agonist analogues inhibit the secretory activities of endocrine and neural cells. Recent studies have suggested that Sms has significant immunomodulatory properties. In this study, we examined the effects of two Sms octapeptide analogues on the inflammatory reaction in vivo. BIM 23014 (Somatulin) and Sandostatin were administered to male Sprague-Dawley rats subject to carrageenin-induced aseptic inflammation, at doses of 2-10 mu g/rat, given either systemically or locally. Animals were killed 7 h after the induction of the inflammation, and the inflammatory exudates were aspirated and quantitated in terms of volume and leukocyte concentration. Sms analogues, administered via either route, significantly reduced the volume and the leukocyte concentration of the exudate in a time- and dose-dependent fashion. In corroboration of these, immunohistochemical evaluation of the levels of local inflammatory mediators, such as immunoreactive (Ir) TNF-alpha, Irsubstance P, and Ircorticotropin-releasing hormone, was inhibited significantly by Sms analogue treatment. These findings suggest that Sms analogues have significant antiinflammatory effects in vivo, associated with suppression of proinflammatory cytokines and neuropeptides. Furthermore, these data suggest that Sms agonists may be useful in the control of inflammatory reaction. C1 NICHHD,DEV ENDOCRINOL BRANCH,BETHESDA,MD 20892. UNIV ATHENS,HIPPOKRATIO GEN HOSP,SCH MED,DEPT ENDOCRINOL,GR-11527 ATHENS,GREECE. NR 41 TC 142 Z9 146 U1 0 U2 0 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 MAY PY 1994 VL 93 IS 5 BP 2000 EP 2006 DI 10.1172/JCI117193 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA NJ960 UT WOS:A1994NJ96000019 PM 7514191 ER PT J AU MUGLIA, LJ JENKINS, NA GILBERT, DJ COPELAND, NG MAJZOUB, JA AF MUGLIA, LJ JENKINS, NA GILBERT, DJ COPELAND, NG MAJZOUB, JA TI EXPRESSION OF THE MOUSE CORTICOTROPIN-RELEASING HORMONE GENE IN-VIVO AND TARGETED INACTIVATION IN EMBRYONIC STEM-CELLS SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE INTERSPECIFIC BACKCROSS ANALYSIS; CHROMOSOME; EMBRYONIC STEM CELLS; FLUORESCENCE-ACTIVATED CELL SORTING; GENE STRUCTURE ID INSULIN-INDUCED HYPOGLYCEMIA; MESSENGER-RNA; HUMAN-PLACENTA; RAT; SEQUENCE; IMMUNE; PROLIFERATION; DISRUPTION; SECRETION; ARTHRITIS AB Corticotropin-releasing hormone (CRH), one of the primary regulators of the hypothalamic-pituitary-adrenal (HPA) axis, exhibits abnormal regulation in pathologic states such as depression and anorexia nervosa. Analysis of the role of CRH in regulation of the HPA axis would be facilitated by the creation of animal models in which CRH gene structure and function could be manipulated. We have determined the DNA sequence of the mouse CRH gene. Using a highly sensitive reverse transcription-polymerase chain reaction method, we have found expression of CRH mRNA in adrenal, ovary, testis, gut, heart, anterior pituitary, lung, and spleen, in addition to cerebral cortex and hypothalamus. Within the spleen, CRH mRNA is localized specifically to T-lymphocytes. We mapped the chromosomal location of mouse CRH via interspecific mouse backcrosses to chromosome 3, which is not the site of any naturally occurring mutations consistent with CRH deficiency. Because of this, we inactivated a CRH allele in mouse embryonic stem (ES) cells by homologous recombination with a mutant mouse CRH gene lacking the entire coding region of preproCRH. Mice chimeric for each of two ES clones with an inactivated CRH allele are being used to generate animals with complete CRH deficiency. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL,BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. RP MUGLIA, LJ (reprint author), CHILDRENS HOSP,DIV ENDOCRINOL,300 LONGWOOD AVE,BOSTON,MA 02115, USA. FU NCI NIH HHS [N01-CO-74101] NR 60 TC 105 Z9 105 U1 0 U2 1 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 MAY PY 1994 VL 93 IS 5 BP 2066 EP 2072 DI 10.1172/JCI117201 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA NJ960 UT WOS:A1994NJ96000027 PM 8182138 ER PT J AU ROSENKRANZWEISS, P SESSA, WC MILSTIEN, S KAUFMAN, S WATSON, CA POBER, JS AF ROSENKRANZWEISS, P SESSA, WC MILSTIEN, S KAUFMAN, S WATSON, CA POBER, JS TI REGULATION OF NITRIC-OXIDE SYNTHESIS BY PROINFLAMMATORY CYTOKINES IN HUMAN UMBILICAL VEIN ENDOTHELIAL-CELLS - ELEVATIONS IN TETRAHYDROBIOPTERIN LEVELS ENHANCE ENDOTHELIAL NITRIC-OXIDE SYNTHASE SPECIFIC ACTIVITY SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE TUMOR NECROSIS FACTOR; INTERLEUKIN; INTERFERON; GTP CYCLOHYDROLASE I; ENDOTHELIUM ID TUMOR-NECROSIS-FACTOR; VASCULAR SMOOTH-MUSCLE; INTERFERON-GAMMA; RELAXING FACTOR; L-ARGININE; DEPENDENT FORMATION; MURINE FIBROBLASTS; MOLECULAR-CLONING; HUMAN HEPATOCYTES; CYCLOHYDROLASE-I AB We have examined cytokine regulation of nitric oxide synthase (NOS) in human umbilical vein endothelial cells (HUVEC). 24-h treatment with IFN-gamma (200 U/ml) plus TNF (200 U/ml) or IL-1 beta (5 U/ml) increased NOS activity in HUVEC lysates, measured as conversion of [C-14]L-arginine to [C-14]L-citrulline. Essentially, all NOS activity in these cells was calcium dependent and membrane associated. Histamine-induced nitric oxide release, measured by chemiluminescence, was greater in cytokine-treated cells than in control cells. Paradoxically, steady-state mRNA levels of endothelial NOS fell by 94 +/- 2.0% after cytokine treatment. Supplementation of HUVEC lysates with exogenous tetrahydrobiopterin (3 mu M) greatly increased total NOS activity, and under these assay conditions, cytokine treatment decreased maximal NOS activity. IFN-gamma plus TNF or IL-1 beta increased endogenous tetrahydrobiopterin levels and GTP cyclohydrolase I activity, the rate-limiting enzyme of tetrahydrobiopterin synthesis. Intracellular tetrahydrobiopterin levels were higher in freshly isolated HUVEC than in cultured cells, but were still limiting. We conclude that inflammatory cytokines increase NOS activity in cultured human endothelial cells by increasing tetrahydrobiopterin levels in the face of falling total enzyme; similar regulation appears possible in vivo. C1 YALE UNIV,SCH MED,BOYER CTR MOLEC MED,MOLEC CARDIOBIOL PROGRAM,NEW HAVEN,CT 06536. NIMH,NEUROCHEM LAB,BETHESDA,MD 20892. RI Sessa, William/B-6844-2011 FU NHLBI NIH HHS [R37-HL36003]; NIDDK NIH HHS [T32-DK07556] NR 70 TC 313 Z9 316 U1 2 U2 9 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 MAY PY 1994 VL 93 IS 5 BP 2236 EP 2243 DI 10.1172/JCI117221 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA NJ960 UT WOS:A1994NJ96000047 PM 7514193 ER PT J AU FOX, JG DEWHIRST, FE TULLY, JG PASTER, BJ YAN, L TAYLOR, NS COLLINS, MJ GORELICK, PL WARD, JM AF FOX, JG DEWHIRST, FE TULLY, JG PASTER, BJ YAN, L TAYLOR, NS COLLINS, MJ GORELICK, PL WARD, JM TI HELICOBACTER HEPATICUS SP-NOV, A MICROAEROPHILIC BACTERIUM ISOLATED FROM LIVERS AND INTESTINAL MUCOSAL SCRAPINGS FROM MICE SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID CAMPYLOBACTER-JEJUNI; SPIRAL BACTERIUM; GASTRIC-CARCINOMA; PYLORI INFECTION; HOMOSEXUAL MEN; STOMACH; GASTROENTERITIS; PHYLOGENY; ABORTION; MUSTELAE AB A bacterium with a spiral shape and bipolar, single, sheathed flagella was isolated from the livers of mice with active, chronic hepatitis. The bacteria also colonized the cecal and colonic mucosae of mice. The bacterium grew at 37 degrees C under microaerophilic and anaerobic conditions, rapidly hydrolyzed urea, was catalase and oxidase positive, reduced nitrate to nitrite, and was resistant to cephalothin and nalidixic acid but sensitive to metronidazole. On the basis of 16S rRNA gene sequence analysis, the organism was classified as a no,el helicobacter, Helicobacter hepaticus. This new helicobacter, like two other murine Helicobacter species, fi. muridarum and ''H. rappini,'' is an efficient colonizer of the gastrointestinal tract, but in addition, it has the pathogenic potential to elicit persistent hepatitis in mice. C1 FORSYTH DENT CTR,DEPT MOLEC GENET,BOSTON,MA 02115. NIAID,MOLEC MICROBIOL LAB,MYCOPLASMA SECT,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,DYNCORP,PROGRAM RESOURCES INC,FREDERICK,MD 21702. NCI,OFF LAB ANIM SCI,VET & TUMOR PATHOL SECT,FREDERICK,MD 21702. RP FOX, JG (reprint author), MIT,DIV COMPARAT MED,CAMBRIDGE,MA 02139, USA. FU NCRR NIH HHS [RR-01046]; NIDCR NIH HHS [DE-08303, DE-10374] NR 41 TC 372 Z9 394 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD MAY PY 1994 VL 32 IS 5 BP 1238 EP 1245 PG 8 WC Microbiology SC Microbiology GA NG217 UT WOS:A1994NG21700018 PM 8051250 ER PT J AU ASIHENE, PJ KLINE, RL MOSS, MW CARELLA, AV QUINN, TC AF ASIHENE, PJ KLINE, RL MOSS, MW CARELLA, AV QUINN, TC TI EVALUATION OF RAPID TEST FOR DETECTION OF ANTIBODY TO HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 AND TYPE-2 SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Note ID ASSAY AB The Genie HIV-1/HIV-2 rapid assay was compared with an enzyme-linked immunosorbent assay and Western blot (immunoblot) by using 540 serum specimens from four different populations. The Genie HIV-1/HIV-2 assay was easy to perform, required no equipment, provided visual results within 10 min, and demonstrated excellent sensitivity and specificity compared with the Western blot. C1 JOHNS HOPKINS UNIV,SCH MED,DIV INFECT DIS,BALTIMORE,MD 21205. NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. NR 5 TC 11 Z9 11 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD MAY PY 1994 VL 32 IS 5 BP 1341 EP 1342 PG 2 WC Microbiology SC Microbiology GA NG217 UT WOS:A1994NG21700036 PM 8051264 ER PT J AU DERREUMAUX, P ZHANG, GH SCHLICK, T BROOKS, B AF DERREUMAUX, P ZHANG, GH SCHLICK, T BROOKS, B TI A TRUNCATED NEWTON MINIMIZER ADAPTED FOR CHARMM AND BIOMOLECULAR APPLICATIONS SO JOURNAL OF COMPUTATIONAL CHEMISTRY LA English DT Article ID MOLECULAR-DYNAMICS; RESOLUTION; OPTIMIZATION; REFINEMENT; ENERGY AB We report the adaptation of the truncated Newton minimization package TNPACK for CHARMM and biomolecular energy minimization. TNPACK is based on the preconditioned linear conjugate-gradient technique for solving the Newton equations. The structure of the problem-sparsity of the Hessian-is exploited for preconditioning. Experience with the new version of TNPACK is presented on a series of molecular systems of biological and numerical interest: alanine dipeptide (N-methyl-alanyl-acetamide), a dimer of N-methyl-acetamide, deca-alanine, mellitin (26 residues), avian pancreatic polypeptide (36 residues), rubredoxin (52 residues), bovine pancreatic trypsin inhibitor (58 residues), a dimer of insulin (99 residues), and lysozyme (130 residues). Detailed comparisons among the minimization algorithms available in CHARMM, particularly those used for large-scale problems, are presented along with new mathematical developments in TNPACK. The new TNPACK version performs significantly better than ABNR, the most competitive minimizer in CHARMM, for all systems tested in terms of CPU time when curvature information (Hessian/vector product) is calculated by a finite-difference of gradients (the numeric option of TNPACK). The remaining derivative quantities are, however, evaluated analytically in TNPACK. The CPU gain is 50% or more (speedup factors of 1.5 to 2.5) for the largest molecular systems tested and even greater for smaller systems (CPU factors of 1 to 4 for small systems and 1 to 5 for medium systems). TNPACK uses curvature information to escape from undesired configurational regions and to ensure the identification of true local minima. It converges rapidly once a convex region is reached and achieves very low final gradient norms, such as of order 10(-8), with little additional work. Even greater overall CPU gains are expected for large-scale minimization problems by making the architectures of CHARMM and TNPACK more compatible with respect to the second-derivative calculations. (C) 1994 by John Wiley & Sons, Inc. C1 NYU,DEPT CHEM,NEW YORK,NY 10012. NYU,COURANT INST MATH SCI,NEW YORK,NY 10012. NIH,DIV COMP RES & TECHNOL,STRUCT BIOL LAB,BETHESDA,MD 20892. INSERM,U279 SDI1572I,F-59019 LILLE,FRANCE. NR 32 TC 42 Z9 42 U1 0 U2 2 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0192-8651 J9 J COMPUT CHEM JI J. Comput. Chem. PD MAY PY 1994 VL 15 IS 5 BP 532 EP 552 DI 10.1002/jcc.540150506 PG 21 WC Chemistry, Multidisciplinary SC Chemistry GA NG572 UT WOS:A1994NG57200005 ER PT J AU LOVE, PE SHORES, EW LEE, EJ GRINBERG, A MUNITZ, TI WESTPHAL, H SINGER, A AF LOVE, PE SHORES, EW LEE, EJ GRINBERG, A MUNITZ, TI WESTPHAL, H SINGER, A TI DIFFERENTIAL-EFFECTS OF ZETA-TRANSGENE AND ETA-TRANSGENE ON EARLY ALPHA/BETA-T-CELL DEVELOPMENT SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID PROTEIN-TYROSINE KINASE; NATURAL-KILLER-CELLS; ANTIGEN RECEPTOR; LYMPHOCYTES-T; MONOCLONAL-ANTIBODY; MOLECULAR-CLONING; V(D)J RECOMBINATION; GENE-EXPRESSION; FC-RECEPTORS; CHAIN GENE AB The zeta-family dimers (zeta, eta, and gamma) are a group of structurally and functionally related proteins that are expressed in developing thymocytes and function as signal transducing subunits of the T cell antigen receptor (TCR) and certain Ig Fc receptors. zeta, eta, and gamma each contain one or more copies of a conserved tyrosine-based activation motif (TAM) that is known to be required for signal transduction. To examine the developmental importance of multiple or individual TAM elements we generated transgenic mice that express: (a) full-length (FL) zeta-chain (3 TAMs); (b) eta-chain, a naturally occurring variant of zeta that is derived from alternative splicing (2 TAMs); or (c) truncated zeta-chain (CT108; 1 TAM), under the control of the human CD2 promoter and regulatory elements. Unexpectedly we found that overexpression of the FL zeta chain caused premature termination of RAG-1 and RAG-2 expression, prevented productive rearrangement of the TCR-alpha and TCR-beta genes and blocked entry of thymocytes into the CD4/CD8 developmental pathway. In contrast, we found that overexpression of eta or CT108 had no effect on normal thymocyte maturation. These results suggest that an early signaling pathway exists in precursor TCR-thymocytes that can regulate RAG-1 and RAG-2 expression and is differentially responsive to individual members of the zeta-family dimers. C1 NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892. RP LOVE, PE (reprint author), NICHHD,MAMMALIAN GENES & DEV LAB,BLDG 6B,ROOM 2B-210,BETHESDA,MD 20892, USA. NR 59 TC 45 Z9 45 U1 0 U2 0 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 MAY 1 PY 1994 VL 179 IS 5 BP 1485 EP 1494 DI 10.1084/jem.179.5.1485 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA NH655 UT WOS:A1994NH65500010 PM 8163933 ER PT J AU TAKAHAMA, Y LETTERIO, JJ SUZUKI, H FARR, AG SINGER, A AF TAKAHAMA, Y LETTERIO, JJ SUZUKI, H FARR, AG SINGER, A TI EARLY PROGRESSION OF THYMOCYTES ALONG THE CD4/CD8 DEVELOPMENTAL PATHWAY IS REGULATED BY A SUBSET OF THYMIC EPITHELIAL-CELLS EXPRESSING TRANSFORMING GROWTH-FACTOR-BETA SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID T-CELL; NEGATIVE SELECTION; POSITIVE SELECTION; ANTIGEN RECEPTOR; CD8+ THYMOCYTES; LYMPHOCYTES-T; MURINE THYMUS; TGF BETA-1; LINE; DIFFERENTIATION AB Precursor cells differentiate into mature CD4(+) and CD8(+) T cells in the inductive environment of the thymus by undergoing a series of distinct developmental steps marked by expression of the coreceptor molecules CD4 and CD8. Among the earliest cells to enter the CD4/CD8 developmental pathway are CD4(-)CD8(lo) precursors cells that differentiate into CD4(+)CD8(+) thymocytes. Here we show that differentiation of precursor cells into CD4(+)CD8(+) thymocytes requires at least one cell division and that their progression through a cell cycle is specifically retarded in the thymus by interaction with thymic epithelial cells that express transforming growth factor beta (TGF-beta) proteins. We also demonstrate that TGF-beta proteins, either in solution or bound to cell membranes, can regulate cell cycle progression and differentiation of CD4(-)CD8(lo) precursor cells into CD4(+)CD8(+) thymocytes. The regulatory effect of TGF-beta is specific for CD4(-)CD8(lo) precursor cells as TGF-beta proteins do not regulate the earlier generation of CD4(-)CD8(lo) precursor cells from CD4(-)CD8(-) thymocytes. Finally, we demonstrate that TGF-beta proteins are expressed in vivo in the intact thymus on subcapsular and cortical thymic epithelium where they can contact developing CD4(-)CD8(lo) precursor cells; Thus, thymic epithelial cells expressing TGF-beta proteins can actively regulate the rate at which CD4(+)CD8(+) thymocytes are generated from CD4(-)CD8(lo) precursor cells. C1 NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892. NCI,CHEMOPREVENT LAB,BETHESDA,MD 20892. UNIV WASHINGTON,DEPT BIOL STRUCT & IMMUNOL,SEATTLE,WA 98195. RI Suzuki, Harumi/L-1271-2013 OI Suzuki, Harumi/0000-0003-3616-9361 FU NIA NIH HHS [AG-04360]; NIAID NIH HHS [AI-24137] NR 55 TC 75 Z9 78 U1 3 U2 4 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 MAY 1 PY 1994 VL 179 IS 5 BP 1495 EP 1506 DI 10.1084/jem.179.5.1495 PG 12 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA NH655 UT WOS:A1994NH65500011 PM 8163934 ER PT J AU WYNN, TA ELTOUM, I OSWALD, IP CHEEVER, AW SHER, A AF WYNN, TA ELTOUM, I OSWALD, IP CHEEVER, AW SHER, A TI ENDOGENOUS INTERLEUKIN-12 (IL12) REGULATES GRANULOMA-FORMATION INDUCED BY EGGS OF SCHISTOSOMA-MANSONI AND EXOGENOUS IL-12 BOTH INHIBITS AND PROPHYLACTICALLY IMMUNIZES AGAINST EGG PATHOLOGY SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID CELL STIMULATORY FACTOR; LYMPHOCYTE MATURATION FACTOR; INVIVO MOLECULAR ANALYSIS; IFN-GAMMA; T-CELLS; HETERODIMERIC CYTOKINE; MESSENGER-RNA; INFECTION; TH2; PROLIFERATION AB Morbidity in humans infected with Schistosoma mansoni results primarily from the deposition of parasite eggs in portal areas where they induce a granulomatous response. In mice infected with this helminth granuloma formation is a CD4(+) T helper (Th) cell-dependent process that is associated with a strong Th2 cytokine response which appears to evolve through a Th0 phase. In this report, we asked whether endogenously synthesized or exogenously induced interferon (IFN)gamma through its suppression of Th2 cell expansion exerts a regulatory role on egg pathology. Depletion of IFN-gamma or natural killer cells resulted in a marked enhancement of granuloma formation around intravenously injected eggs and was associated with increased Th2 and decreased Th1 and interleukin (IL)12 mRNA expression. Similar changes occurred when egg-injected mice were treated with neutralizing monoclonal antibodies specific for IL-12 indicating a role for this cytokine in the regulation of the granulomatous response. In contrast, treatment with exogenous rIL-12 profoundly inhibited primary granuloma formation while increasing IFN-gamma, IL-2, IL-10, and IL-12 pulmonary mRNA levels and suppressing IL-4, IL-5, IL-6, and IL-13 mRNA expression. Cytokine depletion studies indicated that the effects of IL-12 could be attributed primarily to increased IFN-gamma. Importantly, IL-12 also inhibited secondary granuloma formation in mice presensitized with eggs demonstrating a role for the cytokine in reversing established Th2-type responses. Moreover, mice sensitized with eggs in combination with IL-12 to precommit them toward a Th1 response developed only minimal granulomas upon subsequent egg challenge. The latter findings suggest that simultaneous vaccination with antigen plus IL-12 may provide a strategy for the prevention of schistosome egg pathology as well as other diseases stemming from Th2 cytokine production. C1 NIAID,HOST PARASITE RELAT SECT,BETHESDA,MD 20892. RP WYNN, TA (reprint author), NIAID,IMMUNOL & CELL BIOL SECT,PARASIT DIS LAB,BLDG 4-126,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Wynn, Thomas/C-2797-2011; OSWALD, Isabelle/A-8497-2013; OI OSWALD, Isabelle/0000-0001-9918-277X NR 57 TC 282 Z9 283 U1 0 U2 6 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 MAY 1 PY 1994 VL 179 IS 5 BP 1551 EP 1561 DI 10.1084/jem.179.5.1551 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA NH655 UT WOS:A1994NH65500016 PM 7909326 ER PT J AU FINKELMAN, FD MADDEN, KB CHEEVER, AW KATONA, IM MORRIS, SC GATELY, MK HUBBARD, BR GAUSE, WC URBAN, JF AF FINKELMAN, FD MADDEN, KB CHEEVER, AW KATONA, IM MORRIS, SC GATELY, MK HUBBARD, BR GAUSE, WC URBAN, JF TI EFFECTS OF INTERLEUKIN-12 ON IMMUNE-RESPONSES AND HOST PROTECTION IN MICE INFECTED WITH INTESTINAL NEMATODE PARASITES SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID CELL STIMULATORY FACTOR; IMMUNOGLOBULIN ISOTYPE SELECTION; NON-T CELLS; IGE RESPONSE; NIPPOSTRONGYLUS-BRASILIENSIS; HUMAN-LYMPHOCYTES; GOAT ANTIBODY; IFN-GAMMA; MOUSE IGD; NON-B AB The cytokine interleukin (IL) 12 stimulates T cell and natural killer cell Production of interferon (IFN) gamma and inhibits T cell production of IL-4. We investigated the effects of IL-12 on cytokine gene expression, immunoglobulin (Ig)E, mucosal mast cell, and eosinophil responses, and the course of infection in mice inoculated with the nematode parasite Nippostrongylus brasiliensis, as well as the IFN-gamma dependence of these effects. IL-12 stimulated IFN-gamma and IL-10 gene expression during primary and secondary N. Brasiliensis infections and inhibited IL-3; IL-4, IL-5, and IL-9 gene expression during primary infections but had little inhibitory effect during secondary infections. IL-12 inhibited IgE, mucosal mast cell, and blood and tissue eosinophil responses during primary infections, but only eosinophil responses during secondary infections. IL-12 enhanced adult worm survival and egg production during primary, but not secondary infections. IL-12 needed to be administered by day 4 of a primary infection to inhibit IgE and mucosal mast cell responses, and by day 6 to strongly inhibit eosinophil responses and to enhance worm survival and fecundity. Anti-IFN-gamma mAb inhibited the effects of IL-12 on IgE secretion, intestinal mucosal mastocytosis, and parasite survival and fecundity, but did not affect IL-12 inhibition of eosinophilia. These observations indicate that IL-12, if administered during the initiation of an immune response, can change the response from one that is characterized by the production of T helper (Th)2-associated cytokines to one characterized by the production of Th-l associated cytokines. However, IL-12 treatment has less of an effect once the production of Th2-associated cytokines has become established. In addition, our results provide evidence that Th2-associated responses protect against, and/or Th1-associated responses exacerbate, nematode infections. C1 UNIFORMED SERV UNIV HLTH SCI,DEPT PEDIAT,BETHESDA,MD 20814. UNIFORMED SERV UNIV HLTH SCI,DEPT MICROBIOL & IMMUNOL,BETHESDA,MD 20814. NIAID,PARASIT DIS LAB,BETHESDA,MD 20892. HOFFMANN LA ROCHE INC,DEPT INFLAMMAT AUTOIMMUNE DIS,NUTLEY,NJ 07110. GENET INST INC,CAMBRIDGE,MA 02140. USDA ARS,INST LIVESTOCK & POULTRY SCI,HELMINTH DIS LAB,BELTSVILLE,MD 20705. RP FINKELMAN, FD (reprint author), UNIFORMED SERV UNIV HLTH SCI,DEPT MED,4301 JONES BRIDGE RD,BETHESDA,MD 20814, USA. OI Urban, Joseph/0000-0002-1590-8869 FU NIAID NIH HHS [R01-AI121328] NR 48 TC 282 Z9 285 U1 0 U2 3 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 MAY 1 PY 1994 VL 179 IS 5 BP 1563 EP 1572 DI 10.1084/jem.179.5.1563 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA NH655 UT WOS:A1994NH65500017 PM 7909327 ER PT J AU SALOMON, DR MOJCIK, CF CHANG, AC WADSWORTH, S ADAMS, DH COLIGAN, JE SHEVACH, EM AF SALOMON, DR MOJCIK, CF CHANG, AC WADSWORTH, S ADAMS, DH COLIGAN, JE SHEVACH, EM TI CONSTITUTIVE ACTIVATION OF INTEGRIN ALPHA-4-BETA-1 DEFINES A UNIQUE STAGE OF HUMAN THYMOCYTE DEVELOPMENT SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID CELL-ADHESION MOLECULE-1; THYMIC EPITHELIAL-CELLS; HUMAN FETAL THYMUS; T-CELLS; PRECURSOR CELLS; TERMINAL DIFFERENTIATION; ENDOTHELIAL-CELLS; STROMAL CELLS; INDUCED PHOSPHORYLATION; EXTRACELLULAR-MATRIX AB Our understanding of thymocyte development and of the positive and negative selection events involved in shaping the repertoire of mature T lymphocytes has been greatly facilitated by the use of transgenic and gene knockout animals. Much less is known about the factors that control the homing and population of the thymus by T cell precursors and the subsequent migration of developing thymocytes through the thymic architecture. As the integrins represent a candidate group of cell surface receptors that may regulate thymocyte development, we have analyzed the expression and function of alpha 4 beta 1 and alpha 5 beta 1 on human thymocytes. A major portion of double positive (CD4(+)CD8(+)) human thymocytes express alpha 4 beta 1 in a constitutively active form and adhere to fibronectin and vascular cell adhesion molecule 1. alpha 4 beta 1 expression is similar on adherent and nonadherent populations, thus, activity reflects the receptor state and not simple expression. The adherent cells are immature, expressing high levels of CD4/CD8 and low levels of CD3 and CD69. In contrast, nonadherent cells possess the phenotype of thymocytes after positive selection, expressing intermediate levels of CD4 and/or CD8 and high levels of CD3 and CD69. The adherent population fails to respond to activation with anti-CDS and fibronectin, whereas nonadherents exhibit an alpha 5 beta 1-dependent proliferation. Differential regulation of alpha 4 beta 1 and alpha 5 beta 1 receptors may provide a mechanism controlling cellular traffic, differentiation, and positive selection of thymocytes. C1 NIAID,CELLULAR IMMUNOL SECT,IMMUNOL LAB,BETHESDA,MD 20892. NIAID,BIOL RESOURCES BRANCH,BETHESDA,MD 20892. NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892. RI Adams, David/C-9092-2009; Salomon, Daniel/E-9380-2012 FU NIDDK NIH HHS [DK1820] NR 73 TC 72 Z9 72 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 MAY 1 PY 1994 VL 179 IS 5 BP 1573 EP 1584 DI 10.1084/jem.179.5.1573 PG 12 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA NH655 UT WOS:A1994NH65500018 PM 8163937 ER PT J AU POSNETT, DN VISSINGA, CS PAMBUCCIAN, C ROBINSON, MA KOSTYU, D CONCANNON, P WEI, S AF POSNETT, DN VISSINGA, CS PAMBUCCIAN, C ROBINSON, MA KOSTYU, D CONCANNON, P WEI, S TI LEVEL OF HUMAN TCRBV3S1 (V-BETA-3) EXPRESSION CORRELATES WITH ALLELIC POLYMORPHISM IN THE SPACER REGION OF THE RECOMBINATION SIGNAL SEQUENCE SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Note ID GENE-PRODUCTS; BETA-CHAIN; T-CELLS; RECEPTOR; POPULATIONS; COMPLEX AB One of the causes of variations in the expressed human T cell receptor (TCR) BV (V beta) repertoire is genetic variation in the germline DNA. Herein evidence is provided that allelic polymorphism may affect recombination frequency for a specific V gene. Two alleles of the TCR BV3 differ only at a single nucleotide position (C/T) within the 23-bp spacer region of the recombination signal sequence. These alleles are associated with variable percentages of BV3 cells in the peripheral blood, as shown in families and in unrelated normal donors. Individuals homozygous for allele 2 have a mean of 8.1% BV3 cells, heterozygous individuals have a mean of 4.7% BV3 cells, and homozygotes for allele 1 have a mean of 1.2% BV3 cells in CD3(+) CD4(+) peripheral blood T cells. Since the correlation is tight in unrelated individuals and other genetic differences were not found in the vicinity of BV3, we suggest that the spacer region sequence itself modifies recombination efficiency. This allelic system provides an example of a novel mechanism by which cis-acting genetic elements may affect recombination in a natural in vivo system. C1 CORNELL UNIV,GRAD SCH MED SCI,PROGRAM IMMUNOL,NEW YORK,NY 10021. VIRGINIA MASON RES CTR,SEATTLE,WA 98101. UNIV WASHINGTON,SCH MED,DEPT IMMUNOL,SEATTLE,WA 98195. NIAID,IMMUNOGENET LAB,ROCKVILLE,MD 20852. DUKE UNIV,MED CTR,DEPT IMMUNOL,DURHAM,NC 27710. RP POSNETT, DN (reprint author), CORNELL UNIV,COLL MED,DEPT MED,BOX 56,1300 YORK AVE,NEW YORK,NY 10021, USA. FU NIAID NIH HHS [AI-31140, AI-33322]; NIDDK NIH HHS [DK41347] NR 30 TC 76 Z9 76 U1 0 U2 0 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 MAY 1 PY 1994 VL 179 IS 5 BP 1707 EP 1711 DI 10.1084/jem.179.5.1707 PG 5 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA NH655 UT WOS:A1994NH65500035 PM 8163948 ER PT J AU KIM, YH BUCHHOLZ, MA CHREST, FJ NORDIN, AA AF KIM, YH BUCHHOLZ, MA CHREST, FJ NORDIN, AA TI UP-REGULATION OF C-MYC INDUCES THE GENE-EXPRESSION OF THE MURINE HOMOLOGS OF P34(CDC2) AND CYCLIN-DEPENDENT KINASE-2 IN T-LYMPHOCYTES SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CELL-CYCLE; TRANSFERRIN RECEPTOR; HUMAN INTERLEUKIN-2; PROTEIN-KINASE; RETINOBLASTOMA PROTEIN; NUCLEOTIDE-SEQUENCE; CDC28 MUTATION; MESSENGER-RNA; DNA-SYNTHESIS; S-PHASE AB The expression and/or up-regulation of several early T cell activation genes is dependent on signals transmitted through the interaction of IL-2 and IL-2R well before entry of the cells into S phase. In these studies, murine G(0) T cells activated by immobilized anti-CD3 and subsequently blocked in late G(1) expressed normal surface levels and mRNA for IL-2 alpha, IL-2R beta, and transferrin receptor (TfR). However, there was no expression of p34(cdc2), and cyclin-dependent kinase (cdk)-2 was not up-regulated even in the presence of exogenous rIL-2. In addition the accumulation of c-myc-specific mRNA and protein was significantly reduced. Pretreatment of G(0) T cells with c-myc antisense oligonucleotide effectively reduced the level of specific c-myc protein induced by activation of the cells by immobilized anti-CD3. The presence of antisense c-myc oligonucleotide inhibited the expression of cdc2 and cdk2 without affecting the expression of IL-2R alpha and blocked the activated T cells in the G(1) phase. Together these studies demonstrate that c-myc regulates the expression of these cdk and suggest a role for c-myc in the G(1)/S transition. C1 NIA,GERONTOL RES CTR,CLIN IMMUNOL SECT,BALTIMORE,MD 21224. NR 62 TC 30 Z9 31 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 MAY 1 PY 1994 VL 152 IS 9 BP 4328 EP 4335 PG 8 WC Immunology SC Immunology GA NG719 UT WOS:A1994NG71900011 PM 8157956 ER PT J AU SIDNEY, J OSEROFF, C DELGUERCIO, MF SOUTHWOOD, S KRIEGER, JI ISHIOKA, GY SAKAGUCHI, K APPELLA, E SETTE, A AF SIDNEY, J OSEROFF, C DELGUERCIO, MF SOUTHWOOD, S KRIEGER, JI ISHIOKA, GY SAKAGUCHI, K APPELLA, E SETTE, A TI DEFINITION OF A DQ3.1-SPECIFIC BINDING MOTIF SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CLASS-II MOLECULES; HLA-DR MOLECULES; ANTIGEN-PROCESSING MUTANT; INVARIANT CHAIN PEPTIDES; MHC BINDING; MULTIPLE-SCLEROSIS; FINE SPECIFICITY; HIGH-AFFINITY; CELL LINE; T-CELLS AB A quantitative peptide binding assay using purified DQA1*0301/DQB1*0301 (DQ3.1) molecules was developed and validated by examining the correlation between the data obtained in the binding assay with those obtained in inhibition of Ag presentation assays. By the combined use of large libraries of synthetic peptides and of substitution and truncation analogues, a putative DQ3.1 motif was defined. Its most prominent feature is the requirement for two small and/or hydrophobic residues spaced at positions i + 2 and i + 4. This motif is quite different from the motif recognized by DR molecules, but similar to the motif previously defined for certain IA alleles (the putative mouse homologue of DQ). These data suggest that various class II isotypes have evolved to present different peptide structures to each other, thus maximizing the repertoire of different epitopes available to T cell scrutiny. C1 CYTEL CORP,SAN DIEGO,CA 92121. PROCEPT INC,CAMBRIDGE,MA 02139. NCI,BETHESDA,MD 20892. FU NIAID NIH HHS [AI18634] NR 54 TC 44 Z9 45 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 MAY 1 PY 1994 VL 152 IS 9 BP 4516 EP 4525 PG 10 WC Immunology SC Immunology GA NG719 UT WOS:A1994NG71900030 PM 7512598 ER PT J AU SKEEL, A LEONARD, EJ AF SKEEL, A LEONARD, EJ TI ACTION AND TARGET-CELL SPECIFICITY OF HUMAN MACROPHAGE-STIMULATING PROTEIN (MSP) SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HEPATOCYTE GROWTH-FACTOR; AMINO-ACID-SEQUENCE; PERITONEAL-MACROPHAGES; RECEPTOR; IDENTIFICATION; PROTHROMBIN; ACTIVATION; HOMOLOGY; PRODUCT AB Macrophage-stimulating protein (MSP) induces mouse resident peritoneal macrophages to become responsive to the chemoattractant C5a and to ingest C3bi-coated erythrocytes. We now show that MSP action is not limited to complement-induced responses, because it also induced responsiveness to the noncomplement chemoattractant casein. In addition to stimulating responsiveness to attractants, MSP functioned alone as a chemoattractant for resident peritoneal macrophages, with an optimal concentration of approximately 0.2 nM. A critical difference between MSP and C5a is that resident macrophages did not migrate to C5a without an additional stimulus such as MSP in the cell suspension, whereas macrophages suspended in medium alone migrated to MSP in the attractant well. Thus, in contrast to C5a, MSP seems capable of a dual role, both activator and attractant. MSP had no effect on responsiveness of mouse peritoneal exudate macrophages to C5a; nor could it attract exudate macrophages or human blood monocytes. Absorption studies showed that resident macrophages have a receptor for MSP, but exudate macrophages do not. In view of these findings, it seems that the biological role of MSP is not as a recruiter of blood monocytes to sites of inflammation, but as an activator of mature macrophages. The MSP-induced activated state for responsiveness to C5a or C3bi was transient, and decayed at a first order rate with a t1/2 of approximately 1 h. This is a new example of the transience of activation induced in macrophages by proinflammatory stimuli. C1 NCI,FREDERICK CANC RES & DEV CTR,IMMUNOPATHOL SECT,IMMUNOBIOL LAB,FREDERICK,MD 21702. NR 21 TC 56 Z9 56 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 MAY 1 PY 1994 VL 152 IS 9 BP 4618 EP 4623 PG 6 WC Immunology SC Immunology GA NG719 UT WOS:A1994NG71900043 PM 8157975 ER PT J AU SINGH, DP KIKUCHI, T SINGH, VK SHINOHARA, T AF SINGH, DP KIKUCHI, T SINGH, VK SHINOHARA, T TI A SINGLE AMINO-ACID SUBSTITUTION IN-CORE RESIDUES OF S-ANTIGEN PREVENTS EXPERIMENTAL AUTOIMMUNE UVEITIS SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HISTOCOMPATIBILITY COMPLEX BINDING; LYMPHOCYTE CROSS-REACTION; T-CELL RECOGNITION; MOLECULAR MIMICRY; UVEITOPATHOGENIC SITE; ADOPTIVE TRANSFER; ALPHA-TRANSDUCIN; LEWIS RATS; UVEORETINITIS; SEQUENCE AB We have previously reported that microbial Ags, having a three- to six-amino-acid-sequence homology with a uveitopathogenic epitope (peptide M) of retinal soluble protein (S-Ag), induce experimental autoimmune uveitis (EAU). Another uveitopathogenic epitope (peptide G) of S-Ag also was characterized. In addition, we have characterized the core sequences by truncating peptides G and M from amino and carboxyl termini. In this study, we have further defined the core sequences using synthetic octapeptides with a single amino acid substitution. In addition, the analogues of peptides Gm5 or Mm4 are capable of inhibiting the proliferative response of T-lymphocytes from rats immunized with peptides G-8 or M-8, respectively. Co-injection of a pathogenic peptide with nonpathogenic substitution analogues blocked the induction of EAU. These results suggest that specific nonpathogenic analogues with single amino acid substitution derived from pathogenic peptides have potential for prevention and therapy of autoimmune diseases. C1 NEI,RETINAL CELL & MOLEC BIOL LAB,MOLEC BIOL SECT,BETHESDA,MD 20892. SANJAY GANDHI POSTGRAD INST MED SCI,DEPT IMMUNOL,LUCKNOW,UTTAR PRADESH,INDIA. OI Shinohara, Toshimichi/0000-0002-7197-9039 NR 45 TC 21 Z9 21 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 MAY 1 PY 1994 VL 152 IS 9 BP 4699 EP 4705 PG 7 WC Immunology SC Immunology GA NG719 UT WOS:A1994NG71900052 PM 8157981 ER PT J AU WEBER, J GUNN, H YANG, J PARKINSON, D TOPALIAN, S SCHWARTZENTRUBER, D ETTINGHAUSEN, S LEVITT, D ROSENBERG, SA AF WEBER, J GUNN, H YANG, J PARKINSON, D TOPALIAN, S SCHWARTZENTRUBER, D ETTINGHAUSEN, S LEVITT, D ROSENBERG, SA TI A PHASE-I TRIAL OF INTRAVENOUS INTERLEUKIN-6 IN PATIENTS WITH ADVANCED CANCER SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE PHASE I TRIAL; IL-6; ADVANCED CANCER ID HUMAN RECOMBINANT INTERLEUKIN-6; STIMULATORY FACTOR-II; LYMPHOCYTES-T; GROWTH-FACTOR; CELL-LINES; MYELOID-LEUKEMIA; POTENT INDUCER; MICE; DIFFERENTIATION; IL-6 AB Eighteen patients were treated with escalating doses of recombinant, Escherchia coli-derived human interleukin-6 (IL-6) intravenously every 8 h. Therapy was given for two cycles of 7 days each separated by a week off therapy. Fevers and chills were observed in most patients. Mild renal and liver function abnormalities were noted at higher doses of IL-6. Dose-limiting toxicity was reached at 30 mu g/kg i.v. every 8 h due to reversible neurotoxicity, but significant rapidly reversible anemia and hyperglycemia were seen at lower doses. Platelet counts, white brood cell counts, and acute phase reactant levels were substantially elevated. No antitumor responses were seen. A maximum tolerated dose of 10 mu g/kg i.v. every 8 h for two 7-day cycles is recommended for future phase II trials. C1 SANDOZ INC,PHARMACEUT,CYTOKINE DEV UNIT,E HANOVER,NJ. RP WEBER, J (reprint author), NCI,SURG BRANCH,BLDG 10,ROOM 2B42,BETHESDA,MD 20892, USA. NR 44 TC 40 Z9 41 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD MAY PY 1994 VL 15 IS 4 BP 292 EP 302 DI 10.1097/00002371-199405000-00008 PG 11 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA NM388 UT WOS:A1994NM38800008 PM 7520334 ER PT J AU BROWN, CC POLI, G LUBAKI, N STLOUIS, M DAVACHI, F MUSEY, L MANZILA, T KOVACS, A QUINN, TC FAUCI, AS AF BROWN, CC POLI, G LUBAKI, N STLOUIS, M DAVACHI, F MUSEY, L MANZILA, T KOVACS, A QUINN, TC FAUCI, AS TI ELEVATED LEVELS OF TUMOR-NECROSIS-FACTOR-ALPHA IN ZAIRIAN NEONATE PLASMAS - IMPLICATIONS FOR PERINATAL INFECTION WITH THE HUMAN-IMMUNODEFICIENCY-VIRUS SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID HIV-INFECTION; MONONUCLEAR-CELLS; LYMPHOCYTES-B; CHILDREN; INTERLEUKIN-6; EXPRESSION; SERUM; INFANTS; TYPE-1; IL-6 AB Plasma levels of tumor necrosis factor-alpha (TNF alpha) and the ability of plasmas to induce HIV expression in chronically infected cell lines were measured in samples from adults, cord blood, and neonates from Zaire and North America. Plasma levels of TNF alpha were higher in Zairian neonates born to HIV-negative and -positive mothers than in uninfected Zairian adults (612 vs. 128 vs. 8 pg/mL, P < .001); this dichotomy persisted until children were 9 months old. Plasmas from neonates of HIV-negative Zairian mothers also stimulated higher levels of reverse transcriptase from HIV-infected cell lines than did plasmas from HIV-negative Zairian adults (1339 vs. 110 cpm, P < .001). Similar patterns were noted in plasmas from HIV-negative North American adults and neonates; however, TNF alpha levels were markedly lower, and smaller differences were noted among North American adults and neonates than those in the Zairian cohort. Markedly elevated plasma TNF alpha levels in Zairian neonates and infants may play a role in the pathogenesis and progression of HIV disease in this patient population. C1 NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. UNIV SO CALIF,LOS ANGELES CTY MED CTR,LOS ANGELES,CA 90033. CTR DIS CONTROL & PREVENT,ATLANTA,GA. MAMA YEMO HOSP,PROJET SIDA,KINSHASA,ZAIRE. MAMA YEMO HOSP,DEPT PEDIAT,KINSHASA,ZAIRE. NR 36 TC 16 Z9 16 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD MAY PY 1994 VL 169 IS 5 BP 975 EP 980 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA NW346 UT WOS:A1994NW34600005 PM 8169428 ER PT J AU SCHNITTMAN, SM VOGEL, S BASELER, M LANE, HC DAVEY, RT AF SCHNITTMAN, SM VOGEL, S BASELER, M LANE, HC DAVEY, RT TI A PHASE-I STUDY OF INTERFERON-ALPHA-2B IN COMBINATION WITH INTERLEUKIN-2 IN PATIENTS WITH HUMAN-IMMUNODEFICIENCY-VIRUS INFECTION SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID IMMUNE-DEFICIENCY SYNDROME; RENAL-CELL CARCINOMA; KAPOSIS-SARCOMA; LYMPHOBLASTOID INTERFERON; RECOMBINANT INTERLEUKIN-2; ALPHA-INTERFERON; HIV-INFECTION; SYNDROME AIDS; THERAPY; ZIDOVUDINE AB Interferon-alpha (IFN-alpha) can inhibit human immunodeficiency virus (HIV-1) replication and is effective in treating Kaposi's sarcoma; interleukin-2 (IL-2) can increase circulating lymphocytes in HIV-1-infected patients. The safety of combination treatment with recombinant (r)IFN-alpha 2b and IL-2 was evaluated in HIV-1-infected patients with > 200 CD4(+) T cells/mm(3). A maximal tolerated dose of rIFN-alpha 2b was determined for 17 patients; then they received in combination 3, 6, or 12 x 10(6) IU/day rIL-2, given intravenously over 21 days. Twelve patients ultimately received the combination, 9 for the full 21 days. Significant toxicities included flu-like symptoms, anemia, transaminemia, and depression. Transient increases in CD4(+) T cell percentages and spontaneous lymphocyte blast transformation were observed. Quantitative microcultures demonstrate a decline in HIV titers in patients receiving rIFN-alpha 2b (5/9) with a further decline on addition of rIL-2 (7/9). In summary, continuous rIL-2 at 6 X 10(6) IU/day in combination with rIFN-alpha 2b was reasonably tolerated and provided preliminary evidence of immunomodulatory and antiviral activity. C1 NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. PRI DYNCORP,FREDERICK,MD. NR 50 TC 31 Z9 31 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD MAY PY 1994 VL 169 IS 5 BP 981 EP 989 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA NW346 UT WOS:A1994NW34600006 PM 7909550 ER PT J AU THOMAS, DL CANNON, RO SHAPIRO, CN HOOK, EW ALTER, MJ QUINN, TC AF THOMAS, DL CANNON, RO SHAPIRO, CN HOOK, EW ALTER, MJ QUINN, TC TI HEPATITIS-C, HEPATITIS-B, AND HUMAN-IMMUNODEFICIENCY-VIRUS INFECTIONS AMONG NON-INTRAVENOUS DRUG-USING PATIENTS ATTENDING CLINICS FOR SEXUALLY-TRANSMITTED DISEASES SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID RISK-FACTORS; NON-A; HOMOSEXUAL MEN; UNITED-STATES; FEMALE PROSTITUTES; TRANSMISSION; SEROPREVALENCE; HETEROSEXUALS; ASSOCIATION; PREVALENCE AB The seroprevalences of and risk factors for hepatitis C virus (HCV), hepatitis B virus (HBV), human immunodeficiency virus (HIV), and syphilis were determined among 1257 consecutive non-intravenous drug-using patients attending Baltimore sexually transmitted diseases clinics: 122 (9.7%) had antibodies to HCV (anti-HCV), 192 (15.3%) had antibodies to HBV (anti-HBc), 44 (3.5%) had antibodies to HIV (anti-HIV), and 60 (4.8%) were seropositive for syphilis. For males, independent predictors of anti-HCV were age > 29 years and lack of condom use in the month before their visit. Males with any one serologic marker (anti-HCV, anti-HBc, anti-HIV, or syphilis) were more likely to have each of the other markers. For females, anti-HCV was independently associated with age > 29 years and > 1 male sex partner in the prior month. Females with anti-HIV or anti-HBc were more likely to have anti-HCV. These observations among non-intravenous drug-using patients suggest that sexual transmission of HCV may occur. C1 BALTIMORE CITY DEPT HLTH,BALTIMORE,MD. NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. CTR DIS CONTROL & PREVENT,NATL CTR INFECT DIS,DIV VIRAL & RICKETTSIAL DIS,RETROVIRUS BRANCH,ATLANTA,GA. CTR DIS CONTROL & PREVENT,NATL CTR INFECT DIS,DIV VIRAL & RICKETTSIAL DIS,HEPATITIS BRANCH,ATLANTA,GA. RP THOMAS, DL (reprint author), JOHNS HOPKINS UNIV,SCH MED,DIV INFECT DIS,1155 ROSS BLDG,720 RUTLAND AVE,BALTIMORE,MD 21205, USA. RI Quinn, Thomas/A-2494-2010 NR 25 TC 115 Z9 119 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD MAY PY 1994 VL 169 IS 5 BP 990 EP 995 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA NW346 UT WOS:A1994NW34600007 PM 8169429 ER PT J AU TURNER, PF ROCKETT, KA OTTESEN, EA FRANCIS, H AWADZI, K CLARK, IA AF TURNER, PF ROCKETT, KA OTTESEN, EA FRANCIS, H AWADZI, K CLARK, IA TI INTERLEUKIN-6 AND TUMOR-NECROSIS-FACTOR IN THE PATHOGENESIS OF ADVERSE REACTIONS AFTER TREATMENT OF LYMPHATIC FILARIASIS AND ONCHOCERCIASIS SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID MAZZOTTI REACTION; DIETHYLCARBAMAZINE; INFECTION AB Adverse reactions following treatment of onchocerciasis and bancroftian filariasis are common and frequently severe. They are generally caused not by direct drug toxicity but by host inflammatory responses to dying microfilariae. To define the responsible mechanism, serial blood levels of interleukin-6 (IL-6) and tumor necrosis factor (TNF) were studied in 15 microfilaria-positive patients (10 with bancroftian filariasis, 5 with onchocerciasis) and 4 microfilaria-negative persons after diethylcarbamazine treatment. Elevations in IL-6 correlated with the occurrence and severity of clinical symptoms after treatment; for the onchocerciasis patients IL-6 levels directly reflected pretreatment intensity of infection. Serum TNF levels also rose but did not correlate directly with infection intensity or reaction severity. Microfilaria-negative controls remained asymptomatic with no significant rise in either cytokine. These findings suggest an etiologic role for systemically elevated cytokines in the inflammatory reactions developing after treatment of filarial infections in humans. C1 AUSTRALIAN NATL UNIV,JOHN CURTIN SCH MED RES,CANBERRA,ACT,AUSTRALIA. AUSTRALIAN NATL UNIV,DIV BIOCHEM & MOLEC BIOL,CANBERRA,ACT,AUSTRALIA. NIAID,PARASIT DIS LAB,BETHESDA,MD 20892. HOHOE HOSP,ONCHOCERCIASIS CHEMOTHERAPEUT RES CTR,HOHOE,GHANA. RP TURNER, PF (reprint author), JAMES COOK UNIV N QUEENSLAND,ANTON BREINI CTR TROP HLTH & MED,DEPT PUBL HLTH & TROP MED,TOWNSVILLE,QLD 4811,AUSTRALIA. RI Clark, Ian/K-2069-2012 NR 17 TC 33 Z9 34 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD MAY PY 1994 VL 169 IS 5 BP 1071 EP 1075 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA NW346 UT WOS:A1994NW34600019 PM 8169393 ER PT J AU GANN, PH NEVA, FA GAM, AA AF GANN, PH NEVA, FA GAM, AA TI A RANDOMIZED TRIAL OF SINGLE-DOSE AND 2-DOSE IVERMECTIN VERSUS THIABENDAZOLE FOR TREATMENT OF STRONGYLOIDIASIS SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article AB A randomized trial is described comparing ivermectin and thiabendazole for treatment of chronic infection with Strongyloides stercoralis. Subjects received ivermectin (200 mu g/kg) in a single dose, ivermectin (200 mu g/kg) on 2 consecutive days, or thiabendazole (50 mg/kg/day) twice daily for 3 consecutive days. Most subjects (94%) had intermittent symptoms, including urticaria, epigastric pain, and diarrhea. Stools were examined 7 days and 1, 3, 6, 10, and 22 months after treatment. Fifty-three subjects completed at least 3 months of follow-up. Only 1 of 34 and 2 of 19 ivermectin and thiabendazole subjects, respectively, had a stool positive for larvae after treatment. Symptoms were relieved in all 3 groups and eosinophil levels returned to normal in 90% of all subjects by 12 months. Nearly 95% of thiabendazole subjects had short-term adverse effects during therapy versus only 18% of those treated with ivermectin. One dose of ivermectin provides safety and efficacy equivalent to thiabendazole with a much lower prevalence of side effects and, consequently, better compliance. C1 NIAID,PARASIT DIS LAB,BETHESDA,MD 20892. RP GANN, PH (reprint author), NORTHWESTERN UNIV,SCH MED,DEPT PREVENT MED,680 N LAKE SHORE DR,SUITE 1102,CHICAGO,IL 60611, USA. NR 15 TC 122 Z9 129 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD MAY PY 1994 VL 169 IS 5 BP 1076 EP 1079 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA NW346 UT WOS:A1994NW34600020 PM 8169394 ER PT J AU BOURNE, N STANBERRY, LR CONNELLY, BL KURAWADWALA, J STRAUS, SE KRAUSE, PR AF BOURNE, N STANBERRY, LR CONNELLY, BL KURAWADWALA, J STRAUS, SE KRAUSE, PR TI QUANTITY OF LATENCY-ASSOCIATED TRANSCRIPT PRODUCED BY HERPES-SIMPLEX VIRUS IS NOT PREDICTIVE OF THE FREQUENCY OF EXPERIMENTAL RECURRENT GENITAL HERPES SO JOURNAL OF INFECTIOUS DISEASES LA English DT Note ID HUMAN TRIGEMINAL GANGLIA; GUINEA-PIGS; PATHOGENESIS; INFECTION; HYBRIDIZATION; REACTIVATION; INSITU AB The role of the latency-associated transcript (LAT) in control of recurrent herpes simplex virus type 2 (HSV-2) infection was investigated by examining whether LAT concentration in vitro during productive infection or in ganglia during latency correlated with the frequency of recurrent genital herpes. Clinical HSV-2 isolates from frequent or infrequent recurrent genital disease produced comparable amounts of glycoprotein D and infected cell polypeptide 0 RNA, but the isolate from frequent disease produced about seven times more LAT. The guinea pig model of genital herpes was used to determine whether the quantity of LAT produced during acute infection in vitro correlated with recurrence phenotype; the frequency of recurrent disease was similar for the 2 clinical isolates. Likewise, there was no correlation between the recurrence phenotype of individual animals and LAT concentration in their ganglia. Thus, while absence of LAT may impair HSV reactivation and recurrence, once a threshold concentration is exceeded, LAT has no further effect on recurrence frequency. C1 UNIV CINCINNATI,COLL MED,DEPT PEDIAT,CHILDRENS HOSP RES FDN,DIV INFECT DIS,CINCINNATI,OH 45229. NIAID,CLIN INVEST LAB,BETHESDA,MD. US FDA,CTR BIOL EVALUAT & RES,DIV VIRAL PROD,BETHESDA,MD. FU NIAID NIH HHS [AI-22667, AI-29687] NR 15 TC 19 Z9 19 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD MAY PY 1994 VL 169 IS 5 BP 1084 EP 1087 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA NW346 UT WOS:A1994NW34600022 PM 8169396 ER PT J AU FURBERG, CD BERGLUND, G MANOLIO, TA PSATY, BM AF FURBERG, CD BERGLUND, G MANOLIO, TA PSATY, BM TI OVERTREATMENT AND UNDERTREATMENT OF HYPERTENSION SO JOURNAL OF INTERNAL MEDICINE LA English DT Article DE ANTIHYPERTENSIVES; CLINICAL TRIALS; HYPERTENSION; PREVENTION; TREATMENT GUIDELINES ID CORONARY HEART-DISEASE; BLOOD-PRESSURE; MILD HYPERTENSION; SYSTOLIC HYPERTENSION; DOSE-RESPONSE; DRUG; CHLORTHALIDONE; THERAPY; STROKE; TRIAL AB Results from a large number of randomized clinical trials document conclusively that treatment of elevated systolic and/or diastolic blood pressure markedly reduces the risk of cardiovascular complications such as stroke and acute myocardial infarction. Detection, treatment and control of hypertension have major public health implications. A review of the literature suggests the existence of both overtreatment (defined as improper or incorrect diagnosis of hypertension, overaggressive and potentially dangerous blood pressure lowering and the use of expensive antihypertensive drugs with unproven mortality/morbidity benefits) and undertreatment (defined as unrecognized, untreated and poorly controlled hypertension). These current major issues in medicine are discussed. C1 NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,EPIDEMIOL & BIOMETRY PROGRAM,BETHESDA,MD 20892. UNIV WASHINGTON,DEPT MED,EPIDEMIOL & HLTH SERV,SEATTLE,WA. LUND UNIV,DEPT MED,MALMO,SWEDEN. RP FURBERG, CD (reprint author), WAKE FOREST UNIV,BOWMAN GRAY SCH MED,DEPT PUBL HLTH SCI,MED CTR BLVD,WINSTON SALEM,NC 27157, USA. NR 32 TC 21 Z9 21 U1 1 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0954-6820 J9 J INTERN MED JI J. Intern. Med. PD MAY PY 1994 VL 235 IS 5 BP 387 EP 397 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA NK164 UT WOS:A1994NK16400002 PM 8182392 ER PT J AU BULTE, JWM DOUGLAS, T MANN, S FRANKEL, RB MOSKOWITZ, BM BROOKS, RA BAUMGARNER, CD VYMAZAL, J STRUB, MP FRANK, JA AF BULTE, JWM DOUGLAS, T MANN, S FRANKEL, RB MOSKOWITZ, BM BROOKS, RA BAUMGARNER, CD VYMAZAL, J STRUB, MP FRANK, JA TI MAGNETOFERRITIN - CHARACTERIZATION OF A NOVEL SUPERPARAMAGNETIC MR CONTRAST AGENT SO JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article DE CONTRAST MEDIA; IRON; RELAXOMETRY ID FERRITIN-H-CHAIN; ESCHERICHIA-COLI; IRON-OXIDES; PROTEIN; HETEROPOLYMERS; RELAXIVITY; RELAXATION; DESIGN AB A protein-encaged superparamagnetic iron oxide has been developed and characterized hy using horse spleen apoferritin as a novel bioreactive environment. The roughly spherical magnetoferritin molecules, 120 angstrom in diameter, are composed of a monocrystalline maghemite or magnetite core 73 angstrom +/- 14 in diameter. Except for the additional presence of iron-rich molecules of higher molecular weight, the appearance and molecular weight (450 kd) of magnetoferritin are identical to that of natural ferritin; the molecules are externally indistinguishable from their precursor, with a pI (isoelectric point) in the range 4.3-4.6. The measured magnetic moment of the superparamagnetic cores is 13,200 Bohr magnetons per molecule, with TI and T2 relaxivities (r1 and r2) of 8 and 175 L.mmol-1 (Fe).sec-1, respectively, at body temperature and clinical field strengths. The unusually high r2/r1 ratio of 22 is thought to arise from ideal core composition, with no evidence of crystalline paramagnetic inclusions. T2 relaxation enhancement can be well correlated to the field-dependent molecular magnetization, as given by the Langevin magnetization function, raised to a power in the range 1.4-1.6. With its nanodimensional biomimetic protein cage as a rigid, convenient matrix for complexing a plethora of bioactive substances, magnetoferritin may provide a novel template for specific targeting of selected cellular sites. C1 NINCDS, NEUROIMAGING BRANCH, BETHESDA, MD 20892 USA. NCRR, BIOMED ENGN & INSTRUMENTAT PROGRAM, BETHESDA, MD 20892 USA. NIH, OIR, OR, PROT EXPRESS LAB, BETHESDA, MD 20892 USA. UNIV BATH, SCH CHEM, BATH BA2 7AY, AVON, ENGLAND. CALIF POLYTECH STATE UNIV SAN LUIS OBISPO, DEPT PHYS, SAN LUIS OBISPO, CA 93407 USA. UNIV MINNESOTA, DEPT GEOL & GEOPHYS, MINNEAPOLIS, MN 55455 USA. RP NINCDS, DIAGNOST RADIOL RES LAB, BLDG 10, RM B1N256, BETHESDA, MD 20892 USA. RI Bulte, Jeff/A-3240-2008; Mann, Stephen/D-1332-2012; Douglas, Trevor/F-2748-2011 OI Bulte, Jeff/0000-0003-1202-1610; Mann, Stephen/0000-0003-3012-8964; NR 36 TC 121 Z9 122 U1 0 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1053-1807 EI 1522-2586 J9 J MAGN RESON IMAGING JI J. Magn. Reson. Imaging PD MAY-JUN PY 1994 VL 4 IS 3 BP 497 EP 505 DI 10.1002/jmri.1880040343 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NP292 UT WOS:A1994NP29200039 PM 7802866 ER PT J AU GARRETT, DS KUSZEWSKI, J HANCOCK, TJ LODI, PJ VUISTER, GW GRONENBORN, AM CLORE, GM AF GARRETT, DS KUSZEWSKI, J HANCOCK, TJ LODI, PJ VUISTER, GW GRONENBORN, AM CLORE, GM TI THE IMPACT OF DIRECT REFINEMENT AGAINST 3-BOND HN-C-ALPHA-H COUPLING-CONSTANTS ON PROTEIN-STRUCTURE DETERMINATION BY NMR SO JOURNAL OF MAGNETIC RESONANCE SERIES B LA English DT Note ID IMMUNOGLOBULIN-BINDING DOMAIN; NUCLEAR-MAGNETIC-RESONANCE; IMPROVED LINEAR PREDICTION; CRYSTAL-STRUCTURE; 3-DIMENSIONAL STRUCTURE; INTERLEUKIN-1-BETA; RESOLUTION; SPECTROSCOPY; INHIBITOR; SPECTRA C1 NIDDKD,CHEM PHYS LAB,BETHESDA,MD 20892. RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 NR 25 TC 141 Z9 141 U1 0 U2 5 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 1064-1866 J9 J MAGN RESON SER B JI J. Magn. Reson. Ser. B PD MAY PY 1994 VL 104 IS 1 BP 99 EP 103 DI 10.1006/jmrb.1994.1061 PG 5 WC Physics, Atomic, Molecular & Chemical SC Physics GA NK509 UT WOS:A1994NK50900014 PM 8025816 ER PT J AU BEUTLER, JA CLARK, P ALVARADO, AB GOLIK, J AF BEUTLER, JA CLARK, P ALVARADO, AB GOLIK, J TI ESPERAMICIN-P, THE TETRASULFIDE ANALOG OF ESPERAMICIN-A(1) SO JOURNAL OF NATURAL PRODUCTS LA English DT Article AB A minor congener of esperamicin A(1) [1], designated esperamicin P (BMY-41339, 2), was isolated from a fermentation broth of Actinomadura verrucosospora and determined ro differ from esperamicin A, by having a methyl tetrasulfide moiety instead of a methyl trisulfide. It was active against xenografted tumors in mice and exhibited antimicrobial activity. Interconversions of 2 and 1 have been observed for DMSO solutions of both congeners at room temperature. C1 NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,FREDERICK,MD 21702. BRISTOL MYERS SQUIBB CO,ANTITUMOR CHEM,WALLINGFORD,CT 06492. RI Beutler, John/B-1141-2009 OI Beutler, John/0000-0002-4646-1924 NR 9 TC 9 Z9 9 U1 0 U2 1 PU AMER SOC PHARMACOGNOSY PI CINCINNATI PA LLOYD LIBRARY & MUSEUM 917 PLUM ST, CINCINNATI, OH 45202 SN 0163-3864 J9 J NAT PROD JI J. Nat. Prod. PD MAY PY 1994 VL 57 IS 5 BP 629 EP 633 DI 10.1021/np50107a010 PG 5 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA NT322 UT WOS:A1994NT32200010 PM 8064295 ER PT J AU NEWCOMER, S AF NEWCOMER, S TI THE POLITICS OF PREGNANCY - ADOLESCENT SEXUALITY AND PUBLIC-POLICY - LAWSON,A, RHODE,DL SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Book Review RP NEWCOMER, S (reprint author), NICHHD,BETHESDA,MD, USA. NR 1 TC 0 Z9 0 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3018 J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD MAY PY 1994 VL 182 IS 5 BP 311 EP 312 DI 10.1097/00005053-199405000-00019 PG 2 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA NL849 UT WOS:A1994NL84900020 ER PT J AU KORNER, M TARANTINO, N PLESKOFF, O LEE, LM DEBRE, P AF KORNER, M TARANTINO, N PLESKOFF, O LEE, LM DEBRE, P TI ACTIVATION OF NUCLEAR FACTOR KAPPA-B IN HUMAN NEUROBLASTOMA CELL-LINES SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE NUCLEAR FACTOR KAPPA-B; PROTEIN KINASE C; NEUROBLASTOMA; TUMOR NECROSIS FACTOR ALPHA; SIGNAL TRANSDUCTION ID TUMOR-NECROSIS-FACTOR; PROTEIN-KINASE-C; NERVE GROWTH-FACTOR; HUMAN-IMMUNODEFICIENCY-VIRUS; HUMAN NEURO-BLASTOMA; ENHANCER BINDING-ACTIVITY; FACTOR NF-KAPPA; TRANSCRIPTION FACTOR; FACTOR-ALPHA; DNA-BINDING AB The nuclear factor kappa B (NF-kappa B) is a eukaryotic transcription factor. In B cells and macrophages it is constitutively present in cell nuclei, whereas in many other cell types, NF-kappa B translocates from cytosol to nucleus as a result of transduction by tumor necrosis factor alpha (TNF alpha), phorbol ester, and other polyclonal signals. Using neuroblastoma cell lines as models, we have shown that in neural cells NF-kappa B was present in the cytosol and translocated into nuclei as a result of TNF alpha treatment. The TNF alpha-activated NF-kappa B was transcriptionally functional. NF-kappa B activation by TNF alpha was not correlated with cell differentiation or proliferation. However, reagents such as nerve growth factor (NGF) and the phorbol ester phorbol 12-myristate 13-acetate (PMA), which induce phenotypical differentiation of the SH-SY5Y neuroblastoma cell line, activated NF-kappa B, but only in that particular cell line. In a NGF-responsive rat pheochromocytoma cell line, PC12, PMA activated NF-kappa B, whereas NGF did not. In other neuroblastoma cell lines, such as SK-N-Be(2), the lack of PMA induction of differentiation was correlated with the lack of NF-kappa B activation. We found, moreover, that in SK-N-Be(2) cells protein kinase C (PKC) enzymatic activity was much lower compared with that in a control cell line and that the low PKC enzymatic activity was due to low PKC protein expression. NF-kappa B was not activated by retinoic acid, which induced morphological differentiation of all the neuroblastoma cell lines used in the present study. Thus, NF-kappa B activation was not required for neuroblastoma cell differentiation. Furthermore, the results obtained with TNF alpha proved that NF-kappa B activation was not sufficient for induction of neuroblastoma differentiation. C1 NCI,FREDERICK CANC RES FACIL,PROGRAM RESOURCES INC,NUCL ACID & PROT SYNTH LAB,FREDERICK,MD 21701. RP KORNER, M (reprint author), HOP LA PITIE SALPETRIERE,IMMUNOL CELLULAIRE & TISSULAIRE LAB,CNRS,URA 625,BATIMENT CERVI,F-75013 PARIS,FRANCE. NR 55 TC 27 Z9 27 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAY PY 1994 VL 62 IS 5 BP 1716 EP 1726 PG 11 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA NG694 UT WOS:A1994NG69400008 PM 8158122 ER PT J AU SUYAMA, K DYKSTRA, KH MASANA, MI MANJI, HK POTTER, WZ AF SUYAMA, K DYKSTRA, KH MASANA, MI MANJI, HK POTTER, WZ TI IN-VIVO EVIDENCE THAT NONNEURONAL BETA-ADRENOCEPTORS AS WELL AS DOPAMINE-RECEPTORS CONTRIBUTE TO CYCLIC-AMP EFFLUX IN RAT STRIATUM SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE CYCLIC AMP; BETA-ADRENOCEPTORS; DOPAMINE RECEPTORS; FLUOROCITRATE; KAINIC ACID; STRIATUM; MICRODIALYSIS ID CHRONIC ELECTROCONVULSIVE SHOCK; SENSITIVE ADENYLATE-CYCLASE; KAINIC ACID; ADRENERGIC-RECEPTORS; BETA-2-ADRENERGIC RECEPTORS; GLIAL LOCALIZATION; NUCLEUS-ACCUMBENS; SUBSTANTIA-NIGRA; CAUDATE-NUCLEUS; BRAIN DIALYSIS AB We applied in vivo microdialysis to assess the effects of dopaminergic and beta-adrenergic receptor stimulation on cyclic AMP efflux in rat striatum under chloral hydrate anesthesia. Dopamine (up to 1 mM) infused for 20 min through the probe did not increase cyclic AMP, whereas both the selective dopamine D-1 agonist SKF 38393 and D-2 antagonist sulpiride produced modest increases. It is interesting that the beta-adrenoceptor agonist isoproterenol produced a marked increase (204.7% of basal level at 1 mM) which was antagonized by the beta-adrenoceptor antagonist propranolol. Pretreatment with a glial selective metabolic inhibitor, fluorocitrate (1 mM), by a 5-h infusion through the probe attenuated basal cyclic AMP efflux by 30.3% and significantly blocked the response to isoproterenol. By contrast, striatal injection of a neurotoxin, kainic acid (2.5 mu g), 2 days before the dialysis experiment did not affect basal cyclic AMP or the response to isoproterenol, but blocked the response to SKF 38393. These data demonstrate that beta-adrenoceptors as well as dopamine receptors contribute to cyclic AMP efflux in rat striatum in vivo. They also suggest that basal and beta-adrenoceptor-stimulated cyclic AMP efflux are substantially dependent on intact glial cells. C1 NIH,NCRR,BIOMED ENGN & INSTRUMENTAT PROGRAM,BETHESDA,MD. RP SUYAMA, K (reprint author), NIMH,CLIN PHARMACOL SECT,EXPTL THERAPEUT BRANCH,BLDG 10,ROOM 2D-46,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 53 TC 11 Z9 11 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAY PY 1994 VL 62 IS 5 BP 1734 EP 1740 PG 7 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA NG694 UT WOS:A1994NG69400010 PM 8158123 ER PT J AU ZATZ, M AF ZATZ, M TI PHOTOENDOCRINE TRANSDUCTION IN CULTURED CHICK PINEAL CELLS .IV. WHAT DO VITAMIN-A DEPLETION AND RETINALDEHYDE ADDITION DO TO THE EFFECTS OF LIGHT ON THE MELATONIN RHYTHM SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE CIRCADIAN RHYTHMS; PHOTORECEPTORS; PHOTOENTRAINMENT ID N-ACETYLTRANSFERASE ACTIVITY; CIRCADIAN CLOCK; PERTUSSIS TOXIN; GLAND; SENSITIVITY; INVITRO; RETINA; GMP; PHOTOSENSITIVITY; IMMUNOREACTIVITY AB Light has at least two distinguishable effects on the circadian rhythm of melatonin output displayed by dispersed chick pineal cells in static culture: acute suppression of melatonin output and entrainment (phase shifts) of the underlying pacemaker. Previous results indicated that these two effects of light are mediated by different mechanistic pathways. The pathways for the acute and phase-shifting effects of light either branch from the same, single photopigment or differ from the outset, starting from separate photopigments. If a single rhodopsin-like photopigment mediates both effects of light, then vitamin A depletion and retinoid addition should affect both responses in parallel, although not proportionately. We therefore compared the effects of vitamin A depletion and retinoid addition on the acute and phase-shifting effects of light under several experimental conditions. When chick pineal cells were depleted of vitamin A, acute responses to light were markedly reduced. Addition of 11 cis-retinaldehyde specifically restored (and enhanced) the acute response. When allowed to free run in constant red light, depleted cells displayed a rhythm of melatonin output with the same period as that of control cells. In contrast to the acute effects, phase shifts in response to 2- or 4-h light pulses did not differ between depleted and control cells. Addition of retinaldehyde to depleted cells did not, by itself, reduce melatonin output or induce phase shifts. Retinaldehyde did increase the acute response to 4-h light pulses but not the ensuing phase shifts. Responses increased with duration of the light pulse: Both the acute effect and the phase shifts induced by 4-h light pulses were considerably larger than those induced by 2-h (or 1-h) light pulses. Addition of retinaldehyde to depleted cells increased the acute effect of 2-h (or 1-h) light pulses to at least that seen with 4-h light pulses but did not increase the size of the ensuing phase shifts. These results strongly confirm previous dissociations of the mechanistic pathways mediating the acute and phase-shifting effects of light on chick pineal cells. They also support a role for rhodopsin-like photopigment in the acute, but not phase-shifting, response. They favor, but do not prove, the conclusion that separate photopigments mediate the acute and entraining effects of light. RP ZATZ, M (reprint author), NIMH,CELL BIOL LAB,BIOCHEM PHARMACOL SECT,BLDG 36,ROOM 2A-17,BETHESDA,MD 20892, USA. NR 46 TC 29 Z9 30 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAY PY 1994 VL 62 IS 5 BP 2001 EP 2011 PG 11 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA NG694 UT WOS:A1994NG69400044 PM 8158147 ER PT J AU TIAN, B RAUSCHECKER, JP AF TIAN, B RAUSCHECKER, JP TI PROCESSING OF FREQUENCY-MODULATED SOUNDS IN THE CATS ANTERIOR AUDITORY FIELD SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID COMBINATION-SENSITIVE NEURONS; VISUAL-CORTEX; SQUIRREL-MONKEY; AMPLITUDE-MODULATION; CORTICAL FIELDS; CEREBRAL-CORTEX; EARLY BLINDNESS; SINGLE NEURONS; DIRECTION; ORGANIZATION AB 1. Single-neuron activity was recorded from the anterior auditory field (AAF) in the cortex of gas-anesthetized cats. 2. Tone bursts and broad-band complex sounds were used for auditory stimulation. Responses to frequency-modulated (FM) sounds, in particular, were studied systematically. 