FN Thomson Reuters Web of Science™ VR 1.0 PT J AU PAPCIAK, SM CHREST, FJ SCHOONMAKER, M NAGEL, JE ADLER, WH AF PAPCIAK, SM CHREST, FJ SCHOONMAKER, M NAGEL, JE ADLER, WH TI EXPRESSION OF THE IFN-GAMMA GENE IN ACTIVATED T-CELL SUBSETS FROM YOUNG AND OLD MICE SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 9 PY 1995 VL 9 IS 3 BP A242 EP A242 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QL987 UT WOS:A1995QL98701433 ER PT J AU POLACEK, D DEPAOLA, N PRITCHARD, W DAVIES, PF AF POLACEK, D DEPAOLA, N PRITCHARD, W DAVIES, PF TI SPATIAL UP-REGULATION OF GAP JUNCTION CONNEXIN43 MESSENGER-RNA IN ENDOTHELIAL-CELLS EXPOSED TO STEADY LAMINAR AND DISTURBED FLOWS IN-VITRO SO FASEB JOURNAL LA English DT Meeting Abstract C1 UNIV CHICAGO,CHICAGO,IL 60637. RENSSELAER POLYTECH INST,TROY,NY 12180. NIH,BETHESDA,MD 20892. 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 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 9 PY 1995 VL 9 IS 3 BP A267 EP A267 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QL987 UT WOS:A1995QL98701571 ER PT J AU RIZZO, LV STIFF, LR MILLERRIVERO, NE CHAN, CC WIGGERT, B NUSSENBLATT, RB CASPI, RR AF RIZZO, LV STIFF, LR MILLERRIVERO, NE CHAN, CC WIGGERT, B NUSSENBLATT, RB CASPI, RR TI BOTH IL-4 AND IL-10 ARE NEEDED FOR INDUCTION OF ORAL TOLERANCE SO FASEB JOURNAL LA English DT Meeting Abstract C1 NEI,BETHESDA,MD 20892. RI Rizzo, Luiz Vicente/B-4458-2009 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 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 9 PY 1995 VL 9 IS 3 BP A203 EP A203 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QL987 UT WOS:A1995QL98701208 ER PT J AU ROWE, M WIRTHLIN, R MOSAICO, M WAISATH, T PAUL, A RAVUSSIN, E AF ROWE, M WIRTHLIN, R MOSAICO, M WAISATH, T PAUL, A RAVUSSIN, E TI ASSOCIATION OF NON-SILENT MITOCHONDRIAL-DNA POLYMORPHISMS WITH RESTING METABOLIC-RATE SO FASEB JOURNAL LA English DT Meeting Abstract C1 BRIGHAM YOUNG UNIV,PROVO,UT 84602. NIDDKD,CLIN DIABET & NUTR SECT,PHOENIX,AZ 85016. 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 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 9 PY 1995 VL 9 IS 3 BP A281 EP A281 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QL987 UT WOS:A1995QL98701654 ER PT J AU SANZ, J CHUAQUI, R ZHUANG, Z LIOTTA, LA SOBEL, ME EMMERTBUCK, M MERINO, MJ AF SANZ, J CHUAQUI, R ZHUANG, Z LIOTTA, LA SOBEL, ME EMMERTBUCK, M MERINO, MJ TI LOSS OF HETEROZYGOSITY ON CHROMOSOME 11Q12-13 IN MICRODISSECTED HUMAN MALE BREAST CARCINOMAS 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 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 9 PY 1995 VL 9 IS 3 BP A273 EP A273 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QL987 UT WOS:A1995QL98701608 ER PT J AU SICA, A VIGGIANO, V CIPPITELLI, M GHOSH, P RICE, N YOUNG, HA AF SICA, A VIGGIANO, V CIPPITELLI, M GHOSH, P RICE, N YOUNG, HA TI FUNCTIONAL INTERACTION OF NF-KAPPA-B WITH INTERFERON-GAMMA GENOMIC DNA - IDENTIFICATION OF MULTIPLE NF-KAPPA-B AND NF-AT BINDING-SITES SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,LEI,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,ABL,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 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 9 PY 1995 VL 9 IS 3 BP A488 EP A488 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QL987 UT WOS:A1995QL98702854 ER PT J AU SIMEONOVA, PP LUSTER, MI AF SIMEONOVA, PP LUSTER, MI TI MECHANISMS OF ASBESTOS-INDUCED IL-8 RESPONSE 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 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 9 PY 1995 VL 9 IS 3 BP A247 EP A247 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QL987 UT WOS:A1995QL98701457 ER PT J AU SITKOVSKY, M KOSHIBA, M APASOV, S AF SITKOVSKY, M KOSHIBA, M APASOV, S TI EXTRACELLULAR ATP PURINERGIC RECEPTORS MODEL OF T-LYMPHOCYTE DIFFERENTIATION AND EFFECTOR FUNCTIONS SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAID,IMMUNOL 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 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 9 PY 1995 VL 9 IS 3 BP A119 EP A119 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QL987 UT WOS:A1995QL98700695 ER PT J AU SLESINSKI, MJ SUBAR, AF WUN, LM AF SLESINSKI, MJ SUBAR, AF WUN, LM TI INTAKE OF NUTRIENTS IN USERS OF VITAMIN AND MINERAL SUPPLEMENT - THE 1992 NATIONAL-HEALTH INTERVIEW SURVEY SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI,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 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 9 PY 1995 VL 9 IS 3 BP A578 EP A578 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QL987 UT WOS:A1995QL98703375 ER PT J AU SONG, LJ CRADDOCK, T LAL, P COLLINS, GD ADLER, WH AF SONG, LJ CRADDOCK, T LAL, P COLLINS, GD ADLER, WH TI TYROSINE PHOSPHORYLATION IS DIMINISHED IN PMA STIMULATED PBLS FROM ELDERLY INDIVIDUALS SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIA,GERONTOL RES CTR,CLIN IMMUNOL SECT,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 9 PY 1995 VL 9 IS 3 BP A235 EP A235 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QL987 UT WOS:A1995QL98701388 ER PT J AU STIFF, LR RIZZO, LV CHOI, R CASPI, RR AF STIFF, LR RIZZO, LV CHOI, R CASPI, RR TI THE ROLE OF TH1 AND TH2 TYPE CYTOKINES IN THE DEVELOPMENT AND TREATMENT OF EAU SO FASEB JOURNAL LA English DT Meeting Abstract C1 HOWARD HUGHES MED INST,BETHESDA,MD 20817. NEI,BETHESDA,MD 20892. RI Rizzo, Luiz Vicente/B-4458-2009 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 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 9 PY 1995 VL 9 IS 3 BP A217 EP A217 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QL987 UT WOS:A1995QL98701289 ER PT J AU SULLIVAN, D ANGLADE, E SALAMON, C NUSSENBLATT, R CSAKY, K AF SULLIVAN, D ANGLADE, E SALAMON, C NUSSENBLATT, R CSAKY, K TI ADENOVIRUS-MEDIATED GENE-TRANSFER OF TRANSFORMING GROWTH-FACTOR-BETA-1 (TGF-BETA-1) IN CULTURED HUMAN RPE SO FASEB JOURNAL LA English DT Meeting Abstract C1 NEI,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 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 9 PY 1995 VL 9 IS 3 BP A512 EP A512 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QL987 UT WOS:A1995QL98702987 ER PT J AU TATARANNI, PA RAVUSSIN, E AF TATARANNI, PA RAVUSSIN, E TI USE OF DUAL-ENERGY X-RAY ABSORPTIOMETRY IN OBESE INDIVIDUALS SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIDDK,PHOENIX,AZ 85016. 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 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 9 PY 1995 VL 9 IS 3 BP A280 EP A280 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QL987 UT WOS:A1995QL98701645 ER PT J AU TAUB, DD ORTALDO, JR AF TAUB, DD ORTALDO, JR TI CHEMOKINES AND NK CELLS - I-NK CELLS MIGRATE IN RESPONSE TO AND BIND TO BOTH ALPHA-CHEMOKINES AND BETA-CHEMOKINES SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,LEI,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,CSL,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 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 9 PY 1995 VL 9 IS 3 BP A493 EP A493 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QL987 UT WOS:A1995QL98702877 ER PT J AU TAUB, DD SAYERS, TJ CARTER, CRD ORTALDO, JR AF TAUB, DD SAYERS, TJ CARTER, CRD ORTALDO, JR TI CHEMOKINES AND NK CELLS .2. AUGMENTATION OF CYTOLYTIC RESPONSES AND INDUCTION OF CELLULAR DEGRANULATION SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,PRI DYNCORP,CSL,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,PRI DYNCORP,BCDP,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,LEI,FREDERICK,MD 21702. RI Sayers, Thomas/G-4859-2015 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 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 9 PY 1995 VL 9 IS 3 BP A220 EP A220 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QL987 UT WOS:A1995QL98701304 ER PT J AU THUPARI, JN CHREST, FJ ADLER, WH ALLEN, EM AF THUPARI, JN CHREST, FJ ADLER, WH ALLEN, EM TI ADOPTIVE TRANSFER OF AUTOIMMUNE-THYROIDITIS TO BB/WOR BB LINE RATS SO FASEB JOURNAL LA English DT Meeting Abstract C1 UNIV MARYLAND,VET ADM MED CTR,SCH MED,BALTIMORE,MD 21201. NIA,GERONTOL RES CTR,CLIN IMMUNOL SECT,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 9 PY 1995 VL 9 IS 3 BP A527 EP A527 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QL987 UT WOS:A1995QL98703077 ER PT J AU VANRHEE, AM KIM, JG JACOBSON, KA AF VANRHEE, AM KIM, JG JACOBSON, KA TI A MOLECULAR-MODEL OF THE HUMAN ADENOSINE A(2A) RECEPTOR THAT IS CONSISTENT WITH MUTAGENESIS STUDIES SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIDDK,LBC,MOLEC RECOGNIT SECT,BETHESDA,MD 20892. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 9 PY 1995 VL 9 IS 3 BP A122 EP A122 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QL987 UT WOS:A1995QL98700715 ER PT J AU WAGTMANN, N BIASSONI, R CANTONI, C VERDIANI, S MALNATI, M MORETTA, L MORETTA, A LONG, EO AF WAGTMANN, N BIASSONI, R CANTONI, C VERDIANI, S MALNATI, M MORETTA, L MORETTA, A LONG, EO TI THE P58 NK RECEPTORS ARE STRUCTURALLY DIVERSE AND CLONALLY DISTRIBUTED SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAID,IMMUNOGENET LAB,ROCKVILLE,MD 20852. IST NAZL RIC CANC,I-16132 GENOA,ITALY. 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 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 9 PY 1995 VL 9 IS 3 BP A493 EP A493 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QL987 UT WOS:A1995QL98702876 ER PT J AU YAMAMOTO, H FREDMAN, J CROW, M CHENG, L FROEHLICH, J LAKATTA, E KINSELLA, J AF YAMAMOTO, H FREDMAN, J CROW, M CHENG, L FROEHLICH, J LAKATTA, E KINSELLA, J TI PDGF RECEPTOR-TO-NUCLEUS SIGNALING OF THE P91 TRANSCRIPTION FACTOR IN ISOLATED VASCULAR SMOOTH-MUSCLE CELLS SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIH,GRC,CARDIOVASC SCI LAB,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 9 PY 1995 VL 9 IS 3 BP A316 EP A316 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QL987 UT WOS:A1995QL98701856 ER PT J AU YERGEY, A FREEMAN, S KING, J VIEIRA, N WOODHOUSE, L AF YERGEY, A FREEMAN, S KING, J VIEIRA, N WOODHOUSE, L TI INTRODUCTION OF A LIFETIME MEASUREABLE DOSE OF CA-41 INTO BONE AND MEASUREMENT OF TURNOVER SO FASEB JOURNAL LA English DT Meeting Abstract C1 NICHHD,BETHESDA,MD 20892. LAWRENCE LIVERMORE NATL LAB,LIVERMORE,CA 94551. UNIV CALIF BERKELEY,DEPT NUTR SCI,BERKELEY,CA 94720. 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 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 9 PY 1995 VL 9 IS 3 BP A284 EP A284 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QL987 UT WOS:A1995QL98701671 ER PT J AU ZAVERI, N MULLET, D COX, G FERTEL, R AF ZAVERI, N MULLET, D COX, G FERTEL, R TI MODULATION OF NITRIC-OXIDE PRODUCTION IN MURINE MACROPHAGES BY PURINERGIC COMPOUNDS SO FASEB JOURNAL LA English DT Meeting Abstract C1 OHIO STATE UNIV,COLL MED,DEPT PHARMACOL,COLUMBUS,OH 43210. NCI,FCRDC,BRMP,EXPTL IMMUNOL 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 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 9 PY 1995 VL 9 IS 3 BP A119 EP A119 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QL987 UT WOS:A1995QL98700699 ER PT J AU ZIEGLER, R HOOVER, R NOMURA, A WEST, D WU, A PIKE, M AF ZIEGLER, R HOOVER, R NOMURA, A WEST, D WU, A PIKE, M TI WEIGHT CHANGE, RELATIVE WEIGHT, HEIGHT, AND BREAST-CANCER RISK IN ASIAN-AMERICAN WOMEN SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. KUAKINI MED CTR,HONOLULU,HI 96817. NO CALIFORNIA CANC CTR,UNION CITY,CA 94587. UNIV SO CALIF,LOS ANGELES,CA 90033. 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 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 9 PY 1995 VL 9 IS 3 BP A579 EP A579 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA QL987 UT WOS:A1995QL98703379 ER PT J AU DUNTEN, RL WAIT, SJ BACKLUND, PS AF DUNTEN, RL WAIT, SJ BACKLUND, PS TI FRACTIONATION AND CHARACTERIZATION OF PROTEIN C-TERMINAL PRENYLCYSTEINE METHYLESTERASE ACTIVITIES FROM RABBIT BRAIN SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID CATHEPSIN-B; CARBOXYL-METHYLATION; BOVINE BRAIN; G25K; ESTER AB Reversible carboxyl methylation of the C-terminal geranylgeranylcysteine of G25K may regulate its activity and cellular localization. Brain homogenates were examined for enzyme activities which hydrolyze the methyl ester of [H-3]methyl-G25K to produce [H-3]methanol. Methylesterase activity was detected in both soluble and membrane fractions. The soluble activity was fractionated into at least two distinct activities. One soluble activity appears to be due to the lysosomal protease, cathepsin B, based on sensitivity to certain protease inhibitors, acidic pH optimum, size, and ability to cleave the peptide substrate N alpha-CBZ-Arg-Arg-7 amido-4-methylcoumarin. A second soluble activity, associated with a protein of approximately 25 kDa, exhibits a neutral pH optimum, insensitivity to protease inhibitors, and inhibition by the esterase inhibitor, ebelactone B. The membrane fraction contains larger amounts of a similar methylesterase that may represent the physiologically relevant form of the enzyme. (C) 1995 Academic Press, Inc. C1 NIMH,GEN & COMPARAT BIOCHEM LAB,BETHESDA,MD 20892. NR 29 TC 8 Z9 8 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD MAR 8 PY 1995 VL 208 IS 1 BP 174 EP 182 DI 10.1006/bbrc.1995.1320 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA QL172 UT WOS:A1995QL17200024 PM 7887926 ER PT J AU LINK, CJ BOHR, VA AF LINK, CJ BOHR, VA TI 3''-AZIDO-3'-DEOXYTHYMIDINE AND 2',3'-DIDEOXYCYTIDINE DO NOT INHIBIT GENE-SPECIFIC DNA-REPAIR IN HAMSTER-CELLS SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID BONE-MARROW-CELLS; 3'-AZIDO-3'-DEOXYTHYMIDINE; STRAND; DAMAGE AB 3 ''-Azido-3'-deoxythymidine (AZT) was the first approved drug for the treatment of the AIDS; however, despite its usefulness, AZT often produces side effects that require cessation of therapy. 2',3'-Dideoxycytidine (ddC) is a related anti-retroviral agent in advanced stages of clinical testing. A previous report demonstrated that AZT decreased the repair of UV-induced DNA strand breaks in mammalian cells after ultraviolet (UV) irradiation. We studied the effect of AZT and ddC on DNA repair from the hamster DHFR gene of the major UV-induced DNA lesion, cyclobutane pyrimidine dimers (CPDs). We conclude that neither AZT nor ddC inhibited DNA replication or the gene-specific repair of CPDs in the hamster DHFR gene after 8 or 24 hrs of repair incubation at concentrations of 25 mu M and 10 mu M, respectively. (C) 1995 Academic Press, Inc. C1 NCI,MOLEC PHARMACOL LAB,BETHESDA,MD 20892. NIA,MOLEC GENET LAB,BALTIMORE,MD 21224. NR 18 TC 1 Z9 1 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD MAR 8 PY 1995 VL 208 IS 1 BP 198 EP 203 DI 10.1006/bbrc.1995.1323 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA QL172 UT WOS:A1995QL17200027 PM 7887930 ER PT J AU WILLINGER, M AF WILLINGER, M TI SLEEP POSITION AND SUDDEN-INFANT-DEATH-SYNDROME SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material RP WILLINGER, M (reprint author), NICHHD,CTR RES MOTHERS & CHILDREN,PREGNANCY & PERINATOL BRANCH,BETHESDA,MD 20892, USA. NR 15 TC 15 Z9 16 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 MAR 8 PY 1995 VL 273 IS 10 BP 818 EP 819 DI 10.1001/jama.273.10.818 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA QJ750 UT WOS:A1995QJ75000036 PM 7861578 ER PT J AU BERGMANN, U TUUTTILA, A STETLERSTEVENSON, WG TRYGGVASON, K AF BERGMANN, U TUUTTILA, A STETLERSTEVENSON, WG TRYGGVASON, K TI AUTOLYTIC ACTIVATION OF RECOMBINANT HUMAN 72-KILODALTON TYPE-IV COLLAGENASE SO BIOCHEMISTRY LA English DT Article ID TISSUE INHIBITOR; MATRIX METALLOPROTEINASES; INTERSTITIAL COLLAGENASE; PLASMINOGEN-ACTIVATOR; SUBSTRATE-SPECIFICITY; CYSTEINE SWITCH; TUMOR INVASION; HUMAN 72-KDA; BINDING; COMPLEX AB Human 72 kDa type IV collagenase (gelatinase A, MMP-2) was expressed in a baculovirus/ insect cell system. The enzyme was produced in the wild-type form and in two mutant forms, where the active site Glu(375) was substituted by Asp or Gin. The mutated proteins had strongly reduced or no detectable activity, respectively, allowing detailed analysis of rapid autoactivation reactions. MMP-2 was readily degraded to a proenzyme form lacking the first four amino acid residues. This cleavage was shown to be an autolytic process, although enzyme activity was apparently not affected by this truncation. Conversion to the active enzyme form was achieved without external activator in a concentration-dependent manner at 37 degrees C. The activation of MMP-2,was shown to be a stepwise process, probably via a Delta(1-50) form as a highly unstable intermediate. The C-terminal hemopexin-like domain is removed rather early at two cleavage sites, and degradation within the Zn-binding site inactivates the enzyme. The fibronectin- and hemopexin-like domains are stable, although the autodegradation pattern did not show any sequence specificity, except for charged residues in the P-1' position. The results indicate that a specific activator may not be essential for MMP-2. C1 UNIV OULU,BIOCTR,SF-90570 OULU,FINLAND. UNIV OULU,DEPT BIOCHEM,SF-90570 OULU,FINLAND. NCI,PATHOL LAB,BETHESDA,MD 20892. RI Stetler-Stevenson, William/H-6956-2012 OI Stetler-Stevenson, William/0000-0002-5500-5808 NR 50 TC 70 Z9 71 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAR 7 PY 1995 VL 34 IS 9 BP 2819 EP 2825 DI 10.1021/bi00009a011 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QK934 UT WOS:A1995QK93400011 PM 7893694 ER PT J AU STRZELECKA, TE HAYES, JJ CLORE, GM GRONENBORN, AM AF STRZELECKA, TE HAYES, JJ CLORE, GM GRONENBORN, AM TI DNA-BINDING SPECIFICITY OF THE MU NER PROTEIN SO BIOCHEMISTRY LA English DT Article ID HETERONUCLEAR NMR-SPECTROSCOPY; BACTERIOPHAGE-MU; PURIFICATION; REPRESSOR; SEQUENCE; GENE; NLP AB Binding of purified phage Mu Ner protein to a series of DNA fragments was investigated in order to determine the length requirements for tight specific binding. Gel retardation experiments with wild-type 307 base pair (bp) Mu DNA and shorter, synthetic oligonucleotides were performed, and apparent dissociation constants (K-D(app)) were determined from the half-saturation point. While Ner formed four complexes with the 307 bp DNA fragment, only one complex was observed with the shorter DNAs. The 50 and 30 bp fragments had K-D(app) values of 5 and 20 nM, respectively. Ner binding was progressively weaker with decreasing size of the DNA fragments, with no binding observed for 12mers. The shortest DNA fragments which bound well were two 18 bp fragments for which K-D(app) values were in the range of 50-100 nM. The stoichiometry of Ner complexes with the 30 and 18 bp fragments was determined using a modified Ferguson method. Ner was found to form a tetramer on the 30 bp DNA and a dimer on the 18 bp DNA, which makes the latter a good candidate for the study of a Ner-DNA complex by NMR. In order to clarify which DNA regions were important for Ner-DNA binding, hydroxyl radical footprinting was performed for a range of Ner concentrations from 30 to 500 nM. The footprint revealed that Ner contacts the DNA backbone every 12-13 bp, on both strands of the DNA. The order in which protected regions appeared with increasing protein concentration indicated that two Ner monomers bound to DNA simultaneously. A model of Ner binding to DNA is proposed on the basis of these results. C1 NIDDK,CHEM PHYS LAB,BETHESDA,MD 20892. NICHHD,MOLEC EMBRYOL LAB,BETHESDA,MD 20892. RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 NR 33 TC 8 Z9 9 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAR 7 PY 1995 VL 34 IS 9 BP 2946 EP 2955 DI 10.1021/bi00009a026 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QK934 UT WOS:A1995QK93400026 PM 7893708 ER PT J AU PERNASALONSO, R SCHAFFNER, AE HANSEN, CT BARKER, JL DIPORZIO, U AF PERNASALONSO, R SCHAFFNER, AE HANSEN, CT BARKER, JL DIPORZIO, U TI ACETYLCHOLINE ESTERASE AND PERIPHERIN MESSENGER-RNA LEVEL DECREASE IN WOBBLER MOUSE SO NEUROREPORT LA English DT Article DE SPINAL MUSCULAR ATROPHY; MOTONEURON DEGENERATION; SEMIQUANTITATIVE RT-PCR; TRANSCRIPTIONAL REGULATION ID PROTEIN AB HOMOZYGOTE wobbler mice develop motoneurone degeneration. Throughout development the expression of choline acetyltransferase, of trkC receptor and F3 adhesion molecule genes is similar in wobbler and wildtype spinal cord. Acetylcholinesterase mRNA level instead is decreased to about 50% with respect to wild-type values in one forth of P5 and P10 wobbler progeny, putative wr/wr individuals; at P21 its expression is equally highly reduced in known homozygotes and it is reduced to 35% of normal values in about one half of the progeny, putative heterozygotes. Thus, similarly to medium neurofilament gene over-expression, reduced acetylcholinesterase gene expression is an early molecular marker for the wobbler mutation before onset of the illness. C1 NINCDS,NEUROPHYSIOL LAB,BETHESDA,MD 20892. NIH,VET RES BRANCH,BETHESDA,MD 20892. RP PERNASALONSO, R (reprint author), CNR,INT INST GENET & BIOPHYS,VIA MARCONI 10,I-80125 NAPLES,ITALY. FU Fondazione Telethon NR 13 TC 8 Z9 8 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD MAR 7 PY 1995 VL 6 IS 4 BP 597 EP 600 DI 10.1097/00001756-199503000-00003 PG 4 WC Neurosciences SC Neurosciences & Neurology GA QN868 UT WOS:A1995QN86800003 PM 7605908 ER PT J AU FAN, P OZ, M ZHANG, L WEIGHT, FF AF FAN, P OZ, M ZHANG, L WEIGHT, FF TI EFFECT OF COCAINE ON THE 5-HT3 RECEPTOR-MEDIATED ION CURRENT IN XENOPUS OOCYTES SO BRAIN RESEARCH LA English DT Article DE SEROTONIN 5-HT3 RECEPTOR; COCAINE; COMPETITIVE INHIBITION; XENOPUS OOCYTE; VOLTAGE-CLAMP ID ANTAGONISTS; MEMBRANE; NEURONS; BINDING AB The cloned 5-HT3 receptor from NCB-20 neuroblastoma cells was expressed in Xenopus oocytes. In these oocytes, 5-HT, the selective 5-HT3 receptor agonists, 2-methyl-5-HT and m-chlorophenylbiguanide activated an inward current which was sensitive to the specific 5-HT3 receptor antagonist LY278584. Cocaine (0.1 to 10 mu M) reversibly inhibited the current activated by 1 mu M 5-HT in a concentration-dependent manner. The IC50 value is 0.7 mu M and the apparent Hill coefficient is 1.55. This effect of cocaine was not dependent on membrane potential. Cocaine also produced a parallel shift of the 5-HT concentration-response curve to the right and did not reduce the maximal current induced by 5-HT. In the presence of 3 mu M cocaine, the EC(50) value of 5-HT was increased from 3.08 mu M to 6.1 mu M. Other local anesthetics such as tricaine and lidocaine also inhibited the current induced by 5-HT. These results suggest that the 5-HT3 receptors expressed in Xenopus oocytes exhibit properties similar to those in sensory neurons and neuroblastoma cells and were blocked by cocaine in a competitive manner. RP FAN, P (reprint author), NIAAA,MOLEC & CELLULAR NEUROBIOL LAB,12501 WASHINGTON AVE,ROCKVILLE,MD 20852, USA. RI Oz, Murat/E-2148-2012 NR 24 TC 13 Z9 13 U1 3 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD MAR 6 PY 1995 VL 673 IS 2 BP 181 EP 184 DI 10.1016/0006-8993(94)01316-A PG 4 WC Neurosciences SC Neurosciences & Neurology GA QK714 UT WOS:A1995QK71400001 PM 7606430 ER PT J AU JOSEPH, JA VILLALOBOSMOLINA, R YAMAGAMI, K ROTH, GS KELLY, J AF JOSEPH, JA VILLALOBOSMOLINA, R YAMAGAMI, K ROTH, GS KELLY, J TI AGE-SPECIFIC ALTERATIONS IN MUSCARINIC STIMULATION OF K+-EVOKED DOPAMINE RELEASE FROM STRIATAL SLICES BY CHOLESTEROL AND S-ADENOSYL-L-METHIONINE SO BRAIN RESEARCH LA English DT Article DE AGING; DOPAMINE; MUSCARINIC RECEPTOR; S-ADENOSYL-METHIONINE; CHOLESTEROL; STRIATUM ID ADENYLATE-CYCLASE ACTIVITY; POSTMORTEM HUMAN-BRAIN; ALZHEIMERS-DISEASE; SIGNAL TRANSDUCTION; MEMBRANE FLUIDITY; G-PROTEINS; ERYTHROCYTE-MEMBRANES; LIPID-PEROXIDATION; RECEPTOR-BINDING; PLASMA-MEMBRANE AB The present experiments were carried out in order to test the hypothesis that age-related signal transduction (ST) deficits may occur as a result of structural changes in the membrane that are reflected partially as increased membrane microviscosity. Oxotremorine (oxo) enhancement of K+-evoked release of dopamine (K+-ERDA) was examined in superfused striatal slices from mature (6 months) and old (24 months) Wistar rats incubated (1 or 4 h, 37 degrees C) with graded concentrations of S-adenosyl-L-methionine (SAM) or cholesterol hemisuccinate (CHO) in a modified Krebs medium. Tissue was then assessed for one of the following: (a) the degree of ore-enhanced K+-ERDA, (b) carbachol stimulated low K-m GTPase activity, or (c) alterations in membrane microviscosity. In other experiments the tissue was incubated in CHO followed by SAM (or the reverse), and ore-enhanced K+-ERDA examined. Results indicated that SAM treatment increased all the parameters in the striatal tissue from old animals, while CHO had selective, opposite effects in the striatal tissue obtained from young animals. CHO-SAM, or the reverse, produced the same pattern of results. These results suggest that ST deficits may involve age-related structural alterations in membranes that interfere with receptor-G protein coupling/uncoupling. C1 YOSHITOMI PHARMACEUT IND LTD,IRUMA,SAITAMA 358,JAPAN. NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. RP JOSEPH, JA (reprint author), USDA ARS,HUMAN NUTR RES CTR AGING,711 WASHINGTON ST,BOSTON,MA 02111, USA. RI Yamagami, Keiji/E-9500-2012 NR 51 TC 14 Z9 14 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD MAR 6 PY 1995 VL 673 IS 2 BP 185 EP 193 DI 10.1016/0006-8993(94)01311-5 PG 9 WC Neurosciences SC Neurosciences & Neurology GA QK714 UT WOS:A1995QK71400002 PM 7606431 ER PT J AU ARAI, R JACOBOWITZ, DM NAGATSU, I AF ARAI, R JACOBOWITZ, DM NAGATSU, I TI UP-REGULATION OF CALRETININ IN THE SUPRAOPTIC NUCLEUS OF THE RAT AFTER CHRONIC SALT LOADING SO BRAIN RESEARCH LA English DT Note DE CALCIUM-BINDING PROTEIN; CALCIUM BUFFER; CALRETININ; SALT LOADING; HYPOTHALAMIC PARAVENTRICULAR NUCLEUS; SUPRAOPTIC NUCLEUS; RAT ID CALCIUM-BINDING PROTEIN; NEURONS RECORDED INVITRO; IMMUNOHISTOCHEMICAL LOCALIZATION; PARVALBUMIN IMMUNOREACTIVITY; OXYTOCIN NEURONS; NERVOUS-SYSTEM; BRAIN; VASOPRESSIN; CELLS; CALBINDIN-D28K AB We immunocytochemically examined the effect of chronic salt loading on the content of calretinin, a calcium-binding protein, in both the supraoptic nucleus and the magnocellular parts of the hypothalamic paraventricular nucleus. In control rats that were given water for drinking, the supraoptic nucleus contained a cluster of calretinin-stained cells. Drinking 2% sodium chloride solution for 7 days resulted in an increase of the staining intensity of calretinin in cells of the supraoptic nucleus. In both the control and salt-loaded rats, the magnocellular parts of the paraventricular nucleus were almost devoid of calretinin-labeled cells. It is suggested that expression of calretinin in cells of the supraoptic nucleus is up regulated by chronic salt loading. C1 NIMH,CLIN SCI LAB,BETHESDA,MD 20892. RP ARAI, R (reprint author), FUJITA HLTH UNIV,SCH MED,DEPT ANAT,TOYOAKE,AICHI 47011,JAPAN. NR 35 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD MAR 6 PY 1995 VL 673 IS 2 BP 339 EP 343 DI 10.1016/0006-8993(95)00003-9 PG 5 WC Neurosciences SC Neurosciences & Neurology GA QK714 UT WOS:A1995QK71400022 PM 7606450 ER PT J AU STEINER, H GERFEN, CR AF STEINER, H GERFEN, CR TI DYNORPHIN OPIOID INHIBITION OF COCAINE-INDUCED, D1 DOPAMINE RECEPTOR-MEDIATED IMMEDIATE-EARLY GENE-EXPRESSION IN THE STRIATUM SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE KAPPA OPIOID; C-FOS; ZIF 268; STRIATONIGRAL; COCAINE ID FOS-LIKE PROTEIN; RAT SPINAL-CORD; C-FOS; SUBSTANCE-P; STRIATOPALLIDAL NEURONS; DIFFERENTIALLY ALTERS; MATRIX COMPARTMENTS; LOCOMOTOR-ACTIVITY; ADENYLATE-CYCLASE; MESSENGER-RNA AB Neurons in the striatum that project to the substantia nigra contain the opioid peptide dynorphin. Stimulation of D1 dopamine receptors results in increased expression of mRNA encoding dynorphin as well as expression of immediate-early genes such as c-fos in these neurons. Levels of dynorphin vary in different regions of the normal rat striatum, being highest in ventral and medial striatum. In a prior study, we have shown that both regional and temporal patterns of c-fos induction following treatment with the indirect dopamine receptor agonist cocaine are inversely related to those of dynorphin expression. These results suggested that dynorphin is involved in regulating the responsiveness of these neurons to dopamine input. In the present experiments, we examined such a potential role for dynorphin by analyzing the influence of the dynorphin (kappa opioid receptor) agonist spiradoline on immediate-early gene induction by cocaine, and we determined that this immediate-early gene response is mediated by D1 dopamine receptors located in the striatum. As a marker of neuron activation, expression of c-fos and zif 268 immediate-early genes was assessed with quantitative in situ hybridization histochemistry. Results showed that 1) intrastriatal infusion of the D1 dopamine receptor antagonist SCH-23390 (2.5-250 pmol) resulted in a dose-dependent blockade of immediate-early gene induction by cocaine (30 mg/kg); 2) systemic administration of the kappa opioid receptor agonist spiradoline (0.5-10.0 mg/kg) decreased cocaine-induced expression of c-fos and zif 268 mRNAs in striatum in a dose-dependent manner; 3) intrastriatal infusion of spiradoline (1-50 nmol) also suppressed immediate-early gene induction by cocaine, demonstrating that kappa opioid receptors located in the striatum mediate such an effect; and 4) systemic and intrastriatal administration of spiradoline also affected immediate-early gene expression in cortex. These results demonstrate that, in striatum, immediate-early gene induction by cocaine is a D1 dopamine receptor-mediated process that is inhibited by activation of kappa opioid receptors. Therefore, these findings suggest that the striatal dynorphin opioid system acts directly and/or indirectly to inhibit dopamine input to striatonigral neurons through kappa opioid receptor-mediated processes in the striatum. (C) 1995 Wiley-Liss, Inc. C1 NIMH,NEUROANAT SECT,SYST NEUROSCI LAB,BETHESDA,MD 20892. NR 68 TC 86 Z9 87 