3. Linear FM sweeps were centered around the best frequency (BF) of a neuron and had an excursion large enough to cover its whole frequency tuning range. Rate and direction of change of the FM sweeps were varied. 4. In 69% of the FM responses, a peak was found at an instantaneous frequency that corresponded to the BF in the pure-tone response. Thirty-three percent of the units had multiple maxima in their FM response. These secondary maxima were not always reflected in the pure-tone response of the same neurons. 5. The vast majority of AAF neurons showed one of two types of selectivity for FM rate. Depending on the criterion, almost half of the cells (46%) preferred fast changes of >200 Hz/ms (high-pass) in both FM directions. Forty-eight percent of all neurons showed band-pass behavior with a clear preference in the middle range of FM rates in one or both directions. Low-pass or all-pass neurons made up only a small proportion (4 and 1%, respectively) of AAF neurons. 6. When both directions of an FM sweep (low-to-high and high-to-low-frequency) were tested, 66% of the neurons clearly were selective for one direction. This selectivity was not present necessarily at the preferred FM rate. In general, FM direction selectivity was most pronounced at slower FM rates. 7. The selectivity of AAF neurons for the rate and direction of FM sounds makes these neurons suitable for the detection and analysis of communication sounds, which often contain FM components with a particular sweep rate and direction. C1 NIMH,NEUROPHYSIOL LAB,POOLESVILLE,MD 20837. MAX PLANCK INST BIOL CYBERNET,D-72076 TUBINGEN,GERMANY. RI Rauschecker, Josef/A-4120-2013 NR 67 TC 98 Z9 101 U1 4 U2 6 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD MAY PY 1994 VL 71 IS 5 BP 1959 EP 1975 PG 17 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA NL773 UT WOS:A1994NL77300029 PM 8064359 ER PT J AU CAMERA, L KINUYA, S GARMESTANI, K WU, CC BRECHBIEL, MW PAI, LH MCMURRY, TJ GANSOW, OA PASTAN, I PAIK, CH CARRASQUILLO, JA AF CAMERA, L KINUYA, S GARMESTANI, K WU, CC BRECHBIEL, MW PAI, LH MCMURRY, TJ GANSOW, OA PASTAN, I PAIK, CH CARRASQUILLO, JA TI EVALUATION OF THE SERUM STABILITY AND IN-VIVO BIODISTRIBUTION OF CHX-DTPA AND OTHER LIGANDS FOR YTTRIUM LABELING OF MONOCLONAL-ANTIBODIES SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE Y-88; LIGANDS; MONOCLONAL ANTIBODIES; BIODISTRIBUTION; SERUM STABILITY ID BIFUNCTIONAL CHELATE TECHNIQUES; HUMAN COLONIC TUMOR; CARCINOMA XENOGRAFTS; NUDE-MICE; CARCINOEMBRYONIC ANTIGEN; RADIOIMMUNOTHERAPY; Y-90; THERAPY; CANCER; AGENT AB Serum stability and in vivo biodistribution of both A and B isomers of the 2-(p-isothiocyanatobenzyl) (p-SCN-Bz)-cyclohexyldiethylenetriaminepentaacetic acid ligand (CHX-DTPA), a recently developed backbone-substituted derivative of DTPA, were evaluated and compared to those of 2-(p-SCN-Bz)-6-methyl-DTPA (1B4M-DTPA) and 2-(p-SCN-Bz)-1,4,7,10-tetraazacyclododecane tetra-acetic acid (2B-DOTA). Methods: Stability of Y-88-labeled ligands (0.1 mu M) was evaluated in serum for up to 17 days. For biodistribution, ligands were conjugated to monoclonal antibody (Mab) B3, a murine IgG1k, and labeled with Y-88 at 0.1-0.3 mCi/mg. Nontumor-bearing nude mice were injected intravenously with 1-2 mu Ci/4-lO mu g Of Y-88-labeled B3-conjugates and killed at 6 hr and daily up to 168 hr postinjection. Indium-111-(1B4M)-B3 was co-injected in all mice as internal control. Results: Serum stability of Y-88-DOTA failed to show any significant release of activity, whereas pseudo-first-order dissociation rate constants of 3.97 x 10(-3), 2.54 x 10(-3) and 1.46 x 10(-2) (day(-1)) were calculated for Y-88-1B4M, Y-88-CHX-A and Y-88-CHX-B, respectively. Accordingly, cortical bone uptake of Y-88 was significantly higher for all DTPA-derivative chelates than for DOTA. Conclusions: While none of the DTPA-derivative chelates could challenge DOTA in its ability to hold the radioyttrium, significant differences were observed in the kinetic inertness of the A and B isomers of CHX, indicating that the CHX-B ligand is not as suitable for Y-90-labeling of Mabs. C1 NIH,WARREN G MAGNUSON CLIN CTR,DEPT NUCL MED,CHEM SECT,RADIAT ONCOL BRANCH,BETHESDA,MD 20892. NCI,MOLEC BIOL LAB,BETHESDA,MD 20892. RI Carrasquillo, Jorge/E-7120-2010; OI Carrasquillo, Jorge/0000-0002-8513-5734 NR 48 TC 101 Z9 101 U1 0 U2 5 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1994 VL 35 IS 5 BP 882 EP 889 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NK514 UT WOS:A1994NK51400031 PM 8176477 ER PT J AU BARKER, WC BACHARACH, SL FREEDMAN, NMT BARTLETT, ML DILSIZIAN, V AF BARKER, WC BACHARACH, SL FREEDMAN, NMT BARTLETT, ML DILSIZIAN, V TI EXERCISE GATED BLOOD-POOL SPECT FOR SIMULTANEOUS MULTIVIEW WALL-MOTION STUDIES - FEASIBILITY SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1994 VL 35 IS 5 SU S BP P90 EP P90 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NK909 UT WOS:A1994NK90900357 ER PT J AU BERMAN, KF SCHMIDT, PJ OSTREM, JL DANACEAU, MA ESPOSITO, G VANHORN, JD MATTAY, VS RUBINOW, DR WEINBERGER, DR AF BERMAN, KF SCHMIDT, PJ OSTREM, JL DANACEAU, MA ESPOSITO, G VANHORN, JD MATTAY, VS RUBINOW, DR WEINBERGER, DR TI EFFECTS OF GONADAL-STEROIDS ON CEREBRAL BLOOD-FLOW - PATIENTS WITH MENSTRUAL-RELATED MOOD DISORDER AND CONTROLS STUDIED WITH PET DURING MEDICAL OOPHORECTOMY AND HORMONE REPLACEMENT SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIMH,IRP,CLIN BRAIN DISORDERS BRANCH,BETHESDA,MD 20892. NIMH,IRP,BIOL PSYCHIAT BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1994 VL 35 IS 5 SU S BP P53 EP P53 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NK909 UT WOS:A1994NK90900207 ER PT J AU CAMERA, L KINUYA, S GARMESTANI, K BRECHBIEL, MW WU, C PAI, LH MCMURRY, TJ GANSOW, OA PASTAN, I PAIK, CH CARRASQUILLO, JA AF CAMERA, L KINUYA, S GARMESTANI, K BRECHBIEL, MW WU, C PAI, LH MCMURRY, TJ GANSOW, OA PASTAN, I PAIK, CH CARRASQUILLO, JA TI COMPARATIVE BIODISTRIBUTION OF INDIUM AND YTTRIUM LABELED B3 MONOCLONAL-ANTIBODY SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NCI,DEPT NUCL MED,RADIAT ONCOL BRANCH,BETHESDA,MD 20892. NCI,MOLEC BIOL LAB,BETHESDA,MD 20892. RI Carrasquillo, Jorge/E-7120-2010 NR 0 TC 1 Z9 1 U1 0 U2 2 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1994 VL 35 IS 5 SU S BP P63 EP P63 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NK909 UT WOS:A1994NK90900247 ER PT J AU CARRASQUILLO, J MULLIGAN, T CHUNG, Y MILENIC, D LORA, M SCHLOM, J GOECKELER, W FORDYCE, W CHENG, R FEUERESTEIN, I PERENTESIS, P PALK, CH CURT, G COWAN, K OSHAUGHNESSY, J AF CARRASQUILLO, J MULLIGAN, T CHUNG, Y MILENIC, D LORA, M SCHLOM, J GOECKELER, W FORDYCE, W CHENG, R FEUERESTEIN, I PERENTESIS, P PALK, CH CURT, G COWAN, K OSHAUGHNESSY, J TI PHARMACOKINETICS AND BIODISTRIBUTION OF INTRAVENOUS LU-177 CC49 MURINE MONOCLONAL-ANTIBODY (MAB) IN PATIENTS WITH METASTATIC ADENOCARCINOMA SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 DOW CHEM CO USA,NIH,MIDLAND,MI. RI Carrasquillo, Jorge/E-7120-2010 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1994 VL 35 IS 5 SU S BP P100 EP P101 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NK909 UT WOS:A1994NK90900399 ER PT J AU DIVGI, CR SCOTT, AM YOUNG, C KEMENY, N CONTI, J DAGHIGHIAN, F BROUSSARD, E SCHLOM, J LARSON, SM AF DIVGI, CR SCOTT, AM YOUNG, C KEMENY, N CONTI, J DAGHIGHIAN, F BROUSSARD, E SCHLOM, J LARSON, SM TI RADIOIMMUNOTHERAPY (RIT) WITH 1-131 MONOCLONAL-ANTIBODY (MAB) CC49 AND DEOXYSPERGUALINE (DSG) IN METASTATIC COLON-CANCER SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 MEM SLOAN KETTERING CANC CTR,NEW YORK,NY 10021. NCI,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1994 VL 35 IS 5 SU S BP P102 EP P102 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NK909 UT WOS:A1994NK90900406 ER PT J AU FANG, QW LEE, JT CHANG, HK PARK, SG BRECHBIEL, MW GANSOW, OA CARRASQUILLO, JA AF FANG, QW LEE, JT CHANG, HK PARK, SG BRECHBIEL, MW GANSOW, OA CARRASQUILLO, JA TI USE OF MOAB AS A PROTEIN CARRIER OF RECEPTOR-BINDING LIGAND AND IN-111 CHELATOR SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. RI Carrasquillo, Jorge/E-7120-2010 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1994 VL 35 IS 5 SU S BP P29 EP P29 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NK909 UT WOS:A1994NK90900106 ER PT J AU GOLDSTEIN, SR DAUBEWITHERSPOON, ME GREEN, MV AF GOLDSTEIN, SR DAUBEWITHERSPOON, ME GREEN, MV TI A DEVICE FOR CONTINUOUS MEASUREMENT OF HEAD POSITION DURING PET BRAIN IMAGING SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 1 TC 3 Z9 3 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1994 VL 35 IS 5 SU S BP P40 EP P41 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NK909 UT WOS:A1994NK90900154 ER PT J AU GREEN, MV SEIDEL, J GANDLER, WR AF GREEN, MV SEIDEL, J GANDLER, WR TI A SMALL ANIMAL SYSTEM CAPABLE OF PET, SPECT AND PLANAR IMAGING SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 5 Z9 5 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1994 VL 35 IS 5 SU S BP P61 EP P61 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NK909 UT WOS:A1994NK90900239 ER PT J AU JOHN, CS MOODY, TW BOWEN, WD VILNER, BJ VARMA, VM MCAFEE, JG AF JOHN, CS MOODY, TW BOWEN, WD VILNER, BJ VARMA, VM MCAFEE, JG TI SIGMA-RECEPTORS ARE EXPRESSED IN NONSMALL CELL LUNG-CARCINOMA - POTENTIAL USE FOR TUMOR VISUALIZATION SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 GEORGE WASHINGTON UNIV,MED CTR,WASHINGTON,DC 20037. NIDDK,BETHESDA,MD. NR 1 TC 3 Z9 3 U1 0 U2 1 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1994 VL 35 IS 5 SU S BP P248 EP P248 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NK909 UT WOS:A1994NK90901017 ER PT J AU JOHN, CS BOWEN, WD VILNER, BJ MCAFEE, JG AF JOHN, CS BOWEN, WD VILNER, BJ MCAFEE, JG TI SYNTHESIS AND CHARACTERIZATION OF (N-BENZYLPIPERIDIN-4-YL)-4-IODOBENZAMIDE, 4-IBP - A NEW SIGMA-LIGAND - HIGH-AFFINITY BINDING TO MCF-7 BREAST-CANCER CELLS SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 GEORGE WASHINGTON UNIV,MED CTR,WASHINGTON,DC 20037. NIDDK,BETHESDA,MD. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1994 VL 35 IS 5 SU S BP P246 EP P246 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NK909 UT WOS:A1994NK90901010 ER PT J AU JONES, DW COPPOLA, R GOREY, JG SAUNDERS, RC LEE, KS KNABLE, MB WEINBERGER, DR AF JONES, DW COPPOLA, R GOREY, JG SAUNDERS, RC LEE, KS KNABLE, MB WEINBERGER, DR TI CORTICAL RETENTION OF [I-123] IBZM - LACK OF DISPLACEMENT BY HALOPERIDOL IN NONHUMAN PRIMATE EXCLUDES D-4 BINDING SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 ST ELIZABETH HOSP,NIMH,IRP,CLIN BRAIN DISORDERS BRANCH,WASHINGTON,DC. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1994 VL 35 IS 5 SU S BP P199 EP P199 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NK909 UT WOS:A1994NK90900806 ER PT J AU KIM, SE SCHEFFEL, U BOJA, JW KUHAR, MJ AF KIM, SE SCHEFFEL, U BOJA, JW KUHAR, MJ TI EFFECT OF RESERPINE UPON BINDING OF H-3 WIN-35,428 TO DOPAMINE UPTAKE SITES SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 JOHNS HOPKINS MED INST,BALTIMORE,MD 21205. NIDA,ADDICT RES CTR,BALTIMORE,MD 21224. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1994 VL 35 IS 5 SU S BP P199 EP P199 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NK909 UT WOS:A1994NK90900807 ER PT J AU KLESEWETTER, DO LANG, L LEE, JT PARK, SG PALK, CH ECKELMAN, WC AF KLESEWETTER, DO LANG, L LEE, JT PARK, SG PALK, CH ECKELMAN, WC TI THE DEVELOPMENT OF MUSCARINIC AGONISTS FOR USE IN CHARACTERIZING ALZHEIMERS-DISEASE SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1994 VL 35 IS 5 SU S BP P83 EP P84 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NK909 UT WOS:A1994NK90900330 ER PT J AU LANG, L ECKELMAN, WC AF LANG, L ECKELMAN, WC TI ONE-STEP SYNTHESIS OF F-18 LABELED [F-18] N-SUCCINIMIDYL-4-(FLUOROMETHYL)-BENZOATE FOR PROTEIN LABELING SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1994 VL 35 IS 5 SU S BP P249 EP P249 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NK909 UT WOS:A1994NK90901022 ER PT J AU LEE, JT PALK, CH KLESEWETTER, DO PARK, SG ECKELMAN, WC AF LEE, JT PALK, CH KLESEWETTER, DO PARK, SG ECKELMAN, WC TI THE ANALYSIS OF (RR), (RS), (SR), AND (SS) 4-FLUOROALKYL DERIVATIVES OF 3-QUINUCLIDINYL BENZILATE (QNB) IN-VIVO SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 1 U2 1 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1994 VL 35 IS 5 SU S BP P53 EP P53 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NK909 UT WOS:A1994NK90900205 ER PT J AU LEE, JT GARMESTANI, K BRECHBIEL, MW PARK, SG WU, C LE, N GANSOW, OA CARRASQUILLO, JA NEUMANN, RD PAIK, CH AF LEE, JT GARMESTANI, K BRECHBIEL, MW PARK, SG WU, C LE, N GANSOW, OA CARRASQUILLO, JA NEUMANN, RD PAIK, CH TI EVALUATION OF IN-VIVO STABILITY OF 3 GA-67 CHELATOR-MOAB CONJUGATES IN MICE SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. RI Carrasquillo, Jorge/E-7120-2010 NR 0 TC 1 Z9 1 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1994 VL 35 IS 5 SU S BP P29 EP P29 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NK909 UT WOS:A1994NK90900108 ER PT J AU LEE, KS COPPOLA, R SAUNDERS, R GOREY, J HE, XS MATECKA, D DECOSTA, BR GU, ZQ SKOLNICK, P RICE, KC WEINBERGER, DR AF LEE, KS COPPOLA, R SAUNDERS, R GOREY, J HE, XS MATECKA, D DECOSTA, BR GU, ZQ SKOLNICK, P RICE, KC WEINBERGER, DR TI SPECT IMAGING OF DIAZEPAM-INSENSITIVE BENZODIAZEPINE RECEPTORS IN PRIMATES SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIMH,CBDB,WASHINGTON,DC. NIDDKD,MED CHEM LAB,BETHESDA,MD 20892. NIDDKD,NEUROSCI LAB,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1994 VL 35 IS 5 SU S BP P247 EP P247 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NK909 UT WOS:A1994NK90901013 ER PT J AU MCAFEE, JG CARRASQUILLO, JA CAMERA, L OSHAUGHNESSY, JA COWAN, KH NEUMANN, RD AF MCAFEE, JG CARRASQUILLO, JA CAMERA, L OSHAUGHNESSY, JA COWAN, KH NEUMANN, RD TI CHANGES IN SKELETAL IMAGES INDUCED BY GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR (GM-CSF) IN PATIENTS WITH LOCALLY ADVANCED AND METASTATIC BREAST-CANCER SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NCI,DEPT NUCL MED,BETHESDA,MD 20892. NCI,MED BRANCH,BETHESDA,MD 20892. RI Carrasquillo, Jorge/E-7120-2010 NR 0 TC 2 Z9 2 U1 0 U2 1 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1994 VL 35 IS 5 SU S BP P89 EP P89 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NK909 UT WOS:A1994NK90900353 ER PT J AU PAJEVIC, S BACHARACH, SL CARSON, RE DILSIZIAN, V AF PAJEVIC, S BACHARACH, SL CARSON, RE DILSIZIAN, V TI CORRECTION FOR TIME SHIFTS IN THE CARDIAC (H2O)-O-15 BLOODFLOW MODEL SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 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 SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1994 VL 35 IS 5 SU S BP P183 EP P183 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NK909 UT WOS:A1994NK90900736 ER PT J AU PODOLOFF, DA BHADKAMKAR, VA KASI, LP MACEY, DJ ROSENBLUM, MG GRANT, EJ ZHANG, HZ KATZ, RL REIGER, PT LEBHERZ, D SOUTH, MS DHINGRA, K GREINER, JW SCHLOM, J MURRAY, JL AF PODOLOFF, DA BHADKAMKAR, VA KASI, LP MACEY, DJ ROSENBLUM, MG GRANT, EJ ZHANG, HZ KATZ, RL REIGER, PT LEBHERZ, D SOUTH, MS DHINGRA, K GREINER, JW SCHLOM, J MURRAY, JL TI PHASE-II TRIAL OF I-131 CC49 PLUS ALPHA-INTERFERON (RIFN] IN REFRACTORY METASTATIC BREAST-CANCER SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 UNIV TEXAS,MD ANDERSON CANC CTR,HOUSTON,TX. NCI,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1994 VL 35 IS 5 SU S BP P101 EP P101 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NK909 UT WOS:A1994NK90900403 ER PT J AU SCHMIDT, K MIES, G DIENEL, G CRUZ, N CRANE, A SOKOLOFF, L AF SCHMIDT, K MIES, G DIENEL, G CRUZ, N CRANE, A SOKOLOFF, L TI LIMITATIONS OF KINETIC MODELING FOR PREDICTIONS OF INTRACOMPARTMENTAL CONCENTRATIONS FROM TOTAL TISSUE ACTIVITY SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIMH,CEREBRAL METAB LAB,BETHESDA,MD 20892. MAX PLANCK INST NEUROL RES,W-5000 COLOGNE,GERMANY. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1994 VL 35 IS 5 SU S BP P176 EP P176 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NK909 UT WOS:A1994NK90900708 ER PT J AU SEIDEL, J GANDLER, WR GREEN, MV AF SEIDEL, J GANDLER, WR GREEN, MV TI A VERY HIGH-RESOLUTION SINGLE-SLICE SMALL ANIMAL PET SCANNER BASED ON DIRECT-DETECTION OF COINCIDENCE LINE END-POINTS SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 7 Z9 7 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1994 VL 35 IS 5 SU S BP P40 EP P40 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NK909 UT WOS:A1994NK90900152 ER PT J AU SEIDEL, J GREEN, MV DAUBAWITHERSPOON, ME BACHARACH, SL AF SEIDEL, J GREEN, MV DAUBAWITHERSPOON, ME BACHARACH, SL TI CORRECTION FOR COMPTON SCATTER USING THE LOCAL SCATTER FRACTION TO ESTIMATE SMALL-ANGLE SCATTER SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 1 TC 1 Z9 1 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1994 VL 35 IS 5 SU S BP P143 EP P143 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NK909 UT WOS:A1994NK90900578 ER PT J AU VILLEMAGNE, VL GILSON, S KIMES, AS PHILLIPS, RL WONG, DF LIU, X BRIDGE, P HARRIS, PJ DANNALS, RF RUFF, M PERT, C WAGNER, HN LONDON, ED AF VILLEMAGNE, VL GILSON, S KIMES, AS PHILLIPS, RL WONG, DF LIU, X BRIDGE, P HARRIS, PJ DANNALS, RF RUFF, M PERT, C WAGNER, HN LONDON, ED TI EFFECTS OF PEPTIDE-T ON CEREBRAL GLUCOSE-METABOLISM IN AIDS DEMENTIA COMPLEX (ADC) STUDIED BY POSITRON EMISSION TOMOGRAPHY (PET) AND [F-18] FDG SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIDA,ADDICT RES CTR,BALTIMORE,MD 21224. JOHNS HOPKINS MED INST,BALTIMORE,MD 21205. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1994 VL 35 IS 5 SU S BP P118 EP P118 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NK909 UT WOS:A1994NK90900473 ER PT J AU WEINBERG, IN THOMPSON, CJ MURTHY, K MAKO, F AF WEINBERG, IN THOMPSON, CJ MURTHY, K MAKO, F TI FEASIBILITY STUDY FOR LOW-DOSE POSITRON EMISSION MAMMOGRAPHY SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 JOHNS HOPKINS UNIV HOSP,BALTIMORE,MD 21205. NIH,DIAGNOST RADIOL RES LAB,BETHESDA,MD 20892. MCGILL UNIV,MONTREAL,PQ,CANADA. FM TECHNOL,FAIRFAX,VA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1994 VL 35 IS 5 SU S BP P61 EP P62 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NK909 UT WOS:A1994NK90900240 ER PT J AU WU, C BRECHBEIL, MW KOZAK, RW GANSOW, OA AF WU, C BRECHBEIL, MW KOZAK, RW GANSOW, OA TI PREPARATION AND CHARACTERIZATION OF DENDRIMER-BASED POLY-METAL CHELATES AND MONOCLONAL-ANTIBODIES CONJUGATES SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. US FDA,BETHESDA,MD 20014. NR 0 TC 1 Z9 1 U1 0 U2 2 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1994 VL 35 IS 5 SU S BP P62 EP P62 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NK909 UT WOS:A1994NK90900242 ER PT J AU ZEEBERG, BR KIESWETTER, DO LEE, JT PAIK, CH PARK, SG REBA, RC ECKELMAN, WC AF ZEEBERG, BR KIESWETTER, DO LEE, JT PAIK, CH PARK, SG REBA, RC ECKELMAN, WC TI GRAPHICAL ANALYSIS OF FLUOROALKYL QNB DEMONSTRATING IN-VIVO M2 MACHR SELECTIVITY SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 GEORGE WASHINGTON UNIV,WASHINGTON,DC. NIH,BETHESDA,MD 20892. UNIV CHICAGO,CHICAGO,IL 60637. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1994 VL 35 IS 5 SU S BP P200 EP P200 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NK909 UT WOS:A1994NK90900808 ER PT J AU YERGEY, AL ABRAMS, SA VIEIRA, NE ALDROUBI, A MARINI, J SIDBURY, JB AF YERGEY, AL ABRAMS, SA VIEIRA, NE ALDROUBI, A MARINI, J SIDBURY, JB TI DETERMINATION OF FRACTIONAL ABSORPTION OF DIETARY CALCIUM IN HUMANS SO JOURNAL OF NUTRITION LA English DT Article DE MASS SPECTROMETRY; HUMANS; STABLE ISOTOPES; DIETARY CALCIUM ABSORPTION ID STABLE ISOTOPES; MASS-SPECTROMETRY; PREMATURE-INFANTS; KINETICS; TRACERS; CA-46; TESTS AB Four dual-isotopic label methods for determining true fractional absorption of dietary calcium were compared in 23 subjects. The ratio of the integrals of oral label in a 24-h pooled urine to intravenous label in the same urine is called alpha(24h) and was taken as the standard against which the others were compared. alpha(Spot) is the ratio of the fraction of oral label to the fraction of intravenous label in a single urine specimen; alpha(Lag) is the ratio of the level of oral label in blood 4 h after administration to the level of intravenous label in blood 2 h after administration. alpha(Dec) is obtained by deconvoluting response to the intravenous label from the response to the oral tracer. Results were as follows: alpha(24h) = 0.273 +/- 0.124, alpha(Dec) = 0.300 +/- 0.101 (n = 14), alpha(Spot) = 0.359 +/- 0.179, and alpha(Lag) = 0.271 +/- 0.103. The Bland-Altman approach for comparison of methods was used to show that results for alpha(Spot) and alpha(Lag) can be expected, with a 95% confidence limit, to differ from the value of alpha(24h) by 60 and 69%, respectively. The results for alpha(Dec) were shown to be not only indistinguishable from alpha(24h) but identical from a theoretical perspective. C1 USDA ARS,CHILDRENS NUTR RES CTR,HOUSTON,TX. NIH,BIOMED ENGN PROGRAM,BETHESDA,MD 20892. RP YERGEY, AL (reprint author), NICHHD,BETHESDA,MD 20892, USA. RI Aldroubi, Akram/J-7186-2012; OI Abrams, Steven/0000-0003-4972-9233 NR 27 TC 73 Z9 74 U1 0 U2 1 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-3166 J9 J NUTR JI J. Nutr. PD MAY PY 1994 VL 124 IS 5 BP 674 EP 682 PG 9 WC Nutrition & Dietetics SC Nutrition & Dietetics GA NK245 UT WOS:A1994NK24500009 PM 8169659 ER PT J AU DIONNE, RA AF DIONNE, RA TI COMPARISON OF PROPOFOL AND METHOHEXITAL FOR DEEP SEDATION - DISCUSSION SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article RP DIONNE, RA (reprint author), NIDR,BETHESDA,MD 20892, USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD MAY PY 1994 VL 52 IS 5 BP 452 EP 453 DI 10.1016/0278-2391(94)90338-7 PG 2 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA NL839 UT WOS:A1994NL83900005 ER PT J AU KOVACS, G TORY, K KOVACS, A AF KOVACS, G TORY, K KOVACS, A TI DEVELOPMENT OF PAPILLARY RENAL-CELL TUMORS IS ASSOCIATED WITH LOSS OF Y-CHROMOSOME-SPECIFIC DNA-SEQUENCES SO JOURNAL OF PATHOLOGY LA English DT Article DE KIDNEY CANCER; Y CHROMOSOME; RFLP ANALYSIS ID NORMAL KIDNEY TISSUE; CARCINOMA; CYTOGENETICS; TUMORS; TRANSLOCATION; ABERRATIONS; NEOPLASIA; TRISOMY-7; CHILD AB Twenty-two papillary renal cell tumours were analysed by Southern hybridization using eight DNA probes from homologous regions of the X and Y chromosomes and two Y-chromosome-specific DNA probes. Sixteen of the 19 papillary renal cell tumours of male patients showed the loss of Y-chromosome-specific sequences. No loss of heterozygosity was detected in three tumours that developed in females. The frequency of loss of the Y chromosome was established in 50 non-papillary renal cell carcinomas as well. Only seven of the 31 non-papillary renal cell carcinomas obtained from male patients had lost the Y-chromosome-specific sequences, whereas no allelic loss was found in 19 non-papillary tumours obtained from female patients. Papillary renal cell tumours show a strong male preponderance (6:1) and loss of Y chromosome in 84 per cent of the cases, whereas non-papillary renal cell carcinomas show only a slight male preponderance (1.5:1) and the Y chromosome is lost in only 22 per cent of the cases. These data suggest that a tumour suppressor gene is localized at one of the homologous regions of the X and Y chromosomes, the homozygous inactivation of which is associated with the development of papillary renal cell tumours. C1 UNIV ZURICH HOSP,INST NEUROPATHOL,CH-8091 ZURICH,SWITZERLAND. PROGRAM RESOURCES INC,GEN DYNAM CORP,NCI,FREDERICK CANC RES & DEV CTR,FREDERICK,MD. UNIV FREIBURG,INST PATHOL,W-7800 FREIBURG,GERMANY. NR 30 TC 18 Z9 19 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0022-3417 J9 J PATHOL JI J. Pathol. PD MAY PY 1994 VL 173 IS 1 BP 39 EP 44 DI 10.1002/path.1711730107 PG 6 WC Oncology; Pathology SC Oncology; Pathology GA NR379 UT WOS:A1994NR37900006 PM 7931836 ER PT J AU CAMPAIGNE, BN MORRISON, JA SCHUMANN, BC FALKNER, F LAKATOS, E SPRECHER, D SCHREIBER, GB AF CAMPAIGNE, BN MORRISON, JA SCHUMANN, BC FALKNER, F LAKATOS, E SPRECHER, D SCHREIBER, GB TI INDEXES OF OBESITY AND COMPARISONS WITH PREVIOUS NATIONAL SURVEY DATA IN 9-YEAR-OLD AND 10-YEAR-OLD BLACK-AND-WHITE GIRLS - THE NATIONAL HEART, LUNG, AND BLOOD INSTITUTE GROWTH AND HEALTH STUDY SO JOURNAL OF PEDIATRICS LA English DT Article ID BOGALUSA HEART; RISK-FACTORS; CHILDREN; HYPERTENSION; ADOLESCENTS; MATURATION AB Objective: To (I) describe anthropometric and body-size measurements in the National Heart, Lung, and Blood Institute Growth and Health Study (NGHS) population at baseline and (2) examine potential secular trends in the prevalence of obesity in young black and white girls by comparing NGHS baseline data with those of the two National Health and Nutrition Examination Surveys (NHANES I and II) (measured before the NGHS). Design: Cross-sectional analysis of cohort baseline data. Setting: Recruitment in selected schools (Cincinnati and Berkeley) and among the membership of a group health association (Westat). Patients: Enrolled 2379 girls, 9 and 10 years of age, including 1213 black and 1166 white. Measurements: Anthropometric measures, including height, weight, and triceps and subscapular skin folds. Body mass index was used as a measure of body size. Nine- and ten-year-old black girls were taller, heavier, and had larger skin folds than white girls. Compared with age-similar girls in the 1970s, girls in the present study are taller and heavier and have thicker skin folds. The differences in body size were most notable among black girls. Conclusions: Black girls have a greater body mass than white girls even as young as 9 and 10 years of age. The prevalence of obesity appears to be increasing among young girls, especially in black girls. This progression, if not altered, could lead to increased disease in the future for adult women, particularly black women. C1 CHILDRENS HOSP, MED CTR, DIV CARDIOL, CINCINNATI, OH 45229 USA. MARYLAND MED RES INST, BALTIMORE, MD USA. UNIV CALIF BERKELEY, DEPT SOCIAL & ADM HLTH SERV, BERKELEY, CA 94720 USA. NHLBI, ROCKVILLE, MD USA. WESTAT CORP, ROCKVILLE, MD USA. FU NHLBI NIH HHS [HC-55025] NR 31 TC 68 Z9 70 U1 3 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD MAY PY 1994 VL 124 IS 5 BP 675 EP 680 DI 10.1016/S0022-3476(05)81354-X PN 1 PG 6 WC Pediatrics SC Pediatrics GA NK479 UT WOS:A1994NK47900003 PM 8176552 ER PT J AU HUSSON, RN ROSS, LA SANDELLI, S INDERLIED, CB VENZON, D LEWIS, LL WOODS, L CONVILLE, PS WITEBSKY, FG PIZZO, PA AF HUSSON, RN ROSS, LA SANDELLI, S INDERLIED, CB VENZON, D LEWIS, LL WOODS, L CONVILLE, PS WITEBSKY, FG PIZZO, PA TI ORALLY-ADMINISTERED CLARITHROMYCIN FOR THE TREATMENT OF SYSTEMIC MYCOBACTERIUM-AVIUM COMPLEX INFECTION IN CHILDREN WITH ACQUIRED-IMMUNODEFICIENCY-SYNDROME SO JOURNAL OF PEDIATRICS LA English DT Article ID IMMUNE-DEFICIENCY-SYNDROME; INTRACELLULARE BACTEREMIA; AIDS; CIPROFLOXACIN; ETHAMBUTOL; AMIKACIN; RIFAMPIN; THERAPY; INVITRO AB Objective: To determine the safety, tolerance, pharmacokinetics, and antimycobacterial activity of orally administered clarithromycin in children with acquired immunodeficiency syndrome and disseminated Mycobacterium avium complex (MAC) infection. Design: Phase I study with a 10-day pharmacokinetic phase followed by a 12-week continuation therapy phase. Patients: Twenty-five patients with a median age of 8.3 years were enrolled. Ten were receiving zidovudine and 13 were receiving didanosine at the time of enrollment. Intervention: Clarithromycin suspension was administered to each patient at one of three dose levels: 3.75, 7.5, and 15 mg/kg per dose every 12 hours. Clarithromycin and antiretroviral pharmacokinetics were measured during single-drug and concurrent-drug administration. Clinical and laboratory monitoring was performed biweekly. Measurements and main results: Clarithromycin was well tolerated at all dose levels. Plasma clarithromycin concentrations increased proportionately with increasing doses, and significant pharmacokinetic interactions were not observed during concurrent administration with zidovudine or didanosine. Decreases in mycobacterial load in blood were observed only at the highest clarithromycin dose level. Decreased susceptibility to clarithromycin developed rapidly (within 12 to 16 weeks) in the majority of MAC strains isolated from study patients. C1 NCI, PEDIAT BRANCH, BETHESDA, MD 20892 USA. NCI, BIOSTAT & DATA MANAGEMENT SECT, BETHESDA, MD 20892 USA. CHILDRENS HOSP LOS ANGELES, DEPT PEDIAT, LOS ANGELES, CA 90027 USA. CHILDRENS HOSP LOS ANGELES, DEPT PATHOL & LAB MED, LOS ANGELES, CA 90027 USA. NIH, WARREN GRANT MAGNUSON CLIN CTR, DEPT CLIN PATHOL, MICROBIOL SERV, BETHESDA, MD 20892 USA. RI Venzon, David/B-3078-2008 NR 28 TC 27 Z9 27 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD MAY PY 1994 VL 124 IS 5 BP 807 EP 814 DI 10.1016/S0022-3476(05)81380-0 PN 1 PG 8 WC Pediatrics SC Pediatrics GA NK479 UT WOS:A1994NK47900028 PM 8176574 ER PT J AU LOE, H AF LOE, H TI PERIODONTAL-DISEASE AS WE APPROACH THE YEAR 2000 SO JOURNAL OF PERIODONTOLOGY LA English DT Article RP LOE, H (reprint author), NIDR,BETHESDA,MD 20892, USA. NR 3 TC 6 Z9 6 U1 0 U2 0 PU AMER ACAD PERIODONTOLOGY PI CHICAGO PA 737 NORTH MICHIGAN AVENUE, SUITE 800, CHICAGO, IL 60611-2690 SN 0022-3492 J9 J PERIODONTOL JI J. Periodont. PD MAY PY 1994 VL 65 IS 5 SU S BP 464 EP 467 PG 4 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA NM524 UT WOS:A1994NM52400002 PM 8046562 ER PT J AU BROWN, LJ GARCIA, R AF BROWN, LJ GARCIA, R TI UTILIZATION OF DENTAL SERVICES AS A RISK FACTOR FOR PERIODONTITIS SO JOURNAL OF PERIODONTOLOGY LA English DT Article DE DELIVERY OF HEALTH CARE; ORAL HEALTH SURVEYS; PATIENT ACCEPTANCE OF HEALTH CARE; UTILIZATION REVIEW ID SUBGINGIVAL PLAQUE CONTROL; ORAL HYGIENE; LINEAR-MODELS; DISEASE; HEALTH; POPULATION; ADULTS; TEETH AB THE RELATION BETWEEN UTILIZATION OF DENTAL SERVICES from community dentists and the extent and severity of alveolar bone loss is reported for a panel of men followed for over 6 years. Oral health data were collected by the Department of Veterans Affairs, Dental Longitudinal Study, which began in 1969 and still continues. Participants have received regular oral examinations approximately every 3 years. A variety of oral health conditions were assessed, including plaque, calculus, gingival inflammation, probing depth, tooth mobility, clinical attachment level, and alveolar bone loss. Utilization data were abstracted from the dental records of dental offices that participants attended from 1979 through 1988. Multivariate modeling as well as comparisons of high utilizers and non-utilizers indicate that utilization of routine diagnostic and preventive services was not predictive of the extent and severity of periodontitis. C1 US DEPT VET AFFAIRS,WASHINGTON,DC. TUFTS UNIV,BOSTON,MA 02111. RP BROWN, LJ (reprint author), NIDR,WESTWOOD BLDG,ROOM 528,5333 WESTBARD AVE,BETHESDA,MD 20892, USA. NR 71 TC 14 Z9 14 U1 0 U2 0 PU AMER ACAD PERIODONTOLOGY PI CHICAGO PA 737 NORTH MICHIGAN AVENUE, SUITE 800, CHICAGO, IL 60611-2690 SN 0022-3492 J9 J PERIODONTOL JI J. Periodont. PD MAY PY 1994 VL 65 IS 5 SU S BP 551 EP 563 PG 13 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA NM524 UT WOS:A1994NM52400012 PM 8046572 ER PT J AU NOMEIR, AA MCCOMISH, MF MONGAN, AL COVEY, JM FERRALA, NF AF NOMEIR, AA MCCOMISH, MF MONGAN, AL COVEY, JM FERRALA, NF TI LIQUID-CHROMATOGRAPHIC ANALYSIS, STABILITY AND PROTEIN-BINDING STUDIES OF THE ANTI-HIV AGENT BENZOIC-ACID, 2-CHLORO-5[[(1-METHYLETHOXY)THIOXOMETHYL]AMINO]-METHYLETHYL, 1-METHYLETHYL ESTER SO JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS LA English DT Article DE REVERSED-PHASE LC; PROTEIN BINDING; STABILITY; ANTI-HIV AGENT, NSC 629243 AB A method was developed for the assay of benzoic acid, 2-chloro-5-[[(1-methylethoxyl)thioxomethyl]amino]-, 1-methylethyl ester (NSC 629243) in hamster, mouse, human and, to a limited extent, dog plasma. Protein in 0.5 ml of plasma was precipitated with four volumes of methanol and the supernatant was analysed for NSC 629243 by LC. Liquid chromatography was carried out on a reversed-phase Nova-Pak C18 column, with a mobile phase of 60% acetonitrile in water at 1 ml min-1, and the compound was quantified with a UV detector set at 283 nm. Two standard curves of NSC 629243 were needed to cover a concentration range of 0.05-100 mug ml-1. All standard curves had correlation coefficients >0.999. In practice, the minimum quantifiable concentration was approximately 0.05 mug ml-1 in 0.5 ml of plasma. NSC 629243 appeared to have good stability at 37-degrees-C in hamster, human and dog plasma at concentrations of 1 and 50 mug ml-1 (at least 80% remained in plasma after a 4 h incubation). Breakdown occurred in mouse plasma after 1 h at 37-degrees-C, with extensive breakdown occurring after 24 h. NSC 629243 was extensively bound to plasma proteins of Syrian hamsters and humans. The extent of binding ranged from a minimum of 88.6% to a maximum of 99.9% over a concentration range of ca 1-100 mug ml-1. C1 ARTHUR D LITTLE INC,CAMBRIDGE,MA 02140. NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,PHARMACOL BRANCH,BETHESDA,MD 20892. FU NCI NIH HHS [N01-CM-87284] NR 7 TC 1 Z9 1 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0731-7085 J9 J PHARMACEUT BIOMED JI J. Pharm. Biomed. Anal. PD MAY PY 1994 VL 12 IS 5 BP 693 EP 698 DI 10.1016/0731-7085(94)80037-5 PG 6 WC Chemistry, Analytical; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA NT173 UT WOS:A1994NT17300011 PM 7948190 ER PT J AU AGUAYO, LG GROSSIE, J AF AGUAYO, LG GROSSIE, J TI DOPAMINE INHIBITS A SUSTAINED CALCIUM CURRENT THROUGH ACTIVATION OF ALPHA-ADRENERGIC RECEPTORS AND A GTP-BINDING PROTEIN IN ADULT-RAT SYMPATHETIC NEURONS SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID SUPERIOR CERVICAL-GANGLION; ADRENAL CHROMAFFIN CELLS; CHANNELS; MODULATION; NOREPINEPHRINE; FACILITATION; MECHANISM; SECRETION; RELEASE; CLONING AB Although it is suspected that dopamine (DA) inhibits a Ca++ current in sympathetic neurons, the receptor and the Ca++ channel type involved are still unknown. We found that DA caused a reversible inhibition on omega-conotoxin sensitive and resistant Ca++ currents in the superior cervical ganglion (SCG). The concentration of DA that induced half-maximal inhibition was 3.0 mu M. The DA receptor agonists (+)-SKF-38393 (D-1 type) and quinpirole (D-2 type) appeared unable to induce an inhibition of the Ca++ current. Furthermore, the receptor antagonists SCH-23390 (D-1 type) and (-)-sulpiride (D-2 type) did not prevent the inhibitory effect of DA. This suggests that the effect of DA on the Ca++ current was not due to activation of DA receptors. The inhibition of the Ca++ current by DA was reduced by application of 1 mu M phentolamine, a nonselective alpha adrenergic antagonist, and by prazosin and yohimbine, alpha-1 and alpha-2 receptor antagonists, respectively. The beta adrenergic receptor antagonist propranolol did not block the effect of DA. A guanine nucleotide-binding protein appears to be involved in the activation of adrenergic receptors by DA. The addition of GTP-gamma-S (0.1 mM) to the intracellular solution produced an effect similar to that of DA. Incubation of sympathetic neurons with pertussis toxin reduced the effect of DA by 90%. The results indicate that DA reduces the number of available Ca++ channels in sympathetic neurons by activation of alpha adrenergic receptors, which are associated with a pertussis-sensitive GTP-binding protein. C1 NIAAA,PHYSIOL & PHARMACOL STUDIES LAB,ELECTROPHYSIOL SECT,ROCKVILLE,MD 20852. NR 37 TC 23 Z9 23 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD MAY PY 1994 VL 269 IS 2 BP 503 EP 508 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA PB547 UT WOS:A1994PB54700009 PM 8182518 ER PT J AU GHANAYEM, BI SANCHEZ, IM BURKA, LT AF GHANAYEM, BI SANCHEZ, IM BURKA, LT TI INVESTIGATION OF METHACRYLONITRILE METABOLISM AND THE METABOLIC BASIS FOR THE DIFFERENCES IN ITS TOXICITY IN RATS AND MICE SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID URINARY METABOLITES; INVIVO METABOLISM; ACRYLONITRILE; GLUTATHIONE; IDENTIFICATION; NECROSIS; CYANIDE; INVITRO; MOUSE AB Methacrylonitrile (MAN) is an industrial chemical used to manufacture plastics and elastomers. The reported p.o. LD(50) of MAN is 200 to 230 mg/kg in rats and 17 mg/kg in mice. Present investigations were undertaken to further characterize MAN metabolism and to study the metabolic basis for the species differences in its toxicity. Male F344 rats and B6C3F1 mice received a single gavage dose of 11.5 or 1.15 mg of [C-14]MAN/kg and were placed in glass metabolism cages. Elimination of MAN in rats occurred primarily in expired air as unchanged MAN, acetone and CO2. Three major urinary metabolites of MAN were identified as N-acetyl-S-(2-cyanopropyl)-L-cysteine, N-acetyl-S-(2-hydroxypropyl)-L-cysteine and a deoxyuridine isomer. Quantitatively, rats and mice excreted ca. 7 and 49% of the high MAN dose in urine as N-acetyl-S-(2-hydroxypropyl)-L-cysteine, respectively. In addition, rats eliminated significantly more MAN-derived CO2 and deoxyuridine than mice. MAN elimination was almost complete within 24 hr after dosing and the tissue concentrations of MAN-derived radioactivity were, with the exception of the urinary bladder, consistently higher in rats than in mice, in conclusion, a quantitative difference between rats and mice in forming the epoxide intermediate, higher efficiency of mice to conjugate this intermediate with glutathione and greater capacity of rats to degrade it to acetone and CO2 are thought to contribute to the higher sensitivity of mice to MAN acute toxicity. C1 NIEHS,CHEM BRANCH,RES TRIANGLE PK,NC 27709. RP GHANAYEM, BI (reprint author), NIEHS,BIOCHEM RISK ANAL LAB,B3-10,RES TRIANGLE PK,NC 27709, USA. NR 23 TC 11 Z9 11 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD MAY PY 1994 VL 269 IS 2 BP 581 EP 588 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA PB547 UT WOS:A1994PB54700019 PM 8182524 ER PT J AU MCCANN, U HATZIDIMITRIOU, G RIDENOUR, A FISCHER, C YUAN, J KATZ, J RICAURTE, G AF MCCANN, U HATZIDIMITRIOU, G RIDENOUR, A FISCHER, C YUAN, J KATZ, J RICAURTE, G TI DEXFENFLURAMINE AND SEROTONIN NEUROTOXICITY - FURTHER PRECLINICAL EVIDENCE THAT CLINICAL CAUTION IS INDICATED SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID D-FENFLURAMINE; RAT-BRAIN; D-NORFENFLURAMINE; MDMA; PROJECTIONS; DEPLETION; OBESITY AB Dexfenfluramine, a drug used as an appetite suppressant in Europe, is currently under evaluation for approval in the United States. Studies in animals indicate that dexfenfluramine damages brain serotonin neurons, but have been challenged by some because of questions regarding their relevance to humans. The present studies were designed to address the three most salient questions regarding the applicability of preclinical dexfenfluramine neurotoxicity data to humans. Specifically, the present studies sought to determine: 1) whether dexfenfluramine's effects on brain serotonin neurons are transient and related to its therapeutic actions; 2) whether the p.o. route of administration affords protection against dexfenfluramine neurotoxicity; and 3) whether the mouse, an animal thought to best approximate the human with regard to dexfenfluramine metabolism, is sensitive to dexfenfluramine's neurotoxic action. Results from the present study indicate that monkeys continue to show large serotonergic deficits as long as 12 to 17 months after dexfenfluramine treatment, suggesting that dexfenfluramine's effects in nonhuman primates are persistent and unlikely to be related to its therapeutic actions. Furthermore, the present results indicate that the p.o. route of administration affords little or no protection against dexfenfluramine neurotoxicity. Finally, mice, like all other animals tested to date, were found to be susceptible to dexfenfluramine neurotoxicity. Taken together, these findings indicate that concern over possible dexfenfluramine neurotoxicity in humans is warranted, and that physicians and patients alike need to be aware of dexfenfluramine's toxic potential toward brain serotonin neurons. C1 NIMH,BIOL PSYCHIAT BRANCH,ANXIETY & AFFECT DISORDERS SECT,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROL,BALTIMORE,MD 21205. NIDA,ADDICT RES CTR,PSYCHOBIOL SECT,BALTIMORE,MD 21224. OI Katz, Jonathan/0000-0002-1068-1159 FU NIDA NIH HHS [DA06275, DA05707] NR 34 TC 85 Z9 85 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD MAY PY 1994 VL 269 IS 2 BP 792 EP 798 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA PB547 UT WOS:A1994PB54700048 PM 7514223 ER PT J AU PLOPPER, CG WEIR, AJ NISHIO, SJ CHANG, A VOIT, M PHILPOT, RM BUCKPITT, AR AF PLOPPER, CG WEIR, AJ NISHIO, SJ CHANG, A VOIT, M PHILPOT, RM BUCKPITT, AR TI ELEVATED SUSCEPTIBILITY TO 4-IPOMEANOL CYTOTOXICITY IN IMMATURE CLARA CELLS OF NEONATAL RABBITS SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID NEWBORN RAT LUNG; OXYGEN-TOXICITY; BRONCHIOLAR EPITHELIUM; POSTNATAL-DEVELOPMENT; CYTOCHROME-P-450 MONOOXYGENASE; AROMATIC-HYDROCARBONS; PARACETAMOL TOXICITY; METABOLIC-ACTIVATION; REACTIVE METABOLITES; RHESUS-MONKEY AB The bronchiolar Clara cell is one of the primary targets in adult mammals for environmental contaminants metabolized by cytochrome P450 (CYP) monooxygenases. Previous studies show that the onset of CYP expression in Clara cells occurs during postnatal lung development. This study was designed to determine whether differentiating Clara cells are susceptible to CYP-activated cytotoxicants and whether these substances can influence subsequent cytodifferentiation. Adult and neonatal (5-9 days of age) rabbits were given a single dose of 4-ipomeanol (IPO) i.p. and sacrificed 2 or 7 days later. Their lungs were removed and assessed morphologically, immunohistochemically or for CYP activity. Treatment with 10 mg/kg of IPO (0.25 of the LD(50) for adults) killed 6 of 10 neonatal rabbits. At a dose of 5 mg/kg of IPO, most terminal bronchiolar cells were destroyed in the neonatal rabbits. The basal lamina of terminal bronchioles was either bate or lined by squamous or low cuboidal epithelium and macrophages. Terminal bronchiolar epithelium in neonates was minimally affected by a dose of 1 mg/kg of IPO. The terminal bronchioles in adults appeared nearly unaffected by either 1 or 5 mg/kg of IPO. Interalveolar septa were unaffected in all treated animals. Lung microsomal enzymes from neonatal rabbits metabolized IPO to reactive intermediates at less than one-third the rate in the lungs of adults. Seven days (15 days of age) after IPO treatment, CYP activity (as measured by pentoxyresorufin O-dealkylation) was one-half that of age-matched controls after a dose of 5 mg/kg but equaled control activity after 1 mg/kg. Immunohistochemical analysis, using antibodies to CYP2B4, CYP4B and CYP reductase, indicated that the decrease in activity seen with a dose of 5 mg/kg of IPO was the result of a loss of immunoreactive CYP proteins from the cuboidal cells of terminal bronchioles. It was concluded that, in neonatal animals, differentiating Clara cells are more susceptible to injury by bioactivated cytotoxicants than are differentiated cells in adults, despite the neonate's lower levels of CYP monooxygenases. Furthermore, IPO-induced injury impairs the normal pattern of postnatal Clara cell differentiation. C1 UNIV CALIF DAVIS,SCH VET MED,DEPT VET ANAT PHYSIOL & CELL BIOL,DAVIS,CA 95616. UNIV CALIF DAVIS,SCH VET MED,DEPT MOLEC BIOSCI,DAVIS,CA 95616. UNIV CALIF DAVIS,SCH VET MED,OCCUPAT & ENVIRONM HLTH UNIT,DAVIS,CA 95616. NIEHS,CELLULAR & MOLEC PHARMACOL LAB,RES TRIANGLE PK,NC 27709. FU NHLBI NIH HHS [HL43032]; NIEHS NIH HHS [ES04311, P30 ES05707] NR 72 TC 34 Z9 36 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD MAY PY 1994 VL 269 IS 2 BP 867 EP 880 PG 14 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA PB547 UT WOS:A1994PB54700058 PM 8182556 ER PT J AU ANDERSON, JL ROSEN, LN MENDELSON, WB JACOBSEN, FM SKWERER, RG JOSEPHVANDERPOOL, JR DUNCAN, CC WEHR, TA ROSENTHAL, NE AF ANDERSON, JL ROSEN, LN MENDELSON, WB JACOBSEN, FM SKWERER, RG JOSEPHVANDERPOOL, JR DUNCAN, CC WEHR, TA ROSENTHAL, NE TI SLEEP IN FALL WINTER SEASONAL AFFECTIVE-DISORDER - EFFECTS OF LIGHT AND CHANGING SEASONS SO JOURNAL OF PSYCHOSOMATIC RESEARCH LA English DT Article DE SEASONAL AFFECTIVE DISORDER; DEPRESSION; SLEEP; PHOTOTHERAPY; HYPERSOMNIA ID BODY-TEMPERATURE; DEPRESSION; PHOTOTHERAPY; THERAPY; RHYTHM; STATE AB Disturbances of sleep are a hallmark of seasonal affective disorders (SAD), as they are of other mood disorders. Fall/winter SAD patients most often report hypersomnia. Among responses of 293 SAD patients on a symptom questionnaire, complaints of winter hypersomnia (80%) greatly exceeded insomnia (10%), hypersomnia plus insomnia (5%), or no sleep difficulty (5%). Increased sleep length in fall/winter is not unique to SAD. Among 1571 individuals across four latitudes surveyed at random from the general population, winter sleep increases of less-than-or-equal-to 2 hr/day relative to summer were reported by nearly half. However, hypersomnia had a low correlation (r = 0.29) with the total number of other SAD symptoms that were reported in this sample. Ten SAD patients kept daily sleep logs across 1 yr that showed increases in fall and winter (sleeping most in October; least in May) whose maximum averaged 2.7 hr per day more weekend sleep than in spring and summer. These winter increases might have been somewhat attenuated since most received light therapy during part of the winter. Nocturnal EEG recordings of depressed SAD patients in winter showed decreased sleep efficiency, decreased delta sleep percentage, and increased REM density (but normal REM latency) in comparison with recordings: (1) from themselves in summer; (2) from themselves after greater-than-or-equal-to 9 days of light therapy; or (3) from age- and gender-matched healthy controls. Thus, the extent of fall/winter oversleeping recorded by our SAD patients did not differ dramatically from that reported by the general population, but sleep complaints of our SAD patients have been accompanied by features of sleep architecture that are different from healthy controls and are reversed by summer or by bright-light therapy. C1 NIMH,CLIN PSYCHOBIOL BRANCH,OUTPATIENT STUDIES UNIT,BLDG 10-45-239,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. UNIFORMED SERV UNIV HLTH SCI,BETHESDA,MD 20814. SUNY STONY BROOK,STONY BROOK,NY 11794. TRANSCULTURAL MENTAL HLTH INST,WASHINGTON,DC. SARASOTA PALMS HOSP,SARASOTA,FL. NR 46 TC 36 Z9 36 U1 1 U2 7 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0022-3999 J9 J PSYCHOSOM RES JI J. Psychosomat. Res. PD MAY PY 1994 VL 38 IS 4 BP 323 EP 337 DI 10.1016/0022-3999(94)90037-X PG 15 WC Psychiatry SC Psychiatry GA NM070 UT WOS:A1994NM07000006 PM 8064650 ER PT J AU WASSER, SK MONFORT, SL SOUTHERS, J WILDT, DE AF WASSER, SK MONFORT, SL SOUTHERS, J WILDT, DE TI EXCRETION RATES AND METABOLITES OF ESTRADIOL AND PROGESTERONE IN BABOON (PAPIO-CYNOCEPHALUS-CYNOCEPHALUS) FECES SO JOURNAL OF REPRODUCTION AND FERTILITY LA English DT Article ID INTESTINAL METABOLISM; EARLY-PREGNANCY; FECAL STEROIDS; FECES; EXTRACTION; ESTROGENS; ESTRADIOL; URINARY; WOMEN AB Two unanaesthetized female yellow baboons (Papio cynocephalus cynocephalus) were infused (i.v.) with [H-3]oestradiol and two with [H-3]progesterone, early in the follicular phases of their cycles. One month later, the two females infused with [3H]oestradiol were simultaneously infused with [C-14]progesterone and [H-3]dehydroepiandrosterone. All urine and faeces were collected for 96 h after infusion. The proportion of steroid excreted in faeces (versus urine) was 10.0% for oestradiol and 40% for progesterone. Peak excretion in urine occurred 4.5 h after infusion. Peak excretion in faeces occurred an average of 36.4 h after infusion, with remarkable consistency between steroids. Eighty per cent of faecal oestradiol and progesterone metabolites were excreted as free (rather than conjugated) steroids. Simply boiling (20 min) the dried faecal sample in 90% ethanol proved to be the most rapid and efficient means of extracting these steroid metabolites. High pressure liquid chromatography and immunoreactivity studies revealed that oestradiol was excreted in faeces as oestradiol (36%), oestrone (44%) and a conjugated metabolite that co-eluted with oestrone sulfate (20%). Progesterone was excreted as eight different free forms, only a minor portion of which was progesterone, and what appeared to be a conjugated metabolite that co-eluted with pregnanediol-glucuronide (20%). The free progesterone metabolites were identified by gas-chromatography-mass-spectrometery as epimers of 5-pregnane-3-diol and 5-pregnane3-ol-one. These data suggest that currently available immunoassays for free oestradiol and oestrone should adequately characterize faecal oestrogen profiles in baboons. However, high variability in crossreactivities of various progesterone antisera to progesterone metabolites in baboons makes antiserum selection a more serious concern in attempts to quantify faecal progestogen dynamics. All available data suggest considerable interspecific variability in faecal steroid metabolite excretion. This makes species-specific characterizations of the type reported here a necessary step for ensuring the accuracy of faecal endocrine monitoring. C1 NATL ZOOL PK,CTR CONSERVAT & RES,DEPT ANIM HLTH,FRONT ROYAL,VA. NIH,PRIMATE RES UNIT,BETHESDA,MD 20892. RP WASSER, SK (reprint author), UNIV WASHINGTON,DEPT OBSTET & GYNECOL,DIV REPROD ENDOCRINOL,XD-44,SEATTLE,WA 98105, USA. FU NIDDK NIH HHS [DK33400]; NIMH NIH HHS [MH45863] NR 23 TC 156 Z9 166 U1 0 U2 7 PU J REPROD FERTIL INC PI CAMBRIDGE PA 22 NEWMARKET RD, CAMBRIDGE, ENGLAND CB5 8DT SN 0022-4251 J9 J REPROD FERTIL JI J. Reprod. Fertil. PD MAY PY 1994 VL 101 IS 1 BP 213 EP 220 PG 8 WC Reproductive Biology SC Reproductive Biology GA NR795 UT WOS:A1994NR79500031 PM 8064684 ER PT J AU ROTHMAN, RB GENDRON, T HITZIG, P AF ROTHMAN, RB GENDRON, T HITZIG, P TI UNTITLED SO JOURNAL OF SUBSTANCE ABUSE TREATMENT LA English DT Letter ID BEHAVIOR; FENFLURAMINE; INFUSIONS RP ROTHMAN, RB (reprint author), NIDR,ADDICT RES CTR,CLIN PSYCHOPHARMACOL SECT,BETHESDA,MD 20892, USA. NR 14 TC 32 Z9 32 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0740-5472 J9 J SUBST ABUSE TREAT JI J. Subst. Abus. Treat. PD MAY-JUN PY 1994 VL 11 IS 3 BP 273 EP 275 DI 10.1016/0740-5472(94)90086-8 PG 3 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA NQ266 UT WOS:A1994NQ26600013 PM 8072057 ER PT J AU EPSTEIN, SE SPEIR, E UNGER, EF GUZMAN, RJ FINKEL, T AF EPSTEIN, SE SPEIR, E UNGER, EF GUZMAN, RJ FINKEL, T TI THE BASIS OF MOLECULAR STRATEGIES FOR TREATING CORONARY RESTENOSIS AFTER ANGIOPLASTY SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Review ID SMOOTH-MUSCLE CELLS; FIBROBLAST GROWTH-FACTOR; TUMOR-NECROSIS-FACTOR; HUMAN-ENDOTHELIAL-CELLS; RETINOBLASTOMA SUSCEPTIBILITY GENE; RECOMBINANT ADENOVIRUS VECTORS; HUMAN ATHEROSCLEROTIC PLAQUE; RNA INHIBITS PROLIFERATION; MYC MESSENGER-RNA; PROTEIN KINASE-C AB Excessive smooth muscle cell proliferation significantly con tributes to restenosis, which occurs in 25% to 50% of patients within 6 months of coronary angioplasty. Because successful treatment will probably depend on our acquiring a comprehensive knowledge of the molecular and cellular mechanisms involved, this report reviews 1) information relevant to the molecular and cellular mechanisms responsible for the smooth muscle cell(s) response to vascular injury, and 2) several molecular-based therapeutic strategies currently being explored as possible approaches to the control of restenosis, including recombinant DNA technology to target delivery of cytotoxic molecules to proliferating smooth muscle cell(s), antisense strategies to inhibit expression of gene products necessary for cell proliferation and gene therapy. RP EPSTEIN, SE (reprint author), NHLBI,CARDIOL BRANCH,BLDG 10,ROOM 7B15,BETHESDA,MD 20892, USA. NR 186 TC 76 Z9 80 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAY PY 1994 VL 23 IS 6 BP 1278 EP 1288 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PH372 UT WOS:A1994PH37200002 PM 8176084 ER PT J AU MARON, BJ KOGAN, J PROSCHAN, MA HECHT, GM ROBERTS, WC AF MARON, BJ KOGAN, J PROSCHAN, MA HECHT, GM ROBERTS, WC TI CIRCADIAN VARIABILITY IN THE OCCURRENCE OF SUDDEN CARDIAC DEATH IN PATIENTS WITH HYPERTROPHIC CARDIOMYOPATHY SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; CLINICAL MANIFESTATIONS; CARDIOVASCULAR-DISEASE; ATRIAL-FIBRILLATION; PATHO-PHYSIOLOGY; ONSET; RHYTHMS; INTERRELATIONS; TACHYCARDIA; ARRHYTHMIA AB Objectives. The present study examined whether sudden death in patients with hypertrophic cardiomyopathy occurred with a particular pattern of frequency throughout the day. Background. Previous investigators have shown a circadian distribution in the occurrence of sudden death and other cardiovascular events in patients with atherosclerotic coronary artery disease. Sudden death is also an important feature of the natural history of patients with hypertrophic cardiomyopathy. Methods. The study group comprised 94 patients with a time of death (or cardiac arrest) that could be ascertained accurately to the nearest hour. This hourly distribution was analyzed by harmonic regression. Results. Sudden death did not occur uniformly or randomly throughout the day. Rather, it was distributed in a bimodal pattern that conformed to a two harmonic regression model. A disproportionate number of sudden deaths (43 [46%] of 94) occurred in the first peak in midmorning between 7 AM and 1 PM. The second peak of sudden death was less distinct but was in the early evening, between 8 PM and 10 PM. This periodicity in occurrence of sudden cardiac death was not evident for the days of the week or months of the year and, furthermore, did not appear to be influenced by other clinical variables, such as age, gender, severity of symptoms, subaortic gradient or left ventricular wall thickness. Sudden death occurred most commonly during periods of severe exertion (37 [39%] of 94). Conclusions, Sudden death in hypertrophic cardiomyopathy demonstrates a bimodal pattern of circadian variability over the 24-h day, with a prominent midmorning peak similar to that described in patients with coronary artery disease, and a less striking early evening peak of occurrence. These findings suggest that temporally related physiologic changes, possibly in the electrical vulnerability of the myocardial substrate, may play a role in the sudden death of patients with hypertrophic cardiomyopathy. C1 NHLBI,CARDIOL BRANCH,BETHESDA,MD 20892. NHLBI,PATHOL BRANCH,BETHESDA,MD 20892. NIH,BIOSTAT RES BRANCH,BETHESDA,MD 20892. RP MARON, BJ (reprint author), MINNEAPOLIS HEART INST FDN,DIV CARDIOVASC RES,920 E 28TH ST,SUITE 40,MINNEAPOLIS,MN 55407, USA. NR 37 TC 61 Z9 64 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAY PY 1994 VL 23 IS 6 BP 1405 EP 1409 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PH372 UT WOS:A1994PH37200018 PM 8176100 ER PT J AU BROWN, LJ AF BROWN, LJ TI TRENDS IN TOOTH LOSS AMONG UNITED-STATES EMPLOYED ADULTS FROM 1971 TO 1985 SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article ID EXTRACTION; POPULATION AB A comparison of data from a 1971-74 study and a 1985-86 study is used to establish trends in tooth loss among adults. The data show that tooth retention among employed U.S. adults improved almost 15 percent in the decade between the two studies, and edentulism was almost cut in half. RP BROWN, LJ (reprint author), NIDR,PUBL HLTH SERV,BETHESDA,MD 20892, USA. NR 24 TC 25 Z9 25 U1 0 U2 0 PU AMER DENTAL ASSN PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 SN 0002-8177 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD MAY PY 1994 VL 125 IS 5 BP 533 EP 540 PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA NL150 UT WOS:A1994NL15000017 PM 8195495 ER PT J AU DAVIS, H GERGEN, PJ AF DAVIS, H GERGEN, PJ TI MEXICAN-AMERICAN MOTHERS REPORTS OF THE WEIGHTS AND HEIGHTS OF CHILDREN 6 MONTHS THROUGH 11 YEARS OLD SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Article ID RELATIVE WEIGHT; VALIDITY; RELIABILITY; ADOLESCENTS; ACCURACY AB Objective To determine the accuracy Of mothers' reports of their children's weights and heights. Design and Setting Cross-sectional survey of Mexican Americans in five southwestern states. Subjects Interviews were held with mothers of 2,578 children aged 6 months to 11 years old. Main outcome measures Sensitivity and specificity of categories formed from reported values, and correlation of reported and measured values. Results Probability of mothers answering ''don't know'' was 24% for children's weights and 51% for heights. On the average, mothers overestimated weights at the 15th percentile or lower for age and sex and underestimated weights at the 85th percentile or higher. On the average, they underestimated heights. Categories of low and high weight, height, and body mass index were created by applying absolute-value cutoffs to reported values. All the categories had low sensitivity or specificity. Age-group-specific correlation coefficients between reported and measured values ranged from .79 to .89 for weight and from.32 (for 6- through 23-month-olds) to .70 (for 9- through 11-year-olds) for height. Applications The use of categories formed by applying absolute-value cutoffs to mother-reported values results in frequent misclassification of individuals. Therefore, such categories should not be used to estimate relative risks associated with weight, height, and body mass index. The good correlation of mother-reported and measured weights indicates that despite their inaccuracies, reported weights well reflect the relative ranking of measured weights. Thus, the use of reported weights as a continuous variable in multivariate analyses might cause only small errors in the coefficient for weight. C1 NIAID,DIV ALLERGY IMMUNOL & TRANSPLANTAT,BETHESDA,MD 20892. CTR DIS CONTROL & PREVENT,NATL CTR HLTH STAT,DIV HLTH EXAMINAT STAT,HYATTSVILLE,MD 20782. RP DAVIS, H (reprint author), US AGCY INT DEV,1111 N 19TH ST,SUITE 300,ROSSLYN,VA 22209, USA. NR 27 TC 23 Z9 23 U1 0 U2 0 PU AMER DIETETIC ASSN PI CHICAGO PA 216 W JACKSON BLVD #800, CHICAGO, IL 60606-6995 SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD MAY PY 1994 VL 94 IS 5 BP 512 EP 516 DI 10.1016/0002-8223(94)90213-5 PG 5 WC Nutrition & Dietetics SC Nutrition & Dietetics GA NL847 UT WOS:A1994NL84700008 PM 8176125 ER PT J AU IJAMES, CF MARKEY, SP AF IJAMES, CF MARKEY, SP TI A LOW-VOLTAGE ION-TRANSPORT SYSTEM FOR EXTERNAL IONIZATION FOURIER-TRANSFORM MASS-SPECTROMETRY SO JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY LA English DT Article ID CYCLOTRON RESONANCE; ELECTROSPRAY IONIZATION; MAGNETIC-FIELD; ICR AB An efficient ion transport system that interfaces external ion sources with a commercial dual-cell Fourier transform mass spectrometry (FTMS) system so as to retain maximum experimental flexibility has been constructed. Electrostatic lenses were used for ion transfer with potentials less than 200 V to preclude discharges. Spectra were recorded by thermal ionization and by electrospray ionization. Other high pressure ionization methods can be easily added to the external ion source chamber, making this a general solution for ion transport into an FTMS system. The efficiency of ion transfer was measured to be approximately 30%. A pressure ratio of 10(5) between the external ion source chamber and the second cell has been demonstrated. The system incorporates a computer-controlled gate valve to isolate the cell regions from the external ion source chamber, permitting optimal conditions for ion injection and accumulation, and then after closing the valve, recording spectra at low pressure with high resolution. Spectra of Gramicidin S (resolution 90,000 at m/z 1164), aprotinin (resolution 410,000 at m/z 1304), and horse heart cytochrome c (resolution 50,000 at m/z 1546) are shown. C1 NIMH,CLIN SCI LAB,BETHESDA,MD 20892. NR 26 TC 9 Z9 9 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 1044-0305 J9 J AM SOC MASS SPECTR JI J. Am. Soc. Mass Spectrom. PD MAY PY 1994 VL 5 IS 5 BP 398 EP 406 DI 10.1016/1044-0305(94)85055-0 PG 9 WC Biochemical Research Methods; Chemistry, Analytical; Chemistry, Physical; Spectroscopy SC Biochemistry & Molecular Biology; Chemistry; Spectroscopy GA NK792 UT WOS:A1994NK79200009 PM 24222594 ER PT J AU BECKMAN, WC NEWBOLD, RR TENG, CT MCLACHLAN, JA AF BECKMAN, WC NEWBOLD, RR TENG, CT MCLACHLAN, JA TI MOLECULAR FEMINIZATION OF MOUSE SEMINAL-VESICLE BY PRENATAL EXPOSURE TO DIETHYLSTILBESTROL - ALTERED EXPRESSION OF MESSENGER-RNA SO JOURNAL OF UROLOGY LA English DT Article DE DIETHYLSTILBESTROL; LACTOFERRIN; SEMINAL VESICLES; IN SITU HYBRIDIZATION; IMMUNOHISTOCHEMISTRY ID GENE-EXPRESSION; LACTOTRANSFERRIN GENE; REPRODUCTIVE-TRACT; MALE-MICE; SECRETION; PROTEIN; ESTROGEN; PROSTATE; ADENOCARCINOMA; ABNORMALITIES AB Exposure to estrogens during critical stages of development has been reported to cause irreversible changes in estrogen target tissues such as the reproductive tract. In fact, recent studies using mice describe prenatal estrogen exposure resulting in the expression of the major estrogen-inducible uterine secretory protein, lactoferrin (LF), by the seminal vesicles of the male offspring. Thus, we have studied the role of estrogens in abnormal and normal gene expression in the developing male reproductive tract using LF and seminal vesicle secretory protein IV (SVS IV), an androgen-regulated murine seminal vesicle secretory protein, as markers. Lactoferrin and SVS IV protein and mRNA expression were studied in histological samples by using the techniques of in situ hybridization (ISH) and immunohistochemistry (IHC). Seminal vesicle secretory protein IV was expressed in all (100%) epithelial cells of the control seminal vesicle, but this protein was decreased by castration. However, LF expression was undetectable by ISH or IHC in control seminal vesicle epithelium. Lactoferrin was inducible in 2% of the seminal vesicle epithelial cells from adult castrated mice treated with estradiol 17 beta (E(2); 20 mu g./kg./day for 3 days), indicating that a small percentage of the seminal vesicle cells could be induced to secrete LF after modification of the endocrine environment. Prenatal DES treatment (100 mu g./kg. maternal body weight on days 9 through 16 of gestation) resulted in the male offspring exhibiting constitutive expression of LF in 5% of the seminal vesicle epithelial cells, while expression of the androgen-regulated protein SVS IV was slightly decreased. The maximal contrast between LF and SVS IV expression was observed in prenatally DES-treated mice that were subsequently castrated as adults and further treated with E(2); LF was detected in 40% of the epithelial cells in these mice. Double immunostaining techniques revealed that epithelial cells which were making LF had ceased production of SVS IV. Since a large percentage of the epithelial cells in the intact prenatal DES exposed male was capable of expressing the normal gene product, SVS IV, it was concluded that DES treatment during prenatal development appears to imprint or induce estrogenic sensitivity in the adult seminal vesicle, causing increased production of LF. The results suggest that this altered protein response may be ah example of atypical gene expression in male reproductive tract tissues following hormonal manipulation early in development. C1 NATL INST ENVIRONM HLTH SCI, DIV INTRAMURAL RES, REPROD & DEV TOXICOL LAB, RES TRIANGLE PK, NC 27709 USA. NR 37 TC 22 Z9 22 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-5347 J9 J UROLOGY JI J. Urol. PD MAY PY 1994 VL 151 IS 5 BP 1370 EP 1378 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA NG390 UT WOS:A1994NG39000064 PM 8158792 ER PT J AU SIEGSMUND, MJ YAMAZAKI, H PASTAN, I AF SIEGSMUND, MJ YAMAZAKI, H PASTAN, I TI INTERLEUKIN-6 RECEPTOR MESSENGER-RNA IN PROSTATE CARCINOMAS AND BENIGN PROSTATE HYPERPLASIA SO JOURNAL OF UROLOGY LA English DT Article DE PROSTATIC HYPERTROPHY; PROSTATIC NEOPLASMS ID EXOTOXIN FUSION PROTEIN; RENAL-CELL CARCINOMAS; STIMULATORY FACTOR-II; GROWTH-FACTOR; HUMAN-MONOCYTES; TUMOR-CELLS; EXPRESSION; IL-6; DIFFERENTIATION; LYMPHOCYTES AB We investigated the presence of interleukin 6 (IL6) receptors in human prostate carcinomas and benign prostatic hyperplasias. Interleukin 6 receptor expression was measured at the mRNA level by slot blot analysis using a probe that recognizes mRNA encoding the 80-kDa subunit of the IL6 receptor. Significant expression was found in 29 of 37 (78%) samples of benign prostate hyperplasia (BPH) and in 17 of 17 prostate carcinomas. Quantitative analysis of the expression level revealed that 11 of the 29 positive hyperplasia tissues (38%) and 4 carcinoma samples (23.5%) expressed equal or higher levels of IL6 receptor mRNA than the human hepatoma cell line PLC/PRF5, which contains about 2300 IL6 receptors per cell. We also measured IL6 receptor mRNA levels in three human prostate carcinoma cell lines LNCaP, DU145 and PC3, which are known to contain IL6 receptors because they are sensitive to the cytotoxic action of an IL6-toxin fusion protein. We were not able to detect IL6 receptor expression with the slot blot procedure, but we were able to detect IL6 receptor mRNA using a very sensitive PCR assay. Our data provide evidence that IL6 may play a role in the growth of benign and malignant prostate tumors and suggest that the IL6 receptor could be a target for the delivery of therapeutic agents in prostate cancer. C1 NCI,DCBDC,MOLEC BIOL LAB,BETHESDA,MD 20892. TOKAI UNIV,SCH MED,DEPT PATHOL,KANAGAWA,JAPAN. NR 29 TC 76 Z9 78 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-5347 J9 J UROLOGY JI J. Urol. PD MAY PY 1994 VL 151 IS 5 BP 1396 EP 1399 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA NG390 UT WOS:A1994NG39000068 PM 7512667 ER PT J AU WANG, H CHEN, M BERNEMAN, ZN DELGADO, G DIPAOLO, JA AF WANG, H CHEN, M BERNEMAN, ZN DELGADO, G DIPAOLO, JA TI DETECTION OF HUMAN HERPESVIRUS-6 IN PARAFFIN-EMBEDDED TISSUE OF CERVICAL-CANCER BY POLYMERASE CHAIN-REACTION SO JOURNAL OF VIROLOGICAL METHODS LA English DT Article DE POLYMERASE CHAIN REACTION; HHV-6; PARAFFIN-EMBEDDED TISSUE; CERVICAL CANCER ID LYMPHOTROPIC VIRUS; IDENTIFICATION; DNA; SEQUENCES; HHV-6 AB The polymerase chain reaction (PCR) was used to detect human herpesvirus-6 (HHV-6) DNA sequences from paraffin-embedded tissue from cervical cancer patients. Two of eight cases were positive for HHV-6 using two sets of HHV-6 primers. Hybridization of PCR products with specific radioisotope-labeled oligonucleotide probes confirmed the results. Furthermore, HHV-6 typing was possible by adapting restriction endonuclease digestion of PCR product. This method is useful for retrospective studies in investigating the etiologic role of HHV-6 in the development of human diseases. C1 NCI,BIOL LAB,BETHESDA,MD 20892. NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. LOYOLA UNIV,STRITCH SCH MED,DEPT OBSTET & GYNECOL,MAYWOOD,IL 60153. 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 0166-0934 J9 J VIROL METHODS JI J. Virol. Methods PD MAY PY 1994 VL 47 IS 3 BP 297 EP 305 DI 10.1016/0166-0934(94)90026-4 PG 9 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Virology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Virology GA NR661 UT WOS:A1994NR66100005 PM 8071418 ER PT J AU KYOSTIO, SRM OWENS, RA WEITZMAN, MD ANTONI, BA CHEJANOVSKY, N CARTER, BJ AF KYOSTIO, SRM OWENS, RA WEITZMAN, MD ANTONI, BA CHEJANOVSKY, N CARTER, BJ TI ANALYSIS OF ADENOASSOCIATED VIRUS (AAV) WILD-TYPE AND MUTANT REP PROTEINS FOR THEIR ABILITIES TO NEGATIVELY REGULATE AAV P(5) AND P(19) MESSENGER-RNA LEVELS SO JOURNAL OF VIROLOGY LA English DT Article ID LONG TERMINAL REPEAT; ADENOASSOCIATED VIRUS; GENE-EXPRESSION; CELLULAR-TRANSFORMATION; TRANS-ACTIVATION; MAMMALIAN-CELLS; DNA-REPLICATION; AUTO-REGULATION; BINDING-SITE; SEQUENCE AB The rep gene of adeno-associated virus type 2 (AAV) encodes four overlapping Rep proteins that are involved in gene regulation and replication of the virus. We studied here the regulation of mRNA transcribed from the AAV p(5) and p(19) promoters, using transient expression in human 293 cells followed by Northern (RNA) blot analysis of the mRNA. The p(5) transcript encodes the larger Rep proteins, Rep78 and Rep68, while the p(19) transcript encodes the smaller proteins, Rep52 and Rep40. A plasmid (pNTC3) containing the entire AAV genome with an amber mutation in the rep gene accumulated higher levels of p(5) and p(19) mRNA than a plasmid containing the wild-type AAV genome. Addition of increasing amounts of the wild-type rep gene in trans from a heterologous promoter inhibited p(5)- and p(19) mRNA accumulation from pNTC3, indicating that the levels of both transcripts were decreased by the Rep proteins. Cotransfections with plasmids producing individual wild-type Rep proteins in trans showed that p(5) and p(19) mRNA accumulation was inhibited 5- to 10-fold by Rep78 and Rep68 and 2- to 3-fold by Rep52 and Rep40. Analysis of carboxyl-terminal truncation mutants of Rep78 showed that the ability of Rep78 to decrease p(5) and p(19) mRNA levels was lost when 159 or more amino acids were deleted. Rep78 and Rep68 mutants deleted for the methionine at residue 225 showed decreased abilities to down-regulate both p(5) and p(19) transcript levels, while mutants containing a substitution of glycine for the methionine resembled the wild-type Rep78. A Rep78 protein,vith a mutation in the putative nucleoside triphosphate binding site inhibited expression from p(5) but not from p(19), suggesting that the regulation of p(5) transcript levels by Rep78 and Rep68 differs from that of p(19). A deletion analysis of AAV cis sequences revealed that an intact terminal repeat was not required for negative regulation of p(5) and p(19) transcript levels and that the regulation of p(19) mRNA levels by Rep78 did not require the presence of the p(5) promoter. RP KYOSTIO, SRM (reprint author), NIDDK,DEPT MOLEC & CELL BIOL,BLDG 8,RM 309,BETHESDA,MD 20892, USA. NR 51 TC 64 Z9 64 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 1994 VL 68 IS 5 BP 2947 EP 2957 PG 11 WC Virology SC Virology GA NF452 UT WOS:A1994NF45200019 PM 8151765 ER PT J AU NASIOULAS, G ZOLOTUKHIN, AS TABERNERO, C SOLOMIN, L CUNNINGHAM, CP PAVLAKIS, GN FELBER, BK AF NASIOULAS, G ZOLOTUKHIN, AS TABERNERO, C SOLOMIN, L CUNNINGHAM, CP PAVLAKIS, GN FELBER, BK TI ELEMENTS DISTINCT FROM HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 SPLICE SITES ARE RESPONSIBLE FOR THE REV DEPENDENCE OF ENV MESSENGER-RNA SO JOURNAL OF VIROLOGY LA English DT Article ID VIRAL MESSENGER-RNA; GENE-EXPRESSION; PROTEIN; SEQUENCES; IDENTIFICATION; RETROVIRUS; REGION; CELLS; TRANSLATION; INFECTIVITY AB In the absence of the viral regulatory protein Rev, the human immunodeficiency virus type 1 gag/pol and env mRNAs are inefficiently expressed, since nucleocytoplasmic transport, stability, and polysomal loading are impaired. It has been suggested that splicing is necessary for Rev function and that the low expression of the unspliced and intermediate spliced mRNAs in the absence of Rev is associated with specific splice sites. Previous studies identified distinct RNA elements within the gag/pol region responsible for low expression that are not associated with splice sites. Here we study the determinants for Rev dependence of the authentic env mRNA. We demonstrate that upon removal of all the utilized splice sites, the env mRNA is still Rev dependent and Rev responsive for expression in human cells. We have identified several regions within the env mRNA that inhibit expression of a gag-env hybrid mRNA. Elimination of one of these elements, located within the Rev-responsive element, did not result in virus expression, supporting our model that several independently acting elements are responsible for the downregulatory effect. By analogy to the RNA elements within the gag/pol region, we propose that elements unrelated to utilized splice sites are responsible for the posttranscriptional regulation of env mRNA. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,HUMAN RETROVIRUS PATHOGENESIS GRP,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,HUMAN RETROVIRUS SECT,FREDERICK,MD 21702. FU NCI NIH HHS [N01-CO-74101] NR 36 TC 109 Z9 109 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 1994 VL 68 IS 5 BP 2986 EP 2993 PG 8 WC Virology SC Virology GA NF452 UT WOS:A1994NF45200024 PM 8151769 ER PT J AU EARL, PL BRODER, CC LONG, D LEE, SA PETERSON, J CHAKRABARTI, S DOMS, RW MOSS, B AF EARL, PL BRODER, CC LONG, D LEE, SA PETERSON, J CHAKRABARTI, S DOMS, RW MOSS, B TI NATIVE OLIGOMERIC HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 ENVELOPE GLYCOPROTEIN ELICITS DIVERSE MONOCLONAL-ANTIBODY REACTIVITIES SO JOURNAL OF VIROLOGY LA English DT Article ID RECOMBINANT VACCINIA VIRUS; 3RD VARIABLE DOMAIN; NEUTRALIZING ANTIBODIES; CD4 BINDING; IMMUNODOMINANT EPITOPE; ENDOPLASMIC-RETICULUM; TRANSMEMBRANE PROTEIN; SYNTHETIC PEPTIDES; AIDS RETROVIRUS; GP120 IMPORTANT AB We synthesized and purified a recombinant human immunodeficiency virus type 1 (HIV-1) envelope (Env) glycoprotein, lacking the gp120/gp41 cleavage site as well as the transmembrane domain, that is secreted principally as a stable oligomer. Mice were immunized with separated monomeric and oligomeric HIV-1 Env glycoproteins to analyze the repertoire of antibody responses to the tertiary and quaternary structure of the protein. Hybridomas were generated and assayed for reactivity by immunoprecipitation of nondenatured Env protein. A total of 138 monoclonal antibodies (MAbs) were generated and cloned, 123 of which were derived from seven animals immunized with oligomeric Env. Within this group, a significant response was obtained against the gp41 ectodomain; 49 MAbs recognized epitopes in gp41, 82% of which were conformational. The influence of conformation on gp120 antigenicity was less pronounced, with 40% of the anti-gp120 MAbs binding to conformational epitopes, many of which blocked CD4 binding. Surprisingly, less than 7% of the MAbs derived from mice immunized with oligomeric Env recognized the V3 loop. In addition, MAbs to linear epitopes in the C-terminal domain of gp120 were not obtained, suggesting that this region of the protein may be partially masked in the oligomeric molecule. A total of 15 MAbs were obtained from two mice immunized with monomeric Env. Nearly half of these recognized the V3 loop, suggesting that this region may be a less predominant epitope in the context of oligomeric Env than in monomeric protein. Thus, immunization with oligomeric Env generates a large proportion of antibodies' to conformational epitopes in both gp120 and gp41, many of which may be absent from monomeric Env. C1 UNIV PENN,SCH MED,DEPT PATHOL & LAB MED,PHILADELPHIA,PA 19104. RP EARL, PL (reprint author), NIAID,VIRAL DIS LAB,BLDG 4,ROOM 229,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 84 TC 212 Z9 214 U1 1 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 1994 VL 68 IS 5 BP 3015 EP 3026 PG 12 WC Virology SC Virology GA NF452 UT WOS:A1994NF45200028 PM 7512157 ER PT J AU MARTARANO, L STEPHENS, R RICE, N DERSE, D AF MARTARANO, L STEPHENS, R RICE, N DERSE, D TI EQUINE INFECTIOUS-ANEMIA VIRUS TRANSREGULATORY PROTEIN REV CONTROLS VIRAL MESSENGER-RNA STABILITY, ACCUMULATION, AND ALTERNATIVE SPLICING SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; VIRAL MESSENGER-RNA; LONG TERMINAL REPEAT; GENE-EXPRESSION; TYPE-1 REV; MUTATIONAL ANALYSIS; FUNCTIONAL-ANALYSIS; RESPONSIVE ELEMENT; INTRONIC SEQUENCES; ACTING REGULATION AB The cis and trans-acting components of the Rev regulatory pathway employed by equine infectious anemia virus (EIAV) to regulate and coordinate viral gene expression were examined in complementation experiments. Viral protein expression and mRNA expression were compared in cells transiently transfected with wild-type or mutant proviruses in combination with Rev expression plasmids. Mutation of the predicted rev gene abolished Gag protein synthesis, and this defect was complemented, in trans, by Rev. Analysis of viral mRNAs from transfected cells confirmed that EIAV expresses five major mRNAs: the full length and singly spliced mRNAs contain introns and encode viral structural proteins while the three fully spliced mRNAs, encoding nonstructural genes, are generated by alternative splicing. Compared to cells transfected with the wild-type provirus, the intron-containing mRNAs produced from the rev-minus mutant were present at reduced levels in the nuclear RNA fraction and were not detected in the cytoplasm. This pattern of viral mRNA synthesis was restored to the wild-type pattern by providing Rev in trans. In contrast to the intron containing mRNAs, cytoplasmic accumulation of the multiply spliced class of mRNAs was independent of Rev. Closer examination of the multiply spliced class of viral mRNAs by reverse transcriptase-PCR analysis revealed a Rev-dependent alternative splicing phenomenon. In the absence of Rev, proviruses expressed a four-exon mRNA at high levels; the addition of Rev caused both a decrease in the levels of the four-exon mRNA and the appearance of a related mRNA lacking exon 3. The cis-acting RNA elements that mediate Rev responsiveness were studied with deleted proviruses, which revealed that EIAV contains at least two elements located near the ends of the envelope gene. Unlike the Rev-responsive elements in other retroviruses, the cis-acting regions of EIAV do not appear to form complex secondary structures. C1 NCI,FREDERICK CANC RES & DEV CTR,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21702. PRI DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MOLEC VIROL & CARCINOGENESIS LAB,FREDERICK,MD 21702. FU NCI NIH HHS [N01-CO-74102, N01-CO-74101] NR 75 TC 51 Z9 51 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 1994 VL 68 IS 5 BP 3102 EP 3111 PG 10 WC Virology SC Virology GA NF452 UT WOS:A1994NF45200036 PM 8151775 ER PT J AU CAMPBELL, BJ HIRSCH, VM AF CAMPBELL, BJ HIRSCH, VM TI EXTENSIVE ENVELOPE HETEROGENEITY OF SIMIAN IMMUNODEFICIENCY VIRUS IN TISSUES FROM INFECTED MACAQUES SO JOURNAL OF VIROLOGY LA English DT Article ID T-CELL-LINE; NEUTRALIZING ANTIBODIES; MACROPHAGE TROPISM; RHESUS-MONKEYS; PCR-SSCP; HIV-1; DETERMINANT; SEQUENCE; TYPE-1; GP120 AB The extent of virus genetic variation within tissues and peripheral blood mononuclear cells (PBMC) from two simian immunodeficiency virus (SIV)-infected macaques was analyzed. The products of PCR amplification of two regions, region 1 (SIV V1 region) and region 2 (region corresponding to the human immunodeficiency virus V3 cysteine loop and part of the C3 region immediately downstream), of the SIV envelope were examined for single-stranded conformation polymorphism followed by sequence analysis of selected clones. The V1 region of the SIV envelope of viruses present within lymphoid tissues displayed extensive heterogeneity, while viral populations within the PBMC and brain appeared to be less variable. Region 2 heterogeneity in both animals was generally confined to three residues in a tissue-specific manner. In addition, virus from the brains of both animals appeared to be distinct compared with viruses present in other tissues and PBMC of the same animal, both in the pattern of PCR-single-stranded conformation polymorphism SCP and in the sequence of region 2. These studies revealed that the tissues of SIV-infected macaques were a reservoir for viral variants distinct from those seen in PBMC. C1 NIAID,INFECT DIS LAB,IMMUNODEFICIENCY VIRUSES SECT,ROCKVILLE,MD 20852. NR 53 TC 37 Z9 37 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 1994 VL 68 IS 5 BP 3129 EP 3137 PG 9 WC Virology SC Virology GA NF452 UT WOS:A1994NF45200039 PM 8151778 ER PT J AU CICALA, C AVANTAGGIATI, ML GRAESSMANN, A RUNDELL, K LEVINE, AS CARBONE, M AF CICALA, C AVANTAGGIATI, ML GRAESSMANN, A RUNDELL, K LEVINE, AS CARBONE, M TI SIMIAN-VIRUS-40 SMALL-T ANTIGEN STIMULATES VIRAL-DNA REPLICATION IN PERMISSIVE MONKEY CELLS SO JOURNAL OF VIROLOGY LA English DT Article ID PROTEIN PHOSPHATASE-2A; SV40 DNA; DELETION MUTANTS; MICRO-INJECTION; TUMOR-ANTIGEN; PHOSPHORYLATION; TRANSFORMATION; BINDING; INVITRO; SITES AB The simian virus 40 (SV40) large-T antigen is essential for SV40 DNA replication and for late viral gene expression, but the role of the SV40 small-t antigen in these processes is still unclear. We have previously demonstrated that small t inhibits SV40 DNA replication in vitro. In this study, we investigated the effect of small t on SV40 replication in cultured cells. CV1 monkey cell infection experiments indicated that mutant viruses that lack small t replicate less efficiently than the wild-type; virus. We next microinjected CV1 cells with SV40 DNA with and without purified small-t protein and analyzed viral DNA replication efficiency by Southern blotting. Replication of either wild-type SV40 or small-t deletion mutant DNA was increased three- to fivefold in cells coinjected with purified small t. Thus, in contrast to our in vitro observation, small t stimulated viral DNA replication in vivo. This result suggests that small t has cellular effects that are not detectable in a reconstituted in vitro replication system. We also found that small t stimulated progression of permissive monkey cells-but not of nonpermissive rodent cells-from G(0)-G(1) to the S phase of the cell cycle, possibly leading to an optimal intracellular environment for viral replication. C1 NICHHD,DNA REPLICAT REPAIR & MUTAGENESIS SECT,BETHESDA,MD 20892. FREE UNIV BERLIN,INST MOLEK BIOL & BIOCHEM,W-1000 BERLIN 33,GERMANY. NORTHWESTERN UNIV,DEPT MICROBIOL & IMMUNOL,CHICAGO,IL 60611. FU NCI NIH HHS [CA-21327] NR 51 TC 34 Z9 35 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 1994 VL 68 IS 5 BP 3138 EP 3144 PG 7 WC Virology SC Virology GA NF452 UT WOS:A1994NF45200040 PM 8151779 ER PT J AU RAGHEB, JA ANDERSON, WF AF RAGHEB, JA ANDERSON, WF TI UNCOUPLED EXPRESSION OF MOLONEY MURINE LEUKEMIA-VIRUS ENVELOPE POLYPEPTIDES SU AND TM - A FUNCTIONAL-ANALYSIS OF THE ROLE OF TM DOMAINS IN VIRAL ENTRY SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; VESICULAR STOMATITIS-VIRUS; DECAY-ACCELERATING FACTOR; NUCLEOTIDE-SEQUENCE; SYNCYTIUM FORMATION; MEMBRANE ANCHOR; PHOSPHOLIPASE-C; CELL-MEMBRANE; GLYCOPROTEIN; RETROVIRUS AB Moloney murine leukemia virus ecotropic envelope expression plasmids were used to demonstrate that the synthesis of the retroviral envelope SU and TM polypeptides can be uncoupled with retention of biologic activity. By substituting a glycosyl-phosphatidylinositol (GPI) membrane anchor for part or all of the retroviral envelope transmembrane protein and creating several deletion variants of the TM subunit, we have begun to dissect the role of the TM protein in envelope function. We shaw that a GPI-anchored envelope can be incorporated into virions and binds receptor. We found that the envelope cytoplasmic tail, while not required, influences the efficiency of retroviral transduction at some step after membrane fusion (possibly by interacting with core). The membrane-spanning domain of TM is involved in membrane fusion, and this function is distinct from its role as a membrane anchor. As few as eight amino acids of the putative membrane-spanning domain are sufficient to achieve membrane anchoring of envelope but not to mediate membrane fusion. In addition, though not required, the membrane-spanning domain may have some direct role in the incorporation of envelope into virions. Finally, the extraceIlular domain of TM, besides containing the putative fusion domain and interacting with SU, may influence the synthesis or stability and the glycosylation of envelope, possibly by affecting oligomerization of the complex and proper intracellular transit. RP RAGHEB, JA (reprint author), NHLBI, MOLEC HEMATOL BRANCH, BLDG 10, ROOM 7D-18, BETHESDA, MD 20892 USA. NR 50 TC 67 Z9 67 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X EI 1098-5514 J9 J VIROL JI J. Virol. PD MAY PY 1994 VL 68 IS 5 BP 3207 EP 3219 PG 13 WC Virology SC Virology GA NF452 UT WOS:A1994NF45200048 PM 7512161 ER PT J AU RAGHEB, JA ANDERSON, WF AF RAGHEB, JA ANDERSON, WF TI PH-INDEPENDENT MURINE LEUKEMIA-VIRUS ECOTROPIC ENVELOPE-MEDIATED CELL-FUSION - IMPLICATIONS FOR THE ROLE OF THE R-PEPTIDE AND P12E TM IN VIRAL ENTRY SO JOURNAL OF VIROLOGY LA English DT Article ID NUCLEOTIDE-SEQUENCE; SYNCYTIUM FORMATION; MOUSE FIBROBLASTS; SEMLIKI FOREST; RETROVIRUS; RECEPTOR; GLYCOPROTEINS; MEMBRANES; GENE; RECOMBINATION AB Murine leukemia virus ecotropic and amphotropic envelope expression vectors were genetically engineered to generate truncations of the p15E TM cytoplasmic tail. The ecotropic construct CEET has the entire cytoplasmic tail of TM deleted, while the CEETR construct has only the R peptide portion of the tail deleted, thereby producing a TM subunit (p12E) that is identical to the one found in mature virions. The analogous amphotropic constructs were called CAET and CAETR. These envelopes, as opposed to their p15E TM counterparts, mediate cell-to-cell fusion at neutral pH in both transformed and nontransformed cell lines. Though the TM cytoplasmic domain is not required, its presence appears to augment such cell-to-cell fusion. This envelope-dependent fusion requires the presence of the viral receptor on the cell surface. Ecotropic virions bearing the p12E TM contain wild-type levels of the envelope complex and have near-normal titers. In contrast, virions which lack the cytoplasmic domain of TM (e.g., CEET) have 10- to 100-fold-lower titers but contain normal amounts of envelope. Both of the corresponding amphotropic virions contain normal amounts of envelope but have 10- to 100-fold-lower titers. Using immunofluorescent detection of envelope to monitor the fate of receptor-bound virions, we found that ecotropic murine leukemia virus envelope disappears from the cell surface while amphotropic envelope persists on the cell surface after virus binding. This pattern of immunofluorescence is consistent with the proposed routes of cell entry for these viruses, i.e., by endocytosis and direct fusion, respectively. In this assay, ecotropic virions bearing the genetically engineered p12E TM also appear to be internalized despite the ability of their envelope to mediate fusion at neutral pH in the same target cells. Our results show that direct fusion at neutral pH is a natural consequence of the surface expression of the mature ecotropic envelope and its receptor. We propose that the processing of the R peptide from the envelope TM (p15E) to yield p12E, at the time of virus budding or within virions, renders the envelope competent to fuse. RP RAGHEB, JA (reprint author), NHLBI, MOLEC HEMATOL BRANCH, BLDG 10, ROOM 7D-18, BETHESDA, MD 20892 USA. NR 41 TC 159 Z9 159 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X EI 1098-5514 J9 J VIROL JI J. Virol. PD MAY PY 1994 VL 68 IS 5 BP 3220 EP 3231 PG 12 WC Virology SC Virology GA NF452 UT WOS:A1994NF45200049 PM 8151784 ER PT J AU LIVINGSTON, PG KURANE, I LAI, CJ BRAY, M ENNIS, FA AF LIVINGSTON, PG KURANE, I LAI, CJ BRAY, M ENNIS, FA TI RECOGNITION OF ENVELOPE PROTEIN BY DENGUE VIRUS SEROTYPE-SPECIFIC HUMAN CD4(+) CD8(-) CYTOTOXIC T-CELL CLONES SO JOURNAL OF VIROLOGY LA English DT Article ID INTERFERON GAMMA-PRODUCTION; RECOMBINANT VACCINIA VIRUS; MONOCLONAL-ANTIBODIES; NONSTRUCTURAL PROTEIN-NS1; INFLUENZA HEMAGGLUTININ; ANTIGENIC DETERMINANTS; STRUCTURAL PROTEINS; E-GLYCOPROTEIN; LYMPHOCYTES-T; B-CELL AB We analyzed dengue virus-specific CD4(+) CD8(-) cytotoxic T lymphocytes (CTL) at the clonal level to further understand their role in dengue virus infections. Stimulation of peripheral blood mononuclear cells from two dengue virus type 4 (D4V)-immune donors with live D4V or noninfectious D4V antigen generated 17 HLA class II-restricted CD4(+) CTL capable of specific lysis of dengue virus antigen-treated autologous lymphoblastoid cell lines. Thirteen clones were D4V specific, three clones were cross-reactive for D2V and D4V, and one clone was cross-reactive for D1V, D3V, and D4V. Antigen recognition by six D4V-specific clones and three D2V- and D4V-cross-reactive clones was restricted by HLA-DR7. Five D4V-specific CD4(+) CTL clones lysed autologous lymphoblastoid cell lines infected with a dengue virus-vaccinia virus recombinant containing the E gene of D4V, whereas three serotype-cross-reactive CTL clones did not. These results indicate that E-specific clones are serotype specific and HLA-DR7 restricted in these two donors and suggest that a common epitope on E protein may be recognized. E protein-specific CD4(+) CTL may be important mediators of virus clearance especially during reinfection with the same serotype as that in primary infection by providing help for virus-specific antibody production and lysis of virus-infected cells. C1 UNIV MASSACHUSETTS,MED CTR,DEPT MED,DIV INFECT DIS & IMMUNOL,WORCESTER,MA 01655. NIAID,INFECT DIS LAB,BETHESDA,MD 20892. FU NIAID NIH HHS [T32-AI07272, R01-AI30624] NR 34 TC 29 Z9 33 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 1994 VL 68 IS 5 BP 3283 EP 3288 PG 6 WC Virology SC Virology GA NF452 UT WOS:A1994NF45200054 PM 7908702 ER PT J AU KASHANCHI, F SHIBATA, R ROSS, EK BRADY, JN MARTIN, MA AF KASHANCHI, F SHIBATA, R ROSS, EK BRADY, JN MARTIN, MA TI 2ND-SITE LONG TERMINAL REPEAT (LTR) REVERTANTS OF REPLICATION-DEFECTIVE HUMAN-IMMUNODEFICIENCY-VIRUS - EFFECTS OF REVERTANT TATA BOX MOTIFS ON VIRUS INFECTIVITY, LTR-DIRECTED EXPRESSION, IN-VITRO RNA-SYNTHESIS, AND BINDING OF BASAL TRANSCRIPTION FACTORS TFIID AND TFIIA SO JOURNAL OF VIROLOGY LA English DT Article ID NF-KAPPA-B; HTLV-III/LAV; ACTIVATES TRANSCRIPTION; GENE-EXPRESSION; TRANS-ACTIVATOR; T-CELLS; TYPE-1; PROMOTER; ENHANCER; INVITRO AB Second-site revertants from replication-incompetent molecular clones of human immunodeficiency virus (HIV) contain base substitutions adjacent to the TATA motif. The altered TATA box motifs were analyzed for their effect(s) on virus infectivity, long terminal repeat (LTR)-directed expression in transient transfection assays, in vitro RNA synthesis, and assembly of the TFIID-TFIIA preinitiation complex. The revertant TATA boxes accelerated the kinetics of HIV replication when present in the context of an LTR containing a Sp1 mutation (deletion or site specific); no effect was observed on the infectivity of wild-type HIV. In chloramphenicol acetyltransferase assays and in vitro transcription systems, the altered TATA box motifs led to elevated basal levels of RNA synthesis from NP-kB- and Sp1-mutagenized and wild-type templates, respectively, but did not increase responsiveness to Tat transactivation. The revertant TATA boxes accelerated the binding of TFIID and TFIIA to the LTR and stabilized their association with the promoter. The revertants did not assemble a more-processive elongation complex. These results suggest that in the context of an impaired enhancer/promoter (viz., three mutated Sp1 elements), a series of HIV revertants emerge which contain LTR alterations that significantly augment basal RNA synthesis. The TATA motif revertants are capable of rescuing the enhancer/promoter defect and sustain virus infectivity. C1 NCI,MOLEC VIROL LAB,BETHESDA,MD 20892. NIAID,MOLEC MICROBIOL LAB,BETHESDA,MD 20892. NR 52 TC 32 Z9 32 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 1994 VL 68 IS 5 BP 3298 EP 3307 PG 10 WC Virology SC Virology GA NF452 UT WOS:A1994NF45200056 PM 8151790 ER PT J AU HEINEMAN, TC COHEN, JI AF HEINEMAN, TC COHEN, JI TI DELETION OF THE VARICELLA-ZOSTER VIRUS LARGE SUBUNIT OF RIBONUCLEOTIDE REDUCTASE IMPAIRS GROWTH OF VIRUS IN-VITRO SO JOURNAL OF VIROLOGY LA English DT Article ID HERPES-SIMPLEX VIRUS; COMPLETE DNA-SEQUENCE; CELLS; ACYCLOVIR; MUTANT; TYPE-1; POTENTIATION; EXPRESSION; VACCINE; MICE AB Cells infected with varicella-zoster virus (VZV) express a viral ribonucleotide reductase which is distinct from that present in uninfected cells. VZV open reading frames 18 and 19 (ORF18 and ORF19) are homologous to the herpes simplex virus type I genes encoding the smalt and large subunits of ribonucleotide reductase, respectively. We generated recombinant VZV by transfecting cultured cells,vith four overlapping cosmid DNAs. To construct a virus lacking ribonucleotide reductase, we deleted 97% of VZV ORF19 from one of the cosmids. Transfection of this cosmid with the other parental cosmids yielded a VZV mutant with a 2.3-kbp deletion confirmed by Southern blot analysis. Virus-specific ribonucleotide reductase activity was not detected in cells infected,vith VZV lacking ORF19. Infection of melanoma cells with ORF19-deleted VZV resulted in plaques smeller than those produced by infection with the parental VZV. The mutant virus also exhibited a growth rate slightly slower than that of the parental virus. Chemical inhibition of the VZV ribonucleotide reductase has been shown to potentiate the anti-VZV activity of acyclovir. Similarly, the concentration of acyclovir required to inhibit plaque formation by 50% was threefold lower for the VZV ribonucleotide reductase deletion mutants than for parental virus. We conclude that the VZV ribonucleotide reductase large subunit is not essential for virus infection in vitro; however, deletion of the gene impairs the growth of VZV in cell culture and renders the virus more susceptible to inhibition by acyclovir. RP HEINEMAN, TC (reprint author), NIAID,CLIN INVEST LAB,MED VIROL SECT,BLDG 10,ROOM 11N228,BETHESDA,MD 20892, USA. NR 38 TC 32 Z9 33 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 1994 VL 68 IS 5 BP 3317 EP 3323 PG 7 WC Virology SC Virology GA NF452 UT WOS:A1994NF45200058 PM 8151792 ER PT J AU SHIRAI, M OKADA, H NISHIOKA, M AKATSUKA, T WYCHOWSKI, C HOUGHTEN, R PENDLETON, CD FEINSTONE, SM BERZOFSKY, JA AF SHIRAI, M OKADA, H NISHIOKA, M AKATSUKA, T WYCHOWSKI, C HOUGHTEN, R PENDLETON, CD FEINSTONE, SM BERZOFSKY, JA TI AN EPITOPE IN HEPATITIS-C VIRUS CORE REGION RECOGNIZED BY CYTOTOXIC T-CELLS IN MICE AND HUMANS SO JOURNAL OF VIROLOGY LA English DT Article ID NON-B-HEPATITIS; HUMAN-IMMUNODEFICIENCY-VIRUS; MAJOR HISTOCOMPATIBILITY COMPLEX; TOXIC LYMPHOCYTES-T; NON-A-HEPATITIS; SYNTHETIC PEPTIDES; TRANSPLANTATION ANTIGENS; INFLUENZA NUCLEOPROTEIN; ENVELOPE PROTEIN; CYTO-TOXICITY AB Several cytotoxic T-lymphocyte (CTL) epitopes have been defined in hepatitis C virus (HCV) proteins. CTL may play an important role in the control of infection by HCV. Here, we identify a highly conserved antigenic site in the HCV core recognized by both murine and human CTL. Spleen cells from mice immunized with a recombinant vaccinia virus expressing the HCV core gene were restimulated in vitro with 11 peptides from the core protein. CTL from H-2(d) mice responded to a single 16-residue synthetic peptide (HCV 129-144). This conserved epitope was presented by a murine class I major histocompatibility molecule (H-2D(d)) to conventional CD4(-) CD8(+) CTL mapped by using transfectants expressing D-d, L(d), or K-d, but was not seen by CTL restricted by H-2(b). The murine epitope was mapped to the decapeptide LMGYIPLVGA. The same 16-residue peptide was recognized by CTL from two HCV-seropositive patients but not by CTL from any seronegative donors. CTL from two HLA-A2-positive patients with acute and chronic hepatitides C recognized a 9-residue fragment (DLMGYIPLV) of the peptide presented by BLA-A2 and containing an HLA-A2-binding motif, extending only 1 residue beyond the murine epitope. Therefore, this conserved peptide, seen with murine CTL and human CTL with a very prevalent HLA class I molecule, may be a valuable component of an HCV vaccine against a broad range of HCV isolates. This study demonstrates that the screening: for CTL epitopes in mice prior to human study may be useful. C1 NCI, METAB BRANCH, MOLEC IMMUNOGENET & VACCINE RES SECT, BETHESDA, MD 20892 USA. KAGAWA MED SCH, DEPT INTERNAL MED 3, KAGAWA 76107, JAPAN. US FDA, CTR BIOL EVALUAT & RES, HEPATITIS RES LAB, BETHESDA, MD 20892 USA. TORREY PINES INST MOLEC STUDIES, SAN DIEGO, CA 92121 USA. NR 73 TC 139 Z9 142 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X EI 1098-5514 J9 J VIROL JI J. Virol. PD MAY PY 1994 VL 68 IS 5 BP 3334 EP 3342 PG 9 WC Virology SC Virology GA NF452 UT WOS:A1994NF45200060 PM 7512163 ER PT J AU LEW, JF PETRIC, M KAPIKIAN, AZ JIANG, X ESTES, MK GREEN, KY AF LEW, JF PETRIC, M KAPIKIAN, AZ JIANG, X ESTES, MK GREEN, KY TI IDENTIFICATION OF MINIREOVIRUS AS A NORWALK-LIKE VIRUS IN PEDIATRIC-PATIENTS WITH GASTROENTERITIS SO JOURNAL OF VIROLOGY LA English DT Note ID IMMUNE ELECTRON-MICROSCOPY; VIRAL GASTROENTERITIS; CALICIVIRUS; SEQUENCE AB In 1977, 30- to 32-nm virus-like particles, named minireovirus because of their unique morphologic appearance, were detected by electron microscopy in the stools of infants and young children with gastroenteritis. Sequence analysis of approximately 2,800 consecutive bases derived from overlapping PCR clones of a recent minireovirus clinical isolate showed 52% nucleotide sequence identity with the Norwalk virus sequence and, in addition, demonstrated that the genomic organizations of these two viruses were similar. Our data show that minireovirus is a Norwalk-like virus and should now also be included in the Caliciviridae family. C1 HOSP SICK CHILDREN,DEPT MICROBIOL,TORONTO M5G 1X8,ON,CANADA. BAYLOR COLL MED,DIV MOLEC VIROL,HOUSTON,TX 77030. RP LEW, JF (reprint author), NIAID,INFECT DIS LAB,BLDG 7,RM 129,5000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. FU PHS HHS [UO1-A130448] NR 22 TC 71 Z9 72 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 1994 VL 68 IS 5 BP 3391 EP 3396 PG 6 WC Virology SC Virology GA NF452 UT WOS:A1994NF45200068 PM 8151799 ER PT J AU LYNCH, WP BROWN, WJ SPANGRUDE, GJ PORTIS, JL AF LYNCH, WP BROWN, WJ SPANGRUDE, GJ PORTIS, JL TI MICROGLIAL INFECTION BY A NEUROVIRULENT MURINE RETROVIRUS RESULTS IN DEFECTIVE PROCESSING OF ENVELOPE PROTEIN AND INTRACELLULAR BUDDING OF VIRUS-PARTICLES SO JOURNAL OF VIROLOGY LA English DT Note ID HUMAN IMMUNODEFICIENCY VIRUS; IMMUNE-DEFICIENCY SYNDROME; WILD MOUSE RETROVIRUS; ROUS-SARCOMA VIRUS; LEUKEMIA-VIRUS; MONOCLONAL-ANTIBODY; CELLS; DISEASE; GLYCOPROTEINS; LOCALIZATION AB The observation of murine retrovirus infection of microglial cells in brain regions expressing spongiform neurodegenerative changes suggests that these cells may play an important role in pathogenesis. To evaluate this potential in vitro, murine microglial cells were infected in mixed glial cultures with the highly neurovirulent murine retrovirus, FrCas(E). The microglia were then isolated from the mixed cultures on the basis of their differential adherence and shown to be approximately 98% pure. The infected microglia expressed viral envelope protein at the plasma membrane, while viral budding was primarily intracellular. Evaluation of the viral envelope protein by immunoblotting indicated that the immunoreactive species produced was exclusively a 90-kDa precursor protein. Very little of the envelope protein was associated with particles released from these cells, and viral titers in the culture supernatant were low. Interestingly, these cells were still capable of infecting permissive target cells when seeded as infectious centers. This partially defective infection of microglial cells suggests a potential cellular means by which a neurovirulent retrovirus could disrupt normal microglia and in turn central nervous system motor system functioning. C1 CORNELL UNIV,BIOCHEM MOLEC & CELL BIOL SECT,ITHACA,NY 14853. RP LYNCH, WP (reprint author), NIAID,ROCKY MT LABS,PERSISTENT VIRAL DIS LAB,HAMILTON,MT 59840, USA. NR 55 TC 36 Z9 36 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 1994 VL 68 IS 5 BP 3401 EP 3409 PG 9 WC Virology SC Virology GA NF452 UT WOS:A1994NF45200070 PM 8151801 ER PT J AU KOVACS, GR ROSALES, R KECK, JG MOSS, B AF KOVACS, GR ROSALES, R KECK, JG MOSS, B TI MODIFICATION OF THE CASCADE MODEL FOR REGULATION OF VACCINIA VIRUS GENE-EXPRESSION - PURIFICATION OF A PREREPLICATIVE, LATE-STAGE-SPECIFIC TRANSCRIPTION FACTOR SO JOURNAL OF VIROLOGY LA English DT Note ID 5' POLY(A) LEADER; RNA-POLYMERASE; DNA-REPLICATION; IDENTIFICATION; SEQUENCE; SUBUNITS; TEMPLATE AB In vivo and in vitro studies have provided evidence that vaccinia virus late gene transcription factors are intermediate gene products synthesized exclusively after DNA replication. Here, we describe an additional transcription factor (P3 factor) that stimulates late gene transcription between 10- and 40-fold but is made in the absence of viral DNA replication. P3 factor activity was not detected either in uninfected cells or in purified virions. A >1,500-fold purification of P3 factor was achieved by column chromatography of cytoplasmic extracts prepared from cells infected with vaccinia virus in the presence of a DNA replication inhibitor. P3 factor was stage specific, since it could not substitute for early or intermediate transcription factors. Evidence that late stage-specific transcription factors are made both before and after DNA replication necessitates a modification of the cascade model for vaccinia virus gene regulation. C1 NIAID,VIRAL DIS LAB,BETHESDA,MD 20892. NR 29 TC 18 Z9 18 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 1994 VL 68 IS 5 BP 3443 EP 3447 PG 5 WC Virology SC Virology GA NF452 UT WOS:A1994NF45200076 PM 8151806 ER PT J AU SEEMAN, TE CHARPENTIER, PA BERKMAN, LF TINETTI, ME GURALNIK, JM ALBERT, M BLAZER, D ROWE, JW AF SEEMAN, TE CHARPENTIER, PA BERKMAN, LF TINETTI, ME GURALNIK, JM ALBERT, M BLAZER, D ROWE, JW TI PREDICTING CHANGES IN PHYSICAL PERFORMANCE IN A HIGH-FUNCTIONING ELDERLY COHORT - MACARTHUR STUDIES OF SUCCESSFUL AGING SO JOURNALS OF GERONTOLOGY LA English DT Article ID ALAMEDA COUNTY; RISK-FACTORS; DISABILITY; FALLS; OLD AB Background. Performance-based measures of physical performance were examined for an older cohort of relatively high-functioning men and women. Relationships between baseline physical performance and sociodemographic and health status characteristics were also examined. Three-year pattern changes in performance are described, and sociodemographic and health status predictors of change are investigated. Methods. A cohort of relatively high-functioning men and women, aged 70-79, was identified in 1988 by subsampling from three community-based studies on the basis of physical and cognitive function. Baseline in-home assessments included tests of physical performance and measurement of sociodemographic characteristics and health status. A summary measure of physical performance was developed from tests of balance, gait, lower body strength and coordination, and manual dexterity. In-home assessments were repeated at follow-up in 1991. Results. Better physical performance at baseline was more common among males, Whites, those reporting higher income and education, and those with fewer chronic conditions. In linear regression models, declines in performance were predicted by older age, lower income, higher education, relative weight and blood pressure, lower peak expiratory flow, prevalent diabetes and incident health conditions and hospitalizations during follow-up. Improvements in performance were also observed; the only significant association was with race (i.e., being Black). Conclusions. Declines in physical performance within a high-functioning cohort are predictable from sociodemographic and health status characteristics. The patterns of both decline and improvement in performance observed in this cohort suggest that older age is not uniformly associated with declines, indicating the potential for effective interventions to promote more successful aging. C1 YALE UNIV,SCH MED,DEPT MED,NEW HAVEN,CT 06510. NIA,BETHESDA,MD 20892. MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT,BOSTON,MA 02114. DUKE UNIV,MED CTR,DURHAM,NC. CUNY MT SINAI SCH MED,NEW YORK,NY 10029. RP SEEMAN, TE (reprint author), YALE UNIV,SCH MED,DEPT EPIDEMIOL & PUBL HLTH,60 COLL ST,NEW HAVEN,CT 06510, USA. NR 40 TC 208 Z9 208 U1 4 U2 16 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 SN 0022-1422 J9 J GERONTOL JI J. Gerontol. PD MAY PY 1994 VL 49 IS 3 BP M97 EP M108 PG 12 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA NJ544 UT WOS:A1994NJ54400001 PM 8169338 ER PT J AU GARIN, EH BLANCHARD, DK MATSUSHIMA, K DJEU, JY AF GARIN, EH BLANCHARD, DK MATSUSHIMA, K DJEU, JY TI IL-8 PRODUCTION BY PERIPHERAL-BLOOD MONONUCLEAR-CELLS IN NEPHROTIC PATIENTS SO KIDNEY INTERNATIONAL LA English DT Article ID GLOMERULAR-BASEMENT-MEMBRANE; INTERLEUKIN-1; LYMPHOKINE; INVITRO; RNA AB We studied the interleukin 8 (IL-8) gene expression by peripheral blood mononuclear cells (PBMC) and the IL-8 serum concentration in patients with idiopathic minimal lesion nephrotic syndrome (IMLNS) and other glomerulopathies. PBMC from eight of the nine (IMLNS) patients in relapse demonstrated the presence of IL-8 mRNA. All three IMLNS patients in remission (P = 0.0026 when compared to patients in relapse) and the two patients with nephrotic syndrome with other glomerulopathies failed to elicit an IL-8 mRNA response. Eleven of the 12 IMLNS patients in relapse showed IL-8 serum concentration above the level of detection. Only one of the seven patients in remission had detectable serum levels of IL-8 (P = 0.0033 when compared to levels from IMLNS patients in relapse). IL-8 serum levels were not detectable in three patients with nephrotic syndrome and other glomerulopathies. Supernatants of PBMC cultures from IMLNS patients in relapse increased the (35)sulfate uptake by rat GBM. This effect was abolished by the addition of anti-IL-8 neutralizing antibody to the culture media and reproduced by the addition to the media of IL-8 in concentrations found in the serum of IMLNS patients in relapse. Finally, the effect of IL-8 on the (35)sulfate turnover of the glomerular basement membrane (GBM) sulfated compounds was evaluated in vitro. A significant decrease in the percentage of residual (35)sulfate incorporated in the GBM (41 +/- 5, mean +/- sEM) was observed in cultures treated with IL-8 as compared to those that were not treated with IL-8 (58 +/- 8, P < 0.01). Because IL-8 affects the metabolism of GBM compounds that may play a role in glomerular permeability, this lymphokine may have a potential pathogenic role in the proteinuria of IMLNS. C1 UNIV S FLORIDA,H LEE MOFFITT CANC CTR,TAMPA,FL 33682. NCI,FREDERICK,MD 21701. RP GARIN, EH (reprint author), UNIV S FLORIDA,DEPT PEDIAT,DIV NEPHROL,17 DAVIS BLVD,2ND FLOOR,TAMPA,FL 33606, USA. NR 22 TC 54 Z9 61 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD MAY PY 1994 VL 45 IS 5 BP 1311 EP 1317 DI 10.1038/ki.1994.171 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA NF484 UT WOS:A1994NF48400003 PM 8072242 ER PT J AU CZUB, S LYNCH, WP CZUB, M PORTIS, JL AF CZUB, S LYNCH, WP CZUB, M PORTIS, JL TI KINETIC-ANALYSIS OF SPONGIFORM NEURODEGENERATIVE DISEASE INDUCED BY A HIGHLY VIRULENT MURINE RETROVIRUS SO LABORATORY INVESTIGATION LA English DT Article DE GP70; MICROGLIA; ASTROCYTOSIS ID CENTRAL-NERVOUS-SYSTEM; WILD MOUSE RETROVIRUS; LONG TERMINAL REPEAT; SUBACUTE SCLEROSING PANENCEPHALITIS; MOTOR NEURON DISEASE; MEASLES-VIRUS GENES; C RNA VIRUS; LEUKEMIA-VIRUS; NEUROTROPIC RETROVIRUS; INCUBATION PERIOD AB BACKGROUND: A chimeric murine retrovirus, FrCas(E), causes a rapid noninflammatory spongiform neurodegenerative disease of the motor system with an incubation period of 15 to 16 days after neonatal inoculation. Neurovirulence is determined by the viral envelope gene, but the neurodegeneration is an indirect consequence of virus infection, because the neurons that degenerate appear not to be infected. EXPERIMENTAL DESIGN: The current study was undertaken to compare the kinetics of lesion development and the expression of viral envelope protein in the central nervous system (CNS). Neonatal mice were inoculated with FrCas(E) intraperitoneally and were killed at various times for determination of the kinetics of the CNS infection, the distribution of lesion in the CNS, and the distribution of viral envelope protein. In addition, qualitative features of both viral envelope and gag proteins were followed by immunoblot analysis. RESULTS: The lesions induced by FrCas(E) consisted of vacuolar degeneration but without associated astrocytosis, the lack of an astroglial response being a consequence of the rapidity of the disease process. Vacuoles were observed primarily in the neuropil of the motor centers of spinal cord, brain stem, and cerebral cortex. Lesions appeared in all of these areas during a narrow window of time (less than or equal to 3 days). Cells in which viral envelope protein was detected by immunohistochemistry before the appearance of spongiform degeneration included premigratory cerebellar cortical granule neurons as well as vascular elements in the regions that would ultimately exhibit spongiform degeneration. Two forms of viral envelope protein were detected in the CNS. A 70-kilodalton species appeared first, followed by an approximately 64-kilodalton species, which was detected coincident with the first appearance of spongiform lesions. CONCLUSIONS: Astrocytosis is a secondary reaction to the neuronal cytopathology induced by FrCas(E) and appears to be dependent on the developmental state of the CNS. The abrupt, diffuse nature of lesion development in this disease suggests a global effect of the virus infection. Cells of the CNS vasculature (either endothelial cells, perivascular microglial cells, or both) as well as cerebellar granule neurons appear to be seminally involved in the pathogenesis of the spongiform degeneration. The two species of viral envelope protein appear to be expressed by different cell types in the CNS. C1 NIAID,ROCKY MT LABS,PERSISTENT VIRAL DIS LAB,HAMILTON,MT 59840. NR 37 TC 44 Z9 44 U1 1 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD MAY PY 1994 VL 70 IS 5 BP 711 EP 723 PG 13 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA NP120 UT WOS:A1994NP12000014 PM 8196367 ER PT J AU SOLARY, E BERTRAND, R POMMIER, Y AF SOLARY, E BERTRAND, R POMMIER, Y TI APOPTOSIS OF HUMAN LEUKEMIC HL-60 CELLS INDUCED TO DIFFERENTIATE BY PHORBOL ESTER TREATMENT SO LEUKEMIA LA English DT Article ID TOPOISOMERASE-II INHIBITORS; DEATH APOPTOSIS; THYMOCYTE APOPTOSIS; AGING NEUTROPHILS; DNA FRAGMENTATION; TUMOR PROMOTERS; GROWTH-FACTOR; INDUCTION; LINE; RECOGNITION AB In the human leukemic HL-60 cell line, we have reported previously that monocytic/macrophage-like differentiation induced by TPA (12-O-tetradecanoylphorbol-13-acetate) was associated with a decreased sensitivity to various apoptosis-inducing stimuli (Solary, Bertrand, Pommier, Blood 1993;81:1359-1368). In the present study, we studied further the effects of TPA alone on the induction of apoptosis in HL-60 cells. Based on morphology by electron microscopy, identification of internucleosomal DNA cleavage by gel electrophoresis and quantitation of DNA fragmentation by a filter binding assay, we observed that neither morphologic changes nor DNA damage were identified in TPA-differentiated HL-60 cells as long as they kept the adherent phenotype characteristic of this differentiation pathway. However, adherent TPA-treated HL-60 cells that secondarily detached from the flask demonstrated internucleosomal DNA fragmentation associated with morphologic changes characteristic of apoptosis. Similarly, HL-60 cells that never became adherent after TPA treatment underwent rapid apoptosis. Granulocytic differentiation by retinoic acid (RA) treatment also induced apoptosis although more slowly. Interestingly, in both TPA- and HA-treated cells, apoptotic bodies appeared to be phagocytosed by differentiated cells from the same lineage. Internucleosomal DNA fragmentation was also identified in HL-60 cells induced to differentiate by sodium butyrate and dimethylsulfoxide treatment, suggesting that apoptosis could be the common mode of death of terminally differentiated HL-60 cells. C1 NCI,DIV CANC TREATMENT,MOLEC PHARMACOL LAB,DEV THERAPEUT PROGRAM,BETHESDA,MD 20892. NR 41 TC 61 Z9 62 U1 1 U2 5 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0887-6924 J9 LEUKEMIA JI Leukemia PD MAY PY 1994 VL 8 IS 5 BP 792 EP 797 PG 6 WC Oncology; Hematology SC Oncology; Hematology GA NP119 UT WOS:A1994NP11900012 PM 8182936 ER PT J AU ATAL, S ZARNOWSKI, MJ CUSHMAN, SW SAMPUGNA, J AF ATAL, S ZARNOWSKI, MJ CUSHMAN, SW SAMPUGNA, J TI COMPARISON OF BODY-WEIGHT AND ADIPOSE-TISSUE IN MALE C57BI/6J MICE FED DIETS WITH AND WITHOUT TRANS-FATTY-ACIDS SO LIPIDS LA English DT Article ID UNITED-STATES DIET; LIPID CLASSES; HYDROGENATED OILS; ISOMERS; HEPATOMA; LIVER AB The effect of a diet containing trans-fatty acids (tFA) on the fatty acid composition and fat accumulation in adipose tissue was investigated in mice. Male C57Bl/6J mice were fed Control or Trans Diets that were similar, except that 50% of the 18:1, which was all cis in the Control Diet, was replaced by tFA in the Trans Diet. At selected ages, body weight, epididymal fat pad weight, perirenal fat yield, adipose tissue cellularity and fatty acid composition were examined. Over the time period studied (2-24 mon), the proportion of 18:0 and 16:0 tended to decrease while cis 18:1 levels increased. Compared to the Control Diet, the Trans Diet resulted in adipose tissue lipids with higher percentages of 14:0 and 18:2n-6 and lower percentages of cis-18:l and 20:4n-6. in polar lipids, tFA replaced saturated fatty acids, whereas tFA replaced cis-18:1 in the nonpolar lipids. Body weights at 16 and 24 mon of age and epididymal fat pad weights at 8-24 mon of age were lower in mice fed the Trans Diet as compared to those fed the Control Diet. At the ages studied, the Trans Diet also resulted in lower values for perirenal fat weights, triacylglycerol to polar lipid ratios, and adipose cell size. The data suggest that chronic consumption of tFA affects lipid metabolism and results in decreased fat accumulation in murine adipose tissue. C1 UNIV MARYLAND,DEPT CHEM & BIOCHEM,COLLEGE PARK,MD 20742. NIDDKD,BETHESDA,MD 20872. NR 30 TC 15 Z9 15 U1 0 U2 1 PU AMER OIL CHEMISTS SOC PI CHAMPAIGN PA 1608 BROADMOOR DRIVE, CHAMPAIGN, IL 61821-0489 SN 0024-4201 J9 LIPIDS JI Lipids PD MAY PY 1994 VL 29 IS 5 BP 319 EP 325 DI 10.1007/BF02537184 PG 7 WC Biochemistry & Molecular Biology; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Nutrition & Dietetics GA NL232 UT WOS:A1994NL23200002 PM 8015361 ER PT J AU RICK, ME AF RICK, ME TI DIAGNOSIS AND MANAGEMENT OF VON WILLEBRANDS-SYNDROME SO MEDICAL CLINICS OF NORTH AMERICA LA English DT Article ID ACQUIRED VONWILLEBRANDS DISEASE; MOLECULAR-WEIGHT MULTIMERS; VIII PROCOAGULANT ACTIVITY; MODERATE HEMOPHILIA-A; GLYCOPROTEIN IIB-IIIA; PLATELET-AGGREGATION; PLASMA; ANTIGEN; BINDING; DDAVP RP RICK, ME (reprint author), NIH,WARREN G MAGNUSON CLIN CTR,SERV HEMATOL,BETHESDA,MD 20892, USA. NR 65 TC 12 Z9 12 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0025-7125 J9 MED CLIN N AM JI Med. Clin. N. Am. PD MAY PY 1994 VL 78 IS 3 BP 609 EP 623 PG 15 WC Medicine, General & Internal SC General & Internal Medicine GA NK702 UT WOS:A1994NK70200006 PM 8170261 ER PT J AU HSU, SD CISAR, JO SANDBERG, AL KILIAN, M AF HSU, SD CISAR, JO SANDBERG, AL KILIAN, M TI ADHESIVE PROPERTIES OF VIRIDANS STREPTOCCOCAL SPECIES SO MICROBIAL ECOLOGY IN HEALTH AND DISEASE LA English DT Article DE STREPTOCOCCI; ADHESION; COAGGREGATION; ADHESINS; LECTINS; RECEPTORS ID ROOT SURFACES INVIVO; SALIVARY-BACTERIAL INTERACTIONS; STREPTOCOCCUS-MILLERI STRAINS; EARLY MICROBIAL COLONIZATION; ACTINOMYCES-VISCOSUS T14V; ORAL STREPTOCOCCI; DENTAL PLAQUE; HUMAN-ENAMEL; SIALIC-ACID; ELECTRON-MICROSCOPY AB Seventy-one strains of viridans streptococci, classified as Streptococcus sanguis, S. gordonii, S. oralis, S. mitis or S. anginosus by a revised taxonomic scheme, were characterized and compared by their specific adhesive properties. The frequency of bacterial adhesion to saliva-coated hydroxyapatite (SHA) was greater among strains of S. sanguis, S. gordonii and S. oralis than among those of S. mitis and S. anginosus. Similarly, the expression of sialic acid reactive adhesins, detected by neuraminidase sensitive bacterial haemagglutination, was noted more frequently with strains of S. sanguis (19 of 21), S. gordonii (14 of 16) and S. oralis (8 of 11) than those of S. mitis (2 of 12) and S. anginosus (0 of 11). Most strains of S. gordonii (14 of 16) and S. oralis (7 of 11) also aggregated acidic proline rich protein-coated latex beads, but this activity was observed rarely with strains of S. sanguis (2 of 21), & mitis (1 of 12) and & anginosus (0 of 11). Strains of S. anginosus (6 of 11) participated in lactose resistant coaggregations with actinomyces in coaggregation groups A (e.g. Actinomyces viscosus T14V-J1) and B (e.g. A. naeslundii WVU45). Lactose resistant coaggregations were also observed between strains of & gordonii (9 of 16) and actinomyces in coaggregation group A. Lactose sensitive coaggregations occurred between actinomyces and each of 11 S. oralis strains but less frequently with strains of S. sanguis (6 of 21), & gordonii (3 of 16), S. mitis (3 of 12) and S. anginosus (1 of 11). Certain streptococcal strains with receptors for the lactose sensitive lectins of actinomyces, including 9 of 11 S. oralis, also coaggregated frequently with strains of either S. sanguis (10 of 21) or S. gordonii (9 of 16). Further studies with representatives of these latter three streptococcal species suggested that the streptococci with receptors for the GalNAc sensitive lectins of S. sanguis and S. gordonii were those with GalNAcbeta1 --> 3Gal- rather than Galbeta1 --> 3GalNAc-containing cell wall polysaccharides. C1 NIDR,MICROBIAL ECOL LAB,BLDG 30,ROOM 302,BETHESDA,MD 20892. AARHUS UNIV,INST MED MICROBIOL,DK-8000 AARHUS,DENMARK. NR 48 TC 68 Z9 69 U1 0 U2 5 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0891-060X J9 MICROB ECOL HEALTH D JI Microb. Ecol. Health Dis. PD MAY-JUN PY 1994 VL 7 IS 3 BP 125 EP 137 PG 13 WC Ecology; Immunology; Microbiology SC Environmental Sciences & Ecology; Immunology; Microbiology GA NR100 UT WOS:A1994NR10000001 ER PT J AU TILLMANN, U WAGNER, J BOERBOOM, D WESTPHAL, H TREMBLAY, ML AF TILLMANN, U WAGNER, J BOERBOOM, D WESTPHAL, H TREMBLAY, ML TI NUCLEAR-LOCALIZATION AND CELL-CYCLE REGULATION OF A MURINE PROTEIN-TYROSINE-PHOSPHATASE SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID EXPRESSION; SEQUENCE; TRANSCRIPTION; PURIFICATION; TRANSPORT; BINDING; ENCODES; CLONING; FAMILY; SIGNAL AB MPTP is a murine homolog of the human T-cell protein tyrosine phosphatase (PTPase) and the rat PTP-S enzyme. Enzymatic activity of this ubiquitously expressed protein was demonstrated in immunoprecipitates from NIH 3T3 cells and in recombinant protein overexpressed in bacteria. Expression of beta-galactosidase-MPTP chimeric proteins in COS1 cells identified a nuclear localization signal at the carboxyl terminus of the MPTP that was sufficient to direct beta-galactosidase as well as a tagged version of the MPTP to the nucleus. Deletion analysis of amino acids within the nuclear targeting signal showed that this sequence does not conform to the bipartite type of nuclear localization signals. Furthermore, it was shown that the steady-state levels of MPTP RNA fluctuate in a cell cycle-specific manner. On the basis of these experiments, we discuss the possible function of MPTP in the cell cycle and other nuclear processes. C1 MCGILL UNIV,DEPT BIOCHEM,MONTREAL H3G 1Y6,PQ,CANADA. NICHHD,MAMMALIAN GENES & DEV LAB,BETHESDA,MD 20892. NR 38 TC 55 Z9 55 U1 1 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAY PY 1994 VL 14 IS 5 BP 3030 EP 3040 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA NG756 UT WOS:A1994NG75600020 PM 8164659 ER PT J AU DEALDANA, CRV HINNEBUSCH, AG AF DEALDANA, CRV HINNEBUSCH, AG TI MUTATIONS IN THE GCD7 SUBUNIT OF YEAST GUANINE-NUCLEOTIDE EXCHANGE FACTOR EIF-2B OVERCOME THE INHIBITORY EFFECTS OF PHOSPHORYLATED EIF-2 ON TRANSLATION INITIATION SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID AMINO-ACID BIOSYNTHESIS; SACCHAROMYCES-CEREVISIAE; ALPHA-SUBUNIT; FACTOR-II; PROTEIN-SYNTHESIS; GCN4 EXPRESSION; GENERAL CONTROL; KINASE GCN2; CELL-CYCLE; MECHANISM AB Phosphorylation of the a subunit of eukaryotic translation initiation factor 2 (eIF-2 alpha) impairs translation initiation by inhibiting the guanine nucleotide exchange factor for eIF-2, known as eIF-2B. In Saccharomyces cerevisiae, phosphorylation of eIF-2 alpha by the protein kinase GCN2 specifically stimulates translation of GCN4 mRNA in addition to reducing general protein synthesis. We isolated mutations in several unlinked genes that suppress the growth-inhibitory effect of eIF-2 alpha phosphorylation catalyzed by mutationally activated forms of GCN2. These suppressor mutations, affecting eIF-2 alpha and the essential subunits of eIF-2B encoded by GCD7 and GCD2, do not reduce the level of eIF-2 alpha phosphorylation in cells expressing the activated GCN2(c) kinase. Four GCD7 suppressors were shown to reduce the derepression of GCN4 translation in cells containing wild-type GCN2 under starvation conditions or in GCN2(c) strains. A fifth GCD7 allele, constructed in vitro by combining two of the GCD7 suppressors mutations, completely impaired the derepression of GCN4 translation, a phenotype characteristic of deletions in GCN1, GCN2, or GCN3. This double GCD7 mutation also completely suppressed the lethal effect of expressing the mammalian eIF-2 alpha kinase dsRNA-PK in yeast cells, showing that the translational machinery had been rendered completely insensitive to phosphorylated eIF-2. None of the GCD7 mutations had any detrimental effect on cell growth under nonstarvation conditions, suggesting that recycling of eIF-2 occurs efficiently in the suppressor strains. We propose that GCD7 and GCD2 play important roles in the regulatory interaction between eIF-2 and eIF-2B and that the suppressor mutations we isolated in these genes decrease the susceptibility of eIF-2B to the inhibitory effects of phosphorylated eIF-2 without impairing the essential catalytic function of eIF-2B in translation initiation. C1 NICHHD, GENET MOLEC LAB, MOLEC GENET LOWER EUKARYOTES SECT, BETHESDA, MD 20892 USA. RI Vazquez de Aldana, Carlos/B-7772-2008 OI Vazquez de Aldana, Carlos/0000-0002-4513-3654 NR 47 TC 41 Z9 42 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 EI 1098-5549 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAY PY 1994 VL 14 IS 5 BP 3208 EP 3222 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA NG756 UT WOS:A1994NG75600037 ER PT J AU BAE, SC OGAWA, E MARUYAMA, M OKA, H SATAKE, M SHIGESADA, K JENKINS, NA GILBERT, DJ COPELAND, NG ITO, Y AF BAE, SC OGAWA, E MARUYAMA, M OKA, H SATAKE, M SHIGESADA, K JENKINS, NA GILBERT, DJ COPELAND, NG ITO, Y TI PEBP2-ALPHA-B/MOUSE AML1 CONSISTS OF MULTIPLE ISOFORMS THAT POSSESS DIFFERENTIAL TRANSACTIVATION POTENTIALS SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID DROSOPHILA SEGMENTATION GENE; POLYOMAVIRUS ENHANCER; VIRUS ENHANCER; NUCLEAR FACTOR; MOUSE; LEUKEMIA; PROTEIN; CELLS; IDENTIFICATION; BINDING AB A murine transcription factor, PEBP2, is composed of two subunits, alpha and beta. There are two genes in the mouse genome, PEBP2 alpha A and PEBP2 alpha B, which encode the alpha subunit. Two types of the alpha B cDNA clones, alpha B1 and alpha B2, were isolated from mouse fibroblasts and characterized. They were found to represent 3.8- and 7.9-kb transcripts, respectively. The 3.8-kb RNA encodes the previously described alpha B protein referred to as alpha B1, while the 7.9-kb RNA encodes a 387 amino-acid protein, termed alpha B2, which is identical to alpha B1 except that it has an internal deletion of 64 amino acid residues. Both alpha B1 and alpha B2 associate with PEBP2 beta and form a heterodimer. The alpha B2/beta complex binds to the PEBP2 binding site two- to threefold more strongly than the alpha B1/beta complex does. alpha B1 stimulates transcription through the PEBP2 site about 40-fold, while alpha B2 is only about 25 to 35% as active as alpha B1. Transactivation domain is located downstream of the 128-amino-acid runt homology region, referred to as the Runt