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD MAR 6 PY 1995 VL 353 IS 2 BP 200 EP 212 DI 10.1002/cne.903530204 PG 13 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA QF231 UT WOS:A1995QF23100003 PM 7745131 ER PT J AU STANTON, GB BRUCE, CJ GOLDBERG, ME AF STANTON, GB BRUCE, CJ GOLDBERG, ME TI TOPOGRAPHY OF PROJECTIONS TO POSTERIOR CORTICAL AREAS FROM THE MACAQUE FRONTAL EYE FIELDS SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE AUTORADIOGRAPHY; MONKEY; NEURAL CONNECTIVITY; SACCADES; EYE MOVEMENTS ID SUPERIOR TEMPORAL SULCUS; LATERAL INTRAPARIETAL AREA; PARIETAL ASSOCIATION CORTEX; RHESUS-MONKEY; VISUAL AREAS; CORTICOCORTICAL CONNECTIONS; TERMINAL FIELDS; ORGANIZATION; LOBE; MT AB Frontal eye field (FEF) projections to posterior cortical areas were mapped by autoradiography of tritiated amino acids (Leu, Pro) in six macaque monkeys. In three monkeys, the large saccade part of the FEF (lFEF) was identified by microstimulation and injected with tracers. In a fourth monkey, the small saccade part of the FEF (sFEF) was identified by microstimulation and injected with tracer. Tracer injections were placed into the sFEF region of two other monkeys using anatomical landmarks. The IFEF and sFEF generally had distinct and largely segregated projections to posterior cortical areas, and the overall pattern of labeling in visual areas with established topology indicates that lFEF neurons preferentially project to areas having large and eccentric receptive fields, whereas sFEF neurons project to areas having smaller, more centrally located fields. The terminal fields from the sFEF were more widespread than those from lFEF. Projections from sFEF terminated in the lateral intraparietal area (LIP), the ventral intraparietal area (VIP), and the parietal part of visual area V3A, in the fundus of the superior temporal visual area (FST), the middle temporal area (MT), the medial superior temporal area (MST), the temporal part of visual area V4, the inferior temporal area (IT), and the temporal-occipital area (TEO) and in occipital visual areas V2, V3, and V4. Projections from lFEF terminated in parietal areas 7a, LIP, and VIP and the medial part of parietal area PE; in temporal areas MST and the superior temporal polysensory area (STP); and in occipital area V2 and posterior cingulate area 23b. Projections from lFEF and sFEF appeared to terminate in different parts of common target areas in MST, LIP, and V2. The topography of IFEF and sFEF projections to LIP suggests that this posterior eye field may also be organized by saccade amplitude. Most terminal labeling from FEF injections was bilaminar to layers I and V/VI, but labeling in area LIP, area MT, the medial part of area PE, and area 23b was columnar-form to all layers. (C) 1995 Wiley-Liss, Inc. C1 YALE UNIV, SCH MED, NEUROBIOL SECT, NEW HAVEN, CT 06510 USA. NEI, SENSORIMOTOR RES LAB, BETHESDA, MD 20892 USA. RP STANTON, GB (reprint author), HOWARD UNIV, COLL MED, DEPT ANAT, 520 W ST NW, WASHINGTON, DC 20059 USA. OI Bruce, Charles/0000-0002-7481-5793 FU NEI NIH HHS [EY-03763, EY-04740] NR 60 TC 228 Z9 229 U1 1 U2 7 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD MAR 6 PY 1995 VL 353 IS 2 BP 291 EP 305 DI 10.1002/cne.903530210 PG 15 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA QF231 UT WOS:A1995QF23100009 PM 7745137 ER PT J AU PICKAR, D AF PICKAR, D TI PROSPECTS FOR PHARMACOTHERAPY OF SCHIZOPHRENIA SO LANCET LA English DT Review ID D2-DOPAMINE RECEPTOR OCCUPANCY; PHOTON-EMISSION TOMOGRAPHY; PLASMA HOMOVANILLIC-ACID; ANTIPSYCHOTIC-DRUGS; TARDIVE-DYSKINESIA; HUMAN-BRAIN; CLOZAPINE; DOPAMINE; FLUPHENAZINE; NEUROLEPTICS RP PICKAR, D (reprint author), NIMH,EXPTL THERAPEUT BRANCH,NIH BLDG 10-4N212,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 59 TC 118 Z9 118 U1 1 U2 2 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0099-5355 J9 LANCET JI Lancet PD MAR 4 PY 1995 VL 345 IS 8949 BP 557 EP 562 DI 10.1016/S0140-6736(95)90469-7 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA QK444 UT WOS:A1995QK44400014 PM 7539875 ER PT J AU HADZIYANNIS, S TABOR, E KAKLAMANI, E TZONOU, A STUVER, S TASSOPOULOS, N MUELLER, N TRICHOPOULOS, D AF HADZIYANNIS, S TABOR, E KAKLAMANI, E TZONOU, A STUVER, S TASSOPOULOS, N MUELLER, N TRICHOPOULOS, D TI A CASE-CONTROL STUDY OF HEPATITIS-B AND HEPATITIS-C VIRUS-INFECTIONS IN THE ETIOLOGY OF HEPATOCELLULAR-CARCINOMA SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID RISK-FACTORS; ANTIBODIES; POPULATION; PREVALENCE; SMOKING; WOMEN; DIET AB During a 16-month period in 1991-1992, blood samples and questionnaire data were obtained from 65 incident cases of hepatocellular carcinoma (HCC) as well as from 2 control groups of hospitalized patients matched on gender and age, which included 65 metastatic liver cancer (MLC) patients and 65 patients hospitalized for eye, ear, nose or throat conditions. Coded sera were tested for hepatitis B surface antigen (HBsAg), antibody to hepatitis B core antigen, antibody to HBsAg and antibody to hepatitis C virus (anti-HCV) by enzyme immunoassay. The odds ratios (with 95% confidence intervals) in logistic regression modeling comparing the HCC cases to the combined control series were 18.8 (8.2-3.2) for the presence of HBsAg and 7.7 (1.7-35.1) for anti-HCV. In the present hospital-based case-control study anti-HCV testing was conducted on recently collected sera, using a second-generation enzyme immunoassay with confirmation by immunoblot assay. Comparisons with previous work in a similar population demonstrated that, when second-generation anti-HCV assays are applied to sera stored for 7-15 years, confirmatory assays or a higher diagnostic cut-off point may be necessary to ensure that the testing is specific. (C) 1995 Wiley-Liss, Inc. C1 HARVARD UNIV,SCH PUBL HLTH,DEPT EPIDEMIOL,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,CANC RES CTR,BOSTON,MA 02115. NCI,BETHESDA,MD 20892. HIPPOKRATION HOSP,ACAD DEPT MED,ATHENS,GREECE. UNIV ATHENS,SCH MED,DEPT HYG & EPIDEMIOL,ATHENS,GREECE. WESTERN ATTICA GEN HOSP,DEPT MED 1,LIVER UNIT,ATHENS,GREECE. NR 22 TC 61 Z9 63 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD MAR 3 PY 1995 VL 60 IS 5 BP 627 EP 631 DI 10.1002/ijc.2910600510 PG 5 WC Oncology SC Oncology GA QJ771 UT WOS:A1995QJ77100009 PM 7860136 ER PT J AU LEVINE, PH STEMMERMANN, G LENNETTE, ET HILDESHEIM, A SPHIBATA, D NOMURA, A AF LEVINE, PH STEMMERMANN, G LENNETTE, ET HILDESHEIM, A SPHIBATA, D NOMURA, A TI ELEVATED ANTIBODY-TITERS TO EPSTEIN-BARR-VIRUS PRIOR TO THE DIAGNOSIS OF EPSTEIN-BARR-VIRUS-ASSOCIATED GASTRIC ADENOCARCINOMA SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID POLYMERASE CHAIN-REACTION; JAPANESE-AMERICANS; CARCINOMA; HAWAII; LYMPHOMA; STOMACH; CANCER AB Epstein-Barr virus (EBV) has recently been identified in the tumor cells of patients with gastric carcinoma. We tested pre-morbid serum samples from a carefully monitored cohort of Japanese men in order to investigate the possibility that patients with EBV-associated gastric cancer represent a sub-set of individuals with long-standing difficulties in appropriately managing EBV infection. From a serum bank, we obtained 108 samples derived from 54 patients destined to develop gastric adenocarcinoma and 54 controls. Samples were tested under code for antibodies to EBV-capsid antigen, early antigen and nuclear antigen. Individuals who were positive for IgA antibodies against EBV viral-capsid antigen (VCA) and IgG antibodies against the R component of EBV early antigen were at a 3.9-fold and 1.9-fold excess risk of disease, respectively. Antibody titers to EBV VCA were significantly higher in those destined to get EBV-associated gastric cancer than those subsequently developing non-EBV-associated gastric cancer or age-and-gender-matched controls. These findings suggest that the inability to control EBV infection on a long-term basis exists many rears prior to the development of EBV-associated gastric cancer, and that EBV may play an etiologic role in this sub-set of malignancies. (C) 1995 Wiley-Liss, Inc. C1 NCI,EPIDEMIOL BRANCH,BETHESDA,MD 20892. NCI,BIOSTAT PROGRAM,BETHESDA,MD 20892. KUAKINI MED CTR,JAPAN HAWAII CANC STUDY,HONOLULU,HI 96817. UNIV CINCINNATI,DEPT PATHOL & LAB MED,CINCINNATI,OH 45267. VIROLAB INC,BERKELEY,CA 94710. UNIV SO CALIF,LOS ANGELES,CA 90033. NR 19 TC 82 Z9 86 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD MAR 3 PY 1995 VL 60 IS 5 BP 642 EP 644 DI 10.1002/ijc.2910600513 PG 3 WC Oncology SC Oncology GA QJ771 UT WOS:A1995QJ77100012 PM 7860138 ER PT J AU NIGHTINGALE, K WOLFFE, AP AF NIGHTINGALE, K WOLFFE, AP TI METHYLATION AT CPG SEQUENCES DOES NOT INFLUENCE HISTONE-H1 BINDING TO A NUCLEOSOME INCLUDING A XENOPUS-BOREALIS 5-S-RIBOSOMAL RNA GENE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Note ID THYMIDINE KINASE GENE; RNA POLYMERASE-II; DNA METHYLATION; CHROMATIN STRUCTURE; LINKER HISTONES; GLOBIN GENE; TRANSCRIPTION; PROTEIN; H-1; REPRESSION AB We demonstrate that methylation of the 12 dinucleotide CpGs within a GC-rich DNA fragment containing a Xenopus borealis 5 S rRNA gene does not influence histone ill binding to naked or nucleosomal 5 S DNA. Thus a simple mechanism in which histone ill selectively associates with nucleosomes containing methylated CpG cannot explain the repressive effects of methylation on gene activity. C1 NICHHD,MOLEC EMBRYOL LAB,BETHESDA,MD 20892. NR 41 TC 43 Z9 43 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 MAR 3 PY 1995 VL 270 IS 9 BP 4197 EP 4200 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QK084 UT WOS:A1995QK08400005 PM 7876175 ER PT J AU EDWARDS, SL DAVIDSON, VL HYUN, YL WINGFIELD, PT AF EDWARDS, SL DAVIDSON, VL HYUN, YL WINGFIELD, PT TI SPECTROSCOPIC EVIDENCE FOR A COMMON ELECTRON-TRANSFER PATHWAY FOR 2 TRYPTOPHAN TRYPTOPHYLQUINONE ENZYMES SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID QUINOPROTEIN METHYLAMINE DEHYDROGENASE; C-TYPE CYTOCHROMES; PARACOCCUS-DENITRIFICANS; ALCALIGENES-FAECALIS; CRYSTAL-STRUCTURE; METHYLOTROPHIC BACTERIA; 3-DIMENSIONAL STRUCTURE; SECONDARY STRUCTURE; CIRCULAR-DICHROISM; QUINONE COFACTOR AB Aromatic amine dehydrogenase (AADH) and methylamine dehydrogenase (MADH) are the only two enzymes known to use the cofactor tryptophan tryptophylquinone (TTQ). Each catalyzes oxidative deamination of a distinct class of primary amines. A detailed comparison of their circular dichroic spectra indicates that both proteins share a similar fold with their TTQ cofactors residing in similar environments and that this may be a useful diagnostic probe for TTQ enzymes. Alcaligenes faecalis cells induced to express AADH also express a large amount of the blue copper protein, azurin. Oxidized azurin is rapidly reduced by a catalytic amount of AADH in the presence of the substrate, tyramine. Three A. faecalis cytochromes-c and three other cytochromes-c were tested for electron transfer activity with AADH. Azurin markedly facilitated electron transfer from AADH to each cytochrome. This suggests that AADH and azurin may form an electron transfer complex with a c-type cytochrome, analogous to the crystallographically determined MADH-amicyanin-cytochrome c-551i complex (Chen, L., Durley, R. C. E., Matthews, F. S., and Davidson, V. L. (1994) Science 264, 86-90). The similarities of MADH and AADH plus the demonstration of azurin and multiple cytochromes as functional electron-transfer partners suggest that both TTQ-bearing enzymes share common mechanisms for oxidative deamination and subsequent electron transfer. C1 NIAMSD,STRUCT BIOL RES LAB,BETHESDA,MD 20892. UNIV MISSISSIPPI,MED CTR,DEPT BIOCHEM,JACKSON,MS 39216. NIH,OFF DIRECTOR,PROT EXPRESS LAB,BETHESDA,MD 20892. FU NIGMS NIH HHS [GM41574] NR 39 TC 26 Z9 28 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 MAR 3 PY 1995 VL 270 IS 9 BP 4293 EP 4298 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QK084 UT WOS:A1995QK08400020 PM 7876189 ER PT J AU KRISTIE, TM POMERANTZ, JL TWOMEY, TC PARENT, SA SHARP, PA AF KRISTIE, TM POMERANTZ, JL TWOMEY, TC PARENT, SA SHARP, PA TI THE CELLULAR C1 FACTOR OF THE HERPES-SIMPLEX VIRUS ENHANCER COMPLEX IS A FAMILY OF POLYPEPTIDES SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ADENOVIRUS DNA-REPLICATION; NUCLEAR FACTOR-III; HISTONE H2B GENE; OCTAMER-BINDING PROTEINS; OCT-1 HOMEO DOMAIN; RNA POLYMERASE-III; TRANSCRIPTION FACTOR; HELA-CELLS; U2 SNRNA; TRANSACTIVATOR VP16 AB The alpha/immediate early genes of herpes simplex virus are regulated by the specific assembly of a multiprotein enhancer complex containing the Oct-1 POU domain protein, the viral alpha-transinduction factor alpha TIF, (VP16, ICP25), and the C1 cellular factor, The C1 factor from mammalian cells is a heterogeneous but related set of polypeptides that interact directly with the alpha-transinduction factor to form a heteromeric protein complex, The isolation of cDNAs encoding the polypeptides of the C1 factor suggests that these proteins are proteolytic products of a novel precursor. The sequence of the amino termini of these polypeptide products indicate that the proteins are generated by site-specific cleavages within a reiterated 20-amino acid sequence. Although the C1 factor appears to be ubiquitously expressed, it is localized to subnuclear structures in specific cell types. C1 MIT,CTR CANC RES,CAMBRIDGE,MA 02139. MIT,DEPT BIOL,CAMBRIDGE,MA 02139. HARVARD UNIV,MIT,DIV HLTH SCI & TECHNOL,CAMBRIDGE,MA 02139. MERCK & CO INC,MERCK SHARP & DOHME RES LABS,RAHWAY,NJ 07065. RP KRISTIE, TM (reprint author), NIAID,VIRAL DIS LAB,BLDG 4,RM 133,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. OI Pomerantz, Joel L./0000-0002-5030-1018 FU NCI NIH HHS [P01-CA42063, P30-CA14051] NR 64 TC 85 Z9 87 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 MAR 3 PY 1995 VL 270 IS 9 BP 4387 EP 4394 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QK084 UT WOS:A1995QK08400034 PM 7876203 ER PT J AU LUJAN, HD MAROTTA, A MOWATT, MR SCIAKY, N LIPPINCOTTSCHWARTZ, J NASH, TE AF LUJAN, HD MAROTTA, A MOWATT, MR SCIAKY, N LIPPINCOTTSCHWARTZ, J NASH, TE TI DEVELOPMENTAL INDUCTION OF GOLGI STRUCTURE AND FUNCTION IN THE PRIMITIVE EUKARYOTE GIARDIA-LAMBLIA SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ADP-RIBOSYLATION FACTOR; BREFELDIN-A; GUANINE-NUCLEOTIDE; ENDOPLASMIC-RETICULUM; SECRETORY PATHWAY; SACCHAROMYCES-CEREVISIAE; ELECTRON-MICROSCOPY; ORGANELLE STRUCTURE; BINDING PROTEINS; CHOLERA-TOXIN AB A fundamental characteristic of eukaryotic cells is the presence of membrane bound compartments and membrane transport pathways in which the Golgi complex plays a central role in the selective processing, sorting, and secretion of proteins. The parasitic protozoan Giardia lamblia belongs to the earliest identified Lineage among eukaryotes and therefore offers unique insight into the progression from primitive to more complex eukaryotic cells. Here, we report that Giardia trophozoites undergo a developmental induction of Golgi enzyme activities, which correlates with the appearance of a morphologically identifiable Golgi complex, as they differentiate to cysts. Prior to this induction, no morphologically or biochemically identifiable Golgi complex exists within nonencysting cells. Remarkably, protein secretion in both nonencysting and encysting trophozoites is inhibited by brefeldin A, and brefeldin A-sensitive membrane association of ADP-ribosylation factor and beta-COP is observed. These results suggest that the secretory machinery of Giardia resembles that of higher eukaryotes despite the absence of a Golgi complex in nonencysting trophozoites. These findings have implications both for defining the minimal machinery for protein secretion in eukaryotes and for examining the biogenesis of Golgi structure and function. C1 NICHHD, CELL BIOL & METAB BRANCH, BETHESDA, MD 20892 USA. RP LUJAN, HD (reprint author), NIAID, PARASIT DIS LAB, 9000 ROCKVILLE PIKE, BLDG 4, RM 126, BETHESDA, MD 20892 USA. NR 67 TC 123 Z9 129 U1 0 U2 4 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 MAR 3 PY 1995 VL 270 IS 9 BP 4612 EP 4618 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QK084 UT WOS:A1995QK08400065 PM 7876232 ER PT J AU YU, G SHEN, FS STURCH, S AQUINO, A GLAZER, RI FELSTED, RL AF YU, G SHEN, FS STURCH, S AQUINO, A GLAZER, RI FELSTED, RL TI REGULATION OF HIV-1 GAG PROTEIN SUBCELLULAR TARGETING BY PROTEIN-KINASE-C SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; MATRIX PROTEIN; STRUCTURAL PROTEINS; MEMBRANE ASSOCIATION; FINE-STRUCTURE; D RETROVIRUSES; LIFE-CYCLE; TYPE-1; CELLS; PRECURSOR AB The human immunodeficiency virus type 1 internal structural protein precursor, p55, and its corresponding matrix proteolytic fragment, p17, are phosphorylated at Ser(111) by protein kinase C. COS-7 cells transfected with plasmids encoding either the wild-type or Ser(111) --> Ala mutated human immunodeficiency virus type 1 gag gene matrix domain proteins were treated with phorbol 12-myristate 13-acetate (PMA), and the phosphorylation of the expressed p17 proteins was examined by radioimmunoprecipitation, SDS-polyacrylamide gel electrophoresis, and autoradiography, PMA treatment of transfected cells resulted in a 4-5-fold increase in wild-type p17 (but not mutated p17) phosphorylation; however, mutated p17 exhibited a low basal level of phosphorylation that was not affected by PMA, suggesting that additional sites were phosphorylated, PMA treatment of cells expressing wild-type p17 produced a dramatic shift in the localization of p17 from the cytosol to the membrane fraction within 8-15 min, followed by a slow quantitative dissociation of p17 back into the cytosol by 90 min, The cytosol-to-membrane translocation was dependent on N-myristoylated p17 since cells expressing p17 with a Gly(2) --> Ala mutation did not localize to the membrane, PMA also failed to induce the translocation of fully N-myristoylated Ser(111) --> Ala p17, suggesting that p17 phosphorylation at Ser(111) was responsible for membrane association, This conclusion was confirmed by the finding of phosphorylated wild-type p17 in the membrane fraction only after PMA treatment, These results suggest that a ''myristoyl-protein switch'' regulates the reversible membrane targeting of p17 by protein kinase C-mediated phosphorylation. This signal may provide a mechanism for the cellular regulation of virus development through modulation of gag protein-related developmental steps such as capsid targeting, assembly, encapsidation, budding, and maturation. C1 NCI,DIV CANC TREATMENT,BIOL CHEM LAB,DEV THERAPEUT PROGRAM,BETHESDA,MD 20892. NR 39 TC 21 Z9 21 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 MAR 3 PY 1995 VL 270 IS 9 BP 4792 EP 4796 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QK084 UT WOS:A1995QK08400088 PM 7876252 ER PT J AU POWELL, BS COURT, DL INADA, T NAKAMURA, Y MICHOTEY, V CUI, XW REIZER, A SAIER, MH REIZER, J AF POWELL, BS COURT, DL INADA, T NAKAMURA, Y MICHOTEY, V CUI, XW REIZER, A SAIER, MH REIZER, J TI NOVEL PROTEINS OF THE PHOSPHOTRANSFERASE SYSTEM ENCODED WITHIN THE RPON OPERON OF ESCHERICHIA-COLI - ENZYME IIA(NTR) AFFECTS GROWTH ON ORGANIC NITROGEN AND THE CONDITIONAL LETHALITY OF AN ERA(TS) MUTANT SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Review ID GRAM-POSITIVE BACTERIA; SITE-SPECIFIC MUTAGENESIS; RHIZOBIUM-MELILOTI NTRA; AMINO-ACID SEQUENCE; SIGMA-FACTOR GENE; NUCLEOTIDE-SEQUENCE; SALMONELLA-TYPHIMURIUM; PHOSPHOCARRIER PROTEIN; BACILLUS-SUBTILIS; STAPHYLOCOCCUS-CARNOSUS AB Two rpoN-linked Delta Tn10-kan insertions suppress the conditionally lethal era(ts) allele. One truncates rpoN while the second disrupts another gene (ptsN) in the rpoN operon and does not affect classical nitrogen regulation. Neither alter expression of era indicating that suppression is post-translational. Plasmid clones of ptsN prevent suppression by either disruption mutation indicating that this gene is important for lethality caused by era(ts). rpoN and six neighboring genes were sequenced and compared with sequences in the database. Two of these genes encode proteins homologous to Enzyme IIA(Fru) and HPr of the phosphoenolpyruvate:sugar phosphotransferase system. We designate these proteins IIA(Ntr) (ptsN) and NPr (npr). Purified IIA(Ntr) and NPr exchange phosphate appropriately with Enzyme I, HPr, and Enzyme IIA proteins of the phosphoenolpyruvate: sugar phosphotransferase system. Several sugars and tricarboxylic acid cycle intermediates inhibited growth of the ptsN disruption mutant on medium containing an amino acid or nucleoside base as a combined source of nitrogen, carbon, and energy. This growth inhibition was relieved by supplying the ptsN gene or ammonium salts but was not aleviated by altering levels of exogenously supplied cAMP. These results support our previous proposal of a novel mechanism linking carbon and nitrogen assimilation and relates IIA(Ntr) to the unknown process regulated by the essential GTPase Era. C1 NCI, FREDERICK CANC RES & DEV CTR, ABL BASIC RES PROGRAM, CHROMOSOME BIOL LAB, FREDERICK, MD 21702 USA. UNIV TOKYO, INST MED SCI, DEPT TUMOR BIOL, TAKANAWA 108, JAPAN. UNIV CALIF SAN DIEGO, DEPT BIOL, LA JOLLA, CA 92093 USA. FU NCI NIH HHS [N01-CO74101]; NIAID NIH HHS [2RO1AI 14176, 5RO1AI 21702] NR 123 TC 165 Z9 174 U1 2 U2 4 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 MAR 3 PY 1995 VL 270 IS 9 BP 4822 EP 4839 PG 18 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QK084 UT WOS:A1995QK08400092 PM 7876255 ER PT J AU TOMONAGA, T LEVENS, D AF TOMONAGA, T LEVENS, D TI HETEROGENEOUS NUCLEAR RIBONUCLEOPROTEIN-K IS A DNA-BINDING TRANSACTIVATOR SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RNA-BINDING; ESCHERICHIA-COLI; PROTEIN; GENE; PURIFICATION; EXPRESSION; ACID; FMR1 AB We have previously reported that heterogeneous nuclear ribonucleoprotein K (hnRNP K) binds to the pyrimidine-rich strand of the CT element found in the human c-myc gene and activates CT reporter-driven gene expression in vivo. We now characterize the DNA and protein requirements for the interaction of hnRNP K with the CT element, First, hnRNP K is shown to preferentially bind single-stranded DNA over RNA or native double-stranded DNA Using specific oligoribonucleotide or deoxyribonucleotide probes with specific or nonspecific RNA or DNA competitors, electrophoretic mobility shift assay revealed hnRNP K: to be a DNA-binding protein. Specific binding was not simply a reflection of binding to pyrimidine-rich sequences as the number and arrangement of individual CT elements governed interactions with hnRNP K; at least two CT repeats separated by at least three nucleotides are required for binding, indicating the existence of particular stereochemical constraints regulating CT-hnRNP K complex formation. Deletion analysis showed that hnRNP K possesses several nonoverlapping, DNA binding domains, each capable of specific: binding with the CT element and preferring DNA over RNA. Each sequence recognition domain is composed of at least one K homology motif, while a larger portion of hnRNP It may be required for stable RNA binding, Additional experiments indicate that the N-terminal 35 residues of hnRNP K are necessary for transactivating the CT element. These results indicate that hnRNP K is a RNA-binding protein and transcriptional activator. C1 NCI,PATHOL LAB,BETHESDA,MD 20892. RI Levens, David/C-9216-2009 OI Levens, David/0000-0002-7616-922X NR 29 TC 146 Z9 152 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 MAR 3 PY 1995 VL 270 IS 9 BP 4875 EP 4881 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QK084 UT WOS:A1995QK08400098 PM 7876260 ER PT J AU LINNEKIN, D MOU, SM GREER, P LONGO, DL FERRIS, DK AF LINNEKIN, D MOU, SM GREER, P LONGO, DL FERRIS, DK TI PHOSPHORYLATION OF A FES-RELATED PROTEIN IN RESPONSE TO GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HL-60 LEUKEMIA-CELLS; TYROSINE KINASE; ERYTHROPOIETIN RECEPTOR; SIGNAL-TRANSDUCTION; INTERLEUKIN-3; EXPRESSION; DIFFERENTIATION; GENE; IDENTIFICATION; ASSOCIATION AB Previous work has suggested that a 97-kDa protein (p97) is involved in the signal transduction pathway of granulocyte-macrophage colony stimulating factor (GMCSF) as well as interleukin 3, erythropoietin, and interleukin 2, We have examined the relationship of p97 to the protein tyrosine kinase Fes in the GM-CSF signal transduction pathway in erythroid and myeloid cell lines. GM-CSF stimulation of three different cell lines induced tyrosine phosphorylation of p97 as well as a number of other phosphotyrosylproteins. Although each cell Line expressed the proto-oncogene product Fes, antisera specific for Pes did not recognize p97 in immunoblotting experiments. Furthermore, immunodepletion of Fes did not reduce the amount of p97 in GM-CSF treated cells. Two dimensional gel electrophoresis demonstrated that p97 and Fes have similar charge to mass ratios, and limited proteolytic mapping of p97 and Fes suggested that these proteins may be related but are not identical. Our studies demonstrate that p97 is not Fes but is probably a Fes related protein. C1 NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. QUEENS UNIV,DEPT PATHOL,CANC RES LABS,KINGSTON,ON K7L 3N6,CANADA. QUEENS UNIV,DEPT BIOCHEM,CANC RES LABS,KINGSTON,ON K7L 3N6,CANADA. RP LINNEKIN, D (reprint author), NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RECOURSES INC DYNCORP,DIV CANC TREATMENT,FREDERICK,MD 21702, USA. NR 31 TC 19 Z9 19 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 3 PY 1995 VL 270 IS 9 BP 4950 EP 4954 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QK084 UT WOS:A1995QK08400108 PM 7876270 ER PT J AU RIDA, W FAST, P HOFF, R BARKER, L AF RIDA, W FAST, P HOFF, R BARKER, L TI AIDS - MODELING EPIDEMIC CONTROL SO SCIENCE LA English DT Letter RP RIDA, W (reprint author), NIAID,DIV AIDS,VACCINE & PREVENT RES PROGRAM,BETHESDA,MD 20892, USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC ADVAN SCIENCE PI WASHINGTON PA 1333 H ST NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD MAR 3 PY 1995 VL 267 IS 5202 BP 1251 EP 1252 DI 10.1126/science.7871415 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA QK068 UT WOS:A1995QK06800005 PM 7871415 ER PT J AU GURALNIK, JM FERRUCCI, L SIMONSICK, EM SALIVE, ME WALLACE, RB AF GURALNIK, JM FERRUCCI, L SIMONSICK, EM SALIVE, ME WALLACE, RB TI LOWER-EXTREMITY FUNCTION IN PERSONS OVER THE AGE OF 70 YEARS AS A PREDICTOR OF SUBSEQUENT DISABILITY SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID MAINTAINING MOBILITY; PHYSICAL-ACTIVITY; RISK-FACTORS; SELF-REPORT; LATE-LIFE; VALIDITY; HEALTH; ELDERS; COMMUNITY; CAPACITY AB Background. Functional assessment is an important part of the evaluation of elderly persons. We conducted this study to determine whether objective measures of physical function can predict subsequent disability in older persons. Methods. This prospective cohort study included men and women 71 years of age or older who were living in the community, who reported no disability in the activities of daily living, and who reported that they were able to walk one-half mile (0.8 km) and climb stairs without assistance, The subjects completed a short battery of physical-performance tests and participated in a follow-up interview four years later. The tests included an assessment of standing balance, a timed 8-ft (2.4-m) walk at a normal pace, and a timed test of five repetitions of rising from a chair and sitting down. Results. Among the 1122 subjects who were not disabled at base line and who participated in the four-year follow-up, lower scores on the base-line performance tests were associated with a statistically significant, graduated increase in the frequency of disability in the activities of daily living and mobility-related disability at follow-up. After adjustment for age, sex, and the presence of chronic disease, those with the lowest scores on the performance tests were 4.2 to 4.9 times as likely to have disability at four years as those with the highest performance scores, and those with intermediate performance scores were 1.6 to 1.8 times as likely to have disability. Conclusions. Among nondisabled older persons living in the community, objective measures of lower-extremity function were highly predictive of subsequent disability. Measures of physical performance may identify older persons with a preclinical stage of disability who may benefit from interventions to prevent the development of frank disability. C1 NATL INST RES & CARE ELDERLY,HOSP I FRATICINI,DEPT GERIATR,FLORENCE,ITALY. UNIV IOWA,DEPT PREVENT MED & ENVIRONM HLTH,IOWA CITY,IA. RP GURALNIK, JM (reprint author), NIA,EPIDEMIOL DEMOG & BIOMETRY PROGRAM,7201 WISCONSIN AVE,RM 3C-309,BETHESDA,MD 20892, USA. FU NIA NIH HHS [AG-10127-01, N01-AG-0-2106] NR 38 TC 1760 Z9 1781 U1 9 U2 59 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 MAR 2 PY 1995 VL 332 IS 9 BP 556 EP 561 DI 10.1056/NEJM199503023320902 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA QJ090 UT WOS:A1995QJ09000002 PM 7838189 ER PT J AU KOVACS, JA BASELER, M DEWAR, RJ VOGEL, S DAVEY, RT FALLOON, J POLIS, MA WALKER, RE STEVENS, R SALZMAN, NP METCALF, JA MASUR, H LANE, HC AF KOVACS, JA BASELER, M DEWAR, RJ VOGEL, S DAVEY, RT FALLOON, J POLIS, MA WALKER, RE STEVENS, R SALZMAN, NP METCALF, JA MASUR, H LANE, HC TI INCREASES IN CD4 T-LYMPHOCYTES WITH INTERMITTENT COURSES OF INTERLEUKIN-2 IN PATIENTS WITH HUMAN-IMMUNODEFICIENCY-VIRUS INFECTION - A PRELIMINARY-STUDY SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID IMMUNE-DEFICIENCY-SYNDROME; PLACEBO-CONTROLLED TRIAL; HIV-INFECTION; RECOMBINANT INTERLEUKIN-2; INTERFERON-GAMMA; PHASE-I; TYPE-1 INFECTION; KAPOSIS SARCOMA; NATURAL-KILLER; SYNDROME AIDS AB Background. Interleukin-2 is an important regulatory cytokine of the immune system, with potent effects on T cells, B cells, and natural killer cells. In vitro, interleukin-2 can induce the proliferation and differentiation of peripheral-blood mononuclear cells from patients infected with the human immunodeficiency virus (HIV). Methods. We treated 25 HIV-infected patients with interleukin-2 administered as a continuous infusion at a dosage of 