domain. Mouse chromosome mapping studies revealed that alpha A, alpha B, and beta genes are mapped to chromosomes 17, 16, and 8, respectively. The last two genes are syntenic with the human AML1 on chromosome 21q22 and PEBP2 beta/CBF beta on 16q22 detected at the breakpoints of characteristic chromosome translocations of the two different subtypes of acute myeloid leukemia. These results suggest that the previously described chimeric gene products, AML1/MTG8(ETO) and AML1-EAP generated by t(8;21) and t(3;21), respectively, lack the transactivation domain of AML1. C1 KYOTO UNIV,INST VIRUS RES,DEPT VIRAL ONCOL,SAKYO KU,KYOTO 606,JAPAN. KYOTO UNIV,INST VIRUS RES,DEPT MOLEC BIOL & GENET,SAKYO KU,KYOTO 606,JAPAN. NCI,FREDERICK CANC RES & DEV CTR,MAMMALIAN GENET LAB,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. FU NCI NIH HHS [N01-CO-74101] NR 49 TC 205 Z9 209 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAY PY 1994 VL 14 IS 5 BP 3242 EP 3252 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA NG756 UT WOS:A1994NG75600040 PM 8164679 ER PT J AU SESTI, G TULLIO, AN MARINI, MA MANERA, E BORBONI, P ACCILI, D LONGHI, R FUSCO, A LAURO, R MONTEMURRO, A AF SESTI, G TULLIO, AN MARINI, MA MANERA, E BORBONI, P ACCILI, D LONGHI, R FUSCO, A LAURO, R MONTEMURRO, A TI ROLE OF THE EXON-11 OF THE INSULIN-RECEPTOR GENE ON INSULIN BINDING IDENTIFIED BY ANTIPEPTIDE ANTIBODIES SO MOLECULAR AND CELLULAR ENDOCRINOLOGY LA English DT Article DE INSULIN RECEPTOR; ANTIRECEPTOR ANTIBODY ID NEGATIVE COOPERATIVITY; MONOCLONAL-ANTIBODIES; TYROSINE KINASE; ALPHA-SUBUNIT; EXTRACELLULAR DOMAIN; BETA-SUBUNIT; SITE; DISTINCT; SPECIFICITY; VARIANTS AB The insulin receptor exists in two isoforms differing by the absence (HIR-A) or presence (HIR-B) of 12 amino acids in the C-terminus of the alpha-subunit as a consequence of alternative splicing of exon 11. It was shown that the two isoforms exhibit different binding affinities for insulin, thus suggesting that the sequence encoded by exon 11 may be important for insulin binding. To further investigate this issue, we generated polyclonal antibodies against C-terminal peptides of the two HIR alpha-subunit variants. Herein, we characterized two antibodies, PA-11 and PA-12, directed against the C-terminus or the N-terminus of the sequence encoded by exon 11, respectively, and one (PA-13) directed against a sequence in the carboxy-terminal region of the alpha-subunit which is common to HIR-A and HIR-B. Antibodies were characterized for their ability to immunoprecipitate the receptor and to inhibit [I-125]insulin binding to both isoforms. We found that PA-13 immunoprecipitates both the HIR-A and the HIR-B, PA-12 immunoprecipitates exclusively the HIR-B, and PA-11 fails to precipitate both isoforms. Interestingly, PA-12 inhibits specifically insulin to the HIR-B, whereas other PAs fail to affect insulin binding to either isoforms. Furthermore, PA-12 linearises the Scatchard plot of binding data, and retards the dissociation rate of insulin, thus suggesting that antibody affects cooperative interactions among binding sites. We conclude that the sequence encoded by exon 11 may play a role in modulating the binding of insulin to the receptor and negative cooperativity. C1 CNR,IST CHIM ORMONI,MILAN,ITALY. NIDDK,DIABET BRANCH,BETHESDA,MD. RP SESTI, G (reprint author), UNIV ROMA TOR VERGATA,DIPARTIMENTO MED INTERNA,VIA ORAZIO RAIMONDO,I-00173 ROME,ITALY. RI Sesti, Giorgio/B-1509-2012; OI Sesti, Giorgio/0000-0002-1618-7688 NR 34 TC 9 Z9 9 U1 1 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0303-7207 J9 MOL CELL ENDOCRINOL JI Mol. Cell. Endocrinol. PD MAY PY 1994 VL 101 IS 1-2 BP 121 EP 127 DI 10.1016/0303-7207(94)90226-7 PG 7 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA NJ789 UT WOS:A1994NJ78900016 PM 9397944 ER PT J AU LIU, YH TENG, CT AF LIU, YH TENG, CT TI IDENTIFICATION OF THE ESTROGEN SENSITIVE MARKER IN HUMAN ENDOMETRIAL CARCINOMA RL95-2 CELLS SO MOLECULAR AND CELLULAR ENDOCRINOLOGY LA English DT Article DE ESTROGEN; ENDOMETRIUM; RL95-2 CELL; ONCOGENE; C-MYC; C-FOS; LACTOFERRIN ID LACTOFERRIN GENE; C-FOS; STEROID-HORMONES; RIBONUCLEIC-ACID; GROWTH-FACTORS; MOUSE UTERUS; RAT UTERUS; EXPRESSION; MYC; TRANSCRIPTION AB Estrogen exerts a variety of biological effects on human reproductive tissues. However, little is understood about the estrogenic effect on human endometrial cells in vitro. This study was designed to investigate estrogen action on c-myc and c-fos oncogenes and lactoferrin gene expression in human endometrial carcinoma RL95-2 cells. The results indicate that estrogen can induce c-myc oncogene expression in 4 h. Neither c-fos nor the lactoferrin messenger was detectable, nor could they be induced by estrogen. Transfection with human estrogen receptor expression vector to the RL95-2 cells does not restore the estrogen responsiveness. In addition to estrogen, epidermal growth factor (EGF) and tumor promoter 12-O-tetradecanoylphorbol 13-acetate (TPA) can also induce c-myc expression with no effect on c-fos or lactoferrin expression. Our data suggest that the c-myc oncogene in human endometrial carcinoma RL95-2 cells is the sensitive target gene for steroid hormone and growth factor action. C1 NIEHS,REPROD & DEV TOXICOL LAB,RES TRIANGLE PK,NC 27709. NR 21 TC 7 Z9 7 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0303-7207 J9 MOL CELL ENDOCRINOL JI Mol. Cell. Endocrinol. PD MAY PY 1994 VL 101 IS 1-2 BP 167 EP 171 DI 10.1016/0303-7207(94)90231-3 PG 5 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA NJ789 UT WOS:A1994NJ78900021 PM 9397949 ER PT J AU BUTLER, AA AMBLER, GR BREIER, BH LEROITH, D ROBERTS, CT GLUCKMAN, PD AF BUTLER, AA AMBLER, GR BREIER, BH LEROITH, D ROBERTS, CT GLUCKMAN, PD TI GROWTH-HORMONE (GH) AND INSULIN-LIKE GROWTH-FACTOR-I (IGF-I) TREATMENT OF THE GH-DEFICIENT DWARF RAT - DIFFERENTIAL-EFFECTS ON IGF-I TRANSCRIPTION START SITE EXPRESSION IN HEPATIC AND EXTRAHEPATIC TISSUES AND LACK OF EFFECT ON TYPE-I IGF RECEPTOR MESSENGER-RNA EXPRESSION SO MOLECULAR AND CELLULAR ENDOCRINOLOGY LA English DT Article DE INSULIN GROWTH FACTOR-I; TRANSCRIPTION START SITE; MESSENGER-RNA; SPLICE VARIANT; DIFFERENTIAL REGULATION; GROWTH HORMONE; TYPE I INSULIN GROWTH FACTOR RECEPTOR ID MESSENGER RIBONUCLEIC-ACID; LEADER EXONS; GENE-EXPRESSION; SECRETION; PITUITARY; INFUSION; RELEASE; KIDNEY; USAGE AB The rat IGF-I gene consists of six exons, with exons 3 and 4 forming a 'core' mature IGF-I coding region to which alternate 5' and 3' regions are spliced. Transcription occurs from four dispersed start sites (ss) approximate to 382 (ss 1), approximate to 343 (ss 2), approximate to 245 (ss 3) and approximate to 30-40 (ss 4) basepairs (bp) from the 3' end of exon 1, and from a region 50-70 bp from the 3' end of exon 2. The expression of ss mRNAs displays tissue-specific and ontogenic regulation. Alternate splicing of exon 5 produces E-peptide coding domain variants (Ea and Eb mRNAs), with the Eb form found predominantly in the liver. The regulation of IGF-I mRNA expression by GH and IGF-I in the GH-deficient dwarf (dw/dw) rat was investigated using antisense RNA probes in a solution hybridization RNase protection assay to detect leader exon and E domain variant mRNAs. GH treatment of dw/dw and normal Lewis rats increased the expression of all liver leader exon ss and E domain variants coordinately (1.6-1.9-fold increase, p < 0.01), although the increase observed in Eb transcripts was significantly higher in the dw/dw compared to the normal rat (p < 0.05). In kidney, GH treatment significantly increased exon 1 ss 3 and ss 4 transcripts by approximately 40% (p < 0.05). The expression of the other start sites was not affected by GH, suggesting that transcription factors may regulate start site usage independently. GH treatment was associated with a significant increase in IGF-I mRNA expression in skeletal muscle (p < 0.05) but not cardiac muscle or spleen. IGF-I treatment was associated with minor (approximate to 20%) but significant (p < 0.05) reductions in IGF-I mRNA expression in the liver and kidney of dw/dw rats, suggesting that IGF-I can suppress IGF-I mRNA expression. IGF-I treatment did not affect IGF-I mRNA expression in cardiac and skeletal muscle of dw/dw rats. IGF-I receptor mRNA was detected in extrahepatic tissues only, and was not affected by either GH or IGF-I treatment. In summary, start site-specific regulation by GH was observed in kidney. GH increased IGF-I mRNA expression in muscle, kidney and liver, but had no effect in heart or spleen in the dw/dw rat. Our data suggest that systemic IGF-I can feedback on hepatic and renal IGF-I mRNA expression in the GH-deficient state. C1 UNIV AUCKLAND,SCH MED,DEV MED & BIOL RES CTR,AUCKLAND,NEW ZEALAND. NIDDKD,DIABET BRANCH,BETHESDA,MD 20892. RI Breier, Bernhard/D-1176-2009 NR 34 TC 25 Z9 25 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0303-7207 J9 MOL CELL ENDOCRINOL JI Mol. Cell. Endocrinol. PD MAY PY 1994 VL 101 IS 1-2 BP 321 EP 330 DI 10.1016/0303-7207(94)90249-6 PG 10 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA NJ789 UT WOS:A1994NJ78900039 PM 9397967 ER PT J AU KOLBANOVSKAYA, EY OKOROKOV, AL PANOV, KI POLYAKOV, KM HARTLEY, RW KARPEISKII, MY AF KOLBANOVSKAYA, EY OKOROKOV, AL PANOV, KI POLYAKOV, KM HARTLEY, RW KARPEISKII, MY TI BARNASE MUTANT SER57ALA - PRODUCTION AND PROPERTIES SO MOLECULAR BIOLOGY LA English DT Article DE RIBONUCLEASE; BARNASE; SITE-DIRECTED MUTAGENESIS; POLYRIBONUCLEOTIDE HYDROLYSIS ID MICROBIAL RIBONUCLEASES; 3-DIMENSIONAL STRUCTURE; PROTEIN STABILITY; 1.9-A RESOLUTION; MUTAGENESIS; SPECIFICITY; RESIDUES; COMPLEX; FAMILY AB Barnase, an extracellular ribonuclease of Bacillus amyloliquefaciens, is a purine-specific enzyme with clear preference for the guanylic base, especially with short substrates. The work was aimed at ascertaining the role of Ser-57 in the ''recognition loop'' of the RNase in the molecular mechanism of substrate discrimination. The mutant protein with the Ser57 Ala change was expressed in Escherichia coli and used to determine the kinetic parameters of polymeric substrate hydrolysis. The amino acid change was found to have no dramatic effect on polynucleotide cleavage. C1 RUSSIAN ACAD MED SCI,AV SHUBNIKOV CRYSTALLOG INST,MOSCOW 117333,RUSSIA. NIH,BETHESDA,MD 20892. RP KOLBANOVSKAYA, EY (reprint author), RUSSIAN ACAD SCI,VA ENGELHARDT MOLEC BIOL INST,MOSCOW 117984,RUSSIA. NR 30 TC 0 Z9 0 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA CONSULTANTS BUREAU 233 SPRING ST, NEW YORK, NY 10013 SN 0026-8933 J9 MOL BIOL+ JI Mol. Biol. PD MAY-JUN PY 1994 VL 28 IS 3 BP 399 EP 404 PN 2 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PW289 UT WOS:A1994PW28900001 ER PT J AU ACS, G PALKOVITS, M BLUMBERG, PM AF ACS, G PALKOVITS, M BLUMBERG, PM TI [H-3] RESINIFERATOXIN BINDING BY THE HUMAN VANILLOID (CAPSAICIN) RECEPTOR SO MOLECULAR BRAIN RESEARCH LA English DT Article DE VANILLOID RECEPTOR; HUMAN SPINAL CORD; HUMAN MEDULLA OBLONGATA; [H-3] RESINIFERATOXIN BINDING; CAPSAICIN; CAPSAZEPINE ID PRIMARY AFFERENT NEURONS; RESINIFERATOXIN; PHARMACOLOGY; ANALOG AB We report here that we were able to detect the human vanilloid receptor in all three major central endings of primary afferent neurons - in the dorsal horn of the spinal cord, in the cuneate and gracile nuclei and in the spinal nucleus of the trigeminal nerve - and to characterize the binding properties of the receptor in the dorsal horn. Specific [H-3]resiniferatoxin (RTX) binding is thought to represent the vanilloid (capsaicin) receptor. [H-3]RTX binding to membranes obtained from total human spinal cord and dorsal horn followed sigmoidal saturation kinetics indicating apparent positive cooperativity. The cooperativity index determined by fitting the data to the Hill equation was 1.37 +/- 0.02 in the total spinal cord and 1.77 +/- 0.16 in the dorsal horn. The apparent dissociation constants in whole spinal cord and dorsal horn membranes were 915 +/- 12 and 532 +/- 27 pM; the receptor densities were 140 +/- 6 and 227 +/- 15 fmol/mg protein, respectively. Membrane preparations from the spinal nucleus of the trigeminal nerve and the cuneate and gracile nuclei also bound [H-3]RTX in a similar fashion. In parallel experiments, rat spinal cord membranes bound [H-3]RTX with 20- to 40-fold higher affinity, somewhat greater positive cooperativity, but at a 3-fold lower receptor density. As predicted by the modified Hill equation, non-radioactive RTX at low receptor occupancy produced biphasic competition curves. Capsaicin and the competitive antagonist capsazepine also fully displaced specifically: bound [H-3]RTX from human dorsal horn membranes with Ki values of 1.07 +/- 0.04 mu M and 353 +/- 13 nM, respectively; the corresponding Hill coefficients were 1.69 +/- 0.06 and 1.6 +/- 0.02. [H-3]RTX binding was not inhibited by resiniferonol 9,13,14-orthophenylacetate, the biologically inactive parent diterpene of RTX. Capsaicin and capsazepine inhibited specific binding of [H-3]RTX to rat spinal cord membranes with K-i values of 5.3 +/- 0.37 mu M and 3.55 +/- 0.35 mu M and Hill coefficients of 2.03 +/- 0.08 and 1.9 +/- 0.1, respectively. Our results show that there are species differences in the receptor characteristics between man and rat. C1 NCI, CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB, MOLEC MECHANISMS TUMOR PROMOT SECT, BETHESDA, MD 20892 USA. SEMMELWEIS UNIV MED, SCH MED, DEPT ANAT 1, BUDAPEST, HUNGARY. RI Palkovits, Miklos/F-2707-2013 NR 26 TC 20 Z9 20 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD MAY PY 1994 VL 23 IS 3 BP 185 EP 190 DI 10.1016/0169-328X(94)90225-9 PG 6 WC Neurosciences SC Neurosciences & Neurology GA NJ222 UT WOS:A1994NJ22200001 PM 8057776 ER PT J AU BRONSTEIN, DM YE, H PENNYPACKER, KR HUDSON, PM HONG, JS AF BRONSTEIN, DM YE, H PENNYPACKER, KR HUDSON, PM HONG, JS TI ROLE OF A 35 KDA FOS-RELATED ANTIGEN (FRA) IN THE LONG-TERM INDUCTION OF STRIATAL DYNORPHIN EXPRESSION IN THE 6-HYDROXYDOPAMINE LESIONED RAT SO MOLECULAR BRAIN RESEARCH LA English DT Article DE DOPAMINE RECEPTOR; NMDA RECEPTOR; MK-801; OPIOID PEPTIDE; IMMEDIATE-EARLY GENE; TRANSCRIPTION FACTOR; GENE REGULATION; STRIATUM ID D-ASPARTATE RECEPTORS; MESSENGER-RNA LEVELS; C-FOS; INSITU HYBRIDIZATION; GENE-EXPRESSION; SUBSTANCE-P; STRIATOPALLIDAL NEURONS; IMMUNOREACTIVE NEURONS; MATRIX COMPARTMENTS; DOPAMINERGIC SYSTEM AB D-1 dopamine (DA) receptor agonists induce the expression of the opioid peptide dynorphin (DYN) in the striatum, an effect accentuated several fold by removing the dopaminergic innervation to the striatum (e.g., by lesioning the DA cell bodies in the substantia nigra [SN]). D-1 receptor-mediated effects are thought to involve cAMP and/or phosphoinositides as second messengers. However, it is unclear what third messengers are involved in the regulation of DYN expression. The present experiments evaluated the possible role of two families of immediate-early gene (IEG) proteins, Fos and Jun, in the induction of DYN biosynthesis following repeated treatment with DA agonists. In addition, the role of N-methyl-D-aspartate (NMDA) receptors in modulating DA-induced changes in DYN and IEG protein expression was assessed. Adult male rats received unilateral 6-hydroxydopamine (6-OHDA) or sham lesions of the SN. Following a recovery period, animals were injected twice daily with the DA agonist, apomorphine (APO; 5 mg/kg), for 4 or 7 days. As expected, APO induced DYN biosynthesis, at both the peptide and mRNA level, several fold more in the striatum ipsilateral to the 6-OHDA lesion than in the contralateral control side (or a sham lesioned striatum). These effects appeared to be mediated by D-1 receptors since the D-1 agonist, SKF 38393 (5 mg/kg), caused the same changes in DYN expression as APO whereas a D-2 agonist, quinpirole (1 mg/kg), had no effect. Paralleling the increase in DYN expression, APO also induced the expression of c-Fos and Fos-related antigens (FRA's), in particular a 35 kDa FRA, but had no effect on the expression of various Jun-related IEG proteins (i.e., c-Jun, Jun B, Jun D). Consistent with the notion that Fos and FRA proteins alter transcriptional activity by binding to AP-1 (or AP-1-like) DNA sequences in the promoter regions of target genes, we found that repeated APO treatment caused large increases in AP-1 binding activity in striata ipsilateral to 6-OHDA lesions. These data indicate that repeated activation of D-1 receptors increases both the expression of a 35 kDa FRA and AP-1 binding, events which may mediate the large increases in DYN expression in the DA denervated striatum. While co-administration of the NMDA receptor antagonist, MK-801, inhibited APO-induced increases in DYN and Fos/FRA expression in the intact striatum, its only effect in the DA-denervated striatum was a partial (35%) inhibition of the APO-induced increase in DYN-ir concentrations. While NMDA and D1 receptors may interact in regulating DYN expression in the intact striatum, our data suggest that this is not the case in the 6-OHDA lesioned animal. RP BRONSTEIN, DM (reprint author), NIEHS,INTEGRAT BIOL LAB,POB 12233,RES TRIANGLE PK,NC 27709, USA. RI Pennypacker, Keith/I-5092-2012 NR 59 TC 42 Z9 42 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD MAY PY 1994 VL 23 IS 3 BP 191 EP 203 DI 10.1016/0169-328X(94)90226-7 PG 13 WC Neurosciences SC Neurosciences & Neurology GA NJ222 UT WOS:A1994NJ22200002 ER PT J AU GONZALEZ, AM UHL, GR AF GONZALEZ, AM UHL, GR TI CHOLINE/ORPHAN V8-2-1/CREATINE TRANSPORTER MESSENGER-RNA IS EXPRESSED IN NERVOUS, RENAL AND GASTROINTESTINAL SYSTEMS SO MOLECULAR BRAIN RESEARCH LA English DT Note DE CHOLINE TRANSPORTER; CREATINE TRANSPORTER; CHOLINE UPTAKE; HEMICHOLINIUM-3; ACETYLCHOLINE; NERVOUS SYSTEM; GASTROINTESTINAL SYSTEM ID HEMICHOLINIUM-3 BINDING-SITES; RAT-BRAIN; H-3 HEMICHOLINIUM-3; AUTORADIOGRAPHIC DISTRIBUTION; ACETYLCHOLINE SYNTHESIS; DOPAMINE TRANSPORTER; CHOLINERGIC NEURONS; CLONING; SYNAPTOSOMES; MARKER AB Several cDNAs with substantial sequence homologies to members of the neurotransmitter transporter gene family currently remain 'orphan' transporters, without clearly-identified substrates. We were concerned that a cDNA 'V8-2-1' isolated from a ventral midbrain cDNA library in this laboratory and a virtually-identical cDNA 'CHOT1' reported by Mayser et al. [J. Neurochem., 20 (1973) 581-593] might represent such an orphan. Despite initial reports that it could mediate some choline uptake; neither CHOT1 nor V8-2-1 was demonstrated to confer pharmacologically appropriate choline uptake not already present in either Xenopus oocytes or COS cells. Determination of the regional and tissue-specific distribution of mRNA hybridizing with V8-2-1 cDNA was undertaken to aid in identifying its function. Examination of the distribution of V8-2-1 expression reveals several novel features of this transporter gene family member's distribution, including several features that add to current evidence suggesting that the clone may not encode the classical pharmacologically-defined, hemicholinium-3 sensitive high affinity transporter of cholinergic neurons. This data fits with and extends recent data that suggest that this cDNA represent creatine transporter, and provides initial documentation of his regional distribution in brain. C1 NATL INST DRUG ABUSE,ADDICT RES CTR,MOLEC NEUROBIOL BRANCH,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROL & NEUROSCI,BALTIMORE,MD 21224. NR 28 TC 18 Z9 19 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD MAY PY 1994 VL 23 IS 3 BP 266 EP 270 DI 10.1016/0169-328X(94)90233-X PG 5 WC Neurosciences SC Neurosciences & Neurology GA NJ222 UT WOS:A1994NJ22200009 ER PT J AU FAN, L SNYDERWINE, EG AF FAN, L SNYDERWINE, EG TI INHIBITION OF PLASMID REPORTER GENE-EXPRESSION IN CHO CELLS BY DNA-ADDUCTS OF 2-AMINO-3-METHYLIMIDAZO[4,5-F]QUINOLINE AND 2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE SO MOLECULAR CARCINOGENESIS LA English DT Article DE TRANSCRIPTION; TRANSFECTION; HUMAN GROWTH HORMONE; HETEROCYCLIC AMINES; FOOD MUTAGENS/CARCINOGENS ID HETEROCYCLIC AMINES; RNA-POLYMERASE; COOKED FOOD; REPAIR; IDENTIFICATION; TRANSCRIPTION; INVITRO; MUTAGENICITY; CARCINOGEN; STRAND AB 2-Amino-3-methylimidazo[4,5-f]quinoline (IQ) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhlP) are two members of a family of carcinogenic heterocyclic amines (HAs) found in cooked meats that form DNA adducts after activation to N-acetoxy derivatives. The ability of IQ- and PhlP-DNA adducts to inhibit gene expression was investigated using a human growth hormone (hGH) reporter gene in a pUC12-based mammalian expression vector under the control of either the herpes simplex virus-1 thymidine kinase promoter or the human immunodeficiency virus-1 long terminal repeat. The plasmids were treated in vitro with 0, 5, 10, or 40 mu M N-hydroxy-IQ or N-hydroxy-PhlP in the presence of a 10-fold molar excess of acetic anhydride to generate the N-acetoxy derivatives in situ. The adduct levels in the plasmids were quantitated by the P-32-postlabeling method. The adducted (and control) plasmids were each transfected into repair-deficient or -proficient Chinese hamster ovary cells, and expression of hGH was measured by immunoassay of growth hormone secreted into the cell medium. The results showed that IQ- and PhlP-DNA adducts inhibited gene expression in both plasmids and that the degree of inhibition of hGH production was proportional to the levels of IQ- and PhlP-DNA adducts. The degree of inhibition, however, was independent of the promoter, despite the differences in the strengths of the two promoters to drive hGH production. Repair capacity influenced the extent of inhibition of gene expression by HA adducts since, in general, fewer adducts were needed to inhibit reporter gene expression in repair-deficient cells than in repair-proficient cells. In both cell lines, DNA adducts of PhlP appeared to be more potent in inhibiting hGH expression than adducts of IQ. Whether alteration of gene expression by HA adducts plays a role in the carcinogenicity of these compounds deserves further study. (C) 1994 Wiley-Liss, Inc.* RP FAN, L (reprint author), NCI,EXPTL CARCINOGENESIS LAB,BLDG 37,ROOM 3C28,BETHESDA,MD 20892, USA. NR 44 TC 5 Z9 5 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD MAY PY 1994 VL 10 IS 1 BP 30 EP 37 DI 10.1002/mc.2940100106 PG 8 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA NL729 UT WOS:A1994NL72900005 PM 8185827 ER PT J AU ARCHER, TK LEE, HL CORDINGLEY, MG MYMRYK, JS FRAGOSO, G BERARD, DS HAGER, GL AF ARCHER, TK LEE, HL CORDINGLEY, MG MYMRYK, JS FRAGOSO, G BERARD, DS HAGER, GL TI DIFFERENTIAL STEROID-HORMONE INDUCTION OF TRANSCRIPTION FROM THE MOUSE MAMMARY-TUMOR VIRUS PROMOTER SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID POSITIONED NUCLEOSOMES; RECEPTOR-BINDING; MMTV PROMOTER; MESSENGER-RNA; PROGESTERONE-RECEPTOR; REGULATORY ELEMENT; RESPONSE ELEMENTS; CELL-LINE; CHROMATIN; GENES AB The Mouse Mammary Tumor Virus (MMTV) contains sequences in its proximal promoter region to which both glucocorticoid and progesterone receptors can bind. In transient transfection experiments both hormones are able to stimulate transcription from reporter plasmids containing either native or consensus hormone response elements (glucocorticoid response element/progesterone response element). Previous experiments have demonstrated that the MMTV long terminal repeat is reproducibly assembled into a phased array of nucleosomes when stably introduced into cells. Stimulation by glucocorticoids of endogenous templates led to a rapid but transient increase in transcription initiation and mRNA accumulation that can be correlated with increased sensitivity to restriction enzymes. In contrast, experiments using progesterone or a truncated glucocorticoid receptor failed to elicit a similar increase in mRNA levels as dexamethasone from stable chromatin templates. In an attempt to understand this differential response, we have compared the responsiveness of the MMTV promoter to glucocorticoids and progesterone when it is organized in either stable chromatin or in transiently acquired plasmids. Our results demonstrate that the native chromatin structure prevents activation of this locus by progesterone, but permits stimulation by glucocorticoids. C1 NCI, MOLEC VIROL LAB, HORMONE ACT & ONCOGENESIS SECT, BETHESDA, MD 20892 USA. UNIV WESTERN ONTARIO, DEPT OBSTET GYNECOL & BIOCHEM, LONDON REG CANC CTR, LONDON N6A 4L6, ON, CANADA. NR 49 TC 85 Z9 85 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD MAY PY 1994 VL 8 IS 5 BP 568 EP 576 DI 10.1210/me.8.5.568 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA NM208 UT WOS:A1994NM20800004 PM 8058066 ER PT J AU DEY, BR SUKHATME, VP ROBERTS, AB SPORN, MB RAUSCHER, FJ KIM, SJ AF DEY, BR SUKHATME, VP ROBERTS, AB SPORN, MB RAUSCHER, FJ KIM, SJ TI REPRESSION OF THE TRANSFORMING GROWTH-FACTOR-BETA-1 GENE BY THE WILMS-TUMOR SUPPRESSOR WT1 GENE-PRODUCT SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID ACCURATE TRANSCRIPTION INITIATION; FACTOR-A-CHAIN; EXTRACELLULAR-MATRIX; 3T3 CELLS; EXPRESSION; DELETION; BINDING; BETA; TRANSACTIVATION; SEQUENCES AB The Wilms' tumor suppressor gene (WT1) encodes a zinc finger DNA binding protein which functions as a transcriptional repressor. In this study we investigated whether the human transforming growth factor-beta 1 (TGF-beta 1) gene might be a target for transcriptional repression mediated by WT1. Using constructs of the TGF-beta 1 promoter linked to the chloramphenicol acetyl transferase gene, we have demonstrated that the WT1 protein represses expression of the TGF-beta 1 gene through a CGCCCCCGC response element spanning nucleotides -111 to -119 of the TGF-beta 1 promoter. We have also shown in a cotransfection assay that Egr-1, an immediate early growth response gene, activates transcription of the TGF-beta 1 gene through the same response element and that WT1 represses both the basal and Egr-1-induced TGF-beta 1 promoter activity in monkey kidney CV-1 cells. Moreover, WT1 and Egr-1 proteins interact directly with the WT1/Egr-1 response element of the TGF-beta 1 promoter in gel mobility shift assays. These findings provide further definition of transcriptional control of the TGF-beta 1 gene by showing that the WT1 gene product suppresses TGF-beta 1 transcription and that the WT1/Egr-1 consensus element of the human TGF-beta 1 promoter plays a critical role in this repression. C1 NCI, CHEMOPREVENT LAB, BETHESDA, MD 20892 USA. BETH ISRAEL HOSP, DIV RENAL, BOSTON, MA 02215 USA. WISTAR INST ANAT & BIOL, PHILADELPHIA, PA 19104 USA. FU NCI NIH HHS [CA-10817, CA-47983, CA-52009] NR 42 TC 180 Z9 186 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD MAY PY 1994 VL 8 IS 5 BP 595 EP 602 DI 10.1210/me.8.5.595 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA NM208 UT WOS:A1994NM20800007 PM 8058069 ER PT J AU MINOGUCHI, K KIHARA, H NISHIKATA, H HAMAWY, MM SIRAGANIAN, RP AF MINOGUCHI, K KIHARA, H NISHIKATA, H HAMAWY, MM SIRAGANIAN, RP TI SRC FAMILY TYROSINE KINASE LYN BINDS SEVERAL PROTEINS INCLUDING PAXILLIN IN RAT BASOPHILIC LEUKEMIA-CELLS SO MOLECULAR IMMUNOLOGY LA English DT Article DE PROTEIN TYROSINE KINASE LYN; BASOPHILS; MAST CELLS; SRC HOMOLOGY 2 DOMAIN (SH2); PAXILLIN ID AFFINITY IGE RECEPTOR; GROWTH-FACTOR RECEPTORS; PHOSPHOLIPASE-C-GAMMA; ANTIGEN RECEPTOR; SIGNAL TRANSDUCTION; IMMUNOGLOBULIN-E; MONOCLONAL-ANTIBODIES; HISTAMINE-RELEASE; MAST-CELLS; V-SRC AB Aggregation of the high affinity IgE receptors on rat basophilic leukemia (RBL-2H3) cells results in protein tyrosine phosphorylation although the receptor has no intrinsic enzymatic activity. The Src related protein tyrosine kinase p53/56(lyn) present in RBL-2H3 cells could play a role in this reaction. Here we have isolated the cDNA for rat Lyn and found it to be very homologous at the amino acid level to both the human and mouse proteins. A bacterially expressed maltose binding protein-Lyn (MBP-Lyn) fusion protein was already tyrosine phosphorylated and had tyrosine kinase activity. In a filter-binding assay, MBP-Lyn fusion protein (at 0.1 mu M) specifically bound to several proteins of RBL-2H3 cells. In lysates of IgE receptor-activated cells, there was increased binding of MBP-Lyn to 65, 72, 78 and 110 kDa tyrosine phosphorylated proteins. The 72, 78 and 110 kDa tyrosine phosphorylated proteins were precipitated by a fusion protein containing the Lyn Src Homology 2 (SH2) domain. The 72 kDa Lyn binding protein was different from p72(syk). Furthermore, paxillin, a cytoskeletal protein, was identified as one of the Lyn binding proteins. Thus Fc epsilon RI mediated signal transduction in RBL-2H3 cells may result from the interaction of p53/56(lyn) with paxillin, pp72, pp110 and other proteins. RP MINOGUCHI, K (reprint author), NIDR,IMMUNOL LAB,BLDG 10,RM 1N106,BETHESDA,MD 20892, USA. NR 68 TC 29 Z9 29 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD MAY PY 1994 VL 31 IS 7 BP 519 EP 529 PG 11 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA NN223 UT WOS:A1994NN22300003 PM 8190127 ER PT J AU OLAH, ME GALLORODRIGUEZ, C JACOBSON, KA STILES, GL AF OLAH, ME GALLORODRIGUEZ, C JACOBSON, KA STILES, GL TI I-125 4-AMINOBENZYL-5'-N-METHYLCARBOXAMIDOADENOSINE, A HIGH-AFFINITY RADIOLIGAND FOR THE RAT A(3) ADENOSINE RECEPTOR SO MOLECULAR PHARMACOLOGY LA English DT Article ID MOLECULAR-CLONING; BINDING; EXPRESSION; A1; BRAIN AB The rat A, adenosine receptor (AR) is a recently characterized AR subtype cloned from testis and brain cDNA libraries. N-6-2-(4-Amino-3-[I-125]iodophenyl)ethyl adenosine, a high affinity A(1)AR agonist, has served as the only radioligand available for study of the A(3)AR. The relatively low affinity of N-6-2-(4-amino-3-[I-125] iodophenyl)ethyladenosine for the A(3)AR and its greater A(1)AR selectivity necessitate the development of more appropriate radioligands for A(3)AR analysis. This report characterizes I-125-4-aminobenzyl-5'-N-methylcarboxamidoadenosin e (I-125-AB- MECA), a high affinity radioligand for the A(3)AR, in two cell lines that express this AR subtype. Membranes from Chinese hamster ovary (CHO) cells expressing the rat A(3)AR and from the rat mast cell line RBL-2H3 bound I-125-AB-MECA with K-d values of 1.48 +/- 0.33 nM and 3.61 c 0.30 nM, respectively. As determined by I-125- AB-MECA binding, levels of A(3)AR expresssion in the A(3)AR-CHO cell line and RBL-2H3 cells were 3.06 +/- 0.21 pmol/mg and 1.02 +/- 0.13 pmol/mg, respectively. Binding of I-125-AB-MECA was characterized in competition assays. In the A,AR-CHO cell line a potency ord er of cyclohexyl-5'-N-ethylcarboxamidoadenosine (cyclohexyl-NECA) = benzyl-NECA > (-)-N-6-[(R)-phenylisopropyl]adenosine = NECA was observed, and in RBL-2H3 cells (-)-N-6-[(R)-phenylisopropyl]adenosine and NECA were equipotent. Xanthine amine congener (XAC) and 3-cyclopentyl-1,3-dipropylxanthine did not significantly inhibit I-125-AB-MECA binding. The parent compound, AB-MECA, dose-dependently inhibited forskolin-stimulated adenylyl cyclase activity in A(3)AR-CHO cell membranes. I-125-AB-MECA bound to the rat A(1)AR and canine A(2a)AR expressed in COS-7 cells with K-d values of 3.42 +/- 0.43 nM and 25.1 +/- 12.6 nM, respectively. This binding was significantly reduced in the presence of 1 mu M XAC. In RBL-2H3 cells, XAC had no effect on I-125-AB-MECA affinity and reduced the level of radioligand binding by similar to 5%. C1 DUKE UNIV,MED CTR,DEPT MED,DIV CARDIOL,DURHAM,NC 27710. NIDDKD,MOLEC RECOGNIT SECT,BIOORGAN CHEM LAB,BETHESDA,MD 20892. RI Gallo-Rodriguez, Carola/E-1732-2012; Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS [Z01 DK031117-20, Z99 DK999999]; NHLBI NIH HHS [P50HL17670, R01HL35134] NR 20 TC 171 Z9 172 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD MAY PY 1994 VL 45 IS 5 BP 978 EP 982 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA NM738 UT WOS:A1994NM73800021 PM 8190112 ER PT J AU STOJILKOVIC, SS TOMIC, M KUKULJAN, M CATT, KJ AF STOJILKOVIC, SS TOMIC, M KUKULJAN, M CATT, KJ TI CONTROL OF CALCIUM SPIKING FREQUENCY IN PITUITARY GONADOTROPHS BY A SINGLE-POOL CYTOPLASMIC OSCILLATOR SO MOLECULAR PHARMACOLOGY LA English DT Article ID INOSITOL 1,4,5-TRISPHOSPHATE RECEPTOR; CA2+-INDUCED CA2+ RELEASE; PANCREATIC ACINAR-CELLS; INTRACELLULAR CALCIUM; XENOPUS-OOCYTES; CYTOSOLIC CALCIUM; HAMSTER EGGS; CA-2+ TRANSIENTS; RAT GONADOTROPES; LUMINAL CA2+ AB The mechanisms by which the generation and frequency of cytoplasmic Ca2+ oscillations are controlled were investigated in pituitary gonadotrophs. In these cells, two Ca2+-mobilizing receptors, the gonadotropin-releasing hormone and endothelin receptors, induce frequency-modulated Ca2+ spiking at the rate of up to 30 min(-1). The cytoplasmic oscillator is also activated by discharge of luminal Ca2+ (initiated by ionomycin, thapsigargin, or thimerosal) but not by increased voltage-sensitive Ca2+ influx or treatment with caffeine. The basic difference between these two types of Ca2+ oscillations is related to their requirement for inositol-1,4,5-trisphosphate (InsP(3)). Thapsigargin-, thimerosal-, and ionomycin-induced spiking occurs without the rise in InsP(3) production that is essential for the generation of receptor-controlled oscillatory responses. The differential requirement for InsP(3) in the two types of Ca2+ spiking is indicated by two lines of evidence. First, agonist-induced Ca2+ spiking of frequency similar to that of non-receptor-mediated oscillations was accompanied by a significant increase in InsP(3), whereas none of the non-receptor-mediated oscillations was associated with measurable changes in inositol phosphate production. Second, agonist-induced InsP(3) formation and Ca2+ spiking were abolished by treatment with the phospholipase C inhibitors U73122 and neomycin sulfate, whereas non-receptor-mediated Ca2+ spiking was not affected by these agents. When the oscillator was activated by agents that do not increase InsP(3) formation, it operated only at the basal rate of similar to 5 min(-1) and spiking frequency did not rise with increasing drug concentrations, in contrast to the situation in agonist-stimulated gonadotrophs. However, both types of oscillations were affected by depletion of luminal Ca2+ and by changes in the intracellular Ca2+ concentration ([Ca2+](i)) but were not inhibited by ryanodine. These findings are consistent with the operation of a single-pool Ca2+ oscillator that is responsible for generation of both types of Ca2+ oscillations. The oscillator is controlled by the coagonist actions of InsP(3) and Ca2+ on the InsP(3) receptor channels and by the activation of Ca2+-ATPase by rising [Ca2+](i). It can be induced to operate at low frequency without an increase in InsP(3) production by agents that reduce intraluminal [Ca2+](i), and it exhibits a dose-dependent increase in spiking frequency during agonist stimulation.- RP STOJILKOVIC, SS (reprint author), NICHHD,ENDOCRINOL & REPROD RES BRANCH,BLDG 49,ROOM 6A-36,BETHESDA,MD 20892, USA. RI Tomic, Melanija/C-3371-2016 NR 54 TC 49 Z9 49 U1 0 U2 2 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD MAY PY 1994 VL 45 IS 5 BP 1013 EP 1021 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA NM738 UT WOS:A1994NM73800026 PM 8190091 ER PT J AU TENNANT, RW HANSEN, L SPALDING, J AF TENNANT, RW HANSEN, L SPALDING, J TI GENE MANIPULATION AND GENETIC TOXICOLOGY SO MUTAGENESIS LA English DT Article; Proceedings Paper CT Workshop on Gene Manipulation and Genetic Toxicology, at the 17th International Congress of Genetics CY AUG 15-21, 1993 CL BIRMINGHAM, ENGLAND ID TRANSGENIC MICE BEARING; HA-RAS; ONCOGENES; MODELS; CARCINOGENICITY; MUTATION; STEP AB Transgenic mice with recoverable target genes, with genes modified in expression or with ablated gene function provide important tools for defining the biological effects off chemicals. In many cases studies can be conducted with fewer animals and in a shorter timeframe. They also provide important tools for studies of carcinogenesis mechanisms and processes, for early detection of carcinogens and for identification of potential cancer therapies. RP TENNANT, RW (reprint author), NIEHS,ENVIRONM CARCINOGENESIS & MUTAGENESIS LAB,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 21 TC 9 Z9 9 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0267-8357 J9 MUTAGENESIS JI Mutagenesis PD MAY PY 1994 VL 9 IS 3 BP 171 EP 174 DI 10.1093/mutage/9.3.171 PG 4 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA NM558 UT WOS:A1994NM55800002 PM 7934954 ER PT J AU EVANS, MK BOHR, VA AF EVANS, MK BOHR, VA TI GENE-SPECIFIC DNA-REPAIR OF UV-INDUCED CYCLOBUTANE PYRIMIDINE DIMERS IN SOME CANCER-PRONE AND PREMATURE-AGING HUMAN SYNDROMES SO MUTATION RESEARCH LA English DT Article DE DNA REPAIR; GENE-SPECIFIC; CYCLOBUTANE PYRIMIDINE DIMERS; UV-INDUCED; HUMAN SYNDROMES; CANCER-PRONE; PREMATURE AGING; DYSPLASTIC NEVUS SYNDROME; GARDNERS SYNDROME; BLOOMS SYNDROME; DNA-DAMAGE HYPERSENSITIVITY ID DYSPLASTIC NEVUS SYNDROME; ULTRAVIOLET-LIGHT SENSITIVITY; CUTANEOUS MALIGNANT-MELANOMA; DIHYDROFOLATE-REDUCTASE GENE; BLOOMS SYNDROME FIBROBLASTS; SISTER-CHROMATID-EXCHANGE; CULTURED SKIN FIBROBLASTS; PHASE X-IRRADIATION; COCKAYNES-SYNDROME; GARDNERS-SYNDROME AB We have examined the gene-specific DNA repair of UV-induced cyclobutane pyrimidine dimers (CPDs) in fibroblasts from the following cancer prone syndromes: familial dysplastic nevus syndrome (DNS), Gardner's syndrome (GS), and Bloom's syndrome (BS). These heritable human syndromes are associated with DNA damage hypersensitivity and have been considered as potentially DNA repair deficient. Previous determinations of DNA repair in these cell strains have been done solely at the level of the overall genome. That approach is not sensitive enough to detect deficiencies in repair at the level of the gene. Defective preferential repair of active genes may impair survival and affect genomic stability. This is exemplified by the disorder Cockayne's syndrome (CS) which is associated with a selective deficiency in the preferential repair of active genes. In this study, we have used a Cockayne's syndrome cell strain and also a normal human fibroblast cell line as a control. Repair was studied in the transcriptionally active gene dihydrofolate reductase (DHFR), the inactive delta globin gene, and in the c-myc protooncogene. In the DNS, GS and BS cell lines, we find preferential repair similar to that in normal cells. In Cockayne's syndrome cells, there is no preferential repair of the DHFR gene. C1 NCI,MOLEC PHARMACOL LAB,BETHESDA,MD 20892. NR 63 TC 29 Z9 29 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0921-8262 J9 MUTAT RES PD MAY PY 1994 VL 314 IS 3 BP 221 EP 231 DI 10.1016/0921-8777(94)90067-1 PG 11 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA NJ051 UT WOS:A1994NJ05100003 PM 7513055 ER PT J AU GNARRA, JR TORY, K WENG, Y SCHMIDT, L WEI, MH LI, H LATIF, F LIU, S CHEN, F DUH, FM LUBENSKY, I DUAN, DR FLORENCE, C POZZATTI, R WALTHER, MM BANDER, NH GROSSMAN, HB BRAUCH, H POMER, S BROOKS, JD ISAACS, WB LERMAN, MI ZBAR, B LINEHAN, WM AF GNARRA, JR TORY, K WENG, Y SCHMIDT, L WEI, MH LI, H LATIF, F LIU, S CHEN, F DUH, FM LUBENSKY, I DUAN, DR FLORENCE, C POZZATTI, R WALTHER, MM BANDER, NH GROSSMAN, HB BRAUCH, H POMER, S BROOKS, JD ISAACS, WB LERMAN, MI ZBAR, B LINEHAN, WM TI MUTATIONS OF THE VHL TUMOR-SUPPRESSOR GENE IN RENAL-CARCINOMA SO NATURE GENETICS LA English DT Article ID VONHIPPEL-LINDAU DISEASE; CELL CARCINOMA; LINES; CANCER AB Multiple, bilateral renal carcinomas are a frequent occurrence in von Hippel-Lindau (VHL) disease. To elucidate the aetiological role of the VHL gene in human kidney tumorigenesis, localized and advanced tumours from 110 patients with sporadic renal carcinoma were analysed for VHL mutations and loss of heterozygosity (LOH). VHL mutations were identified in 57% of clear cell renal carcinomas analysed and LOH was observed in 98% of those samples. Moreover, VHL was mutated and lost in a renal tumour from a patient with familial renal carcinoma carrying the constitutional translocation, t(3;8)(p14;q24). The identification of VHL mutations in a majority of localized and advanced sporadic renal carcinomas and in a second form of hereditary renal carcinoma indicates that the VHL gene plays a critical part in the origin of this malignancy. C1 NCI,SURG BRANCH,UROL ONCOL SECT,BETHESDA,MD 20892. NCI,PATHOL LAB,BETHESDA,MD 20892. NCI,FREDERICK CANC RES & DEV CTR,IMMUNOBIOL LAB,FREDERICK,MD 21702. DYNCORP INC,PROGRAM RESOURCES,FREDERICK,MD 21702. CORNELL UNIV,NEW YORK HOSP,CTR MED,DEPT UROL,NEW YORK,NY. UNIV MICHIGAN,UROL SECT,ANN ARBOR,MI 48109. TECH UNIV MUNICH,MOLEC PATHOL LAB,D-81675 MUNICH,GERMANY. UNIV HEIDELBERG,SURG CLIN,HEIDELBERG,GERMANY. JOHNS HOPKINS MED INST,JAMES BUCHANAN BRADY UROL INST,BALTIMORE,MD 21205. NR 28 TC 1173 Z9 1195 U1 6 U2 29 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1061-4036 J9 NAT GENET JI Nature Genet. PD MAY PY 1994 VL 7 IS 1 BP 85 EP 90 DI 10.1038/ng0594-85 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA NJ842 UT WOS:A1994NJ84200019 PM 7915601 ER PT J AU RISINGER, JI BERCHUCK, A KOHLER, MF BOYD, J AF RISINGER, JI BERCHUCK, A KOHLER, MF BOYD, J TI MUTATIONS OF THE E-CADHERIN GENE IN HUMAN GYNECOLOGIC CANCERS SO NATURE GENETICS LA English DT Article ID CELL-ADHESION MOLECULE; TUMOR SUPPRESSOR GENE; PROSTATE-CANCER; EXPRESSION; CARCINOMA; CHROMOSOME-16; UVOMORULIN; ADENOCARCINOMA; PROGRESSION; ALLELOTYPE AB Expression of the E-cadherin cell adhesion molecule is reduced in several types of human carcinomas, and the protein serves as an invasion suppressor in vitro. To determine if mutations of the E-cadherin gene (on chromosome 16q22) contribute to epithelial tumorigenesis, 135 carcinomas of the endometrium and ovary were examined for alterations in the E-cadherin coding region. Four mutations were identified: one somatic nonsense and one somatic missense mutation, both with retention of the wildtype alleles, and two missense mutations with somatic loss of heterozygosity in the tumour tissue. These data support the classification of E-cadherin as a human tumour suppressor gene. C1 NIEHS,GYNECOL PATHOBIOL GRP,MOLEC CARCINOGENESIS LAB,RES TRIANGLE PK,NC 27709. DUKE UNIV,MED CTR,DEPT OBSTET & GYNECOL,DURHAM,NC 27710. NR 31 TC 249 Z9 254 U1 0 U2 2 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1061-4036 J9 NAT GENET JI Nature Genet. PD MAY PY 1994 VL 7 IS 1 BP 98 EP 102 DI 10.1038/ng0594-98 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA NJ842 UT WOS:A1994NJ84200021 PM 8075649 ER PT J AU SMITH, LJ REDFIELD, C SMITH, RAG DOBSON, CM CLORE, GM GRONENBORN, AM WALTER, MR NAGANBUSHAN, TL WLODAWER, A AF SMITH, LJ REDFIELD, C SMITH, RAG DOBSON, CM CLORE, GM GRONENBORN, AM WALTER, MR NAGANBUSHAN, TL WLODAWER, A TI COMPARISON OF 4 INDEPENDENTLY DETERMINED STRUCTURES OF HUMAN RECOMBINANT INTERLEUKIN-4 SO NATURE STRUCTURAL BIOLOGY LA English DT Article ID NUCLEAR-MAGNETIC-RESONANCE; X-RAY-DIFFRACTION; 3-DIMENSIONAL SOLUTION STRUCTURE; INTERPROTON DISTANCE RESTRAINTS; CRYSTAL-STRUCTURE; SECONDARY STRUCTURE; MOLECULAR-DYNAMICS; PROTEIN STRUCTURES; SINGLE-CRYSTALS; HIGH-RESOLUTION AB Four independent structures of human interleukin-4, two determined by nuclear magnetic resonance techniques and two ky X-ray diffraction, have keen compared in detail. The core of this four helix bundle protein is very similar in all the structures but there are some differences in loop regions that are known to be mobile in solution. Careful comparison of the experimental data sets and the methods of analysis of the different laboratories has provided clues to the sources of most of the differences, and also answered some general questions about the accuracy of protein structure determination by these two techniques. C1 UNIV OXFORD,NEW CHEM LAB,OXFORD OX1 3QT,ENGLAND. SMITHKLINE BEECHAM PHARMACEUT,HARLOW CM19 5AD,ESSEX,ENGLAND. NIDDKD,CHEM PHYS LAB,BETHESDA,MD 20892. UNIV ALABAMA,DEPT PHARMACOL,BIRMINGHAM,AL 35294. SCHERING PLOUGH CORP,RES INST,BLOOMFIELD,NJ 07003. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MACROMOLEC STRUCT LAB,FREDERICK,MD 21702. RP SMITH, LJ (reprint author), UNIV OXFORD,OXFORD CTR MOLEC SCI,S PARKS RD,OXFORD OX1 3QT,ENGLAND. RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 NR 30 TC 37 Z9 38 U1 0 U2 2 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1072-8368 J9 NAT STRUCT BIOL JI Nat. Struct. Biol. PD MAY PY 1994 VL 1 IS 5 BP 301 EP 310 DI 10.1038/nsb0594-301 PG 10 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA PH948 UT WOS:A1994PH94800011 PM 7664036 ER PT J AU SOKOLOFF, L AF SOKOLOFF, L TI AGRANOFF,BERNARD,WILLIAM, A MODERN-DAY THUDICHUM - FOREWORD SO NEUROCHEMICAL RESEARCH LA English DT Item About an Individual RP SOKOLOFF, L (reprint author), NIMH,CEREBRAL METAB LAB,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0364-3190 J9 NEUROCHEM RES JI Neurochem. Res. PD MAY PY 1994 VL 19 IS 5 BP 529 EP 531 DI 10.1007/BF00971326 PG 3 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA NH866 UT WOS:A1994NH86600001 PM 8065508 ER PT J AU RIBEIRO, P KAUFMAN, S AF RIBEIRO, P KAUFMAN, S TI THE EFFECT OF TETRAHYDROBIOPTERIN ON THE IN-SITU PHOSPHORYLATION OF TYROSINE-HYDROXYLASE IN RAT STRIATAL SYNAPTOSOMES SO NEUROCHEMICAL RESEARCH LA English DT Article DE TETRAHYDROBIOPTERIN; TYROSINE HYDROXYLASE; PHOSPHORYLATION; SYNAPTOSOMES ID NITRIC-OXIDE SYNTHASE; SEPIAPTERIN REDUCTASE; BRAIN; COFACTOR; BIOPTERIN; DOPAMINE; IDENTIFICATION; BIOSYNTHESIS; PURIFICATION; PHOSPHATASE AB Tetrahydrobiopterin (BH4), the obligatory cofactor of the aromatic amino acid hydroxylases, decreased the in situ P-32-phosphorylation of tyrosine hydroxylase (TH) in rat striatal synaptosomes. Incubation of pre-P-32-labeled synaptosomes with BH4 in the presence of a permeant analogue of cAMP decreased the cAMP-stimulated level of P-32 label incorporation into TH by about 50%, as determined by immunoprecipitaiion and autoradiography of SDS-polyacrylamide gels. The extent of inhibition mirrored changes in intrasynaptosomal BH4 levels and varied both as a function of BH4 concentration and length of incubation. A similar decrease in the amount of TH P-32-labeling was observed with the precursor of BH4, sepiapterin. This effect, in turn, was reversed by the inhibitor of sepiapterin reductase, N-acetyl-serotonin. Finally, exposure of pre-P-32-labeled synaptosomes to the inhibitor of protein phosphatase 2A, okadaic acid, blocked the response to BH4. Collectively, the data suggest that BH4 stimulates the dephosphorylation of TH in situ and thus may play a dual role both as a cofactor for catalysis and a regulator of hydroxylase activity. RP RIBEIRO, P (reprint author), NIMH,NEUROCHEM LAB,BLDG 36,RM 3D30,BETHESDA,MD 20892, USA. NR 31 TC 7 Z9 7 U1 0 U2 1 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0364-3190 J9 NEUROCHEM RES JI Neurochem. Res. PD MAY PY 1994 VL 19 IS 5 BP 541 EP 548 DI 10.1007/BF00971328 PG 8 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA NH866 UT WOS:A1994NH86600003 PM 7915013 ER PT J AU SMITH, CB YU, WHA AF SMITH, CB YU, WHA TI RATES OF PROTEIN-SYNTHESIS IN THE REGENERATING HYPOGLOSSAL NUCLEUS - EFFECTS OF TESTOSTERONE TREATMENT SO NEUROCHEMICAL RESEARCH LA English DT Article DE REGENERATION; AXOTOMY; MOTONEURONS; ANDROGENS; LEUCINE ID DEVELOPING NEUROMUSCULAR SYSTEM; DIMORPHIC SPINAL NUCLEUS; STEM MOTOR NUCLEI; GLUCOSE-UTILIZATION; HORMONAL-CONTROL; NERVOUS-SYSTEM; SEX DIFFERENCE; AXOTOMY; ANDROGEN; BRAIN AB Rates of protein synthesis (1CPS(leu)) along the entire rostral to caudal extent of the hypoglossal nucleus were determined in adult, female rats with the quantitative autoradiographic L-[1-C-14]leucine method two and five weeks after unilateral hypoglossal axotomy with and without chronic treatment with testosterone. Rates of protein synthesis were increased on the axotomized side, and the increases were greater in the rostral portion of the nucleus at both time points examined. The effects of axotomy on 1CPS(leu) were less at five weeks post-axotomy than at two weeks. In spite of the fact that testosterone has been shown to accelerate both the rate of outgrowth of regenerating cranial motor nerves (Kujawa et al., J. Neurosci. 11:3898-3906, 1991) and the recovery of function (Kujawa et al., Exp. Neurol. 105:80-85, 1989) and to attenuate the loss of neurons (Yu et al., Exp. Neurol. 80:349-360, 1983) there were no effects of testosterone on 1CPS(leu) in the hypoglossal nucleus in either sham-operated or axotomized rats. C1 CUNY,SCH MED,DEPT CELL BIOL & ANAT SCI,NEW YORK,NY 10031. RP SMITH, CB (reprint author), US PHS,NIMH,CEREBRAL METAB LAB,BLDG 36,ROOM 1A-05,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 33 TC 2 Z9 2 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0364-3190 J9 NEUROCHEM RES JI Neurochem. Res. PD MAY PY 1994 VL 19 IS 5 BP 623 EP 629 DI 10.1007/BF00971339 PG 7 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA NH866 UT WOS:A1994NH86600014 PM 8065519 ER PT J AU CLARK, M SMITH, MA WEISS, SRB POST, RM AF CLARK, M SMITH, MA WEISS, SRB POST, RM TI MODULATION OF HIPPOCAMPAL GLUCOCORTICOID AND MINERALOCORTICOID RECEPTOR MESSENGER-RNA EXPRESSION BY AMYGDALOID KINDLING SO NEUROENDOCRINOLOGY LA English DT Article DE GLUCOCORTICOID RECEPTOR; HIPPOCAMPUS; KINDLING; MESSENGER RNA; MINERALOCORTICOID RECEPTOR; SEIZURE ID RAT-BRAIN; MESSENGER-RNAS; SYNAPTIC REORGANIZATION; INDUCED SEIZURES; ADRENALECTOMY; LOCALIZATION; EPILEPSY; SURVIVAL; NEURONS; MODEL AB In situ hybridization was used to examine the effects of amygdala kindling on the expression of mRNAs for mineralocorticoid receptors (MR) and glucocorticoid receptors (GR) in the rat hippocampus. Kindling increased MR mRNA levels in the dentate gyrus of the hippocampus 4 h after the last seizure, and these levels remained elevated 24 h later, but returned to baseline at 4 days. The only other hippocampal region that showed changes was the ipsilateral CA2 subfield where MR mRNA was significantly increased only at the 4-hour time point. Kindling also increased the levels of GR mRNA in the dentate gyrus at 4 h; however, GR mRNA levels significantly decreased below control values at 24 h before returning to normal at 4 days. These data indicate differential transient alterations in hippocampal MR and GR receptor mRNA expression following amygdala-kindled seizures. RP CLARK, M (reprint author), NIMH,BIOL PSYCHIAT BRANCH,BLDG 10,ROOM 3N212,BETHESDA,MD 20892, USA. NR 36 TC 20 Z9 20 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0028-3835 J9 NEUROENDOCRINOLOGY JI Neuroendocrinology PD MAY PY 1994 VL 59 IS 5 BP 451 EP 456 DI 10.1159/000126691 PG 6 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA NJ492 UT WOS:A1994NJ49200006 PM 8022520 ER PT J AU PASCUALLEONE, A VALLSSOLE, J BRASILNETO, JP COHEN, LG HALLETT, M AF PASCUALLEONE, A VALLSSOLE, J BRASILNETO, JP COHEN, LG HALLETT, M TI AKINESIA IN PARKINSONS-DISEASE .1. SHORTENING OF SIMPLE REACTION-TIME WITH FOCAL, SINGLE-PULSE TRANSCRANIAL MAGNETIC STIMULATION SO NEUROLOGY LA English DT Article ID STEREOTYPED VOLUNTARY MOVEMENTS; TARGETED FORCE IMPULSES; BASAL GANGLIA; MOTOR CORTEX; ELECTRICAL-STIMULATION; SOMATOSENSORY STIMULI; TRAJECTORY CONTROL; HUMAN-BRAIN; PERFORMANCE; EXECUTION AB We studied the effects of transcranial magnetic stimulation (TMS) of the motor cortex on simple reaction time (RT) in 10 patients with Parkinson's disease compared with 10 age-matched normal controls. The subjects flexed their right elbow rapidly in response to a visual go-signal. In random trials, TMS was applied to the left motor cortex at varying delays after the go-signal. In trials without TMS, RT was longer in the patients. However, in the trials with subthreshold TMS, RT in the patients became as fast as RT in trials without TMS in the controls. This shortening was associated with normalization of the voluntary triphasic EMG pattern and the pre-movement cortical excitability increase. C1 NINCDS,MED NEUROL BRANCH,HUMAN MOTOR CONTROL SECT,HUMAN CORT PHYSIOL UNIT,BETHESDA,MD 20892. RI Pascual-Leone, Alvaro/G-6566-2011; Brasil-Neto, Joaquim/A-1171-2009 NR 59 TC 130 Z9 136 U1 0 U2 2 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAY PY 1994 VL 44 IS 5 BP 884 EP 891 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA NL811 UT WOS:A1994NL81100018 PM 8190292 ER PT J AU PASCUALLEONE, A VALLSSOLE, J BRASILNETO, JP CAMMAROTA, A GRAFMAN, J HALLETT, M AF PASCUALLEONE, A VALLSSOLE, J BRASILNETO, JP CAMMAROTA, A GRAFMAN, J HALLETT, M TI AKINESIA IN PARKINSONS-DISEASE .2. EFFECTS OF SUBTHRESHOLD REPETITIVE TRANSCRANIAL MOTOR CORTEX STIMULATION SO NEUROLOGY LA English DT Article ID FOCAL MAGNETIC STIMULATOR; SIMPLE REACTION-TIME; SOMATOSENSORY STIMULI; HEARING-LOSS; PERFORMANCE; MOVEMENTS; ELECTRODES; INDUCTION; EXECUTION; EPILEPSY AB We studied the effects of repetitive transcranial stimulation of the motor cortex (rTMS) on choice reaction time (cRT), movement time (MT), and error rate (ER) in a serial reaction-time task in six medicated patients with Parkinson's disease (PD) and 10 age-matched normal controls. In normal subjects, subthreshold 5-Hz rTMS did not significantly change cRT, slightly shortened MT, but increased ER. In the patients, rTMS significantly shortened cRT and MT without affecting ER. These effects did not impair procedural learning. Performance on a grooved pegboard test was improved by rTMS in the same PD patients, especially when they were off medications, but worsened in the normal subjects. Repetitive, subthreshold motor cortex stimulation can improve performance in patients with PD and could be useful therapeutically. C1 NINCDS,MED NEUROL BRANCH,HUMAN MOTOR CONTROL SECT,HUMAN CORT PHYSIOL UNIT,BETHESDA,MD 20892. NINCDS,MED NEUROL BRANCH,COGNIT NEUROSCI SECT,BETHESDA,MD 20892. RI Pascual-Leone, Alvaro/G-6566-2011; Brasil-Neto, Joaquim/A-1171-2009; OI Grafman, Jordan H./0000-0001-8645-4457 NR 54 TC 196 Z9 208 U1 0 U2 8 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAY PY 1994 VL 44 IS 5 BP 892 EP 898 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA NL811 UT WOS:A1994NL81100019 PM 8190293 ER PT J AU ALEXANDER, EL RANZENBACH, MR KUMAR, AJ KOZACHUK, WE ROSENBAUM, AE PATRONAS, N HARLEY, JB REICHLIN, M AF ALEXANDER, EL RANZENBACH, MR KUMAR, AJ KOZACHUK, WE ROSENBAUM, AE PATRONAS, N HARLEY, JB REICHLIN, M TI ANTI-RO(SS-A) AUTOANTIBODIES IN CENTRAL-NERVOUS-SYSTEM DISEASE-ASSOCIATED WITH SJOGRANS SYNDROME (CNS-SS) - CLINICAL, NEUROIMAGING, AND ANGIOGRAPHIC CORRELATES SO NEUROLOGY LA English DT Article ID PRIMARY SJOGRENS SYNDROME; INFLAMMATORY VASCULAR-DISEASE; NEONATAL LUPUS SYNDROME; REVISED CRITERIA; ERYTHEMATOSUS; ANTIBODIES; CLASSIFICATION; ANTIGEN; EXPRESSION; RESPONSES AB Objective: To examine in Sjogren's syndrome (SS) the interrelationship between the presence of the anti-Ro(SS-A) antibody response and (1) concomitant presence and type (ie, focal or nonfocal) of CNS disease (CNS-SS), (2) cross-sectional brain MRI or CT, and (3) abnormal cerebral angiography. Methods: Neurologic, neuroimaging, and angiographic features of CNS-SS patients were correlated with the presence of precipitating anti-Ro(SS-A) autoantibodies detected by gel double-immunodiffusion or quantitative ELISA, which detects antibodies directed against the 60-kd peptide. Statistical analyses were per formed using Fisher's exact test (two-tailed) with Haldane's adjustment and odds ratio with Cornfield 95% confidence intervals. Results: Precipitating antibodies against the Ro(SS-A) antigen, determined by gel double-immunodiffusion, were present in an increased frequency in CNS-SS patients with (1) documented clinical CNS disease, (2) focal clinical CNS manifestations and serious complications, (3) large regions of increased signal intensity, consistent with ischemia/infarcts on brain MRI scans or regions of decreased attenuation consistent with infarcts on CT, and (4) abnormal cerebral angiograms consistent with small-vessel angiitis. Finally, the anti-Ro(SS-A) antibody response in CNS was directed against the 60-kd peptide specificity, determined by ELISA. Conclusions: Clinical, neuroimaging (cerebral CT), and angiographic observation suggest that a subset of anti-Ro(SS-A) antibody-positive, in contrast with -negative, CNS-SS patients have more serious and extensive CNS disease, some with frank cerebral angiopathy. Anti-Ro(SS-A) antibodies are postulated to play a role in mediating or potentiating vascular injury in CNS-SS. C1 GEORGETOWN UNIV,DEPT RADIOL,WASHINGTON,DC. MD ANDERSON CANC CTR,DEPT RADIOL,HOUSTON,TX. WALLACE LABS,PRINCETON,NJ. SUNY HLTH SCI CTR,SYRACUSE,NY 13210. NIH,BETHESDA,MD 20892. OKLAHOMA MED RES FDN,ARTHRITIS & IMMUNOL PROGRAM,OKLAHOMA CITY,OK 73104. RP ALEXANDER, EL (reprint author), JOHNS HOPKINS UNIV,SCH MED,JOHNS HOPKINS ASTHMA & ALLERGY CTR,DEPT MED,BALTIMORE,MD 21224, USA. FU NHLBI NIH HHS [HL34723]; NIAMS NIH HHS [AR25650, AR39577] NR 39 TC 91 Z9 94 U1 2 U2 4 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAY PY 1994 VL 44 IS 5 BP 899 EP 908 PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA NL811 UT WOS:A1994NL81100020 PM 8190294 ER PT J AU WALSH, SL GILSON, SF JASINSKI, DR STAPLETON, JM PHILLIPS, RL DANNALS, RF SCHMIDT, J PRESTON, KL GRAYSON, R BIGELOW, GE SULLIVAN, JT CONTOREGGI, C LONDON, ED AF WALSH, SL GILSON, SF JASINSKI, DR STAPLETON, JM PHILLIPS, RL DANNALS, RF SCHMIDT, J PRESTON, KL GRAYSON, R BIGELOW, GE SULLIVAN, JT CONTOREGGI, C LONDON, ED TI BUPRENORPHINE REDUCES CEREBRAL GLUCOSE-METABOLISM IN POLYDRUG ABUSERS SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE OPIOID; BUPRENORPHINE; GLUCOSE METABOLISM; DRUG ABUSE; HUMAN BRAIN IMAGING ID POSITRON EMISSION TOMOGRAPHY; CENTRAL NERVOUS-SYSTEM; OPIATE RECEPTOR-BINDING; HUMAN-BRAIN; MORPHINE; AGONIST; AMPHETAMINE; ADDICTION; EFFICACY; ETHANOL AB Buprenorphine is a mixed opioid agonist-antagonist, which acts as a partial mu agonist and a kappa antagonist. The present study evaluated the acute effects of buprenorphine on cerebral glucose metabolism (CMRglc) in six human substance abusers using a double-blind, placebo-controlled, counterbalanced, crossover design. Each subject participated in two positron emission tomographic (PET) studies, 1 week apart, following the injection of buprenorphine (1 mg, intramuscularly) and placebo. Buprenorphine significantly reduced CMRglc and the regional cerebral metabolic rate for glucose (rCMRglc) by up to 32% in all but three of 22 bilateral and in 4 midline regions (p < .05). No region showed an increase in rCMRglc. Buprenorphine also produced miosis, respiratory depression, and subjective ratings of euphoria and sedation in comparison to placebo (p < .05). These observations extend previous findings of reduced CMRglc following acute treatment with morphine and other nonopioid euphorigenic drugs. C1 NATL INST DRUG ABUSE,ADDICT RES CTR,NEUROIMAGING & DRUG ACT SECT,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,SCH MED,DEPT PSYCHIAT & BEHAV SCI,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT MED,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT RADIOL,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT ANESTHESIOL,BALTIMORE,MD. UNIV MARYLAND,SCH MED,DEPT PHARMACOL & EXPTL THERAPEUT,BALTIMORE,MD 21201. RI Preston, Kenzie/J-5830-2013 OI Preston, Kenzie/0000-0003-0603-2479 FU NCRR NIH HHS [5 M01 RR02719]; NIDA NIH HHS [NIDA T32 DA07209, NIDA R18 DA06120] NR 54 TC 21 Z9 23 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD MAY PY 1994 VL 10 IS 3 BP 157 EP 170 PG 14 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA NV555 UT WOS:A1994NV55500002 PM 7916913 ER PT J AU PHILLIPS, RL HERNING, R LONDON, ED AF PHILLIPS, RL HERNING, R LONDON, ED TI MORPHINE EFFECTS ON THE SPONTANEOUS ELECTROENCEPHALOGRAM IN POLYDRUG ABUSERS - CORRELATIONS WITH SUBJECTIVE SELF-REPORTS SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE ELECTROENCEPHALOGRAPHY; MORPHINE; OPIATE; REINFORCEMENT; DRUG ABUSE ID ALFENTANIL ANESTHESIA; EEG; FENTANYL; RAT; SUFENTANIL; INCREASES; NALOXONE; SPECTRA; MALES; POWER AB The spontaneous electroencephalogram (EEG) was recorded after the intramuscular (IM) injection of morphine sulfate (15, 30 mg) or saline (0.9% NaCl). Correlations between changes in EEG spectral power and subjective self-reports, as measured on subscales of the Addiction Research Center Inventory (ARCI), were evaluated. Morphine increased alpha(1) and alpha(2) power and theta power, and attenuated the increase in delta power observed after placebo. Positive correlations were found between the change in alpha(1), alpha(2), beta(1), and beta(2) power in response to 30 mg of morphine and scores on Morphine-Benzedrine Group (MBG) subscale of the ARCI. Negative relationships were observed between changes in alpha(1), and beta(2) and scores on the Pentobarbital Chlorpromazine Alcohol Group (PCAG) subscale. The findings indicate that positive subjective effects of opioids, as measured by the MBG subscale, ave related to increases in alpha and beta activity and are associated with reduction of opioid-induced sedation, as measured by the PCAG subscale. C1 NATL INST DRUG ABUSE,ADDICT RES CTR,NEUROIMAGING & DRUG ACT SECT,NEUROSCI BRANCH,BALTIMORE,MD 21224. NATL INST DRUG ABUSE,ADDICT RES CTR,MED AFFAIRS BRANCH,BALTIMORE,MD 21224. JOHNS HOPKINS MED INST,DEPT RADIOL,BALTIMORE,MD 21205. UNIV MARYLAND,SCH MED,DEPT PHARMACOL & EXPTL THERAPEUT,BALTIMORE,MD 21201. NR 55 TC 12 Z9 13 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD MAY PY 1994 VL 10 IS 3 BP 171 EP 181 PG 11 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA NV555 UT WOS:A1994NV55500003 PM 7916914 ER PT J AU MOLCHAN, SE MATOCHIK, JA ZAMETKIN, AJ SZYMANSKI, HV CANTILLON, M COHEN, RM SUNDERLAND, T AF MOLCHAN, SE MATOCHIK, JA ZAMETKIN, AJ SZYMANSKI, HV CANTILLON, M COHEN, RM SUNDERLAND, T TI A DOUBLE FDG PET STUDY OF THE EFFECTS OF SCOPOLAMINE IN OLDER ADULTS SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE MEMORY; SCOPOLAMINE; ALZHEIMERS DISEASE; (18)-FLUORO-2-DEOXY-2-D-GLUCOSE; POSITRON EMISSION TOMOGRAPHY ID POSITRON EMISSION TOMOGRAPHY; CEREBRAL GLUCOSE-UTILIZATION; ALZHEIMERS-DISEASE; HUMAN-BRAIN; SENILE DEMENTIA; REGIONAL DISTRIBUTION; CHOLINERGIC SYSTEM; COGNITIVE FUNCTION; ENERGY-METABOLISM; RECEPTOR-BINDING AB Two consecutive positron emission scans were done in one session using a double injection method of [F-18]2-fluoro-2-deoxyglucose administration to examine the effects of the antimuscarinic drug scopolamine on cerebral glucose metabolism in ten older adults. Scopolamine causes temporary memory impairment, and its effects have been used to model aspects of the cognitive impairment that occur in Alzheimer's disease (AD). Cortical metabolic rates of patients with AD have been reported to be depressed, especially in parietal, temporal, and frontal association areas. After scopolamine administration to the elderly volunteers, absolute and normalized glucose metabolic rates were depressed in prefrontal and occipital regions and increased in parietal-occipital cortical regions and a left middle temporal region. These changes in the older volunteers are generally not consistent with changes seen in AD. We conclude that deficits in muscarinic system function may contribute to some but not all of the hypometabolic changes seen in AD patients. C1 NIMH,GERIAT PSYCHIAT SECT,BETHESDA,MD 20892. NIMH,CLIN SCI LAB,CLIN BRAIN IMAGING SECT,BETHESDA,MD 20892. NIMH,CEREBRAL METAB LAB,BETHESDA,MD 20892. VET ADM MED CTR,DEPT PSYCHIAT,BUFFALO,NY 14215. NR 63 TC 19 Z9 19 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD MAY PY 1994 VL 10 IS 3 BP 191 EP 198 PG 8 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA NV555 UT WOS:A1994NV55500005 PM 7916916 ER PT J AU LIPSKA, BK WEINBERGER, DR AF LIPSKA, BK WEINBERGER, DR TI SUBCHRONIC TREATMENT WITH HALOPERIDOL AND CLOZAPINE IN RATS WITH NEONATAL EXCITOTOXIC HIPPOCAMPAL DAMAGE SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE HALOPERIDOL; CLOZAPINE; NEONATAL LESION; HIPPOCAMPUS; IBOTENIC ACID; STEREOTYPY; APOMORPHINE ID DOPAMINERGIC SUPER-SENSITIVITY; LOCOMOTOR-ACTIVITY; ANTIPSYCHOTIC-DRUGS; NUCLEUS ACCUMBENS; NEUROLEPTIC DRUGS; INDUCED CATALEPSY; APOMORPHINE; SCHIZOPHRENIA; AMPHETAMINE; STRIATUM AB We have previously demonstrated that rats with neonatal excitotoxic hippocampal damage manifest abnormal dopamine (DA)-related behaviors after puberty, a phenomenon that has implications for art animal model of schizophrenia. In this study we investigated the effects of subchronic treatment with haloperidol and clozapine in these animals. The ventral hippocampus (VH) of rat pups was lesioned with ibotenic acid on postnatal day 7 (PD7). Starting at PD56, rats were treated for 21 days with either vehicle (VEH), haloperidol (HAL) (0.1 mg/kg, IP), or clozapine (CLOZ) (4 mg/kg, IF). Spontaneous locomotor activity was measured 0.5 hour after the last injection. Apomorphine (APO)-induced stereotypy and locomotion were evaluated five days later. The VH lesioned rats treated with VEH expressed enhanced novelty- and apomorphine-induced hyperlocomotion, as well as potentiated apomorphine-induced stereotypic behaviors as compared to sham-lesioned counterparts. Spontaneous locomotor activity was suppressed by haloperidol but not by clozapine in the sham-operated group, whereas both drugs were effective in suppressing hyperlocomotion in the VH lesioned rats. Withdrawal supersensitivity to apomorphine was seen in the haloperidol but not in the clozapine-treated lesioned rats, and none of the drugs produced significant supersensitivity in the sham-operated animals. These results indicate that the two neuroleptics exerted differential behavioral effects in neurologically intact and hippocampally lesioned animals, and that these effects were also drug-specific. RP LIPSKA, BK (reprint author), NIMH,ST ELIZABETHS HOSP,CTR NEUROSCI,CLIN BRAIN DISORDERS BRANCH,INTRAMURAL RES PROGRA,WASHINGTON,DC 20032, USA. RI Lipska, Barbara/E-4569-2017 NR 39 TC 107 Z9 111 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD MAY PY 1994 VL 10 IS 3 BP 199 EP 205 PG 7 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA NV555 UT WOS:A1994NV55500006 PM 7916917 ER PT J AU VAUPEL, P SCHAEFER, C OKUNIEFF, P AF VAUPEL, P SCHAEFER, C OKUNIEFF, P TI INTRACELLULAR ACIDOSIS IN MURINE FIBROSARCOMAS COINCIDES WITH ATP DEPLETION, HYPOXIA, AND HIGH-LEVELS OF LACTATE AND TOTAL P(I) SO NMR IN BIOMEDICINE LA English DT Article ID P-31 NMR-SPECTROSCOPY; MAGNETIC-RESONANCE SPECTROSCOPY; TUMOR ENERGY-METABOLISM; SIZE DEPENDENT CHANGES; RAT MAMMARY-TUMORS; TENSION MEASUREMENTS; LOCAL HYPERTHERMIA; ENDOCRINE THERAPY; FIBRO-SARCOMA; GROWTH-RATE AB Bioenergetic and metabolic status of murine FSaII tumours were evaluated using P-31 MRS, acid extracts ('global' techniques) and quantitative bioluminescence ('microregional' assay). Data obtained from s.c. tumours of varying sizes (44-600 mm3) have been correlated with the oxygenation status evaluated using O2-sensitive needle electrodes. Beta-NTP/P(i) and phosphocreatine (PCr)/P(i) ratios derived from P-31 MRS were positively correlated to the median tissue pO2 values. pH declined during growth with intracellular acidosis being evident in tumours >350 mm3. Whereas lactic acid formation greatly contributed to this decline in small- and medium-sized tumours, ATP hydrolysis and slowing down of the activities of pumps involved in pH(i) regulation seem to be major factors responsible for intracellular acidification in bulky tumours. PCr levels decreased at an early growth stage, whilst ATP concentrations dropped in bulky malignancies only, coinciding with a decrease in adenylate energy charge and a substantial rise in the levels of total P(i). MRS observable (mobile) P(i) was consistently lower than [P(i)] measured in acid extracts. On average, median pO2 values of ca 10 mmHg represent a critical threshold for energy metabolism. At higher median O2 tensions, levels of ATP, phosphomonoester and total P(i) were relatively constant. This coincided with intracellular alkalosis or neutrality and stable adenylate ratios. On average, median pO2 values < 10 mmHg coincided with intracellular acidosis, ATP depletion, a drop in energy charge and rising P(i) levels. C1 NCI,RADIAT ONCOL BRANCH,BETHESDA,MD 20892. RP VAUPEL, P (reprint author), UNIV MAINZ,INST PHYSIOL & PATHOPHYSIOL,DUESBERGWEG 6,D-55099 MAINZ,GERMANY. NR 56 TC 43 Z9 44 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0952-3480 J9 NMR BIOMED JI NMR Biomed. PD MAY PY 1994 VL 7 IS 3 BP 128 EP 136 DI 10.1002/nbm.1940070305 PG 9 WC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy SC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy GA NP211 UT WOS:A1994NP21100004 PM 8080714 ER PT J AU KRATZKE, RA OTTERSON, GA HOGG, A COXON, AB GERADTS, J COWELL, JK KAYE, FJ AF KRATZKE, RA OTTERSON, GA HOGG, A COXON, AB GERADTS, J COWELL, JK KAYE, FJ TI PARTIAL INACTIVATION OF THE RB PRODUCT IN A FAMILY WITH INCOMPLETE PENETRANCE OF FAMILIAL RETINOBLASTOMA AND BENIGN RETINAL TUMORS SO ONCOGENE LA English DT Article ID LARGE T-ANTIGEN; GENE-PRODUCT; SUSCEPTIBILITY GENE; CELLULAR PROTEINS; MOLECULAR-CLONING; BINDING PROTEIN; EXPRESSION; MUTATIONS; IDENTIFICATION; TRANSCRIPTION AB While familial retinoblastoma has served as the paradigm for the two-hit theory of tumorigenesis and for the concept of the tumor suppressor gene, the etiology of incomplete penetrance of familial retinoblastoma is poorly understood. To address the molecular basis for this phenotype we have studied the functional properties of a mutant Rb gene identified in a kindred with incomplete penetrance of familial retinoblastoma and evidence for regressed retinal lesions (retinomas). In contrast to all previously isolated RB mutant proteins, we demonstrated that the mutant product from this kindred retained the wildtype properties of nuclear localization, the ability to undergo hyperphosphorylation in vivo, and the capacity to suppress growth of RB((-)) cells. Protein binding ('pocket') activity, however, was defective defining a new class of RB mutant with partial inactivation. The presence of this unique RB mutant in the germline of obligate carriers with incomplete penetrance and regressed retinal lesions suggests a molecular basis for this phenotype and supports the hypothesis that a minimum 'RB threshold' level of protein binding activity is required to suppress tumorigenesis. C1 USN,NCI,MED ONCOL BRANCH,BETHESDA,MD 20889. UNIFORMED SERV UNIV HLTH SCI,BETHESDA,MD 20889. INST CHILD HLTH,IMPERIAL CANC RES FUND,LONDON WC1N 1EH,ENGLAND. MOLEC ONCOL INC,GAITHERSBURG,MD 20878. RI kaye, frederic/E-2437-2011; OI Cowell, John/0000-0002-2079-5950 NR 60 TC 55 Z9 56 U1 0 U2 2 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD MAY PY 1994 VL 9 IS 5 BP 1321 EP 1326 PG 6 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA NH401 UT WOS:A1994NH40100002 PM 8152792 ER PT J AU SCOTT, MH HEJTMANCIK, JF WOZENCRAFT, LA REUTER, LM PARKS, MM KAISERKUPFER, MI AF SCOTT, MH HEJTMANCIK, JF WOZENCRAFT, LA REUTER, LM PARKS, MM KAISERKUPFER, MI TI AUTOSOMAL-DOMINANT CONGENITAL CATARACT - INTEROCULAR PHENOTYPIC VARIABILITY SO OPHTHALMOLOGY LA English DT Article; Proceedings Paper CT Meeting of the Infectious-Disease-Society CY OCT, 1993 CL NEW ORLEANS, LA SP INFECTIOUS DIS SOC ID GENETIC-HETEROGENEITY; LINKAGE; RETINOBLASTOMA; TRANSLOCATION; HAPTOGLOBIN; MICROCORNEA; FAMILY AB Purpose: While intrafamilial morphologic heterogeneity of autosomal dominant congenital cataracts has been well established, interocular variation in individual patients of described pedigrees is small. The authors describe a seven-generation family with 48 of 138 individuals known to be affected with autosomal dominant congenital cataracts of the pulverulent type. Affected patients exhibit a seemingly random expression of either unilateral or bilateral lens opacities. Methods: Ophthalmic and medical histories were obtained, complete ophthalmologic examinations were performed, blood samples were drawn, and transformed lymphoblastoid lines were established on 53 patients. Eighty-five members of the family were unable to be examined. Results: Twenty-eight of the 53 individuals examined had congenital cataracts. Of these patients, 19 eyes (8 right eyes and 11 left eyes) were unilateral and 9 were bilateral. The clinically unaffected eye in patients with unilateral cataracts showed no evidence of lenticular opacity under detailed slit-lamp examination. Severity of the cataracts included a subtle unilateral zonular cataract with 20/20 visual acuity, bilateral inner fetal nuclear pulverulent opacities with 20/16 visual acuity in both eyes, and dense unilateral and bilateral nuclear cataracts requiring early surgical removal. Incorporating the historic data on patients who were not examined, we found 48 affected members (28 unilateral, 17 bilateral, 3 obligate carriers who were not examined). Conclusions: Hereditary cataracts typically are symmetric in affected individuals. The authors describe a large pedigree with the apparently random expression of an autosomal dominant gene as either unilateral or bilateral cataract. To their knowledge, this is the first such family described in the literature. Currently, work is under way to determine if the causative gene is linked to previously defined cataract loci on chromosomes 1, 2, or 16. C1 NEI,BETHESDA,MD 20892. NR 34 TC 60 Z9 62 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD MAY PY 1994 VL 101 IS 5 BP 866 EP 871 PG 6 WC Ophthalmology SC Ophthalmology GA NL822 UT WOS:A1994NL82200023 PM 8190472 ER PT J AU RAJE, NS RAO, SR IYER, RS KELKAR, RS PAI, SK NAIR, CN KURKURE, PA MAGRATH, IT ADVANI, SH AF RAJE, NS RAO, SR IYER, RS KELKAR, RS PAI, SK NAIR, CN KURKURE, PA MAGRATH, IT ADVANI, SH TI INFECTION ANALYSIS IN ACUTE LYMPHOBLASTIC-LEUKEMIA - A REPORT OF 499 CONSECUTIVE EPISODES IN INDIA SO PEDIATRIC HEMATOLOGY AND ONCOLOGY LA English DT Article DE ACUTE LYMPHOBLASTIC LEUKEMIA; EMPIRIC ANTIBIOTICS; INFECTION ID CANCER-PATIENTS; FUNGAL-INFECTIONS; THERAPY; GRANULOCYTOPENIA; MALIGNANCIES; VANCOMYCIN AB The use of empirical antibiotic combinations in the treatment of febrile neutropenic patients has decreased complication-related mortality in cancer patients. We have analyzed retrospectively 499 consecutive episodes of fever in 432 patients with acute lymphoblastic leukemia over a 5-year period. We have compared various antibiotic combinations used empirically in our study. Of the febrile episodes, 92% were neutropenic. The most common site of clinical documentation was the lung. The most common pathogen isolated in our setting was Pseudomonas aeuroginosa (27.27%). The overall response rate to first-line empirical antibiotic combination was seen in 61.92%, the best results being with ceftazidime and amikacin combination (65.69%). A uniform antibiotic policy resulted in a decrease in mortality, with the number of deaths decreasing significantly in the 1989 to 1991 era (P = 0.00000003). The other contributing factors were an improvement in the supportive care with a reduction in length of hospital stay during induction. Our fungal isolates demonstrated 11 patients with documented fungal infection with a positive outcome in 8 patients. C1 TATA MEM HOSP,DEPT MICROBIOL,BOMBAY 400012,INDIA. NCI,LYMPHOMA BIOL SECT,BETHESDA,MD 20892. RP RAJE, NS (reprint author), TATA MEM HOSP,DEPT MED ONCOL,DIV MED ONCOL,BOMBAY 400012,INDIA. NR 17 TC 18 Z9 20 U1 0 U2 0 PU HEMISPHERE PUBL CORP PI BRISTOL PA 1900 FROST ROAD, SUITE 101, BRISTOL, PA 19007-1598 SN 0888-0018 J9 PEDIATR HEMAT ONCOL JI Pediatr. Hematol. Oncol. PD MAY-JUN PY 1994 VL 11 IS 3 BP 271 EP 280 DI 10.3109/08880019409141670 PG 10 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA NL437 UT WOS:A1994NL43700007 PM 8060811 ER PT J AU GLADSTONE, IM LEVINE, RL AF GLADSTONE, IM LEVINE, RL TI OXIDATION OF PROTEINS IN NEONATAL LUNGS SO PEDIATRICS LA English DT Article DE OXIDATIVE STRESS; CARBONYL ASSAY; PROTEIN OXIDATION; OXYGEN TOXICITY; VENTILATION OF THE NEONATE ID METAL-CATALYZED OXIDATION; BRONCHOPULMONARY DYSPLASIA; GLUTAMINE-SYNTHETASE; HYDROGEN-PEROXIDE; INFANTS; INACTIVATION; ENZYMES; BRAIN; CONSEQUENCES; SECRETIONS AB Objective. To develop a method capable of quantifying the oxidative modification of proteins in pulmonary fluid obtained during routine suctioning of neonates receiving ventilation, thus providing an integrated assessment of antioxidant defenses. Design. Consecutive sample of neonates receiving ventilation. Setting. Neonatal intensive care unit. Patients. Twenty-six neonates receiving ventilation with a gestational age of 24 to 42 weeks, from whom 246 samples were collected and analyzed. Measurements and results. The carbonyl content in the lavage samples was measured by reaction with 2,4-dinitrophenylhydrazine followed by high-pressure liquid chromatography. Oxidation of proteins caused introduction of carbonyl groups into the side chains of the protein, providing a convenient and relatively specific marker of oxidative damage. On the first day of life, the initial protein-bound carbonyl for each neonate was usually low and consequently was not significantly related to birth weight, gestational age, or initial ventilatory requirements. Examination of the changes in pulmonary protein carbonyl in the first days of life revealed correlations of interest. In the first day of life, four neonates whose average inspired oxygen were < 40% showed no increase in carbonyl content, whereas four neonates whose inspired oxygen was > 40% showed an average increase in carbonyl of 51% (P < .001). Also, the need for ventilation > 3 days was correlated with elevated carbonyl in those first 3 days. The carbonyl content averaged over the first 3 days was 0.13 +/- 0.02 mol carbonyl/mol protein for the eight neonates receiving ventilation < 72 hours, whereas the nine needing longer ventilation had a carbonyl content of 0.28 +/- 0.03 mol carbonyl/mol protein (P < .05). Seven neonates were treated with dexamethasone because of ventilator dependence at 14 days of age. In these neonates, treatment was associated with a 50% reduction in carbonyl content within 48 hours (P < .02). Conclusions. Oxidative damage to pulmonary proteins can be quantitated in samples obtained during routine suctioning of neonates receiving ventilation. The amount of oxidatively modified protein may provide a quantitative assessment of oxygen toxicity and of pulmonary antioxidant defenses. C1 NHLBI,BIOCHEM LAB,BETHESDA,MD 20892. USN,NATL MED CTR,DEPT PEDIAT,BETHESDA,MD. RI Levine, Rodney/D-9885-2011 NR 38 TC 88 Z9 89 U1 0 U2 0 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD, ELK GROVE VILLAGE, IL 60007-1098 SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD MAY PY 1994 VL 93 IS 5 BP 764 EP 768 PG 5 WC Pediatrics SC Pediatrics GA NJ374 UT WOS:A1994NJ37400012 PM 8165075 ER PT J AU WILLINGER, M HOFFMAN, HJ HARTFORD, RB AF WILLINGER, M HOFFMAN, HJ HARTFORD, RB TI INFANT SLEEP POSITION AND RISK FOR SUDDEN-INFANT-DEATH-SYNDROME - REPORT OF MEETING HELD JANUARY 13 AND 14, 1994, NATIONAL-INSTITUTES-OF-HEALTH, BETHESDA, MD SO PEDIATRICS LA English DT Article DE SUDDEN INFANT DEATH SYNDROME ID COT DEATH; TASMANIA; COHORT AB Objective. To evaluate the current knowledge on the relationship between infant sleep position and sudden infant death syndrome (SIDS), and to determine how the information can be used to guide further activities in the United States. Methods. Data from international vital statistics, epidemiologic studies of SIDS risk factors, and studies of outcomes of public health interventions that advocated nonprone sleeping to reduce the risk for SIDS were discussed at a meeting held by the National Institute of Child Health and Human Development (NICHD) with co-sponsorship from the National Institute on Deafness and Other Communication Disorders (NIDCD), and the National Center for Health Statistics (NCHS) on January 13, and 14, 1994. Results. Trends in postneonatal mortality and SIDS rates from 1980 through 1992 were evaluated for Australia, Britain, New Zealand, the Netherlands, Norway, Sweden, and the United States. All of the countries that experienced a rapid decline in prone sleeping also had reductions of approximately 50% in their SIDS rates. Postneonatal mortality rates dropped as well, with the reduction in SIDS being the primary contributor to the reported declines. The major behavioral change in all targeted populations was in sleep position. No significant changes were observed in the proportion of parents who smoked cigarettes, or in breast-feeding. Preliminary data from population-based studies showed there were no reported adverse outcomes associated with a change to side or back sleep position, such as an increase in deaths due to aspiration or in apparent life-threatening events. Conclusion. The overwhelming opinion of the assembled experts was that the evidence justified greater effort to reach parents with the American Academy of Pediatrics' recommendation that healthy infants, when being put down to sleep, be positioned on their side or back. C1 NIDCD,OFF DIRECTOR,EPIDEMIOL STAT & DATA SYST BRANCH,BETHESDA,MD. CTR DIS CONTROL & PREVENT,NATL CTR HLTH STAT,OFF INT STAT,HYATTSVILLE,MD 20782. RP WILLINGER, M (reprint author), NICHHD,CTR RES MOTHERS & CHILDREN,PREGNANCY & PERINATOL BRANCH,BLDG 6100,4B03D,6100 EXECUT BLVD,ROCKVILLE,MD 20852, USA. NR 45 TC 195 Z9 197 U1 2 U2 3 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD, ELK GROVE VILLAGE, IL 60007-1098 SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD MAY PY 1994 VL 93 IS 5 BP 814 EP 819 PG 6 WC Pediatrics SC Pediatrics GA NJ374 UT WOS:A1994NJ37400022 PM 8165085 ER PT J AU KATTWINKEL, J BROOKS, J KEENAN, ME MALLOY, M AF KATTWINKEL, J BROOKS, J KEENAN, ME MALLOY, M TI INFANT SLEEP POSITION AND SUDDEN-INFANT-DEATH-SYNDROME (SIDS) IN THE UNITED-STATES - JOINT COMMENTARY FROM THE AMERICAN-ACADEMY-OF-PEDIATRICS AND SELECTED AGENCIES OF THE FEDERAL-GOVERNMENT SO PEDIATRICS LA English DT Article C1 NIDOCD,BETHESDA,MD. NHLBI,NATL CTR SLEEP DISORDERS RES,BETHESDA,MD 20892. CONSUMER PROD SAFETY COMMISS,WASHINGTON,DC. US HLTH RESOURCES & SERV ADM,BUR MATERNAL & CHILD HLTH,ROCKVILLE,MD. US HLTH RESOURCES & SERV ADM,BUR HLTH RESOURCES DEV,ROCKVILLE,MD. US HLTH RESOURCES & SERV ADM,BUR HLTH CARE DELIVERY & ASSISTANCE,ROCKVILLE,MD. US HLTH RESOURCES & SERV ADM,BUR HLTH PROFESS,ROCKVILLE,MD. RP KATTWINKEL, J (reprint author), NICHHD,BETHESDA,MD 20892, USA. NR 1 TC 44 Z9 44 U1 0 U2 0 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD, ELK GROVE VILLAGE, IL 60007-1098 SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD MAY PY 1994 VL 93 IS 5 BP 820 EP 820 PG 1 WC Pediatrics SC Pediatrics GA NJ374 UT WOS:A1994NJ37400023 PM 8165086 ER PT J AU ZAHN, TP KRUESI, MJP LEONARD, HL RAPOPORT, JL AF ZAHN, TP KRUESI, MJP LEONARD, HL RAPOPORT, JL TI AUTONOMIC ACTIVITY AND REACTION-TIME IN RELATION TO EXTROVERSION AND BEHAVIORAL IMPULSIVITY IN CHILDREN AND ADOLESCENTS SO PERSONALITY AND INDIVIDUAL DIFFERENCES LA English DT Article ID INTROVERSION-EXTRAVERSION; DISHABITUATION; HABITUATION; INTERVIEW; CAFFEINE AB Children and adolescents (N = 45) had skin conductance and heart rate recorded continuously during a rest period, presentation of tones, and a simple reaction time test and were assessed for extraversion and behavioral impulsivity. The major aims were: (1) to generalize previous findings of smaller electrodermal responsivity to moderate stimuli and faster reaction time in extraverts, which had been reported for adult samples, to normal children; (2) to test the hypothesis that increasing arousal and stimulus significance by means of task performance would alter the negative correlation between extraversion and responsivity as had been shown in previous studies using different methods; and (3) to determine if extraversion and impulsivity interacted in their effects on these variables. Results showed that extraversion (independent of age and sex) was consistently negatively correlated with skin conductance response magnitudes to all stimuli-somewhat more strongly for reaction-time stimuli-and was negatively correlated with reaction time. This generalizes previous results to children and to significant stimuli. Behavioral impulsivity, which was independent of extraversion, was positively correlated with responsivity. The two variables together accounted for up to 33% of the variance of the responsivity measures. The results suggest that the positive relationship between extraversion and speed of reaction may be partially mediated by electrodermal responsivity. They are also consistent with a model of higher dopaminergic activity in extraverts. C1 NIMH,CHILD PSYCHIAT BRANCH,BETHESDA,MD 20892. RP ZAHN, TP (reprint author), LAB PSYCHOL & PSYCHOPATHOL,BLDG 10,ROOM 4C110,BETHESDA,MD 20892, USA. NR 24 TC 11 Z9 11 U1 1 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0191-8869 J9 PERS INDIV DIFFER JI Pers. Individ. Differ. PD MAY PY 1994 VL 16 IS 5 BP 751 EP 758 DI 10.1016/0191-8869(94)90216-X PG 8 WC Psychology, Social SC Psychology GA NG479 UT WOS:A1994NG47900010 ER PT J AU LAU, KR EVANS, RL CASE, RM AF LAU, KR EVANS, RL CASE, RM TI INTRACELLULAR CL- CONCENTRATION IN STRIATED INTRALOBULAR DUCTS FROM RABBIT MANDIBULAR SALIVARY-GLANDS SO PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY LA English DT Article DE SALIVARY GLAND; STRIATED DUCTS; INTRALOBULAR DUCTS; INTRACELLULAR CL-; FLUORESCENCE; MQAE; DIDS; AMILORIDE ID REABSORPTIVE SWEAT-DUCT; CYSTIC-FIBROSIS; MAIN DUCT; BASOLATERAL MEMBRANE; CELL-MEMBRANES; TRANSPORT; ELECTROLYTE; SECRETION; CONDUCTANCE; EPITHELIUM AB Intralobular striated ducts have been isolated from rabbit mandibular salivary glands and maintained in primary culture for up to 2 days. Such ducts were loaded with the Cl--sensitive fluorescent dye N-(ethoxycarbonylmethyl)-(6-methoxyquinolinium bromide) (MQAE) and intracellular Cl- concentration ([Cl-](i)) monitored using a fluorescence microscope. Intracellular Cl- could be rapidly and reversibly emptied from striated duct cells by replacing Cl- in the superfusing solution with NO3- [Cl-](i) could be lowered by removal of external Na+, exposure to 10 mu M amiloride or to 10 mu M 4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid (DIDS). Both amiloride and DIDS were able to inhibit the recovery of [Cl-](i) after an initial exposure to Na+- or Cl--free solution. The amiloride derivatives, benzamil (2 mu M) and N-isobutyl-N-methylamiloride (MIBA), (10 mu M) also lowered [Cl-](i) by similar amounts as 10 mu M amiloride. Varying external K+ concentration ([K+](degrees)) also affected [Cl-](i). Increasing [K+](degrees) increased [Cl-](i), but decreasing [K+](degrees) did not decrease [Cl-](i). Instead, [Cl-](i) was also increased when [K+](degrees) was lowered below the control value. Bumetanide (0.1 mM) lowered [Cl-](i) by only a small amount, while ouabain (1 mM) had no significant effect on [Cl-](i). These data are consistent with current models of electrolyte transport in salivary ducts which include Cl- channels, Na+ channels, and Na+/H+ exchangers in the apical membrane. The effects of low [K+](degrees) can be interpreted in terms of a K+-dependent exit mechanism for Cl-. C1 NIDR,CLIN INVEST & PATIENT CARE BRANCH,BETHESDA,MD 20892. RP LAU, KR (reprint author), UNIV MANCHESTER,DEPT PHYSIOL SCI,OXFORD RD,MANCHESTER M13 9PT,ENGLAND. FU Wellcome Trust NR 46 TC 25 Z9 25 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0031-6768 J9 PFLUG ARCH EUR J PHY JI Pflugers Arch. PD MAY PY 1994 VL 427 IS 1-2 BP 24 EP 32 DI 10.1007/BF00585938 PG 9 WC Physiology SC Physiology GA NH697 UT WOS:A1994NH69700004 PM 8058473 ER PT J AU GORDON, CJ DUNCAN, WC AF GORDON, CJ DUNCAN, WC TI AUTONOMIC AND BEHAVIORAL THERMOREGULATION IN THE GOLDEN-HAMSTER DURING SUBCHRONIC ADMINISTRATION OF CLORGYLINE SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE TEMPERATURE REGULATION; BEHAVIOR; METABOLIC RATE; CORE TEMPERATURE; FOOD CONSUMPTION; MOTOR ACTIVITY; ANTIDEPRESSANT; CHRONIC TREATMENT ID MONOAMINE-OXIDASE INHIBITORS; BODY-TEMPERATURE; SYRIAN-HAMSTERS; RATS; PARGYLINE; STATES; BRAIN; DRUGS; SLEEP AB Chronic administration of clorgyline, a type-A monoamine oxidase inhibitor, leads to a decrease in peritoneal (i.e., core) temperature of golden hamsters. To better understand the mechanisms of clorgyline's thermoregulatory effects, autonomic and behavioral thermoregulatory effecters were measured in Syrian hamsters following chronic infusion of clorgyline via a minipump (2 mg/kg/day). Metabolic rate, evaporative water loss, motor activity, and core temperature were measured after 60 min of exposure to ambient temperatures (T-a) of 5, 20, 30, and 35 degrees C. Behavioral thermoregulatory responses were assessed by measuring selected T-a and motor activity of the same animals in a temperature gradient over the course of 23 h. Metabolic rate and motor activity were significantly elevated in clorgyline-treated hamsters exposed to a T-a of 5 degrees C. There were no effects of clorgyline on evaporative water loss. In the temperature gradient the mean selected T-a of clorgyline-treated hamsters was nearly equal to that of the saline-treated hamsters, 30.7 and 31.2 degrees C, respectively. On the other hand, the mode of selected T-a in the clorgyline group was 2.8 degrees C higher than that of the saline group. Motor activity in the gradient was significantly elevated and food consumption was depressed by clorgyline treatment. Overall, these findings indicate that chronic clorgyline treatment in the golden hamster results in novel autonomic and behavioral modification; it stimulates metabolic thermogenesis during cold exposure, but appears to increase the behavioral zone of thermoneutrality. This latter effect may mean an improvement in heat tolerance, suggesting that this drug might assist in the adaptation to warm temperatures. C1 NIMH,CLIN PSYCHOBIOL BRANCH,BETHESDA,MD 20892. RP GORDON, CJ (reprint author), US EPA,HLTH EFFECTS RES LAB,DIV NEUROTOXICOL,MD-74B,RES TRIANGLE PK,NC 27711, USA. NR 27 TC 2 Z9 2 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD MAY PY 1994 VL 48 IS 1 BP 119 EP 125 DI 10.1016/0091-3057(94)90507-X PG 7 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA NG481 UT WOS:A1994NG48100019 PM 8029282 ER PT J AU TELLA, SR AF TELLA, SR TI DIFFERENTIAL BLOCKADE OF CHRONIC VERSUS ACUTE EFFECTS OF INTRAVENOUS COCAINE BY DOPAMINE-RECEPTOR ANTAGONISTS SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE COCAINE; BEHAVIORAL SENSITIZATION; DOPAMINE RECEPTOR SUBTYPES; HALOPERIDOL R(+)-SCH-23390 ID RAT NUCLEUS-ACCUMBENS; CONDITIONED PLACE PREFERENCE; AMPHETAMINE TREATMENT; BEHAVIORAL SENSITIZATION; BRAIN; RELEASE; INVITRO; SENSITIVITY; ENHANCEMENT; STRIATUM AB The objectives of this study were to investigate behavioral sensitization to repeated once daily IV injections of cocaine, and to determine whether dopamine receptor antagonists differentially block chronic versus acute cocaine effects. Acute cocaine (0.3-3.0 mg/kg) produced a dose-dependent increase in both horizontal and stereotypic movements in male Sprague-Dawley rats. Repeated once daily injections of 1 or 3 mg/kg of cocaine augmented these effects. Pretreatment with either the D-2 dopamine receptor antagonist haloperidol (0.03-0.3 mg/ kg) or the D-1 dopamine receptor antagonist R(+)-SCH-23390 (0.003-0.1 mg/kg) dose dependently attenuated cocaine's behavioral effects in both sensitized and cocaine-naive animals. There was a rightward shift in the dose-effect relationship of these antagonists in blocking the expression of behavioral sensitization as compared to their ability to block the acute behavioral effects of cocaine. These results indicate that repeated once daily IV injections of cocaine produced behavioral sensitization and both D-1 and D-2 dopamine receptor antagonists attenuated the expression of this sensitization. The data also suggest that dopamine receptor antagonists were more potent in blocking cocaine's effects in cocaine-naive animals than in cocaine-sensitized animals. C1 GEORGETOWN UNIV,SCH MED,DEPT PHARMACOL,WASHINGTON,DC 20007. RP TELLA, SR (reprint author), NIDA,ADDICT RES CTR,PRECLIN PHARMACOL LAB,BEHAV PHARMACOL & GENET SECT,POB 5180,BALTIMORE,MD 21224, USA. NR 42 TC 52 Z9 52 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD MAY PY 1994 VL 48 IS 1 BP 151 EP 159 DI 10.1016/0091-3057(94)90511-8 PG 9 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA NG481 UT WOS:A1994NG48100023 PM 8029285 ER PT J AU BOSTROM, AAS FORBES, JA ADOLFSSON, C BEAVER, WT BELL, WE AF BOSTROM, AAS FORBES, JA ADOLFSSON, C BEAVER, WT BELL, WE TI EVALUATION OF BROMFENAC AND IBUPROFEN FOR PAIN AFTER ORTHOPEDIC-SURGERY SO PHARMACOTHERAPY LA English DT Article ID POSTOPERATIVE PAIN; ASPIRIN AB Study Objectives. To determine the relative analgesic potency and adverse effect liability of bromfenac 25, 50, and 100 mg, and ibuprofen 200 and 400 mg in the treatment of postoperative pain after orthopedic Design. Randomized, double-blind, single-dose, parallel-group relative potency assay with evaluations at 30 minutes and then at hourly intervals for up to 6 hours, Setting. Two wards of the orthopedic surgery department at the Centralsjukhuset (Central Hospital) in Karlstad, Sweden. Patients. Two hundred inpatients with steady, moderate or severe pain within 72 hours after orthopedic surgery. Interventions. Patients received a single oral dose of bromfenac 25, 50, or 100 mg, or ibuprofen 200 or 400 mg, when they experienced steady, moderate or severe pain that, in their opinion, required an analgesic. Using a self-rating record, subjects rated their pain and its relief for 6 hours after medicating. Measurements and Main Results. The study was a valid relative potency assay with estimates of bromfenac's potency relative to ibuprofen ranging from 10.9 (nurse's global evaluation) to 16.7 (sum of hourly analog pain intensity difference scores). That is, 11-16 times the dose of ibuprofen must be administered to equal the analgesic effect of bromfenac. Patients who had eaten breakfast or lunch within 60 minutes before or 30 minutes after receiving the study medication (''fed'' patients) had lower efficacy scores than those who had not ingested food within these time constraints before or after receiving the study medication (''fasted' patients). Furthermore, patients who had eaten before receiving the study medication had significantly lower efficacy scores than those who had eaten after receiving the study medication. Conclusions. The relative potency of the analgesic effect of bromfenac to ibuprofen is 11-16.7 in patients with pain after orthopedic surgery. Fed patients may have lower analgesic efficacy than fasted patients. Adverse effects for both bromfenac and ibuprofen were transient and consistent with the pharmacologic profiles of the drugs. C1 CENT HOSP KARLSTAD,ORTHOPED SURG CLIN,KARLSTAD,SWEDEN. JOHNS HOPKINS UNIV,SCH MED,DEPT PSYCHIAT,BALTIMORE,MD 21205. GEORGETOWN UNIV,SCH MED,DEPT PHARMACOL,WASHINGTON,DC 20057. GEORGETOWN UNIV,SCH MED,DEPT ANESTHESIA,WASHINGTON,DC 20057. NATL INST NEUROL DISORDERS & STROKE,BETHESDA,MD. NR 12 TC 20 Z9 20 U1 0 U2 0 PU PHARMACOTHERAPY PUBLICATIONS INC PI BOSTON PA NEW ENGLAND MEDICAL CENTER BOX 806 171 HARRISON AVE, BOSTON, MA 02111 SN 0277-0008 J9 PHARMACOTHERAPY JI Pharmacotherapy PD MAY-JUN PY 1994 VL 14 IS 3 BP 305 EP 313 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA NN342 UT WOS:A1994NN34200005 PM 7937271 ER PT J AU MASOLIVER, J WEISS, GH AF MASOLIVER, J WEISS, GH TI TELEGRAPHERS EQUATIONS WITH VARIABLE PROPAGATION SPEEDS SO PHYSICAL REVIEW E LA English DT Article ID ANOMALOUS DIFFUSION; WALK AB All derivations of the one-dimensional telegrapher's equation, based on the persistent random walk model, assume a constant speed of signal propagation. We generalize here the model to allow for a variable propagation speed and study several limiting cases in detail. We also show the connections of this model with anomalous diffusion behavior and with inertial dichotomous processes. C1 NIH,DIV COMP RES & TECHNOL,BETHESDA,MD 20892. RP MASOLIVER, J (reprint author), UNIV BARCELONA,DEPT FIS FONAMENTAL,DIAGONAL 647,E-08028 BARCELONA,SPAIN. RI Masoliver, Jaume/F-7198-2016 OI Masoliver, Jaume/0000-0002-5810-879X NR 10 TC 24 Z9 25 U1 1 U2 5 PU AMERICAN PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 1063-651X J9 PHYS REV E JI Phys. Rev. E PD MAY PY 1994 VL 49 IS 5 BP 3852 EP 3854 DI 10.1103/PhysRevE.49.3852 PN A PG 3 WC Physics, Fluids & Plasmas; Physics, Mathematical SC Physics GA NN994 UT WOS:A1994NN99400044 ER PT J AU KAWATE, R TALAN, MI ENGEL, BT AF KAWATE, R TALAN, MI ENGEL, BT TI SYMPATHETIC NERVOUS ACTIVITY TO BROWN ADIPOSE-TISSUE INCREASES IN COLD-TOLERANT MICE SO PHYSIOLOGY & BEHAVIOR LA English DT Article DE COLD ACCLIMATION; COLD EXPOSURE; COLD STRESS; MOUSE; SYMPATHETIC NERVE ID METABOLIC HEAT-PRODUCTION; MALE C57BL/6J MICE; NOREPINEPHRINE TURNOVER; ACCLIMATED RATS; THERMOGENESIS; STIMULATION; NERVES; STRESS; RESPONSES; SKIN AB Brown adipose tissue (BAT) is thought to be responsible for increased heat production in cold-acclimated rodents. We measured sympathetic nerve activity (SNA) in interscapular BAT (IBAT) during cold stimulation in cold-acclimated C57BL/6J mice (ACCLI). Cold acclimation was achieved (cold tolerance was increased) by repeated exposure to cold stress every other week for 3 weeks. We compared SNA in these animals with SNA in mice that had no previous cold stress experience (naive). During the test, mice were anesthetized by urethane and isoflurane and were paralyzed with vecuronium bromide. Sympathetic nerve activity was recorded directly from one of the fine nerves to IBAT. The animal's body caudal to the pelvic area was covered with a plastic bag containing a slurry of ice water to decrease colonic temperature 7 degrees C below control level, which took approximately 20 min. Interscapular BAT-SNA increased during cold stress in both groups, but ACCLI mice had higher IBAT-SNA during cold stress than naive mice. These findings confirmed the hypothesis that during the acute cold exposure, cold-acclimated mice have greater sympathetic outflow to BAT adipocytes. C1 NIA,GERONTOL RES CTR,BEHAV SCI LAB,BALTIMORE,MD 21224. NR 23 TC 19 Z9 22 U1 1 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0031-9384 J9 PHYSIOL BEHAV JI Physiol. Behav. PD MAY PY 1994 VL 55 IS 5 BP 921 EP 925 DI 10.1016/0031-9384(94)90080-9 PG 5 WC Psychology, Biological; Behavioral Sciences SC Psychology; Behavioral Sciences GA NF077 UT WOS:A1994NF07700020 PM 8022914 ER PT J AU GOZES, I GLOWA, J BRENNEMAN, DE MCCUNE, SK LEE, E WESTPHAL, H AF GOZES, I GLOWA, J BRENNEMAN, DE MCCUNE, SK LEE, E WESTPHAL, H TI LEARNING DEFICIENCIES IN TRANSGENIC MICE WITH REDUCED BRAIN VASOACTIVE-INTESTINAL-PEPTIDE SO POLISH JOURNAL OF CHEMISTRY LA English DT Note ID TOXIN-A-CHAIN; VIP; POLYPEPTIDE; EXPRESSION; GENE; IMPAIRMENT; ANTAGONIST; CELLS; RAT C1 NIMH,CLIN NEUROENDOCRINOL BRANCH,BIOPSYCHOL UNIT,BETHESDA,MD 20892. NICHHD,LDN,DEV & MOLEC PHARMACOL SECT,BETHESDA,MD 20892. NICHHD,MAMMALIAN GENES & DEV LAB,BETHESDA,MD 20892. RP GOZES, I (reprint author), TEL AVIV UNIV,SACKLER SCH MED,DEPT CHEM PATHOL,TEL AVIV,ISRAEL. NR 17 TC 0 Z9 0 U1 2 U2 2 PU POLISH CHEMICAL SOCIETY PI WARSAW PA C/O POLISH ACAD SCIENCES, INST PHYSICAL CHEMISTRY, UL KASPRZAKA 44/52, 01-224 WARSAW, POLAND SN 0137-5083 J9 POL J CHEM JI Pol. J. Chem. PD MAY PY 1994 VL 68 IS 5 BP 1057 EP 1060 PG 4 WC Chemistry, Multidisciplinary SC Chemistry GA NH916 UT WOS:A1994NH91600027 ER PT J AU YAMAMOTO, M TAKAHASHI, K OHYAMA, M SASAMATA, M YATSUGI, SI OKADA, M ENDOH, H AF YAMAMOTO, M TAKAHASHI, K OHYAMA, M SASAMATA, M YATSUGI, SI OKADA, M ENDOH, H TI POSSIBLE INVOLVEMENT OF CENTRAL CHOLINERGIC SYSTEM IN AMELIORATING EFFECTS OF INDELOXAZINE, A CEREBRAL ACTIVATOR, ON DISTURBANCE OF LEARNING-BEHAVIOR IN RATS SO PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY LA English DT Review DE ACETYLCHOLINE; ACETYLCHOLINE DISRUPTION; INDELOXAZINE HYDROCHLORIDE; PASSIVE AVOIDANCE; RAT ID HYDROCHLORIDE; MEMORY; MICE AB 1. Effects of indeloxazine, a cerebral activator, on passive avoidance learning by disruption of cholinergic transmission were studied in rats. 2. The shortened latency was prolonged when indeloxazine was administered before training in rats subjected to scopolamine-injection, ethylcholine aziridinium ion (AF64A)-treatment and nucleus basalis magnocellularis (NBM) lesion. 3. Indeloxazine administered immediately after training also showed ameliorating effects on passive avoidance in NBM-lesioned rats. 4. Indeloxazine increased extracellular acetylcholine concentration in the frontal cortex of rats. 5. Indeloxazine possesses facilitatory effects on cerebral function in part due to activation of the central cholinergic system. C1 YAMANOUCHI PHARMACEUT CO LTD,CENT RES LABS,TOKYO 174,JAPAN. NIH,GERONTOL RES CTR,BETHESDA,MD. RP YAMAMOTO, M (reprint author), YAMANOUCHI PHARMACEUT CO LTD,APPL PHARMACOL & DEV LABS,ITABASHI KU,AZUSAWA 1-1-8,TOKYO 174,JAPAN. NR 15 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 0278-5846 J9 PROG NEURO-PSYCHOPH JI Prog. Neuro-Psychopharmacol. Biol. Psychiatry PD MAY PY 1994 VL 18 IS 3 BP 603 EP 613 DI 10.1016/0278-5846(94)90016-7 PG 11 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA NL449 UT WOS:A1994NL44900016 PM 8078992 ER PT J AU KARANIAN, JW KIM, HY YERGEY, JA SALEM, N AF KARANIAN, JW KIM, HY YERGEY, JA SALEM, N TI LIPOXYGENASE STIMULATING EFFECTS OF HYDROXYLATED DOCOSAHEXAENOATES PRODUCED BY HUMAN PLATELETS SO PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS LA English DT Article ID ARACHIDONIC-ACID METABOLISM; SMOOTH-MUSCLE; RAT AORTA; 5-LIPOXYGENASE; LEUKOTRIENES; BIOSYNTHESIS; INHIBITION; MODULATION; ACTIVATION; OXIDATION AB Human platelet suspensions are capable of lipoxygenating docosahexaenoic acid (22:6n3) to an 11(S)-OH-, 14(S)-OH- or 17(S)-OH-22:6n3. The structure and stereochemical purity of these derivatives were confirmed by GC/MS and chiral phase LC analysis. The purified OH-22:6n3 positional isomers which are formed by human platelets were capable of inducing a concentration-dependent contractile response in the guinea-pig lung parenchymal strip at sub-micromolar concentrations. OH-22:6n3 may act in part through stimulation of leukotriene (LT) production as an increase in peptidyl-LT levels (LTC(4), LTD(4) and LTE(4)) occurred during the OH-22:6n3-induced contraction in this preparation. Both specific lipoxygenase inhibitors (caffeic acid, 20 uM and NDGA, 50 uM) and a LT receptor antagonist (FPL55712, 20 uM) significantly inhibited the contractile response. Moreover, the OH-22:6n3 positional isomers induced a concentration-dependent increase in LTB(4) and LTC(4) production in the guinea-pig chopped lung preparation. Other hydroxylated fatty acids and parent fatty acids which were tested (12-OH-20:4n6, 5-OH-20:4n6, 12-OH-20:5n3, 20:5n3 and 22:6n3) did not significantly contract this airway smooth muscle preparation or alter LT production. The hydroxylated 22:6n3 metabolites may modulate airway smooth muscle function in. part through the release of peptidyl-LTs from the guinea-pig lung. C1 MERCK FROSST CANADA INC,POINTE CLAIRE H9R 4P8,PQ,CANADA. RP KARANIAN, JW (reprint author), NIAAA,DICBR,MEMBRANE BIOCHEM & BIOPHYS LAB,BLDG 10 3C-102,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 35 TC 4 Z9 4 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH, MIDLOTHIAN, SCOTLAND EH1 3AF SN 0952-3278 J9 PROSTAG LEUKOTR ESS JI Prostaglandins Leukot. Essent. Fatty Acids PD MAY PY 1994 VL 50 IS 5 BP 271 EP 278 DI 10.1016/0952-3278(94)90166-X PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism GA NH163 UT WOS:A1994NH16300011 PM 8066103 ER PT J AU PTITSYN, OB AF PTITSYN, OB TI KINETIC AND EQUILIBRIUM INTERMEDIATES IN PROTEIN-FOLDING SO PROTEIN ENGINEERING LA English DT Review DE FOLDING INTERMEDIATES; PHASE TRANSITIONS; PROTEIN FOLDING ID MOLTEN-GLOBULE STATE; CARBONIC-ANHYDRASE-B; ALPHA-LACTALBUMIN; SECONDARY STRUCTURE; CYTOCHROME-C; GUANIDINE-HYDROCHLORIDE; CIRCULAR-DICHROISM; COMPACT STATE; STABILITY; BARNASE C1 NCI,MATH BIOL LAB,BETHESDA,MD 20892. RP PTITSYN, OB (reprint author), RUSSIAN ACAD SCI,INST PROT RES,PUSHCHINO 142292,RUSSIA. NR 60 TC 98 Z9 103 U1 0 U2 5 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0269-2139 J9 PROTEIN ENG JI Protein Eng. PD MAY PY 1994 VL 7 IS 5 BP 593 EP 596 DI 10.1093/protein/7.5.593 PG 4 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA NM001 UT WOS:A1994NM00100001 PM 8073028 ER PT J AU REITER, Y BRINKMANN, U WEBBER, KO JUNG, SH LEE, BK PASTAN, I AF REITER, Y BRINKMANN, U WEBBER, KO JUNG, SH LEE, BK PASTAN, I TI ENGINEERING INTERCHAIN DISULFIDE BONDS INTO CONSERVED FRAMEWORK REGIONS OF FV FRAGMENTS - IMPROVED BIOCHEMICAL CHARACTERISTICS OF RECOMBINANT IMMUNOTOXINS CONTAINING DISULFIDE-STABILIZED FV SO PROTEIN ENGINEERING LA English DT Article DE ANTIBODY; DSFV; MAB B3; PSEUDOMONAS EXOTOXIN ID SINGLE-CHAIN FV; PSEUDOMONAS EXOTOXIN; DIHYDROFOLATE-REDUCTASE; ESCHERICHIA-COLI; PROTEIN; BINDING; SUBTILISIN; MUTAGENESIS; STRATEGIES AB Using molecular modeling technology, we have recently identified two positions in conserved framework regions of antibody Fv fragments (Fvs) that are distant from CDRs, and potentially can be used to make recombinant Fv fragments in which the unstable V-H and V-L heterodimer is stabilized by an interchain disulfide bond inserted between structurally conserved framework positions. A disulfide bond has been introduced at one of these positions, V(H)44-V(L)105, and shown to stabilize various Fvs that retain full binding and specificity. Recombinant immunotoxins, e.g. B3(dsFv)-PE38KDEL in which this disulfide-stabilized Fv moiety is connected to a truncated form of Pseudomonas exotoxin (PE; PE38KDEL) which contains the translocation and ADP ribosylation domains, are indistinguishable in binding and specificity from its single-chain immunotoxin counterparts. We have now analyzed the alternative position, (V(H)111-V(L)48), predicted by the modeling methodology, for disulfide stabilization of mAb B3(Fv) by producing a recombinant immunotoxin with such disulfide-stabilized (ds) Fv. This immunotoxin was also very active and retained full specificity to B3 antigen-positive cells. However, it was 2- to 3-fold less active than the V(H)44-V(L)105 dsFv-molecule. We also tested various biochemical features of V(H)44-V(L)105 and V(H)111-V(L)48 dsFv immunotoxins and compared them with the corresponding single-chain immunotoxin. We found the dsFv immunotoxins were more stable in human serum and more resistant to thermal and chemical denaturation than the single chain (sc) Fv immunotoxin. Because dsFv immunotoxins and dsFvs have full activity and specificity and improved stability, they may be more useful than scFv immunotoxins as therapeutic and diagnostic agents. RP REITER, Y (reprint author), NCI,DIAG & CTRS,DIV CANC BIOL,MOLEC BIOL LAB,BLDG 37,ROOM 4E16,BETHESDA,MD 20892, USA. RI Lee, Byungkook/E-4564-2011 OI Lee, Byungkook/0000-0002-3339-4582 NR 31 TC 90 Z9 93 U1 2 U2 4 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0269-2139 J9 PROTEIN ENG JI Protein Eng. PD MAY PY 1994 VL 7 IS 5 BP 697 EP 704 DI 10.1093/protein/7.5.697 PG 8 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA NM001 UT WOS:A1994NM00100013 PM 8073039 ER PT J AU YOUNG, L JERNIGAN, RL COVELL, DG AF YOUNG, L JERNIGAN, RL COVELL, DG TI A ROLE FOR SURFACE HYDROPHOBICITY IN PROTEIN-PROTEIN RECOGNITION SO PROTEIN SCIENCE LA English DT Article DE BINDING SITES; CD4; HIV; HLA; HYDROPHOBICITY; RESIDUE-RESIDUE INTERACTIONS ID HYDROGEN-BONDING REGIONS; DIRECTED DRUG DESIGN; HUMAN CD4; CRYSTAL-STRUCTURES; BINDING; PEPTIDES; COMPLEX; SITES; CONFORMATIONS; ASSOCIATION AB The role of hydrophobicity as a determinant of protein-protein interactions is examined. Surfaces of ape-protein targets comprising 9 classes of enzymes, 7 antibody fragments, hirudin, growth hormone, and retinol-binding protein, and their associated ligands with available X-ray structures for their complexed forms, are scanned to determine clusters of surface-accessible amino acids. Clusters of surface residues are ranked on the basis of the hydrophobicity of their constituent amino acids. The results indicate that the location of the co-crystallized ligand is commonly found to correspond with one of the strongest hydrophobic clusters on the surface of the target molecule. In 25 of 38 cases, the correspondence is exact, with the position of the most hydrophobic cluster coinciding with more than one-third of the surface buried by the bound ligand. The remaining 13 cases demonstrate this correspondence within the top 6 hydrophobic clusters. These results suggest that surface hydrophobicity can be used to identify regions of a protein's surface most likely to interact with a binding ligand. This fast and simple procedure may be useful for identifying small sets of well-defined loci for possible ligand attachment. C1 NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,BIOMED SUPERCOMP LAB,FREDERICK,MD 21702. NCI,DIV CANC BIOL DIAG & CTR,MATH BIOL LAB,BETHESDA,MD 20892. RI Jernigan, Robert/A-5421-2012 FU NCI NIH HHS [N01-CO-74102] NR 56 TC 268 Z9 274 U1 1 U2 10 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0961-8368 J9 PROTEIN SCI JI Protein Sci. PD MAY PY 1994 VL 3 IS 5 BP 717 EP 729 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NH623 UT WOS:A1994NH62300001 PM 8061602 ER PT J AU FISCHER, D WOLFSON, H LIN, SL NUSSINOV, R AF FISCHER, D WOLFSON, H LIN, SL NUSSINOV, R TI 3-DIMENSIONAL, SEQUENCE ORDER-INDEPENDENT STRUCTURAL COMPARISON OF A SERINE-PROTEASE AGAINST THE CRYSTALLOGRAPHIC DATABASE REVEALS ACTIVE-SITE SIMILARITIES - POTENTIAL IMPLICATIONS TO EVOLUTION AND TO PROTEIN-FOLDING SO PROTEIN SCIENCE LA English DT Article DE COMPUTER VISION; PROTEASE ACTIVE SITES; PROTEIN DATABASE STRUCTURAL COMPARISON; PROTEIN FOLDING; 3D PROTEIN MOTIFS ID RESOLUTION; MOTIFS; REFINEMENT; CRYSTAL AB We have recently developed a fast approach to comparisons of 3-dimensional structures. Our method is unique, treating protein structures as collections of unconnected points (atoms) in space. It is completely independent of the amino acid sequence order. It is unconstrained by insertions, deletions, and chain directionality. It matches single, isolated amino acids between 2 different structures strictly by their spatial positioning regardless of their relative sequential position in the amino acid chain. It automatically detects a recurring 3D motif in protein molecules. No predefinition of the motif is required. The motif can be either in the interior of the proteins or on their surfaces. In this work, we describe an enhancement over our previously developed technique, which considerably reduces the complexity of the algorithm. This results in an extremely fast technique. A typical pairwise comparison of 2 protein molecules requires less than 3 s on a workstation. We have scanned the structural database with dozens of probes, successfully detecting structures that are similar to the probe. To illustrate the power of this method, we compare the structure of a trypsin-like serine protease against the structural database. Besides detecting homologous trypsin-like proteases, we automatically obtain 3D, sequence order-independent, active-site similarities with subtilisin-like and sulfhydryl proteases. These similarities equivalence isolated residues, not conserving the linear order of the amino acids in the chains. The active-site similarities are well known and have been detected by manually inspecting the structures in a time-consuming, laborious procedure. This is the first time such equivalences are obtained automatically from the comparison of full structures. The far-reaching advantages and the implications of our novel algorithm to studies of protein folding, to evolution, and to searches for pharmacophoric patterns are discussed. C1 NCI,FREDERICK CANC RES FACIL,PRI DYNCORP,MATH BIOL LAB,FREDERICK,MD 21702. TEL AVIV UNIV,SCH MATH SCI,DEPT COMP SCI,IL-69978 TEL AVIV,ISRAEL. TEL AVIV UNIV,FAC MED,SACKLER INST MOLEC MED,IL-69978 TEL AVIV,ISRAEL. RI Wolfson, Haim/A-1837-2011 FU NCI NIH HHS [1-CO-74102] NR 24 TC 84 Z9 85 U1 0 U2 1 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0961-8368 J9 PROTEIN SCI JI Protein Sci. PD MAY PY 1994 VL 3 IS 5 BP 769 EP 778 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NH623 UT WOS:A1994NH62300006 PM 8061606 ER PT J AU JUNG, SH PASTAN, I LEE, B AF JUNG, SH PASTAN, I LEE, B TI DESIGN OF INTERCHAIN DISULFIDE BONDS IN THE FRAMEWORK REGION OF THE FV FRAGMENT OF THE MONOCLONAL-ANTIBODY B3 SO PROTEINS-STRUCTURE FUNCTION AND GENETICS LA English DT Article DE IMMUNOGLOBULIN; ANTIBODY; MAB B3; PROTEIN ENGINEERING; DISULFIDE BOND ID T-CELL RECEPTOR; DIHYDROFOLATE-REDUCTASE; 3-DIMENSIONAL STRUCTURE; PSEUDOMONAS EXOTOXIN; ESCHERICHIA-COLI; SUBTILISIN BPN'; PROTEIN; BINDING; STABILIZATION; STABILITY AB The Fv fragments are the smallest units of antibodies that retain the specific antigen binding characteristics of the whole molecule and are being used for the diagnosis and therapy of human diseases. These are noncovalently associated heterodimers of the heavy (V-H) and the light (V-L) chain variable domains, which, without modification, tend to dissociate, unfold, and/or nonspecifically aggregate. The fragment is usually stabilized by producing it as a single chain recombinant molecule in which the two chains are linked by means of a short polypeptide linker. An alternative strategy is to connect the two chains by means of an interchain disulfide bond. We used molecular graphics and other modeling tools to identify two possible interchain disulfide bond sites in the framework region of the Fv fragment of the monoclonal mouse antibody (mAb)B3. The mAb B3 binds to many human cancer cells and is being used in the development of a new anticancer agent. The two sites identified are V(H)44-V(L)105 and V(H)111-V(L)48. (V(H)44-V(L)100 and V(H)105-V(L)43 in the numbering scheme of Kabat et al., ''Sequence of Proteins of Immunological Interest,'' U.S. DHHS, NIH publication No. 91-3242, 1991.) This design was recently tested using the chimeric protein composed of a truncated form of Pseudomonas exotoxin and the Fv fragment of mAb B3 with the engineered disulfide bond at V(H)44-V(L)105 (Brinkmann et al., Proc. Natl. Acad. Sci. U.S.A. 90:7538, 1993). The chimeric toxin was found to be just as active as the corresponding single chain counterpart and considerably more stable. Because these disulfide bond sites are in the framework region, they can be located from sequence alignment alone. We expect that the disulfide bond at these sites will stabilize the Fv fragment of most antibodies and the antigen-specific portion of the T-cell receptors, which are homologous. (C) 1994 Wiley-Liss, Inc. C1 NCI,DIV CANC BIOL DIAG & CTR,MOLEC BIOL LAB,BETHESDA,MD 20892. RI Lee, Byungkook/E-4564-2011 OI Lee, Byungkook/0000-0002-3339-4582 NR 42 TC 46 Z9 52 U1 0 U2 6 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0887-3585 J9 PROTEINS JI Proteins PD MAY PY 1994 VL 19 IS 1 BP 35 EP 47 DI 10.1002/prot.340190106 PG 13 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA NJ755 UT WOS:A1994NJ75500005 PM 8066084 ER PT J AU LEIKIN, S PARSEGIAN, VA AF LEIKIN, S PARSEGIAN, VA TI TEMPERATURE-INDUCED COMPLEMENTARITY AS A MECHANISM FOR BIOMOLECULAR ASSEMBLY SO PROTEINS-STRUCTURE FUNCTION AND GENETICS LA English DT Note DE MOLECULAR RECOGNITION; PROTEIN ASSEMBLY; PROTEIN FOLDING; PROTEIN INTERACTIONS ID DNA DOUBLE HELICES; HYDRATION FORCES; PHOSPHOLIPID-BILAYERS; RECOGNITION AB Recent advances in the measurement and theory of ''hydration'' interactions between biomolecules provide a basis on which to formulate mechanisms of biomolecular recognition. In this paper we have developed a mathematical formalism for analyzing specificity encoded in dynamic distributions of surface polar groups, a formalism that incorporates newly recognized properties of directly measured ''hydration'' forces. As expected, attraction between surfaces requires complementary patterns of surface polar groups. In contrast to usual expectations, thermal motion can create these complementary surface configurations. We have demonstrated that assembly can occur with an increase in conformational entropy of polar residues. Elevated temperature then facilitates recognition rather than hinders it. This mechanism might underlie some temperature-favored assembly reactions common in biological systems that are usually associated with the ''hydrophobic effect'' only. (C) 1994 Wiley-Liss, Inc. RP LEIKIN, S (reprint author), NIH,DIV COMP RES & TECHNOL,STRUCT BIOL LAB,BLDG 12A,ROOM 2041,BETHESDA,MD 20892, USA. RI Leikin, Sergey/A-5518-2008 OI Leikin, Sergey/0000-0001-7095-0739 NR 22 TC 18 Z9 18 U1 1 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0887-3585 J9 PROTEINS JI Proteins PD MAY PY 1994 VL 19 IS 1 BP 73 EP 76 DI 10.1002/prot.340190109 PG 4 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA NJ755 UT WOS:A1994NJ75500008 PM 8066088 ER PT J AU JACOBSEN, FM MUELLER, EA ROSENTHAL, NE ROGERS, S HILL, JL MURPHY, DL AF JACOBSEN, FM MUELLER, EA ROSENTHAL, NE ROGERS, S HILL, JL MURPHY, DL TI BEHAVIORAL-RESPONSES TO INTRAVENOUS META-CHLOROPHENYLPIPERAZINE IN PATIENTS WITH SEASONAL AFFECTIVE-DISORDER AND CONTROL SUBJECTS BEFORE AND AFTER PHOTOTHERAPY SO PSYCHIATRY RESEARCH LA English DT Article DE AFFECTIVE DISORDER; SEROTONIN; LIGHT TREATMENT ID SEROTONIN AGONIST; NEURO-ENDOCRINE; PANIC DISORDER; MELATONIN; HUMANS; LIGHT; DEPRESSION; 5-HYDROXYTRYPTOPHAN; NEUROENDOCRINE; ANTIDEPRESSANT AB A comparison of the baseline and post-infusion effects of the serotonin agonist meta-chlorophenylpiperazine (m-CPP) in 10 patients with seasonal affective disorder (SAD) and 11 healthy control subjects revealed significantly different subjective response profiles between the groups. Several baseline and m-CPP-stimulated responses in symptoms putatively related to serotonergic function changed significantly after a week's exposure to phototherapy in the SAD patients but not the control subjects. Before phototherapy, depressed patients with SAD reported activation-euphoria responses to m-CPP and significant decreases in carbohydrate hunger, but insignificant changes in feeling slowed or sleepy, while control subjects reported no mood or appetite changes but significant increases in feeling slowed down following m-CPP. After phototherapy, which led to a significant reduction in baseline depressive symptom ratings to near-euthymic levels in the SAD patients, almost all of the patients' responses to m-CPP were normalized and no longer differed from the control subjects' responses. These results provide evidence of a possible dysregulation in serotonergic neurotransmission in depressed SAD patients that normalizes following treatment with phototherapy. C1 GEORGE WASHINGTON UNIV,SCH MED,WASHINGTON,DC. GEORGETOWN UNIV,SCH MED,WASHINGTON,DC. NIDA,BIOMETR BRANCH,BETHESDA,MD. NIMH,CLIN PSYCHOBIOL BRANCH,ENVIRONM PSYCHIAT SECT,BETHESDA,MD 20892. RP JACOBSEN, FM (reprint author), NIMH,CTR CLIN,CLIN SCI LAB,10-3D41,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 52 TC 40 Z9 40 U1 1 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD MAY PY 1994 VL 52 IS 2 BP 181 EP 197 DI 10.1016/0165-1781(94)90087-6 PG 17 WC Psychiatry SC Psychiatry GA NT919 UT WOS:A1994NT91900008 PM 7972574 ER PT J AU WEINSTEIN, EA AF WEINSTEIN, EA TI THE CLASSIFICATION OF DELUSIONAL MISIDENTIFICATION SYNDROMES SO PSYCHOPATHOLOGY LA English DT Article; Proceedings Paper CT Conference on Delusional Misidentification Syndromes CY 1993 CL HOSPITAL SAINTE ANNE, PARIS, FRANCE HO HOSPITAL SAINTE ANNE ID CAPGRAS SYNDROME; REDUPLICATIVE PARAMNESIA; PATIENT; HEMORRHAGE AB The delusional misidentification syndromes are characterized by a belief in duplicates and replacements. They can be classified as forms of reduplication expressed in the modalities of person, place, time and event, objects, parts of the body and the self. Common features are selectivity, coexistence of forms, intact recognition and faulty identification, depersonalization, and symbolic representation of the patient's feelings, experiences and problems. A neural substrate of altered connectivity of multimodal cortical association areas and paralimbic and limbic structures resulting in a cognitive-perceptual-affective dissonance is suggested. C1 NIA, NEUROSCI LAB, BETHESDA, MD 20892 USA. NR 43 TC 29 Z9 29 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0254-4962 J9 PSYCHOPATHOLOGY JI Psychopathology PD MAY-OCT PY 1994 VL 27 IS 3-5 BP 130 EP 135 PG 6 WC Psychiatry SC Psychiatry GA PN447 UT WOS:A1994PN44700004 PM 7846227 ER PT J AU GINSKI, MJ WITKIN, JM AF GINSKI, MJ WITKIN, JM TI SENSITIVE AND RAPID BEHAVIORAL DIFFERENTIATION OF N-METHYL-D-ASPARTATE RECEPTOR ANTAGONISTS SO PSYCHOPHARMACOLOGY LA English DT Article DE NMDA RECEPTOR ANTAGONISTS; DISSOCIATIVE ANESTHETICS; BEHAVIORAL EFFECTS; LOCOMOTOR ACTIVITY; MICE ID EXCITATORY AMINO-ACIDS; SCHEDULE-CONTROLLED BEHAVIOR; CENTRAL NERVOUS-SYSTEM; NMDA RECEPTOR; INDUCED CONVULSIONS; PHENCYCLIDINE PCP; RATS; MICE; MK-801; RESPONSES AB Behavioral effects of PCP-type noncompetitive antagonists of N-methyl-D-aspartate (NMDA) receptors overlap with those of a host of other centrally acting compounds. In the present experiment, locomotor activity and performance on an inverted screen test in untrained mice were used to differentiate PCP-type noncompetitive NMDA antagonists from other drug classes. These uncompetitive NMDA antagonists [PCP, dizocilpine, (-)-MK-801, TCP, (+)-SKF 10,047, dextrorphan, ketamine] produced dose-related increases in locomotor activity and the percentage of mice falling off an inverted, elevated wire mesh screen. Both effects demonstrated stereoselectivity, occurred at comparable dose levels, and were within the range of doses producing other biological effects (e.g., anticonvulsant). The potencies of these drugs for producing behavioral effects were positively correlated with affinities for PCP ([H-3]MK-801) but not sigma([H-3]SKF 10,047) receptors. Although muscarinic antagonists (benactyzine, atropine) produced effects in the same direction, locomotor stimulation was small and occurred at lower doses than those inducing screen failures. Competitive NMDA antagonists (LY 274614, LY 233536, CPP, NPC 12626), sigma receptor ligands (DTG, dextromethorphan), postsynaptic dopamine agonists (quinpirole, SKF 38393) and antagonists (haloperidol, SCH 39166), and some depressant compounds (morphine, diazepam) increased failures on the screen test but decreased locomotor activity. Ligands of the polyamine regulatory site of the NMDA receptor (ifenprodil, SL 82.0715-10) and the AMPA receptor antagonist NBQX decreased locomotor activity without increasing screen failures. An antagonist of the strychnine-insensitive glycine receptor (7-chlorokynurenic acid) did not affect performance on either test. Psychomotor stimulants (cocaine and methamphetamine) stimulated locomotor activity without affecting screen performance. The only false positives occurred with barbiturates (pentobarbital, phenobarbital). Nonetheless, the present procedure demonstrates excellent sensitivity and power for rapid discrimination of uncompetitive NMDA antagonists. C1 NIDA,ADDICT RES CTR,PSYCHOBIOL SECT,DRUG DEV GRP,BALTIMORE,MD 21224. NR 76 TC 66 Z9 66 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 MAY PY 1994 VL 114 IS 4 BP 573 EP 582 DI 10.1007/BF02244987 PG 10 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA NM774 UT WOS:A1994NM77400006 PM 7855218 ER PT J AU POPIK, P LAYER, RT SKOLNICK, P AF POPIK, P LAYER, RT SKOLNICK, P TI THE PUTATIVE ANTI-ADDICTIVE DRUG IBOGAINE IS A COMPETITIVE INHIBITOR OF [H-3] MK-801 BINDING TO THE NMDA RECEPTOR COMPLEX SO PSYCHOPHARMACOLOGY LA English DT Note DE MK-801 (DIZOCILPINE); IBOGAINE; NMDA RECEPTORS; DRUG ABUSE ID TOLERANCE; MK-801; COCAINE; AMPHETAMINE; ANTAGONIST; BLOCKADE; ETHANOL; POTENT; RATS AB Ibogaine is a putative anti-addictive drug with potential efficacy for the treatment of opiate, stimulant, and alcohol abuse. We now report ibogaine is a competitive inhibitor (K-i, 1.01 +/- 0.1 mu M) of [H-3]MK-801 binding to N-methyl-D-aspartate (NMDA) receptor coupled cation channels. Since MK-801 can attenuate the development of tolerance to morphine and alcohol as well as sensitization to stimulants in preclinical studies, the reported ability of ibogaine to modify drug-seeking behavior in man may be attributable to a blockade of NMDA receptor coupled cation channels. RP POPIK, P (reprint author), NIDDK,NEUROSCI LAB,BLDG 8,ROOM 111,BETHESDA,MD 20892, USA. RI Popik, Piotr/R-5383-2016 OI Popik, Piotr/0000-0003-0722-1263 NR 17 TC 71 Z9 71 U1 0 U2 3 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD MAY PY 1994 VL 114 IS 4 BP 672 EP 674 DI 10.1007/BF02245000 PG 3 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA NM774 UT WOS:A1994NM77400019 PM 7531855 ER PT J AU KATON, W GONZALES, J AF KATON, W GONZALES, J TI A REVIEW OF RANDOMIZED TRIALS OF PSYCHIATRIC CONSULTATION-LIAISON STUDIES IN PRIMARY-CARE SO PSYCHOSOMATICS LA English DT Article ID DISTRESSED HIGH UTILIZERS; HEALTH-SERVICES RESEARCH; DEPRESSION; RECOGNITION; MANAGEMENT; PHYSICIANS; PATTERNS; MODEL AB The field of consultation-liaison (C-L) psychiatry has developed a variety of research interventions to try to improve the recognition and treatment of mental disorders in primary care. The authors review the results of three generations of randomized trials of mental health interventions developed by C-L psychiatrists. In general, these trials have been more successful in improving detection of mental illness and increasing the application of mental health treatments by primary care physicians than in changing patient outcomes. The results of these randomized trials are interpreted by using models developed in the health services field. C1 NIMH,DIV EPIDEMIOL & SERV RES,PRIMARY CARE RES PROGRAM,SERV RES BRANCH,ROCKVILLE,MD 20857. RP KATON, W (reprint author), UNIV WASHINGTON,SCH MED,DEPT PSYCHIAT & BEHAV SCI,DIV CONSULTAT LIAISON,SEATTLE,WA 98195, USA. NR 35 TC 102 Z9 105 U1 1 U2 7 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD MAY-JUN PY 1994 VL 35 IS 3 BP 268 EP 278 PG 11 WC Psychiatry; Psychology SC Psychiatry; Psychology GA NJ604 UT WOS:A1994NJ60400005 PM 8036256 ER PT J AU MACHER, A GOOSBY, E BARKER, L VOLBERDING, P GOLDSCHMIDT, R BALANO, KB WILLIAMS, A HOENIG, L GOULD, B DANIELS, E AF MACHER, A GOOSBY, E BARKER, L VOLBERDING, P GOLDSCHMIDT, R BALANO, KB WILLIAMS, A HOENIG, L GOULD, B DANIELS, E TI EDUCATING PRIMARY-CARE PROVIDERS ABOUT HIV DISEASE - MULTIDISCIPLINARY INTERACTIVE MECHANISMS SO PUBLIC HEALTH REPORTS LA English DT Article; Proceedings Paper CT 9th International Conference on AIDS CY JUN 07-11, 1993 CL BERLIN, GERMANY AB As HIV-related prophylactic and therapeutic research findings continue to evolve, the Health Resources and Services Administration (HRSA) of the Public Health Service has created multidisciplinary mechanisms to disseminate new treatment options and educate