6 to 18 million IU per bay for 5 days every 8 weeks during a period of 7 to 25 months. All patients also received at least one approved antiviral agent. Immunologic and virologic variables were monitored monthly. Results. In 6 of 10 patients with base-line CD4 counts higher than 200 per cubic millimeter, interleukin-2 therapy was associated with at least a 50 percent increase in the number of CD4 cells. Changes ranged from -81 to +2211 cells per cubic millimeter. Interleukin-2 therapy resulted in a decline in the percentage of CD8 lymphocytes expressing HLA-DR and an increase in the percentage of CD4 lymphocytes that were positive for the p55 chain of the interleukin-2 receptor. Four patients had a transient but consistent increase in the plasma HIV RNA level at the end of each infusion. In the remaining 15 patients, who had CD4 counts of 200 or fewer cells per cubic millimeter, interleukin-2 therapy was associated with increased viral activation, few immunologic improvements, and substantial toxic effects. Conclusions. Intermittent courses of interleukin-2 can improve some of the immunologic abnormalities associated with HIV infection in patients with more than 200 CD4 cells per cubic millimeter. C1 NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. NIAID,WARREN GRANT MAGNUSON CLIN CTR,DEPT CRIT CARE MED,BETHESDA,MD. PROGRAM RESOURCES INC DYNCORP,FREDERICK,MD. OI Polis, Michael/0000-0002-9151-2268 FU NIAID NIH HHS [N01-AI-05058] NR 44 TC 380 Z9 383 U1 0 U2 0 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 MAR 2 PY 1995 VL 332 IS 9 BP 567 EP 575 DI 10.1056/NEJM199503023320904 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA QJ090 UT WOS:A1995QJ09000004 PM 7646637 ER PT J AU MORRIS, C BENJES, S HAATAJA, L LEDBETTER, DH HEISTERKAMP, N GROFFEN, J AF MORRIS, C BENJES, S HAATAJA, L LEDBETTER, DH HEISTERKAMP, N GROFFEN, J TI SPATIAL-ORGANIZATION OF ABR AND CRK GENES ON HUMAN-CHROMOSOME BAND 17P13.3 SO ONCOGENE LA English DT Note DE ABR GENE; CRK GENE; CHROMOSOME; 17P13.3; D17S34 ID GUANINE-NUCLEOTIDE EXCHANGE; INTERPHASE CELL-NUCLEI; MILLER-DIEKER SYNDROME; HYPERVARIABLE RFLP; DNA-SEQUENCES; ONCOGENE; PROTEIN; P53; LOCALIZATION; HOMOLOGY AB Deletion of part or all of chromosome 17p is among the most frequent chromosome abnormalities in human cancer. We show that the CRK and ABR genes are close to a marker on chromosome 17p13.3, D17S34, which is frequently deleted in different tumours, and demonstrate that CRK is centromeric to ABR. CRK and ABR may be involved in cancer themselves, or otherwise may function as points of reference for further experiments to clone genes from chromosome 17p which may play a role in cancer. C1 CHILDRENS HOSP LOS ANGELES,DEPT PATHOL,MOLEC DIAGNOSIS SECT,LOS ANGELES,CA 90027. CHRISTCHURCH HOSP,CYTOGENET & MOLEC ONCOL UNIT,CHRISTCHURCH,NEW ZEALAND. NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. RI Morris, Christine/G-1690-2011 FU NCI NIH HHS [CA47456] NR 36 TC 17 Z9 17 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HANTS, ENGLAND RG21 2XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD MAR 2 PY 1995 VL 10 IS 5 BP 1009 EP 1011 PG 3 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA QL038 UT WOS:A1995QL03800023 PM 7898918 ER PT J AU AMOROSA, JK LARAYACUASAY, LR SOHN, L LOEB, DM GELLER, NL STYLIANOU, M NOSHER, JL AF AMOROSA, JK LARAYACUASAY, LR SOHN, L LOEB, DM GELLER, NL STYLIANOU, M NOSHER, JL TI RADIOLOGIC-DIAGNOSIS OF CYSTIC-FIBROSIS IN ADULTS AND CHILDREN SO ACADEMIC RADIOLOGY LA English DT Article DE CYSTIC FIBROSIS; BRASFIELD SCORE; SHWACHMAN-KULCZYEKI CLASSIFICATION; CHEST RADIOGRAPH; DIFFERENTIAL DIAGNOSIS OF CHRONIC LUNG DISEASE AB Rationale and Objectives. Most radiologists are familiar with the classic chest radiographic findings of cystic fibrosis (CF) when these occur in children. We hypothesized that given the same findings, a diagnosis of CF would be less likely to be considered in an adult than in a child. Methods. We compiled 30 pediatric and 28 adult CF chest radiographs and obtained two independent readings on each by different general radiologists among the eight who volunteered to participate as they performed their daily clinical work. The cases were presented to the readers so that they did not know which radiographs were part of the study. The association between the correct diagnosis of CF and whether the patient was an adult or a child was assessed using odds ratios and logistic regression, so that Brasfield score, Schwachman-Kulczycki score, and the patient's sex could also be considered as predictive of correct diagnosis. Results. In 67% of the pediatric cases, at least one of the radiologists considered CF as a possible diagnosis, whereas they considered CF a possibility in only 50% of the adults. Both radiologists suggested the correct diagnosis in 40% of pediatric cases and only 14% of adult cases (p < .05). Conclusion. Because the radiographic findings were similar in the two groups of patients according to severity groupings, we believe CF was less commonly considered in the adult patient because of the traditional belief that CF is a childhood disease. C1 UNIV MED & DENT NEW JERSEY,ROBERT WOOD JOHNSON MED SCH,DEPT PEDIAT,NEW BRUNSWICK,NJ 08903. NHLBI,BIOSTAT RES BRANCH,BETHESDA,MD 20892. RP AMOROSA, JK (reprint author), UNIV MED & DENT NEW JERSEY,ROBERT WOOD JOHNSON MED SCH,DEPT RADIOL,NEW BRUNSWICK,NJ 08903, USA. NR 8 TC 4 Z9 4 U1 0 U2 1 PU ASSOC UNIV RADIOLOGISTS PI RESTON PA 1891 PRESTON WHITE DR, RESTON, VA 22091 SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD MAR PY 1995 VL 2 IS 3 BP 222 EP 225 DI 10.1016/S1076-6332(05)80169-2 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA QP037 UT WOS:A1995QP03700006 PM 9419552 ER PT J AU HU, WX CAO, Y LI, XY LEO, ML YAO, KT AF HU, WX CAO, Y LI, XY LEO, ML YAO, KT TI COMPARISON OF NPC TRANSFORMING GENE TX TO IG-KAPPA CONSTANT-REGION GENE AND THEIR EXPRESSIONS IN DIFFERENT CELL-LINES SO ACTA BIOCHIMICA ET BIOPHYSICA SINICA LA Chinese DT Article DE NASOPHARYNGEAL CARCINOMA (NPC); TRANSFORMING GENE TX; IG LIGHT CHAIN KAPPA GENE; GENE EXPRESSION ID IMMUNOGLOBULIN AB We have compared the nucleotide sequence and amino acid sequence of coding product of human immunoglobulin light chain kappa constant region gene (IGKC) to those of human nasopharyngeal carcinoma(NPC) transforming gene (Tx gene)2.8kb EcoR I fragment. The results show that the homology of these two genes is as high as 99.5% and 100% in coding region, indicating that Tx gene and kappa gene are the same gene. This conclusion is. also supported by restriction :mapping and Southern blot analysis of the two genes. Meanwhile, the expressions ;of Tx gene and kappa gene in different malignant cell lines have been investigated. Interestingly, the kappa gene is not only expressed in B lymphatic cell lines (RAji, B95-8, BJAB), but also expressed in NPC cell lines (CNE2, CNE1, HNE1). The expression of this gene has not been detected in human T lymphatic cell lines (Hut 102, MT 2) and in human cervical cell lines (HT-S, ME-180, Hela). The relationship between the expression of kappa gene and NPC carcinogenesis is being investigated. C1 NCI,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. HUNAN MED UNIV,INST CANC RES,CHANGSHA 410078,PEOPLES R CHINA. NR 6 TC 4 Z9 4 U1 0 U2 0 PU SHANGHAI INST BIOCHEMISTRY, ACADEMIA SINICA PI SHANGHAI PA 320 YUE-YANG ROAD, SHANGHAI 20031, PEOPLES R CHINA SN 0582-9879 J9 ACTA BIOCH BIOPH SIN JI Acta Biochim. Biophsy. Sin. PD MAR PY 1995 VL 27 IS 2 BP 215 EP 221 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA RA076 UT WOS:A1995RA07600015 ER PT J AU SUZUKI, K PARKER, CC PENTCHEV, PG KATZ, D GHETTI, B DAGOSTINO, AN CARSTEA, ED AF SUZUKI, K PARKER, CC PENTCHEV, PG KATZ, D GHETTI, B DAGOSTINO, AN CARSTEA, ED TI NEUROFIBRILLARY TANGLES IN NIEMANN-PICK DISEASE TYPE-C SO ACTA NEUROPATHOLOGICA LA English DT Article DE NEURONAL STORAGE DISEASE; CHOLESTEROL METABOLISM; TAU; PAIRED HELICAL FILAMENTS; LYSOSOMAL DISEASE ID APOLIPOPROTEIN-E; ALZHEIMERS-DISEASE; IMMUNOREACTIVITY; CHOLESTEROL; DEMENTIA; PLAQUES; PROTEIN AB Niemann-Pick disease type C (NPC) is an autosomal recessive disease, belonging to a clinically heterogeneous group of lipid storage diseases, distinguished by a unique error in cellular trafficking of exogenous cholesterol, associated with lysosomal accumulation of unesterified cholesterol. Unlike Niemann-Pick disease types A and B, there is no primary genetic defect in sphingomyelinase in NPC. During the routine neuropathological study of NPC patients, we found neurofibrillary tangles (NFT) in a series of cases with a slowly progressive chronic course. These were not associated with P-amyloid deposits. The NFT were most frequent in the orbital gyrus, cingulate gyrus and entorhinal region of the cerebral cortex, but were also frequently found in the basal ganglia, thalamus and hypothalamus. In one of the most severely affected case, the NFT were even found in the neurons in the inferior olivary nucleus and in the spinal cord. The NFT were immunostained with Alz 50, and consisted of paired helical filaments. The distribution of the neurons bearing the NFT was generally similar to that of the swollen storage neurons, and storage neurons often contained NFT in their perikarya and/or in the meganeurites. However, neurons with NFT could be noted without swollen perikarya. The coexistence of neuronal storage and NFT in NPC without amyloid deposits suggests that perturbed cholesterol metabolism and/or lysosomal membrane trafficking may play a role in the formation of NFT, and that amyloid deposits are not necessarily the prerequisite for NFT formation. The results of our study also suggest that NFT formation may be a rather nonspecific cellular reaction of neurons to certain slowly progressive metabolic perturbations of an as yet undefined nature. C1 UNIV N CAROLINA,SCH MED,BRAIN & DEV RES CTR,CHAPEL HILL,NC 27599. NINCDS,DEV & METAB NEUROL BRANCH,BETHESDA,MD 20892. NCI,PATHOL LAB,BETHESDA,MD 20892. NINCDS,OFF CLIN DIRECTOR,BETHESDA,MD 20892. INDIANA UNIV,MED CTR,DEPT PATHOL & LAB MED,INDIANAPOLIS,IN. OREGON HLTH SCI UNIV,DEPT PATHOL,PORTLAND,OR 97201. RP SUZUKI, K (reprint author), UNIV N CAROLINA,SCH MED,DEPT PATHOL,CB 7525,CHAPEL HILL,NC 27599, USA. FU NIA NIH HHS [AG 10133]; NICHD NIH HHS [HD03110]; NINDS NIH HHS [NS 24453] NR 34 TC 128 Z9 132 U1 0 U2 3 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0001-6322 J9 ACTA NEUROPATHOL JI Acta Neuropathol. PD MAR PY 1995 VL 89 IS 3 BP 227 EP 238 PG 12 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA QJ441 UT WOS:A1995QJ44100005 PM 7754743 ER PT J AU SALIVE, ME JONES, CA GURALNIK, JM AGODOA, LY PAHOR, M WALLACE, RB AF SALIVE, ME JONES, CA GURALNIK, JM AGODOA, LY PAHOR, M WALLACE, RB TI SERUM CREATININE LEVELS IN OLDER ADULTS - RELATIONSHIP WITH HEALTH-STATUS AND MEDICATIONS SO AGE AND AGEING LA English DT Article ID RENAL-FUNCTION; DIABETIC NEPHROPATHY; BLOOD-PRESSURE; ANTIHYPERTENSIVE TREATMENT; KIDNEY; AGE; EPIDEMIOLOGY; CLEARANCE AB We aimed to examine the association of serum creatinine with health status and current medications in the population of older adults. We employed a cross-sectional study within an ongoing cohort of 3999 residents of three communities of the Established Populations for Epidemiologic Studies of the Elderly who had venepuncture at the 6-year follow-up when they were aged 71 years and older. Serum creatinine levels, history of diabetes and heart attack, current medications, and blood pressure were measured. Creatinine levels were higher in men than in women, and in blacks than in whites. Higher creatinine levels were observed in persons with a history of diabetes or heart attack, and in those reporting use of cimetidine and diuretic medications. Persons taking frusemide and the potassium-sparing diuretics had higher creatinine levels than those taking thiazides. This study confirms associations of higher creatinine with male sex, older age, black race, history of diabetes and cimetidine use reported from cross-sectional research in younger populations and in smaller, more selected groups of older adults. Longitudinal studies will be necessary to strengthen our understanding of the causes of changes in kidney function in the older population. C1 NIADDKD,DIV KIDNEY UROL & HEMATOL DIS,BETHESDA,MD 20892. NIH,BETHESDA,MD 20892. UNIV IOWA,DEPT PREVENT & ENVIRONM HLTH,IOWA CITY,IA 52242. RP SALIVE, ME (reprint author), NIA,EPIDEMIOL DEMOG & BIOMETRY PROGRAM,BETHESDA,MD 20892, USA. FU NIA NIH HHS [N01-AG-02105, N01-AG-02107, N01-AG-02106] NR 41 TC 31 Z9 31 U1 3 U2 3 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0002-0729 J9 AGE AGEING JI Age Ageing PD MAR PY 1995 VL 24 IS 2 BP 142 EP 150 DI 10.1093/ageing/24.2.142 PG 9 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA QM504 UT WOS:A1995QM50400012 PM 7793337 ER PT J AU KRONER, BL GOEDERT, JJ BLATTNER, WA WILSON, SE CARRINGTON, MN MANN, DL OBRIEN, SJ WILLOUGHBY, A KESSEL, W DONFIELD, SM MCKINLAY, SM ALEDORT, LM ARKIN, S EYSTER, ME PATTISHALL, EG HILGARTNER, MW KONKLE, B WHITE, GC COHEN, AR BRAY, GL LUBAN, N KESSLER, CM RAGNI, MV LEDERMAN, MM LEISSINGER, C SIROIS, P MANCOJOHNSON, M DEMOERLOOSE, P MAHE, A HATZAKIS, A MANDALAKI, T SCHRAMM, W EICHINGER, S STINGL, G GOMPERTS, ED HOOTS, WK LOVELAND, KA KISKER, CT STEHBENS, AA CONTANT, CF HUSZTI, H SWINDELLS, S MANGOS, J WARRIER, I SHAPIRO, AD DAVIGNON, GF WICKLUND, BM WINKLER, C AF KRONER, BL GOEDERT, JJ BLATTNER, WA WILSON, SE CARRINGTON, MN MANN, DL OBRIEN, SJ WILLOUGHBY, A KESSEL, W DONFIELD, SM MCKINLAY, SM ALEDORT, LM ARKIN, S EYSTER, ME PATTISHALL, EG HILGARTNER, MW KONKLE, B WHITE, GC COHEN, AR BRAY, GL LUBAN, N KESSLER, CM RAGNI, MV LEDERMAN, MM LEISSINGER, C SIROIS, P MANCOJOHNSON, M DEMOERLOOSE, P MAHE, A HATZAKIS, A MANDALAKI, T SCHRAMM, W EICHINGER, S STINGL, G GOMPERTS, ED HOOTS, WK LOVELAND, KA KISKER, CT STEHBENS, AA CONTANT, CF HUSZTI, H SWINDELLS, S MANGOS, J WARRIER, I SHAPIRO, AD DAVIGNON, GF WICKLUND, BM WINKLER, C TI CONCORDANCE OF HUMAN-LEUKOCYTE ANTIGEN HAPLOTYPE-SHARING, CD4 DECLINE AND AIDS IN HEMOPHILIC SIBLINGS SO AIDS LA English DT Article DE HUMAN LEUKOCYTE ANTIGEN; HEMOPHILIA; AIDS; SIBLINGS ID HUMAN-IMMUNODEFICIENCY-VIRUS; TYPE-1 INFECTION; DNA; HIV; SUSCEPTIBILITY; POLYMORPHISM; DISEASE; PLASMA; STAGE AB Objective: To assess the association between human leukocyte antigen (HLA) haplotypes and the incidence rates of CD4 decline to <20% and to AIDS. Design: Retrospective cohort study of 95 HIV-1-infected hemophilic sibling pairs. Methods: HLA haplotype-sharing between siblings was assigned on the basis of serologic typing of HLA class I alleles and molecular typing of HLA class II alleles. Concordance of time to CD4 decline to <20% and to AIDS within and between sibling pairs was assessed by analysis of variance models and calculations of intraclass correlation coefficients. The age-adjusted relative risks of these two endpoints for unique class II haplotypes were determined from proportional hazards models. Results: Sibling pairs sharing one or two haplotypes were significantly concordant in CD4 decline and AIDS status within 5 years of seroconversion. No concordance was found in pairs sharing zero haplotypes. At 6-10 years after seroconversion, significant concordance of these two endpoints was also observed in the pairs sharing one haplotype. The concordant results were not explained by the use of zidovudine within the pairs. Among the individuals in this cohort, the relative hazards for CD4 decline to <20% and for AIDS were significantly elevated for one class II haplotype (DQB1*0501, DQA1*0101, DRB1*0101). In addition, the risk for AIDS was significantly increased for two other class II haplotypes (DQB1*0603, DQA1*0103, DRB1*1300, DRB3*0202 and DQB1*0301, DQA1*0501, DRB1*1400, DRB3*0202) and significantly decreased for one haplotype (DQB1*0302, DQA1*0301, DRB1*0401, DRB4*0101). Conclusions: These data demonstrate that HIV-1 disease progression is associated with the genes in the major histocompatibility complex that regulate the host's immune response. C1 NCI,VIRAL EPIDEMIOL BRANCH,FREDERICK,MD 21701. NCI,PROGRAM RESOURCES INC DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21701. NCI,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21701. RP KRONER, BL (reprint author), RES TRIANGLE INST,EPIDEMIOL & MED STUDIES PROGRAM,6101 EXECUT BLVD,SUITE 365,ROCKVILLE,MD 20852, USA. FU NCI NIH HHS [N01-CP-33002] NR 18 TC 42 Z9 42 U1 1 U2 4 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0269-9370 J9 AIDS JI Aids PD MAR PY 1995 VL 9 IS 3 BP 275 EP 280 PG 6 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA QJ626 UT WOS:A1995QJ62600009 PM 7755916 ER PT J AU PIALOUX, G EXCLER, JL RIVIERE, Y GONZALEZCANALI, G FEUILLIE, V COULAUD, P GLUCKMAN, JC MATTHEWS, TJ MEIGNIER, B KIENY, MP GONNET, P DIAZ, I MERIC, C PAOLETTI, E TARTAGLIA, J SALOMON, H PLOTKIN, S AF PIALOUX, G EXCLER, JL RIVIERE, Y GONZALEZCANALI, G FEUILLIE, V COULAUD, P GLUCKMAN, JC MATTHEWS, TJ MEIGNIER, B KIENY, MP GONNET, P DIAZ, I MERIC, C PAOLETTI, E TARTAGLIA, J SALOMON, H PLOTKIN, S TI A PRIME-BOOST APPROACH TO HIV PREVENTIVE VACCINE USING A RECOMBINANT CANARYPOX VIRUS EXPRESSING GLYCOPROTEIN-160 (MN) FOLLOWED BY A RECOMBINANT GLYCOPROTEIN-160 (MN/LAI) SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID CYTOLYTIC LYMPHOCYTES-T; IMMUNODEFICIENCY-VIRUS; ENVELOPE GLYCOPROTEINS; NAIVE ADULTS; GP160; CELL; IMMUNIZATION; CHIMPANZEES; INDUCTION; SEQUENCE AB The safety and the immunogenicity of a recombinant canarypox live vector expressing the human immuno-deficiency virus type 1 (HIV-1) gp160 gene from the MN isolate, ALVAC-HIV (vCP125), followed by booster injections of a soluble recombinant hybrid envelope glycoprotein MN/LAI (rgpl60), were evaluated in vaccinia-immune, healthy adults at low risk for acquiring HIV-1 infection, Volunteers (n = 20) received vCP125 (10(6) TCID50) at 0 and 1 month, followed randomly by rgpl60 formulated in alum or in Freund's incomplete adjuvant (FIA) at 3 and 6 months. Local and systemic reactions were mild or moderate and resolved within the first 72 hr after immunization. No significant biological changes in routine tests were observed in any volunteer. Two injections of vCP125 did not elicit antibodies. Neutralizing antibodies (NA) against the HIV-1 MN isolate were detected in 65 and 90% of the subjects after the first and the second rgp 160 booster injections, respectively, Six months after the last boost, only 55% were still positive, Seven of 14 sera with the highest NA titers against MN weakly cross-neutralized the HIV-1 SF2 isolate; none had NA against the HIV-1 LAI or against a North American primary isolate. Specific lymphocyte T cell proliferation to rgp 160 was detected in 25% of the subjects after vCP125 acid in all subjects after the first booster injection and 12 months after the first injection, An envelope-specific cytotoxic lymphocyte activity was found in 39% of the volunteers and characterized for some of them as CD3(+), CD8(+), MHC class I restricted. The adjuvant formulation did not influence significantly the immune responses, This prime-boost vaccine approach using a nonreplicating recombinant live vector, ALVAC-HIV (vCP125), and an rgpl60 was safe in humans and did induce both humoral and cell-mediated immune responses. C1 PASTEURS MERIEUX SERUMS & VACCINS,F-92430 MARNES COQUETTE,FRANCE. HOP INST PASTEUR,PARIS,FRANCE. INST PASTEUR,PARIS,FRANCE. HOP LA PITIE SALPETRIERE,PARIS,FRANCE. CNRS,URA 1463,PARIS,FRANCE. DUKE UNIV,DURHAM,NC. TRANSGENE SA,STRASBOURG,FRANCE. VIROGENET,ALBANY,NY. NCI,BETHESDA,MD 20892. THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,PHILADELPHIA,PA 19107. NR 27 TC 127 Z9 131 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD MAR PY 1995 VL 11 IS 3 BP 373 EP 381 DI 10.1089/aid.1995.11.373 PG 9 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA QP480 UT WOS:A1995QP48000007 PM 7598771 ER PT J AU ABIMIKU, AG FRANCHINI, G ALDRICH, K MYAGKIKH, M MARKHAM, P GARD, E GALLO, RC ROBERTGUROFF, M AF ABIMIKU, AG FRANCHINI, G ALDRICH, K MYAGKIKH, M MARKHAM, P GARD, E GALLO, RC ROBERTGUROFF, M TI HUMORAL AND CELLULAR IMMUNE-RESPONSES IN RHESUS MACAQUES INFECTED WITH HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-2 SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID TOXIC LYMPHOCYTES-T; CYNOMOLGUS MONKEYS; SEROPOSITIVE INDIVIDUALS; CYTOTOXIC LYMPHOCYTES; INSITU HYBRIDIZATION; MACACA-NEMESTRINA; VIRAL REPLICATION; PERIPHERAL-BLOOD; HUMAN RETROVIRUS; HIV-2 INFECTION AB Eighteen rhesus macaques were inoculated with either an infectious molecularly cloned human immunodeficiency virus type 2 (HIV-2)(SBW/ISY), Or With one of eight mutants defective in one or more accessory genes, The immune responses generated by the macaques were monitored for up to 2 years postinfection, All the macaques except those that received mutants lacking the vpr or vif genes demonstrated low to moderate antibody titers, Macaques inoculated with vpx(-) mutants exhibited a persistent serological response, suggesting continuous virus expression even in the absence of detectable virus in the peripheral blood mononuclear cells (PBMCs), Neutralizing antibodies developed in only four macaques, In general, low-level cytotoxic T lymphocyte (CTL) activity, not clearly HIV-2 specific, was detected in PBMCs, However, one virus-negative macaque exhibited significant HIV-2-specific CTL activity in an enriched CD8(+) cell population from PBMCs, suggesting clearance of the viral infection, In addition, CTL activity against the Env and Gag/Pol epitopes of HIV-2 by CD8(+) lymphocytes from the spleens and lymph nodes of two infected macaques, in one case requiring CD8(+) T cell enrichment and in the other clearly evident in unfractionated tissue lymphocytes, was demonstrated for the first time, This sequestration of tissue CTLs occurred in the absence of significant levels of circulating CTLs in the blood, Our results suggest that routine monitoring of PBMCs may sometimes be inadequate for detecting cell-mediated immune responses. Elucidation of immune correlates of vaccine protection may therefore require sampling of lymphoid tissues and assessment of enriched CD8(+) populations. C1 NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. ADV BIOSCI LABS INC,DEPT CELL BIOL,KENSINGTON,MD 20895. NR 66 TC 14 Z9 14 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD MAR PY 1995 VL 11 IS 3 BP 383 EP 393 DI 10.1089/aid.1995.11.383 PG 11 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA QP480 UT WOS:A1995QP48000008 PM 7786583 ER PT J AU ANDERSON, LM CHHABRA, SK NERURKAR, PV SOULIOTIS, VL KYRTOPOULOS, SA AF ANDERSON, LM CHHABRA, SK NERURKAR, PV SOULIOTIS, VL KYRTOPOULOS, SA TI ALCOHOL-RELATED CANCER RISK - A TOXICOKINETIC HYPOTHESIS SO ALCOHOL LA English DT Article; Proceedings Paper CT Symposium on Alcohol and Cancer CY JUN 19, 1994 CL KAMAPALI BEACH, HI SP RES SOC ALCOHOLISM DE ETHANOL; NITROSAMINE; ALCOHOL; TOXICOKINETICS; RODENT TUMORIGENESIS; NONHUMAN PRIMATE; DNA ADDUCTS; LIVER; LUNG; CYTOCHROME P450; CYP2E1; CARCINOGEN METABOLISM; PRENATAL EXPOSURE ID INDUCIBLE CYTOCHROME-P450 CYP2E1; N-NITROSODIMETHYLAMINE; LUNG-CANCER; CHRONIC ETHANOL; RAT-LIVER; HEPATOCELLULAR-CARCINOMA; NITROSAMINE METABOLISM; GENETIC-POLYMORPHISM; LIPID-PEROXIDATION; EXPOSURE OCCURS AB Consumption of alcoholic beverages is an accepted social custom world-wide. This makes its involvement in events contributing to human cancer risk very important. Although it is neither tumorigenic nor genotoxic in animals, ethanol can potentiate the carcinogenic risk associated with certain environmentally present agents. The reasons for such a synergistic action are speculative, but among theories postulated may be ethanol's ability to modify the toxicokinetics/dynamics of carcinogen metabolism. Experiments conducted with rodents and primates support this hypothesis, demonstrating increased exposure of posthepatic organs to nitrosamines when given in combination with ethanol, followed by enhancement of DNA adduct formation and, at least in rodents, of tumor development. In addition, ethanol may induce enzymes responsible for carcinogen activation, including hepatic cytochrome P450 2E1 in rodents and humans, and in lung, kidney, and brain in rodents. Studies have also shown that these effects can extend to the next generation via maternal and in utero fetal exposure. What impact such ethanol-induced modulations have on tumorigenesis during childhood and later stages of life needs to be investigated further. C1 NATL HELLEN RES FDN, INST BIOL RES & BIOTECHNOL, GR-11635 ATHENS, GREECE. RP ANDERSON, LM (reprint author), NCI, FREDERICK CANC RES & DEV CTR, COMPARAT CARCINOGENESIS LAB, DIV CANC ETIOL, BLDG 538, FREDERICK, MD 21702 USA. NR 84 TC 50 Z9 52 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-8329 EI 1873-6823 J9 ALCOHOL JI Alcohol PD MAR-APR PY 1995 VL 12 IS 2 BP 97 EP 104 DI 10.1016/0741-8329(94)00089-1 PG 8 WC Substance Abuse; Pharmacology & Pharmacy; Toxicology SC Substance Abuse; Pharmacology & Pharmacy; Toxicology GA QN755 UT WOS:A1995QN75500004 PM 7772272 ER PT J AU NOVORADOVSKY, AG SANDOVAL, C GUDERIAN, RH ZIMMERMAN, PA NUTMAN, TB GOLDMAN, D AF NOVORADOVSKY, AG SANDOVAL, C GUDERIAN, RH ZIMMERMAN, PA NUTMAN, TB GOLDMAN, D TI DETECTION OF ALDEHYDE DEHYDROGENASE-DEFICIENCY IN CHACHI INDIANS, ECUADOR SO ALCOHOL LA English DT Article DE ALDEHYDE DEHYDROGENASE; ENZYME DEFICIENCY; ISOELECTRIC FOCUSING; SOUTH AMERICAN INDIANS ID HAIR ROOTS; ISOZYMES; ALCOHOL; AMERICAN; LOCUS AB The activity of mitochondrial aldehyde dehydrogenase (ALDH2) was tested by isoelectric focusing of hair root extracts from 50 Chachi Indians (Ecuador). Quality of extracts and the intactness of cytoplasmic and mitochondrial enzymes were ascertained by assaying of phosphoglucomutase (PGM) and malate dehydrogenase (MDH) in the same extracts. Three of the 39 successfully assayed Chachi Indian samples showed virtual absence of the ALDH2 band on the isoelectropherogram, and the control enzymes were stained normally in these subjects. These data confirm the existence of a mitochondrial ALDH deficiency among South American Indians. The molecular origin of the ALDH2 deficiency in this population is unknown. C1 VOZANDES HOSP,QUITO,ECUADOR. NIAID,PARASIT DIS LAB,BETHESDA,MD 20892. RP NOVORADOVSKY, AG (reprint author), NIAAA,NEUROGENET LAB,12501 WASHINGTON AVE,ROCKVILLE,MD 20852, USA. RI Goldman, David/F-9772-2010 OI Goldman, David/0000-0002-1724-5405 NR 16 TC 8 Z9 8 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0741-8329 J9 ALCOHOL JI Alcohol PD MAR-APR PY 1995 VL 12 IS 2 BP 159 EP 161 DI 10.1016/0741-8329(94)00085-9 PG 3 WC Substance Abuse; Pharmacology & Pharmacy; Toxicology SC Substance Abuse; Pharmacology & Pharmacy; Toxicology GA QN755 UT WOS:A1995QN75500014 PM 7772268 ER PT J AU NOVORADOVSKY, AG KIDD, J KIDD, K GOLDMAN, D AF NOVORADOVSKY, AG KIDD, J KIDD, K GOLDMAN, D TI APPARENT MONOMORPHISM OF ALDH2 IN 7 AMERICAN-INDIAN POPULATIONS SO ALCOHOL LA English DT Article DE ALDEHYDE DEHYDROGENASE; POLYMORPHISM; ALLELE-SPECIFIC AMPLIFICATION; SINGLE-STRANDED CONFORMATION POLYMORPHISM; SOUTH AMERICAN INDIANS ID ALDEHYDE DEHYDROGENASE AB Deficiency of mitochondrial aldehyde dehydrogenase (ALDH2) has been previously reported in South American Indians. We therefore assayed five individuals from each of five South American Indian populations (Quechua, Karitiana, Ticuna, Surui, Guahiba), and two North American populations (Maya and Moskoke) for the presence of the Oriental ALDH(2)(2) variant. These samples were also surveyed for other alleles altering ALDH2 function. Allele-specific amplification assay (ASA) did not detect the ALDH(2)(2) allele in any of the New World populations studied. The entire coding sequence of the ALDH2 cDNA was enzymatically amplified in partially overlapping fragments. Each fragment was digested using restriction endonucleases and subfragments 148-285 b.p. in length were analyzed by the single-stranded conformation polymorphism (SSCP) technique. No variants were detected within the coding region of the ALDH2 gene in any of the seven American Indian populations. Three potentially correct explanations for these results are suggested. First, an ALDH2 polymorphism is present but undetectable by SSCP; second, none of the studied individuals were ALDH2 negative; third, the polymorphism occurs beyond the coding region of ALDH2 gene. C1 YALE UNIV,SCH MED,DEPT GENET,NEW HAVEN,CT 06510. RP NOVORADOVSKY, AG (reprint author), NIAAA,NEUROGENET LAB,12501 WASHINGTON AVE,ROCKVILLE,MD 20852, USA. RI Goldman, David/F-9772-2010 OI Goldman, David/0000-0002-1724-5405 NR 8 TC 14 Z9 16 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0741-8329 J9 ALCOHOL JI Alcohol PD MAR-APR PY 1995 VL 12 IS 2 BP 163 EP 167 DI 10.1016/0741-8329(94)00086-7 PG 5 WC Substance Abuse; Pharmacology & Pharmacy; Toxicology SC Substance Abuse; Pharmacology & Pharmacy; Toxicology GA QN755 UT WOS:A1995QN75500015 PM 7772269 ER PT J AU DIODATI, JG CANNON, RO HUSSAIN, N QUYYUMI, AA AF DIODATI, JG CANNON, RO HUSSAIN, N QUYYUMI, AA TI INHIBITORY EFFECT OF NITROGLYCERIN AND SODIUM-NITROPRUSSIDE ON PLATELET ACTIVATION ACROSS THE CORONARY CIRCULATION IN STABLE ANGINA-PECTORIS SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID ARTERY DISEASE; INTRAVENOUS NITROGLYCERIN; MYOCARDIAL-INFARCTION; ORGANIC NITRATES; MORNING INCREASE; BLEEDING-TIME; AGGREGATION; MECHANISMS; PATHOGENESIS; PROSTACYCLIN AB This study assessed the inhibitory effect of nitroglycerin and sodium nitroprusside on platelet aggregation in a model of platelet activation across coronary circulation. Platelet aggregation is believed to contribute to the precipitation of acute ischemic syndromes. We previously showed that rapid atrial pacing in patients with stable coronary artery disease (CAD) causes platelet hyperaggregability during blood passage in coronary circulation. Because nitroglycerin and sodium nitroprusside have been shown to inhibit platelet aggregation, we examined the effect of these drugs on this model of