primary care providers at rural and urban sites throughout our nation's health care system. HRSA has implemented (a) the International State-of-the-Art HIV Clinical Conference Call Series, (b) the national network of AIDS Education and Training Centers, (c) the nationwide HIV Telephone Consultation Service, and (d) the Clinical Issues Subcommittee of the HRSA AIDS Advisory Committee. These collaborative and comprehensive efforts at HIV information dissemination target physicians, nurses, physician assistants, dentists, clinical pharmacists, mental health care providers, case managers, and allied health professionals. The sites where they provide care include public health clinics; county, State and Federal correctional facilities; private practice offices; community and academic hospitals; military and Veterans Administration facilities; hemophilia centers; schools of medicine, nursing, and dentistry; departments of health; chronic care facilities; visiting nurse and home care agencies; health maintenance organizations; and Indian Health Service clinics and hospitals. C1 US BUR HLTH RESOURCES DEV,DIV HIV SERV,ROCKVILLE,MD. US BUR HLTH PROFESS,DIV MED,HLTH PROFESS HIV EDUC BRANCH,ROCKVILLE,MD. UNIV CALIF SAN FRANCISCO,SAN FRANCISCO GEN HOSP,AIDS PROGRAM,SAN FRANCISCO,CA 94110. UNIV CALIF SAN FRANCISCO,SAN FRANCISCO GEN HOSP,FAMILY PRACTICE INPATIENT SERV,SAN FRANCISCO,CA 94110. UNIV CALIF SAN FRANCISCO,SAN FRANCISCO GEN HOSP,HIV TEL CONSULTAT SERV,SAN FRANCISCO,CA 94110. NIAID,DIV AIDS,CLIN RES PROGRAM,BETHESDA,MD 20892. YALE UNIV,SCH NURSING,DIV ADULT HLTH,NEW HAVEN,CT 06520. DEPT VET AFFAIRS OUTPATIENT CLIN,SPECIAL IMMUNOL SECT,OAKLAND PK,FL. FLORIDA STATE UNIV,TALLAHASSEE,FL 32306. RP MACHER, A (reprint author), US PHS,BUR HLTH PROFESS,AIDS EDUC & TRAINING CTR PROGRAM,ROOM 7-05,PARKLAWN BLDG,ROCKVILLE,MD 20857, USA. NR 2 TC 5 Z9 5 U1 0 U2 2 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 MAY-JUN PY 1994 VL 109 IS 3 BP 305 EP 310 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA NQ568 UT WOS:A1994NQ56800001 PM 8190853 ER PT J AU GIFT, HC CORBIN, SB NOWJACKRAYMER, RE AF GIFT, HC CORBIN, SB NOWJACKRAYMER, RE TI PUBLIC KNOWLEDGE OF PREVENTION OF DENTAL DISEASE SO PUBLIC HEALTH REPORTS LA English DT Article ID ORAL HEALTH; ATTITUDES; PHYSICIANS; CHILDREN AB The authors present data describing the level and extent of the general public's knowledge of oral diseases and their prevention. They discuss data from the 1990 National Health Interview Survey's Health Promotion and Disease Prevention Supplement in the context of national oral health objectives. They focus on demographic and socioeconomic differences seen in the public's knowledge of the preventive purposes of fluorides and dental sealants for dental caries and of symptoms of gum disease. Reported low levels of knowledge regarding oral disease symptoms and their prevention show the continuing trend reported during the past decade. Racial and ethnic minorities and groups with low levels of formal education demonstrate the least knowledge of prevention of oral diseases. For example, 76 percent of those with more than 12 years of schooling know the preventive purpose of water fluoridation, compared with 61 percent of those with 12 years, and 36 percent of those with less than 12 years of school. Efforts to increase levels of knowledge about oral disease prevention are required to achieve national objectives for oral health. C1 CTR DIS CONTROL,NATL CTR PREVENT SERV,DIV ORAL HLTH,ATLANTA,GA 30333. RP GIFT, HC (reprint author), NIDR,EPIDEMIOL & ORAL DIS PREVENT PROGRAM,DIS PREVENT & HLTH PROMOT,BETHESDA,MD 20892, USA. NR 45 TC 18 Z9 20 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 MAY-JUN PY 1994 VL 109 IS 3 BP 397 EP 404 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA NQ568 UT WOS:A1994NQ56800011 PM 8190863 ER PT J AU TOKUNAGA, M LAND, CE TOKUOKA, S NISHIMORI, I SODA, M AKIBA, S AF TOKUNAGA, M LAND, CE TOKUOKA, S NISHIMORI, I SODA, M AKIBA, S TI INCIDENCE OF FEMALE BREAST-CANCER AMONG ATOMIC-BOMB SURVIVORS, 1950-1985 SO RADIATION RESEARCH LA English DT Article ID HIROSHIMA; NAGASAKI; WOMEN; MORTALITY; INFANCY; RISK AB An incidence survey among atomic bomb survivors identified 807 breast cancer cases, and 20 second breast cancers. As in earlier surveys of the Life Span Study population, a strongly linear radiation dose response was found, with the highest dose-specific excess relative risk (ERR) among survivors under 20 years old at the time of the bombings. Sixty-eight of the cases were under 10 years old at exposure, strengthening earlier reports of a marked excess risk associated with exposure during infancy and childhood. A much lower, but marginally significant, dose response was seen among women exposed at 40 years and older. It was not possible, however, to discriminate statistically between age at exposure and age at observation for risk as the more important determinant of ERR per unit dose. A 13-fold ERR at 1 Sv was found for breast cancer occurring before age 35, compared to a 2-fold excess after age 35, among survivors exposed before age 20. This a posteriori finding, based on 27 exposed, known-dose, early-onset cases, suggests the possible existence of a susceptible genetic subgroup. Further studies, involving family histories of cancer and investigations at the molecular level, are suggested to determine whether such a subgroup exists. C1 NCI,RADIAT EPIDEMIOL BRANCH,BETHESDA,MD 20852. RADIAT EFFECTS RES FDN,DEPT EPIDEMIOL PATHOL,HIROSHIMA,JAPAN. KAGOSHIMA MUNICIPAL HOSP,DEPT PATHOL,KAGOSHIMA,JAPAN. RADIAT EFFECTS RES FDN,DEPT EPIDEMIOL,HIROSHIMA,JAPAN. NR 41 TC 180 Z9 184 U1 1 U2 5 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 MAY PY 1994 VL 138 IS 2 BP 209 EP 223 DI 10.2307/3578591 PG 15 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA NH841 UT WOS:A1994NH84100008 PM 8183991 ER PT J AU SHAMKHANI, H ANDERSON, LM HENDERSON, CE MOSKAL, TJ RUNOWICZ, CD DOVE, LF JONES, AB CHANEY, SG RICE, JM POIRIER, MC AF SHAMKHANI, H ANDERSON, LM HENDERSON, CE MOSKAL, TJ RUNOWICZ, CD DOVE, LF JONES, AB CHANEY, SG RICE, JM POIRIER, MC TI DNA-ADDUCTS IN HUMAN AND PATAS MONKEY MATERNAL AND FETAL TISSUES INDUCED BY PLATINUM DRUG CHEMOTHERAPY SO REPRODUCTIVE TOXICOLOGY LA English DT Article DE HUMAN; PATAS MONKEY; CISPLATIN; CARBOPLATIN; DNA ADDUCTS; TRANSPLACENTAL; CISPLATIN-DNA ELISA; ATOMIC ABSORBENCY SPECTROMETRY ID EPITHELIAL OVARIAN-CARCINOMA; CANCER-CHEMOTHERAPY; SKIN TUMORS; CISPLATIN; PREGNANCY; MOUSE; CARCINOGENICITY; QUANTITATION; ANTIBODIES; INDUCTION AB Platinum-DNA adducts in placenta and blood from a woman exposed to 200 Mg/M2 of cis-diamminedichloroplatinum(II) (cisplatin) and 300 Mg/M2 diamminecyclobutanedicarboxylatoplatinum(II) (carboplatin) for ovarian cancer have been documented by cisplatin-DNA enzyme-linked immunosorbent assay (ELISA) and atomic absorbance spectrometry (AAS). A patas monkey model was used to investigate transplacentally induced cisplatin-DNA damage in fetal tissues. During the last trimester of gestation, 5 patas monkeys were given multiple doses of cisplatin to mimic human ovarian cancer treatment. In spite of careful choice of dose and treatment conditions, cumulative toxicity occurred in monkeys given doses comparable on a mg/m2 basis to those received by the human. A total dose of 12 mg/m2 (0.625 mg/kg body weight), given in the last trimester, supported fetal viability, and multiple tissues, taken by cesarean section, were examined in the fetal monkeys. By cisplatin-DNA ELISA and AAS, maternal tissues from the monkey receiving the highest dose contained approximately twice as much DNA damage as the fetal tissues. A similar relationship was observed when we compared DNA adduct formation in fetal liver and biopsies of liver taken from the monkey dams at cesarean delivery. In all of the monkey pairs studied there were very significant levels of DNA damage in the placenta, and high adduct levels in brains of fetuses that survived treatment. Thus cisplatin does cross the placenta in the patas monkey. These observations imply that the human fetus, for which the total maternal dose was approximately 5.4 mg platinum drug/kg body weight, may also have sustained some DNA damage. C1 NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BLDG 37,RM 3B25,BETHESDA,MD 20892. NCI,FCRDC,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21701. UNIV N CAROLINA,DEPT BIOCHEM & BIOPHYS,CHAPEL HILL,NC 27514. BIOQUAL INC,ROCKVILLE,MD. MONTEFIORE MED CTR,DEPT OBSTET & GYNECOL,BRONX,NY 10467. NR 38 TC 17 Z9 17 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 MAY-JUN PY 1994 VL 8 IS 3 BP 207 EP 216 DI 10.1016/0890-6238(94)90004-3 PG 10 WC Reproductive Biology; Toxicology SC Reproductive Biology; Toxicology GA NQ437 UT WOS:A1994NQ43700003 PM 8075509 ER PT J AU TABACOVA, S LITTLE, RE BALABAEVA, L PAVLOVA, S PETROV, I AF TABACOVA, S LITTLE, RE BALABAEVA, L PAVLOVA, S PETROV, I TI COMPLICATIONS OF PREGNANCY IN RELATION TO MATERNAL LIPID PEROXIDES, GLUTATHIONE, AND EXPOSURE TO METALS SO REPRODUCTIVE TOXICOLOGY LA English DT Article DE LEAD; CADMIUM; ARSENIC; METALS; GLUTATHIONE; LIPID PEROXIDES; TOXEMIA; PREECLAMPSIA; PRETERM BIRTH; ANEMIA ID METALLOTHIONEIN; TOXICITY; PREECLAMPSIA; INDUCTION; LEAD; ZINC; MICE AB Lipid peroxides, glutathione, and metals (lead, cadmium, and arsenic) were measured in pregnant women residing in the vicinity of a copper smelter. A diagnosis of pregnancy complications experienced by each woman was made on the basis of interview and clinical record. Patients were assigned to groups of normal or pathologic pregnancies (threatened spontaneous abortion, toxemia, and anemia) according to this diagnosis. Biochemical changes suggestive of increased lipid peroxidation and decreased antioxidant protection (involving the reduced: oxidized glutathione balance) were found in the diagnostic groups of pregnancy complications. These changes were independent of measured maternal variables. Maternal exposure to metals (as indicated by blood lead and cadmium) was associated with a decrease in reduced glutathione in blood. Since increased lipid peroxidation has been implicated in other studies as a pathogenetic factor for maternal toxemia, it is suggested that exposure to metals during gestation could enhance the development of pregnancy complications by increasing lipid peroxidation via depletion of reduced glutathione reserves. C1 NIEHS,POB 12233,MAIL DROP A3-05,RES TRIANGLE PK,NC 27703. NATL CTR HYG ECOL & NUTR,SOFIA,BULGARIA. CLIN OCCUPAT DIS,SOFIA,BULGARIA. NR 27 TC 24 Z9 25 U1 0 U2 3 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 MAY-JUN PY 1994 VL 8 IS 3 BP 217 EP 224 DI 10.1016/0890-6238(94)90005-1 PG 8 WC Reproductive Biology; Toxicology SC Reproductive Biology; Toxicology GA NQ437 UT WOS:A1994NQ43700004 PM 8075510 ER PT J AU LITMAN, RE HOMMER, DW RADANT, A CLEM, T PICKAR, D AF LITMAN, RE HOMMER, DW RADANT, A CLEM, T PICKAR, D TI QUANTITATIVE EFFECTS OF TYPICAL AND ATYPICAL NEUROLEPTICS ON SMOOTH-PURSUIT EYE TRACKING IN SCHIZOPHRENIA SO SCHIZOPHRENIA RESEARCH LA English DT Article DE EYE TRACKING; TYPICAL NEUROLEPTIC; CLOZAPINE; INTRUSIVE SACCADE ID DORSOLATERAL PREFRONTAL CORTEX; TARDIVE-DYSKINESIA; CORTICAL CONTROL; VISUAL PURSUIT; MOVEMENTS; SACCADES; DYSFUNCTION; CLOZAPINE; PERFORMANCE; DISORDER AB Smooth pursuit eye movement (SPEM) gain, total saccades, and subtypes of saccades were quantified from the visual pursuit tracking of 26 fluphenazine-treated patients with schizophrenia and 42 normal controls. Tracking was repeated in 16 patients who underwent a placebo-controlled, double-blind crossover comparison of fluphenazine and clozapine. Fluphenazine-treated patients showed significant reduction in SPEM gain and significant increases in both total, intrusive, and anticipatory saccades and in saccadic amplitude, when compared to controls. Clozapine significantly reduced SPEM gain and significantly increased total and catch-up saccades, when compared to placebo or fluphenazine. High amplitude of intrusive saccades in drug-free patients predicted poor response to clozapine, suggesting that intact frontal cortical function may enable optimal clozapine response. RP LITMAN, RE (reprint author), NIMH,CLIN STUDIES SECT,EXPTL THERAPEUT BRANCH,NIH BLDG 10-4N214,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 67 TC 48 Z9 48 U1 2 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAY PY 1994 VL 12 IS 2 BP 107 EP 120 DI 10.1016/0920-9964(94)90068-X PG 14 WC Psychiatry SC Psychiatry GA NK059 UT WOS:A1994NK05900002 PM 8043521 ER PT J AU LEVAY, S HAMER, DH AF LEVAY, S HAMER, DH TI EVIDENCE FOR A BIOLOGICAL INFLUENCE IN MALE HOMOSEXUALITY SO SCIENTIFIC AMERICAN LA English DT Article RP LEVAY, S (reprint author), NCI,GENE STRUCT & REGULAT SECT,BETHESDA,MD 20892, USA. NR 4 TC 42 Z9 44 U1 5 U2 27 PU SCI AMERICAN INC PI NEW YORK PA 415 MADISON AVE, NEW YORK, NY 10017 SN 0036-8733 J9 SCI AM JI Sci.Am. PD MAY PY 1994 VL 270 IS 5 BP 44 EP 49 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NG636 UT WOS:A1994NG63600008 PM 8197444 ER PT J AU BURTON, AA FLYNN, JA NEUMANN, TM WILSON, C QUINN, TC HOOK, EW AF BURTON, AA FLYNN, JA NEUMANN, TM WILSON, C QUINN, TC HOOK, EW TI ROUTINE SEROLOGIC SCREENING FOR SYPHILIS IN HOSPITALIZED-PATIENTS - HIGH PREVALENCE OF UNSUSPECTED INFECTION IN THE ELDERLY SO SEXUALLY TRANSMITTED DISEASES LA English DT Article ID IMMUNODEFICIENCY-VIRUS HIV; ASSOCIATION; POPULATION AB Background and Objectives: To evaluate the potential yield of routine serologic testing for syphilis in hospitalized patients. Study Design: Sera from consecutive patients admitted to an inpatient general medical service of a Baltimore hospital were tested using the RPR and FTA-ABS tests for syphilis. Two hundred ninety-one (149 males and 142 females) of 344 patients (85%) hospitalized during the study period participated, with ages ranging from 17 to 98 years. Seventy-seven percent of participants were African-American. Results of serologic tests for syphilis and human immunodeficiency virus were correlated with questionnaire responses. Associations were sought between results of serologic testing and demographic characteristics, medical problems, and a history of syphilis. Results: No patient had an admitting diagnosis of syphilis. Thirty-seven patients (13%) had both reactive RPR and FTA-ABS tests. Although serologic evidence of syphilis was significantly associated with age older than 50 years and with a history of syphilis, 59% of patients with both reactive RPR and PTA-ARS tests did not give a history of syphilis. Ten percent of patients were HIV seropositive; however HIV seropositivity was not significantly associated with serologic evidence of syphilis. Conclusion: Unsuspected latent syphilis was common in this population. Routine serologic screening for syphilis should be considered in some hospitals. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT MED,BALTIMORE,MD 21205. NIAID,BETHESDA,MD 20892. BALTIMORE CITY DEPT HLTH,BALTIMORE,MD. FU NIAID NIH HHS [AI 27727] NR 14 TC 4 Z9 5 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0148-5717 J9 SEX TRANSM DIS JI Sex. Transm. Dis. PD MAY-JUN PY 1994 VL 21 IS 3 BP 133 EP 136 DI 10.1097/00007435-199405000-00002 PG 4 WC Infectious Diseases SC Infectious Diseases GA NN124 UT WOS:A1994NN12400002 PM 8073341 ER PT J AU BURCHFIEL, CM CURB, JD RODRIGUEZ, BL ABBOTT, RD CHIU, D YANO, K AF BURCHFIEL, CM CURB, JD RODRIGUEZ, BL ABBOTT, RD CHIU, D YANO, K TI GLUCOSE-INTOLERANCE AND 22-YEAR STROKE INCIDENCE - THE HONOLULU HEART PROGRAM SO STROKE LA English DT Article DE CEREBRAL HEMORRHAGE; DIABETES MELLITUS; EPIDEMIOLOGY; GLUCOSE; RISK FACTORS ID DEPENDENT DIABETES-MELLITUS; TRANSIENT ISCHEMIC ATTACK; RISK-FACTORS; JAPANESE MEN; CARDIOVASCULAR-DISEASE; INSULIN RESISTANCE; FOLLOW-UP; HEMORRHAGIC STROKE; SERUM-CHOLESTEROL; MORTALITY AB Background and Purpose This study was conducted to determine whether glucose intolerance and diabetes increase the risk of thromboembolic, hemorrhagic, and total stroke independent of other risk factors. Methods Among 7549 Japanese-American men aged 45 to 68 years and free of coronary heart disease and stroke during 1965 to 1968, history of diabetes, diabetic medication, and nonfasting glucose 1 hour after a 50-g load were used to classify subjects into four glucose tolerance categories. Incidence of stroke over 22 years was ascertained using comprehensive hospital-based surveillance. Age- and risk factor-adjusted relative risks of stroke were determined using a Cox proportional hazards model. Results A total of 374 thromboembolic, 128 hemorrhagic, and 36 type-unknown strokes occurred. Incidence of thromboembolic but not hemorrhagic stroke increased with worsening glucose tolerance category. Compared with the ''low-normal'' (glucose <151 mg/dL) group, subjects in the ''high-normal'' (151 to 224 mg/dL), ''asymptomatic high'' (greater than or equal to 225 mg/dL), and ''known diabetes'' groups all had significantly elevated age-adjusted relative risks of thromboembolic stroke. After adjustment for other risk factors, relative risks remained significantly elevated for the asymptomatic high and known diabetes groups (1.43 and 2.45; 95% confidence intervals, 1.00 to 2.04 and 1.73 to 3.47, respectively). Associations were the same in hypertensive and nonhypertensive subjects and similar but slightly stronger in younger (aged 45 to 54 years) than in older (aged 55 to 68 years) men. Conclusions Subjects with diabetes and elevated glucose appear to be at increased risk of thromboembolic but not hemorrhagic stroke. These associations were largely independent of other cardiovascular disease risk factors. Excess risk is apparent in older as well as younger diabetic individuals and in hypertensive and nonhypertensive subjects with diabetes. C1 UNIV HAWAII,NHLBI,EPIDEMIOL & BIOMETRY PROGRAM,HONOLULU EPIDEMIOL RES SECT,HONOLULU,HI. UNIV HAWAII MANOA,JOHN A BURNS SCH MED,DEPT MED,HONOLULU,HI. UNIV VIRGINIA,SCH MED,DEPT MED,DIV BIOSTAT,CHARLOTTESVILLE,VA 22908. RP BURCHFIEL, CM (reprint author), UNIV HAWAII MANOA,KUAKINI MED CTR,HONOLULU HEART PROGRAM,347 N KUAKINI ST,HONOLULU,HI 96817, USA. FU NHLBI NIH HHS [N01-HC-95099] NR 67 TC 136 Z9 142 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0039-2499 J9 STROKE JI Stroke PD MAY PY 1994 VL 25 IS 5 BP 951 EP 957 PG 7 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA NH560 UT WOS:A1994NH56000005 PM 8165689 ER PT J AU PORTIS, JL AF PORTIS, JL TI ENDOGENOUS RETROVIRAL ENVELOPE ANTIGENS RECOGNIZED BY B-LYMPHOCYTES DURING GRAFT-VERSUS-HOST REACTION SO TOHOKU JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE ENDOGENOUS RETROVIRUS; GRAFT-VERSUS-HOST REACTION; B LYMPHOCYTES; MONOCLONAL ANTIBODIES ID MURINE LEUKEMIA-VIRUS; WILD MICE; MONOCLONAL-ANTIBODIES; RMCF GENE; RESISTANCE; ERYTHROLEUKEMIA; IDENTIFICATION; PROVIRUSES; SYSTEM AB We recovered anti-murine retroviral hybridomas from the spleen cells of (B6xD2) F-1 mice in which graft-versus-host reaction (GVHR) had been induced by the infusion of spleen cells from either parent. The antibodies mere specific for envelope proteins of endogenous retroviruses, and have provided a convenient way of classifying viruses based on their host range. They also have revealed considerable serologic heterogeneity within each host-range group. We have utilized these antibodies to characterize endogenous envelope glycoproteins in uninoculated mice. In this report I have attempted to synthesize the results of studies carried out by a number of senior investigators as well as postdoctoraI fellows who have graced the Laboratory of Persistent Viral Diseases over the last 10 years. Some of the information on the nature of the endogenous glycoproteins expressed within the hematopoietic compartment of DBA/2 and C57BL mice has provided a basis for speculation, offered at the end of the report, on the possibility that anti-retroviral autoantibodies generated during the course of GVHR may be antigen-driven. RP PORTIS, JL (reprint author), NIAID, ROCKY MT LABS, PERSISTENT VIRAL DIS LAB, 903 S 4TH ST, HAMILTON, MT 59840 USA. NR 18 TC 2 Z9 2 U1 0 U2 0 PU TOHOKU UNIV MEDICAL PRESS PI SENDAI PA 2-1, SEIRYO-MACHI, AOBA-KU, SENDAI, MIYAGI 980-8575, JAPAN SN 0040-8727 EI 1349-3329 J9 TOHOKU J EXP MED JI Tohoku J. Exp. Med. PD MAY PY 1994 VL 173 IS 1 BP 83 EP 89 DI 10.1620/tjem.173.83 PG 7 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA PE585 UT WOS:A1994PE58500007 PM 7809913 ER PT J AU GOURLEY, MF KISCH, WJ MOJCIK, CF KING, LB KRIEG, AM STEINBERG, AD AF GOURLEY, MF KISCH, WJ MOJCIK, CF KING, LB KRIEG, AM STEINBERG, AD TI ROLE OF ENDOGENOUS RETROVIRUSES IN AUTOIMMUNE-DISEASES SO TOHOKU JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE ENDOGENOUS RETROVIRUS; SYSTEMIC LUPUS ERYTHEMATOSUS; AUTOIMMUNITY; ANTISENSE; POLYTROPIC RETROVIRUS ID VIRAL ENVELOPE GLYCOPROTEIN; RECOMBINANT INBRED LINES; MURINE LEUKEMIA-VIRUS; MAMMARY-TUMOR VIRUS; NZB MICE; FAS ANTIGEN; CELL; EXPRESSION; IMMUNE; MOUSE AB Retroviruses have been implicated in the pathogenesis of murine and human lupus; however, many positive findings have been followed by alternative explanations. Initial findings implicating xenotropic retroviruses mere subsequently invalidated. The first solid demonstration that endogenous retroviruses mediate disease mas the study of SL/Ni mice. Here budding ecotropic retroviral particles from arterial smooth muscle cells caused an antibody response to the particles with subsequent complement deposition. Our laboratory has focused on derangements in endogenous MCF retroviral expression. We found that lupus-prone NZB, BXSB and MRL strains have a marked increase in expression of Mpmv RNA in their thymuses while bone marrow expression did not differ from normal strains. Sequence analysis demonstrated mutations in the NZB endogenous retroviruses which could alter expression. A phosphorothioate antisense oligonucleotide to the initiation sequence of Mpmv caused lymphocyte activation in vivo in normal mice, providing further evidence for in vivo effects of Mpmv and potential for pathological abnormalities in lupus-prone strains. C1 UNIV IOWA, IOWA CITY, IA USA. MITRE CORP, MCLEAN, VA USA. RP GOURLEY, MF (reprint author), NIAMS, ARTHRIT & RHEUMATISM BRANCH, CELLULAR IMMUNOL SECT, BLDG 10, ROOM 9N216, BETHESDA, MD 20892 USA. NR 30 TC 5 Z9 5 U1 0 U2 0 PU TOHOKU UNIV MEDICAL PRESS PI SENDAI PA 2-1, SEIRYO-MACHI, AOBA-KU, SENDAI, MIYAGI 980-8575, JAPAN SN 0040-8727 EI 1349-3329 J9 TOHOKU J EXP MED JI Tohoku J. Exp. Med. PD MAY PY 1994 VL 173 IS 1 BP 105 EP 114 DI 10.1620/tjem.173.105 PG 10 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA PE585 UT WOS:A1994PE58500009 PM 7809902 ER PT J AU CHERIAN, MG HOWELL, SB IMURA, N KLAASSEN, CD KOROPATNICK, J LAZO, JS WAALKES, MP AF CHERIAN, MG HOWELL, SB IMURA, N KLAASSEN, CD KOROPATNICK, J LAZO, JS WAALKES, MP TI CONTEMPORARY-ISSUES IN TOXICOLOGY - ROLE OF METALLOTHIONEIN IN CARCINOGENESIS SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article ID B6C3F1 MOUSE-LIVER; BLADDER-TUMOR; IMMUNOHISTOCHEMICAL LOCALIZATION; CIS-DIAMMINEDICHLOROPLATINUM; HEPATIC METALLOTHIONEIN; CADMIUM PRETREATMENT; ANTITUMOR-ACTIVITY; ANTICANCER DRUGS; CARCINOMA-CELLS; RENAL TOXICITY AB Metallothionein (MT) is a low-mo-lecular-weight protein (6800 Da) and one-third of its amino acids are cysteine residues. The 20 cysteines coordinate 7 metal atoms (zinc, copper, and/or cadmium). This protein is extremely inducible by metals as well as a number of organic compounds. MT is thought to be an important intracellular storage site for zinc and possibly other essential trace elements. In addition, tolerance to cadmium toxicity is often due to the induction of MT, which sequesters cadmium and lowers its concentration at critical intracellular sites. Recently it has been proposed that MT might play important roles in several aspects of the carcinogenic process. In this context a symposium was held recently on this topic at the 1993 Annual Society of Toxicology Meeting. At this symposium Dr. Cherian discussed the expression of MT in various human tumors and its use as a potential marker of tumor differentiation or cell proliferation. Dr. Imura provided data illustrating that induction of MT can be used as an adjunct in cancer chemotherapy, in preventing toxicity caused by gamma-irradiation or cisplatin (CDDP) and other chemotherapeutics. Induction of MT has been suggested to be an important mechanism of resistance of tumor cells to chemotherapeutic agents, such as CDDP. This is controversial, and various views on this topic were presented by Drs. Howell, Late, and Koropatnick. Dr. Waalkes then discussed the role of MT in the carcinogenic and anticarcinogenic effects of metals. (C) 1994 Academic Press, Inc. C1 NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,INORGAN CARCINOGENESIS LAB,FREDERICK,MD 21702. UNIV WESTERN ONTARIO,HLTH SCI CTR,DEPT PATHOL,LONDON N6A 5C1,ON,CANADA. UNIV CALIF SAN DIEGO,CTR CANC,DEPT MED,LA JOLLA,CA 92093. KITASATO UNIV,SCH PHARMACEUT SCI,DEPT PUBL HLTH,MINATO KU,TOKYO 108,JAPAN. UNIV KANSAS,MED CTR,DEPT PHARMACOL TOXICOL & THERAPEUT,KANSAS CITY,KS 66103. UNIV WESTERN ONTARIO,LONDON REG CANC CTR,DEPT ONCOL,LONDON N6A 4L6,ON,CANADA. UNIV PITTSBURGH,SCH MED,DEPT PHARMACOL,PITTSBURGH,PA 15261. NR 36 TC 143 Z9 146 U1 0 U2 7 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 MAY PY 1994 VL 126 IS 1 BP 1 EP 5 DI 10.1006/taap.1994.1083 PG 5 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA NL854 UT WOS:A1994NL85400001 PM 8184419 ER PT J AU BLAZKA, ME HARRY, GJ LUSTER, MI AF BLAZKA, ME HARRY, GJ LUSTER, MI TI EFFECT OF LEAD ACETATE ON NITRITE PRODUCTION BY MURINE BRAIN ENDOTHELIAL-CELL CULTURES SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article ID OXIDE; CAPILLARIES; CALMODULIN; ACTIVATION; RAT AB One of the mechanisms by which lead may cause a perturbation in the nervous system is the alteration of endothelial cell function. This study investigated the effect of lead acetate on constitutive and cytokine-induced production of nitrite, a marker of nitric oxide, in brain microvascular endothelial cells. Nitric oxide synthase may be a target for lead and changes in its function can result in a cascade of physiological effects seen in vivo. Concentrations of 10, 100, and 1000 nM lead acetate, in the presence or absence of 100 ng lipopolysaccharide/ml, 400 U interferon-gamma/ml and 100 U tumor necrosis factor-alpha/ml, were added to confluent cultures of brain microvascular endothelial cells. Concentrations of lead acetate as low as 10 nM decreased constitutive levels of nitrite by 50% without inhibiting the inducible levels. Addition of 1 mu M lead acetate had no effect on [H-3]L-leucine incorporation, lactate dehydrogenase release, or cellular morphology, indicating that the effect was selective. Increasing the concentration of extracellular calcium to 2 mM abolished the inhibitory effect of lead acetate on the constitutive production of nitrite. These studies suggest that low concentrations of lead are capable of inhibiting nitrite produced by the calcium-dependent constitutive form of nitric oxide synthase while the calcium-independent, inducible form of nitric oxide synthase is not affected. These data provide another testable hypothesis for the as yet undetermined mechanisms of lead neurotoxicity. (C) 1994 Academic Press, Inc. RP BLAZKA, ME (reprint author), NIEHS, ENVIRONM IMMUNOL & NEUROBIOL SECT, POB 12233, RES TRIANGLE PK, NC 27709 USA. NR 29 TC 26 Z9 32 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0041-008X EI 1096-0333 J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD MAY PY 1994 VL 126 IS 1 BP 191 EP 194 DI 10.1006/taap.1994.1107 PG 4 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA NL854 UT WOS:A1994NL85400025 PM 7514316 ER PT J AU SLOAND, EM KUMAR, P YU, M KLEIN, HG AF SLOAND, EM KUMAR, P YU, M KLEIN, HG TI EFFECT OF AMPHOTERICIN-B AND FLUCONAZOLE ON PLATELET MEMBRANE-GLYCOPROTEINS SO TRANSFUSION LA English DT Article ID MONOCLONAL-ANTIBODY; HUMAN-ERYTHROCYTES; TRANSFUSIONS; AGGREGATION; COMPLEX; SURFACE; STORAGE; IB; CIRCULATION; ANTIBIOTICS AB Background: Fever, chills, and reduced platelet recovery may result when platelets are transfused simultaneously with amphotericin B. Amphotericin B reportedly increases the pitting of membranes in stored platelets. Study Design and Methods: The effects of amphotericin B and another antifungal agent, fluconazole, on platelet membrane glycoproteins (GP) were examined by the incubation of split aliquots of fresh and stored platelet concentrates (PCs) with these drugs for 3 days in storage bags. To determine the effect of storage, PCs were stored for 5 days, and aliquots removed on Days 1 through 5 were placed in platelet storage bags with 4 mu g per mL of amphotericin B for 2 to 6 hours. Membrane glycoprotein expression was assessed by flow cytometry with fluorescein isothiocyanate-labeled monoclonal antibodies (MoAbs) directed against the following antigens: GPIb (CD42b), CD63 (an activation protein), P-selectin (CD62), and GPIIb/IIIa (CD41a). Results: Amphotericin B produced a concentration-dependent decrease in the surface binding of CD42b MoAb with no consistent changes in the binding of CD41a, CD63, or CD62 MoAbs after a 3-day exposure. Stored but not-fresh PCs showed decreased binding of MoAb CD42b after a 6-hour exposure to amphotericin B (4 mu g/mL). Fluconazole produced no changes. When the binding of MoAb CD42b to permeabilized platelets was used to measure total platelet content, amphotericin B (4 mu g/mL) decreased MoAb CD42b binding tb a similar degree in fresh and stored platelets. Inhibition of aggregation to ADP and collagen and ADP and epinephrine was seen in stored but not fresh PCs. Conclusion: Therapeutic levels of amphotericin B resulted in partial loss of total platelet GPIb in fresh and stored PCs, but decreased surface expression of platelet membrane GPIb only in stored platelets. This difference between fresh and stored platelets may be related to the limited reservoir of GPIb available for redistribution to the membrane in the previously stored PCs and may account for the decreased recovery of transfused platelets observed in some patients receiving amphotericin B. C1 GEORGETOWN UNIV,MED CTR,DEPT MED,WASHINGTON,DC 20007. NIH,WARREN G MAGNUSON CLIN CTR,DEPT TRANSFUS MED,BETHESDA,MD 20892. RP SLOAND, EM (reprint author), NHLBI,BLDG 31,ROOM 5A50,BETHESDA,MD 20892, USA. NR 25 TC 9 Z9 9 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 SN 0041-1132 J9 TRANSFUSION JI Transfusion PD MAY PY 1994 VL 34 IS 5 BP 415 EP 420 DI 10.1046/j.1537-2995.1994.34594249054.x PG 6 WC Hematology SC Hematology GA NP054 UT WOS:A1994NP05400012 PM 8191567 ER PT J AU STEHLING, L LUBAN, NLC ANDERSON, KC SAYERS, MH LONG, A ATTAR, S LEITMAN, SF GOULD, SA KRUSKALL, MS GOODNOUGH, LT HINES, DM AF STEHLING, L LUBAN, NLC ANDERSON, KC SAYERS, MH LONG, A ATTAR, S LEITMAN, SF GOULD, SA KRUSKALL, MS GOODNOUGH, LT HINES, DM TI GUIDELINES FOR BLOOD UTILIZATION REVIEW SO TRANSFUSION LA English DT Article ID TRANSFUSION PRACTICES; CELL TRANSFUSION; STRATEGIES; THERAPY; INFECTION; SYSTEM; RISK C1 UNIV WASHINGTON,DEPT MED,DIV HEMATOL,SEATTLE,WA 98195. UNIV WASHINGTON,PUGET SOUND BLOOD CTR,SEATTLE,WA. NIH,DEPT TRANSFUS MED,BLOOD SERV SECT,BETHESDA,MD 20892. AMER ASSOC BLOOD BANKS,TECH AFFAIRS,BETHESDA,MD. HARVARD UNIV,BETH ISRAEL HOSP,SCH MED,BOSTON,MA. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA. CHILDRENS HOSP,BLOOD BANK,WASHINGTON,DC. GEORGE WASHINGTON UNIV,SCH MED,DEPT PEDIAT,WASHINGTON,DC 20052. GEORGE WASHINGTON UNIV,SCH MED,WASHINGTON,DC. ST MARYS REG BLOOD BANK,GRAND JCT,CO. UNIV ILLINOIS,COLL MED,DEPT SURG,CHICAGO,IL. MICHAEL REESE HOSP & MED CTR,CHICAGO,IL 60616. WASHINGTON UNIV,MED CTR,DEPT MED,ST LOUIS,MO. WASHINGTON UNIV,MED CTR,DEPT PATHOL,ST LOUIS,MO. UNIV MARYLAND,MED CTR,DEPT THORAC & CARDIOVASC SURG,BALTIMORE,MD 21201. RP STEHLING, L (reprint author), BLOOD SYST INC,DEPT MED AFFAIRS,POB 1867,E OAK ST,SCOTTSDALE,AZ, USA. NR 29 TC 75 Z9 76 U1 0 U2 1 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 SN 0041-1132 J9 TRANSFUSION JI Transfusion PD MAY PY 1994 VL 34 IS 5 BP 438 EP 448 DI 10.1046/j.1537-2995.1994.34594249058.x PG 11 WC Hematology SC Hematology GA NP054 UT WOS:A1994NP05400016 PM 8191570 ER PT J AU HENGEN, PN AF HENGEN, PN TI METHODS AND REAGENTS - USE OF P-33 - A SAFER WAY TO SEQUENCE SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Article ID DNA AB Methods and reagents is a unique monthly column that highlights current discussions in the newsgroup bionet.molbio.methods-reagnts, available on the Internet. Since questions about laboratory safety procedures are common on the net, this month's column discusses the use of the radioisotope P-33 as an alternative to P-32. RP HENGEN, PN (reprint author), NCI,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702, USA. NR 6 TC 0 Z9 0 U1 1 U2 1 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 MAY PY 1994 VL 19 IS 5 BP 227 EP 229 DI 10.1016/0968-0004(94)90027-2 PG 3 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NM069 UT WOS:A1994NM06900011 PM 8048165 ER PT J AU CULVER, KW BLAESE, RM AF CULVER, KW BLAESE, RM TI GENE-THERAPY FOR CANCER SO TRENDS IN GENETICS LA English DT Review ID CELLS; INVIVO; POTENT; TUMORS AB Initiation of clinical trials of gene therapies for cancer has been made possible by two major technological advances: the ability to clone genes that constitute the genetic basis of carcinogenesis or that have therapeutic potential, and the development of an increasing number of gene transfer methods. As a result, 30 experimental trials of gene therapy for the treatment of human cancer have been approved in the United States of America. Here, we discuss the current status of gene therapy for cancer together with future directions for its development. C1 NIH,BETHESDA,MD 20892. RP CULVER, KW (reprint author), IOWA METHODIST MED CTR,HUMAN GENE THERAPY RES INST,1415 WOODLAND AVE,DES MOINES,IA 50309, USA. NR 26 TC 142 Z9 142 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0168-9525 J9 TRENDS GENET JI Trends Genet. PD MAY PY 1994 VL 10 IS 5 BP 174 EP 178 DI 10.1016/0168-9525(94)90095-7 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA NJ258 UT WOS:A1994NJ25800008 PM 8036720 ER PT J AU CADET, JL AF CADET, JL TI FREE-RADICALS AND NEURODEGENERATION SO TRENDS IN NEUROSCIENCES LA English DT Letter ID TARDIVE-DYSKINESIA; VITAMIN-E; METHAMPHETAMINE; STRESS; BRAIN RP NIDA, ADDICT RES CTR, NEUROSCI BRANCH, POB 5180, BALTIMORE, MD 21224 USA. NR 24 TC 8 Z9 8 U1 2 U2 2 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0166-2236 J9 TRENDS NEUROSCI JI Trends Neurosci. PD MAY PY 1994 VL 17 IS 5 BP 192 EP 193 PG 2 WC Neurosciences SC Neurosciences & Neurology GA NK101 UT WOS:A1994NK10100005 PM 7520200 ER PT J AU BRAWLEY, OW THOMPSON, IM AF BRAWLEY, OW THOMPSON, IM TI CHEMOPREVENTION OF PROSTATE-CANCER SO UROLOGY LA English DT Article ID ANDROGEN ABLATION THERAPY; PROGRAMMED CELL-DEATH; RAT VENTRAL PROSTATE; UNITED-STATES; ALPHA-DIFLUOROMETHYLORNITHINE; ORNITHINE DECARBOXYLASE; BETA-CAROTENE; DIET; MEN; EPIDEMIOLOGY C1 BROOKE ARMY MED CTR,SERV UROL,FT SAM HOUSTON,TX 78234. NCI,DIV CANC PREVENT & CONTROL,FT SAM HOUSTON,TX. NR 57 TC 29 Z9 29 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 MAY PY 1994 VL 43 IS 5 BP 594 EP 599 DI 10.1016/0090-4295(94)90169-4 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA NJ426 UT WOS:A1994NJ42600002 PM 8165761 ER PT J AU PARTIN, AW PEARSON, JD LANDIS, PK CARTER, HB POUND, CR CLEMENS, JQ EPSTEIN, JI WALSH, PC AF PARTIN, AW PEARSON, JD LANDIS, PK CARTER, HB POUND, CR CLEMENS, JQ EPSTEIN, JI WALSH, PC TI EVALUATION OF SERUM PROSTATE-SPECIFIC ANTIGEN VELOCITY AFTER RADICAL PROSTATECTOMY TO DISTINGUISH LOCAL RECURRENCE FROM DISTANT METASTASES SO UROLOGY LA English DT Article ID RADIATION-THERAPY; CANCER; ADENOCARCINOMA; RADIOTHERAPY; CARCINOMA; DISEASE; MARGINS; MARKER; PSA; MEN AB Objective. Serum prostate-specific antigen (PSA) values are most useful for prediction of disease recurrence after surgery. It is unknown whether a detectable PSA level after surgery indicates a local recurrence potentially benefiting from pelvic irradiation or distant metastases requiring hormonal treatment. Methods. We analyzed postoperative rate of change of serum PSA levels as a predictor of local versus distant disease recurrence after radical prostatectomy. Between 1982 and 1991, 1,058 men underwent radical prostatectomy for localized prostate cancer and follow-up consisted of determining serum PSA levels and digital rectal examinations. Clinical follow-up of 542 men for four or more years and 78 men for eight or more years yielded ten-year actuarial disease recurrence rates of 4 percent for local recurrence, 8 percent for distant metastases, and 23 percent for an isolated elevation of serum PSA level only. Fifty-one patients with isolated elevations of PSA levels only were followed expectantly until they were diagnosed with either local or distant metastases. Results. A linear mixed effects regression analysis was used to model these data. Using these models, the time to a serum PSA level of 0.5 ng/mL, the PSA level one year following surgery, pathologic stage, Gleason sum, and the rate of change of PSA (PSA velocity [PSAV]) were tested as predictors of local versus distant metastases. A combination of PSAV, pathologic stage, and Gleason grade best distinguished local from distant metastases. Conclusions. These data suggest that PSAV in men with an isolated elevation of PSA levels following radical prostatectomy might aid in clinical decision making. C1 JOHNS HOPKINS UNIV, SCH MED, DEPT UROL, BALTIMORE, MD 21205 USA. JOHNS HOPKINS UNIV, SCH MED, DEPT PATHOL, BALTIMORE, MD 21205 USA. JOHNS HOPKINS MED INST, JAMES BUCHANAN BRADY UROL INST, BALTIMORE, MD 21205 USA. NIAAA, GERONTOL RES CTR, LONGITUDINAL STUDIES BRANCH, ROCKVILLE, MD 20852 USA. FU NCI NIH HHS [P50-CA 58236-01] NR 27 TC 286 Z9 295 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 EI 1527-9995 J9 UROLOGY JI Urology PD MAY PY 1994 VL 43 IS 5 BP 649 EP 659 DI 10.1016/0090-4295(94)90180-5 PG 11 WC Urology & Nephrology SC Urology & Nephrology GA NJ426 UT WOS:A1994NJ42600015 PM 7513108 ER PT J AU MAURY, WJ CARPENTER, S GRAVES, K CHESEBRO, B AF MAURY, WJ CARPENTER, S GRAVES, K CHESEBRO, B TI CELLULAR AND VIRAL SPECIFICITY OF EQUINE INFECTIOUS-ANEMIA VIRUS TAT TRANSACTIVATION SO VIROLOGY LA English DT Article ID LONG TERMINAL REPEAT; RNA-BINDING PROTEIN; IMMUNODEFICIENCY-VIRUS; TRANS-ACTIVATION; HIV-1 TAT; HUMAN CHROMOSOME-12; TRANSCRIPTIONAL REGULATION; GENE-EXPRESSION; NUCLEAR-PROTEIN; LENTIVIRUS TAT AB Lentiviruses vary in their dependence on a functional tat gene during their viral life cycle. To begin to understand the viral and cellular parameters controlling equine infectious anemia virus (EIAV) transactivation, we investigated Tat function and Tat and LTR structural requirements necessary for successful transactivation. EIAV Tat expression was required for detection of viral antigens from a full-length provirus. The level of transactivation by EIAV Tat as measured by LTR-CAT assays correlated well with viral antigen expression. Using horse/mouse somatic cell hybrids (SCH), a single SCH line which supported EIAV transactivation was identified, indicating that the presence of specific horse chromosomes provided cellular factors required for transactivation. Transformed cell lines from several different species were also tested and found to differ in their ability to support EIAV transactivation. A canine cell line, Cf2Th, which was permissive for EIAV transactivation, and a human cell line, HeLa, which was not permissive for EIAV transactivation, were used to map regions of the LTR and Tat that were important in cell-specific transactivation. As expected, the R region of EIAV LTR was required for transactivation by EIAV Tat in all cell lines studied. Similarly, the R region of HIV LTR was necessary for transactivation by HIV Tat. However, the composition of the Us region also influenced transactivation in a cell-specific manner. In Cf2Th cells, replacement of EIAV U3 sequences with HIV U3 sequences resulted in high basal (nontransactivated) expression, and as a result, only a twofold increase in expression was observed in the presence of EIAV Tat. Similar studies using HIV Tat demonstrated that transactivation occurred in Cf2Th cells when either EIAV or HIV U3 sequences were present in the LTR. In contrast, transactivation by either HIV or EIAV Tat in HeLa cells required the presence of HIV enhancer sequences. These findings suggested that the ability of transactivation to occur in some cell lines may involve interactions between cell-specific transcription factors and the activation domain of Tat. For transactivation in other cell lines, Tat appeared to require more ubiquitious factors that interact with both EIAV and HIV U3 sequences. (C) 1994 Academic Press, Inc. C1 IOWA STATE UNIV SCI & TECHNOL,COLL VET MED,DEPT MICROBIOL IMMUNOL & PREVENT MED,AMES,IA 50011. UNIV KENTUCKY,DEPT VET SCI,LEXINGTON,KY 40546. RP MAURY, WJ (reprint author), NIAID,ROCKY MT LABS,LPVD,HAMILTON,MT 59840, USA. FU NIAID NIH HHS [AI 30025] NR 64 TC 21 Z9 22 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 MAY 1 PY 1994 VL 200 IS 2 BP 632 EP 642 DI 10.1006/viro.1994.1226 PG 11 WC Virology SC Virology GA NG523 UT WOS:A1994NG52300031 PM 8178449 ER PT J AU ENSOLI, F ENSOLI, B THIELE, CJ AF ENSOLI, F ENSOLI, B THIELE, CJ TI HIV-1 GENE-EXPRESSION AND REPLICATION IN NEURONAL AND GLIAL-CELL LINES WITH IMMATURE PHENOTYPE - EFFECTS OF NERVE GROWTH-FACTOR SO VIROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; TUMOR NECROSIS FACTOR; LONG TERMINAL REPEAT; HTLV-III; PRODUCTIVE INFECTION; AIDS; BRAINS; DIFFERENTIATION; CHILDREN; TYPE-1 AB Encephalopathy and neurological disorders are a major manifestation of pediatric AIDS. Although HIV-1 can replicate in cells of neuronal and glial origin, it is yet unclear whether immature neural cells, which are present during nervous system development, can support HIV-1 replication and whether neurotrophic factors can modulate HIV-1 gene expression. In this study we show that a glial cell line with a phenotype closely resembling immature glial cells is more permissive to HIV-1 infection and replication than a neuroblastic cell line. After HIV-1 infection or after transfection of these cells with the HIV-1 LTR-CAT reporter gene alone or in the presence of Tat, both HIV-1 replication and viral gene expression progressively decrease in the neuronal cell line, while they increase in the glial cell line. In both cell types viral gene expression and replication are augmented by the addition to the cells of nerve growth factor (NGF) at concentrations which induce neuronal differentiation. However, these effects are again more evident with the glial cell type, suggesting that immature glial cells may represent one of the major targets and reservoirs of HIV-1 in the developing nervous system. As NGF and Tat act synergistically in inducing HIV-1 gene expression, these data also suggest that during development the presence of high levels of neural trophic factors may activate viral replication and render the CNS more susceptible to the deleterious effects of HIV-1 infection. (C) 1994 Academic Press, Inc. C1 NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. RP ENSOLI, F (reprint author), NCI,PEDIAT BRANCH,CELL & MOLEC BIOL SECT,BLDG 10,BETHESDA,MD 20892, USA. RI Ensoli, Barbara/J-9169-2016 OI Ensoli, Barbara/0000-0002-0545-8737 NR 50 TC 30 Z9 30 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 MAY 1 PY 1994 VL 200 IS 2 BP 668 EP 676 DI 10.1006/viro.1994.1230 PG 9 WC Virology SC Virology GA NG523 UT WOS:A1994NG52300035 PM 8178451 ER PT J AU GONDA, MA LUTHER, DG FONG, SE TOBIN, GJ AF GONDA, MA LUTHER, DG FONG, SE TOBIN, GJ TI BOVINE IMMUNODEFICIENCY VIRUS - MOLECULAR-BIOLOGY AND VIRUS-HOST INTERACTIONS SO VIRUS RESEARCH LA English DT Article; Proceedings Paper CT Symposium on the Comparative Biology of Lentivirus Infections CY JUN 14-15, 1993 CL WASHINGTON, DC SP REGISTRY COMPARAT PATHOL ID MULTIPLE RETROVIRAL INFECTIONS; BIOLOGICALLY-ACTIVE PROVIRUSES; LONG TERMINAL REPEAT; WESTERN-BLOT ASSAY; LEUKEMIA-VIRUS; HIV-INFECTION; NUCLEOTIDE-SEQUENCE; VISNA VIRUS; RECOMBINANT BACULOVIRUS; PERSISTENT INFECTION C1 LOUISIANA STATE UNIV,DEPT VET SCI,BATON ROUGE,LA 70803. RP GONDA, MA (reprint author), NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,CELL & MOLEC STRUCT LAB,FREDERICK,MD 21702, USA. NR 100 TC 78 Z9 81 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-1702 J9 VIRUS RES JI Virus Res. PD MAY PY 1994 VL 32 IS 2 BP 155 EP 181 PG 27 WC Virology SC Virology GA NL495 UT WOS:A1994NL49500005 PM 8067052 ER PT J AU HIRSCH, VM JOHNSON, PR AF HIRSCH, VM JOHNSON, PR TI PATHOGENIC DIVERSITY OF SIMIAN IMMUNODEFICIENCY VIRUSES SO VIRUS RESEARCH LA English DT Article; Proceedings Paper CT Symposium on the Comparative Biology of Lentivirus Infections CY JUN 14-15, 1993 CL WASHINGTON, DC SP REGISTRY COMPARAT PATHOL DE SIMIAN IMMUNODEFICIENCY VIRUS; PATHOGENESIS; DIVERSITY ID AFRICAN-GREEN MONKEYS; T-LYMPHOTROPIC RETROVIRUS; MACAQUE MONKEYS; RHESUS-MONKEYS; PRIMATE LENTIVIRUS; EXPERIMENTAL-INFECTION; GENETIC DIVERSITY; HIGHLY DIVERGENT; CERCOCEBUS-ATYS; SOOTY MANGABEY AB The SIV family is a diverse group of viruses that vary considerably in pathogenesis and virulence in their natural host species or macaques. Although the disease induced by the SIVsm subtype in particular is remarkably similar to human AIDS, it must be remembered that this is an experimental animal model. Therefore, although the pathogenesis of SIVsm (and other viruses) in macaques offers an relevant animal model for pathogenesis and vaccine trials, the interactions of these viruses in their natural host, and virus-, or host-specific effects have been poorly characterized. This animal model offers a unique opportunity to study the details of the pathogenesis of immunodeficiency and to define host and viral factors responsible for disease progression. C1 OHIO STATE UNIV,CHILDRENS HOSP RES FDN,DEPT PEDIAT,COLUMBUS,OH 43205. RP HIRSCH, VM (reprint author), NIAID,INFECT DIS LAB,IMMUNODEFICIENCY VIRUSES SECT,12441 PARKLAWN DR,ROCKVILLE,MD 20852, USA. RI Johnson, Philip/A-6892-2009 NR 73 TC 124 Z9 125 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-1702 J9 VIRUS RES JI Virus Res. PD MAY PY 1994 VL 32 IS 2 BP 183 EP 203 DI 10.1016/0168-1702(94)90041-8 PG 21 WC Virology SC Virology GA NL495 UT WOS:A1994NL49500006 PM 8067053 ER PT J AU MCCLURKIN, JW OPTICAN, LM RICHMOND, BJ AF MCCLURKIN, JW OPTICAN, LM RICHMOND, BJ TI CORTICAL FEEDBACK INCREASES VISUAL INFORMATION TRANSMITTED BY MONKEY PARVOCELLULAR LATERAL GENICULATE-NUCLEUS NEURONS SO VISUAL NEUROSCIENCE LA English DT Article DE CORTICOGENICULATE FEEDBACK; TEMPORAL ENCODING; TRANSMITTED INFORMATION ID TWO-DIMENSIONAL PATTERNS; INFERIOR TEMPORAL CORTEX; SINGLE UNITS; 2-DIMENSIONAL PATTERNS; RESPONSE PROPERTIES; BEHAVING PRIMATES; X-CELL; Y-CELL; CAT; PATHWAY AB We studied the effect of cooling the striate cortex on parvocellular lateral geniculate nucleus (PLGN) neurons in awake monkeys. Cooling the striate cortex produced both facilitation and inhibition of the responses of all neurons, depending on the stimulus presented. Cooling the striate cortex also altered the temporal distribution of spikes in the responses of PLGN neurons. Shannon's information measure revealed that cooling the striate cortex reduced the average stimulus-related information transmitted by all PLGN neurons. The reduction in transmitted information was associated with both facilitation and inhibition of the response. Cooling the striate cortex reduced the amount of information transmitted about all of the stimulus parameters tested: pattern, luminance, spatial contrast, and sequential contrast. The effect of cooling was nearly the same for codes based on the number of spikes in the response as for codes based on their temporal distribution. The reduction in transmitted information occurred because the differences among the responses to different stimuli (signal separation) were reduced, not because the variability of the responses to individual stimuli (noise) was increased. We conclude that one function of corticogeniculate feedback is to improve the ability of PLGN neurons to discriminate among stimuli by enhancing the differences among their responses. C1 NIMH,NEUROPSYCHOL LAB,BETHESDA,MD 20892. RP MCCLURKIN, JW (reprint author), NEI,SENSORIMOTOR RES LAB,BLDG 49,ROOM 2A50,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 52 TC 55 Z9 57 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0952-5238 J9 VISUAL NEUROSCI JI Visual Neurosci. PD MAY-JUN PY 1994 VL 11 IS 3 BP 601 EP 617 PG 17 WC Neurosciences; Ophthalmology SC Neurosciences & Neurology; Ophthalmology GA NH296 UT WOS:A1994NH29600015 PM 8038131 ER PT J AU CHABNER, BA AF CHABNER, BA TI UNTITLED SO WORLD JOURNAL OF SURGERY LA English DT Letter ID II BREAST-CANCER; CHEMOTHERAPY RP CHABNER, BA (reprint author), NCI,DIV CANC TREATMENT,BETHESDA,MD 20892, USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0364-2313 J9 WORLD J SURG JI World J.Surg. PD MAY-JUN PY 1994 VL 18 IS 3 BP 441 EP 441 PG 1 WC Surgery SC Surgery GA NU903 UT WOS:A1994NU90300021 ER PT J AU HERBERMAN, RB AF HERBERMAN, RB TI UNTITLED SO WORLD JOURNAL OF SURGERY LA English DT Letter RP HERBERMAN, RB (reprint author), UNIV PITTSBURGH,SCH MED,NSABP,PITTSBURGH,PA, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0364-2313 J9 WORLD J SURG JI World J.Surg. PD MAY-JUN PY 1994 VL 18 IS 3 BP 442 EP 442 PG 1 WC Surgery SC Surgery GA NU903 UT WOS:A1994NU90300022 ER PT J AU JENSEN, RT AF JENSEN, RT TI ZOLLINGER-ELLISON SYNDROME - PAST, PRESENT AND FUTURE CONTROVERSIES SO YALE JOURNAL OF BIOLOGY AND MEDICINE LA English DT Article; Proceedings Paper CT Lester Dragstedt Centenary Symposium CY OCT 01, 1993 CL YALE UNIV SCH MED, NEW HAVEN, CT HO YALE UNIV SCH MED ID MULTIPLE ENDOCRINE NEOPLASIA; ISLET-CELL TUMORS; GASTRIC HYPERSECRETORY STATES; LONG-TERM EFFICACY; DUODENAL GASTRINOMAS; ENDOSCOPIC ULTRASONOGRAPHY; EXPLORATORY LAPAROTOMY; METASTATIC GASTRINOMA; LOCALIZE GASTRINOMAS; SURGICAL-MANAGEMENT AB It is fitting that the Zollinger-Ellison syndrome (ZES) be included in the Lester Dragstedt Symposium because Dr. Dragstedt had a long-time interest in this disease, having been one of the five discussants of the original article and subsequently reporting with Dr. Oberhelman on nine cases. The approach to therapy of ZES has been controversial from the beginning, and a number of controversies remain. In this article, four different controversies are analyzed from the prospective of the past (Zollinger-Dragstedt era, 1955-1980), present and what may happen in the future in light of recent results. Specifically analyzed are: 1) the role of gastric surgery in the management; 2) whether gastrinoma removal without aggressive resection in patients with ZES without MEN-I is the preferred surgical therapy; 3) whether patients with MEN-I should undergo routine surgical exploration; and 4) whether most gastrinomas will be localized preoperatively. An analysis of recent advances suggests there may be marked changes in the future from our current and our past approaches. RP JENSEN, RT (reprint author), NIDDKD,DIGEST DIS BRANCH,BLDG 10,ROOM 9C-103,10 CTR DR,MSC 1804,BETHESDA,MD 20892, USA. NR 108 TC 4 Z9 4 U1 0 U2 0 PU YALE J BIOL MED INC PI NEW HAVEN PA 333 CEDAR ST, NEW HAVEN, CT 06510 SN 0044-0086 J9 YALE J BIOL MED JI Yale J. Biol. Med. PD MAY-AUG PY 1994 VL 67 IS 3-4 BP 195 EP 214 PG 20 WC Biology; Medicine, General & Internal; Medicine, Research & Experimental SC Life Sciences & Biomedicine - Other Topics; General & Internal Medicine; Research & Experimental Medicine GA RQ807 UT WOS:A1994RQ80700015 PM 7502529 ER PT J AU MCMAHON, RP PROSCHAN, M GELLER, NL STONE, PH SOPKO, G AF MCMAHON, RP PROSCHAN, M GELLER, NL STONE, PH SOPKO, G TI SAMPLE-SIZE CALCULATION FOR CLINICAL-TRIALS IN WHICH ENTRY CRITERIA AND OUTCOMES ARE COUNTS OF EVENTS SO STATISTICS IN MEDICINE LA English DT Article ID CORONARY-ARTERY DISEASE; REGRESSION; VARIABILITY AB In many chronic diseases, therapy aims to prevent or reduce the frequency of episodes of a disease manifestation, for example cardiac ischaemic episodes or epileptic seizures. Entry criteria for clinical trials typically include a minimum number of episodes within a baseline period, and regression to the mean should be anticipated. The distribution of the number of episodes at follow-up, the statistical power for treatment comparisons, and the difficulty of recruitment will depend on the entry criterion chosen. A gamma-Poisson mixture model is employed to describe the regression to the mean when the entry criterion and outcome measure are counts of discrete events. Sample size formulae which take account of the entry criterion are derived for comparison of mean number of events at follow-up and the proportion of patients with zero events at follow-up. Application of these formulae to screening data from the Aymptomatic Cardiac Ischemia Pilot (ACIP) Study is presented as an example. C1 NHLBI,BIOSTAT RES BRANCH,BETHESDA,MD 20892. BRIGHAM & WOMENS HOSP,DIV CARDIOVASC,BOSTON,MA 02115. NHLBI,DIV HEART & VASC DIS,BETHESDA,MD 20892. RP MCMAHON, RP (reprint author), MARYLAND MED RES INST,600 WYNDHURST AVE,BALTIMORE,MD 21210, USA. RI McMahon, Robert/C-5462-2009 FU NHLBI NIH HHS [N01-HV-1814] NR 15 TC 12 Z9 12 U1 0 U2 2 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 APR 30 PY 1994 VL 13 IS 8 BP 859 EP 870 DI 10.1002/sim.4780130806 PG 12 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA NL147 UT WOS:A1994NL14700005 PM 8047740 ER PT J AU TASAKI, I BYRNE, PM AF TASAKI, I BYRNE, PM TI TEMPERATURE-CHANGES ASSOCIATED WITH EXCITATION OF THE ELECTRIC ORGAN IN THE AFRICAN ELECTRIC CATFISH SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID NERVE AB By using heat-sensors made from synthetic pyroelectric film, it was shown that excitation of the Malapterurus electric organ brings about first a rapid rise, then a slow fall and finally a very slow rise in the temperature of the organ. Difficulties encountered in determining these rapid temperature changes by the method of employing thermistor probes are pointed out. (C) 1994 Academic Press, Inc. RP TASAKI, I (reprint author), NIMH,CELL BIOL LAB,BETHESDA,MD 20892, USA. NR 10 TC 1 Z9 1 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 APR 29 PY 1994 VL 200 IS 2 BP 704 EP 709 DI 10.1006/bbrc.1994.1507 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA NH738 UT WOS:A1994NH73800005 PM 8179603 ER PT J AU DEOLIVEIRA, AM VISWANATHAN, M HEEMSKERK, FMJ CORREA, FMA SAAVEDRA, JM AF DEOLIVEIRA, AM VISWANATHAN, M HEEMSKERK, FMJ CORREA, FMA SAAVEDRA, JM TI SPECIFIC, NON-ANGIOTENSIN, [I-125] CGP-42112 BINDING-SITES IN RAT SPLEEN MACROPHAGES SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID MONONUCLEAR-CELLS; RECEPTORS; BRAIN; LIVER AB We report the novel expression of a high affinity non-angiotensin II binding site to [I-125]CGP 42112, predominantly localized to the red pulp of the rat spleen and to isolated rat spleen macrophages. Binding is not inhibited by angiotensin II, related peptides or AT(1) or AT(2) receptor ligands, and is not affected by several growth factors and cytokines involved in macrophage function. Thus, CGP 42112 recognizes binding sites other than angiotensin II AT(2) sites in rat macrophages. CGP 42112 and related peptides might influence the regulation of macrophage function. (C) 1994 Academic Press, Inc. C1 NIMH,CLIN SCI LAB,PHARMACOL SECT,BETHESDA,MD 20892. RI Correa, Fernando /D-1614-2012 OI Correa, Fernando /0000-0003-4067-9524 NR 21 TC 15 Z9 15 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 APR 29 PY 1994 VL 200 IS 2 BP 1049 EP 1058 DI 10.1006/bbrc.1994.1556 PG 10 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA NH738 UT WOS:A1994NH73800054 PM 8179581 ER PT J AU LAN, MS KAJIYAMA, W DONADEL, G LU, J NOTKINS, AL AF LAN, MS KAJIYAMA, W DONADEL, G LU, J NOTKINS, AL TI CDNA SEQUENCE AND GENOMIC ORGANIZATION OF MOUSE SECRETIN SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID AMINO-ACID-SEQUENCE; EXPRESSION; CELL; RNA; DNA AB A murine insulinoma library was constructed by subtracting glucagonoma cDNAs from insulinoma cDNAs. Comparison of the nucleotide sequence of one of the clones with sequences from the GenBank database showed that it was a member of the secretin family. The clone, 490 bp long, encodes a protein of 133 amino acids consisting of a signal peptide, a N-terminal peptide, secretin, and a C-terminal peptide, which showed 88% and 80% homology with rat and porcine secretin precursor proteins, respectively. The translated secretin peptide showed a unique Met to Thr substitution at position 5 as compared to the secretins from other species. That the Met to Thr substitution was not tumor-related was demonstrated by the fact that an identical sequence was found in cDNA from normal mouse intestine. Studies on the mouse secretin gene revealed that it contains four exons separated by 81 bp, 110 bp, and 96 bp introns. (C) 1994 Academic Press, Inc. RP NIDR, ORAL MED LAB, BLDG 30, RM 121, BETHESDA, MD 20892 USA. NR 18 TC 12 Z9 14 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X EI 1090-2104 J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD APR 29 PY 1994 VL 200 IS 2 BP 1066 EP 1071 DI 10.1006/bbrc.1994.1558 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA NH738 UT WOS:A1994NH73800056 PM 8179583 ER PT J AU DIETRICH, DR CANDRIAN, R MARSMAN, DS POPP, JA KAUFMANN, WK SWENBERG, JA AF DIETRICH, DR CANDRIAN, R MARSMAN, DS POPP, JA KAUFMANN, WK SWENBERG, JA TI RETROSPECTIVE ASSESSMENT OF LIVER-CELL PROLIFERATION VIA PCNA - A COMPARISON WITH TRITIATED-THYMIDINE SO CANCER LETTERS LA English DT Article DE PCNA; TRITIATED THYMIDINE; CELL PROLIFERATION; LIVER; RETROSPECTIVE ID DNA POLYMERASE-DELTA; NUCLEAR ANTIGEN PCNA; AUXILIARY PROTEIN; CYCLIN PCNA; ENHANCEMENT METHOD; PARAFFIN SECTIONS; S-PHASE; EXPRESSION; TISSUES AB Cell proliferation (S phase response) in archival liver tissues of partially hepatectomized rats was determined via proliferating cell nuclear antigen (PCNA) immunohistochemistry. These results were compared with the S phase response assessed previously in the same tissues via tritiated thymidine (Tdr) autoradiography. The effect of prolonged tissue fixation on PCNA immunohistochemistry was compared in two studies: study A, the liver was fixed for a maximum of 7 days and then embedded in paraffin and stored for similar to 18 months, while in study B, the liver was fixed in formalin for 7 years and then embedded in paraffin and stored for similar to 18 months until sectioning and immunostaining. PCNA immunostaining was successful in the liver sections of both studies, irrespective of the length of formalin fixation. Furthermore, the S phase labeling indices (LI) determined via PCNA and Tdr were comparable, although not identical, in the two studies. Therefore, use of PCNA immunohistochemistry should allow retrospective staining of rodent tissues for the assessment of cell proliferative activity in formalin-fixed organs from previously conducted toxicity and carcinogenicity studies. C1 UNIV ZURICH,CH-8603 SCHWERZENBACH,SWITZERLAND. CHEM IND INST TOXICOL,RES TRIANGLE PK,NC 27709. NIEHS,RES TRIANGLE PK,NC 27709. STERLING WINTHROP,DIV PHARMACEUT RES,COLLEGEVILLE,PA 19426. UNIV N CAROLINA,DEPT PATHOL,CHAPEL HILL,NC 27514. UNIV N CAROLINA,DEPT ENVIRONM SCI & ENGN,CHAPEL HILL,NC 27514. RP DIETRICH, DR (reprint author), ETH ZURICH,INST TOXICOL,SCHORENSTR 16,CH-8603 SCHWERZENBACH,SWITZERLAND. NR 25 TC 14 Z9 14 U1 0 U2 0 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 APR 29 PY 1994 VL 79 IS 1 BP 45 EP 51 DI 10.1016/0304-3835(94)90061-2 PG 7 WC Oncology SC Oncology GA NL808 UT WOS:A1994NL80800007 PM 7910515 ER PT J AU WERNER, H RAUSCHER, FJ SUKHATME, VP DRUMMOND, IA ROBERTS, CT LEROITH, D AF WERNER, H RAUSCHER, FJ SUKHATME, VP DRUMMOND, IA ROBERTS, CT LEROITH, D TI TRANSCRIPTIONAL REPRESSION OF THE INSULIN-LIKE GROWTH-FACTOR-I RECEPTOR (IGF-I-R) GENE BY THE TUMOR-SUPPRESSOR WT1 INVOLVES BINDING TO SEQUENCES BOTH UPSTREAM AND DOWNSTREAM OF THE IGF-I-R GENE-TRANSCRIPTION START SITE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ZINC FINGER PROTEIN; WILMS-TUMOR; PROMOTER REGION; MESSENGER-RNA; EXPRESSION; LOCUS; INITIATOR; CLONING; KIDNEY AB The insulin-like growth factor-I receptor (IGF-I-R) has been implicated in the etiology and/or progression of Wilms' tumor, a pediatric malignancy of the kidney that is often associated with deletion or mutation of the WT1 tumor suppressor gene. The expression of the IGF-I-R gene is increased in Wilms' tumor as compared with normal kidney tissue. Furthermore, the levels of IGF-I-R mRNA in individual tumors have been shown to be inversely correlated to the levels of WT1 mRNA, suggesting that the expression of the IGF-I R gene is under the negative control of WT1. The activity of an IGF-I R promoter/luciferase construct in Chinese hamster ovary cells was reduced by cotransfection of a WT1 expression vector. An analysis of various reporter constructs containing different portions of the IGF-I-R 5'-flanking and 5'-untranslated regions suggested that the effect of WT1 depends on the number of WT1 binding sites present, with sites located both upstream and downstream of the IGF-I-R transcription start site involved in mediating this effect. Using the purified zinc finger domain of WT1 in gel retardation and DNase I footprinting assays, we mapped five sites in the 5'-flanking and six sites in the 5'-untranslated regions that were involved in WT1 binding. In addition, the initiator element of the IGF-I-R gene contains a sequence that binds WT1. Thus, the repression of IGF-I-R promoter activity by the WT1 tumor suppressor gene product involves multiple interactions of its zinc finger domain with WT1 binding sites located both 5' and 3' of the transcription initiation site. C1 WISTER INST ANAT & BIOL,PHILADELPHIA,PA 19104. BETH ISRAEL HOSP,DIV RENAL,BOSTON,MA 02215. HARVARD UNIV,SCH MED,BOSTON,MA 02215. RP WERNER, H (reprint author), NIDDKD,DIABET BRANCH,BLDG 10,ROOM 8S-239,BETHESDA,MD 20892, USA. OI Roberts, Charles/0000-0003-1756-5772 FU NCI NIH HHS [CA 10817, CA 47983, CA 52009] NR 31 TC 140 Z9 143 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 APR 29 PY 1994 VL 269 IS 17 BP 12577 EP 12582 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NH716 UT WOS:A1994NH71600034 PM 8175666 ER PT J AU GAO, WY AGBARIA, R DRISCOLL, JS MITSUYA, H AF GAO, WY AGBARIA, R DRISCOLL, JS MITSUYA, H TI DIVERGENT ANTI-HUMAN-IMMUNODEFICIENCY-VIRUS ACTIVITY AND ANABOLIC PHOSPHORYLATION OF 2',3'-DIDEOXYNUCLEOSIDE ANALOGS IN RESTING AND ACTIVATED HUMAN-CELLS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN THYMIDINE KINASE-1; REVERSE-TRANSCRIPTASE; REPLICATION; TYPE-1; DNA; (-)-2'-DEOXY-3'-THIACYTIDINE; 3'-AZIDO-3'-DEOXYTHYMIDINE; 2',3'-DIDEOXYADENOSINE; 2',3'-DIDEOXYINOSINE; DIDEOXYNUCLEOSIDES AB The mechanism of divergent anti-human immunodeficiency virus type I (HIV-I) activity of various 2',3'-dideoxynucleoside analogs (ddNs) in peripheral blood mononuclear cells (PBM) was studied. We demonstrate that the in vitro anti-EW-l activity of various ddNs varies profoundly and that the divergent antiviral activity is related to the extent of anabolic phosphorylation of each ddN and its counterpart 2' deoxynucleoside (dN). We