platelet activation. During catheterization of 19 patients with CAD (>50% diameter narrowing of epicardial coronary arteries), we measured platelet aggregation (using whole blood platelet aggregometry) on blood samples obtained simultaneously from the coronary sinus and aorta at rest, and 2 minutes after onset of rapid atrial pacing. This procedure was repeated during an intravenous infusion of either nitroglycerin (n = 9) or sodium nitroprusside (n = 10). There was no arteriovenous difference in platelet aggregation under resting conditions. Atrial pacing caused an increase in platelet aggregation in coronary sinus blood (+64 +/- 9%; p <0.01), but not in arterial blood (15 +/- 12% decrease; p = NS). This increase was transient and returned toward baseline 10 minutes after termination of pacing. Although resting platelet aggregation was not affected by nitroglycerin or sodium nitroprusside, activation of platelets with atrial pacing across the coronary bed was stopped by pretreatment with therapeutic doses of nitroglycerin or sodium nitroprusside. When coronary blood flow increases in patients with CAD, platelets are activated and aggregate more easily. This activation can be blunted by pretreatment with nitroglycerin or sodium nitroprusside. This mechanism may in part explain the beneficial effect of nitrovasodilators in acute ischemic syndromes, and may contribute to the therapeutic value of these agents in stable CAD. C1 NHLBI,CARDIOL BRANCH,BETHESDA,MD 20892. NR 30 TC 22 Z9 22 U1 0 U2 0 PU CAHNERS PUBL CO PI NEW YORK PA 249 WEST 17 STREET, NEW YORK, NY 10011 SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD MAR 1 PY 1995 VL 75 IS 7 BP 443 EP 448 DI 10.1016/S0002-9149(99)80578-5 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA QH855 UT WOS:A1995QH85500004 PM 7863986 ER PT J AU CHOI, BW BACHARACH, SL BARBOUR, DJ LEON, MB MCCARTHY, KE BONOW, RO AF CHOI, BW BACHARACH, SL BARBOUR, DJ LEON, MB MCCARTHY, KE BONOW, RO TI LEFT-VENTRICULAR SYSTOLIC DYSFUNCTION DIASTOLIC FILLING CHARACTERISTICS AND EXERCISE CARDIAC RESERVE IN MITRAL-STENOSIS SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Note ID CORONARY-ARTERY DISEASE C1 AJOU UNIV,SCH MED,DEPT CARDIOL,SUWON 442749,SOUTH KOREA. RP CHOI, BW (reprint author), NHLBI,CARDIOL BRANCH,BETHESDA,MD 20892, USA. NR 10 TC 6 Z9 7 U1 0 U2 0 PU CAHNERS PUBL CO PI NEW YORK PA 249 WEST 17 STREET, NEW YORK, NY 10011 SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD MAR 1 PY 1995 VL 75 IS 7 BP 526 EP 529 DI 10.1016/S0002-9149(99)80599-2 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA QH855 UT WOS:A1995QH85500025 PM 7864006 ER PT J AU FORMAN, MR HUNDT, GL BERENDES, HW ABUSAAD, K ZANGWILL, L CHANG, D BELLMAKER, I ABUSAAD, I GRAUBARD, BI AF FORMAN, MR HUNDT, GL BERENDES, HW ABUSAAD, K ZANGWILL, L CHANG, D BELLMAKER, I ABUSAAD, I GRAUBARD, BI TI UNDERNUTRITION AMONG BEDOUIN ARAB CHILDREN - A FOLLOW-UP OF THE BEDOUIN INFANT-FEEDING STUDY SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE GROWTH; NUTRITIONAL STATUS; SOCIAL CHANGE ID GROWTH; SIZE AB After 10 y of urban settlement, 680 Bedouin Arab children, who had had anthropometric assessment from birth (1981-1982) through early childhood, were reassessed in 1991-1992 to compare the rates of stunting in early and later childhood as well as to describe the factors influencing current height-for-age. Stunting had dropped from 32.7% at 18 mo to 7.2% at 10 y in the 1981 birth cohort and dropped from 17.5% at 9 mo to 8.2% at 9 y in the 1982 birth cohort. Based on a multiple-linear-regression analysis, height in early childhood and maternal height were statistically significantly and positively associated with current mean height-for-age in both cohorts. In the 1982 cohort socioeconomic status in early childhood was positively and current family size was negatively and significantly associated with current mean height-for-age. Thus, conditions that were present in early childhood had the largest influence on current height. In 1992, 10% and 6% of the infant siblings of the 1981 and 1982 cohorts, respectively, were stunted compared with 17% and 1% of the siblings aged 1-2 y of the respective cohorts. Therefore, the high rates of early childhood stunting in 1981-1982 appeared to be a birth cohort-specific phenomenon. C1 UNIV BIRMINGHAM,DIV CANC PREVENT & CONTROL,BIRMINGHAM B15 2TT,W MIDLANDS,ENGLAND. NICHHD,DIV EPIDEMIOL BIOSTAT & PREVENT RES,BETHESDA,MD 20892. BEN GURION UNIV NEGEV,FAC HLTH SCI,BEER SHEVA,ISRAEL. BEN GURION UNIV NEGEV,DEPT EDUC,IL-84105 BEER SHEVA,ISRAEL. RP FORMAN, MR (reprint author), NCI,DIV CANC PREVENT & CONTROL,CPRP,CPSB,EXECUT PLAZA N,SUITE 211,6130 EXECUT BLVD,BETHESDA,MD 20892, USA. NR 18 TC 17 Z9 17 U1 1 U2 1 PU AMER SOC CLIN NUTRITION INC PI BETHESDA PA 9650 ROCKVILLE PIKE SUBSCRIPTIONS, RM L-2310, BETHESDA, MD 20814-3998 SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD MAR PY 1995 VL 61 IS 3 BP 495 EP 500 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA QJ901 UT WOS:A1995QJ90100007 PM 7872212 ER PT J AU CROSS, NA HILLMAN, LS ALLEN, SH KRAUSE, GF VIEIRA, NE AF CROSS, NA HILLMAN, LS ALLEN, SH KRAUSE, GF VIEIRA, NE TI CALCIUM HOMEOSTASIS AND BONE METABOLISM DURING PREGNANCY, LACTATION, AND POSTWEANING - A LONGITUDINAL-STUDY SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE PREGNANCY; LACTATION; POSTWEANING; CALCIUM ABSORPTION; BONE TURNOVER; PARATHYROID HORMONE; PHOSPHORUS; BONE MARKERS ID RESISTANT ACID-PHOSPHATASE; HORMONE-RELATED PROTEIN; PARATHYROID-HORMONE; ALKALINE-PHOSPHATASE; POSTMENOPAUSAL OSTEOPOROSIS; IMMUNORADIOMETRIC ASSAY; INORGANIC-PHOSPHATE; DIETARY CALCIUM; SMALL-INTESTINE; I PROCOLLAGEN AB Ten women were followed serially to determine the effect of stages of reproduction on calcium and bone metabolism. The study periods were nonpregnant nonlactating, the end of each trimester of gestation, 3 mo lactation, and postweaning. Comparisons were with nonpregnant nonlactating status for each individual. Fractional calcium absorption (P < 0.0001) and concentrations of 1,25-dihydroxyvitamin D (P < 0.01) were higher in the second and third trimesters. Total urinary calcium was higher during pregnancy and lower postweaning. Parathyroid hormone (PTH) concentrations were higher only postweaning (P < 0.01). Markers of bone turnover increased at the third trimester and during lactation: serum tartrate resistant acid phosphatase and bone specific alkaline phosphatase, and urinary deoxypyridinoline (P < 0.01). Serum procollagen I carboxypeptides increased only in the third trimester (P < 0.01). Bone mineral density by single-photon absorptiometry did not differ by period. We conclude that absorption and urinary excretion of calcium increase during pregnancy whereas bone turnover increases during late pregnancy and lactation; only renal changes consistent with an increase in PTH were seen postweaning. C1 UNIV MISSOURI,DEPT CHILD HLTH,COLUMBIA,MO 65201. UNIV MISSOURI,DEPT FOOD SCI & NUTR,COLUMBIA,MO 65211. UNIV MISSOURI,DEPT MED,COLUMBIA,MO. UNIV MISSOURI,DEPT STAT,COLUMBIA,MO 65211. HARRY S TRUMAN VA HOSP,COLUMBIA,MO. NICHHD,BETHESDA,MD 20892. NR 65 TC 256 Z9 264 U1 1 U2 10 PU AMER SOC CLIN NUTRITION INC PI BETHESDA PA 9650 ROCKVILLE PIKE SUBSCRIPTIONS, RM L-2310, BETHESDA, MD 20814-3998 SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD MAR PY 1995 VL 61 IS 3 BP 514 EP 523 PG 10 WC Nutrition & Dietetics SC Nutrition & Dietetics GA QJ901 UT WOS:A1995QJ90100009 PM 7872214 ER PT J AU GOYER, RA AF GOYER, RA TI NUTRITION AND METAL TOXICITY SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article; Proceedings Paper CT Symposium on Nutrition and Environmental Health, at Experimental Biology 94 CY APR 24-26, 1994 CL ANAHEIM, CA SP AMER SOC CLIN NUTR INC, NIEHS DE NUTRITION; DEFICIENCIES; TOXICITY; LEAD; CADMIUM; MERCURY; CALCIUM; IRON; ZINC; SELENIUM ID CALCIUM CHANNELS; ZINC-DEFICIENCY; LEAD; CADMIUM; RATS; ABSORPTION; MITOCHONDRIA; METABOLISM; TRANSPORT; METALLOTHIONEIN AB Lead, cadmium, and mercury are toxic metals that are not essential for nutrition. However, the toxic effects of these metals may be mediated or enhanced by interactions or deficiencies of nutritionally essential metals. Lead competes with calcium, inhibiting the release of neurotransmitters, and interferes with the regulation of cell metabolism by binding to second-messenger calcium receptors, blocking calcium trans port by calcium channels and calcium-sodium ATP pumps, and by competing for calcium-binding protein sites and uptake by mitochondria. Dietary deficiencies of calcium, iron, and zinc enhance the effects of lead on cognitive and behavioral development. Iron deficiency increases the gastrointestinal absorption of cadmium, and cadmium competes with zinc for binding sites on metallothionein, which is important in the storage and transport of zinc during development. Selenium protects from mercury and methyl mercury toxicity by preventing damage from free radicals or by forming inactive selenium mercury complexes. RP GOYER, RA (reprint author), NIEHS, WC-05, RES TRIANGLE PK, NC 27707 USA. NR 59 TC 62 Z9 63 U1 1 U2 6 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9165 EI 1938-3207 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD MAR PY 1995 VL 61 IS 3 SU S BP 646S EP 650S PG 5 WC Nutrition & Dietetics SC Nutrition & Dietetics GA QK832 UT WOS:A1995QK83200005 PM 7879732 ER PT J AU LANDS, WEM AF LANDS, WEM TI LONG-TERM FAT INTAKE AND BIOMARKERS SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article; Proceedings Paper CT Symposium on Nutrition and Environmental Health, at Experimental Biology 94 CY APR 24-26, 1994 CL ANAHEIM, CA SP AMER SOC CLIN NUTR INC, NIEHS DE ADIPOSE; ARACHIDONIC ACID; EICOSAPENTAENOIC ACID; HIGHLY UNSATURATED FATTY ACID; N-3 FATTY ACIDS; N-6 FATTY ACIDS; N-7 FATTY ACIDS; N-9 FATTY ACIDS; PLASMA ID ACID DEFICIENCY; PLASMA-LIPIDS; MEN AB The patterns of fatty acids maintained in human tissues reflect the dietary abundances of n-3 and n-6 fatty acids and the selectivities of the various lipid-metabolizing enzymes and transport systems in tissues. Similar selectivities for enzymes of mice, rats, and humans permit data from all three to be used in predicting average long-term tissue responses to different diets. The participation of the highly unsaturated fatty acids arachidonate (an n-6 acid) and eicosapentaenoate (an n-3 acid) in chronic pathophysiological events gives importance to predicting their tissue abundance. The average proportions in tissue phospholipids are hyperbolically related to dietary supplies of their precursors linoleate (18:2n-6) and linolenate (18:3n-3). In contrast, the precursors are maintained in tissue triacylglycerols in a linear relation to their average dietary supply. RP LANDS, WEM (reprint author), NIAAA, DIV BASIC RES, 6000 EXECUT BLVD, MSC 7003, ROCKVILLE, MD 20892 USA. NR 21 TC 68 Z9 71 U1 0 U2 2 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9165 EI 1938-3207 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD MAR PY 1995 VL 61 IS 3 SU S BP 721S EP 725S PG 5 WC Nutrition & Dietetics SC Nutrition & Dietetics GA QK832 UT WOS:A1995QK83200016 PM 7879743 ER PT J AU BECKNER, ME HEFFESS, CS OERTEL, JE AF BECKNER, ME HEFFESS, CS OERTEL, JE TI OXYPHILIC PAPILLARY THYROID CARCINOMAS SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE PAPILLARY THRYOID CARCINOMA; OXYPHILIC CELLS; HURTHLE CELLS ID HURTHLE-CELL TUMORS; FOLLOW-UP; GLAND; NEOPLASMS; VARIANT; DIFFERENTIATION; LESIONS; PROGNOSIS AB Oxyphilic papillary carcinomas of the thyroid hare not been extensively studied because they are rare. The morphology and behavior of 34 cases were described. The average age was 44.1 years, the female-to-male ratio was 3.9:1, and the average diameter of the tumors was 2.3 cm. All had papillary structures present. In 31 cases, there was capsular or parenchymal invasion. Six cancers had local lymph node metastases. The average follow-up for 29 patients was 8.1 years. Tumors reappeared in four patients; one patient died from recurrent disease, one patient,vith disease died due to an unrelated carcinoma, and two patients were treated successfully. Twenty-seven patients at the end of follow-up were alive with no detectable thyroid cancer. The majority of patients remained free of tumor, especially those younger than 50 years. C1 ARMED FORCES INST PATHOL,DEPT OTOLARYNG & ENDOCRINE PATHOL,WASHINGTON,DC 20306. NCI,PATHOL LAB,BETHESDA,MD 20892. RI Ain, Kenneth/A-5179-2012 OI Ain, Kenneth/0000-0002-2668-934X NR 56 TC 43 Z9 43 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD MAR PY 1995 VL 103 IS 3 BP 280 EP 287 PG 8 WC Pathology SC Pathology GA QL595 UT WOS:A1995QL59500005 PM 7872249 ER PT J AU LEE, A SKELLY, ME KINGMA, DW MEDEIROS, LJ AF LEE, A SKELLY, ME KINGMA, DW MEDEIROS, LJ TI B-CELL CHRONIC LYMPHOCYTIC-LEUKEMIA FOLLOWED BY HIGH-GRADE T-CELL LYMPHOMA - AN UNUSUAL VARIANT OF RICHTERS-SYNDROME SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Note DE B-CELL CHRONIC LYMPHOCYTIC LEUKEMIA; T-CELL LARGE CELL IMMUNOBLASTIC LYMPHOMA; EPSTEIN-BARR VIRUS ID NON-HODGKINS-LYMPHOMA; EPSTEIN-BARR-VIRUS; TRANSFORMATION; DISEASE; CLONES AB A 70-year-old woman with a 2-year history of B-cell chronic lymphocytic leukemia (CLL) developed headache, fever, chills, and weakness. Bone marrow examination revealed both CLL and large cell immunoblastic lymphoma (Richter's syndrome). As expected, the CLL was of B-cell lineage. The neoplasm expressed low-density monotypic IgM lambda, the pan-B-cell antigens CD19, CD20, and CDw75, and the CD5 and CD43 antigens. The large cell immunoblastic lymphoma was of T-cell lineage, positive for the CD45RB, CD3, CD45RO, and CD43 antigens, and negative for the CD20 and CDw75 antigens. Both neoplastic components were negative for Epstein-Barr virus RNA and latent membrane protein. Although 3% to 5% of patients with B-cell CLL may develop higher-grade lymphoma, usually the lymphoma is of B-cell lineage and often represents a histologic manifestation of clonal evolution. Less commonly, B-CLL patients mag. develop transformation to a higher grade tumor that resembles Hodgkin's disease. Both the usual form of Richter's syndrome and particularly the Hodgkin's variant of Richter's syndrome may be associated,with Epstein-Barr virus. Patients with B-cell CLL rarely develop a higher grade lymphoma of T-cell lineage. To our knowledge, only one other example has been reported in the literature. Epstein-Barr virus was not associated with either neoplasm in this case. C1 BROWN UNIV,RHODE ISL HOSP,DEPT PATHOL,PROVIDENCE,RI 02903. GOOD SAMARITAN REG HLTH CTR,DEPT PATHOL,MT VERNON,IL. NCI,PATHOL LAB,BETHESDA,MD. NR 22 TC 30 Z9 30 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD MAR PY 1995 VL 103 IS 3 BP 348 EP 352 PG 5 WC Pathology SC Pathology GA QL595 UT WOS:A1995QL59500017 PM 7872259 ER PT J AU ATKINS, J GLASS, C MACLEOD, B MADEWELL, W SHADE, B BRADLEY, JC HAND, MM HORAN, M AF ATKINS, J GLASS, C MACLEOD, B MADEWELL, W SHADE, B BRADLEY, JC HAND, MM HORAN, M TI 9-1-1 - RAPID IDENTIFICATION AND TREATMENT OF ACUTE MYOCARDIAL-INFARCTION - NATIONAL HEART-ATTACK ALERT PROGRAM COORDINATING COMMITTEE ACCESS TO CARE SUBCOMMITTEE SO AMERICAN JOURNAL OF EMERGENCY MEDICINE LA English DT Review DE MYOCARDIAL INFARCTION; EMERGENCY MEDICAL SERVICES; EMS COMMUNICATION SYSTEMS; 9-1-1 AB The sooner a person who is experiencing symptoms and signs of an acute myocardial infarction (AMI) (including out-of-hospital cardiac arrest) receives medical treatment, the greater his or her chances of survival and limitation of infarct size. A universal 9-1-1 emergency telephone system makes it possible for AMI patients or those around them to easily and quickly call for help and for emergency medical services (EMS) personnel to rapidly and accurately locate the patient. This article by the Access to Care Subcommittee of the National Heart Attack Alert Program (NHAAP) Coordinating Committee describes the history of 9-1-1, ifs key elements, its current implementation status, and existing State legislation and standards. Currently, approximately 78% of the United States population, mainly in urban areas, has access to a 9-1-1 system. Approximately 195 United States cities with a population of greater than 100,000 people have access to enhanced 9-1-1. It is the contention of the NHAAP that 9-1-1 services should be universally available to all Americans to ensure seamless access to EMS and, potentially, early detection, evaluation, and treatment for AMI. This article reports several key recommendations for achieving this goal. ((C) 1995 by W.B. Saunders Company) C1 NHLBI,OFF PREVENT EDUC & CONTROL,NATL HEART ATTACK ALERT PROGRAM,BETHESDA,MD 20892. NR 0 TC 16 Z9 16 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0735-6757 J9 AM J EMERG MED JI Am. J. Emerg. Med. PD MAR PY 1995 VL 13 IS 2 BP 188 EP 195 PG 8 WC Emergency Medicine SC Emergency Medicine GA QQ147 UT WOS:A1995QQ14700017 ER PT J AU WEBBER, LS OSGANIAN, V LUEPKER, RV FELDMAN, HA STONE, EJ ELDER, JP PERRY, CL NADER, PR PARCEL, GS BROYLES, SL MCKINLAY, SM AF WEBBER, LS OSGANIAN, V LUEPKER, RV FELDMAN, HA STONE, EJ ELDER, JP PERRY, CL NADER, PR PARCEL, GS BROYLES, SL MCKINLAY, SM TI CARDIOVASCULAR RISK-FACTORS AMONG THIRD GRADE CHILDREN IN 4 REGIONS OF THE UNITED-STATES - THE CATCH STUDY SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE BLOOD PRESSURE; CHILD; ETHNIC GROUPS; LIPIDS; OBESITY; RISK FACTORS ID BOGALUSA HEART; BLOOD-PRESSURE; BIRACIAL COMMUNITY; HEALTH PROMOTION; CHOLESTEROL LEVELS; SERUM-CHOLESTEROL; ADOLESCENT TRIAL; YOUNG ADULTHOOD; DISTRIBUTIONS; CHILDHOOD AB Data on cardiovascular risk factors (body mass index, triceps and subscapular skinfolds, blood pressure, serum total cholesterol, high density lipoprotein (HDL) cholesterol, and apolipoprotein B) were collected as part of the baseline examination (fall 1991) of the Child and Adolescent Trial for Cardiovascular Health, a multicenter school-based intervention study for promoting healthful behaviors. A total of 5,106 third grade children (mean age, 8.76 years) in four states (California, Louisiana, Minnesota, and Texas) were examined. After excluding 194 children of other or unknown origin, the study population consisted of 3,530 Anglo-American children, 674 African-American children, and 708 Latino children. African-American children were the tallest by 1-3 cm (p < 0.0001), while Latino children had the largest body mass index (p < 0.05). Blood pressure levels were similar for boys and girls and among the three races, but systolic levels were 2 mmHg higher in Texas than at the other sites. Serum total cholesterol levels were 5 mg/dl higher in girls than in boys (p < 0.05), while HDL cholesterol levels were 2 mg/dl higher in boys (p < 0.05). HDL cholesterol levels were highest in African-Americans (55.5 mg/dl) compared with Anglo-Americans (50.7 mg/dl) and Latinos (51.3 mg/dl) (p < 0.0001). C1 NEW ENGLAND RES INST INC,WATERTOWN,MA. UNIV MINNESOTA,SCH PUBL HLTH,DIV EPIDEMIOL,MINNEAPOLIS,MN 55455. NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,PREVENT & DEMONSTRAT RES BRANCH,BETHESDA,MD 20892. SAN DIEGO STATE UNIV,GRAD SCH PUBL HLTH,DIV HLTH PROMOT,SAN DIEGO,CA 92182. UNIV CALIF SAN DIEGO,DEPT PEDIAT,DIV COMMUNITY PEDIAT,SAN DIEGO,CA 92103. UNIV TEXAS,HLTH SCI CTR,CTR HLTH PROMOT RES & DEV,HOUSTON,TX. RP WEBBER, LS (reprint author), TULANE UNIV,SCH PUBL HLTH & TROP MED,DEPT BIOSTAT & EPIDEMIOL,1501 CANAL ST,NEW ORLEANS,LA 70112, USA. FU NHLBI NIH HHS [U01-HL-39880, U01-HL-39906, U01-HL-39852] NR 48 TC 80 Z9 82 U1 3 U2 3 PU AMER J EPIDEMIOLOGY PI BALTIMORE PA 624 N BROADWAY RM 225, BALTIMORE, MD 21205 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD MAR 1 PY 1995 VL 141 IS 5 BP 428 EP 439 PG 12 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA QL096 UT WOS:A1995QL09600007 PM 7879787 ER PT J AU PISCITELLI, SC MINOR, JR AF PISCITELLI, SC MINOR, JR TI ROLE OF INTERLEUKIN-2 IN MANAGING INFECTION WITH THE HUMAN-IMMUNODEFICIENCY-VIRUS SO AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY LA English DT Article C1 NIH,WARREN G MAGNUSON CLIN CTR,DEPT PHARM,CLIN PHARMACOKINET RES LAB,BETHESDA,MD 20892. NR 9 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEALTH-SYSTEM PHARMACISTS PI BETHESDA PA 7272 WISCONSIN AVE, BETHESDA, MD 20814 SN 1079-2082 J9 AM J HEALTH-SYST PH JI Am. J. Health-Syst. Pharm. PD MAR 1 PY 1995 VL 52 IS 5 BP 541 EP 542 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA QP484 UT WOS:A1995QP48400019 PM 7606563 ER PT J AU FREBOURG, T BARBIER, N YAN, YX GARBER, JE DREYFUS, M FRAUMENI, J LI, FP FRIEND, SH AF FREBOURG, T BARBIER, N YAN, YX GARBER, JE DREYFUS, M FRAUMENI, J LI, FP FRIEND, SH TI GERM-LINE P53 MUTATIONS IN 15 FAMILIES WITH LI-FRAUMENI SYNDROME SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID CANCER-PRONE FAMILY; BREAST-CANCER; SPLICING MUTATION; GENE; PROTEIN; PATIENT; PEDIGREE; TUMORS; SITE AB Germ-line mutations of the tumor-suppressor gene p53 have been observed in some families with the Li-Fraumeni syndrome (LFS), a familial cancer syndrome in which affected relatives develop a diverse set of early-onset malignancies including breast carcinoma, sarcomas, and brain tumors. The analysis of the p53 gene in LFS families has been limited, in most studies to date, to the region between exon 5 and exon 9. In order to determine the frequency and distribution of germ-line p53 mutations in LFS, we sequenced the 10 coding exons of the p53 gene in lymphocytes and fibroblast cell lines derived from 15 families with the syndrome. Germ-line mutations were observed in eight families. Six mutations were missense mutations located between exons 5 and 8. One mutation was a nonsense mutation in exon 6, and one mutation was a splicing mutation in intron 4, generating aberrant shorter p53 RNA(s). In three families, a mutation of the p53 gene was observed in the fibroblast cell line derived from the proband. However, the mutation was not found in affected relatives in two families and in the blood from the one individual, indicating that the mutation probably occurred during cell culture in vitro. In four families, no mutation was observed. This study indicates that germ-line p53 mutations in LFS are mostly located between exons 5 and 8 and that similar to 50% of patients with LFS have no germ-line mutations in the coding region of the p53 gene. The observation of p53 mutations occurring during primary cultures of human fibroblasts shows that analysis for germ-line p53 mutations must be performed on cells that have not been grown in vitro. C1 MASSACHUSETTS GEN HOSP E,DIV MOLEC GENET,BOSTON,MA. CHILDRENS HOSP,DEPT PEDIAT,DIV HEMATOL ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CANC EPIDEMIOL & CANC CONTROL,BOSTON,MA 02115. NCI,DIV CANC ETIOL,EPIDEMIOL & BIOSTAT PROGRAM,BETHESDA,MD 20892. NR 49 TC 138 Z9 142 U1 2 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD MAR PY 1995 VL 56 IS 3 BP 608 EP 615 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA QK918 UT WOS:A1995QK91800008 PM 7887414 ER PT J AU JESUDASAN, RA RAHMAN, RA CHANDRASHEKHARAPPA, S EVANS, GA SRIVATSAN, ES AF JESUDASAN, RA RAHMAN, RA CHANDRASHEKHARAPPA, S EVANS, GA SRIVATSAN, ES TI DELETION AND TRANSLOCATION OF CHROMOSOME 11Q13 SEQUENCES IN CERVICAL-CARCINOMA CELL-LINES SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID POLYMERASE CHAIN-REACTION; SQUAMOUS-CELL; HUMAN PAPILLOMAVIRUSES; UTERINE CERVIX; CANCER; LOCUS; GENE; HETEROZYGOSITY; NEOPLASIA; ONCOGENE AB Molecular genetic studies on HeLa cell-derived nontumorigenic and tumorigenic hybrids have previously localized the HeLa cell tumor-suppressor gene to the long arm of chromosome 11. Extensive molecular and cytogenetic studies on HeLa cells have shown chromosome band 11q13 to be rearranged in this cell line. To determine whether q13 rearrangement is a nonrandom event in cervical carcinomas, six different human papilloma virus (HPV)-positive (HeLa, SiHa, Caski, C4-I, Me180, and Ms751) and two different HPV-negative (C33A and HT3) cell lines were studied. Long-range restriction mapping using a number of q13-specific probes showed molecular rearrangements within 75 kb of INT2 probe in three HPV-positive cell lines (HeLa, SiHa, and Caski) and in an HPV-negative cell line (HT3). FISH using an INT2 YAC identified a breakpoint within the sequences spanned by this YAC in two of the cell lines, HeLa and Caski. INT2 cosmid derived from this YAC showed deletion of cosmid sequences in two other cell lines, SiHa and C33A. These two cell lines, however, retained cosmid sequences of Cyclin D1, a probe localized 100 kb proximal to INT2. Deletions being the hallmark of a tumor-suppressor gene, we conclude that the 100-kb interval between the two cosmids might contain sequences of the cervical carcinoma tumor-suppressor gene. C1 UNIV CALIF LOS ANGELES,SCH MED,VET ADM MED CTR,DEPT SURG,LOS ANGELES,CA 90073. SPECIAL DIAGNOST,CLIN GENET CTR,LA MIRADA,CA. NATL CTR HUMAN GENOME RES,GENE TRANSFER LAB,BETHESDA,MD. UNIV TEXAS,SW MED CTR,MCDERMOTT CTR,DALLAS,TX. FU NCI NIH HHS [CA47206] NR 28 TC 51 Z9 52 U1 0 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD MAR PY 1995 VL 56 IS 3 BP 705 EP 715 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA QK918 UT WOS:A1995QK91800021 PM 7887426 ER PT J AU BOLES, DJ PROIA, RL AF BOLES, DJ PROIA, RL TI THE MOLECULAR-BASIS OF HUXA MESSENGER-RNA DEFICIENCY CAUSED BY THE MOST COMMON TAY-SACHS-DISEASE MUTATION SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID HUMAN BETA-HEXOSAMINIDASE; MESSENGER-RNA DEGRADATION; ALPHA-CHAIN; NONSENSE MUTATION; CYSTIC-FIBROSIS; GENE; REDUCE; JEWISH; EXPRESSION; INSERTION AB Tay-Sachs disease (TSD) is a catastrophic neurodegenerative disorder caused by mutations in the HEXA gene. The most common TSD allele worldwide contains a 4-bp insertion in exon 11 that produces a downstream premature termination codon. Despite normal transcription of this allele, HEXA mRNA is severely reduced, indicating that the HEXA transcript must be unstable. Minigenes of HEXA were constructed and expressed in mouse L cells, to investigate the relationship between the 4-bp insertion and mRNA deficiency. We conclude that the mRNA instability is caused by the premature termination codon and not by a cryptic mutation or by the 4-bp insertion directly and that degradation occurs coincident with or after splicing. C1 NIDDKD,GENET & BIOCHEM BRANCH,BIOCHEM GENET SECT,BETHESDA,MD 20892. RI Proia, Richard/A-7908-2012 NR 39 TC 13 Z9 14 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD MAR PY 1995 VL 56 IS 3 BP 716 EP 724 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA QK918 UT WOS:A1995QK91800022 PM 7887427 ER PT J AU LONG, JC WILLIAMS, RC URBANEK, M AF LONG, JC WILLIAMS, RC URBANEK, M TI AN E-M ALGORITHM AND TESTING STRATEGY FOR MULTIPLE-LOCUS HAPLOTYPES SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID RANDOMLY MATING POPULATIONS; LINKAGE DISEQUILIBRIUM; ALLELES AB This paper gives an expectation maximization (EM) algorithm to obtain allele frequencies, haplotype frequencies, and gametic disequilibrium coefficients for multiple-locus systems. It permits high polymorphism and null alleles at all loci. This approach effectively deals with the primary estimation problems associated with such systems; that is, there is not a one-to-one correspondence between phenotypic and genotypic categories, and sample sizes tend to be much smaller than the number of phenotypic categories. The EM method provides maximum-likelihood estimates and therefore allows hypothesis tests using likelihood ratio statistics that have chi(2) distributions with large sample sizes. We also suggest a data resampling approach to estimate test statistic sampling distributions. The resampling approach is more computer intensive, but it is applicable to all sample sizes. A strategy to test hypotheses about aggregate groups of gametic disequilibrium coefficients is recommended. This strategy minimizes the number of necessary hypothesis tests while at the same time describing the structure of disequilibrium. These methods are applied to three unlinked dinucleotide repeat loci in Navajo Indians and to three linked HLA loci in Gila River (Pima) Indians. The likelihood functions of both data sets are shown to be maximized by the EM estimates, and the testing strategy provides a useful description of the structure of gametic disequilibrium. Following these applications, a number of simulation experiments are performed to test how well the likelihood-ratio statistic distributions are approximated by chi(2) distributions. In most circumstances the chi(2) grossly underestimated the probability of type I errors. However, at times they also overestimated the type 1 error probability. Accordingly, we recommend hypothesis tests that use the resampling method. C1 ARIZONA STATE UNIV,DEPT ANTHROPOL,TEMPE,AZ 85287. RP LONG, JC (reprint author), NIAAA,NEUROGENET LAB,12501 WASHINGTON AVE,ROCKVILLE,MD 20852, USA. NR 41 TC 436 Z9 447 U1 1 U2 4 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD MAR PY 1995 VL 56 IS 3 BP 799 EP 810 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA QK918 UT WOS:A1995QK91800031 PM 7887436 ER PT J AU JOHNSON, ES DALMAS, D NOSS, J MATANOSKI, GM AF JOHNSON, ES DALMAS, D NOSS, J MATANOSKI, GM TI CANCER MORTALITY AMONG WORKERS IN ABATTOIRS AND MEATPACKING PLANTS - AN UPDATE SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE BOVINE LEUKEMIA VIRUS; PAPILLOMA VIRUSES; CANCER; ABATTOIRS; MEATPACKING PLANTS; WOMENS HEALTH ID BOVINE LEUKEMIA-VIRUS; LUNG-CANCER; MEAT INDUSTRY; SLAUGHTERHOUSE WORKERS; WHITE MALES; BUTCHERS; MILK; RISK; PAPILLOMAVIRUSES; TRANSMISSION AB Workers in abattoirs and meatpacking plants have potential for exposure to bovine leukemia virus (BLV) and bovine papilloma viruses (BPV), which are oncogenic in cattle. These workers also have increased exposure to human papilloma viruses (HPV) and certain chemical carcinogens. We investigated whether such a group showed increased risk of cancers. We report mortality results after an additional 9-year follow-up of a previously studied group of 5,522 workers in abattoirs and 4,589 workers in meatpacking plants. Excess risk of all cancers combined, cancers of the lung, buccal cavity and pharynx, esophagus, colon, bladder, kidney, and bone was observed. Since factors such as tobacco smoking, alcohol, and diet, which have known associations with some of these cancers, were not taken into account, the significance of these findings is not known, except for lung cancer, for which occupational factors are probably involved. Because some of these findings have been consistently reported before, studies that will control for confounding factors as well are now urgently needed. (C) 1995 Wiley-Liss, Inc.* C1 TULANE UNIV,MED CTR,CTR BIOENVIRONM RES,NEW ORLEANS,LA 70112. NIEHS,EPIDEMIOL BRANCH,ENVIRONM & MOLEC EPIDEMIOL SECT,RES TRIANGLE PK,NC. WESTAT CORP,RES TRIANGLE PK,NC. JOHNS HOPKINS UNIV,BALTIMORE,MD. RP JOHNSON, ES (reprint author), TULANE UNIV,MED CTR,DEPT BIOSTAT & EPIDEMIOL,1430 TULANE AVE,NEW ORLEANS,LA 70112, USA. FU NCI NIH HHS [CA 30410] NR 71 TC 35 Z9 36 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD MAR PY 1995 VL 27 IS 3 BP 389 EP 403 DI 10.1002/ajim.4700270308 PG 15 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA QK457 UT WOS:A1995QK45700007 PM 7747745 ER PT J AU LANE, HC POLIS, MA MURPHY, R NUSSENBLATT, AB MASUR, H AF LANE, HC POLIS, MA MURPHY, R NUSSENBLATT, AB MASUR, H TI PHOSPHONOFORMATE FOR CMV RETINITIS IN AIDS - REPLY SO AMERICAN JOURNAL OF MEDICINE LA English DT Letter ID FOSCARNET C1 NORTHWESTERN UNIV,SCH MED,CHICAGO,IL. NEI,BETHESDA,MD 20892. NIH,WARREN GRANT MAGNUSON CLIN CTR,BETHESDA,MD 20892. RP LANE, HC (reprint author), NIAID,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU CAHNERS PUBL CO PI NEW YORK PA 249 WEST 17 STREET, NEW YORK, NY 10011 SN 0002-9343 J9 AM J MED JI Am. J. Med. PD MAR PY 1995 VL 98 IS 3 BP 317 EP 318 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA QL368 UT WOS:A1995QL36800023 ER PT J AU SCHILDKRAUT, JM COLLINS, NK DENT, GA TUCKER, JA BARRETT, JC BERCHUCK, A BOYD, J AF SCHILDKRAUT, JM COLLINS, NK DENT, GA TUCKER, JA BARRETT, JC BERCHUCK, A BOYD, J TI LOSS OF HETEROZYGOSITY ON CHROMOSOME 17Q11-21 IN CANCERS OF WOMEN WHO HAVE BOTH BREAST AND OVARIAN-CANCER SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE OVARIAN CANCER; BREAST CANCER; CHROMOSOME 17Q; LOSS OF HETEROZYGOSITY; BRCA1 ID FAMILIAL BREAST; ALLELE LOSSES; CARCINOMA; PROGRESSION; LINKAGE; REGION; LOCUS; GENE AB OBJECTIVE: Our purpose was to determine the frequency of allele loss in the region of the BRCA1 gene In cancers of women who have both breast and ovarian cancer. STUDY DESIGN: Four polymorphic microsatellite markers on chromosome 17q11-21 were examined by the polymerase chain reaction in deoxyribonucleic acid from paraffin blocks of normal tissues, breast cancers, and ovarian cancers in 24 women who had primary cancers in both sites. RESULTS: Loss of heterozygosity was seen in one or more markers on chromosome 17q11-q21 in 46% of breast cancers and 78% of ovarian cancers. In 38% of cases allele loss was seen in both cancers, and in all these cases the same allele was lost in both cancers. Significantly younger ages at diagnosis of both breast and ovarian cancer were noted among cases with allele loss in both cancers compared with cases in which allele loss was found only in the ovarian cancer (p < 0.05). CONCLUSIONS: Because cases in which 17q11-21 allele loss was seen in both cancers had a young age of onset and the same allele was always deleted in-both cancers, hereditary alterations in BRCA1 may play a role in this subset. The older age of onset in cases in which allele loss was seen only in the ovarian cancer suggests that the development of these cancers is not related to an inherited defect in BRCA1. C1 DUKE UNIV,MED CTR,DUKE COMPREHENS CANC CTR,DEPT OBSTET & GYNECOL,DIV GYNECOL ONCOL,DURHAM,NC 27710. DUKE UNIV,MED CTR,CANC PREVENT DETECT & CONTROL RES PROGRAM,DURHAM,NC 27710. NIEHS,MOLEC CARCINOGENESIS LAB,RES TRIANGLE PK,NC 27709. UNIV N CAROLINA,SCH MED,DEPT PATHOL,CHAPEL HILL,NC. UNIV SO ALABAMA,MED CTR,DEPT PATHOL,MOBILE,AL. NR 18 TC 18 Z9 19 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD MAR PY 1995 VL 172 IS 3 BP 908 EP 913 DI 10.1016/0002-9378(95)90020-9 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA QM795 UT WOS:A1995QM79500020 PM 7892884 ER PT J AU COX, JT LORINCZ, AT SCHIFFMAN, MH SHERMAN, ME CULLEN, A KURMAN, RJ AF COX, JT LORINCZ, AT SCHIFFMAN, MH SHERMAN, ME CULLEN, A KURMAN, RJ TI HUMAN PAPILLOMAVIRUS TESTING BY HYBRID CAPTURE APPEARS TO BE USEFUL IN TRIAGING WOMEN WITH A CYTOLOGIC DIAGNOSIS OF ATYPICAL SQUAMOUS CELLS OF UNDETERMINED SIGNIFICANCE SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE ATYPICAL SQUAMOUS CELLS OF UNDETERMINED SIGNIFICANCE; HYBRID CAPTURE; HUMAN PAPILLOMAVIRUS DEOXYRIBONUCLEIC ACID TESTING ID PAPANICOLAOU SMEAR; INTRAEPITHELIAL NEOPLASIA; CERVICAL CYTOLOGY; ASSOCIATION AB OBJECTIVE: Our purpose was to determine the clinical value of human papillomavirus deoxyribonucleic acid testing with the hybrid capture test, specifically to examine whether human papillomavirus testing could identify which women with Papanicolaou smears read as atypical squamous cells of undetermined significance were most likely to have histologically confirmed cervical intraepithelial neoplasia. STUDY DESIGN: Hybrid capture testing for 14 human papillomavirus types, repeat Papanicolaou smears, and colposcopically directed biopsies were performed concurrently on 217 women referred to a student health colposcopy clinic with a previous Papanicolaou smear read as atypical squamous cells of undetermined significance. RESULTS: Human papillomavirus deoxyribonucleic acid positivity was associated with an eightfold increased likelihood of histologic confirmation of cervical intraepithelial neoplasia. The sensitivity of hybrid capture for any cervical intraepithelial neoplasia was 86% (43/50) and for grade 2 or 3 was 93% (14/15), whereas the corresponding values for the repeat Papanicolaou smear were 60% (30/50) and 73% (11/15), respectively. Moreover, high viral levels of human papillomavirus types known to be associated with cervical cancer were strongly predictive or high-grade cervical intraepithelial neoplasia. CONCLUSION'S: Testing for human papillomavirus deoxyribonucleic acid with hybrid capture appears to offer an effective means by which patients whose cervical Papanicolaou smears have been read as atypical squamous cells of undetermined significance could be triaged for colposcopy. In particular, sensitivity for high-grade cervical intraepithelial neoplasia could be maintained and specificity markedly improved by referring only those patients who had elevated levels of human papillomavirus deoxyribonucleic acid of cancer-associated viral types. C1 NCI,EPIDEMIOL & BIOSTAT PROGRAM,BETHESDA,MD 20892. JOHNS HOPKINS MED INST,DEPT PATHOL,BALTIMORE,MD 21205. JOHNS HOPKINS MED INST,DEPT OBSTET & GYNECOL,BALTIMORE,MD 21205. RP COX, JT (reprint author), UNIV CALIF SANTA BARBARA,CTR STUDENT HLTH,DIGENE DIAGNOST INC,HLTH SERV,SANTA BARBARA,CA 93106, USA. NR 26 TC 348 Z9 359 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD MAR PY 1995 VL 172 IS 3 BP 946 EP 954 DI 10.1016/0002-9378(95)90026-8 PG 9 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA QM795 UT WOS:A1995QM79500026 PM 7892889 ER PT J AU YOON, BH ROMERO, R KIM, CJ JUN, JK GOMEZ, R CHOI, JH SYN, HC AF YOON, BH ROMERO, R KIM, CJ JUN, JK GOMEZ, R CHOI, JH SYN, HC TI AMNIOTIC-FLUID INTERLEUKIN-6 - A SENSITIVE TEST FOR ANTENATAL DIAGNOSIS OF ACUTE INFLAMMATORY LESIONS OF PRETERM PLACENTA AND PREDICTION OF PERINATAL MORBIDITY SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE AMNIOTIC FLUID; INTERLEUKIN-6; HISTOLOGIC CHORIOAMNIONITIS; NEONATAL MORBIDITY ID BLOOD-CELL COUNT; HISTOLOGIC CHORIOAMNIONITIS; INTACT MEMBRANES; PREMATURE RUPTURE; GRAM STAIN; LABOR; INFECTION; TERM; MICROBIOLOGY; WOMEN AB OBJECTIVE: Our purpose was to determine whether amniotic fluid concentrations of interleukin-6 are of value in the antenatal diagnosis of acute inflammatory lesions (histologic chorioamnionitis) of preterm placenta and in the prediction of perinatal morbidity and mortality. STUDY DESIGN: The relation among placental histologic findings, perinatal outcome, and amniotic fluid interleukin-6 concentrations was examined in 50 consecutive patients who delivered preterm neonates within 72 hours after amniocentesis. Interleukin-6 was determined by enzyme-linked immunosorbent assays. Receiver-operator characteristic curve was used for analysis. RESULTS: Patients with acute histologic chorioamnionitis had significantly higher median amniotic fluid interleukin-6 concentrations than patients without histologic chorioamnionitis (median 70.8 ng/ml, range 0.7 to 499.2 ng/ml vs median 2.9 ng/ml, range 0.8 to 16.0 ng/ml, respectively; p < 0.00001). An amniotic fluid interteukin-6 concentration > 17 ng/ml had a sensitivity of 79% (23/29) and a specificity of 100% (21/21) in the diagnosis of acute histologic: chorioamnionitis and a sensitivity of 69% (18/26) and a specificity of 79% (19/24) in the prediction of significant neonatal morbidity (defined as neonatal sepsis, respiratory distress syndrome, pneumonia, intraventricular hemorrhage, bronchopulmonary dysplasia, or necrotizing enterocolitis) and mortality. These sensitivities were significantly higher than those of amniotic fluid culture (79% vs 38%, p < 0.005; 69% vs 27%, p < 0.01, respectively). CONCLUSIONS: Amniotic fluid interleukin-6 is a sensitive test for the prospective diagnosis of acute histologic chorioamnionitis and the identification of neonates at risk for significant morbidity and mortality. C1 SEOUL NATL UNIV HOSP,DEPT OBSTET & GYNECOL,SEOUL 110744,SOUTH KOREA. SEOUL NATL UNIV HOSP,DEPT PATHOL,SEOUL 110744,SOUTH KOREA. SEOUL NATL UNIV HOSP,DEPT PEDIAT,SEOUL 110744,SOUTH KOREA. NICHHD,PERINATOL RES BRANCH,BETHESDA,MD 20892. RI Seoul National University, Pathology/B-6702-2012; Yoon, Bo Hyun/H-6344-2011; Jun, Jong Kwan/D-5776-2012 OI Jun, Jong Kwan/0000-0002-0242-1736 NR 23 TC 304 Z9 311 U1 0 U2 3 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD MAR PY 1995 VL 172 IS 3 BP 960 EP 970 DI 10.1016/0002-9378(95)90028-4 PG 11 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA QM795 UT WOS:A1995QM79500028 PM 7892891 ER PT J AU DICKERSON, AE OAKLEY, F AF DICKERSON, AE OAKLEY, F TI COMPARING THE ROLES OF COMMUNITY-LIVING PERSONS AND PATIENT POPULATIONS SO AMERICAN JOURNAL OF OCCUPATIONAL THERAPY LA English DT Article DE ROLE, OCCUPATIONAL ID LIFE SATISFACTION; OCCUPATIONAL BEHAVIOR; ROLE CHECKLIST; PERSPECTIVE; RELIABILITY; DISORDER; THERAPY AB Objectives. This study compares the occupational role profile of a large sample of community-living persons without disabilities with the profile of a population of patients with psychosocial or physical disabilities and suggests areas of occupational therapy intervention. Methods. The Role Checklist was used to compare the roles of 1,020 community-living persons without disabilities with the roles of 292 adults with physical lit or psychosocial disabilities. Specifically, community-living persons were matched to the entire patient group, a group of patients with psychosocial dysfunction, and a group of patients with physical dysfunction to compare the groups in terms of their past, present, and future role profiles and the value they assigned to those roles. Results. There were significant differences in the types of roles identified In general, the patients identified involvement in fewer present roles than the community-living persons. Differences between the two groups also appeared in the identification of future roles and value of those roles. Conclusions. Roles appear to be affected by disability, whether physical or psychosocial in nature. If role participation is seen as part of the occupational functioning of the person, occupational therapy needs to address this area. C1 NIH,OCCUPAT THERAPY SECT,BETHESDA,MD 20892. RP DICKERSON, AE (reprint author), E CAROLINA UNIV,DEPT OCCUPAT THERAPY,306D BELK BLDG,GREENVILLE,NC 27858, USA. NR 26 TC 6 Z9 6 U1 0 U2 1 PU AMER OCCUPATION THERAPY ASSN PI ROCKVILLE PA 1383 PICCARD DRIVE PO BOX ROCKVILLE, MD 20850-4375 SN 0272-9490 J9 AM J OCCUP THER JI Am. J. Occup. Ther. PD MAR PY 1995 VL 49 IS 3 BP 221 EP 228 PG 8 WC Rehabilitation SC Rehabilitation GA QG802 UT WOS:A1995QG80200005 PM 7741155 ER PT J AU SNOW, JB AF SNOW, JB TI NEWS FROM THE NATIONAL-INSTITUTE-ON-DEAFNESS-AND-OTHER-COMMUNICATION-DISORDERS SO AMERICAN JOURNAL OF OTOLOGY LA English DT Editorial Material RP SNOW, JB (reprint author), NIDCD,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0192-9763 J9 AM J OTOL JI Am. J. Otol. PD MAR PY 1995 VL 16 IS 2 BP 253 EP 256 PG 4 WC Otorhinolaryngology SC Otorhinolaryngology GA QK481 UT WOS:A1995QK48100023 PM 8572129 ER PT J AU ZHUANG, ZP BERTHEAU, P EMMERTBUCK, MR LIOTTA, LA GNARRA, J LINEHAN, WM LUBENSKY, IA AF ZHUANG, ZP BERTHEAU, P EMMERTBUCK, MR LIOTTA, LA GNARRA, J LINEHAN, WM LUBENSKY, IA TI A MICRODISSECTION TECHNIQUE FOR ARCHIVAL DNA ANALYSIS OF SPECIFIC CELL-POPULATIONS IN LESIONS LESS-THAN-1 MM IN SIZE SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Note ID POLYMERASE CHAIN-REACTION; VONHIPPEL-LINDAU DISEASE; PCR CONTAMINATION; CARCINOMA; TISSUE; LIGHT AB We have developed a microdissection technique that allows for procurement and analysis of specific, minute cell populations from routine, 5-mu, formalin-fixed, paraffin-embedded histological tissue sections, Lesions <1 mm in size can be specifically examined Cells of interest are procured tender direct microscopic visualization followed by a single-step DNA extraction and subsequent polymerase chain reaction. Amplification of DNA from selected cell populations was demonstrated by detecting a loss of heterozygosity (LOH) at the von Hippel-Lindau disease (VHL) gene in an atypical renal lesion and a renal cell carcinoma in a kidney of a VHL patient, Moreover, previously unrecognized LON on the short arm of chromosome 3 (3p25-26) was detected in microdissected colorectal carcinoma cells he a non-VHL patient with sporadic colon carcinoma This technique should prove useful in DNA studies of small lesions and cell populations. Furthermore, microscopic premalignant, in situ, and invasive lesions can be selectively examined. C1 NCI,PATHOL LAB,BETHESDA,MD 20892. NCI,SURG BRANCH,BETHESDA,MD 20892. HOSP ST LOUIS,ANAT PATHOL LAB,PARIS,FRANCE. NR 16 TC 299 Z9 331 U1 0 U2 1 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD MAR PY 1995 VL 146 IS 3 BP 620 EP 625 PG 6 WC Pathology SC Pathology GA QL395 UT WOS:A1995QL39500008 PM 7887444 ER PT J AU GEORGE, MS KETTER, TA PAREKH, PI HORWITZ, B HERSCOVITCH, P POST, RM AF GEORGE, MS KETTER, TA PAREKH, PI HORWITZ, B HERSCOVITCH, P POST, RM TI BRAIN ACTIVITY DURING TRANSIENT SADNESS AND HAPPINESS IN HEALTHY WOMEN SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article; Proceedings Paper CT Annual Meeting of the Society-for-Biological-Psychiatry CY MAY 18-21, 1994 CL PHILADELPHIA, PA SP Soc Biol Psychiat ID POSITRON EMISSION TOMOGRAPHY; COMPLEX PARTIAL SEIZURES; MULTIPLE-SCLEROSIS; CEREBRAL METABOLISM; GLUCOSE-METABOLISM; MAJOR DEPRESSION; CINGULATE CORTEX; MOOD DISORDERS; FRONTAL-CORTEX; PANIC DISORDER AB Objective: The specific rain regions involved in the normal emotional states of transient sadness or happiness are poorly understood. The authors therefore sought to determine if (H2O)-O-15 positron emission tomography (PET) might demonstrate changes in regional cerebral blood flow (rCBF) associated with transient sadness or happiness in healthy adult women. Method: Eleven healthy and never mentally ill adult women were scanned, by using PET and (H2O)-O-15, during happy, sad, and neutral states induced by recalling affect-appropriate life events and looking at happy, sad, or neutral human faces. Results: Compared to the neutral condition, transient sadness significantly activated bilateral limbic and paralimbic structures (cingulate, medial prefrontal, and mesial temporal cortex), as well as brainstem, thalamus, and caudate/putamen. In contrast, transient happiness had no areas of significantly increased activity but was associated with significant and widespread reductions in cortical rCBF, especially in the right perfrontal and bilateral temporal-parietal regions. Conclusions: Transient sadness and happiness in healthy volunteer women are accompanied by significant changes in regional brain activity in the limbic system, as well as other brain regions. Transient sadness and happiness affect different brain regions in divergent directions and are not merely opposite activity in identical brain regions. These findings have implications for understanding the neural substrates of both normal and pathological emotion. C1 NIA,NEUROSCI LAB,BETHESDA,MD. NIH,CTR CLIN,POSITRON EMISS TOMOG IMAGING SECT,BETHESDA,MD 20892. RP GEORGE, MS (reprint author), NIMH,BIOL PSYCHIAT BRANCH,BLDG 10,RM 3N212,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 116 TC 535 Z9 539 U1 4 U2 28 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD MAR PY 1995 VL 152 IS 3 BP 341 EP 351 PG 11 WC Psychiatry SC Psychiatry GA QJ604 UT WOS:A1995QJ60400004 PM 7864258 ER PT J AU WINOKUR, G CORYELL, W AKISKAL, HS MASER, JD KELLER, MB ENDICOTT, J MUELLER, T AF WINOKUR, G CORYELL, W AKISKAL, HS MASER, JD KELLER, MB ENDICOTT, J MUELLER, T TI ALCOHOLISM IN MANIC-DEPRESSIVE (BIPOLAR) ILLNESS - FAMILIAL ILLNESS, COURSE OF ILLNESS, AND THE PRIMARY-SECONDARY DISTINCTION SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID AFFECTIVE-DISORDER; CRITERIA AB Objective: This 5-year follow-up study was designed to explore the factors that might lead to alcoholism in patients with bipolar disorder. Method: The authors studied patients with bipolar illness (70 with alcoholism and 161 without), their relatives, and a comparison group composed of relatives' acquaintances. All were evaluated with versions of the Schedule for Affective Disorders and Schizophrenia, and diagnoses were made according to the Research Diagnostic Criteria. Thirty of the bipolar alcoholic patients whose affective disorder was primary were also compared with 34 whose alcoholism was primary. Results: Alcoholism was more frequent in the bipolar patients than in the comparison subjects. There were no significant differences between the alcoholic and nonalcoholic bipolar patients in family history of alcoholism or affective disorders, suggesting that bipolar illness with alcoholism is not explicable by a family history of alcoholism and that the alcoholism seen in bipolar illness is dissimilar to alcoholism as a primary disorder. Alcoholism associated with bipolar illness was more likely to remit than primary alcoholism. There was no significant difference in family history between the patients with primary alcoholism and those with primary bipolar disorder. The patients with primary alcoholism had significantly fewer episodes of affective disorder during followup, suggesting that their type of bipolar illness was less severe and may have needed the added insult of alcoholism to make it manifest. Conclusions: The study supports the idea that not all alcoholism is primary with a corresponding familial diathesis. Rather, alcoholism associated with bipolar disorder is often a secondary complication. C1 NIMH,COLLABORAT PROGRAM PSYCHOBIOL DEPRESS CLIN STUDIE,BETHESDA,MD. RP WINOKUR, G (reprint author), UNIV IOWA HOSP & CLIN,DEPT PSYCHIAT,200 HAWKINS DR,2887 JPP,IOWA CITY,IA 52242, USA. FU NIMH NIH HHS [R01 MH025478] NR 18 TC 142 Z9 142 U1 0 U2 3 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD MAR PY 1995 VL 152 IS 3 BP 365 EP 372 PG 8 WC Psychiatry SC Psychiatry GA QJ604 UT WOS:A1995QJ60400007 PM 7864261 ER PT J AU CORYELL, W ENDICOTT, J MASER, JD KELLER, MB LEON, AC AKISKAL, HS AF CORYELL, W ENDICOTT, J MASER, JD KELLER, MB LEON, AC AKISKAL, HS TI LONG-TERM STABILITY OF POLARITY DISTINCTIONS IN THE AFFECTIVE-DISORDERS SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID BIPOLAR AFFECTIVE-DISORDER; MAJOR DEPRESSION; FOLLOW-UP; ILLNESS; INTERVIEW; UNIPOLAR; FAMILY AB Objective: This analysis aimed to quantify the long-term stability of distinctions between nonbipolar, bipolar II, and bipolar I affective disorders and to determine the predictors of shifts in patients' diagnoses among these categories. Method: Probands entered the study as they sought treatment for manic, major depressive, or schizoaffective disorder diagnosed according to the Research Diagnostic Criteria. After thorough baseline evaluations, 605 patients with nonbipolar major depressive disorder or schizoaffective disorder, depressed type; 96 with bipolar II disorder; and 231 with bipolar I disorder or schizoaffective disorder, manic type, began the follow-up study. Direct interviews took place at 6-month intervals for the first 5 years and annually thereafter. Results: Only 20 (5.2%) of the 381 initially nonbipolar probands who completed 10 years of follow-up developed mania during that time, and only 19 (5.0%) developed hypomania. A slightly higher proportion of the 67 who began with bipolar II disorder developed mania during the 10 years. Although 101 (66.4%) of the 152 bipolar I or schizoaffective manic probands developed subsequent manic episodes, only 11 (7.2%) developed hypomanic episodes and no mania. Young age at intake and at onset and chronicity of the index episode predicted shifts from nonbipolar to bipolar II disorder. Psychosis and a family history of mania predicted shifts from nonbipolar to bipolar I disorder. Conclusions: The high stability of baseline distinctions between nonbipolar, bipolar II, and bipolar I disorders, in combination with previously described family study data, strongly supports the separation of these disorders for both clinical and research purposes. C1 NIMH,COLLABORAT PROGRAM PSYCHOBIOL DEPRESS CLIN STUDIE,BETHESDA,MD. FU NIMH NIH HHS [R01 MH059691] NR 29 TC 254 Z9 262 U1 0 U2 2 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD MAR PY 1995 VL 152 IS 3 BP 385 EP 390 PG 6 WC Psychiatry SC Psychiatry GA QJ604 UT WOS:A1995QJ60400010 PM 7864264 ER PT J AU KRAMER, RA ALLEN, L GERGEN, PJ AF KRAMER, RA ALLEN, L GERGEN, PJ TI HEALTH AND SOCIAL CHARACTERISTICS AND CHILDRENS COGNITIVE-FUNCTIONING - RESULTS FROM A NATIONAL COHORT SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID BIRTH-WEIGHT; SCHOOL PERFORMANCE; GESTATIONAL-AGE; INTELLIGENCE; ACHIEVEMENT; PREVALENCE; BEHAVIOR; EXPOSURE AB Objectives. The purpose of this study was to examine the associations between cognitive functioning in children and sociodemographic, family, and health characteristics. Methods. Data from phase 1 of the third National Health and Nutrition Examination Survey were used to evaluate performance on standardized cognitive tests in a representative sample of 2531 children 6 to 16 years of age. Multivariate analyses were used to assess independent associations between covariates and test performance. Results. Lower income, minority status, and lower education of an adult reference person (one of the persons in the household who owned or rented the home) were independently associated with poorer performance on all cognitive subtests. To a lesser degree, general health status, history of birth complications, and sex also were independent predictors of performance for some of the subtests. Conclusions. These findings illustrate disparities in cognitive functioning across sociodemographic and health characteristics of children in the US population. They suggest the need for public health policies to take a multifaceted approach to optimizing childhood environments in order to overcome the effects of socioeconomic and minority status. C1 NYU,SCH EDUC,DEPT APPL PSYCHOL,NEW YORK,NY. NIAID,DIV ALLERGY IMMUNOL & TRANSPLANTAT,BETHESDA,MD. RP KRAMER, RA (reprint author), NATL CTR HLTH STAT,DIV HLTH EXAMINAT STAT,DATA DIMENS BRANCH,ROOM 1064,6525 BELCREST RD,HYATTSVILLE,MD 20782, USA. NR 65 TC 47 Z9 48 U1 3 U2 7 PU AMER PUBLIC HEALTH ASSN INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD MAR PY 1995 VL 85 IS 3 BP 312 EP 318 DI 10.2105/AJPH.85.3.312 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA QM393 UT WOS:A1995QM39300007 PM 7892911 ER PT J AU BURTON, LC STEINWACHS, DM GERMAN, PS SHAPIRO, S BRANT, LJ RICHARDS, TM CLARK, RD AF BURTON, LC STEINWACHS, DM GERMAN, PS SHAPIRO, S BRANT, LJ RICHARDS, TM CLARK, RD TI PREVENTIVE SERVICES FOR THE ELDERLY - WOULD COVERAGE AFFECT UTILIZATION AND COSTS UNDER MEDICARE SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID CARE AB Objectives. This study was undertaken to determine whether adding a benefit for preventive services to older Medicare beneficiaries would affect utilization and costs under Medicare. Methods. The demonstration used an experimental design, enrolling 4195 older, community-dwelling Medicare recipients. Medicare claims data for the 2 years in which the preventive visits occurred were compared for the intervention (n = 2105) and control (n = 2090) groups. Monthly allowable charges for Part A and Part B services and number of hospital discharges and ambulatory visits were compared. Results. There were no significant differences in the charges between the groups owing to the intervention, although total charges were somewhat lower for the intervention group even when the cost of the intervention was included. Charges for both groups rose significantly as would be expected for an aging population. A companion paper describes a modest health benefit. Conclusions. There appears to be a modest health benefit with no negative cost impact. This finding gives an early quantitative basis for the discussion of whether to extend Medicare benefits to include a general preventive visit from a primary care clinician. C1 NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. RP BURTON, LC (reprint author), JOHNS HOPKINS MED INST,SCH HYG & PUBL HLTH,CTR HLTH SERV RES & DEV,624 N BROADWAY,BALTIMORE,MD 21205, USA. NR 13 TC 32 Z9 32 U1 0 U2 3 PU AMER PUBLIC HEALTH ASSN INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD MAR PY 1995 VL 85 IS 3 BP 387 EP 391 DI 10.2105/AJPH.85.3.387 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA QM393 UT WOS:A1995QM39300020 PM 7892924 ER PT J AU OVERPECK, MD KOTCH, JB AF OVERPECK, MD KOTCH, JB TI THE EFFECT OF US CHILDRENS ACCESS TO CARE ON MEDICAL ATTENTION FOR INJURIES SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Note ID UNITED-STATES; SERVICES; SAMPLE AB This analysis examined the effect of access to care on nonfatal medically attended injury rates for US children in 1988. Rates of medically attended injury were about the same for children with health insurance and Medicaid, after adjustment for other characteristics. However. lack of medical care coverage (health insurance or Medicaid) had the effect of decreasing the rates of both total and serious medically attended injury compared with the rates for children with coverage. For children without coverage, as many as 30% of total injuries and 40% of serious injuries may not have been attended in 1988. C1 UNIV N CAROLINA,DEPT MATERNAL & CHILD HLTH,CHAPEL HILL,NC. RP OVERPECK, MD (reprint author), NICHHD,EPIDEMIOL BRANCH,61000 EXECUT BLVD,ROOM 7B03,BETHESDA,MD 20892, USA. NR 29 TC 34 Z9 34 U1 0 U2 0 PU AMER PUBLIC HEALTH ASSN INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD MAR PY 1995 VL 85 IS 3 BP 402 EP 404 DI 10.2105/AJPH.85.3.402 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA QM393 UT WOS:A1995QM39300024 PM 7892928 ER PT J AU GIERLOWSKI, TC RON, E SCHNEIDER, AB AF GIERLOWSKI, TC RON, E SCHNEIDER, AB TI THE ACCURACY OF SIBLINGS FAMILY HISTORY REPORTS OF THYROID AND OTHER CANCERS SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Letter ID RADIATION C1 UNIV ILLINOIS,MICHAEL REESE HOSP & MED CTR,COLL MED,DIV ENDOCRINOL & METAB,CHICAGO,IL 60616. NCI,RADIAT EPIDEMIOL BRANCH,BETHESDA,MD 20892. FU NCI NIH HHS [N01-CP-05609, CA21518, N01-CP-85604] NR 7 TC 7 Z9 7 U1 0 U2 0 PU AMER PUBLIC HEALTH ASSN INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD MAR PY 1995 VL 85 IS 3 BP 408 EP 409 DI 10.2105/AJPH.85.3.408 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA QM393 UT WOS:A1995QM39300026 PM 7892930 ER PT J AU OGNIBENE, FP SHELHAMER, JH HOFFMAN, GS KERR, GS REDA, D FAUCI, AS LEAVITT, RY AF OGNIBENE, FP SHELHAMER, JH HOFFMAN, GS KERR, GS REDA, D FAUCI, AS LEAVITT, RY TI PNEUMOCYSTIS-CARINII PNEUMONIA - A MAJOR COMPLICATION OF IMMUNOSUPPRESSIVE THERAPY IN PATIENTS WITH WEGENERS GRANULOMATOSIS SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article ID ACQUIRED IMMUNODEFICIENCY SYNDROME; TRIMETHOPRIM-SULFAMETHOXAZOLE; PULMONARY COMPLICATIONS; METHOTREXATE THERAPY; RHEUMATOID-ARTHRITIS; CYCLOPHOSPHAMIDE; INFECTION AB The risk factors and clinical and laboratory parameters in Pneumocystis carinii pneumonia in patients with Wegener's granulomatosis have not been well characterized. We undertook a retrospective chart review of all patients with a diagnosis of Wegener's granulomatosis and P. carinii pneumonia who were followed at the National Institute of Allergy and Infectious Diseases of the National Institutes of Health. The chart review focused on clinical, laboratory, and roentgenologic evidence of P. carinii pneumonia. Eleven cases of P. carinii pneumonia were diagnosed in some 180 patients with Wegener's granulomatosis, for an overall incidence of approximately 6%. All patients developed P. carinii pneumonia either during the initial course of treatment or during therapy for recurrent Wegener's granulomatosis. All patients were receiving daily glucocorticoids and a second immunosuppressive therapy. Lymphocytopenia was noted in all patients, with a mean +/- SEM total lymphocyte count of 303 +/- 69 cells/mu L. All patients tested (10 of 11) were seronegative for human immunodeficiency virus (HIV) infection. Eight presented with worsening chest roentgenograms compared with baseline, whereas three presented