also show that certain ddNs cause a reduction of their counterpart dNTP formation in PBM in the following order: 2',3'-dideoxycytidine (ddC) >> 2',3'-didehydro-2',3'-dideoxythymidine (d4T), 3'-thia-2',3'-dideoxycytidine (3TC), 2'3'-dideoxyinosine (ddI), 2',3'-dideoxyguanosine (ddG) > 3'-azido-2',3'-dideoxythymidine (AZT) > 2'-beta-fluoro-2',3'-dideoxyadenosine (F-ara-ddA). Based on the phosphorylation profiles, anti-HIV-1 ddNs can be classified into two groups: (i) cell-activation-dependent ddNs such as AZT and d4T that are preferentially phosphorylated, yield higher ratios of ddNTP/dNTP, and exert more potent anti-HIV-1 activity in activated cells than in resting cells; and (ii) cell-activation-independent ddNs including ddI (and 2',3'-dideoxyadenosine), F-ara-ddA, ddG, ddC, and 3TC that produce higher ratios of ddNTP/dNTP and exert more potent anti-HIV-1 activity in resting cells. These data should provide a basis for the elucidation of the mechanism of the divergent antiretroviral activity of ddNs. C1 NCI,MED BRANCH,EXPTL RETROVIROL SECT,BETHESDA,MD 20892. NCI,MED CHEM LAB,BETHESDA,MD 20892. NR 31 TC 210 Z9 211 U1 1 U2 3 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 APR 29 PY 1994 VL 269 IS 17 BP 12633 EP 12638 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NH716 UT WOS:A1994NH71600043 PM 8175673 ER PT J AU PORRAS, A MUSZYNSKI, K RAPP, UR SANTOS, E AF PORRAS, A MUSZYNSKI, K RAPP, UR SANTOS, E TI DISSOCIATION BETWEEN ACTIVATION OF RAF-1 KINASE AND THE 42-KDA MITOGEN-ACTIVATED PROTEIN-KINASE 90-KDA-S6 KINASE (MAPK/RSK) CASCADE IN THE INSULIN/RAS PATHWAY OF ADIPOCYTIC DIFFERENTIATION OF 3T3-L1 CELLS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MAP KINASE; SIGNAL TRANSDUCTION; XENOPUS OOCYTES; RAS; SERINE; PHOSPHORYLATION; EXPRESSION; STIMULATION; P21RAS; RECEPTOR AB Insulin treatment of untransfected 3T3 L1 cells quickly induced activation of a cytosolic 42-kDa mitogen-activated protein kinase (MAPK) and a 90-kDa S6 kinase (RSK). The activation of these cytosolic kinases was also mimicked by Res expression (in the absence of insulin) in the same cells transfected with inducible ras oncogenes. Furthermore, insulin-induced activation of MAPK and RSK could be blocked by expression of a transfected inducible dominant negative Ras mutant (Asn-17). These results indicate that Ras proteins are obligatory intermediates in the activation of the cytosolic MAPK/RSK cascade by insulin. Insulin treatment of 3T3 L1 cells or expression of transfected res oncogenes resulted also in hyperphosphorylation of cellular Raf-l. Insulin-induced Raf hyperphosphorylation was inhibited by expression of an inducible dominant negative Res mutant (Asn-17). We also showed that expression of transfected raf oncogenes induces adipocytic differentiation, as detected by expression of the specific adipocytic marker aP2. In addition, insulin-induced differentiation was significantly blocked by expression of a dominant negative raf mutant. Interestingly, however, the expression of transfected raf oncogenes did not induce MAPK or RSK activation, and the insulin-induced activation of these kinases was not blocked by expression of transfected dominant negative raf mutants. These results are consistent with Raf kinases acting downstream of Ras, but not upstream of MAPK and RSK in insulin-signaling pathways leading to 3T3 L1 differentiation. C1 NCI,MOLEC & CELLULAR BIOL LAB,BETHESDA,MD 20892. NCI,FREDERICK CANC RES & DEV CTR,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21701. RI Porras, Almudena/N-2121-2015 OI Porras, Almudena/0000-0002-6495-3308 NR 59 TC 78 Z9 78 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 APR 29 PY 1994 VL 269 IS 17 BP 12741 EP 12748 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NH716 UT WOS:A1994NH71600058 PM 8175686 ER PT J AU MEERZAMAN, D CHARLES, P DASKAL, E POLYMEROPOULOS, MH MARTIN, BM ROSE, MC AF MEERZAMAN, D CHARLES, P DASKAL, E POLYMEROPOULOS, MH MARTIN, BM ROSE, MC TI CLONING AND ANALYSIS OF CDNA-ENCODING A MAJOR AIRWAY GLYCOPROTEIN, HUMAN TRACHEOBRONCHIAL MUCIN (MUC5) SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article AB Two unique nucleotide probes for human tracheobronchial mucin glycoprotein (TBM) were generated via polymerase chain reaction with degenerate primers deduced from the TBM:TR-3A tryptic peptide sequence and were used to isolate a 3.6 kilobase cDNA, clone NP3a, from a human nasal polyp cDNA library. Clone NP3a was localized to chromosome 11 and contained a 3168 nucleotide open reading frame which encoded three TBM peptide fragments, thus confirming that clone NP3a partially encodes TBM. TBM also contains five tandem repeats of TTVGP/S and an octapeptide GQCGTCTN, which is conserved in human intestinal mucin MUC2 and rat intestinal mucin-like protein (MLP) suggesting that this sequence has a functional significance for secreted mucins. TBM has amino acid similarity to the cysteine-rich domains at the carboxyl termini of MUC2, rat MLP, bovine and porcine submaxillary mucins, and human von Willebrand factor. Strikingly, a large percentage of the cysteine residues in the overlaps are highly conserved: 90% in MUC2 and von Willebrand factor, 80% in bovine submaxillary mucin, 70% in porcine submaxillary mucin, and 64% in rat MLP, suggesting that conserved cysteines may be important for the tertiary structure of secreted glycoproteins. These studies demonstrate that clone NP3a is a candidate for MUC5, making it the only human mucin gene reported to date whose gene product has been isolated from airway secretions. C1 GEORGE WASHINGTON UNIV, CHILDRENS NATL MED CTR, CHILDRENS RES INST, CTR MOLEC MECHANISMS DIS, WASHINGTON, DC 20010 USA. GEORGE WASHINGTON UNIV, DEPT PEDIAT, WASHINGTON, DC 20010 USA. GEORGE WASHINGTON UNIV, DEPT BIOCHEM & MOLEC BIOL, WASHINGTON, DC 20010 USA. ST ELIZABETH HOSP, NIMH, CTR NEUROSCI, BIOCHIM GENET LAB, WASHINGTON, DC 20032 USA. NIMH, CLIN NEUROSCI BRANCH, BETHESDA, MD 20892 USA. NR 53 TC 148 Z9 150 U1 0 U2 1 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 APR 29 PY 1994 VL 269 IS 17 BP 12932 EP 12939 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NH716 UT WOS:A1994NH71600085 ER PT J AU SHI, HP TENG, CT AF SHI, HP TENG, CT TI CHARACTERIZATION OF A MITOGEN-RESPONSE UNIT IN THE MOUSE LACTOFERRIN GENE PROMOTER SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID EPIDERMAL GROWTH-FACTOR; TRANSCRIPTION FACTOR; LACTOTRANSFERRIN GENE; ESTROGEN-RECEPTOR; REGULATORY REGION; BINDING; TRANSFERRIN; EXPRESSION; PROTEIN; CELLS AB Lactoferrin is present in a variety of tissues and biological fluids; however, the amount differs significantly due to differential expressions. We have previously demonstrated that the mouse lactoferrin gene is regulated by estrogen through an estrogen-response DNA element located at -349, upstream from the transcription start site (+1). In this report, we characterized by deletion and mutation analyses a cluster of mitogen-response elements located between -80 and -40 of the mouse lactoferrin promoter. We demonstrated that the chimeric chloramphenicol acetyltransferase reporter constructs (the -103 to +1 sequence of the mouse lactoferrin gene) containing the mitogen-response unit of the lactoferrin gene were stimulated by cAMP, forskolin, 12-O-tetradecanoylphorbol-13-acetate, and epidermal growth factor/recombinant transforming growth factor-alpha (EGF/TGF-alpha) in a time- and dose-dependent manner. The sequence at position -52 to -40 (mLF-CRE) of the gene conferred transcriptional activation in the presence of forskolin, cyclic AMP, and 12-O-tetradecanoylphorbol-13-acetate in transiently transfected human endometrium carcinoma RL95-2 cells, whereas the region at -80 to -60 responded to EGF/TGF-alpha stimulation. Overexpression of the catalytic unit of protein kinase C or protein kinase A in the RL95-2 cells elevated the chloramphenicol acetyltransferase activity of the reporter construct 5-6-fold. The mobility shift assay suggested that AP1 and CREB or related proteins participated in complex formation with the mLF-CRE, whereas different proteins bound to the EGF/TGF-alpha-response element. C1 NIEHS,REPROD & DEV TOXICOL LAB,RES TRIANGLE PK,NC 27709. NR 55 TC 29 Z9 29 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 APR 29 PY 1994 VL 269 IS 17 BP 12973 EP 12980 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NH716 UT WOS:A1994NH71600091 PM 8175715 ER PT J AU WANG, SM MILNE, GWA NICKLAUS, MC MARQUEZ, VE LEE, J BLUMBERG, PM AF WANG, SM MILNE, GWA NICKLAUS, MC MARQUEZ, VE LEE, J BLUMBERG, PM TI PROTEIN-KINASE-C - MODELING OF THE BINDING-SITE AND PREDICTION OF BINDING CONSTANTS SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID MOLECULAR-FIELD ANALYSIS; TUMOR PROMOTERS; PHORBOL ESTERS; SEMIEMPIRICAL METHODS; STRUCTURAL BASIS; 2ND MESSENGERS; DIACYLGLYCEROL; RECEPTOR; ACTIVATION; ANALOGS AB A detailed examination of the mode of binding of phorbol esters to protein kinase C led to a model of the phorbol binding site in the enzyme. The efficacy with which various synthetic diacylglycerol analogs and ribonolactones are able to bind to this site was determined by means of semiempirical quantum mechanical calculations using PM3, and an estimate of the binding energy was made: in each case. Sixteen synthetic analogs of 1,2-diacylglycerol and two natural products were studied, and their calculated energies of binding to this model were correlated with the measured K-i values. The binding energies calculated for this receptor model, together with solubility and entropy considerations, allow prediction through regressive fit of free energies of binding which correlate very well with the measured binding constants. C1 NCI,DIV CANC TREATMENT,MED CHEM LAB,BETHESDA,MD 20892. NCI,DIV CANC ETIOL,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BETHESDA,MD 20892. RI Wang, Shaomeng/E-9686-2010; Nicklaus, Marc/N-4183-2014 NR 48 TC 27 Z9 28 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD APR 29 PY 1994 VL 37 IS 9 BP 1326 EP 1338 DI 10.1021/jm00035a013 PG 13 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA NJ887 UT WOS:A1994NJ88700013 PM 8176711 ER PT J AU URABE, K AROCA, P TSUKAMOTO, K MASCAGNA, D PALUMBO, A PROTA, G HEARING, VJ AF URABE, K AROCA, P TSUKAMOTO, K MASCAGNA, D PALUMBO, A PROTA, G HEARING, VJ TI THE INHERENT CYTOTOXICITY OF MELANIN PRECURSORS - A REVISION SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH LA English DT Article DE PIGMENTATION; MELANIN; MELANOGENESIS; CYTOTOXICITY ID MAMMALIAN MELANOGENESIS; DOPACHROME TAUTOMERASE; TUMOR-CELLS; TOXICITY; BIOSYNTHESIS; TYROSINASE; 5,6-DIHYDROXYINDOLE; MECHANISM; SURVIVAL; GROWTH AB The potential cytotoxicity of the melanogenic intermediates DOPA, (L-3,4-dihydroxyphenylalanine) and DHI (5,6-dihydroxyindole) has long been recognized and exploited as a targeting concept in experimental melanoma therapy. In recent years, however, a novel branchpoint in the melanin biosynthetic pathway has been shown to divert the metabolism of DOP-Achrome to a carboxylated derivative termed DHICA (DHI-2-carboxylic acid) rather than to DHI. In order to evaluate the biological implications of this regulatory control, we have reexamined the inherent cytotoxicity of DHICA versus DHI on different cell lines. We found that under the usual conditions of the biological assay, the apparent cytotoxicity of the two indoles reflect their instability in the culture medium, the less stable DHI being generally more toxic than DHICA to melanoma cells and nonmelanocytic cells. Moreover, the observed cytotoxic effects increased with the time of incubation and were markedly reduced by the addition of catalase to the medium, suggesting that they were probably due to the generation of reactive oxygen species (particularly H2O2) during the autoxidation of the melanin precursors outside the cells. To circumvent this problem, we then tested the diacetylated derivatives of DHI and DHICA (DAI and DAICA) which are sufficiently stable until taken up into the cells whereupon they may be converted by endogenous esterases back to the parent indoles. Although DAI proved to be cytotoxic for nonmelanocytic cells, it had no detectable activity on melanoma cells, whereas DAICA showed no effect on any of the cells examined. These results, when combined with other studies, point to a reconsideration of the inherent cytotoxicity of the 5,6-dihydroxyindoles, as well as DOPA, to melanin producing cells. C1 NCI, CELL BIOL LAB, BETHESDA, MD 20892 USA. YAMANASHI MED COLL, DEPT DERMATOL, YAMANASHI 40938, JAPAN. UNIV NAPLES, DEPT ORGAN CHEM, NAPLES, ITALY. Staz Zool Anton Dohrn, DEPT BIOCHEM, I-80121 NAPLES, ITALY. NR 33 TC 105 Z9 109 U1 0 U2 8 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 APR 28 PY 1994 VL 1221 IS 3 BP 272 EP 278 DI 10.1016/0167-4889(94)90250-X PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA NJ518 UT WOS:A1994NJ51800008 PM 8167148 ER PT J AU BROWN, KE HIBBS, JR GALLINELLA, G ANDERSON, SM LEHMAN, ED MCCARTHY, P YOUNG, NS AF BROWN, KE HIBBS, JR GALLINELLA, G ANDERSON, SM LEHMAN, ED MCCARTHY, P YOUNG, NS TI RESISTANCE TO PARVOVIRUS B19 INFECTION DUE TO LACK OF VIRUS RECEPTOR (ERYTHROCYTE P-ANTIGEN) SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID MONOCLONAL-ANTIBODIES; INVITRO; DISEASE; ANEMIA; CELLS; SERUM; LIVER AB Background. The presence of aspecific cellular receptor is thought to be necessary for susceptibility to viral infection. The erythrocyte P antigen is the cellular receptor for parvovirus B19. We hypothesized that the rare persons with the p phenotype, whose erythrocytes do not have this receptor, would be naturally resistant to B19 infection, which causes erythema infectiosum. Methods. Blood samples were collected from two populations in cross-sectional studies. We determined the P antigen phenotype of the red cells and tested plasma for anti-B19-specific antibodies. Bone marrow from donors of known P antigen phenotype was inoculated with parvovirus B19. Infectivity was measured by assays of erythroid progenitor cells, dot blot analysis, and in situ hybridization for B19 DNA, and an immunofluorescence assay for viral-capsid proteins. Results. Of the 17 subjects with the p red-cell phenotype, who did not have P antigen on their erythrocytes, none (0 of 11 and 0 of 6) had serologic evidence of previous parvovirus B19 infection. In contrast, the seropositivity rates in the two control groups were 71 percent (53 of 75, P<0.001) and 47 percent (32 of 68, P = 0.03). In vitro, bone marrow from donors with the p phenotype maintained normal erythropoiesis despite very high concentrations of virus, with no evidence of infection of erythroid progenitor cells by parvovirus B19. Conclusions. People who do not have P antigen, which is the cellular receptor for parvovirus B19, are naturally resistant to infection with this pathogen. C1 MT EATON CLIN,MT EATON,OH. AMER RED CROSS,CLEVELAND,OH. RP BROWN, KE (reprint author), NHLBI,HEMATOL BRANCH,BLDG 10,RM 7C218,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 29 TC 184 Z9 196 U1 1 U2 5 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 APR 28 PY 1994 VL 330 IS 17 BP 1192 EP 1196 DI 10.1056/NEJM199404283301704 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA NG586 UT WOS:A1994NG58600004 PM 8139629 ER PT J AU SORLIE, P BACKLUND, E JOHNSON, NJ AF SORLIE, P BACKLUND, E JOHNSON, NJ TI MORTALITY AMONG HISPANICS - REPLY SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter RP SORLIE, P (reprint author), NIH,BETHESDA,MD, USA. NR 1 TC 2 Z9 2 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 APR 27 PY 1994 VL 271 IS 16 BP 1238 EP 1239 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA NG362 UT WOS:A1994NG36200017 ER PT J AU FRADKIN, JE GORDEN, P AF FRADKIN, JE GORDEN, P TI DEVELOPING THE CLINICAL-APPLICATION OF GENETIC DIAGNOSIS - THE ROLE OF NIDDK SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter ID FIBROSIS RP FRADKIN, JE (reprint author), NIDDK,BETHESDA,MD, USA. NR 5 TC 0 Z9 0 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 APR 27 PY 1994 VL 271 IS 16 BP 1240 EP 1240 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA NG362 UT WOS:A1994NG36200020 PM 8151899 ER PT J AU KAWAKAMI, Y ELIYAHU, S DELGADO, CH ROBBINS, PF RIVOLTINI, L TOPALIAN, SL MIKI, T ROSENBERG, SA AF KAWAKAMI, Y ELIYAHU, S DELGADO, CH ROBBINS, PF RIVOLTINI, L TOPALIAN, SL MIKI, T ROSENBERG, SA TI CLONING OF THE GENE CODING FOR A SHARED HUMAN-MELANOMA ANTIGEN RECOGNIZED BY AUTOLOGOUS T-CELLS INFILTRATING INTO TUMOR SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE TUMOR ANTIGEN; IMMUNOTHERAPY; HLA A2; MELANOCYTE; MART-1 ID CYTOLYTIC LYMPHOCYTES-T; METASTATIC MELANOMA; MALIGNANT-MELANOMA; CDNA CLONING; IDENTIFICATION; IMMUNOTHERAPY; RESTRICTION; IMMUNOSELECTION; INTERLEUKIN-2; EXPRESSION AB By cDNA expression cloning we have isolated a gene encoding a shared human melanoma antigen recognized by HLA-A2 restricted autologous and allogeneic tumor-infiltrating lymphocytes (TILs) from patients with metastatic melanoma. By using both transient and stable expression systems, transfection of this gene into non-antigen-expressing HLA-A2(+) cell lines resulted in recognition by the antigen-specific TILs. The sequence of this cDNA revealed a previously undescribed putative transmembrane protein whose expression was restricted to melanoma and melanocyte cell lines and human retina but no other fresh or cultured normal tissues tested or other tumor histologies. Thus, we have identified a gene encoding a melanocyte lineage-specific protein (MART-1; melanoma antigen recognized by T cells 1) that is a widely shared melanoma antigen recognized by the T lymphocytes of patients with established malignancy. Identification of this gene opens possibilities for the development of immunotherapies for patients with melanoma. C1 NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. RP KAWAKAMI, Y (reprint author), NCI,SURG BRANCH,BLDG 10,BETHESDA,MD 20892, USA. RI Kawakami, Yutaka /E-7429-2013; OI Kawakami, Yutaka /0000-0003-4836-2855; Rivoltini, Licia/0000-0002-2409-6225 NR 37 TC 922 Z9 929 U1 3 U2 11 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 APR 26 PY 1994 VL 91 IS 9 BP 3515 EP 3519 DI 10.1073/pnas.91.9.3515 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NJ034 UT WOS:A1994NJ03400009 PM 8170938 ER PT J AU KOKUBO, T YAMASHITA, S HORIKOSHI, M ROEDER, RG NAKATANI, Y AF KOKUBO, T YAMASHITA, S HORIKOSHI, M ROEDER, RG NAKATANI, Y TI INTERACTION BETWEEN THE N-TERMINAL DOMAIN OF THE 230-KDA SUBUNIT AND THE TATA BOX-BINDING SUBUNIT OF TFIID NEGATIVELY REGULATES TATA-BOX BINDING SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID PROTEIN; GENE; IDENTIFICATION; TRANSCRIPTION; COACTIVATORS; PROMOTER; MUTANTS; CCG1 AB Transcription initiation factor TFIID plays a central role in transcriptional regulation. Drosophila TFIID is a multimeric protein consisting of the TATA box-binding polypeptide (TBP) and a number of tightly associated polypeptides. Previously, the largest submit of TFIID (p230) was cloned and demonstrated to inhibit the TATA-box binding of TBP in the absence of other subunits. Here we demonstrate that p230 contains at least two sites of interaction with TBP and that the N-terminal site mediates both strong physical interactions with TBP and inhibition of the TBP function. A detailed mutagenesis study shows that the inhibitory domain is indistinguishable from the strong TBP-binding domain, thus indicating that interaction of the p230 N-terminal region with TBP may directly control TATA-box binding. C1 NICHHD,BETHESDA,MD 20892. NINCDS,BETHESDA,MD 20892. ROCKEFELLER UNIV,BIOCHEM & MOLEC BIOL LAB,NEW YORK,NY 10021. UNIV TOKYO,INST MOLEC & CELLULAR BIOSCI,BUNKYO KU,TOKYO 113,JAPAN. FU NCI NIH HHS [CA42567]; NIAID NIH HHS [AI27397]; NIGMS NIH HHS [GM45258] NR 26 TC 66 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 APR 26 PY 1994 VL 91 IS 9 BP 3520 EP 3524 DI 10.1073/pnas.91.9.3520 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NJ034 UT WOS:A1994NJ03400010 PM 8170939 ER PT J AU SMYTHE, JA SUN, D THOMSON, M MARKHAM, PD REITZ, MS GALLO, RC LISZIEWICZ, J AF SMYTHE, JA SUN, D THOMSON, M MARKHAM, PD REITZ, MS GALLO, RC LISZIEWICZ, J TI A REV-INDUCIBLE MUTANT GAG GENE STABLY TRANSFERRED INTO T-LYMPHOCYTES - AN APPROACH TO GENE-THERAPY AGAINST HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 INFECTION SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE SIMIAN IMMUNODEFICIENCY VIRUS; RETROVIRUS INHIBITION; GAG POLYPEPTIDE ID TRANS-ACTIVATOR GENE; HTLV-III; EXPRESSION REQUIRES; TARGET SEQUENCE; HIV-1; RNA; REPLICATION; PROTEIN; BINDING; RETROVIRUS AB One strategy for somatic gene therapy for human immunodeficiency virus type 1 (HIV-1) infection is based on the regulated expression of dominant negative mutants of the HIV-1 gag gene. To limit expression of the mutant Gag polypeptide to HIV-1-infected cells, we have constructed a replication-defective retroviral vector that contains a Rev-responsive element. By using this construct we have obviated problems that can be associated with constitutive expression of an exogenous gene, an important step toward developing a human therapy. In uncloned T lymphocytes infected (transduced) with this retroviral construct, HIV-1 replication was inhibited by 94% with a concomitant decrease in the cytopathic effects of the virus. In addition, simian immunodeficiency virus (SIV) replication was also shown to be significantly inhibited, suggesting that this mutant Gag protein may have antiviral efficacy against a broad range of primate lentiviruses and that an SIV/macaque model can be used for further in vivo studies. These results have important implications in assessing the potential of somatic gene therapy in the treatment of HIV-1 infection. C1 NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. ADV BIOSCI LABS INC,KENSINGTON,MD 20895. NR 35 TC 36 Z9 36 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 APR 26 PY 1994 VL 91 IS 9 BP 3657 EP 3661 DI 10.1073/pnas.91.9.3657 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NJ034 UT WOS:A1994NJ03400039 PM 8170964 ER PT J AU WISEMAN, RW COCHRAN, C DIETRICH, W LANDER, ES SODERKVIST, P AF WISEMAN, RW COCHRAN, C DIETRICH, W LANDER, ES SODERKVIST, P TI ALLELOTYPING OF BUTADIENE-INDUCED LUNG AND MAMMARY ADENOCARCINOMAS OF B6C3F1 MICE - FREQUENT LOSSES OF HETEROZYGOSITY IN REGIONS HOMOLOGOUS TO HUMAN TUMOR-SUPPRESSOR GENES SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE ALLELE LOSS; RESTRICTION FRAGMENT LENGTH POLYMORPHISM; MICROSATELLITE DNA; SIMPLE SEQUENCE LENGTH POLYMORPHISM ID PRIMARY BREAST-CANCER; LENGTH POLYMORPHISMS; TRANSGENIC MICE; HUMAN NEOPLASIA; OVARIAN-CANCER; P53 MUTATIONS; MOUSE; PROGRESSION; LOCUS; CARCINOGENESIS AB To identify the potential involvement of tumor-suppressor gene inactivation during neoplastic development in B6C3F1 mice, genetic losses were determined from allelotypes of butadiene-induced lung and mammary adenocarcinomas. By using length polymorphisms in restriction fragments and simple sequence repeats, or ''microsatellites,'' markers on each autosome were analyzed for allele losses in tumor DNAs. Losses of heterozygosity on chromosome 11 were observed at several loci surrounding the p53 tumor-suppressor gene (Trp53) in 12 of 17 mammary tumors and 2 of 8 lung tumors. Although most of these alterations appeared to result from nondisjunction, at least two examples of somatic recombination or deletion were also observed. Southern analysis revealed a homozygous deletion of the remaining Trp53 allele of one of these mammary tumors. Losses of heterozygosity were also detected at the Rb-1 tumor-suppressor gene in 7 of 17 mammary tumors and 1 lung tumor, Finally, frequent allele losses were observed on chromosome 4 in lung tumors. Analysis of nine chromosome 4 loci defined an interstitial deletion containing the Ifa gene cluster in one of the lung tumors. A tumor-suppressor gene was previously mapped to this region of chromosome 4 in studies with somatic cell hybrids. In addition, homozygous deletions hare been reported in a homologous region of human chromosome 9p for acute lymphocytic leukemias, glioblastomas, melanomas, and lung carcinomas. These findings suggest that the inactivation of tumor-suppressor genes including Trp53, Rb-1, and an unidentified gene on chromosome 4 plays a significant role during carcinogenesis in mice. C1 MIT,CTR GENOME RES,WHITEHEAD INST BIOMED RES,CAMBRIDGE,MA 02139. MIT,DEPT BIOL,CAMBRIDGE,MA 02139. RP WISEMAN, RW (reprint author), NIEHS,MOLEC CARCINOGENESIS LAB,RES TRIANGLE PK,NC 27709, USA. FU NHGRI NIH HHS [R01 HG00126, P50 HG00098] NR 55 TC 80 Z9 82 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 APR 26 PY 1994 VL 91 IS 9 BP 3759 EP 3763 DI 10.1073/pnas.91.9.3759 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NJ034 UT WOS:A1994NJ03400060 PM 8170984 ER PT J AU ROSALES, R SUTTER, G MOSS, B AF ROSALES, R SUTTER, G MOSS, B TI A CELLULAR FACTOR IS REQUIRED FOR TRANSCRIPTION OF VACCINIA VIRAL INTERMEDIATE-STAGE GENES SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID DEPENDENT RNA-POLYMERASE; VIRUS EARLY GENES; CAPPING ENZYME; MUTATIONAL ANALYSIS; DNA-REPLICATION; KAPPA-B; PURIFICATION; VIRIONS; PROMOTERS; CELLS AB The cytoplasmic location of vaccinia virus replication and evidence that the multisubunit DNA-dependent RNA polymerase, early and late stage transcription factors, capping and methylating enzymes, and poly(A) polymerase are virus encoded raised the possibility that all of the proteins needed for viral mRNA synthesis are of viral origin. Previous studies showed that four components from infected cells, the viral RNA polymerase and capping enzyme and two factors called vaccinia virus intermediate transcription factors (VITFs) 1 and 2, can reconstitute transcription of vaccinia virus intermediate-stage genes in vitro. Here, we demonstrate that VITF-2 can be isolated from the nuclei of uninfected HeLa cells as well as from the cytoplasm of infected cells. The proteins with VITF-2 activity from uninfected and infected cells cochromatographed and cosedimented, suggesting that they are identical. VITF-2 activity was found in extracts of other uninfected human and monkey cells but not in nonpermissive Trichoplusia ni insect cells or in conditionally permissive rabbit kidney 13 cells. VITF-2 activity was present, however, in a permissive line of rabbit kidney 13 cells that had been stably transfected with the vaccinia virus KIL host range gene. We suggest that the VITF-2 level acts as a gauge of the permissive state of the cell and thereby regulates the length of the early prereplicative phase of the infection. C1 NIAID,VIRAL DIS LAB,BETHESDA,MD 20892. NR 48 TC 64 Z9 64 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 APR 26 PY 1994 VL 91 IS 9 BP 3794 EP 3798 DI 10.1073/pnas.91.9.3794 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NJ034 UT WOS:A1994NJ03400067 PM 8170989 ER PT J AU BARBAS, CF HU, D DUNLOP, N SAWYER, L CABABA, D HENDRY, RM NARA, PL BURTON, DR AF BARBAS, CF HU, D DUNLOP, N SAWYER, L CABABA, D HENDRY, RM NARA, PL BURTON, DR TI IN-VITRO EVOLUTION OF A NEUTRALIZING HUMAN-ANTIBODY TO HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 TO ENHANCE AFFINITY AND BROADEN STRAIN CROSS-REACTIVITY SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE PASSIVE IMMUNIZATION; VIRAL NEUTRALIZATION; PHAGE DISPLAY; COMBINATORIAL LIBRARIES; COMPLEMENTARITY-DETERMINING REGIONS ID HUMAN MONOCLONAL-ANTIBODY; SOLUBLE CD4; GP120; INFECTION; PREVENTION; IMMUNIZATION; CHIMPANZEES; RETROVIRUS; LIBRARIES; RECEPTOR AB A method is described that allows for the improvement of antibody affinity. This method, termed complementary-determining region (CDR) walking, does not require structural information on either antibody or antigen. Complementary-determining regions are targeted for random mutagenesis followed by selection for fitness, in this case increased binding affinity, by the phage-display approach. The current study targets a human CD4-binding-site anti-gp120 antibody that is potently and broadly neutralizing. Evolution of affinity of this antibody demonstrates in this case that affinity can be increased while reactivity to variants of human immunodeficiency virus type 1 is broadened. The neutralizing ability of this antibody is improved, as assayed with laboratory and primary clinical isolates of human inmunodeficiency virus type 1. The ability to produce human antibodies of exceptional affinity and broad neutralizing ability has implications for the therapeutic and prophylactic application of antibodies for human immunodeficiency virus type 1 infection. C1 SCRIPPS RES INST, DEPT IMMUNOL, LA JOLLA, CA 92037 USA. NCI, FREDERICK CANC RES & DEV CTR, VIRUS BIOL SECT, TUMOR CELL BIOL LAB, FREDERICK, MD 21702 USA. CALIF DEPT HLTH SERV, VIRAL & RICKETTSIAL DIS LAB, BERKELEY, CA 94704 USA. RP BARBAS, CF (reprint author), SCRIPPS RES INST, DEPT MOLEC BIOL, 10666 N TORREY PINES RD, LA JOLLA, CA 92037 USA. FU NIAID NIH HHS [AI33292] NR 40 TC 195 Z9 198 U1 1 U2 4 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 APR 26 PY 1994 VL 91 IS 9 BP 3809 EP 3813 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NJ034 UT WOS:A1994NJ03400070 PM 8170992 ER PT J AU LUSSO, P SECCHIERO, P CROWLEY, RW GARZINODEMO, A BERNEMAN, ZN GALLO, RC AF LUSSO, P SECCHIERO, P CROWLEY, RW GARZINODEMO, A BERNEMAN, ZN GALLO, RC TI CD4 IS A CRITICAL COMPONENT OF THE RECEPTOR FOR HUMAN HERPESVIRUS-7 - INTERFERENCE WITH HUMAN-IMMUNODEFICIENCY-VIRUS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID MARROW TRANSPLANTATION; INFECTION; PREVALENCE; RETROVIRUS; ANTIBODY; ANTIGEN; HBLV; AIDS AB In this study, we demonstrate that the glycoprotein CD4, a member of the immunoglobulin superfamily, is a critical component of the receptor for human herpesvirus 7 (HHV-7), a recently discovered T-lymphotropic human herpesvirus. A selective and progressive downregulation of the surface membrane expression of CD4 was observed in human CD4(+) T cells in the course of HHV-7 infection. Various murine monoclonal antibodies to CD4 and the recombinant soluble form of human CD4 caused a dose-dependent inhibition of HHV-7 infection in primary CD4(+) T lymphocytes. Moreover, radiolabeled HHV-7 specifically bound to cervical carcinoma cells (HeLa) expressing human CD4. A marked reciprocal interference was observed between HHV-7 and human immunodeficiency virus (HIV), the retrovirus that causes the acquired immunodeficiency syndrome and also uses CD4 as a receptor. Previous exposure of CD4(+) T cells to HHV-7 dra matically interfered with infection by both primary and in vitro-passaged HIV-1 isolates. Reciprocally, persistent infection with HIV-1 or treatment with the soluble form of gp120, the CD4-binding envelope glycoprotein of HIV-1, rendered CD4(+) T cells resistant to HHV-7 infection. These data indicate that CD4 is critically involved in the receptor mechanism for HHV-7. The antagonistic effect between HHV-7 and HIV could be exploited to devise therapeutic approaches to AIDS. RP LUSSO, P (reprint author), NCI,TUMOR CELL BIOL LAB,BLDG 37,ROOM 6A09,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI secchiero, paola/G-9689-2015 OI secchiero, paola/0000-0003-4101-7987 NR 20 TC 159 Z9 170 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 APR 26 PY 1994 VL 91 IS 9 BP 3872 EP 3876 DI 10.1073/pnas.91.9.3872 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NJ034 UT WOS:A1994NJ03400083 PM 7909607 ER PT J AU DAMATO, RJ LIN, CM FLYNN, E FOLKMAN, J HAMEL, E AF DAMATO, RJ LIN, CM FLYNN, E FOLKMAN, J HAMEL, E TI 2-METHOXYESTRADIOL, AN ENDOGENOUS MAMMALIAN METABOLITE, INHIBITS TUBULIN POLYMERIZATION BY INTERACTING AT THE COLCHICINE SITE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE ANGIOGENESIS INHIBITION; GLUTAMATE; DIETHYLSTILBESTROL; COMBRETASTATIN A-4; 17-ETHYNYLESTRADIOL ID MICROTUBULE-ASSOCIATED PROTEINS; BINDING; INVITRO; DIETHYLSTILBESTROL; SEPARATION; MECHANISM; ANALOGS; CELLS; BRAIN AB A metabolite of estradiol, 2-methoxyestradiol (2ME), inhibits angiogenesis in the chicken embryo chorioallantoic membrane assay. Since 2ME causes mitotic perturbations, we examined its interactions with tubulin. In our standard 1.0 M glutamate system (plus 1.0 mM MgCl2 at 37 degrees C), superstoichiometric concentrations (relative to tubulin) of 2ME inhibited the nucleation and propagation phases of tubulin assembly but did not affect the reaction extent. Although polymer formed in the presence of 2ME was more cold-stable than control polymer, morphology was little changed. Under suboptimal reaction conditions (0.8 M glutamate/no MgCl2 at 26 degrees C), substoichiometric 2ME totally inhibited polymerization. No other estrogenic compound was as effective as 2ME as an inhibitor of polymerization or of the binding of colchicine to tubulin. Inhibition of colchicine binding was competitive (K-i, 22 mu M). Thus, a mammalian metabolite of estradiol binds to the colchicine site of tubulin and, depending on reaction conditions, either inhibits assembly or seems to be incorporated into a polymer with altered stability properties. C1 NCI,DIV CANC TREATMENT,MOLEC PHARMACOL LAB,DEV THERAPEUT PROGRAM,BETHESDA,MD 20892. RP DAMATO, RJ (reprint author), HARVARD UNIV,CHILDRENS HOSP,SCH MED,DEPT SURG RES,BOSTON,MA 02115, USA. NR 29 TC 341 Z9 345 U1 0 U2 4 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 APR 26 PY 1994 VL 91 IS 9 BP 3964 EP 3968 DI 10.1073/pnas.91.9.3964 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NJ034 UT WOS:A1994NJ03400102 PM 8171020 ER PT J AU ANAGNOSTOU, A LIU, ZY STEINER, M CHIN, K LEE, ES KESSIMIAN, N NOGUCHI, CT AF ANAGNOSTOU, A LIU, ZY STEINER, M CHIN, K LEE, ES KESSIMIAN, N NOGUCHI, CT TI ERYTHROPOIETIN RECEPTOR MESSENGER-RNA EXPRESSION IN HUMAN ENDOTHELIAL-CELLS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID POLYMERASE CHAIN-REACTION; MESSENGER-RNA; BONE-MARROW; STEM-CELLS; GENE; MODULATION; INVITRO; QUANTITATION; CYTOKINE; BLOOD AB A previous report demonstrated that endothelial cells have erythropoietin receptors and respond to this hormone with enhanced proliferation. The present study demonstrates the existence of mRNA for erythropoietin receptor in human umbilical vein endothelial cells. We have reverse transcribed mRNA of endothelial cells and then used different PCR primers to amplify erythropoietin receptor target cDNA between exons 5 and 6 as well as 3-5 in addition to an internal standard DNA fragment. Correspondence of size as well as location of restriction endonuclease scission (Ava II) was used in comparing the amplified fragments of human endothelial cell erythropoietin receptor to those of two human erythroleukemia cell lines, OCIM1 and K562. No alpha- or gamma-globin mRNA was detected in endothelial cells but was readily demonstrable in OCIM1 cells. In addition, to determine whether the expression of human erythropoietin receptor on endothelial cells occurs in vivo, sections of umbilical cord and placenta were immuno stained with antibodies against the extracellular portion of the receptor; the results showed strong positive staining of the vascular endothelium. C1 MEM HOSP RHODE ISL,PAWTUCKET,RI 02860. BROWN UNIV,SCH MED,DIV HEMATOL ONCOL,PAWTUCKET,RI 02860. BROWN UNIV,SCH MED,DEPT PATHOL,PAWTUCKET,RI 02860. NIDDKD,BIOL CHEM LAB,BETHESDA,MD 20892. NR 37 TC 445 Z9 466 U1 1 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 APR 26 PY 1994 VL 91 IS 9 BP 3974 EP 3978 DI 10.1073/pnas.91.9.3974 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NJ034 UT WOS:A1994NJ03400104 PM 8171022 ER PT J AU PAGE, DM ALEXANDER, J SNOKE, K APPELLA, E SETTE, A HEDRICK, SM GREY, HM AF PAGE, DM ALEXANDER, J SNOKE, K APPELLA, E SETTE, A HEDRICK, SM GREY, HM TI NEGATIVE SELECTION OF CD4(+) CD8(+) THYMOCYTES BY T-CELL RECEPTOR PEPTIDE ANTAGONISTS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; INVITRO CLONAL DELETION; PIGEON CYTOCHROME-C; ANTIGEN RECEPTOR; RECOGNITION; MHC; AFFINITY; CHAIN; DETERMINANT; HYBRIDOMA AB Antigen-induced activation of T-cells can be specifically inhibited by antigen analogs that have been termed T-cell receptor peptide antagonists. These antagonists appear to act by inducing the formation of nonstimulatory or partially stimulatory complexes between T-cell receptors and the major histocompatibility complex molecules presenting the peptides. Herein, we have investigated the effect of T-cell receptor peptide antagonists on thymocyte negative selection. First, peptide antagonists were identified for the cytochrome c-specific T-cell clone AD10. These peptides were then tested for their ability to induce negative selection in an in vitro model system using thymocytes from mice transgenic for the AD10 T-cell receptor. Though unable to induce mature T-cell activation, the T- cell receptor peptide antagonists induced deletion of CD4(+) CD8(+) thymocytes. These results suggest that negative selection of CD4(+) CD8(+) thymocytes can be induced by T-cell receptor interactions of a lower affinity than those required for mature T-cell activation. C1 UNIV CALIF SAN DIEGO,CTR CANC,LA JOLLA,CA 92093. CYTEL CORP,SAN DIEGO,CA 92121. NCI,BETHESDA,MD 20892. RP PAGE, DM (reprint author), UNIV CALIF SAN DIEGO,DEPT BIOL,LA JOLLA,CA 92093, USA. FU NIAID NIH HHS [AI18634, AI08248, AI21372] NR 31 TC 84 Z9 84 U1 0 U2 4 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 APR 26 PY 1994 VL 91 IS 9 BP 4057 EP 4061 DI 10.1073/pnas.91.9.4057 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NJ034 UT WOS:A1994NJ03400121 PM 7909610 ER PT J AU DEMAZANCOURT, P CARNEIRO, EM ATWATER, I BOSCHERO, AC AF DEMAZANCOURT, P CARNEIRO, EM ATWATER, I BOSCHERO, AC TI PROLACTIN TREATMENT INCREASES GLUT2 BUT NOT THE G-PROTEIN SUBUNIT CONTENT IN CELL-MEMBRANES FROM CULTURED NEONATAL RAT ISLETS SO FEBS LETTERS LA English DT Article DE ISLET; NEONATAL RAT; GLUT2; G PROTEIN; PROLACTIN ID ENHANCES INSULIN-SECRETION; PANCREATIC BETA-CELLS; GROWTH-HORMONE; GLUCOSE; STIMULATION; DECREASES; RELEASE; CA-2+ AB Neonatal rat islets exhibit a reduced secretory response to glucose, compared to adult rat islets. The maturation of the secretory response is stimulated by prolactin (PRL). We show here by immunoblot analysis that PRL increases the beta-cell/liver glucose transporter GLUT2 in membrane fractions from cultured neonatal rat islets. This increase (+ 86%) may explain, at least in part, the development of a mature glucose response. G proteins modulate insulin secretion from pancreatic beta-cells. We show here by immunoblot analysis that, in contrast to the effect on GLUT2, PRL treatment does not modify the G protein subunits alpha i2, alpha i3, alpha o, alpha s, alpha q and beta 35 and beta 36, in cultured neonatal islets. C1 NIDDKD,MOLEC PATHOPHYSIOL BRANCH,BETHESDA,MD 20892. NIDDKD,CELL BIOL & GENET LAB,BETHESDA,MD 20892. RP DEMAZANCOURT, P (reprint author), CTR HOSP INTERCOMMUNAL,CENT BIOL LAB,F-78303 POISSY,FRANCE. RI Carneiro, Everardo /D-4758-2012; Boschero, Antonio/O-7525-2014 OI Boschero, Antonio/0000-0003-3829-8570 NR 25 TC 9 Z9 9 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD APR 25 PY 1994 VL 343 IS 2 BP 137 EP 140 DI 10.1016/0014-5793(94)80305-6 PG 4 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA NJ163 UT WOS:A1994NJ16300008 PM 8168618 ER PT J AU WILBUR, WJ LIU, JS AF WILBUR, WJ LIU, JS TI ENERGY-DISTRIBUTION OF THE COMPACT STATES OF A PEPTIDE-CHAIN SO MACROMOLECULES LA English DT Article ID STATISTICAL-MECHANICS; SEQUENCE; MODEL AB We assume that the energy of contact between residues of a peptide chain is governed by an interaction matrix and derive a number of relationships between this interaction matrix and the energy spectrum over the compact states of the peptide chain. If the random energy model (REM) with a fixed number of contacts is assumed, the energy spectrum for the compact states of a peptide is known to be Gaussian. This leads to clear relations between the Hamiltonian, the energy spectrum, and the probability of a random peptide folding to a native state. While these developments are of great theoretical interest, it is evident that structural predictions for real proteins require a more detailed Hamiltonian which distinguishes the different types of residue-residue contacts. Here we consider a Hamiltonian which takes the form of an energy matrix and which explicitly defines the energy of the different types of residue-residue contacts. Statistical conditions are discussed for the contact sets of the compact states which again lead to a Gaussian energy distribution as a limiting form for large numbers of contacts. As for the REM, a simple relation exists between the energy matrix and the resulting energy spectrum. This in turn leads to predictions relating the energy matrix and the probability of a native state, and we show how such predictions may be extended to the case where the number of contacts is variable over the set of compact states. We further give the form of the energy matrix that will maximize the probability of a native state when the individual interaction energies obey certain plausible constraints. While these results may be regarded as exact for the limiting Gaussian distributions, we discuss the approximate nature of the results in realistic cases. C1 HARVARD UNIV,DEPT STAT,CAMBRIDGE,MA 02138. RP WILBUR, WJ (reprint author), NIH,NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,BLDG 38A,ROOM 85806,8600 ROCKVILLE PIKE,BETHESDA,MD 20894, USA. NR 16 TC 5 Z9 5 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0024-9297 J9 MACROMOLECULES JI Macromolecules PD APR 25 PY 1994 VL 27 IS 9 BP 2432 EP 2438 DI 10.1021/ma00087a011 PG 7 WC Polymer Science SC Polymer Science GA NJ226 UT WOS:A1994NJ22600011 ER PT J AU THOMAS, DA DUBNER, R RUDA, MA AF THOMAS, DA DUBNER, R RUDA, MA TI NEONATAL CAPSAICIN TREATMENT IN RATS RESULTS IN SCRATCHING BEHAVIOR WITH SKIN DAMAGE - POTENTIAL MODEL OF NONPAINFUL DYSESTHESIA SO NEUROSCIENCE LETTERS LA English DT Article DE NEONATE; CAPSAICIN; MORPHINE; NALOXONE; PRURITUS; ITCH; RAT ID PRIMARY SENSORY NEURONS; GENE-RELATED PEPTIDE; SUBSTANCE-P; DEVELOPMENTAL ALTERATIONS; ALTERNATIVE HYPOTHESIS; NOCICEPTIVE THRESHOLD; ALLODYNIA; AGONISTS; MORPHINE; ITCH AB We administered capsaicin or vehicle in 2-day-old rat pups, and for over 6 months examined the rats for damaged skin and for the behaviors of scratching, gnawing and biting their skin. By 35 days of age, all rats in the capsaicin group (n = 10) had damaged skin (i.e., lesions, hair loss and red skin) on the rostral half of their bodies. Skin damage remained prevalent over 6 months, whereas vehicle-treated rats (n = 8) had virtually no skin damage. Gnawing and biting behaviors were rarely observed, however, rats in the capsaicin group frequently scratched themselves. There was a significant positive correlation between the frequency at which rats scratched themselves and the total area of skin damage. Morphine (3.0 mg/kg, i.p.) greatly increased scratching behavior in only the capsaicin-treated rats and naloxone (0.5 mg/kg, i.p.) significantly reduced scratching in these rats. Thus, neonatal capsaicin, in its destruction of the majority of primary afferent C-fibers, is capable of inducing opioid-sensitive scratching behavior. C1 NIDR,NEUROBIOL & ANESTHESIOL BRANCH,BETHESDA,MD 20892. NR 34 TC 21 Z9 23 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD APR 25 PY 1994 VL 171 IS 1-2 BP 101 EP 104 DI 10.1016/0304-3940(94)90615-7 PG 4 WC Neurosciences SC Neurosciences & Neurology GA NH345 UT WOS:A1994NH34500027 PM 7521945 ER PT J AU SEI, Y VONLUBITZ, DKJE BASILE, AS BORNER, MM LIN, RCS SKOLNICK, P FOSSOM, LH AF SEI, Y VONLUBITZ, DKJE BASILE, AS BORNER, MM LIN, RCS SKOLNICK, P FOSSOM, LH TI INTERNUCLEOSOMAL DNA FRAGMENTATION IN GERBIL HIPPOCAMPUS FOLLOWING FOREBRAIN ISCHEMIA SO NEUROSCIENCE LETTERS LA English DT Article DE APOPTOSIS; DNA FRAGMENTATION; ISCHEMIA; HIPPOCAMPUS; PROGRAMMED CELL DEATH ID DELAYED NEURONAL DEATH; PROGRAMMED CELL-DEATH; MEDIATED NEUROTOXICITY; CEREBRAL-ISCHEMIA; PROTEIN-SYNTHESIS; APOPTOSIS; CLEAVAGE; DAMAGE; BRAIN AB Internucleosomal DNA fragmentation, the characteristic feature of programmed cell death, was demonstrated in gerbil hippocampus following 10 min of forebrain ischemia. Quantitative analysis revealed the presence of DNA fragments as early as 12 h after ischemia, reaching a maximum at 48 h. Measurable DNA fragmentation was still present in 3/3 subjects 96 h after the ischemic insult. In situ staining of hippocampus demonstrated pronounced DNA fragmentation that was localized in the CA1 region. The localization of fragmented DNA to the CA1 is consistent with the vulnerability of this layer to ischemic insult, and indicates that DNA fragmentation may be associated with the delayed loss of CA1 neurons in this model of forebrain ischemia. C1 NIDDKD,NEUROSCI LAB,BETHESDA,MD 20892. NIDDKD,BIOORGAN CHEM LAB,BETHESDA,MD 20892. NCI,CLIN PHARMACOL BRANCH,BETHESDA,MD 20892. HAHNEMANN UNIV,DEPT PHYSIOL & BIOPHYS,PHILADELPHIA,PA 19102. RI Borner, Markus/B-7583-2011 NR 24 TC 86 Z9 92 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD APR 25 PY 1994 VL 171 IS 1-2 BP 179 EP 182 DI 10.1016/0304-3940(94)90634-3 PG 4 WC Neurosciences SC Neurosciences & Neurology GA NH345 UT WOS:A1994NH34500046 PM 8084486 ER PT J AU GARRUTO, RM BROWN, P AF GARRUTO, RM BROWN, P TI TAU-PROTEIN, ALUMINUM, AND ALZHEIMERS-DISEASE SO LANCET LA English DT Editorial Material RP GARRUTO, RM (reprint author), NIH,CENT NERVOUS SYST STUDIES LAB,BETHESDA,MD 20892, USA. NR 13 TC 13 Z9 13 U1 0 U2 1 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD APR 23 PY 1994 VL 343 IS 8904 BP 989 EP 989 DI 10.1016/S0140-6736(94)90119-8 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA NG682 UT WOS:A1994NG68200002 PM 7909086 ER PT J AU BOGAZZI, F HUDSON, LD NIKODEM, VM AF BOGAZZI, F HUDSON, LD NIKODEM, VM TI A NOVEL HETERODIMERIZATION PARTNER FOR THYROID-HORMONE RECEPTOR - PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Note ID 9-CIS RETINOIC ACID; RXR-BETA; RESPONSE ELEMENTS; GENE; BINDING AB Retinoid-like receptors play a central role in hormonal responses by forming heterodimers with other nuclear hormone receptors. In this study we have identified the peroxisome proliferator-activated receptor (PPAR) as a new thyroid hormone receptor (THR) auxiliary nuclear protein, heterodimerizing with THR in solution. Although these heterodimers do not recognize a classical thyroid hormone response element (TRE) characterized by direct repeat separated by four nucleotides (DR + 4), PPAR behaves as a dominant negative regulator of thyroid hormone (TH) action. However a TH-dependent positive effect is elicited by selective interaction of the THR beta-PPAR but not the THR alpha-PPAR heterodimer with a novel TRE (DR + 2). The critical region of THR beta was mapped to 3 amino acids in the distal box of the DNA binding domain. Hence, PPAR can positively or negatively influence TH action depending on TRE structure and THR isotype. C1 NIDDK,MECHANISMS GENE REGULAT SECT,GENET & BIOCHEM BRANCH,BETHESDA,MD 20892. NINCDS,VIRAL & MOLEC PATHOGENESIS LAB,BETHESDA,MD 20892. RI BOGAZZI, FAUSTO/I-2087-2012 OI BOGAZZI, FAUSTO/0000-0001-5975-4411 NR 18 TC 114 Z9 115 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 APR 22 PY 1994 VL 269 IS 16 BP 11683 EP 11686 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NG377 UT WOS:A1994NG37700003 PM 8163464 ER PT J AU RUVINOV, SB MILES, EW AF RUVINOV, SB MILES, EW TI THERMAL INACTIVATION OF TRYPTOPHAN SYNTHASE - STABILIZATION BY PROTEIN-PROTEIN INTERACTION AND PROTEIN-LIGAND INTERACTION SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Note ID DODECAMERIC GLUTAMINE-SYNTHETASE; AMINO-ACID SUBSTITUTIONS; ESCHERICHIA-COLI; SALMONELLA-TYPHIMURIUM; ALPHA-SUBUNIT; BETA-SUBUNIT; ALPHA-2-BETA-2 COMPLEX; BIENZYME COMPLEX; FLEXIBLE LOOP; SCANNING CALORIMETRY AB This study investigates effects of ligands on thermal inactivation of the tryptophan synthase alpha and beta(2) subunits alone and in the alpha(2) beta(2) complex. Addition of pyridoxal phosphate to the apo-beta(2) subunit increases the temperature of one-half inactivation (T-i) from 52 to 77 degrees C. Ligands that promote association of the alpha and holo-beta(2) subunits markedly stabilize the more temperature-labile alpha subunit in the alpha(2) beta(2) complex from irreversible thermal denaturation. The combination of a beta(2) subunit ligand (L-serine) with an a subunit ligand (alpha-glycerol 3-phosphate) raises the inactivation temperature (T-i) of the alpha subunit in the holo-alpha(2) beta(2) complex from 54 to 66 degrees C. In contrast, values of T-i for inactivation of the alpha and beta subunits in the holo-alpha(2) beta(2) complex are more similar to respective values for the isolated alpha subunit (50 degrees C) and holo-beta(2) subunit (77 degrees C). Surprisingly, the addition of L- serine results in a larger decrease in the T-i of the beta(2) subunit in the holo-alpha(2) beta(2) complex (78 degrees C --> 64 degrees C) than in T-i of the holo-beta(2) subunit alone (77 degrees C --> 71 degrees C). The observation that ligands have different effects on the isolated and associated subunits provides evidence that the alpha and beta(2) subunits do not fully dissociate during thermal inactivation of the alpha(2) beta(2) complex at pH 7.8 and at similar to 0.1 ionic strength. Our results demonstrate that linkage between protein-ligand interactions and protein-protein interactions affects the conformational stability of the tryptophan synthase alpha(2) beta(2) complex. C1 NIDDK, BIOCHEM PHARMACOL LAB, BETHESDA, MD 20892 USA. NR 43 TC 14 Z9 14 U1 0 U2 0 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 APR 22 PY 1994 VL 269 IS 16 BP 11703 EP 11706 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NG377 UT WOS:A1994NG37700008 PM 8163467 ER PT J AU BENYA, RV KUSUI, T SHIKADO, F BATTEY, JF JENSEN, RT AF BENYA, RV KUSUI, T SHIKADO, F BATTEY, JF JENSEN, RT TI DESENSITIZATION OF NEUROMEDIN-B RECEPTORS (NMB-R) ON NATIVE AND NMB-R-TRANSFECTED CELLS INVOLVES DOWN-REGULATION AND INTERNALIZATION SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BOMBESIN-LIKE PEPTIDES; PANCREATIC ACINAR-CELLS; EPIDERMAL GROWTH-FACTOR; CENTRAL-NERVOUS-SYSTEM; PROTEIN-KINASE-C; SWISS 3T3 CELLS; PHOSPHOINOSITIDE HYDROLYSIS; GASTROINTESTINAL-TRACT; INOSITOL PHOSPHATES; LIGAND-BINDING AB The receptor for neuromedin B (NMB-R), a mammalian bombesin-related peptide, is widely distributed in the central nervous system and gastrointestinal tract. While it is known that this receptor is coupled to phospholipase C, like many other phospholipase C-activating receptors, little is known about regulation of the NMB-R subsequent to agonist stimulation. We studied both native NMB-R on C-6 rat glioblastoma cells and wild type NMB-R cloned from rat esophageal muscle which was stably transfected into Balb/3T3 fibroblasts. Both cell types rapidly increased [H-3]inositol phosphates and [Ca2+](i) in response to 1 mu M NMB, whereas preincubation with 3 nM NMB for 3 h markedly attenuated the ability of 1 mu M NMB, but not 1 mu M endothelin-1, to alter either cell type's biological activity. Prolonged exposure to 3 nM NMB caused a rapid decrease in the number of NMB-R, with the maximal receptor down-regulation seen at 24 h due to NMB-R internalization. After maximal downregulation, removal of agonist resulted in a rapid restoration of NMB-R to the cell surface of both cell types. NMB-R recovery at 6 h was blocked by monensin, an inhibitor of receptor recycling, but was not affected by cycloheximide, a protein synthesis inhibitor. Resensitization to agonist paralleled the recovery of MMB-R in both cell types, and resensitization likewise was blocked by monensin. Our data demonstrate that the NMB-R undergoes rapid homologous desensitization consequent to agonist stimulation, which is mediated by receptor down-regulation and which, in turn, is regulated by internalization. During resensitization, NMB-R reappearance on the cell surface membrane is independent of protein synthesis and is due to a recycling from an intracellular site. C1 NCI,BIOL CHEM LAB,DEV THERAPEUT PROGRAM,BETHESDA,MD 20892. RP BENYA, RV (reprint author), NIDDKD,DIGEST DIS BRANCH,BETHESDA,MD 20892, USA. NR 65 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 APR 22 PY 1994 VL 269 IS 16 BP 11721 EP 11728 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NG377 UT WOS:A1994NG37700011 PM 8163469 ER PT J AU MANDON, E KEMPNER, ES ISHIHARA, M HIRSCHBERG, CB AF MANDON, E KEMPNER, ES ISHIHARA, M HIRSCHBERG, CB TI A MONOMERIC PROTEIN IN THE GOLGI MEMBRANE CATALYZES BOTH N-DEACETYLATION AND N-SULFATION OF HEPARAN-SULFATE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FIBROBLAST GROWTH-FACTOR; RADIATION-INACTIVATION; RAT-LIVER; TARGET ANALYSIS; MOLECULAR-SIZE; CELL-SURFACE; SULFOTRANSFERASE; PROTEOGLYCANS; RECEPTOR; BINDING AB Recent studies have shown that the rat liver heparan sulfate N-deacetylase/N-sulfotransferase is a glycoprotein encoded by a single polypeptide chain of 882 amino acids. Using radiation inactivation analyses, we have now determined that in rat liver Golgi vesicles the target size for the N-deacetylase is 88 +/- 14 kDa, whereas that of the N-sulfotransferase is 92 +/- 8 kDa. These results, together with previous biochemical and molecular cloning approaches, demonstrate that 1) in rat Liver Golgi membranes there exists only one population of molecules expressing both activities, 2) the active protein in the Golgi membrane functions as a monomer, and 3) there is no evidence that a large independent protein acts as a regulator of either activity. C1 UNIV MASSACHUSETTS, MED CTR, DEPT BIOCHEM & MOLEC BIOL, WORCESTER, MA 01655 USA. NIAMSD, PHYS BIOL LAB, BETHESDA, MD 20892 USA. GLYCOMED INC, ALAMEDA, CA 94501 USA. FU NIGMS NIH HHS [GM34396] NR 40 TC 31 Z9 32 U1 1 U2 1 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 APR 22 PY 1994 VL 269 IS 16 BP 11729 EP 11733 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NG377 UT WOS:A1994NG37700012 PM 8163470 ER PT J AU RASCON, A DEGERMAN, E TAIRA, M MEACCI, E SMITH, CJ MANGANIELLO, V BELFRAGE, P TORNQVIST, H AF RASCON, A DEGERMAN, E TAIRA, M MEACCI, E SMITH, CJ MANGANIELLO, V BELFRAGE, P TORNQVIST, H TI IDENTIFICATION OF THE PHOSPHORYLATION SITE IN-VITRO FOR CAMP-DEPENDENT PROTEIN-KINASE ON THE RAT ADIPOCYTE CGMP-INHIBITED CAMP-PHOSPHODIESTERASE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CYCLIC-AMP PHOSPHODIESTERASE; ADIPOSE-TISSUE; INSULIN; PURIFICATION; PARTICULATE; ACTIVATION; SEPARATION; LIPOLYSIS AB Rat adipocyte cGMP-inhibited cAMP phosphodiesterase (cGI-PDE) appears to be dually regulated in intact cells by serine phosphorylations induced by isoprenaline and insulin, respectively (Degerman, E., Smith, C. J., Tornqvist, H., Vasta, V., Belfrage, P., and Manganiello, V. C. (1990) Proc. Natl. Acad. Sci. U. S. A. 87, 533-537; Smith, C. J., Vasta, V., Degerman, E., Belfrage, P., and Manganiello, V. C. (1991) J. Biol. Chem. 266, 13385-13390). Since cAMP-dependent protein kinase (cAMP-PK) catalyzes the beta-adrenergic effects, the site in the isolated cGI-PDE phosphorylated by this kinase was explored. A peptide, LRRSSGASGLLTSEHHSR (P18), corresponding to the amino acid sequence Leu(429)-Arg(440) in the putative regulatory domain of the rat adipocyte cGI-PDE was synthesized. It contains a consensus substrate sequence -RRXS- for cAMP-PK within two tryptic cleavage sites and was readily phosphorylated by cAMP-PK. Two phosphopeptides, identified as RS-[P-32]SGASGLLTSEHHSR and S-[P-32]SGASGLLTSEHHSR, were obtained after stoichiometric phosphorylation and trypsinization of the peptide. These two peptides and the two main tryptic phosphopeptides obtained from immunoisolated [P-32]cGI-PDE phosphorylated with cAMP-PK in a solubilized crude adipocyte membrane fraction were immunoprecipitated by an affinity-purified polyclonal antibody raised against P18 and exhibited the same chromatographic and electrophoretic profiles in three different separation systems. Similar radiosequencing profiles indicated that the second most N-terminal serine, corresponding to Ser-427 in the intact cGI-PDE, was phosphorylated by cAMP-PK in both P18 and authentic cGI-PDE. It is concluded that serine 427 is the target for cAMP-PK phosphorylation of the rat adipocyte cGI-PDE in vitro. C1 LUND UNIV,DEPT MED & PHYSIOL CHEM,S-22100 LUND,SWEDEN. LUND UNIV,DEPT PAEDIAT,S-22100 LUND,SWEDEN. NHLBI,CELLULAR METAB LAB,BETHESDA,MD 20892. NR 19 TC 37 Z9 37 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 APR 22 PY 1994 VL 269 IS 16 BP 11962 EP 11966 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NG377 UT WOS:A1994NG37700046 PM 8163498 ER PT J AU YOO, SH AF YOO, SH TI PH-DEPENDENT INTERACTION OF CHROMOGRANIN-A WITH INTEGRAL MEMBRANE-PROTEINS OF SECRETORY VESICLE INCLUDING 260-KDA PROTEIN REACTIVE TO INOSITOL 1,4,5-TRISPHOSPHATE RECEPTOR ANTIBODY SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CONFORMATIONAL CHANGE; CHROMAFFIN GRANULES; NERVOUS-TISSUE; INSP3 RECEPTOR; EXPRESSION; CA-2+; CA2+ AB Chromogranin A is a high capacity, low affinity Ca2+-binding protein suggested to be responsible for the Ca2+ storage function of the secretory vesicle, which has been identified as a major inositol 1,4,5-trisphosphate (IP3)-sensitive intracellular Ca2+ store of adrenal medullary chromaffin cells. Moreover, chromogranin A has recently been shown to interact with the vesicle membrane at the intravesicular pH of 5.5 and to be released from it at a near physiological pH of 7.5 (Yoo, S. H. (1993) Biochemistry 32, 8213-8219). In the present study, chromogranin A is shown to interact with several integral membrane proteins of secretory vesicles at pH 5.5 but not at pH 7.5. One of the chromogranin A-interacting membrane proteins had a mass of 260 kDa and reacted with the IP3 receptor antibody. This result suggested not only the existence of the IP3 receptor in the vesicle membrane but also the existence of direct communication between chromogranin A and the IP3 receptor. In addition, the pH-dependent interaction of chromogranin A with integral membrane proteins implies an important role for chromogranin A in the sorting process of the vesicle membrane proteins during vesicle biogenesis in the trans-Golgi network. RP YOO, SH (reprint author), NIDOCD,CELLULAR BIOL LAB,BETHESDA,MD 20892, USA. NR 33 TC 66 Z9 66 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 APR 22 PY 1994 VL 269 IS 16 BP 12001 EP 12006 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NG377 UT WOS:A1994NG37700052 PM 8163503 ER PT J AU SARKAR, FH SMITH, MR HOOVER, T PRINCLER, G CRISSMAN, JD VISSCHER, DW LONGO, DL KUNG, HF RAZIUDDIN AF SARKAR, FH SMITH, MR HOOVER, T PRINCLER, G CRISSMAN, JD VISSCHER, DW LONGO, DL KUNG, HF RAZIUDDIN TI C-ERBB-2 PROMOTER-SPECIFIC DNA-BINDING PROTEIN ISOLATED FROM HUMAN BREAST-CANCER TISSUES DISPLAYS MITOGENIC ACTIVITY SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GROWTH-FACTOR-RECEPTOR; LONG TERMINAL REPEAT; HUMAN MAMMARY-TUMORS; NEU PROTOONCOGENE; EGF RECEPTOR; CELL-LINE; ONCOGENE; TRANSFORMATION; REGION; GENE AB Amplification and overexpression of the c-erbB-2 gene appears to play a role in the pathogenesis of human breast and other cancers. Frequent amplification (20-30%) of the c-erbB-2 gene was observed in human adenocarcinomas of kidney, pancreas, lung, ovarian, and breast cancer. The gene product is a 185-kDa glycoprotein that has intrinsic tyrosine kinase activity and is believed to be a receptor. Several candidate ligands have been described. In the present study we have identified and purified a novel DNA-binding protein from malignant human breast tissues. The protein binds to a core element (-22 to +9, +1 being the transcription start site) of the c-erbB-2 promoter region in a sequence-specific manner. The affinity-purified protein has the ability to induce DNA synthesis in quiescent NIH/3T3 cells, suggesting that the factor has mitogenic activity. The purified protein induces c-erbB-2 expression on the surface of microinjected NIH/3T3 cells. This DNA-binding protein is a sequence-specific cellular factor that is associated with high level expression of the c-erbB-2 gene and appears to play a role in cell transformation. Understanding the control and expression of this DNA-binding protein may shed light on the mechanism(s) of c-erbB-2 gene regulation and its potential role in the pathogenesis of human adenocarcinomas. C1 NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21702. WAYNE STATE UNIV,SCH MED,DEPT PATHOL,DETROIT,MI 48201. NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. NR 39 TC 11 Z9 11 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 APR 22 PY 1994 VL 269 IS 16 BP 12285 EP 12289 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NG377 UT WOS:A1994NG37700092 PM 7909319 ER PT J AU TAKIMOTO, CH KLECKER, RW DAHUT, WL YEE, LK STRONG, JM ALLEGRA, CJ GREM, JL AF TAKIMOTO, CH KLECKER, RW DAHUT, WL YEE, LK STRONG, JM ALLEGRA, CJ GREM, JL TI ANALYSIS OF THE ACTIVE LACTONE FORM OF 9-AMINOCAMPTOTHECIN IN PLASMA USING SOLID-PHASE EXTRACTION AND HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY SO JOURNAL OF CHROMATOGRAPHY B-BIOMEDICAL APPLICATIONS LA English DT Article ID XENOGRAFTS; CAMPTOTHECIN; INHIBITION; CANCER; MICE AB We have developed a sensitive HPLC assay to quantitate the active lactone form of 9-aminocamptothecin (9AC) in human plasma over the concentration range 10-0.25 nM (0.091 ng/ml). Solid-phase extraction separated 9AC lactone from its less active metabolite, 9AC carboxylate, allowing samples to be stored for up to two months prior to reversed-phase HPLC analysis. An acidic (pH 2.55) isocratic HPLC mobile phase was used to enhance 9AC fluorescence resulting in an over 50-fold increase in assay sensitivity compared to previous methods. This assay was able to measure steady-state 9AC lactone concentrations even at the lowest dose level of 9AC used in our Phase I clinical trial. C1 US FDA,CTR DRUG EVALUAT & RES,OFF RES RESOURCES,DIV CLIN PHARMACOL,ROCKVILLE,MD 20850. RP TAKIMOTO, CH (reprint author), USN,NATL MED CTR,NCI,DIV CANC TREATMENT,MED ONCOL BRANCH,BETHESDA,MD 20889, USA. NR 9 TC 60 Z9 61 U1 2 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-4347 J9 J CHROMATOGR B JI J. Chromatogr. B-Biomed. Appl. PD APR 22 PY 1994 VL 655 IS 1 BP 97 EP 104 DI 10.1016/0378-4347(94)00051-4 PG 8 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA NJ139 UT WOS:A1994NJ13900013 PM 8061838 ER PT J AU REIN, KS BADEN, DG GAWLEY, RE AF REIN, KS BADEN, DG GAWLEY, RE TI CONFORMATIONAL-ANALYSIS OF THE SODIUM-CHANNEL MODULATOR, BREVETOXIN-A, COMPARISON WITH BREVETOXIN-B CONFORMATIONS, AND A HYPOTHESIS ABOUT THE COMMON PHARMACOPHORE OF THE SITE-5 TOXINS SO JOURNAL OF ORGANIC CHEMISTRY LA English DT Article ID RAT-BRAIN SYNAPTOSOMES; PTYCHODISCUS-BREVIS; MOLECULAR MECHANICS; BINDING; RECEPTOR; PHARMACOLOGY; MEMBRANES; SOFTWARE AB The marine neurotoxins brevetoxin A, brevetoxin B, and ciguatoxin bind to the same site (site 5) on the voltage-gated sodium channel. This work, and the following paper in this issue, describe efforts to identify the common pharmacophore and to develop a ligand-receptor model for the binding of these neurotoxins to site 5. Conformational analysis of brevetoxin A has been completed using ah internal coordinate Monte Carlo search protocol. Within 6 kcal/mol of the global minimum (in vacuo), there are 48 conformations of brevetoxin A. In chloroform or water solvent, the calculated relative energies change, but no new minima appear. Like brevetoxin B, brevetoxin A has both straight and bent conformers available. Elimination of several G-ring crown conformers from consideration and comparison of the two brevetoxin backbones indicates that those that match most closely in overall shape and location of functional groups are straight. We postulate that the common pharmacophore is a roughly cigar-shaped molecule (similar to 30 Angstrom long) bound to its receptor primarily by hydrophobic and nonpolar solvation forces, possibly aided by strategically placed,hydrogen bonds near the site of the lactone carbonyl in the receptor. C1 UNIV MIAMI,ROSENSTIEL SCH MARINE & ATMOSPHER SCI,NIEHS,CTR MARINE & FRESHWATER BIOMED SCI,MIAMI,FL 33149. UNIV MIAMI,DEPT CHEM,CORAL GABLES,FL 33124. NR 27 TC 57 Z9 61 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-3263 J9 J ORG CHEM JI J. Org. Chem. PD APR 22 PY 1994 VL 59 IS 8 BP 2101 EP 2106 DI 10.1021/jo00087a027 PG 6 WC Chemistry, Organic SC Chemistry GA NJ137 UT WOS:A1994NJ13700027 ER PT J AU REIN, KS LYNN, B GAWLEY, RE BADEN, DG AF REIN, KS LYNN, B GAWLEY, RE BADEN, DG TI BREVETOXIN-B - CHEMICAL MODIFICATIONS, SYNAPTOSOME BINDING, TOXICITY, AND AN UNEXPECTED CONFORMATIONAL EFFECT SO JOURNAL OF ORGANIC CHEMISTRY LA English DT Article ID SENSITIVE SODIUM-CHANNELS; RAT-BRAIN SYNAPTOSOMES; RED TIDE ORGANISM; PTYCHODISCUS-BREVIS; GYMNODINIUM-BREVE; CIGUATOXIN; TOXIN; ASSIGNMENTS; JAVANICUS; SITES AB Five naturally occurring brevetoxins and seven synthetically modified brevetoxins were examined for their affinity for site 5 of the voltage-gated sodium channel and their toxicity to mosquito fish, Gambusia affinis. All but three of the toxins studied still retained some affinity for their receptor site (IC50's in the range of 1-100 nM). Compound 7, having all three carbon-carbon double bonds reduced, is almost 3 orders of magnitude less strongly bound than 4, which has only two carbon-carbon bonds reduced. This large effect resulting from H-ring reduction was unexpected, due to the similarity of this region of the molecule to the corresponding region of brevetoxin-A, which has a fully saturated eight-membered G-ring and is the most strongly bound toxin of those studied. Conformational analysis revealed that the unsaturated H-ring of brevetoxin B favors the boat-chair conformation as does the saturated G-ring of brevetoxin A. Upon reduction, the H-ring of brevetoxin B shifts to a crown conformation. This subtle change in conformational preference induces a significant change in the gross shape of the molecule, which we believe is responsible for the loss of binding affinity and toxicity. C1 UNIV MIAMI,ROSENSTIEL SCH MARINE & ATMOSPHER SCI,NIEHS,CTR MARINE & FRESHWATER BIOMED SCI,MIAMI,FL 33149. UNIV MIAMI,DEPT CHEM,CORAL GABLES,FL 33124. NR 42 TC 64 Z9 69 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-3263 J9 J ORG CHEM JI J. Org. Chem. PD APR 22 PY 1994 VL 59 IS 8 BP 2107 EP 2113 DI 10.1021/jo00087a028 PG 7 WC Chemistry, Organic SC Chemistry GA NJ137 UT WOS:A1994NJ13700028 ER PT J AU ALEXANDER, D AF ALEXANDER, D TI ADOLESCENT HEALTH STUDY SO SCIENCE LA English DT Letter RP ALEXANDER, D (reprint author), NICHHD,BETHESDA,MD 20892, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD APR 22 PY 1994 VL 264 IS 5158 BP 490 EP 490 DI 10.1126/science.264.5158.490 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NH010 UT WOS:A1994NH01000006 PM 17732719 ER PT J AU CAMPBELL, M FELBER, BK NASIOULAS, G AFONINA, E PAVLAKIS, GN AF CAMPBELL, M FELBER, BK NASIOULAS, G AFONINA, E PAVLAKIS, GN TI INHIBITION OF REV-MEDIATED HIV-1 EXPRESSION BY AB RNA-BINDING PROTEIN ENCODED BY THE INTERFERON-INDUCIBLE 9-27 GENE (RETRACTION OF VOL 259, PG 1314, 1993) SO SCIENCE LA English DT Correction, Addition RP CAMPBELL, M (reprint author), FREDERICK CANC RES & DEV CTR,ADV BIOSCI LABS INC,FREDERICK,MD 21702, USA. NR 1 TC 2 Z9 2 U1 1 U2 5 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD APR 22 PY 1994 VL 264 IS 5158 BP 492 EP 492 DI 10.1126/science.8160005 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NH010 UT WOS:A1994NH01000010 PM 8160005 ER PT J AU WICKNER, RB AF WICKNER, RB TI [URE3] AS AN ALTERED URE2 PROTEIN - EVIDENCE FOR A PRION ANALOG IN SACCHAROMYCES-CEREVISIAE SO SCIENCE LA English DT Article ID SHUTTLE VECTORS; STRANDED-RNA; YEAST; DNA; MITOCHONDRIAL; POLYMERASE; SCRAPIE; GENES AB A cytoplasmically inherited element, [URE3], allows yeast to use ureidosuccinate in the presence of ammonium ion. Chromosomal mutations in the URE2 gene produce the same phenotype. [URE3] depends for its propagation on the URE2 product (Ure2p), a negative regulator of enzymes of nitrogen metabolism. Saccharomyces cerevisiae strains cured of [URE3] with guanidium chloride were shown to return to the [URE3]-carrying state without its introduction from other cells. Overproduction of Ure2p increased the frequency with which a strain became [URE3] by 100-fold. In analogy to mammalian prions, [URE3] may be an altered form of Ure2p that is inactive for its normal function but can convert normal Ure2p to the altered form. The genetic evidence presented here suggests that protein-based inheritance, involving a protein unrelated to the mammalian prion protein, can occur in a microorganism. RP NIDDKD, BIOCHEM PHARMACOL LAB, GENET SIMPLE EUKARYOTES SECT, ROOM 207, BLDG 8, BETHESDA, MD 20892 USA. NR 29 TC 846 Z9 865 U1 3 U2 33 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 EI 1095-9203 J9 SCIENCE JI Science PD APR 22 PY 1994 VL 264 IS 5158 BP 566 EP 569 DI 10.1126/science.7909170 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NH010 UT WOS:A1994NH01000036 PM 7909170 ER PT J AU WOZNIAK, LA SOCHACKI, M MITSUYA, H KAGEYAMA, S STEC, WJ AF WOZNIAK, LA SOCHACKI, M MITSUYA, H KAGEYAMA, S STEC, WJ TI A NEW CLASS OF DINUCLEOTIDE ANALOGS - THE SYNTHESIS OF 3'-O-THYMIDYLYL(5'-DEOXY-5'-SELENE-THYMIDYLYL)-SE-PHOSPHOROSELENOLATE, ITS O-METHYL ESTER AND METHANEPHOSPHONATE DERIVATIVES SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article ID NUCLEOSIDES AB Title compounds 12, 13 and 14 have been prepared via alkylation of 5'-O-protected nucleoside 3'-O-(O-alkylphosphoroselenoates) (5, 6) and -3'-O-(methanephosphonoselenoates) (7). After deprotection, 5'-deoxy-5'-selene dinucleoside Se-phosphates and Se-phosphonates have been obtained with good yields. Their chemical and antiviral (HIV-1) properties have also been examined. C1 POLISH ACAD SCI,CTR MOLEC & MACROMOLEC STUDIES,PL-90363 LODZ,POLAND. NCI,MED BRANCH,EXPTL RETROVIROL SECT,BETHESDA,MD 20892. RI Sochacki, Marek/H-1874-2011 NR 11 TC 6 Z9 6 U1 1 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD APR 21 PY 1994 VL 4 IS 8 BP 1033 EP 1036 DI 10.1016/S0960-894X(01)80676-4 PG 4 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA NH740 UT WOS:A1994NH74000014 ER PT J AU VONLUBITZ, DKJE LIN, RCS MELMAN, N JI, XD CARTER, MF JACOBSON, KA AF VONLUBITZ, DKJE LIN, RCS MELMAN, N JI, XD CARTER, MF JACOBSON, KA TI CHRONIC ADMINISTRATION OF SELECTIVE ADENOSINE A(1) RECEPTOR AGONIST OR ANTAGONIST IN CEREBRAL-ISCHEMIA SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE ADENOSINE; ISCHEMIA; ADENOSINE RECEPTOR; THERAPY; (GERBIL) ID ADENYLATE CYCLASE SYSTEM; RAT-BRAIN; CELL-DEATH; HIPPOCAMPUS; PROTECTION; RELEASE; SLICES; DAMAGE; PHENYLISOPROPYLADENOSINE; POTENTIATION AB The effect of chronic administration of selective adenosine A(1) receptor agonists and antagonists on the outcome of cerebral ischemia is entirely unknown. Therefore, we have investigated the impact of such regimens on the hippocampal adenosine A(1) receptor density, and on the recovery from 10 min forebrain ischemia in gerbils. While acutely administered N-6-cyclopentyladenosine (CPA) given at 0.02 mg/kg resulted only in a significant reduction of mortality, at 1 mg/kg it improved both survival and neuronal preservation in the hippocampal CA1 region. Acute treatment with 1,3-dipropyl-8-cyclopentylxanthine (CPX) significantly worsened the outcome and enhanced neuronal destruction. The effects of chronic administration of these drugs (15 days followed by 1 drug-free day) were opposite. Thus, although chronic CPA at 0.02 mg/kg did not have any effect at all, at 1 mg/kg both survival and neuronal preservation were significantly poorer than in controls, while chronic CPX resulted in a significant improvement of both measures. These results were not accompanied by adenosine A(1) receptor up- or downregulation. Our study indicates that highly selective adenosine analogues may have therapeutic potential in treatment of cerebral ischemia/stroke and possibly other neurodegenerative disorders as well. C1 HAHNEMANN UNIV, DEPT PHYSIOL & BIOPHYS, PHILADELPHIA, PA 19102 USA. RP NIDDK, BIOORGAN CHEM LAB, MOLEC RECOGNIT SECT, BLDG 8, RM 111, BETHESDA, MD 20892 USA. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS [Z01 DK031117-20, Z99 DK999999] NR 65 TC 68 Z9 68 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 EI 1879-0712 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD APR 21 PY 1994 VL 256 IS 2 BP 161 EP 167 DI 10.1016/0014-2999(94)90241-0 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA NH589 UT WOS:A1994NH58900007 PM 8050467 ER PT J AU FANAROFF, AA KORONES, SB WRIGHT, LL WRIGHT, EC POLAND, RL BAUER, CB TYSON, JE PHILIPS, JB EDWARDS, W LUCEY, JF CATZ, CS SHANKARAN, S OH, W CASSADY, G BRAUNE, K HACK, M NEWMAN, NS LITTLE, G NATTIE, C BAIN, RP VERTER, J YOUNES, N HAWES, S MURAN, G BANDSTRA, ES MARTINEZ, S YAFFE, SJ MALLOY, M COOKE, R MOORE, J BURCHFIELD, J HORBAR, JD LEAHY, K AF FANAROFF, AA KORONES, SB WRIGHT, LL WRIGHT, EC POLAND, RL BAUER, CB TYSON, JE PHILIPS, JB EDWARDS, W LUCEY, JF CATZ, CS SHANKARAN, S OH, W CASSADY, G BRAUNE, K HACK, M NEWMAN, NS LITTLE, G NATTIE, C BAIN, RP VERTER, J YOUNES, N HAWES, S MURAN, G BANDSTRA, ES MARTINEZ, S YAFFE, SJ MALLOY, M COOKE, R MOORE, J BURCHFIELD, J HORBAR, JD LEAHY, K TI A CONTROLLED TRIAL OF INTRAVENOUS IMMUNE GLOBULIN TO REDUCE NOSOCOMIAL INFECTIONS IN VERY-LOW-BIRTH-WEIGHT INFANTS SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID INTENSIVE-CARE UNITS; PREMATURE-INFANTS; NEONATAL SEPSIS; CLINICAL-TRIALS; IMMUNOGLOBULIN; PREVENTION; PROPHYLAXIS; EFFICACY; THERAPY AB Background. Nosocomial infections are a major cause of morbidity and mortality in premature infants. As a rule, their low serum gamma globulin levels at birth subsequently decline to hypogammaglobulinemic values; hence, prophylactic administration of intravenous immune globulin may reduce the rate of hospital-acquired infections. Methods. In this prospective, multicenter, two-phase controlled trial, 2416 infants were stratified according to birth weight (501 to 1000 g and 1001 to 1500 g) and randomly assigned to an intravenous immune globulin group (n = 1204) or a control group (n = 1212). Control infants were given placebo infusions during phase 1 of the study (n = 623) but were not given any infusions during phase 2 (n = 589). Infants weighing 501 to 1000 g at birth were given 900 mg of immune globulin per kilogram of body weight, and infants weighing 1001 to 1500 g at birth were given a dose of 700 mg per kilogram. The immune globulin infusions were repeated every 14 days until the infants weighed 1800 g, were transferred to another center, died, or were sent home from the hospital. Results. Nosocomial infections of the blood, meninges, or urinary tract occurred in 439 of the 2416 infants (18.2 percent): 208 (17.3 percent) in the immune globulin group and 231 (19.1 percent) in the control group (relative risk, 0.91; 95 percent confidence interval, 0.77 to 1.08). Septicemia occurred in 15.5 percent of the immune globulin recipients and 17.2 percent of the controls. During phase 1 the rate of nosocomial infections was 13.4 percent in the immune globulin group and 17.8 percent in the control group; the respective rates during phase 2 were 21.0 percent and 20.4 percent. The predominant organisms included gram-positive cocci (53.0 percent), gram-negative bacilli (22.4 percent), and candida species (16.0 percent). Adverse reactions were rarely observed during the infusions. Immune globulin therapy had no effect on respiratory distress syndrome, bronchopulmonary dysplasia, intracranial hemorrhage, the duration of hospitalization, or mortality. The incidence of necrotizing enterocolitis was 12.0 percent in the immune globulin group and 9.5 percent in the control group. Conclusions. Prophylactic use of intravenous immune globulin failed to reduce the incidence of hospital-acquired infections in very-low-birth-weight infants. C1 CASE WESTERN RESERVE UNIV,CLEVELAND,OH 44106. UNIV TENNESSEE CTR HLTH SCI,MEMPHIS,TN 38163. NICHHD,BETHESDA,MD 20892. GEORGE WASHINGTON UNIV,CTR BIOSTAT,ROCKVILLE,MD. WAYNE STATE UNIV,DETROIT,MI 48202. UNIV MIAMI,MIAMI,FL 33152. UNIV TEXAS,SW MED CTR,DALLAS,TX 75230. UNIV ALABAMA,BIRMINGHAM,AL 35294. DARTMOUTH COLL,HITCHCOCK MED CTR,HANOVER,NH 03756. UNIV VERMONT,BURLINGTON,VT 05405. BROWN UNIV,PROVIDENCE,RI 02912. FU NICHD NIH HHS [U10 HD21415, U10 HD19897, U10 HD21364] NR 29 TC 115 Z9 118 U1 1 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 APR 21 PY 1994 VL 330 IS 16 BP 1107 EP 1113 DI 10.1056/NEJM199404213301602 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA NF699 UT WOS:A1994NF69900002 PM 8133853 ER PT J AU FAMILARI, M ALMOUZNI, G WOLFFE, AP AF FAMILARI, M ALMOUZNI, G WOLFFE, AP TI ISOLATION OF A POTENTIALLY FUNCTIONAL Y-BOX PROTEIN (MSY-1) PROCESSED PSEUDOGENE FROM MOUSE - EVOLUTIONARY RELATIONSHIPS WITHIN THE EF1(A)/DBPB/YB-1 GENE FAMILY SO GENE LA English DT Note DE RECOMBINANT DNA; NUCLEOTIDE SEQUENCE; EXPRESSION; RETROPOSON; RIPPING ID CCAAT BINDING-PROTEIN; DNA-BINDING; SEQUENCE-ANALYSIS; ESCHERICHIA-COLI; EXPRESSION; INVITRO; CLONING; SHOCK AB A processed pseudogene from Mus musculus, designated psi MSY-2, was obtained from a genomic library by screening with a MSY-1 cDNA (encoding mouse Y-box factor 1) probe. Mouse psi MSY-2 is intronless and has an ORF with an in-frame translational stop. The pseudogene has repeat sequences at the 5' and 3' boundaries, suggestive of an origin as a retroposon, and exhibits mutagenesis of CpG residues at a frequency at least tenfold higher than predicted from random mutagenesis. This indicates that 'repeat-induced point mutagenesis' or ripping has occurred. We find that the mouse genome contains many DNA sequences with homology to a cDNA encoding the DNA-binding domain of the Y-box proteins. We estimate that there are at least 15 copies per haploid genome. C1 NICHHD,MOLEC EMBRYOL LAB,BETHESDA,MD 20892. NR 23 TC 8 Z9 8 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 APR 20 PY 1994 VL 141 IS 2 BP 255 EP 259 DI 10.1016/0378-1119(94)90581-9 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA NJ563 UT WOS:A1994NJ56300017 PM 8163198 ER PT J AU COIA, GM WHITE, PS MEYER, TJ WINK, DA KEEFER, LK DAVIS, WM AF COIA, GM WHITE, PS MEYER, TJ WINK, DA KEEFER, LK DAVIS, WM TI PREPARATION OF OSMIUM HYDRAZIDO COMPLEXES BY INTERCEPTION OF AN OSMIUM(IV) IMIDO INTERMEDIATE SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Note ID REDUCTION; CLEAVAGE; BOND C1 UNIV N CAROLINA,DEPT CHEM,VENABLE & KENAN LABS,CHAPEL HILL,NC 27599. NCI,FREDERICK CANC RES & DEV CTR,CHEM SECT,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21702. MIT,DEPT CHEM,CAMBRIDGE,MA 02139. RI Keefer, Larry/N-3247-2014 OI Keefer, Larry/0000-0001-7489-9555 NR 10 TC 21 Z9 21 U1 0 U2 2 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 APR 20 PY 1994 VL 116 IS 8 BP 3649 EP 3650 DI 10.1021/ja00087a081 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA NG889 UT WOS:A1994NG88900081 ER PT J AU GAIL, MH BENICHOU, J AF GAIL, MH BENICHOU, J TI EPIDEMIOLOGY AND BIOSTATISTICS PROGRAM OF THE NATIONAL-CANCER-INSTITUTE SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID BREAST-CANCER; ONSET RP GAIL, MH (reprint author), NATL CANC INST,DIV CANC ETIOL,EXECUT PLAZA N,RM 403,6120 EXECUT BLVD,ROCKVILLE,MD 20892, USA. NR 15 TC 51 Z9 51 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 APR 20 PY 1994 VL 86 IS 8 BP 573 EP 575 DI 10.1093/jnci/86.8.573 PG 3 WC Oncology SC Oncology GA NF214 UT WOS:A1994NF21400002 PM 8179704 ER PT J AU EKBOM, A MCLAUGHLIN, JK KARLSSON, BM NYREN, O GRIDLEY, G ADAMI, HO FRAUMENI, JF AF EKBOM, A MCLAUGHLIN, JK KARLSSON, BM NYREN, O GRIDLEY, G ADAMI, HO FRAUMENI, JF TI PANCREATITIS AND PANCREATIC-CANCER - A POPULATION-BASED STUDY SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID PAST MEDICAL HISTORY; CARCINOMA; RISK; ALCOHOL; DISEASE; SMOKING; TORONTO; COFFEE; DIET AB Background: Little is known about the etiology of cancer of the exocrine portion of the pancreas, which produces a variety of digestive enzymes. Smoking, certain dietary factors, and diabetes mellitus are considered to be risk factors, although the risk estimates are modest in most instances. A recent cohort study of patients with chronic pancreatitis indicated a ninefold to 16-fold increased risk for pancreatic cancer. Purpose: Our purpose was to evaluate the relationship between various clinical types of pancreatitis and pancreatic cancer. Methods: Data for this study were collected from all inpatient medical institutions in Sweden from 1965 until 1983 by the Swedish National Board of Health and Welfare. Data were recorded on individual hospital admissions and discharges in the Inpatient Register. All patients with records in the Inpatient Register coded for acute, chronic, or unspecified pancreatitis were considered for inclusion in the study. A population-based cohort of 7956 patients with at least one discharge diagnosis of pancreatitis was monitored (up to 19 years of follow-up) for the occurrence of pancreatic cancer by record linkages to the Swedish Cancer Registry and Registry of Causes of Death. Results: A total of 46 pancreatic cancers were diagnosed during followup compared with 21 expected (standardized incidence ratio [SIR] of 2.2; 95% confidence interval [CI] 1.6-2.9) for the Uppsala Health Care Region. The excess risk for women and men was similar-most pronounced during the first period of follow-up (2-4 years) after discharge and close to unity after more than 10 years of follow-up. Patients with chronic pancreatitis and patients with more than one discharge diagnosis of either acute or unspecified pancreatitis were at higher risk (SIR = 3.8; 95% CI 1.4-8.2 and SIR = 4.8; 95% CI 1.9-9.9, respectively) compared with those with only one discharge of acute (SIR = 1.6; 95% CI 0.9-2.7) or unspecified (SIR = 2.1; 95% CI 1.2-3.2) pancreatitis. Conclusions: Our finding of a moderate excess of pancreatic cancer among patients with pancreatitis, especially the chronic or recurrent forms, supports some earlier clinical and case-control studies, but it is not consistent with the ninefold to 16-fold risk reported in a recent cohort study. The absence of an increased risk 10 years or more after first discharge for pancreatitis argues against a straightforward causal relationship. Because of the relatively short interval between diagnosis of pancreatitis and pancreatic cancer, it is possible that some forms of pancreatitis are a precursor to pancreatic cancer or that shared risk factors for both diseases (e.g., cigarette smoking) may also be involved. C1 HARVARD UNIV,SCH PUBL HLTH,DEPT EPIDEMIOL,BOSTON,MA. NATL CANC INST,EPIDEMIOL & BIOSTAT PROGRAM,BETHESDA,MD. RP EKBOM, A (reprint author), UNIV UPPSALA HOSP,CANC EPIDEMIOL UNIT,S-75185 UPPSALA,SWEDEN. NR 23 TC 136 Z9 139 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 APR 20 PY 1994 VL 86 IS 8 BP 625 EP 627 DI 10.1093/jnci/86.8.625 PG 3 WC Oncology SC Oncology GA NF214 UT WOS:A1994NF21400013 PM 8145277 ER PT J AU JURETIC, D HENDLER, RW KAMP, F CAUGHEY, WS ZASLOFF, M WESTERHOFF, HV AF JURETIC, D HENDLER, RW KAMP, F CAUGHEY, WS ZASLOFF, M WESTERHOFF, HV TI MAGAININ OLIGOMERS REVERSIBLY DISSIPATE DELTA-MU(H+) IN CYTOCHROME-OXIDASE LIPOSOMES SO BIOCHEMISTRY LA English DT Article ID ANTIMICROBIAL ACTIVITY; OXIDATIVE-PHOSPHORYLATION; PHOSPHOLIPID-VESICLES; RESPIRATORY CONTROL; LIPID BILAYERS; XENOPUS-LAEVIS; FROG-SKIN; PEPTIDES; MEMBRANES; IMMUNITY AB Magainin peptides present in the skin of Xenopus laevis and identified as antimicrobial agents are shown to decrease the membrane potential in cytochrome oxidase liposomes. They also released respiratory control with a third or higher order concentration dependence. Respiratory control was restored by proteolytic digestion of the added magainin. The amount of magainin required for half-maximal stimulation of respiration was proportional to lipid concentration. At appreciably higher concentrations magainins inhibited uncoupled respiration. The results are discussed in terms of a model in which most of the added magainin adsorbs as a monomer to the membranes but equilibrates with a multimeric pore that causes rather general permeability of membranes. The ensuing ion permeation dissipates membrane potential and stimulates respiration. C1 NHLBI, CELL BIOL LAB, MEMBRANE ENZYMOL SECT, BETHESDA, MD 20892 USA. UNIV AMSTERDAM, BIOCTR, EC SLATER INST BIOCHEM RES, 1018 TV AMSTERDAM, NETHERLANDS. COLORADO STATE UNIV, DEPT BIOCHEM, FT COLLINS, CO 80523 USA. CHILDRENS HOSP PHILADELPHIA, DEPT PEDIAT, PHILADELPHIA, PA 19104 USA. CHILDRENS HOSP PHILADELPHIA, DEPT GENET, DIV HUMAN GENET, PHILADELPHIA, PA 19104 USA. MAGAININ SCI INC, PLYMOUTH MEETING, PA USA. NETHERLANDS CANC INST, DIV MOLEC BIOL, 1066 CX AMSTERDAM, NETHERLANDS. RI Westerhoff, Hans/I-5762-2012 OI Westerhoff, Hans/0000-0002-0443-6114 NR 50 TC 40 Z9 40 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD APR 19 PY 1994 VL 33 IS 15 BP 4562 EP 4570 DI 10.1021/bi00181a017 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NH493 UT WOS:A1994NH49300017 PM 8161511 ER PT J AU HENDLER, RW DANCSHAZY, Z BOSE, S SHRAGER, RI TOKAJI, Z AF HENDLER, RW DANCSHAZY, Z BOSE, S SHRAGER, RI TOKAJI, Z TI INFLUENCE OF EXCITATION-ENERGY ON THE BACTERIORHODOPSIN PHOTOCYCLE SO BIOCHEMISTRY LA English DT Article ID HALOBACTERIUM-HALOBIUM; PURPLE MEMBRANE; SCHIFF-BASE; RESONANCE RAMAN; CHROMOPHORE; FORMS AB Kinetic curves for the bacteriorhodopsin (BR) photocycle were obtained both at 570 and at 412 nm at a series of increasing levels of intensity of the exciting laser. Singular value decomposition (SVD) of these curves showed two transitions in the kinetic profiles that occurred at specific levels of actinic light. This means that the photocycle was influenced by photon density in two ways. In a separate application of SVD, time-resolved optical spectra were analyzed at each of many levels of exciting laser intensities. The studies showed that the transition at the low level of laser intensity was due principally to an increase in the amount of BR that was turning over. The transition at the higher level of laser intensity showed a fundamental change in kinetics of the photocycle. At low intensity levels, the fast form of M (M(f)) predominated, whereas at high levels the slow form of M (M(s)) predominated. A distinction was found between M(f) and M(s), in that the former decayed directly to the O intermediate whereas the latter decayed. C1 NIH,DIV COMP RES & TECHNOL,BETHESDA,MD 20892. HUNGARIAN ACAD SCI,BIOL RES CTR,INST BIOPHYS,H-6701 SZEGED,HUNGARY. RP HENDLER, RW (reprint author), NHLBI,CELL BIOL LAB,BETHESDA,MD 20892, USA. NR 28 TC 32 Z9 32 U1 1 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD APR 19 PY 1994 VL 33 IS 15 BP 4604 EP 4610 DI 10.1021/bi00181a022 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NH493 UT WOS:A1994NH49300022 PM 8161516 ER PT J AU PAVLOV, YI MINNICK, DT IZUTA, S KUNKEL, TA AF PAVLOV, YI MINNICK, DT IZUTA, S KUNKEL, TA TI DNA-REPLICATION FIDELITY WITH 8-OXODEOXYGUANOSINE TRIPHOSPHATE SO BIOCHEMISTRY LA English DT Article ID I KLENOW FRAGMENT; ESCHERICHIA-COLI; POLYMERASE-I; MUTATIONAL SPECIFICITY; IONIZING-RADIATION; MUTT PROTEIN; INVITRO; SITE; 8-HYDROXYGUANINE; MUTATOR AB Oxidative metabolism is known to generate mutagenic compounds within cells, among which is 8-oxodeoxyguanosine. Here the mutagenic potential of the triphosphate form of this base analog (8-O-dGTP) is investigated during replication in vitro of the lacZ alpha-complementation sequence in M13mp2 DNA. Adding 8-O-dGTP at equimolar concentration with the normal dNTPs to polymerization reactions decreases the fidelity of DNA synthesis by exonuclease-deficient Klenow, T4, and Thermus thermophilus DNA polymerases. Sequence analysis of mutants suggests that 8-O-dGMP is misincorporated opposite template adenines, yielding A --> C transversions. The degree of polymerase selectivity against this error is enzyme-dependent, with rates varying by >25-fold. To determine if the A.8-O-dGMP mispair is proofread, a direct comparison of the fidelity of proofreading-proficient and proofreading-deficient Klenow and T4 DNA polymerases was made. Although the exonuclease activity of Klenow polymerase did not substantially reduce overall misincorporation of 8-O-dGMP, misincorporation was lower for the proofreading-proficient T4 enzyme as compared to its proofreading-deficient derivative. These data suggest that the A.8-O-dGMP mispair can be proofread. The mutagenic potential of 8-O-dGTP with eukaryotic systems was also examined. Misincorporation of 8-O-dGTP opposite adenine was observed during SV40 origin-dependent replication of double-stranded DNA in HeLa cell extracts. When present during replication at a concentration equal to the four normal dNTPs, 8-O-dGTP was at least 13-fold more mutagenic for A.T --> C.G transversions than was a 100-fold excess of normal dGTP. These data suggest that 8-O-dGTP could be highly mutagenic during nuclear genomic replication in eukaryotes, with a specificity similar to that in Escherichia coli. DNA polymerase gamma, the replicative polymerase for mitochondrial DNA, also readily misincorporated 8-O-dGMP opposite adenine despite the presence of a highly active proofreading exonuclease activity. Given the amount of oxidative metabolism occurring in mitochondria, this result has implications for the stability of the mitochondrial genome and for the origin of degenerative diseases resulting from mitochondrial mutations. C1 NIEHS,MOLEC GENET LAB,RES TRIANGLE PK,NC 27709. ST PETERSBURG STATE UNIV,DEPT GENET,ST PETERSBURG 199034,RUSSIA. NR 46 TC 133 Z9 137 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD APR 19 PY 1994 VL 33 IS 15 BP 4695 EP 4701 DI 10.1021/bi00181a029 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NH493 UT WOS:A1994NH49300033 PM 8161527 ER PT J AU AHMED, SA MILES, EW AF AHMED, SA MILES, EW TI AN ALTERNATE OPEN CONFORMATION OF THE TRYPTOPHAN SYNTHASE ALPHA-2-BETA-2 COMPLEX SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 3 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 APR 19 PY 1994 VL 8 IS 7 BP A1280 EP A1280 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA NH516 UT WOS:A1994NH51600337 ER PT J AU ANDERSON, LM FORNWALD, LW BEEBE, LE AF ANDERSON, LM FORNWALD, LW BEEBE, LE TI SUPPRESSION OF PULMONARY CYTOCHROME-P450 2B IN AH-RESPONSIVE AND NONRESPONSIVE MICE BY AROCLOR-1254 SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI,FCRDC,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21702. PRI DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. NR 0 TC 0 Z9 0 U1 1 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 APR 19 PY 1994 VL 8 IS 7 BP A1383 EP A1383 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA NH516 UT WOS:A1994NH51600934 ER PT J AU ANGOV, E CAMERINIOTERO, RD AF ANGOV, E CAMERINIOTERO, RD TI THE RECA GENE FROM THERMUS-AQUATICUS - CLONING, EXPRESSION AND BIOCHEMICAL-CHARACTERIZATION SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIDDKD,GENET & BIOCHEM BRANCH,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 APR 19 PY 1994 VL 8 IS 7 BP A1331 EP A1331 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA NH516 UT WOS:A1994NH51600635 ER PT J AU APPLEBY, SB RISTIMAKI, A CROFFORD, L WILDER, RL HLA, T AF APPLEBY, SB RISTIMAKI, A CROFFORD, L WILDER, RL HLA, T TI STRUCTURE AND REGULATION OF EXPRESSION OF THE CYCLOOXYGENASE-2 GENE SO FASEB JOURNAL LA English DT Meeting Abstract C1 AMER RED CROSS,HOLLAND LAB,ROCKVILLE,MD. NIAMS,BETHESDA,MD. RI Hla, Timothy/G-5873-2012; Crofford, Leslie/J-8010-2013 OI Hla, Timothy/0000-0001-8355-4065; 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 APR 19 PY 1994 VL 8 IS 7 BP A1462 EP A1462 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA NH516 UT WOS:A1994NH51601397 ER PT J AU AZNAVOORIAN, S STRACKE, ML MCCLANAHAN, J PARSONS, J LIOTTA, LA AF AZNAVOORIAN, S STRACKE, ML MCCLANAHAN, J PARSONS, J LIOTTA, LA TI THE ROLE OF VITRONECTIN AND THE VITRONECTIN RECEPTOR ALPHA-NU-BETA-3 IN THE MIGRATION OF HUMAN-MELANOMA CELLS 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 APR 19 PY 1994 VL 8 IS 7 BP A1452 EP A1452 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA NH516 UT WOS:A1994NH51601339 ER PT J AU BAE, YS NOH, DY RHEE, SG AF BAE, YS NOH, DY RHEE, SG TI CHEMICAL CROSS-LINKING OF PHOSPHOLIPASE ISOZYMES AND THEIR ASSOCIATED PROTEINS SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI,BIOCHEM 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 APR 19 PY 1994 VL 8 IS 7 BP A1438 EP A1438 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA NH516 UT WOS:A1994NH51601255 ER PT J AU BAI, G KUSIAK, JW AF BAI, G KUSIAK, JW TI THE PROXIMAL 5' FLANKING SEQUENCE OF THE RAT N-METHYL-D-ASPARTATE (NMDA) RECEPTOR-1 (NR1) GENE DETERMINES NEURONAL EXPRESSION IN TRANSIENT TRANSFECTION ASSAYS SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIH,GERONTOL RES CTR,MOLEC NEUROBIOL UNIT,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 APR 19 PY 1994 VL 8 IS 7 BP A1274 EP A1274 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA NH516 UT WOS:A1994NH51600307 ER PT J AU BALASUNDARAM, D DINMAN, JD TABOR, CW TABOR, H AF BALASUNDARAM, D DINMAN, JD TABOR, CW TABOR, H TI ELEVATED PUTRESCINE LEVELS INCREASE +1 RIBOSOMAL FRAMESHIFTING EFFICIENCY IN MUTANTS OF SACCHAROMYCES-CEREVISIAE SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIDDKD,BIOCHEM PHARMACOL 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 APR 19 PY 1994 VL 8 IS 7 BP A1306 EP A1306 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA NH516 UT WOS:A1994NH51600490 ER PT J AU BAROUCH, W PRASAD, K GREENE, L EISENBERG, E AF BAROUCH, W PRASAD, K GREENE, L EISENBERG, E TI ACTIVATION OF HSP70 ATPASE ACTIVITY BY CLATHRIN BASKETS PLUS COFACTOR IN THE ABSENCE OF CLATHRIN UNCOATING SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI,CELL BIOL LAB,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 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 APR 19 PY 1994 VL 8 IS 7 BP A1312 EP A1312 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA NH516 UT WOS:A1994NH51600531 ER PT J AU BARRY, JA GAWRISCH, K AF BARRY, JA GAWRISCH, K TI NMR EVIDENCE FOR SURFACE INTERACTIONS OF ETHANOL WITH LIPID BILAYERS SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAAA,ROCKVILLE,MD 20852. 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 APR 19 PY 1994 VL 8 IS 7 BP A1453 EP A1453 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA NH516 UT WOS:A1994NH51601343 ER PT J AU BAXEVANIS, AD BRYANT, SH LANDSMAN, D AF BAXEVANIS, AD BRYANT, SH LANDSMAN, D TI 3-DIMENSIONAL STRUCTURAL ALIGNMENT AND PHYLOGENETIC ANALYSIS OF THE HMG-1 BOX DNA-BINDING PROTEINS SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIH,NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,BETHESDA,MD 20892. NR 1 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 APR 19 PY 1994 VL 8 IS 7 BP A1271 EP A1271 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA NH516 UT WOS:A1994NH51600287 ER PT J AU BECERRA, SP WU, YQ NOTARIO, V CHADER, GJ AF BECERRA, SP WU, YQ NOTARIO, V CHADER, GJ TI PIGMENT EPITHELIUM-DERIVED FACTOR - CHARACTERIZATION USING A HIGHLY SPECIFIC POLYCLONAL ANTIBODY SO FASEB JOURNAL LA English DT Meeting Abstract C1 NEI,BETHESDA,MD 20892. GEORGETOWN UNIV,SCH MED,WASHINGTON,DC 20007. 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 APR 19 PY 1994 VL 8 IS 7 BP A1302 EP A1302 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA NH516 UT WOS:A1994NH51600466 ER PT J AU BEEBE, LE FORNWALD, LW ANDERSON, LM AF BEEBE, LE FORNWALD, LW ANDERSON, LM TI LACK OF AN ACUTE EFFECT OF 2,3,7,8-TCDD ON CAMP-DEPENDENT PROTEIN-KINASE (PKA) IN MOUSE-LIVER SO FASEB JOURNAL LA English DT Meeting Abstract C1 PRI DYNCORP,BIOL & CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. NCI,FCRDC,COMPARAT CARCINOGENESIS LAB,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 APR 19 PY 1994 VL 8 IS 7 BP A1436 EP A1436 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA NH516 UT WOS:A1994NH51601246 ER PT J AU BEG, ZH STONIK, JA HOEG, JM BREWER, HB AF BEG, ZH STONIK, JA HOEG, JM BREWER, HB TI PROTEIN KINASE-C-MEDIATED REVERSIBLE PHOSPHORYLATION OF APOLIPOPROTEIN-B-100 FROM HUMAN PLASMA AND HEPG-2 CELLS SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI,MOLEC DIS BRANCH,BETHESDA,MD 20892. ALIGARH MUSLIM UNIV,JAWAHARLAL NEHRU MED COLL,DEPT BIOCHEM,ALIGARH 202001,UTTAR PRADESH,INDIA. 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 APR 19 PY 1994 VL 8 IS 7 BP A1327 EP A1327 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA NH516 UT WOS:A1994NH51600608 ER PT J AU BELL, JB ECKERT, K JOYCE, C KUNKEL, TA AF BELL, JB ECKERT, K JOYCE, C KUNKEL, TA TI IDENTIFICATION OF ANTIMUTATOR AND MUTATOR PHENOTYPES AMONG ESCHERICHIA-COLI DNA-POLYMERASE DERIVATIVES SO FASEB JOURNAL LA English DT Meeting Abstract C1 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 APR 19 PY 1994 VL 8 IS 7 BP A1332 EP A1332 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA NH516 UT WOS:A1994NH51600637 ER PT J AU BOLES, DJ PROIA, RL AF BOLES, DJ PROIA, RL TI STABILITY AND PROCESSING OF BETA-HEXOSAMINIDASE-A MESSENGER-RNA IN THE PRESENCE OF A COMMON 4BP INSERTION SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIDDK,GENET & BIOCHEM BRANCH,BETHESDA,MD 20892. RI Proia, Richard/A-7908-2012 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 APR 19 PY 1994 VL 8 IS 7 BP A1268 EP A1268 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA NH516 UT WOS:A1994NH51600270 ER PT J AU BROYLES, RH KYKER, KD BLAIR, FC KURIEN, BT STEWART, DR BERG, PE SCHECHTER, AN AF BROYLES, RH KYKER, KD BLAIR, FC KURIEN, BT STEWART, DR BERG, PE SCHECHTER, AN TI DEVELOPMENTAL REGULATION OF THE HUMAN ADULT BETA-GLOBIN GENE SO FASEB JOURNAL LA English DT Meeting Abstract C1 UNIV OKLAHOMA,HLTH SCI CTR,OKLAHOMA CITY,OK 73190. UNIV MARYLAND,BALTIMORE,MD 21201. NIH,BETHESDA,MD 20892. RI Kurien, Biji/C-2392-2008 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 APR 19 PY 1994 VL 8 IS 7 BP A1272 EP A1272 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA NH516 UT WOS:A1994NH51600295 ER PT J AU BURKE, TR SMYTH, MS OTAKA, A NOMIZU, M ROLLER, PP WOLF, G CASE, R SHOELSON, SE AF BURKE, TR SMYTH, MS OTAKA, A NOMIZU, M ROLLER, PP WOLF, G CASE, R SHOELSON, SE TI PHOSPHATASE-RESISTANT SH2 DOMAIN INHIBITORS SO FASEB JOURNAL LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,BOSTON,MA 02115. NCI,DTP,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 APR 19 PY 1994 VL 8 IS 7 BP A1222 EP A1222 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA NH516 UT WOS:A1994NH51600008 ER PT J AU BURROWS, SD HENSLEY, P FRANKLIN, SG WHITE, JR DOYLE, ML BROOKS, IS MCNULTY, DE SCOTT, M KNUTSON, J PORTER, D YOUNG, PR AF BURROWS, SD HENSLEY, P FRANKLIN, SG WHITE, JR DOYLE, ML BROOKS, IS MCNULTY, DE SCOTT, M KNUTSON, J PORTER, D YOUNG, PR TI PURIFICATION AND CHARACTERIZATION OF INTERLEUKIN-8 (IL-8) - DEMONSTRATION OF DIMER DISSOCIATION SO FASEB JOURNAL LA English DT Meeting Abstract C1 SMITHKLINE BEECHAM PHARMACEUT,KING OF PRUSSIA,PA 19406. NHLBI,LCB,BETHESDA,MD 20892. RI Brooks, Ian/E-7052-2010 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 APR 19 PY 1994 VL 8 IS 7 BP A1293 EP A1293 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA NH516 UT WOS:A1994NH51600416 ER PT J AU BUTZOW, JJ FRASIER, TL JANZEN, C CHATTERJI, D EICHHORN, GL AF BUTZOW, JJ FRASIER, TL JANZEN, C CHATTERJI, D EICHHORN, GL TI MODIFIED PREPARATION AND ZN CONTENT OF RNA-POLYMERASE-II OF YEAST SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. NR 2 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 APR 19 PY 1994 VL 8 IS 7 BP A1344 EP A1344 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA NH516 UT WOS:A1994NH51600710 ER PT J AU CASASFINET, JR PLOUG, M BALDWIN, ET DANO, K ERICKSON, JW AF CASASFINET, JR PLOUG, M BALDWIN, ET DANO, K ERICKSON, JW TI STRUCTURAL-ANALYSIS OF THE SOLUBLE HUMAN UROKINASE-TYPE PLASMINOGEN-ACTIVATOR RECEPTOR (UPAR), AND ITS CONSTITUENT DOMAINS SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI,FCRDC,PRI DYNCORP,FREDERICK,MD 21702. RIGSHOSP,FINSENLAB,DK-2100 COPENHAGEN,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 APR 19 PY 1994 VL 8 IS 7 BP A1352 EP A1352 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA NH516 UT WOS:A1994NH51600756 ER PT J AU CHAE, HZ CHUNG, SJ RHEE, SG AF CHAE, HZ CHUNG, SJ RHEE, SG TI ENZYMATIC REGENERATION SYSTEM OF THIOL-SPECIFIC ANTIOXIDANT SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI,BIOCHEM 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 APR 19 PY 1994 VL 8 IS 7 BP A1358 EP A1358 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA NH516 UT WOS:A1994NH51600793 ER PT J AU CHAMBERLIN, ME LEI, KJ CHOU, JY AF CHAMBERLIN, ME LEI, KJ CHOU, JY TI DIFFERENTIAL EXPRESSION OF HUMAN PREGNANCY-SPECIFIC GLYCOPROTEIN GENES SO FASEB JOURNAL LA English DT Meeting Abstract C1 NICH,HUMAN GENET BRANCH,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 APR 19 PY 1994 VL 8 IS 7 BP A1336 EP A1336 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA NH516 UT WOS:A1994NH51600666 ER PT J AU CHEN, FS WAGNER, PD AF CHEN, FS WAGNER, PD TI 14-3-3 PROTEINS BIND TO HISTONE AND AFFECT BOTH HISTONE PHOSPHORYLATION AND DEPHOSPHORYLATION SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI,BIOCHEM 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 APR 19 PY 1994 VL 8 IS 7 BP A1316 EP A1316 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA NH516 UT WOS:A1994NH51600550 ER PT J AU CHOUDHURY, BK HOU, EW KAWAI, Y LI, SSL AF CHOUDHURY, BK HOU, EW KAWAI, Y LI, SSL TI CLONING AND EXPRESSION OF CDNAS ENCODING THE ENHANCER OF SPLIT GROUCHO GENES FROM HUMAN, MOUSE AND XENOPUS SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIEHS,MOLEC GENET LAB,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 APR 19 PY 1994 VL 8 IS 7 BP A1333 EP A1333 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA NH516 UT WOS:A1994NH51600645 ER PT J AU CIOTTI, M HUANG, T OWENS, IS AF CIOTTI, M HUANG, T OWENS, IS TI CHARACTERIZATION OF 2 MICROREGIONS IN THE HUMAN MAJOR BILIRUBIN UDP-GLUCURONOSYLTRANSFERASE ISOZYME SO FASEB JOURNAL LA English DT Meeting Abstract C1 NICHHD,HUMAN GENET BRANCH,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 APR 19 PY 1994 VL 8 IS 7 BP A1441 EP A1441 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA NH516 UT WOS:A1994NH51601275 ER PT J AU COLLINS, FS AF COLLINS, FS TI THE HUMAN GENOME PROJECT 1994 SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIH,NATL CTR HUMAN GENOME RES,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 APR 19 PY 1994 VL 8 IS 7 BP A1260 EP A1260 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA NH516 UT WOS:A1994NH51600223 ER PT J AU DAS, RB VONDERHAAR, BK AF DAS, RB VONDERHAAR, BK TI TRANSDUCTION OF PROLACTINS GROWTH SIGNAL THROUGH BOTH LONG AND SHORT FORMS OF THE PROLACTIN RECEPTOR SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI,TUMOR IMMUNOL & BIOL LAB,BETHESDA,MD 20892. NR 1 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 APR 19 PY 1994 VL 8 IS 7 BP A1317 EP A1317 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA NH516 UT WOS:A1994NH51600557 ER PT J AU DAVIS, DA WINGFIELD, PT STAHL, SJ KAUFMAN, J LEVINE, RL AF DAVIS, DA WINGFIELD, PT STAHL, SJ KAUFMAN, J LEVINE, RL TI THE ROLE OF CYSTEINES IN THE INHIBITION OF THE HIV-1 PROTEASE BY COPPER AND COPPER-COMPLEXES SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. PROT EXPRESS LAB,BETHESDA,MD 20892. RI Levine, Rodney/D-9885-2011 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 APR 19 PY 1994 VL 8 IS 7 BP A1373 EP A1373 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA NH516 UT WOS:A1994NH51600882 ER PT J AU DE, SK MARSH, JW AF DE, SK MARSH, JW TI HIV-1 NEF INHIBITS A COMMON ACTIVATION PATHWAY IN NIH-3T3 CELLS SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIMH,MOLEC BIOL 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 APR 19 PY 1994 VL 8 IS 7 BP A1414 EP A1414 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA NH516 UT WOS:A1994NH51601118 ER PT J AU DEGERMAN, E RASCON, A TORNQVIST, H TAIRA, M LEROY, MJ MURATA, T BELFRAGE, P MANGANIELLO, VC AF DEGERMAN, E RASCON, A TORNQVIST, H TAIRA, M LEROY, MJ MURATA, T BELFRAGE, P MANGANIELLO, VC TI IDENTIFICATION OF THE CAMP-DEPENDENT PROTEIN-KINASE (CAMP-PK) PHOSPHORYLATION SITE ON THE RAT ADIPOCYTE TYPE-III CGMP-INHIBITED (CGI-PDE) PHOSPHODIESTERASE SO FASEB JOURNAL LA English DT Meeting Abstract C1 LUND UNIV,S-22101 LUND,SWEDEN. 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 APR 19 PY 1994 VL 8 IS 7 BP A1328 EP A1328 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA NH516 UT WOS:A1994NH51600618 ER PT J AU DEGTYAREV, MY SPIEGEL, AM JONES, TLZ AF DEGTYAREV, MY SPIEGEL, AM JONES, TLZ TI BETA-GAMMA-SUBUNITS ARE REQUIRED FOR MEMBRANE ATTACHMENT OF A MUTANT, NONPALMITOYLATED G-PROTEIN ALPHA(I)-SUBUNIT SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIDDK,MOLEC PATHYOPHYSIOL BRANCH,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 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 APR 19 PY 1994 VL 8 IS 7 BP A1431 EP A1431 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA NH516 UT WOS:A1994NH51601215 ER PT J AU DEMENDEZ, I ADAMS, AG LETO, TL AF DEMENDEZ, I ADAMS, AG LETO, TL TI ROLE OF SH3 DOMAINS IN ASSEMBLY OF THE NADPH OXIDASE IN WHOLE CELLS SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAID,HOST DEF LAB,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 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 APR 19 PY 1994 VL 8 IS 7 BP A1349 EP A1349 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA NH516 UT WOS:A1994NH51600740 ER PT J AU DENKINS, YM PAWLOSKY, RJ SALEM, N AF DENKINS, YM PAWLOSKY, RJ SALEM, N TI THE EFFECT OF A CORN-OIL BASED DIET ON LONG-CHAIN POLYUNSATURATED FATTY-ACID FORMATION DURING NEURAL DEVELOPMENT SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAAA,ROCKVILLE,MD 20852. 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 APR 19 PY 1994 VL 8 IS 7 BP A1471 EP A1471 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA NH516 UT WOS:A1994NH51601451 ER PT J AU DREW, PD NAGLE, JW BIDDISON, WE OZATO, K BECKER, KG AF DREW, PD NAGLE, JW BIDDISON, WE OZATO, K BECKER, KG TI ISOLATION AND CHARACTERIZATION OF NOVEL ZINC-FINGER CDNAS FROM HUMAN BRAIN BY AUTOMATED DNA-SEQUENCING SO FASEB JOURNAL LA English DT Meeting Abstract C1 NINCDS,NEUROIMMUNOL BRANCH,BETHESDA,MD 20892. NINCDS,NEUROGENET BRANCH,BETHESDA,MD 20892. NICHHD,MOLEC GROWTH REGULAT 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 APR 19 PY 1994 VL 8 IS 7 BP A1260 EP A1260 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA NH516 UT WOS:A1994NH51600225 ER PT J AU DUNTEN, RL WAIT, SJ BACKLUND, PS AF DUNTEN, RL WAIT, SJ BACKLUND, PS TI PURIFICATION AND CHARACTERIZATION OF A NOVEL PROTEIN C-TERMINAL PRENYL-CYSTEINE METHYLESTERASE ACTIVITY FROM RABBIT BRAIN SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIMH,GEN & COMPARAT BIOCHEM 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 APR 19 PY 1994 VL 8 IS 7 BP A1360 EP A1360 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA NH516 UT WOS:A1994NH51600804 ER PT J AU FAUST, LP ELBENNA, J CHRISTENSEN, B CHANOCK, SJ BABIOR, BM AF FAUST, LP ELBENNA, J CHRISTENSEN, B CHANOCK, SJ BABIOR, BM TI THE STUDY OF P47(PHOX)PHOSPHORYLATION BY SITE-DIRECTED MUTAGENESIS IN B-LYMPHOCYTES SO FASEB JOURNAL LA English DT Meeting Abstract C1 Scripps Res Inst, RES INST, LA JOLLA, CA 92037 USA. NCI, PEDIAT BRANCH, 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 APR 19 PY 1994 VL 8 IS 7 BP A1348 EP A1348 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA NH516 UT WOS:A1994NH51600737 ER PT J AU FELSENFELD, G BOYES, J BRESNICK, E CHUNG, J CLARK, D STUDITSKY, V AF FELSENFELD, G BOYES, J BRESNICK, E CHUNG, J CLARK, D STUDITSKY, V TI CHROMATIN STRUCTURE AND THE REGULATION OF GLOBIN GENE-EXPRESSION SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIDDK,MOLEC BIOL 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 APR 19 PY 1994 VL 8 IS 7 BP A1326 EP A1326 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA NH516 UT WOS:A1994NH51600603 ER PT J AU FEWELL, JW KUFF, EL PRABHAKAR, BS AF FEWELL, JW KUFF, EL PRABHAKAR, BS TI ACCESSIBILITY OF KU EPITOPES VARIES WITH CELL-DENSITY IN CULTURE SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. UNIV TEXAS,GALVESTON,TX 77555. 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 APR 19 PY 1994 VL 8 IS 7 BP A1390 EP A1390 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA NH516 UT WOS:A1994NH51600980 ER PT J AU FISHER, MA JIN, D AF FISHER, MA JIN, D TI ASSOCIATION KINETICS AND STABILITY OF OPEN COMPLEXES FORMED AT ESCHERICHIA-COLI PYRBI PROMOTER SO FASEB JOURNAL LA English DT Meeting Abstract C1 RANDOLPH MACON COLL,DEPT CHEM,ASHLAND,VA 23005. NCI,MOLEC BIOL 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 APR 19 PY 1994 VL 8 IS 7 BP A1269 EP A1269 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA NH516 UT WOS:A1994NH51600273 ER PT J AU FISHER, RJ FIVASH, M CASAFINET, J BLADEN, S MCNITT, KL AF FISHER, RJ FIVASH, M CASAFINET, J BLADEN, S MCNITT, KL TI REAL-TIME BIACORE MEASUREMENTS OF ESCHERICHIA-COLI SINGLE-STRANDED-DNA BINDING-PROTEIN TO POLYDEOXYTHYMIDYLIC ACID REVEAL SINGLE STATE KINETICS WITH STERIC COOPERATIVITY SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI,FCRDC,CELLULAR BIOCHEM LAB,FREDERICK,MD 21702. NCI,FCRDC,DATA MANAGEMENT SERV INC,FREDERICK,MD 21702. NCI,FCRDC,PRI DYNCORP,STRUCT BIOCHEM PROGRAM,FREDERICK,MD 21702. RI Fisher, Robert/B-1431-2009 NR 0 TC 2 Z9 2 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 APR 19 PY 1994 VL 8 IS 7 BP A1271 EP A1271 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA NH516 UT WOS:A1994NH51600288 ER PT J AU FRIGUET, B SZWEDA, LI STADTMAN, ER AF FRIGUET, B SZWEDA, LI STADTMAN, ER TI INHIBITION OF THE MULTICATALYTIC PROTEASE BY 4-HYDROXY-2-NONENAL MODIFIED PROTEIN SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI,BIOCHEM 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 APR 19 PY 1994 VL 8 IS 7 BP A1357 EP A1357 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA NH516 UT WOS:A1994NH51600788 ER PT J AU GATES, D KASHIWAYA, Y VEECH, RL AF GATES, D KASHIWAYA, Y VEECH, RL TI ADJUSTMENT OF KOBS OF CREATINE-KINASE AND OTHER EQUILIBRIUM-CONSTANTS FOR PH AND FREE [MG2+] SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAAA,METAB LAB,ROCKVILLE,MD 20852. 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 APR 19 PY 1994 VL 8 IS 7 BP A1299 EP A1299 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA NH516 UT WOS:A1994NH51600450 ER PT J AU GILLETTE, JR SUGIYAMA, K DARBYSHIRE, JF AF GILLETTE, JR SUGIYAMA, K DARBYSHIRE, JF TI MECHANISMS OF SEQUENTIAL METABOLISM IN-VITRO - A STUDY OF THE FORMATION OF 16-ALPHA-HYDROXYANDROSTENEDIONE FROM TESTOSTERONE BY PURIFIED RAT CYP2C11 SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI,CHEM PHARMACOL 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 APR 19 PY 1994 VL 8 IS 7 BP A1249 EP A1249 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA NH516 UT WOS:A1994NH51600162 ER PT J AU GLADYSHEV, VN KHANGULOV, SV AXLEY, MJ STADTMAN, TC AF GLADYSHEV, VN KHANGULOV, SV AXLEY, MJ STADTMAN, TC TI SELENIUM IS COORDINATED WITH MOLYBDENUM IN FORMATE DEHYDROGENASE-H FROM ESCHERICHIA-COLI SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI,LB,BETHESDA,MD 20892. 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 APR 19 PY 1994 VL 8 IS 7 BP A1368 EP A1368 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA NH516 UT WOS:A1994NH51600851 ER PT J AU GOLDSTEIN, JA GHANAYEM, BI FALETTO, M LASKER, J SULLIVAN, T ROMKESSPARKS, M RAUCY, J WILKINSON, G MEYER, U DEMORAIS, SMF AF GOLDSTEIN, JA GHANAYEM, BI FALETTO, M LASKER, J SULLIVAN, T ROMKESSPARKS, M RAUCY, J WILKINSON, G MEYER, U DEMORAIS, SMF TI ALTERATIONS IN HUMAN CYP2C19, THE MAJOR S-MEPHENYTOIN 4'-HYDROXYLASE, IN POOR METABOLIZERS OF S-MEPHENYTOIN SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIEHS,RES TRIANGLE PK,NC 27709. CUNY MT SINAI SCH MED,NEW YORK,NY 10029. UNIV NEW MEXICO,ALBUQUERQUE,NM 87131. VANDERBILT UNIV,MED CTR,SCH MED,NASHVILLE,TN 37232. UNIV BASEL,CH-4056 BASEL,SWITZERLAND. 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 APR 19 PY 1994 VL 8 IS 7 BP A1257 EP A1257 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA NH516 UT WOS:A1994NH51600211 ER PT J AU GONZALEZ, FJ LEE, YH AF GONZALEZ, FJ LEE, YH TI MECHANISMS OF LIVER-SPECIFIC EXPRESSION OF RAT HEPATIC P450 GENES 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 APR 19 PY 1994 VL 8 IS 7 BP A1242 EP A1242 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA NH516 UT WOS:A1994NH51600121 ER PT J AU HAFT, CR TAYLOR, SI AF HAFT, CR TAYLOR, SI TI A JUXTAMEMBRANE DILEUCINE MOTIF - INVOLVEMENT IN THE INTERNALIZATION AND DEGRADATION OF THE INSULIN-RECEPTOR (IR) SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIH,DIABET BRANCH,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 APR 19 PY 1994 VL 8 IS 7 BP A1319 EP A1319 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA NH516 UT WOS:A1994NH51600569 ER PT J AU HAMASAKI, N TABOR, CW TABOR, H AF HAMASAKI, N TABOR, CW TABOR, H TI SPERMIDINE BIOSYNTHESIS AND THE SPE3 GENE IN SACCHAROMYCES-CEREVISIAE SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIDDKD,BIOCHEM PHARMACOL 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 APR 19 PY 1994 VL 8 IS 7 BP A1443 EP A1443 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA NH516 UT WOS:A1994NH51601287 ER PT J AU HOLTE, LL PETER, SA SINNWELL, T GAWRISCH, K AF HOLTE, LL PETER, SA SINNWELL, T GAWRISCH, K TI DEUTERIUM NMR ORDER PARAMETERS PROBE THE INFLUENCE OF FATTY-ACID UNSATURATION ON CHAIN MOTION IN PHOSPHATIDYLCHOLINES SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAAA,ROCKVILLE,MD 20852. 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 APR 19 PY 1994 VL 8 IS 7 BP A1450 EP A1450 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA NH516 UT WOS:A1994NH51601327 ER PT J AU HWANG, SC LEE, KH SHIN, SH LEE, SB PARK, DJ RHEE, SG AF HWANG, SC LEE, KH SHIN, SH LEE, SB PARK, DJ RHEE, SG TI DISTRIBUTION OF PHOSPHOLIPASE-C ISOZYMES IN ENDOCRINE GLANDS AND CELL-LINES SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI,BIOCHEM 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 APR 19 PY 1994 VL 8 IS 7 BP A1438 EP A1438 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA NH516 UT WOS:A1994NH51601258 ER PT J AU ITOH, K MOUSSAVI, RS ADELSTEIN, RS AF ITOH, K MOUSSAVI, RS ADELSTEIN, RS TI NERVE-SPECIFIC EXPRESSION OF A NONMUSCLE MYOSIN HEAVY-CHAIN SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI,MOLEC CARDIOL LAB,BETHESDA,MD 20892. NR 1 TC 1 Z9 1 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 APR 19 PY 1994 VL 8 IS 7 BP A1303 EP A1303 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA NH516 UT WOS:A1994NH51600476 ER PT J AU IZZO, JA SHERMAN, CA KUSIAK, JW AF IZZO, JA SHERMAN, CA KUSIAK, JW TI ALTERNATIVE RNA SPLICING OF THE MOUSE GLUR2 GENE SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIA,GRC,MOLEC NEUROBIOL UNIT,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 APR 19 PY 1994 VL 8 IS 7 BP A1268 EP A1268 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA NH516 UT WOS:A1994NH51600272 ER PT J AU JENG, JG SOH, YJ LEE, J SONG, BJ AF JENG, JG SOH, YJ LEE, J SONG, BJ TI ISOLATION AND CHARACTERIZATION OF A CDNA CLONE CODING FOR A PYRUVATE DEHYDROGENASE-E1-ALPHA ISOFORM FROM RAT TESTIS SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAAA,NEUROGENET LAB,ROCKVILLE,MD 20852. 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 APR 19 PY 1994 VL 8 IS 7 BP A1348 EP A1348 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA NH516 UT WOS:A1994NH51600733 ER PT J AU JOE, YA PARK, MH AF JOE, YA PARK, MH TI STRUCTURE-FUNCTION-RELATIONSHIPS FOR POSTTRANSLATIONAL SYNTHESIS OF DEOXYHYPUSINE IN EIF-5A SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIDR,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 APR 19 PY 1994 VL 8 IS 7 BP A1291 EP A1291 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA NH516 UT WOS:A1994NH51600407 ER PT J AU JOHNSON, AC YAMAZAKI, H PIEBENGA, E BEGUINOT, L AF JOHNSON, AC YAMAZAKI, H PIEBENGA, E BEGUINOT, L TI EXPRESSION AND CHARACTERIZATION OF THE HUMAN TRANSCRIPTIONAL REPRESSOR GCF IN CANCER CELL-LINES SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI,DCBDC,MOLEC BIOL 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 APR 19 PY 1994 VL 8 IS 7 BP A1397 EP A1397 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA NH516 UT WOS:A1994NH51601017 ER PT J AU JONES, CR NIMS, RW AF JONES, CR NIMS, RW TI INDUCTION OF HEPATIC CYTOCHROME-P450 IN MALE F344 RATS EXPOSED TO VARIOUS DIETARY CONCENTRATIONS OF DEXAMETHASONE SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIA,NEUROSCI LAB,BETHESDA,MD 20892. NCI,FCRDC,COMPARAT CARCINOGENESIS,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 APR 19 PY 1994 VL 8 IS 7 BP A1251 EP A1251 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA NH516 UT WOS:A1994NH51600176 ER PT J AU KAHN, RA RANDAZZO, P ZHANG, C TERUI, T ROSENWALD, A CAVENAGH, M AF KAHN, RA RANDAZZO, P ZHANG, C TERUI, T ROSENWALD, A CAVENAGH, M TI ADP-RIBOSYLATION FACTORS (ARF) - ROLES OF N-MYRISTOYLATION AND PHOSPHOLIPID-BINDING IN ITS STRUCTURE AND FUNCTIONS 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 APR 19 PY 1994 VL 8 IS 7 BP A1430 EP A1430 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA NH516 UT WOS:A1994NH51601211 ER PT J AU KASHIWAYA, Y VEECH, RL PASSONNEAU, JV AF KASHIWAYA, Y VEECH, RL PASSONNEAU, JV TI METABOLIC CONTROL ANALYSES OF GLYCOLYTIC METABOLISM IN WORKING PERFUSED RAT-HEART SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAAA,LMMB,ROCKVILLE,MD 20852. 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 APR 19 PY 1994 VL 8 IS 7 BP A1285 EP A1285 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA NH516 UT WOS:A1994NH51600368 ER PT J AU KASUYA, J GOKO, H MEACCI, E TAIRA, M MANGANIELLO, V FUJITAYAMAGUCHI, Y AF KASUYA, J GOKO, H MEACCI, E TAIRA, M MANGANIELLO, V FUJITAYAMAGUCHI, Y TI MOLECULAR AND GENOMIC ANALYSES OF HUMAN CGMP-INHIBITED CAMP-PHOSPHODIESTERASE (CGI-PDE) SO FASEB JOURNAL LA English DT Meeting Abstract C1 CITY HOPE NATL MED CTR,BECKMAN RES INT,DUARTE,CA 91010. NHLBI,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 APR 19 PY 1994 VL 8 IS 7 BP A1400 EP A1400 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA NH516 UT WOS:A1994NH51601036 ER PT J AU KENNEY, NJ HUANG, RP JOHNSON, G OKAMURA, D MATHENY, W PLOWMAN, G SMITH, GH SALOMON, DS ADAMSON, ED AF KENNEY, NJ HUANG, RP JOHNSON, G OKAMURA, D MATHENY, W PLOWMAN, G SMITH, GH SALOMON, DS ADAMSON, ED TI HETEROGENEOUS EXPRESSION OF AMPHIREGULIN (AR) AND CRIPTO (CR-1) IN THE DEVELOPING MOUSE MAMMARY-GLAND SO FASEB JOURNAL LA English DT Meeting Abstract C1 BRISTOL MYERS SQUIBB PHARMACEUT RES INST,SEATTLE,WA 98121. US FDA,CELL BIOL LAB,BETHESDA,MD 20892. LA JOLLA CANC RES FDN,LA JOLLA,CA 92027. NCI,TUMOR IMMUNOL & BIOL,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 APR 19 PY 1994 VL 8 IS 7 BP A1419 EP A1419 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA NH516 UT WOS:A1994NH51601146 ER PT J AU KIM, CG PARK, DE RHEE, SG AF KIM, CG PARK, DE RHEE, SG TI THE DISCRETE NUCLEAR-LOCALIZATION OF BETA-TYPE PHOSPHOLIPASE-C SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI,BIOCHEM 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 APR 19 PY 1994 VL 8 IS 7 BP A1457 EP A1457 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA NH516 UT WOS:A1994NH51601370 ER PT J AU KIM, HY EDSALL, L MA, YC AF KIM, HY EDSALL, L MA, YC TI PREFERENTIAL HYDROLYSIS OF DOCOSAHEXAENOIC ACID (22-6N3) AND ARACHIDONIC-ACID (20-4N6) FROM BRAIN SYNAPTOSOMES BY COBRA VENOM AND RAT-BRAIN PHOSPHOLIPASE-A(2) ACTIVITY SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAAA,DICBR,LMBB,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 APR 19 PY 1994 VL 8 IS 7 BP A1403 EP A1403 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA NH516 UT WOS:A1994NH51601054 ER PT J AU KIM, IY VERES, Z STADTMAN, TC AF KIM, IY VERES, Z STADTMAN, TC TI EFFECTS OF MONO AND DIVALENT METAL-IONS ON ESCHERICHIA-COLI SELENOPHOSPHATE SYNTHETASE-ACTIVITY SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI,LB,BETHESDA,MD 20892. NR 1 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 APR 19 PY 1994 VL 8 IS 7 BP A1412 EP A1412 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA NH516 UT WOS:A1994NH51601106 ER PT J AU KING, C EISENBERG, E GREENE, L AF KING, C EISENBERG, E GREENE, L TI POLYMERIZATION OF HSP70 BY DNAJ IN THE PRESENCE OF ATP SO FASEB JOURNAL LA English DT Meeting Abstract C1 HOWARD UNIV,WASHINGTON,DC 20059. NHLBI,CELL BIOL 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 APR 19 PY 1994 VL 8 IS 7 BP A1354 EP A1354 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA NH516 UT WOS:A1994NH51600767 ER PT J AU KING, MT VEECH, RL AF KING, MT VEECH, RL TI ETHANOL INCREASES CYTOSOLIC INORGANIC-PHOSPHATE IN LIVER BY MOVING PI FROM MITOCHONDRIA TO CYTOSOL SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAAA,METAB LAB,ROCKVILLE,MD 20852. 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 APR 19 PY 1994 VL 8 IS 7 BP A1299 EP A1299 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA NH516 UT WOS:A1994NH51600453 ER PT J AU KLEINER, DE STETLERSTEVENSON, WG AF KLEINER, DE STETLERSTEVENSON, WG TI TIMP-2 CHANGES THE KINETIC MECHANISM OF IN-VITRO ACTIVATION AND SELF-CLEAVAGE OF GELATINASE-A SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI,PATHOL 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 APR 19 PY 1994 VL 8 IS 7 BP A1372 EP A1372 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA NH516 UT WOS:A1994NH51600875 ER PT J AU KOENIG, BW GAWRISCH, K FERRETTI, JA AF KOENIG, BW GAWRISCH, K FERRETTI, JA TI STRUCTURE DETERMINATION OF A PEPTIDE FRAGMENT CORRESPONDING TO THE C-TERMINUS OF GP41 OF HIV IN MEMBRANE MIMETIC ENVIRONMENTS USING DIFFERENT NMR-TECHNIQUES SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NHLBI,BETHESDA,MD 20892. NIAAA,ROCKVILLE,MD 20852. NR 1 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 APR 19 PY 1994 VL 8 IS 7 BP A1353 EP A1353 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA NH516 UT WOS:A1994NH51600765 ER PT J AU KONG, SK CHOCK, PB AF KONG, SK CHOCK, PB TI PURIFICATION AND CHARACTERIZATION OF A NOVEL PROTEIN-KINASE INVOLVED IN PHOSPHORYLATION OF AN UBIQUITIN CARRIER ENZYME SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI,BIOCHEM 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 APR 19 PY 1994 VL 8 IS 7 BP A1434 EP A1434 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA NH516 UT WOS:A1994NH51601232 ER PT J AU KOZYAVKIN, S KRAH, R GELLERT, M STETTER, K LAKE, J SLESAREV, A AF KOZYAVKIN, S KRAH, R GELLERT, M STETTER, K LAKE, J SLESAREV, A TI STRUCTURE AND PROPERTIES OF HYPERTHERMOPHILIC DNA TOPOISOMERASES SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIDDK,MOLEC BIOL LAB,BETHESDA,MD. UNIV REGENSBURG,LEHRSTUHL MIKROBIOL,W-8400 REGENSBURG,GERMANY. UNIV CALIF LOS ANGELES,INST MOLEC BIOL,LOS ANGELES,CA 90024. 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 APR 19 PY 1994 VL 8 IS 7 BP A1272 EP A1272 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA NH516 UT WOS:A1994NH51600294 ER PT J AU KUNDU, GC MANTILE, G MIELE, L CORDELLAMIELE, E MUKHERJEE, AB AF KUNDU, GC MANTILE, G MIELE, L CORDELLAMIELE, E MUKHERJEE, AB TI HIGH-AFFINITY BINDING OF HUMAN CLARA CELL 10KDA PROTEIN ON NIH 3T3 CELL-SURFACE - ITS SIMILARITY TO GROUP-I PHOSPHOLIPASE-A(2) RECEPTOR SO FASEB JOURNAL LA English DT Meeting Abstract C1 NICHHD,HGB,DEV GENET SECT,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 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 APR 19 PY 1994 VL 8 IS 7 BP A1407 EP A1407 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA NH516 UT WOS:A1994NH51601077 ER PT J AU KUTTY, RK BRIGHTWELL, J KUTTY, G NAGINENI, CN HOOKS, JJ CHADER, GJ WIGGERT, B AF KUTTY, RK BRIGHTWELL, J KUTTY, G NAGINENI, CN HOOKS, JJ CHADER, GJ WIGGERT, B TI SCINTILLATION PROXIMITY RT-PCR (SPRT-PCR) ASSAY FOR HEME OXYGENASE-1 (HO-1) AND HEME OXYGENASE-2 (HO-2) - A SIMPLE AND SENSITIVE METHOD TO ESTIMATE OXIDATIVE DAMAGE TO HUMAN-CELLS AND TISSUES SO FASEB JOURNAL LA English DT Meeting Abstract C1 NEI,BETHESDA,MD 20892. 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 APR 19 PY 1994 VL 8 IS 7 BP A1400 EP A1400 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA NH516 UT WOS:A1994NH51601035 ER PT J AU LAUE, L HSUEH, A CUTLER, GB CHAN, WY AF LAUE, L HSUEH, A CUTLER, GB CHAN, WY TI CONSTITUTIVELY ACTIVATING MUTATIONS AT MULTIPLE SITES WITHIN THE HUMAN LUTEINIZING-HORMONE RECEPTOR (HLHR) IN FAMILIAL MALE PRECOCIOUS PUBERTY (FMPP) SO FASEB JOURNAL LA English DT Meeting Abstract C1 GEORGETOWN UNIV,MED CTR,WASHINGTON,DC 20007. STANFORD UNIV,MED CTR,STANFORD,CA 94305. NICHHD,DEB,BETHESDA,MD 20892. NR 0 TC 5 Z9 5 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 APR 19 PY 1994 VL 8 IS 7 BP A1320 EP A1320 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA NH516 UT WOS:A1994NH51600576 ER PT J AU LEE, CM STEVENS, LA TSAI, SC LEE, YT MOSS, J VAUGHAN, M AF LEE, CM STEVENS, LA TSAI, SC LEE, YT MOSS, J VAUGHAN, M TI EXPRESSION OF ADP-RIBOSYLATION FACTORS IN HUMAN ENDOTHELIAL-CELLS SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI,CELLULAR METAB LAB,BETHESDA,MD 20892. NATL TAIWAN UNIV HOSP,TAIPEI 10016,TAIWAN. 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 APR 19 PY 1994 VL 8 IS 7 BP A1396 EP A1396 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA NH516 UT WOS:A1994NH51601014 ER PT J AU LEE, FJS STEVENS, LA HALL, LM KAO, YL MURTAGH, JJ MOSS, J VAUGHAN, M AF LEE, FJS STEVENS, LA HALL, LM KAO, YL MURTAGH, JJ MOSS, J VAUGHAN, M TI MOLECULAR CHARACTERIZATION OF CLASS-II (DARF2) AND CLASS-III (DARF3), GUANINE NUCLEOTIDE-DEPENDENT ADP-RIBOSYLATION FACTORS IN DROSOPHILA-MELANOGASTER SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. SUNY BUFFALO,BUFFALO,NY 14260. 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 APR 19 PY 1994 VL 8 IS 7 BP A1433 EP A1433 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA NH516 UT WOS:A1994NH51601226 ER PT J AU LEE, KH LIM, Y HWANG, SC SHIN, SW BAE, YS NOH, DY LEE, SB RHEE, SG AF LEE, KH LIM, Y HWANG, SC SHIN, SW BAE, YS NOH, DY LEE, SB RHEE, SG TI IDENTIFICATION OF PLC ISOZYMES IN HEMATOPOIETIC-CELLS AND LYMPHOID-TISSUES SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI,BIOCHEM 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 APR 19 PY 1994 VL 8 IS 7 BP A1438 EP A1438 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA NH516 UT WOS:A1994NH51601260 ER PT J AU LEE, SB RHEE, SG AF LEE, SB RHEE, SG TI CLONING, SEQUENCING, AND PURIFICATION OF PHOSPHOLIPASE-C-DELTA-4 SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI,BIOCHEM 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 APR 19 PY 1994 VL 8 IS 7 BP A1437 EP A1437 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA NH516 UT WOS:A1994NH51601254 ER EF