with normal chest roentgenograms. We conclude that P. carinii is a common opportunistic pathogen in patients with Wegener's granulomatosis receiving immunosuppressive therapy. Therapeutic immunosuppression (daily glucocorticoids and immunosuppressive agents) and the resultant lymphocytopenia, as well as the lymphocyte and monocyte functional abnormalities caused by glucocorticoids, may be the most likely factors predisposing to P. carinii pneumonia in patients with Wegener's granulomatosis. Based on our data, all patients with Wegener's granulomatosis should be given chemoprophylaxis against P. carinii while they are receiving daily glucocorticoids. Clinicians should evaluate these patients for P. carinii if there is even a minor clinical or roentgenographic change in their status. C1 NIAID,WARREN G MAGNUSON CLIN CTR,DEPT CRIT CARE MED,BETHESDA,MD 20892. NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. NR 30 TC 132 Z9 139 U1 1 U2 2 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD MAR PY 1995 VL 151 IS 3 BP 795 EP 799 PG 5 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA QL391 UT WOS:A1995QL39100036 PM 7881673 ER PT J AU WEBSTER, CT GORDIN, FM MATTS, JP KORVICK, JA MILLER, C MUTH, K BROWN, LS BESCH, CL KUMI, JO SALVESON, C BINCSIK, A IRVIN, K MAIATICO, G AF WEBSTER, CT GORDIN, FM MATTS, JP KORVICK, JA MILLER, C MUTH, K BROWN, LS BESCH, CL KUMI, JO SALVESON, C BINCSIK, A IRVIN, K MAIATICO, G TI 2-STAGE TUBERCULIN SKIN TESTING IN INDIVIDUALS WITH HUMAN-IMMUNODEFICIENCY-VIRUS INFECTION SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article ID DRUG-USERS; ANERGY AB In this study we estimated occurrence of the booster effect in a population infected with the human immunodeficiency virus (HIV) and assessed the relation between the booster effect, T-lymphocyte CD4 cell counts, tuberculosis risk categories, and HIV exposure categories. Patients were recruited from 13 participating sites of the Terry Beirn Community Programs for Clinical Research on AIDS (CPCRA). A two-stage tuberculin skin test was applied to 709 HIV-infected patients using the Mantoux method. An induration reading < 5 mm on the first test and greater than or equal to 5 mm on the second skin test defined the booster effect. Overall, 18 patients, or 2.7% (95% confidence interval, 1.6 to 4.2) experienced the booster ef feet. Boosted responses were seen in eight (2.1%) anergic patients, six (4.5%) nonanergic patients, and four (2.5%) with anergy status unknown. Boosting was noted in 1 of the 131 women enrolled. Age, race, CD4 cell count, injection drug use, anergy status, tuberculosis risk categories, and HIV exposure categories were not predictive of boosting. The booster effect occurs in a small percentage of HIV-infected patients tested, thus identifying small numbers of patients with latent tuberculosis infection. The two-stage procedure is probably of limited value in the diagnosis of latent tuberculosis in HIV-infected persons. C1 WASHINGTON REG AIDS PROGRAM,WASHINGTON,DC. VET AFFAIRS MED CTR,WASHINGTON,DC 20422. UNIV MINNESOTA,SCH PUBL HLTH,CPCRA STAT CTR,DIV BIOSTAT,MINNEAPOLIS,MN 55455. NIAID,DIV AIDS,BETHESDA,MD 20892. ROW SCI,CPCRA OPERAT CTR,ROCKVILLE,MD. COLUMBIA UNIV,ADDICT RES & TREATMENT CORP,NEW YORK,NY. COLUMBIA UNIV,HARLEM HOSP,NEW YORK,NY. LOUISIANA COMMUNITY AIDS RES PROGRAM,NEW ORLEANS,LA. HENRY FORD HOSP,DETROIT,MI 48202. RES & EDUC GRP,PORTLAND,OR. DELAWARE CPCRA,WILMINGTON,DE. RP WEBSTER, CT (reprint author), RICHMOND AIDS CONSORTIUM,POB 980049,RICHMOND,VA 23298, USA. NR 17 TC 13 Z9 13 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD MAR PY 1995 VL 151 IS 3 BP 805 EP 808 PG 4 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA QL391 UT WOS:A1995QL39100038 PM 7881675 ER PT J AU HUNNINGHAKE, GW KALICA, AR AF HUNNINGHAKE, GW KALICA, AR TI APPROACHES TO THE TREATMENT OF PULMONARY FIBROSIS SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Editorial Material C1 NHLBI,DIV LUNG DIS,LUNG BIOL & DIS PROGRAM,BETHESDA,MD 20892. UNIV IOWA,COLL MED,DIV PULM CRIT CARE & OCCUPAT MED,IOWA CITY,IA. NR 0 TC 73 Z9 76 U1 2 U2 2 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD MAR PY 1995 VL 151 IS 3 BP 915 EP 918 PG 4 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA QL391 UT WOS:A1995QL39100057 PM 7881692 ER PT J AU KORST, RJ MCELVANEY, NG CHU, CS ROSENFELD, MA MASTRANGELI, A HAY, J BRODY, SL EISSA, NT DANEL, C JAFFE, HA CRYSTAL, RG AF KORST, RJ MCELVANEY, NG CHU, CS ROSENFELD, MA MASTRANGELI, A HAY, J BRODY, SL EISSA, NT DANEL, C JAFFE, HA CRYSTAL, RG TI GENE-THERAPY FOR THE RESPIRATORY MANIFESTATIONS OF CYSTIC-FIBROSIS SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article; Proceedings Paper CT Symposium on Cystic Fibrosis - From the Gene to the Cure, at the American-Lung-Association/American-Thoracic-Society International Conference CY MAY 17, 1993 CL SAN FRANCISCO, CA SP AMER LUNG ASSOC, AMER THORAC SOC ID TRANSMEMBRANE CONDUCTANCE REGULATOR; DEPENDENT PROTEIN-KINASE; BIOELECTRIC POTENTIAL DIFFERENCE; AIRWAY EPITHELIAL-CELLS; ION-TRANSPORT DEFECT; CHLORIDE CHANNELS; LUNG TRANSPLANTATION; NONSENSE MUTATIONS; ADENOVIRUS VECTORS; CFTR AB Cystic fibrosis (CF) is caused by mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The major manifestations are on the airway epithelial surface, with purulent mucus, recurrent infections, chronic inflammation, and loss of lung function. Consequent to mutations in both parental genes, airway epithelial cells have insufficient CFTR function. Because this can be corrected in vitro by transfer of the normal CFTR gene into airway epithelial cells, it is reasonable to hypothesize that the respiratory manifestations of CF could be prevented by transfer of the normal human CFTR cDNA to the airway epithelium in vivo. Over the past 6 years, our laboratory has developed a strategy to accomplish this goal using a replication deficient E1(-)E3(-) recombinant adenovirus (Ad) serotype 5 vector containing the normal human CFTR cDNA (AdCFTR). Studies with experimental animals demonstrate that with administration of such a vector to the airways, the human CFTR cDNA could be transferred to the airway epithelium, with expression of the human CFTR cDNA for at least 6 weeks. Extensive preclinical studies in vitro and in vivo demonstrated that the risks to humans were sufficiently low to initiate a Phase I trial using the AdCTTR vector to treat the respiratory manifestations of CF in humans. Following approval by the National Heart, Lung, and Blood Institute Institutional Review Board, the National Institutes of Health Biosafety Committee, the National Institutes of Health Recombinant DNA Advisory Committee, and the Food and Drug Administration, we initiated the first human trial of gene therapy for CF on April 17, 1993. The clinical study is still ongoing, with safety and efficacy data being evaluated, but there is clear evidence that it is feasible to transfer and express the normal CFTR cDNA to the airway epithelium in vivo in individuals with CF. C1 NEW YORK HOSP,CORNELL MED CTR,DIV PULM & CRIT CARE MED,NEW YORK,NY 10021. NHLBI,PULM BRANCH,BETHESDA,MD 20892. RI McElvaney, Noel/A-6809-2010 NR 115 TC 32 Z9 32 U1 0 U2 1 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD MAR PY 1995 VL 151 IS 3 SU S BP S75 EP S87 PG 13 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA QN121 UT WOS:A1995QN12100007 PM 7533609 ER PT J AU CLARK, AB RANDELL, SH NETTESHEIM, P GRAY, TE BAGNELL, B OSTROWSKI, LE AF CLARK, AB RANDELL, SH NETTESHEIM, P GRAY, TE BAGNELL, B OSTROWSKI, LE TI REGULATION OF CILIATED CELL-DIFFERENTIATION IN CULTURES OF RAT TRACHEAL EPITHELIAL-CELLS SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article ID HUMAN NASAL EPITHELIUM; INHALATION INJURY; EXPRESSION; CILIOGENESIS; MARKERS; GENE; PROLIFERATION; KERATINOCYTES; REGENERATION; EXPOSURE AB The cellular pathway of ciliated cell differentiation and its regulation is poorly defined. To begin to understand the process of ciliated cell. differentiation, we sought to identify factors regulating ciliated cell development in vitro. Rat tracheal epithelial (RTE) cells were cultured on collagen gel-coated membranes at an air-liquid interface in hormone- and growth factor-supplemented medium (complete medium [CM]). Under these conditions, RTE cells first proliferate and then differentiate into a pseudostratified mucociliary epithelium. Ciliated cell differentiation was measured using a monoclonal antibody, RTE(3), which was shown to specifically react with the plasma membrane of ciliated cells. Cultures were immunostained in situ, and the percentage of the culture surface covered with ciliated cells was estimated using videomicroscopy and an image analysis program. If an air-liquid interface was not created and the cells were maintained in the submerged state, ciliated cell differentiation was suppressed 25-fold. Culture in the absence of mitogenic components present in CM, including epidermal growth factor (EGF), cholera toxin (CT), or bovine pituitary extract, resulted in 2- to 4-fold increases in the percentage of ciliated cells. When both EGF and CT were removed from the media, DNA synthesis and total cell number was reduced, while ciliated cell differentiation increased as much as 5-fold. These results demonstrate that submersion inhibits, while withdrawal of mitogenic compounds promotes, ciliated cell differentiation in vitro. C1 NIEHS,PULM PATHOBIOL LAB,AIRWAY CELL BIOL GRP,RES TRIANGLE PK,NC 27709. UNIV N CAROLINA,DEPT PATHOL,CHAPEL HILL,NC. NR 32 TC 51 Z9 52 U1 1 U2 2 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 1044-1549 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD MAR PY 1995 VL 12 IS 3 BP 329 EP 338 PG 10 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA QL388 UT WOS:A1995QL38800012 PM 7873199 ER PT J AU TERUYAFELDSTEIN, J TEMECK, BK SLOAS, MM KINGMA, DW RAFFELD, M PASS, HI MUELLER, B JAFFE, ES AF TERUYAFELDSTEIN, J TEMECK, BK SLOAS, MM KINGMA, DW RAFFELD, M PASS, HI MUELLER, B JAFFE, ES TI PULMONARY MALIGNANT-LYMPHOMA OF MUCOSA-ASSOCIATED LYMPHOID-TISSUE (MALT) ARISING IN A PEDIATRIC HIV-POSITIVE PATIENT SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Note DE MALIGNANT LYMPHOMA; MALT LYMPHOMA; LUNG; PEDIATRIC; HIV POSITIVE ID B-CELL LYMPHOMA; NON-HODGKINS LYMPHOMA; FEATURES; DIAGNOSIS; DISEASE AB A malignant lymphoma arising in the lung of a pediatric HIV-positive patient exhibited histologic and clinical features of low-grade B-cell lymphoma of mucosa-associated lymphoid tissue (MALT). Clinically, the neoplasm consisted of a 4-cm mass in the left-upper lobe of the lung of a 7-year-old girl, The lung mass was surgically resected. Monoclonal immunoglobulin heavy and light chain gene rearrangements were shown by Southern blot. Monoclonality of light chain expression was demonstrated by immunohistochemistry. Coexpression of Leu-22 (CD43) by the tumor cells supported the diagnosis of lymphoma. The remainder of the pulmonary parenchyma distal to the mass was associated with pulmonary lymphoid hyperplasia/lymphocytic interstitial pneumonitis, which may have been a predisposing factor. Gastric MALT lymphomas have recently been described in adult HIV-antibody-positive patients. Ours represents the first reported case of a pulmonary MALT lymphoma in a pediatric HIV-positive patient, In addition, at age 7, this is the youngest patient reported with a MALT lymphoma. C1 NCI,PATHOL LAB,HEMATOPATHOL SECT,BETHESDA,MD 20892. NCI,SURG BRANCH,BETHESDA,MD 20892. NCI,PEDIAT BRANCH,BETHESDA,MD 20892. NR 29 TC 60 Z9 61 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD MAR PY 1995 VL 19 IS 3 BP 357 EP 363 DI 10.1097/00000478-199503000-00014 PG 7 WC Pathology; Surgery SC Pathology; Surgery GA QJ447 UT WOS:A1995QJ44700014 PM 7872434 ER PT J AU WYATT, RJ ANGRIST, B KAROUM, F AF WYATT, RJ ANGRIST, B KAROUM, F TI URINARY DOPAMINE METABOLITES DURING COCAINE ABSTINENCE SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Article ID BRAIN; ABUSE; REDUCTION; CATECHOLAMINES; BROMOCRIPTINE; SCHIZOPHRENIA; WITHDRAWAL; RECEPTORS; CORTEX AB The authors compared catecholamine concentrations measured on 2-hour urine collections of recently hospitalized cocaine abusers (CAs; n = 17) with those of detoxified alcoholic patients (APs; n = 20) and staff normal-control subjects (NCs; n = 23). CAs had been abstinent for G-8 days; APs had been abstinent for 9-53 days. Compared with NCs, the recently abstinent CAs had a decrease in the dopamine metabolite, 3,4-dihydroxyphenylacetic acid (DOPAC), and a decrease in Sum dopamine/Sum norepinephrine (the molar sum of dopamine and its metabolites/the molar sum of norepinephrine and its metabolites). The dopamine metabolite, 3-methoxytyramine (3-MT) was increased. The detoxified APs had increases in the norepinephrine metabolites normetanephrine and 3-methoxy-4-hydroxyphenylglycol in addition to elevated 3-MT. Sum dopamine/Sum norepinephrine was decreased in RPs compared with NCs. The authors discuss differences in light of other findings related to recent abstinence after cocaine and alcohol abuse. RP WYATT, RJ (reprint author), NIMH,ST ELIZABETHS HOSP,CTR NEUROSCI,NEUROPSYCHIAT BRANCH,2700 MARTIN LUTHER KING JR AVE SE,WASHINGTON,DC 20032, USA. NR 47 TC 4 Z9 4 U1 1 U2 1 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 1055-0496 J9 AM J ADDICTION JI Am. J. Addict. PD SPR PY 1995 VL 4 IS 2 BP 133 EP 140 PG 8 WC Substance Abuse SC Substance Abuse GA QW579 UT WOS:A1995QW57900005 ER PT J AU PHILIBERT, RA HAWKINS, GA DAMSCHRODERWILLIAMS, P STUBBLEFIELD, BK MARTIN, BM GINNS, EI AF PHILIBERT, RA HAWKINS, GA DAMSCHRODERWILLIAMS, P STUBBLEFIELD, BK MARTIN, BM GINNS, EI TI DIRECT SEQUENCING OF TRINUCLEOTIDE REPEATS FROM COSMID GENOMIC DNA-TEMPLATE SO ANALYTICAL BIOCHEMISTRY LA English DT Note C1 AMER BREEDERS SERV,DE FOREST,WI 53532. RP PHILIBERT, RA (reprint author), NIMH,CLIN NEUROSCI BRANCH,BLDG 49,ROOM B1EE16,BETHESDA,MD 20892, USA. NR 6 TC 13 Z9 13 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD MAR 1 PY 1995 VL 225 IS 2 BP 372 EP 374 DI 10.1006/abio.1995.1174 PG 3 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA QK470 UT WOS:A1995QK47000031 PM 7762809 ER PT J AU NARITSIN, DB BONI, RL MARKEY, SP AF NARITSIN, DB BONI, RL MARKEY, SP TI PENTAFLUOROBENZYLATION METHOD FOR QUANTIFICATION OF ACIDIC TRYPTOPHAN-METABOLITES USING ELECTRON-CAPTURE NEGATIVE-ION MASS-SPECTROMETRY SO ANALYTICAL CHEMISTRY LA English DT Article ID PERFORMANCE LIQUID-CHROMATOGRAPHY; GAS-CHROMATOGRAPHY; QUINOLINIC ACID; RAT-BRAIN; KYNURENIC ACID; CEREBROSPINAL-FLUID; ARACHIDONIC-ACID; HUMAN-SERUM; PLASMA; ESTERIFICATION AB An improved pentafluorobenzylation method was developed for derivatization of L-tryptophan and its acidic metabolites (L-kynurenine, kynurenic acid, anthranilic acid, xanthurenic acid, 3-hydroxyanlranilic acid, picolinic acid, quinolinic acid) present at trace levels in aqueous samples. This method employs lyophilization of aqueous samples in the presence of excess tetrabutylammonium hydrogen sulfate, followed by base-catalyzed anhydrous pentafluorobenzylation. A comparison with other published methods shows the advantage of this modification for the derivatization of kynurenine metabolites. The derivatives were analyzed by gas chromatography/electron capture negative ion mass spectrometry (GC/ECNI-MS) or liquid chromatography/particle beam/ ECNI-MS (LC/ECNI-MS). The detection limits for injected standards are in the femtogram range by GC/ECNI-MS and in the low picogram range by LC/ECNI-MS. GC/ ECNIMS is 3.6 (xanthurenic acid) to 66 (quinolinic acid) times more sensitive than LC/ECNI-MS. The simultaneous determination of two neuroactive metabolites, quinolinic and kynurenic acids, in culture medium is presented. The minimum measurable concentrations of these metabolites in 100 mu L of culture medium are 0.11 nM for quinolinic acid and 0.21 nM for kynurenic acid. C1 NIMH,CLIN SCI LAB,ANALYT BIOCHEM SECT,BETHESDA,MD 20892. NR 33 TC 33 Z9 33 U1 1 U2 8 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0003-2700 J9 ANAL CHEM JI Anal. Chem. PD MAR 1 PY 1995 VL 67 IS 5 BP 863 EP 870 DI 10.1021/ac00101a012 PG 8 WC Chemistry, Analytical SC Chemistry GA QK144 UT WOS:A1995QK14400020 PM 7762823 ER PT J AU COHEN, SG BIANCHINE, PJ AF COHEN, SG BIANCHINE, PJ TI HYMENOPTERA, HYPERSENSITIVITY, AND HISTORY - A PROLOGUE TO CURRENT DAY CONCEPTS AND PRACTICES IN THE DIAGNOSIS, TREATMENT, AND PREVENTION OF INSECT STING ALLERGY SO ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY LA English DT Review ID IMPORTED FIRE ANT; WHOLE-BODY EXTRACTS; BEE VENOM; IMMUNOTHERAPY; SENSITIVITY RP COHEN, SG (reprint author), NIAID,DIV INTRAMURAL RES,SOLAR BLDG,RM 2C37,BETHESDA,MD, USA. NR 158 TC 1 Z9 1 U1 0 U2 2 PU AMER COLL ALLERGY ASTHMA IMMUNOLOGY PI ARLINGTON HTS PA 85 WEST ALGONQUIN RD SUITE 550, ARLINGTON HTS, IL 60005 SN 1081-1206 J9 ANN ALLERG ASTHMA IM JI Ann. Allergy Asthma Immunol. PD MAR PY 1995 VL 74 IS 3 BP 198 EP 217 PG 20 WC Allergy; Immunology SC Allergy; Immunology GA QM749 UT WOS:A1995QM74900002 PM 7889376 ER PT J AU HORNE, MDK MAY, DJ ALEXANDER, HR STEINHAUS, EP WHITMAN, ED CHANG, RC DOPPMAN, JL AF HORNE, MDK MAY, DJ ALEXANDER, HR STEINHAUS, EP WHITMAN, ED CHANG, RC DOPPMAN, JL TI VENOGRAPHIC SURVEILLANCE OF TUNNELED VENOUS ACCESS DEVICES IN ADULT ONCOLOGY PATIENTS SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article DE CATHETERS; THROMBOSIS; VENOGRAPHY; VENOUS ACCESS ID CATHETER-RELATED COMPLICATIONS; STEM-CELL TRANSPLANTATION; SUBCLAVIAN VEIN; MARROW TRANSPLANTATION; PARENTERAL-NUTRITION; THROMBOSIS; HICKMAN; CHEMOTHERAPY; EXPERIENCE; SYSTEM AB Background: Tunneled venous access devices (VADs) are often essential in the care of patients with advanced malignancies, but they carry an uncertain risk of thrombosis. Methods: To determine the incidence of venoocclusion related to silicone VADs in a population of adult oncology patients, we prospectively studied 50 individuals with upper extremity venograms similar to 6 weeks after their VADs had been implanted. Twenty-one of these patients were reevaluated with venograms similar to 12 weeks after catheterization. In addition, venograms were performed on a separate group of 24 patients who needed catheterization of axillary-subclavian veins that had been catheterized in the past. Results: The 6-week venograms in the prospective study showed partial venous obstruction in 15 patients (30%), whereas three (6%) had developed symptomatic total venoocclusion by this time. The 12-week venograms showed two additional complete occlusions, Venograms of 30 previously catheterized veins showed complete venoocclusion in nine (30%), although only two had a history of thrombosis. Conclusions: Our observations indicate that VADs frequently cause partial venoocclusion within the first 6 weeks of catheterization and that permanent venous damage from VADs is common, even without a history of VAD-related thrombosis. C1 NCI,SURG BRANCH,BETHESDA,MD 20892. NIH,WARREN G MAGNUSON CLIN CTR,DEPT RADIOL,BETHESDA,MD 20892. RP HORNE, MDK (reprint author), NIH,WARREN G MAGNUSON CLIN CTR,DEPT CLIN PATHOL,ROOM 2C390,BLDG 10,BETHESDA,MD 20892, USA. NR 28 TC 41 Z9 42 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD MAR PY 1995 VL 2 IS 2 BP 174 EP 178 DI 10.1007/BF02303635 PG 5 WC Oncology; Surgery SC Oncology; Surgery GA QH868 UT WOS:A1995QH86800015 PM 7728573 ER PT J AU LAI, SL BRAUCH, H KNUTSEN, T JOHNSON, BE NAU, MM MITSUDOMI, T TSAI, CM WHANGPENG, J ZBAR, B KAYE, FJ GAZDAR, AF AF LAI, SL BRAUCH, H KNUTSEN, T JOHNSON, BE NAU, MM MITSUDOMI, T TSAI, CM WHANGPENG, J ZBAR, B KAYE, FJ GAZDAR, AF TI MOLECULAR-GENETIC CHARACTERIZATION OF NEUROENDOCRINE LUNG-CANCER CELL-LINES SO ANTICANCER RESEARCH LA English DT Article DE NEUROENDOCRINE LUNG CANCER CELL LINES; MOLECULAR GENETIC CHARACTERIZATION ID HUMAN-TUMORS; SHORT ARM; CHROMOSOME-3; CARCINOMA; SITES; HETEROZYGOSITY; EXPRESSION; MUTATIONS; ESTABLISHMENT; POLYMORPHISM AB Small cell lung cancels express neuroendocrine (NE) cell features, while most non-SCLC tumors lack these features. We studied the cytogenetic and genetic alterations in cell lines derived from three unusual subtypes of lung cancer including carcinoids, non-small cell lung cancers expressing NE properties (NSCLC-NE) and extrapulmonary small cell cancels (ExPuSC) and compared them with those of SCLC and NSCLC lines. Our studies included: cytogenetic studies, restriction fragment length polymorphism (RFLP) analyses with 8 probes spanning commonly deleted loci on chromosomes 3p, 13q and 17p, retinoblastoma gene product (RE) expression, and mutations in the I as and p53 genes. We also summarize previously published data on in vitro chemosensitivity patterns and and MDRI gene expression. Our studies demonstrate that all three of the NE cell subtypes have their own distinctive genotypes and phenotypes, each having some similarities and dissimilarities with SCLC and NSCLC. C1 UNIV TEXAS,SW MED CTR,SIMMONS CANC CTR,DALLAS,TX 75235. UNIV TEXAS,SW MED CTR,DEPT PATHOL,DALLAS,TX 75235. NCI,MED ONCOL BRANCH,BETHESDA,MD. NCI,MED BRANCH,BETHESDA,MD 20892. NCI,FREDERICK CANC RES FACIL 2,IMMUNOL LAB,FREDERICK,MD. RI kaye, frederic/E-2437-2011; OI Mitsudomi, Tetsuya/0000-0001-9860-8505 NR 45 TC 29 Z9 30 U1 1 U2 1 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDNTIOU-KALAMOU RD KAPANDRITI, POB 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD MAR-APR PY 1995 VL 15 IS 2 BP 225 EP 231 PG 7 WC Oncology SC Oncology GA QZ543 UT WOS:A1995QZ54300001 PM 7762988 ER PT J AU BERGAN, RC KYLE, E CONNELL, Y NECKERS, L AF BERGAN, RC KYLE, E CONNELL, Y NECKERS, L TI INHIBITION OF PROTEIN-TYROSINE KINASE-ACTIVITY IN INTACT-CELLS BY THE APTAMERIC ACTION OF OLIGODEOXYNUCLEOTIDES SO ANTISENSE RESEARCH AND DEVELOPMENT LA English DT Article ID ABL AB Direct interaction of oligodeoxynucleotides (ODNs) with proteins represents one of the nonantisense-mediated effects of ODNs. Phosphorothioate-capped ODNs have been shown to inhibit directly the in vitro kinase activity of the chronic myelogenous leukemia-associated protein-tyrosine kinase p210(bcr-abl). In this study we have determined the efficacy of this aptameric ODN in a cellular system using the K562 chronic myelogenous leukemia-derived cell line, Significant effects upon cellular phosphotyrosine content, as well as cellular growth in soft agar, are observed. These effects are sequence specific and are not mediated through changes in p2l0(bcr-abl) protein levels. Additional ODNs are described that also reduce cellular phosphotyrosine levels and inhibit growth in soft agar but do not inhibit p210(bcr-abl) kinase activity in vitro. C1 NCI,CLIN PHARMACOL BRANCH,BETHESDA,MD 20892. RP BERGAN, RC (reprint author), NCI,MED ONCOL BRANCH,BLDG 10,ROOM 12N226,BETHESDA,MD 20892, USA. NR 18 TC 35 Z9 35 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1050-5261 J9 ANTISENSE RES DEV JI Antisense Res. Dev. PD SPR PY 1995 VL 5 IS 1 BP 33 EP 38 PG 6 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA QU701 UT WOS:A1995QU70100005 PM 7542047 ER PT J AU BUCKHEIT, RW FLIAKASBOLTZ, V DECKER, WD ROBERSON, JL STUP, TL PYLE, CA WHITE, EL MCMAHON, JB CURRENS, MJ BOYD, MR BADER, JP AF BUCKHEIT, RW FLIAKASBOLTZ, V DECKER, WD ROBERSON, JL STUP, TL PYLE, CA WHITE, EL MCMAHON, JB CURRENS, MJ BOYD, MR BADER, JP TI COMPARITIVE ANTI-HIV EVALUATION OF DIVERSE HIV-1-SPECIFIC REVERSE-TRANSCRIPTASE INHIBITOR-RESISTANT VIRUS ISOLATES DEMONSTRATES THE EXISTENCE OF DISTINCT PHENOTYPIC SUBGROUPS SO ANTIVIRAL RESEARCH LA English DT Article DE HIV-1-SPECIFIC INHIBITOR; ANTI-HIV ACTIVITY; COMBINATION THERAPY; DRUG RESISTANCE; PHENOTYPIC SUBGROUPS ID HUMAN-IMMUNODEFICIENCY; NONNUCLEOSIDE INHIBITORS; ANTIVIRAL ACTIVITY; TIBO DERIVATIVES; ANGSTROM RESOLUTION; CRYSTAL-STRUCTURE; NATURAL-PRODUCTS; VIRAL RESISTANCE; ZIDOVUDINE AZT; TYPE-1 AB We have biologically and biochemically evaluated a structurally diverse group of HIV-l-specific reverse transcriptase (RT) inhibitors and determined that the members of this class share many common properties. These include reproducible and selective antiviral activity against a panel of biologically distinct laboratory and clinical strains of HIV-1, activity against HIV-1 in a wide variety of cultured and fresh human cells, and potent inhibition of HIV-1 RT when evaluated using a heteropolymeric ribosomal RNA template assay. Each of the HIV-l-specific compounds was capable of inhibiting HIV replication when challenged at high m.o.i., further distinguishing them from the nucleoside analogs 3'-azido-3'-deoxythymidine (AZT) and 2',3'-dideoxycytidine (ddC). When tested in combination with AZT, each of the HIV-l-specific compounds synergistically inhibited the replication of HIV-1. HIV-1 isolates resistant to different HIV-l-specific inhibitors exhibited heterogeneous patterns of cross-resistance to other members of this pharmaco-logic class. Four distinct phenotypic classes have been defined through the use of drug-resistant virus isolates which derive from distinct mutations in the RT. These results indicate that the various subgroups of HIV-1-specific inhibitors interact differently with HIV-1 RT, suggesting important potential implications for drug combination therapeutic strategies. C1 SO RES INST,DEPT MICROBIOL RES,BIRMINGHAM,AL 35255. NCI,DIV CANC TREATMENT,DRUG DISCOVERY RES & DEV LAB,DEV THERAPEUT PROGRAM,FREDERICK,MD 21702. NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,ANTIVIRAL EVALUAT BRANCH,BETHESDA,MD 20892. RP BUCKHEIT, RW (reprint author), FREDERICK CANC RES & DEV CTR,SO RES INST,VIROL RES GRP,431 AVIAT WAY,FREDERICK,MD 21701, USA. FU NCI NIH HHS [N01-CM-37818]; NIAID NIH HHS [P30 AI27767, N01-AI-05087] NR 50 TC 59 Z9 60 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-3542 J9 ANTIVIR RES JI Antiviral Res. PD MAR PY 1995 VL 26 IS 2 BP 117 EP 132 DI 10.1016/0166-3542(94)00069-K PG 16 WC Pharmacology & Pharmacy; Virology SC Pharmacology & Pharmacy; Virology GA QN651 UT WOS:A1995QN65100002 PM 7541618 ER PT J AU RIOS, M MUNOZ, M TORRENCE, PF SPENCER, E AF RIOS, M MUNOZ, M TORRENCE, PF SPENCER, E TI EFFECT OF INTERFERON AND 2',5'-OLIGOADENYLATES ON ROTAVIRUS RNA-SYNTHESIS SO ANTIVIRAL RESEARCH LA English DT Article DE INTERFERON; 2',5'-OLIGOADENYLATE; ROTAVIRUS ID DOUBLE-STRANDED-RNA; TREATED HELA-CELLS; MESSENGER-RNA; ACTIVATION; ENDORIBONUCLEASE; INHIBITION; (2'-5')OLIGOADENYLATE; POLYMERASE; VIRUS; REPLICATION AB Based on the antiviral effect of interferon on rotavirus replication the inhibitory effect of 2',5'-oligoadenylates on MRNA and double-stranded RNA synthesis was studied using an in vitro assay. The chemically synthesized olgonucleotides were used to determine several characteristics of the inhibitory effect, such as chain length, presence of phosphate residues at the 5'-end, and the 2',5'-phosphodiester bond itself. In vitro transcription was inhibited by oligos with 5 or more adenine residues at a final concentration of 100 mu M or greater. This result makes rotavirus transcriptase different from other viruses in which the inhibitory effects are associated with dinucleotides and trinucleotides. The inhibitory effect was increased when the oligo contained a phosphate residue at the 5'-end; in this case, inhibition was also seen at lower oligo concentrations as well as at shorter oligo chain length. The study of the kinetics of inhibition showed that the inhibition by p(A2'p5')(3)3A was competitive with a K-i value of 256 mu M. The effect of the oligonucleotides on the in vitro viral RNA replication showed that the 2',5'-oligoadenylates were not able to significantly inhibit the in vitro rotavirus RNA synthesis. The lack of inhibition in the in vitro assay was very peculiar since RNA transcription and replication involves the viral RNA polymerase, VP1. C1 UNIV CHILE,INST NUTR & TECNOL ALIMENTOS,UNIDAD VIROL,SANTIAGO 11,CHILE. NIDDKD,MED CHEM LAB,BIOMED CHEM SECT,BETHESDA,MD 20892. NR 24 TC 1 Z9 1 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-3542 J9 ANTIVIR RES JI Antiviral Res. PD MAR PY 1995 VL 26 IS 2 BP 133 EP 143 DI 10.1016/0166-3542(94)00070-O PG 11 WC Pharmacology & Pharmacy; Virology SC Pharmacology & Pharmacy; Virology GA QN651 UT WOS:A1995QN65100003 PM 7605112 ER PT J AU ZONDERMAN, AB GIAMBRA, LM ARENBERG, D RESNICK, SM COSTA, PT AF ZONDERMAN, AB GIAMBRA, LM ARENBERG, D RESNICK, SM COSTA, PT TI CHANGES IN IMMEDIATE VISUAL MEMORY PREDICT COGNITIVE IMPAIRMENT SO ARCHIVES OF CLINICAL NEUROPSYCHOLOGY LA English DT Article ID ADRDA WORK GROUP; ALZHEIMERS-DISEASE; CLINICAL-DIAGNOSIS; RETENTION TEST; OLD-AGE; DEMENTIA AB Six-year changes in immediate visual memory performance assessed by the Benton Visual Retention (BVR) test predicted Alzheimer's disease (AD) prior to its onset. Subjects of this study were 371 community-dwelling adult participants in the Baltimore Longitudinal Study of Aging, seven of whom received probable or definite AD diagnoses using DSM-III-R and NINCDS-ADRDA criteria. Subjects with diagnoses of AD had larger changes in immediate memory performance over the 6-year interval prior to the estimated onset of their disease than subjects without AD. Six-year longitudinal change as well as level in immediate visual memory performance also predicted subsequent cognitive performance 6-15 and 16-22 years later even after adjusting for the influences of age general-ability and initial immediate memory. These results provide evidence that change and level in immediate visual memory performance has long-term prognostic significance over as many as 16-22 years. These results further suggest that change in recent memory performance, an important component in AD diagnoses, may be an important precursor of the development of the disease. C1 JOHNS HOPKINS UNIV,SCH MED,BALTIMORE,MD. RP ZONDERMAN, AB (reprint author), NIA,GERONTOL RES CTR,PERSONAL & COGNIT LAB,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. OI Costa, Paul/0000-0003-4375-1712; Zonderman, Alan B/0000-0002-6523-4778 NR 31 TC 58 Z9 59 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0887-6177 J9 ARCH CLIN NEUROPSYCH JI Arch. Clin. Neuropsychol. PD MAR-APR PY 1995 VL 10 IS 2 BP 111 EP 123 DI 10.1016/0887-6177(94)00040-9 PG 13 WC Psychology, Clinical; Psychology SC Psychology GA QJ432 UT WOS:A1995QJ43200004 PM 14589733 ER PT J AU BLAUVELT, A PLOTT, RT SPOONER, K STEARN, B DAVEY, RT TURNER, ML AF BLAUVELT, A PLOTT, RT SPOONER, K STEARN, B DAVEY, RT TURNER, ML TI EOSINOPHILIC FOLLICULITIS ASSOCIATED WITH THE ACQUIRED-IMMUNODEFICIENCY-SYNDROME RESPONDS WELL TO PERMETHRIN SO ARCHIVES OF DERMATOLOGY LA English DT Letter ID PUSTULAR FOLLICULITIS; INFECTION RP BLAUVELT, A (reprint author), NCI,DERMATOL BRANCH,BLDG 10,BETHESDA,MD 20892, USA. NR 5 TC 30 Z9 30 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD MAR PY 1995 VL 131 IS 3 BP 360 EP 361 DI 10.1001/archderm.131.3.360 PG 2 WC Dermatology SC Dermatology GA QM006 UT WOS:A1995QM00600025 PM 7887675 ER PT J AU WYATT, RJ AF WYATT, RJ TI RISKS OF WITHDRAWING ANTIPSYCHOTIC MEDICATIONS SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Note ID CHRONIC-SCHIZOPHRENIC PATIENTS; NEUROLEPTIC WITHDRAWAL; NATURAL COURSE; LONG-TERM; DISCONTINUATION; MAINTENANCE; TRIAL; DRUG; OUTPATIENTS; DURATION RP WYATT, RJ (reprint author), NIMH,ST ELIZABETHS HOSP,CTR NEUROSCI,NEUROPSYCHIAT BRANCH,2700 MARTIN LUTHER KING JR AVE,WASHINGTON,DC 20032, USA. NR 29 TC 30 Z9 31 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD MAR PY 1995 VL 52 IS 3 BP 205 EP 208 PG 4 WC Psychiatry SC Psychiatry GA QL313 UT WOS:A1995QL31300007 PM 7872847 ER PT J AU SMITH, GR ROST, K KASHNER, TM AF SMITH, GR ROST, K KASHNER, TM TI A TRIAL OF THE EFFECT OF A STANDARDIZED PSYCHIATRIC-CONSULTATION ON HEALTH OUTCOMES AND COSTS IN SOMATIZING PATIENTS SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID SOMATIZATION DISORDER; MEDICAL OUTCOMES; COMMUNITY; DISABILITY; DEPRESSION; SYMPTOMS AB Background: Patients who somatize but who do not meet criteria for somatization disorder are common in the community. Virtually no research has been conducted to determine how to treat these patients. Methods: We conducted a randomized controlled clinical trial of a psychiatric consultation intervention we had previously shown to improve the management of somatization disorder. The study population included 51 physicians treating 56 somatizing patients who had a history of seeking help for six to 12 lifetime unexplained physical symptoms. At the onset of the experiment, physicians randomized to the treatment condition received a consultation letter recommending a specific management approach; physicians randomized to the control/crossover condition received the consultation letter after 12 months. Data on health outcomes and charges were collected every 4 months for 2 years after randomization for 96% of subjects who entered the study. Results: Patients of physicians who received the intervention reported significantly increased physical functioning, an improvement that remained stable during the year after the intervention. The intervention reduced annual medical care charges by $289 (95% confidence interval, $40 to $464) in 1990 constant dollars, which equates to a 32.9% reduction in the annual median cost of their medical care. Conclusions: Somatizing patients with a lifetime history of six to 12 unexplained physical symptoms reported better physical functioning after their primary care physician was provided appropriate treatment recommendations via a psychiatric consultation. Such a consultation is cost-effective because it reduces subsequent charges for medical care, while improving health outcomes in a chronically impaired population. C1 UNIV ARKANSAS MED SCI HOSP,NIMH,CTR RURAL MENTAL HEALTHCARE RES,DEPT PSYCHIAT & BEHAV SCI,LITTLE ROCK,AR. VET AFFAIRS HLTH SERV,RES & DEV FIELD PROGRAM MENTAL HLTH,LITTLE ROCK,AR. UNIV TEXAS,SW MED SCH,DEPT PSYCHIAT,DALLAS,TX. VET AFFAIRS MED CTR,RES SERV,DALLAS,TX. FU NIMH NIH HHS [R01 MH46090, P50 MH48197] NR 28 TC 193 Z9 196 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD MAR PY 1995 VL 52 IS 3 BP 238 EP 243 PG 6 WC Psychiatry SC Psychiatry GA QL313 UT WOS:A1995QL31300012 PM 7872852 ER PT J AU THEODORE, WH AF THEODORE, WH TI PHENYTOIN AND CEREBELLAR ATROPHY SO ARCHIVES OF NEUROLOGY LA English DT Letter RP THEODORE, WH (reprint author), NIH,BLDG 10,ROOM 5C-205,BETHESDA,MD 20892, USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD MAR PY 1995 VL 52 IS 3 BP 232 EP 232 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA QK739 UT WOS:A1995QK73900006 PM 7872873 ER PT J AU KADOR, PF TAKAHASHI, Y WYMAN, M FERRIS, F AF KADOR, PF TAKAHASHI, Y WYMAN, M FERRIS, F TI DIABETESLIKE PROLIFERATIVE RETINAL CHANGES IN GALACTOSE-FED DOGS SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID ALDOSE REDUCTASE; RETINOPATHY AB Objective: To determine whether diabeteslike lesions associated with the proliferative stage of diabetic retinopathy develop in galactose-fed dogs, since studies designed to define the complex biochemical effects of prolonged hyperglycemia on retinal vessels have been hampered by the lack of an animal model that mirrors both the early and advanced stages of diabetic retinopathy. Methods: Eyes from 9-month-old male beagles fed a daily diet containing either 30% nonnutrient filler (control diet) or 30% galactose (galactose diet) for up to 84 months were enucleated and histologically examined. Results: Retinal vessel changes associated with the proliferative stage were observed in two of nine galactose-fed dogs while the remainder demonstrated retinal changes that included the appearance of microaneurysms, acellular capillary beds associated with areas of nonperfusion, and intraretinal microvascular abnormalities. Proliferative changes were evidenced by the formation of preretinal fibrous membranes and the appearance of fibrovascular membranes on the retinal surface and on the posterior hyaloid membrane. No retinal lesions were observed in similar dogs fed a control diet for up to 84 months. Conclusion: The galactose-fed dog appears to be the first animal model that can develop diabeteslike retinal vessel changes associated with both the early and advanced stages of retinopathy, including the proliferative stage. RP KADOR, PF (reprint author), NEI,OCULAR THERAPEUT LAB,BLDG 10,ROOM 10B11,BETHESDA,MD 20892, USA. NR 12 TC 52 Z9 57 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD MAR PY 1995 VL 113 IS 3 BP 352 EP 354 PG 3 WC Ophthalmology SC Ophthalmology GA QL316 UT WOS:A1995QL31600021 PM 7887849 ER PT J AU MALLOY, MH GRAUBARD, B AF MALLOY, MH GRAUBARD, B TI ACCESS TO HOME APNEA MONITORING AND ITS IMPACT ON REHOSPITALIZATION AMONG VERY-LOW-BIRTH-WEIGHT INFANTS SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE LA English DT Article ID BRONCHOPULMONARY DYSPLASIA; RESPIRATORY ILLNESS; RE-HOSPITALIZATION; DEATH SYNDROME; MORTALITY; HEALTH; SURVIVORS; MORBIDITY; GROWTH AB Objective: To examine the relationship between home apnea monitoring and sociodemographic, socioeconomic, and medical factors and the risk for rehospitalization among very-low-birth-weight infants (birth weight (1500 g). Design and Setting: Analysis of live infants born weighing less than 1500 g; these data were obtained from the 1988 National Maternal and Infant Health Survey. Data from this survey were obtained by maternal questionnaires and from birth certificates and medical records. Outcome Measure: One or more hospitalizations after discharge from the hospital of delivery. Results: Home apnea monitor use was strikingly lower among black infants (19.8%) compared with nonblack infants (43.7%) (P<.001). The rate of rehospitalization for blacks was 24.8%, which was lower than the rate of 34.3% for nonblacks (P=.001). Neither annual family in-come nor method of hospital payment was associated with rehospitalization. The use of an apnea monitor in the home was associated with an increased odds ratio for rehospitalization for both blacks (odds ratio, 2.56; 95% confidence interval, 1.56 to 4.21) and nonblacks (odds ratio, 2.28; 95% confidence interval, 1.51 to 3.45). With adjustment for the use of an apnea monitor, the odds ratio for rehospitalization of blacks vs nonblacks was no longer significant (odds ratio, 0.80; 95% confidence interval, 0.60 to 1.08). Conclusions: The use of an apnea monitor in the home was highly associated with an increased risk for rehospitalization. Whether this increased risk was attributable to a valid reason for rehospitalization or to closer scrutiny of the infant could not be determined. The lower prevalence of apnea monitor use among blacks is unexplained. C1 NCI,BETHESDA,MD 20892. RP MALLOY, MH (reprint author), UNIV TEXAS,MED BRANCH,DEPT PEDIAT,GALVESTON,TX 77555, USA. FU NHLBI NIH HHS [R03-HL48932] NR 31 TC 7 Z9 7 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 1072-4710 J9 ARCH PEDIAT ADOL MED JI Arch. Pediatr. Adolesc. Med. PD MAR PY 1995 VL 149 IS 3 BP 326 EP 332 PG 7 WC Pediatrics SC Pediatrics GA QK484 UT WOS:A1995QK48400020 PM 7858696 ER PT J AU IKEWAKI, K ZECH, LA KINDT, M BREWER, HB RADER, DJ AF IKEWAKI, K ZECH, LA KINDT, M BREWER, HB RADER, DJ TI APOLIPOPROTEIN A-II PRODUCTION-RATE IS A MAJOR FACTOR REGULATING THE DISTRIBUTION OF APOLIPOPROTEIN-A-I AMONG HDL SUBCLASSES LPA-I AND LPA-I-A-II IN NORMOLIPIDEMIC HUMANS SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE APOA-I; APOA-II; KINETICS; RADIOTRACER; HDLS ID HIGH-DENSITY-LIPOPROTEIN; CORONARY-ARTERY DISEASE; FRACTIONAL CATABOLIC RATE; TRANSGENIC MICE; CHOLESTEROL LEVELS; HEART-DISEASE; PARTICLES; ATHEROSCLEROSIS; METABOLISM; GENE AB HDLs are heterogeneous in their apolipoprotein composition. Apolipoprotein (ape) A-I and apoA-II are the major proteins found in HDL and form the two major HDL subclasses: those that contain only apoA-I (LpA-I) and those that contain both apoA-I and apoA-II (LpA-I:A-II). Substantial evidence indicates that these two subclasses differ in their in vivo metabolism and effect on atherosclerosis, with LpA-I the more specifically protective subfraction against atherosclerosis. The purpose of this study was to investigate the effect of apoA-I: and apoA-II production and catabolism on plasma LpA-I and LpA-I:A-II levels. Fifty normolipidemic subjects (those with HDL cholesterol levels in the top and bottom tenth percentiles were excluded) underwent kinetic studies with radiolabeled apoA-I and apoA-II, and the kinetic parameters of apoA-I and apoA-II were correlated with LpA-I and LpA-I:A-II levels. ApoA-I levels were strongly correlated with apoA-I residence times and less strongly correlated with apoA-I production rates. In contrast, apoA-II levels were correlated only with apoA-II production rates and not with apoA-II residence times. Levels of apoA-I in LpA-I were correlated with apoA-I residence times, whereas levels of apoA-I in LpA-I:A-II were correlated primarily with apoA-II production rates. The fraction of apoA-I in LpA-I was highly inversely correlated with apoA-II production rate (r=-.67, P<.001). In multiple regression analysis, apoA-II production rate was the most significant independent variable determining percent apoA-I in LpA-I among all the kinetic parameters. These results indicate that in normolipidemic individuals (1) apoA-I levels are regulated primarily by apoA-I catabolism and apoA-II levels by apoA-II production; (2) the rate of catabolism of apoA-I is an important factor determining LpA-I levels, while the rate of apoA-II production is the major determinant of the amount of apoA-I in LpA-I:A-II; and (3) the rate of apoA-II production is a major factor determining the distribution of apoA-I between LpA-I and LpA-I:A-II, thereby possibly modulating susceptibility to atherosclerosis in humans. C1 NHLBI,MOLEC DIS BRANCH,BETHESDA,MD 20892. NR 32 TC 68 Z9 70 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscl. Thromb. Vasc. Biol. PD MAR PY 1995 VL 15 IS 3 BP 306 EP 312 PG 7 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA QL090 UT WOS:A1995QL09000002 PM 7749839 ER PT J AU THORP, BH JAKOWLEW, SB GODDARD, C AF THORP, BH JAKOWLEW, SB GODDARD, C TI AVIAN DYSCHONDROPLASIA - LOCAL DEFICIENCIES IN GROWTH-FACTORS ARE INTEGRAL TO THE ETIOPATHOGENESIS SO AVIAN PATHOLOGY LA English DT Article ID TIBIAL DYSCHONDROPLASIA; FACTOR-BETA; FACTOR-I; BONE-CELLS; CHONDROCYTES; CARTILAGE; HORMONE; PLATE; EXPRESSION; CHICKENS AB Rabbit polyclonal antibodies to chicken transforming growth factor-beta 3 (TGF-beta 3) and to insulin-like growth factor-I (IGF-I) were used to detect the two growth factors in normal and dyschondroplastic broiler growth plates (physes). Histomorphometry was used to estimate the percentage of chondrocytes containing IGF-I and TGF-beta 3 in the lower proliferative, transitional and hypertrophic zones of the growth plate. In the normal chick growth plates IGF-I was present in 63% of transitional chondrocytes and in 67% of hypertrophic chondrocytes and TGF-beta 3 was present in 81% of transitional chondrocytes and in 93% of hypertrophic chondrocytes. Both growth factors were found to be deficient within transitional chondrocytes at sites of dyschondroplasia, a condition in which there is a local defect in chondrocyte differentiation and the subsequent replacement of the cartilage by bone. In addition, both growth factors were identified in chondrocytes within areas of repair, where chondrocyte differentiation and endochondral ossification have resumed. This supports the hypothysis that the reduction in TGF-beta 3 and IGF-I in dyschondroplasia is integral to the aetiopathogenesis and indicative that both these growth factors are part of the cascade of events associated with chondrocyte differentiation during endochondral ossification. C1 NCI,BIOMARKERS & PREVENT RES BRANCH,ROCKVILLE,MD 20850. RP THORP, BH (reprint author), ROSLIN INST EDINBURGH,ROSLIN EH25 9PS,MIDLOTHIAN,SCOTLAND. NR 41 TC 21 Z9 22 U1 0 U2 1 PU WORLD VETERINARY POULTRY ASSN PI NEWBURY PA INSTITUTE ANIMAL HEALTH, COMPTON LABORATORY, COMPTON NR, NEWBURY, BERKS, ENGLAND RG16, ONN SN 0307-9457 J9 AVIAN PATHOL JI Avian Pathol. PD MAR PY 1995 VL 24 IS 1 BP 135 EP 148 DI 10.1080/03079459508419054 PG 14 WC Veterinary Sciences SC Veterinary Sciences GA QQ141 UT WOS:A1995QQ14100010 PM 18645771 ER PT J AU HIBBS, J YOUNG, NS AF HIBBS, J YOUNG, NS TI VIRUSES, VIRULENCE AND PATHOGENICITY SO BAILLIERES CLINICAL HAEMATOLOGY LA English DT Review ID PROGRAMMED CELL-DEATH; HEPATITIS-C VIRUS; LYMPHOCYTIC CHORIOMENINGITIS VIRUS; TUMOR-NECROSIS-FACTOR; DEPENDENT DIABETES-MELLITUS; RETINOBLASTOMA GENE-PRODUCT; MYELIN BASIC-PROTEIN; MULTIPLE-SCLEROSIS; APLASTIC-ANEMIA; IMMUNODEFICIENCY-VIRUS C1 NHLBI,HEMATOL BRANCH,BETHESDA,MD 20892. RP HIBBS, J (reprint author), UNIV MINNESOTA HOSP,DEPT INTERNAL MED,DIV INFECT DIS,MINNEAPOLIS,MN 55455, USA. NR 213 TC 1 Z9 1 U1 0 U2 1 PU BAILLIERE TINDALL PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0950-3536 J9 BAILLIERE CLIN HAEM JI Baillieres Clin. Haematol. PD MAR PY 1995 VL 8 IS 1 BP 1 EP 23 DI 10.1016/S0950-3536(05)80230-6 PG 23 WC Hematology SC Hematology GA QW108 UT WOS:A1995QW10800002 PM 7663043 ER PT J AU YOUNG, NS AF YOUNG, NS TI B19 PARVOVIRUS SO BAILLIERES CLINICAL HAEMATOLOGY LA English DT Review ID RED-CELL APLASIA; SYSTEMIC LUPUS-ERYTHEMATOSUS; LINKED-IMMUNOSORBENT-ASSAY; INFECTIOSUM 5TH DISEASE; BONE-MARROW NECROSIS; HEREDITARY SPHEROCYTOSIS; CANINE PARVOVIRUS; HEMOLYTIC-ANEMIA; PROGENITOR CELLS; PARVOVIRUS-B19-RELATED PANCYTOPENIA RP YOUNG, NS (reprint author), NHLBI,HEMATOL BRANCH,BLDG 10,BETHESDA,MD 20892, USA. NR 186 TC 24 Z9 25 U1 0 U2 1 PU BAILLIERE TINDALL PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0950-3536 J9 BAILLIERE CLIN HAEM JI Baillieres Clin. Haematol. PD MAR PY 1995 VL 8 IS 1 BP 25 EP 56 DI 10.1016/S0950-3536(05)80231-8 PG 32 WC Hematology SC Hematology GA QW108 UT WOS:A1995QW10800003 PM 7663050 ER PT J AU FRANCHINI, G STREICHER, H AF FRANCHINI, G STREICHER, H TI HUMAN T-CELL LEUKEMIA-VIRUS SO BAILLIERES CLINICAL HAEMATOLOGY LA English DT Review ID LEUKEMIA-LYMPHOMA VIRUS; TROPICAL SPASTIC PARAPARESIS; I-ASSOCIATED MYELOPATHY; PAPUA-NEW-GUINEA; COMPLETE NUCLEOTIDE-SEQUENCE; OPEN READING FRAME; NON-HUMAN PRIMATES; HTLV-I; INTERLEUKIN-2 RECEPTOR; GENE-EXPRESSION RP FRANCHINI, G (reprint author), NCI,TUMOR CELL BIOL LAB,ANIM MODEL & VACCINE SECT,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 108 TC 9 Z9 9 U1 0 U2 0 PU BAILLIERE TINDALL PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0950-3536 J9 BAILLIERE CLIN HAEM JI Baillieres Clin. Haematol. PD MAR PY 1995 VL 8 IS 1 BP 131 EP 148 DI 10.1016/S0950-3536(05)80235-5 PG 18 WC Hematology SC Hematology GA QW108 UT WOS:A1995QW10800007 PM 7663044 ER PT J AU SING, GK RUSCETTI, FW AF SING, GK RUSCETTI, FW TI THE ROLE OF HUMAN CYTOMEGALOVIRUS IN HEMATOLOGICAL DISEASES SO BAILLIERES CLINICAL HAEMATOLOGY LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; BONE-MARROW TRANSPLANTATION; BLOOD MONONUCLEAR-CELLS; TUMOR-NECROSIS-FACTOR; HEMATOPOIETIC PROGENITOR CELLS; HUMAN PERIPHERAL-BLOOD; LONG TERMINAL REPEAT; INSITU HYBRIDIZATION; VIRAL REPLICATION; GENE-EXPRESSION C1 NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,LEUKOCYTE BIOL LAB,FREDERICK,MD 21702. RP SING, GK (reprint author), ROYAL BRISBANE HOSP FDN,BANCROFT CTR,CLIN RES CTR,BRISBANE,QLD 4029,AUSTRALIA. NR 93 TC 13 Z9 13 U1 1 U2 1 PU BAILLIERE TINDALL PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0950-3536 J9 BAILLIERE CLIN HAEM JI Baillieres Clin. Haematol. PD MAR PY 1995 VL 8 IS 1 BP 149 EP 163 DI 10.1016/S0950-3536(05)80236-7 PG 15 WC Hematology SC Hematology GA QW108 UT WOS:A1995QW10800008 PM 7663045 ER PT J AU LUSSO, P GALLO, RC AF LUSSO, P GALLO, RC TI HUMAN HERPESVIRUS-6 SO BAILLIERES CLINICAL HAEMATOLOGY LA English DT Review ID POLYMERASE CHAIN-REACTION; VIRUS HUMAN HERPESVIRUS-6; PRIMARY CYTOMEGALOVIRUS-INFECTION; NEUTRALIZING ANTIBODY-RESPONSE; BONE-MARROW TRANSPLANTATION; EPSTEIN-BARR-VIRUS; EXANTHEM-SUBITUM; LYMPHOTROPIC VIRUS; T-CELLS; FULMINANT-HEPATITIS RP NCI, TUMOR CELL BIOL LAB, BLDG 37, ROOM 6D30, 9000 ROCKVILLE PIKE, BETHESDA, MD 20892 USA. NR 145 TC 14 Z9 14 U1 0 U2 1 PU BAILLIERE TINDALL PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0950-3536 J9 BAILLIERE CLIN HAEM JI Baillieres Clin. Haematol. PD MAR PY 1995 VL 8 IS 1 BP 201 EP 223 DI 10.1016/S0950-3536(05)80238-0 PG 23 WC Hematology SC Hematology GA QW108 UT WOS:A1995QW10800010 PM 7663047 ER PT J AU RUSCETTI, SK AF RUSCETTI, SK TI ERYTHROLEUKEMIA INDUCTION BY THE FRIEND SPLEEN FOCUS-FORMING VIRUS SO BAILLIERES CLINICAL HAEMATOLOGY LA English DT Review ID PROTEIN TYROSINE PHOSPHORYLATION; MURINE ERYTHROPOIETIN RECEPTOR; ERYTHROID CELL-PROLIFERATION; ENV-GENE; MEMBRANE GLYCOPROTEIN; ENVELOPE GENE; TRANSCRIPTION FACTOR; GP55 GLYCOPROTEIN; PROGENITOR CELLS; LEUKEMIA-VIRUS RP RUSCETTI, SK (reprint author), NCI,FREDERICK CANC RES & DEV CTR,MOLEC ONCOL LAB,FREDERICK,MD 21702, USA. NR 125 TC 20 Z9 20 U1 0 U2 0 PU BAILLIERE TINDALL PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0950-3536 J9 BAILLIERE CLIN HAEM JI Baillieres Clin. Haematol. PD MAR PY 1995 VL 8 IS 1 BP 225 EP 247 DI 10.1016/S0950-3536(05)80239-2 PG 23 WC Hematology SC Hematology GA QW108 UT WOS:A1995QW10800011 PM 7663048 ER PT J AU YOUNG, NS AF YOUNG, NS TI VIRUSES AS AGENTS OF HEMATOLOGICAL DISEASE - PREFACE SO BAILLIERES CLINICAL HAEMATOLOGY LA English DT Editorial Material RP YOUNG, NS (reprint author), NHLBI,HEMATOL BRANCH,BLDG 10,BETHESDA,MD 20892, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BAILLIERE TINDALL PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0950-3536 J9 BAILLIERE CLIN HAEM JI Baillieres Clin. Haematol. PD MAR PY 1995 VL 8 IS 1 BP R9 EP R9 DI 10.1016/S0950-3536(05)80229-X PG 1 WC Hematology SC Hematology GA QW108 UT WOS:A1995QW10800001 ER PT J AU WALSH, TJ LYMAN, CA PIZZO, PA AF WALSH, TJ LYMAN, CA PIZZO, PA TI LABORATORY DIAGNOSIS OF INVASIVE FUNGAL-INFECTIONS IN PATIENTS WITH NEOPLASTIC DISEASES SO BAILLIERES CLINICAL INFECTIOUS DISEASES LA English DT Review ID LATEX AGGLUTINATION-TEST; BLOOD CULTURE SYSTEM; BONE-MARROW TRANSPLANTATION; LINKED IMMUNOSORBENT-ASSAY; MAJOR CYTOPLASMIC ANTIGEN; POLYMERASE CHAIN-REACTION; DOT-IMMUNOBINDING ASSAY; CANDIDA-ALBICANS; CANCER-PATIENTS; LYSIS-CENTRIFUGATION C1 UNIFORMED SERV UNIV HLTH SCI,BETHESDA,MD. RP WALSH, TJ (reprint author), NCI,PEDIAT BRANCH,INFECT DIS SECT,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 219 TC 7 Z9 7 U1 0 U2 0 PU BAILLIERE TINDALL PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 1071-6564 J9 BAILLIERE CLIN INF D JI Baillieres Clin. Infect. Dis. PD MAR PY 1995 VL 2 IS 1 BP 25 EP 70 PG 46 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA QY221 UT WOS:A1995QY22100004 ER PT J AU FREED, WJ SMITH, TD AF FREED, WJ SMITH, TD TI PRINCIPLES OF BRAIN-TISSUE ENGINEERING SO BEHAVIORAL AND BRAIN SCIENCES LA English DT Discussion ID ADRENAL-MEDULLA GRAFTS; PARKINSONS-DISEASE; ASTROGLIAL CELLS; CAUDATE-NUCLEUS; TRANSPLANTATION; AUTOGRAFT; RECEPTORS; RECOVERY; SURVIVAL AB It is often presumed that effects of neural tissue tranplants are due to release of neurotransmitter. In many cases, however, effects attributed to transplants may be related to phenomena such as trophic effects mediated by glial cells or even tissue reactions to injury. Any conclusion regarding causation of graft effects must be based on the control groups or other comparisons used. In human clinical studies, for example, comparing the same subject before and after transplantation allows for many interpretations of the causes of clinical changes. C1 ST ELIZABETH HOSP,NIMH,CTR NEUROSCI,CLIN BRAIN DISORDERS BRANCH,WASHINGTON,DC 20032. RP FREED, WJ (reprint author), ST ELIZABETH HOSP,NIMH,CTR NEUROSCI,NEUROPSYCHIAT BRANCH,2700 MARTIN LUTHER KING AVE,WASHINGTON,DC 20032, USA. NR 27 TC 0 Z9 0 U1 0 U2 1 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0140-525X J9 BEHAV BRAIN SCI JI Behav. Brain Sci. PD MAR PY 1995 VL 18 IS 1 BP 58 EP 60 PG 3 WC Psychology, Biological; Behavioral Sciences; Neurosciences SC Psychology; Behavioral Sciences; Neurosciences & Neurology GA QY120 UT WOS:A1995QY12000017 ER PT J AU STANFIELD, BB AF STANFIELD, BB TI DIFFICULTIES INHERENT IN THE RESTORATION OF DYNAMICALLY REACTIVE BRAIN SYSTEMS SO BEHAVIORAL AND BRAIN SCIENCES LA English DT Discussion ID CORTICAL-NEURONS; REORGANIZATION AB The responses displayed by an injured or diseased nervous system are complex. Some of the responses may effect a functional reorganization of the affected neural circuitry. Strategies aimed at the restoration of function, whether or not these involve transplantation, need to recognize the innate reactive capacity of the nervous system to damage. More successful strategies will probably incorporate, rather than ignore, the adaptive responses of the compromised neural systems. RP STANFIELD, BB (reprint author), NIMH,CTR ANIM,NEUROPHYSIOL LAB,POB 608,POOLESVILLE,MD 20837, USA. NR 8 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0140-525X J9 BEHAV BRAIN SCI JI Behav. Brain Sci. PD MAR PY 1995 VL 18 IS 1 BP 71 EP 71 PG 1 WC Psychology, Biological; Behavioral Sciences; Neurosciences SC Psychology; Behavioral Sciences; Neurosciences & Neurology GA QY120 UT WOS:A1995QY12000030 ER PT J AU SHIPPENBERG, TS BALSKUBIK, R AF SHIPPENBERG, TS BALSKUBIK, R TI INVOLVEMENT OF THE MESOLIMBIC DOPAMINE SYSTEM IN MEDIATING THE AVERSIVE EFFECTS OF OPIOID ANTAGONISTS IN THE RAT SO BEHAVIOURAL PHARMACOLOGY LA English DT Article DE CONDITIONED PLACE AVERSIONS; CTOP; MESOLIMBIC DOPAMINE SYSTEM; NALOXONE; OPIOID RECEPTOR ANTAGONISTS; PLACE PREFERENCE CONDITIONING; RAT; 6-HYDROXYDOPAMINE ID MOTIVATIONAL PROPERTIES; NUCLEUS-ACCUMBENS; RECEPTORS; KAPPA; MU; AGONISTS; OPIATE; PLACE; NALOXONE; RELEASE AB An unbiased place preference conditioning procedure was used to examine the neural substrates mediating the aversive effects of opioid antagonists in the rat. Microinjection of the non-selective opioid receptor antagonist naloxone into either the ventral tegmental area (VTA) or the nucleus accumbens (NAc) produced significant aversions for an environment previously paired with its administration. The minimum doses producing these effects were 10.0 and 7.5 mu g, respectively. Microinjections into either the caudate/putamen or medial prefrontal cortex were without effect. Place aversions of equivalent magnitude were also observed in response to the intra-VTA or intra-NAc administration of the highly selective mu opioid receptor antagonist CTOP. Doses as low as 0.3 mu g resulted in significant effects. 6-hydroxydopamine lesions of the NAc attenuated the aversive effect of intra-VTA CTOP. Such lesions did not modify the aversive effects of intra-NAc CTOP; they also failed to modify the aversive effects of systemically administered naloxone. These data demonstrate that the blockade of either VTA or NAc mu opioid receptors is sufficient for the expression of the aversive effects of opioid antagonists. Furthermore, they suggest that whereas the aversive effects of intracranially applied opioid antagonists may involve both a mesolimbic DA-dependent (VTA) and independent (NAc) component, the aversive effects produced by systemically administered opioid receptor antagonists are independent of mesolimbic DA neurons. C1 MAX PLANCK INST PSYCHIAT,INST CLIN,DEPT NEUROENDOCRINOL,DRUG ABUSE RES UNIT,W-8000 MUNICH 90,GERMANY. MAX PLANCK INST PSYCHIAT,DEPT NEUROPHARMACOL,W-8033 MARTINSRIED,GERMANY. RP SHIPPENBERG, TS (reprint author), NIDA,PRECLIN PHARMACOL LAB,INTRAMURAL RES PROGRAM,BEHAV PHARMACOL & GENET SECT,POB 5180,BALTIMORE,MD 21224, USA. NR 31 TC 34 Z9 34 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0955-8810 J9 BEHAV PHARMACOL JI Behav. Pharmacol. PD MAR PY 1995 VL 6 IS 2 BP 99 EP 106 PG 8 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA QP065 UT WOS:A1995QP06500001 ER PT J AU KATZ, JL ALLING, K SHORES, E WITKIN, JM AF KATZ, JL ALLING, K SHORES, E WITKIN, JM TI EFFECTS OF D1 DOPAMINE AGONISTS ON SCHEDULE-CONTROLLED BEHAVIOR IN THE SQUIRREL-MONKEY SO BEHAVIOURAL PHARMACOLOGY LA English DT Article DE (+)-AMPHETAMINE; COCAINE; D1 RECEPTOR AGONISTS; PSYCHOMOTOR STIMULANT EFFECTS; SKF 38393; SKF 75670; SKF 77434; SKF 81297; SKF 82958; SQUIRREL MONKEY ID RECEPTOR AGONISTS; COCAINE; ANTAGONISTS; COMBINATION; RAT; HYPERACTIVITY; EFFICACY; CYCLASE; DRUGS AB Behavioral effects of several dopamine D1 receptor agonists were compared with those of cocaine and (+)-amphetamine in squirrel monkeys trained to press a response key under a fixed-interval schedule of electric shock presentation. Cocaine (0.03 to 0.3 mg/kg) and (+)-amphetamine (0.01 to 0.1 mg/kg) at low to intermediate doses increased rates of responding under the fixed-interval schedule; at higher doses each of these drugs decreased response rates. In contrast, neither full nor partial D1 receptor agonists produced reliable increases in response rates. Rather, these drugs decreased rates of responding in a dose-related manner. These results with schedule-controled behavior in primates support earlier findings in rodents that indicate that D1 agonist actions result in effects quite different from the characteristic psychomotor stimulant effects produced by cocaine or (+)-amphetamine; and they further suggest that those characteristic stimulant effects are more probably due to stimulation of other dopamine receptors. RP KATZ, JL (reprint author), NIDA,DIV INTRAMURAL RES,ADDICT RES CTR,PSYCHOBIOL SECT,POB 5180,BALTIMORE,MD 21224, USA. OI Katz, Jonathan/0000-0002-1068-1159 NR 39 TC 14 Z9 14 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0955-8810 J9 BEHAV PHARMACOL JI Behav. Pharmacol. PD MAR PY 1995 VL 6 IS 2 BP 143 EP 148 PG 6 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA QP065 UT WOS:A1995QP06500006 ER PT J AU RASMUSSEN, G RASMUSSEN, C AF RASMUSSEN, G RASMUSSEN, C TI CALMODULIN-DEPENDENT PROTEIN-KINASE-II IS REQUIRED FOR G(1)/S PROGRESSION IN HELA-CELLS SO BIOCHEMISTRY AND CELL BIOLOGY-BIOCHIMIE ET BIOLOGIE CELLULAIRE LA English DT Article DE CALMODULIN; PROTEIN KINASE; CELL CYCLE; HELA ID ASPERGILLUS-NIDULANS; NUCLEAR-LOCALIZATION; BINDING PROTEIN; DNA-REPLICATION; MAMMALIAN-CELLS; CYCLE; EXPRESSION; GENE; ACTIVATION; CALCIUM AB Calmodulin (CaM) has been previously shown to be essential for cell cycle progression in eukaryotic cells, being required at the G(1)/S,G(2)/M, and metaphase-anaphase transitions. Little is known about the specific CaM-dependent enzymes that mediate Ca2+/CaM signaling to affect cell proliferation. In this study we show that inhibition of calmodulin kinase II (CaMKII) in HeLa cells using the CaMKII inhibitor KN-93 causes cell cycle arrest, demonstrating that CaMKII is required for cell cycle progression. Detailed analysis of arrest cells suggests that CaMKII is required for the initiation of DNA synthesis. Cells treated with KN-93 arrest with a G(1) DNA content, but with elevated cyclin-dependent histone H1 kinase activity, suggesting that CaMKII may act at a point very close to the onset of DNA synthesis in mammalian cells. C1 UNIV ALBERTA,DEPT ANAT & CELL BIOL,EDMONTON,AB T6G 2H7,CANADA. UNIV ALBERTA,DEPT BIOCHEM,EDMONTON,AB T6G 2H7,CANADA. UNIV ALBERTA,DEPT ONCOL,EDMONTON,AB T6G 2H7,CANADA. UNIV ALBERTA,NCI,MOLEC MECH GROWTH CONTROL GRP,EDMONTON,AB T6G 2H7,CANADA. NR 28 TC 43 Z9 43 U1 0 U2 0 PU NATL RESEARCH COUNCIL CANADA PI OTTAWA PA RESEARCH JOURNALS, MONTREAL RD, OTTAWA ON K1A 0R6, CANADA SN 0829-8211 J9 BIOCHEM CELL BIOL JI Biochem. Cell Biol. PD MAR-APR PY 1995 VL 73 IS 3-4 BP 201 EP 207 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA RN027 UT WOS:A1995RN02700010 PM 7576494 ER PT J AU KRAUSE, M AF KRAUSE, M TI MYOD AND MYOGENESIS IN C-ELEGANS SO BIOESSAYS LA English DT Review ID MUSCLE-SPECIFIC GENES; CAENORHABDITIS-ELEGANS; DNA-BINDING; ENHANCER-BINDING; CELL LINEAGE; EMBRYOS; FAMILY; EXPRESSION; MEMBER; DIFFERENTIATION AB One of the goals in developmental biology is the identification of key regulatory genes that govern the transition of embryonic cells from a pluripotent potential to a specific, committed cell fate. During vertebrate skeletal myogenesis, this transition is regulated by the MyoD family of genes. C. elegans has muscle analogous to vertebrate skeletal muscle and has a gene (hlh-1) related to the MyoD family. The molecular and genetic characterization of hlh-1 shows that it is very similar to the vertebrate MyoD family in many respects, including its expression pattern and DNA binding activity. The hlh-1 product is required for proper myogenesis, but it is not required for myogenic commitment during embryogenesis in the nematode. The role of this MyoD-related gene in nematode myogenesis is discussed and compared to those of the vertebrate MyoD family. RP KRAUSE, M (reprint author), NIDDKD,MOLEC BIOL LAB,BETHESDA,MD 20892, USA. OI Krause, Michael/0000-0001-6127-3940 NR 44 TC 25 Z9 30 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 0265-9247 J9 BIOESSAYS JI Bioessays PD MAR PY 1995 VL 17 IS 3 BP 219 EP 228 DI 10.1002/bies.950170308 PG 10 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA QQ311 UT WOS:A1995QQ31100007 PM 7748176 ER PT J AU CHIZMADZHEV, YA SHCHERBAKOV, AA COHEN, FS ZIMMERBERG, J AF CHIZMADZHEV, YA SHCHERBAKOV, AA COHEN, FS ZIMMERBERG, J TI THEORETICAL-MODEL OF FUSION PORE EVOLUTION SO BIOLOGICHESKIE MEMBRANY LA Russian DT Article ID SECRETORY VESICLE; MEMBRANE-FUSION; EXOCYTOSIS; MECHANISM; PROTEIN; EVENTS; FORMS AB For description of a fusion pore evolution, theoretical model was developed. According to this model, both radius r and length 2R are considered as dynamical variables. The energy consisting of the beading elasticity term and tension term is considered as a function of r and R and has a form of inclined canyon with flanking energy barriers, and the height of one of these barriers decreases as the dimensions increase. The motion of the pore in the space of dimensions is described by Fokker - Planck equation. In the case of fusion pore, the migrational terms are essentially greater then the diffusional ones, so the motion call be described by the mechanical equations. If the mobility along r-coordinate is much higher than the one along R-coordinate, the evolution of the pore induces 3 stages: rapid widening at small r, long plateau, related to the slow motion along the canyon, and at last, fast wedenin. This pattern accords to the experimental results on exocytosis and cell fusion with planar bilayer membranes. C1 RUSH MED COLL,DEPT PHYSIOL,CHICAGO,IL 60612. NIH,BETHESDA,MD 20892. RP CHIZMADZHEV, YA (reprint author), RUSSIAN ACAD SCI,AN FRUMKIN ELECTROCHEM INST,MOSCOW,RUSSIA. RI Chizmadzhev, Yuri/L-1984-2013 NR 22 TC 6 Z9 10 U1 0 U2 1 PU MEZHDUNARODNAYA KNIGA PI MOSCOW PA 39 DIMITROVA UL., 113095 MOSCOW, RUSSIA SN 0233-4755 J9 BIOL MEMBRANY JI Biol. Membr. PD MAR-APR PY 1995 VL 12 IS 2 BP 208 EP 224 PG 17 WC Cell Biology SC Cell Biology GA RP986 UT WOS:A1995RP98600012 ER PT J AU FOLLMANN, D WU, M AF FOLLMANN, D WU, M TI AN APPROXIMATE GENERALIZED LINEAR-MODEL WITH RANDOM EFFECTS FOR INFORMATIVE MISSING DATA SO BIOMETRICS LA English DT Article DE INFORMATIVE CENSORING; LONGITUDINAL DATA; REPEATED MEASURES; SAMPLE SELECTION MODELS ID LONGITUDINAL DATA; SAMPLE SELECTION; INFERENCE; BIAS AB This paper develops a class of models to deal with missing data from longitudinal studies. We assume that separate models for the primary response and missingness (e.g., number of missed visits) are linked by a common random parameter. Such models have been developed in the econometrics (Heckman, 1979, Econometrica 47, 153-161) and biostatistics (Wu and Carroll, 1988, Biometrics 44, 175-188) literature for a Gaussian primary response. We allow the primary response, conditional on the random parameter, to follow a generalized linear model and approximate the generalized linear model by conditioning on the data that describes missingness. The resultant approximation is a mixed generalized linear model with possibly heterogeneous random effects. An example is given to illustrate the approximate approach, and simulations are performed to critique the adequacy of the approximation for repeated binary data. RP FOLLMANN, D (reprint author), NHLBI,OFF BIOSTAT RES,FED BLDG ROOM 2A11,BETHESDA,MD 20892, USA. NR 22 TC 154 Z9 154 U1 6 U2 13 PU INTERNATIONAL BIOMETRIC SOC PI WASHINGTON PA 808 17TH ST NW SUITE 200, WASHINGTON, DC 20006-3910 SN 0006-341X J9 BIOMETRICS JI Biometrics PD MAR PY 1995 VL 51 IS 1 BP 151 EP 168 DI 10.2307/2533322 PG 18 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA QX733 UT WOS:A1995QX73300014 PM 7766771 ER PT J AU LANDIN, R FREEDMAN, LS CARROLL, RJ AF LANDIN, R FREEDMAN, LS CARROLL, RJ TI ADJUSTING FOR TIME TRENDS WHEN ESTIMATING THE RELATIONSHIP BETWEEN DIETARY-INTAKE OBTAINED FROM A FOOD FREQUENCY QUESTIONNAIRE AND TRUE AVERAGE INTAKE SO BIOMETRICS LA English DT Article DE BIAS IN MEASURING DIET; ERRORS-IN-VARIABLES; LINEAR REGRESSION; MEASUREMENT ERROR ID MEASUREMENT ERROR; REPRODUCIBILITY; VALIDITY; CANCER AB In measuring food intake, three common methods are used: 24-hour recalls, food frequency questionnaires and food records. Food records or 24-hour recalls are often thought to be the most reliable, but they are difficult and expensive to obtain. The question of interest to us is to use the food records or 24-hour recalls to examine possible systematic biases in questionnaires as a measure of usual food intake. In Freedman, et al. (1991), this problem is addressed through a linear errors in variables analysis. Their model assumes that all measurements on a given individual have the same mean and variance. However, such assumptions may be violated in at least two circumstances, as in for example the Women's Health Trial Vanguard Study and in the Finnish Smokers' Study. First, some studies occur over a period of years, and diets may change over the course of the study. Second, measurements might be taken at different times of the year, and it is known that diets differ on the basis of seasonal factors. In this paper, we will suggest new models incorporating mean and variance offsets, i.e., changes in the population mean and variance for observations taken at different time points. The parameters in the model are estimated by simple methods, and the theory of unbiased estimating equations (M-estimates) is used to derive asymptotic covariance matrix estimates. The methods are illustrated with data from the Women's Health Trial Vanguard Study. C1 NCI,DCPC,BIOMETRY BRANCH,BETHESDA,MD 20892. TEXAS A&M UNIV,DEPT STAT,COLLEGE STN,TX 77843. RP LANDIN, R (reprint author), MARION MERRELL DOW INC,10400 HICKMAN MILLS DR,KANSAS CITY,MO 64137, USA. NR 9 TC 12 Z9 12 U1 0 U2 3 PU INTERNATIONAL BIOMETRIC SOC PI WASHINGTON PA 808 17TH ST NW SUITE 200, WASHINGTON, DC 20006-3910 SN 0006-341X J9 BIOMETRICS JI Biometrics PD MAR PY 1995 VL 51 IS 1 BP 169 EP 181 DI 10.2307/2533323 PG 13 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA QX733 UT WOS:A1995QX73300015 PM 7766772 ER PT J AU BENICHOU, J GAIL, MH AF BENICHOU, J GAIL, MH TI METHODS OF INFERENCE FOR ESTIMATES OF ABSOLUTE RISK DERIVED FROM POPULATION-BASED CASE-CONTROL STUDIES SO BIOMETRICS LA English DT Article DE ABSOLUTE RISK; RELATIVE RISK; FOLLOW-UP DATA; EMBEDDED CASE CONTROL DATA; COMPONENTS OF VARIABILITY; IMPLICIT DELTA METHOD ID BREAST-CANCER; INDIVIDUALIZED PROBABILITIES; NONPARAMETRIC-ESTIMATION; CONFIDENCE-INTERVALS; ATTRIBUTABLE RISK; MODELS; PARAMETERS AB The absolute risk is the probability of developing a given disease over a specified time interval given age and risk factors. Gall, et al. (1989, Journal of the National Cancer Institute 81, 1879-1888) obtained point estimates from population-based case control data by combining relative risk estimates from the case control data and composite incidence estimates from the cohort data. They also obtained variance estimates, but they only took into account the variability in estimating relative risks. In this paper, we present variance estimates that take into account all components of variability, namely the variance of relative risk estimates and of baseline incidence estimates, as well as the covariance between the two, the latter term being obtained by using implicit delta method arguments (Benichou and Gall, 1989, The American Statistician 43, 41-44). Simulations demonstrate the validity of such variance estimates as well as of corresponding confidence intervals. These methods are applied to a population-based case control study of breast cancer. RP BENICHOU, J (reprint author), NCI,6130 EXECUT BLVD,EPN-403,ROCKVILLE,MD 20892, USA. NR 29 TC 35 Z9 35 U1 0 U2 4 PU INTERNATIONAL BIOMETRIC SOC PI WASHINGTON PA 808 17TH ST NW SUITE 200, WASHINGTON, DC 20006-3910 SN 0006-341X J9 BIOMETRICS JI Biometrics PD MAR PY 1995 VL 51 IS 1 BP 182 EP 194 DI 10.2307/2533324 PG 13 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA QX733 UT WOS:A1995QX73300016 PM 7766773 ER PT J AU BAKER, SG AF BAKER, SG TI EVALUATING MULTIPLE DIAGNOSTIC-TESTS - WITH PARTIAL VERIFICATION SO BIOMETRICS LA English DT Note DE COMPOSITE LINEAR MODEL; MISSING DATA; NONIGNORABLE NONRESPONSE; ROC CURVE ID LOG-LINEAR-MODELS; CATEGORICAL-DATA; SELECTION BIAS; EM ALGORITHM; MISCLASSIFICATION ERRORS; DISEASE VERIFICATION; REGRESSION-ANALYSIS; MAXIMUM-LIKELIHOOD; SUBJECT; SENSITIVITY AB To evaluate diagnostic tests, one would ideally like to verify, for example, with a biopsy, the disease state of all subjects in a study. Often, however, not all subjects are verified. Previous methods for evaluation assume that the decision to verify depends only on recorded variables. Sometimes, particularly if the disease process is not well understood, the decision to verify may also depend on unrecorded variables related to disease. We propose a method to estimate the true- and false-positive rates of multiple tests while adjusting for the effect, on the decision to verify, of unrecorded variables related to disease. To put the estimates into a more usable form, we develop a simple algorithm for creating a receiver-operating curve which maximizes the true-positive rate, given the false-positive rate. We apply the methodology to data on the early detection of prostate cancer using ultrasonography, digital rectal exam, and prostate specific antigen. RP BAKER, SG (reprint author), NCI, DIV CANC PREVENT & CONTROL,BIOMETRY BRANCH, EPN 344,6130 EXECUT BLVD, MSC 7354, BETHESDA, MD 20892 USA. NR 41 TC 40 Z9 41 U1 1 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0006-341X EI 1541-0420 J9 BIOMETRICS JI Biometrics PD MAR PY 1995 VL 51 IS 1 BP 330 EP 337 DI 10.2307/2533339 PG 8 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA QX733 UT WOS:A1995QX73300031 PM 7539300 ER PT J AU NAM, JM AF NAM, JM TI SIMPLE TEST FOR THE HARDY-WEINBERG LAW FOR HLA DATA WITH NO OBSERVED DOUBLE BLANKS SO BIOMETRICS LA English DT Article DE BIAS-CORRECTED BERNSTEINS ESTIMATOR; GENERALIZED STEVENS TEST; HARDY-WEINBERG HLA SYSTEM AB Eguchi and Matsuura (1990, Biometrics 46, 415-426) noted that the generalized Stevens test statistic for the Hardy-Weinberg law for human leukocyte antigen (HLA) data yields an excessively large value when no double blanks are observed. In this paper, we investigate this aberrant case. The inflated value of the test statistic is caused mainly by a seriously biased Bernstein's estimator of the recessive. We propose the generalized Stevens test using bias-corrected Bernstein's estimators for HLA data with no observed double blanks. An example illustrates the correction of the test statistic. RP NAM, JM (reprint author), NATL CANC INST,BIOSTAT BRANCH,6130 EXECUT BLVD,EPN-403,ROCKVILLE,MD 20892, USA. NR 11 TC 2 Z9 2 U1 0 U2 1 PU INTERNATIONAL BIOMETRIC SOC PI WASHINGTON PA 808 17TH ST NW SUITE 200, WASHINGTON, DC 20006-3910 SN 0006-341X J9 BIOMETRICS JI Biometrics PD MAR PY 1995 VL 51 IS 1 BP 354 EP 357 DI 10.2307/2533343 PG 4 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA QX733 UT WOS:A1995QX73300035 PM 7766790 ER PT J AU LUNSFORD, RD AF LUNSFORD, RD TI RECOVERY OF RNA FROM ORAL STREPTOCOCCI SO BIOTECHNIQUES LA English DT Note ID ACID RP LUNSFORD, RD (reprint author), NIDR,BLDG 30,RM 312,30 CONVENT DR MSC 4350,BETHESDA,MD 20892, USA. NR 6 TC 15 Z9 15 U1 0 U2 0 PU EATON PUBLISHING CO PI NATICK PA 154 E. CENTRAL ST, NATICK, MA 01760 SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD MAR PY 1995 VL 18 IS 3 BP 412 EP 414 PG 3 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QK713 UT WOS:A1995QK71300012 PM 7540019 ER PT J AU MIYAJIMA, I LEVITT, L HARA, T BEDELL, MA COPELAND, NG JENKINS, NA MIYAJIMA, A AF MIYAJIMA, I LEVITT, L HARA, T BEDELL, MA COPELAND, NG JENKINS, NA MIYAJIMA, A TI THE MURINE INTERLEUKIN-3 RECEPTOR-ALPHA SUBUNIT GENE - CHROMOSOMAL LOCALIZATION, GENOMIC STRUCTURE, AND PROMOTER FUNCTION SO BLOOD LA English DT Article ID COLONY-STIMULATING FACTOR; Y PSEUDOAUTOSOMAL REGION; HUMAN ERYTHROPOIETIN RECEPTOR; GM-CSF; TRANSCRIPTION FACTORS; HEMATOPOIETIC-CELLS; LINKAGE MAP; MOUSE; ORGANIZATION; EXPRESSION AB The interleukin-3 receptor (IL-3R) is composed of alpha and beta subunits, members of the class I cytokine receptor family. Here we describe isolation and characterization of the chromosomal gene for the mouse IL-3R alpha subunit (mIL-3R alpha). Whereas the human IL-3R alpha gene is tightly linked with the granulocyte-macrophage colony-stimulating factor receptor alpha subunit (GM-CSFR alpha) gene in the pseudoautosomal region of the X and Y chromosomes, the mIL-3R alpha gene (II3ra) is located in the proximal region of mouse chromosome 14, separated from the mouse GM-CSFR alpha gene, which is on chromosome 19. The mIL-3R alpha gene spans about 10 kb and is divided into 12 exons. All the exon-intron boundaries possess the splicing junction consensus sequences (5'GT-AG3'), and the whole genomic structure is similar to those of the previously reported class I cytokine receptor genes. There are two major transcription initiation sites that are located at 215 and 188 nucleotides upstream of the initiator codon. The promoter region is GC-rich and contains potential binding sites for GATA, Ets, c-myb,, Sp1, Ap-2, and G-C boxes, but not a typical TATA or CAAT sequence. A fusion gene containing 0.8 kb of the 5' noncoding sequence linked to the firefly luciferase gene directed the transcription in mouse mast cells but not in fibroblasts or T cells, suggesting that this promoter functions in a cell type-specific manner. Further sequential deletion of the 5' region suggests two potential regulatory regions for transcription of the mIL-3R alpha gene. (C) 1995 by The American Society of Hematology. C1 DNAX RES INST MOLEC & CELLULAR BIOL INC,PALO ALTO,CA 94304. NCI,FREDERICK CANC RES & DEV CTR,MAMMALIAN GENET LAB,FREDERICK,MD 21702. FU NCI NIH HHS [N01-CO-74101] NR 44 TC 39 Z9 39 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD MAR 1 PY 1995 VL 85 IS 5 BP 1246 EP 1253 PG 8 WC Hematology SC Hematology GA QJ435 UT WOS:A1995QJ43500013 PM 7858255 ER PT J AU AGARWAL, R DOREN, S HICKS, B DUNBAR, CE AF AGARWAL, R DOREN, S HICKS, B DUNBAR, CE TI LONG-TERM CULTURE OF CHRONIC MYELOGENOUS LEUKEMIA MARROW-CELLS ON STEM-CELL FACTOR-DEFICIENT STROMA FAVORS BENIGN PROGENITORS SO BLOOD LA English DT Article ID CHRONIC MYELOID-LEUKEMIA; RECEPTOR TYROSINE KINASE; C-KIT LIGAND; MOLECULAR-CLONING; HEMATOPOIESIS INVITRO; EXPRESSION; PURIFICATION; MECHANISMS; GENERATION; SELECTION AB Long-term culture of marrow from patients with chronic myelogenous leukemia (CML) has been reported to favor the outgrowth of bcr/abl(-) progenitor cells in some patients. We examined the effect of the presence of soluble or transmembrane forms of stem cell factor (SCF) in long-term cultures of CML marrow. CD34-enriched cells from CML patients in advanced chronic phase or accelerated phase were plated on immortalized fetal liver stromal cells from homozygous SCF-deficient Sl/Sl mice (Sl/Sl(4)) with or without the addition of soluble human SCF, Sl/Sl(4) cells expressing high levels of the transmembrane form of human SCF (Sl/Sl(h220)), or primary human allogeneic stroma. Cells were removed from cultures and plated weekly in colony assays. The clonagenic cell output from cultures completely lacking SCF was lower over the first 2 to 3 weeks, but by 5 weeks was similar to the clonagenic cell output from the other culture conditions. Analysis of bcr/abl transcripts from individual colonies showed a lower percentage of malignant progenitors present in long-term cultures completely deficient in SCF than under the other culture conditions, particularly compared with primary human stroma-containing long-term cultures. SCF may specifically favor malignant versus benign progenitor cells present in the marrow of CML patients, and an abnormal proliferative response to SCF in very primitive cells may be an underlying defect in the pathophysiology of this disease. C1 NHLBI,HEMATOL BRANCH,BETHESDA,MD 20892. CHILDRENS HOSP,MED CTR,CINCINNATI,OH 45229. NR 32 TC 45 Z9 45 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD MAR 1 PY 1995 VL 85 IS 5 BP 1306 EP 1312 PG 7 WC Hematology SC Hematology GA QJ435 UT WOS:A1995QJ43500021 PM 7532038 ER PT J AU LEE, S ZAMBAS, E GREEN, ED REDMAN, C AF LEE, S ZAMBAS, E GREEN, ED REDMAN, C TI ORGANIZATION OF THE GENE ENCODING THE HUMAN KELL BLOOD-GROUP PROTEIN SO BLOOD LA English DT Article ID NEUTRAL ENDOPEPTIDASE 24.11; RED-CELL MEMBRANE; LEUKEMIA ANTIGEN; MONOCLONAL-ANTIBODIES; UNTRANSLATED REGIONS; GROUP LOCUS; COMMON; GLOBIN; PROMOTER; GLYCOPROTEIN AB Kell is one of the major blood group systems in human erythrocytes. It is a complex system containing a large number of different antigens. Previously we cloned the Kell cDNA, which was predicted to encode an integral membrane protein with 731 amino acids. Now we have isolated overlapping genomic clones and determined the exon-intron structure of the KEL gene: it spans approximate to 21.5 kb with its coding sequence being organized in 19 exons that range in size from 63 bp to 288 bp. The size of introns ranges from 93 bp to approximate to 6 kb. The donor and acceptor splice sites all conform to the consensus splicing sequences. Exon 1 encodes only the initiation amino acid, methionine, and contains a consensus Spl binding site. The single membrane spanning region of Kell protein is encoded in exon 3 and the putative zinc endopeptidase active site is in exon 16. The amino acids encoded by the 19 exons are identical to those of a person with a common Kell phenotype, as determined by RNA polymerase chain reaction of peripheral blood. Amplification of cDNA 5' ends, derived from human fetal liver, indicated three transcription initiation sites located 30, 81, and 120 bp upstream of the initiation codon. The 5' flanking region of KEL from -176 does not contain a TATA sequence, but has possible GATA-1 binding sites and has significant promoter activity when determined by chloramphenicol acetyltrasferase activity in K562 cells. (C) 1995 by The American Society of Hematology. C1 NEW YORK BLOOD CTR,LINDSLEY F KIMBALL RES INST,NEW YORK,NY 10021. NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD. FU NHLBI NIH HHS [HL35841] NR 33 TC 53 Z9 54 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD MAR 1 PY 1995 VL 85 IS 5 BP 1364 EP 1370 PG 7 WC Hematology SC Hematology GA QJ435 UT WOS:A1995QJ43500029 PM 7858266 ER PT J AU HORNE, MK ALKINS, BR AF HORNE, MK ALKINS, BR TI IMPORTANCE OF PF4 IN HEPARIN-INDUCED THROMBOCYTOPENIA - CONFIRMATION WITH GRAY PLATELETS SO BLOOD LA English DT Letter RP HORNE, MK (reprint author), NIH,WARREN G MAGNUSON CLIN CTR,DEPT CLIN PATHOL,HEMATOL SECT,BETHESDA,MD 20892, USA. NR 6 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 0006-4971 J9 BLOOD JI Blood PD MAR 1 PY 1995 VL 85 IS 5 BP 1408 EP 1409 PG 2 WC Hematology SC Hematology GA QJ435 UT WOS:A1995QJ43500039 PM 7858274 ER PT J AU WEISS, SRB CLARK, M ROSEN, JB SMITH, MA POST, RM AF WEISS, SRB CLARK, M ROSEN, JB SMITH, MA POST, RM TI CONTINGENT TOLERANCE TO THE ANTICONVULSANT EFFECTS OF CARBAMAZEPINE - RELATIONSHIP TO LOSS OF ENDOGENOUS ADAPTIVE-MECHANISMS SO BRAIN RESEARCH REVIEWS LA English DT Review DE CONTINGENT TOLERANCE; ANTICONVULSANT; KINDLING; THYROTROPIN-RELEASING-HORMONE; GABA; CORTICOTROPIN-RELEASING-FACTOR; NEUROPEPTIDE Y; GROWTH FACTOR; CARBAMAZEPINE ID AMYGDALA-KINDLED SEIZURES; CORTICOTROPIN-RELEASING HORMONE; TRIGEMINAL NEURALGIA; LIMBIC SEIZURES; MESSENGER-RNA; NEUROTROPHIC FACTOR; RAT HIPPOCAMPUS; C-FOS; BRAIN; EXPRESSION AB Contingent tolerance to the anticonvulsant effects of carbamazepine on amygdala kindled seizures develops when the drug is repeatedly given prior to but not after the electrical stimulation. Such tolerance can be reversed by kindling the rats for several days without drug or even by continuing to give the drug but after each seizure has occurred. Contingent tolerance can be slowed by reducing the electrical stimulus intensity and by chronic continuous (as opposed to repeated paired) drug administration. Contingent cross-tolerance has been demonstrated from carbamazepine to PK11195 (a drug active at peripheral-type benzodiazepine receptors) and valproate, but not to clonazepam and diazepam (two drugs active at central-type benzodiazepine receptors) or phenytoin. Endogenous physiological changes occur in conjunction with contingent tolerance, exemplified by the decrease in seizure threshold that returns to normal upon reversal of tolerance. We suggest that contingent tolerance is associated with a loss of seizure-induced adaptations, since many biochemical changes that occur following seizures (or in non-tolerant animals given drug after seizures) are not observed in tolerant animals. These include a loss of seizure-induced up-regulation of GABA, receptors and a loss of increases in mRNA expression for corticotropin-releasing-factor (CRF), thyrotropin-releasing-hormone (TRH), neuropeptide Y (NPY), glucocorticoid receptors and brain-derived neurotrophic factor (BDNF). Thus, several putative seizure-induced anticonvulsant adaptations, such as increases in GABA, receptors and TRH and NPY mRNA fail to occur in tolerant animals. These findings are consistent with the novel observations that, paradoxically, seizures themselves appear to facilitate the anticonvulsant effects of carbamazepine or diazepam on amygdala kindled seizures. That is, animals given a 'vacation' from seizures show a decreased response to these agents, a phenomenon we have called the 'time-off seizure' effect. Thus, seizures are postulated to induce adaptive changes that influence seizure thresholds and potentiate the anticonvulsant effects of exogenously administered drugs such as carbamazepine and diazepam. Taken together, these data suggest that seizures are associated with endogenous adaptations lasting days to weeks and that a selective failure of some of these to occur during contingent drug administration may underlie the development of contingent tolerance. These observations suggest that endogenous, illness-related mechanisms may participate both in the therapeutic responses of some agents and that their failure to occur could relate to loss of drug efficacy via tolerance; these processes may reveal new potential targets for therapeutic intervention. RP WEISS, SRB (reprint author), NIMH,BIOL PSYCHIAT BRANCH,BLDG 10-3N212,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 93 TC 57 Z9 57 U1 0 U2 2 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 MAR PY 1995 VL 20 IS 3 BP 305 EP 325 DI 10.1016/0165-0173(95)00002-K PG 21 WC Neurosciences SC Neurosciences & Neurology GA RF103 UT WOS:A1995RF10300003 PM 7550363 ER PT J AU HARTGE, P DEVESA, S AF HARTGE, P DEVESA, S TI OVARIAN-CANCER, OVULATION AND SIDE OF ORIGIN SO BRITISH JOURNAL OF CANCER LA English DT Note DE OVARIAN CANCER; OVULATION AB Reports of more right-sided ovarian cancers and more ovulations in the right ovary seemed to offer powerful support for the theory that ovulation, per se, leads to ovarian cancer risk. We examined laterality in 25 692 epithelial ovarian cancers diagnosed in 1973-89 included in the US Surveillance, Epidemiology, and End Results system of cancer registries. Ovarian cancer occurred equally often in the left and right ovaries in this large series of incident cases. RP HARTGE, P (reprint author), NCI,DIV CANC ETIOL,EPIDEMIOL & BIOSTAT PROGRAM,EXECUT PLAZA N 443,BETHESDA,MD 20892, USA. NR 7 TC 9 Z9 9 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HANTS, ENGLAND RG21 2XS SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD MAR PY 1995 VL 71 IS 3 BP 642 EP 643 DI 10.1038/bjc.1995.126 PG 2 WC Oncology SC Oncology GA QJ295 UT WOS:A1995QJ29500039 PM 7880751 ER PT J AU BERNSTEIN, EF SCHUSTER, MG STIERITZ, DD HEUMAN, PC UITTO, J AF BERNSTEIN, EF SCHUSTER, MG STIERITZ, DD HEUMAN, PC UITTO, J TI DISSEMINATED CUTANEOUS PSEUDALLESCHERIA-BOYDII SO BRITISH JOURNAL OF DERMATOLOGY LA English DT Note ID CENTRAL NERVOUS-SYSTEM; ALLESCHERIA-BOYDII; INFECTION; LEUKEMIA; MYCOSES; PATIENT; AGENTS AB As increasingly aggressive chemotherapeutic regimens are used to treat malignancy, more patients will become susceptible to various opportunistic pathogens. Specifically, several fungal organisms previously viewed as relatively non-pathogenic are more frequently causing serious disease in these patients. Identification of these organisms is of paramount importance, as some are relatively resistant to standard antifungal therapies. We report a patient with disseminated cutaneous Pseudallescheria boydii, diagnosed from histopathological examination and culture of a skin biopsy specimen, Identification of the organism was achieved shortly before the patient died, Clinicians must be aware of the numerous emerging opportunistic pathogens, which may require special culture techniques for diagnosis and varied or combined modes of therapy. C1 THOMAS JEFFERSON UNIV,DEPT MOLEC BIOL & BIOCHEM,PHILADELPHIA,PA 19107. NCI,RADIAT BIOL BRANCH,BETHESDA,MD 20892. UNIV PENN,DEPT MED,DIV INFECT DIS,PHILADELPHIA,PA. HAHNEMANN UNIV,DEPT MICROBIOL & IMMUNOL,PHILADELPHIA,PA 19102. HAHNEMANN UNIV,CLIN LABS,PHILADELPHIA,PA 19102. RP BERNSTEIN, EF (reprint author), THOMAS JEFFERSON UNIV,DEPT DERMATOL,233 S 10TH ST,SUITE 450,PHILADELPHIA,PA 19107, USA. NR 30 TC 28 Z9 28 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0007-0963 J9 BRIT J DERMATOL JI Br. J. Dermatol. PD MAR PY 1995 VL 132 IS 3 BP 456 EP 460 DI 10.1111/j.1365-2133.1995.tb08683.x PG 5 WC Dermatology SC Dermatology GA QM412 UT WOS:A1995QM41200020 PM 7718466 ER PT J AU NAPARSTEK, E OR, R NAGLER, A CIVIDALLI, G ENGELHARD, D AKER, M GIMON, Z MANNY, N SACKS, T TOCHNER, Z WEISS, L SAMUEL, S BRAUTBAR, C HALE, G WALDMANN, H STEINBERG, SM SLAVIN, S AF NAPARSTEK, E OR, R NAGLER, A CIVIDALLI, G ENGELHARD, D AKER, M GIMON, Z MANNY, N SACKS, T TOCHNER, Z WEISS, L SAMUEL, S BRAUTBAR, C HALE, G WALDMANN, H STEINBERG, SM SLAVIN, S TI T-CELL-DEPLETED ALLOGENEIC BONE-MARROW TRANSPLANTATION FOR ACUTE-LEUKEMIA USING CAMPATH-1 ANTIBODIES AND POSTTRANSPLANT ADMINISTRATION OF DONORS PERIPHERAL-BLOOD LYMPHOCYTES FOR PREVENTION OF RELAPSE SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE ALLOGENEIC BMT; T-CELL DEPLETION; DONOR LYMPHOCYTES ID VERSUS-HOST DISEASE; CHRONIC MYELOGENOUS LEUKEMIA; TOTAL LYMPHOID IRRADIATION; MINIMAL RESIDUAL DISEASE; TERM FOLLOW-UP; CHRONIC GRAFT; RISK-FACTORS; MONOCLONAL-ANTIBODIES; MURINE LEUKEMIA; INVITRO AB One hundred and forty-six patients with acute leukaemia (81 with ANLL and 65 with ALL) received allogeneic bone marrow transplantation from their fully matched siblings. 121 patients underwent T-cell depletion (TCD) using Campath 1 monoclonal rat anti-human lymphocyte (CDw52) antibodies; 67 with Campath 1M and 54 with Campath 1G isotypes. Patients were conditioned for transplant using either total body irradiation combined with chemotherapy (125 patients) or busulfan and cyclophosphamide (21 patients). 112 recipients of T-cell depleted allografts received in addition total lymphoid irradiation (TLI) for prevention of rejection, Engraftment of neutrophils (>0.5 x 10(9)/l) and platelets (>25 x 10(9)/l) occurred on days 15 and 18, and on days 18 and 20 in recipients of Campath 1M and Campath 1G treated marrows respectively. Rejection was documented in 6.8% of T-cell depleted transplants. Leukaemia relapse-free survival at 2 years was 83% for patients transplanted in first CR, 76% in second CR (P-2 = 0.34) and 42% in advanced leukaemia (P-2 = 0.009). 81 marrow recipients, 38 with Campath 1M and 43 with Campath 1G treated marrow, received post-transplant graded increments of donor's peripheral blood lymphocytes (PBL) to induce graft-versus-leukaemia (GVL) effects. Administration of donor's PBL was associated with clinically significant GVHD and with decreased relapse rate especially in patients with ALL. Our data suggest that in patients receiving marrow allografts depleted of T cells by Campath 1 monoclonal antibodies, rejection can be reduced by adequate pregrafting immunosuppression. In patients with advanced disease, post-transplant cell-mediated immunotherapy (CMI) using donor's PBL may be beneficial; however, further studies are needed to define the optimal schedule of CMI for safe and effective prevention of relapse following TCD bone marrow transplantation in malignant haematological diseases. C1 HADASSAH UNIV HOSP,CANC IMMUNOBIOL RES LAB,IL-91120 JERUSALEM,ISRAEL. HADASSAH UNIV HOSP,DEPT PAEDIAT,IL-91120 JERUSALEM,ISRAEL. HADASSAH UNIV HOSP,DEPT SURG,IL-91120 JERUSALEM,ISRAEL. HADASSAH UNIV HOSP,DEPT BLOOD BANK,IL-91120 JERUSALEM,ISRAEL. HADASSAH UNIV HOSP,DEPT INFECT DIS,IL-91120 JERUSALEM,ISRAEL. HADASSAH UNIV HOSP,DEPT ONCOL,IL-91120 JERUSALEM,ISRAEL. HADASSAH UNIV HOSP,TISSUE TYPING LAB,IL-91120 JERUSALEM,ISRAEL. UNIV CAMBRIDGE,DEPT PATHOL,CAMBRIDGE,ENGLAND. NCI,DIV CANC TREATMENT,BIOSTAT & DATA MANAGEMENT SECT,BETHESDA,MD 20892. RP NAPARSTEK, E (reprint author), HADASSAH UNIV HOSP,DEPT BONE MARROW TRANSPLANT,POB 12000,IL-91120 JERUSALEM,ISRAEL. NR 51 TC 131 Z9 132 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD MAR PY 1995 VL 89 IS 3 BP 506 EP 515 DI 10.1111/j.1365-2141.1995.tb08356.x PG 10 WC Hematology SC Hematology GA QL341 UT WOS:A1995QL34100011 PM 7734348 ER PT J AU HENRIKSEN, TB HEDEGAARD, M SECHER, NJ WILCOX, AJ AF HENRIKSEN, TB HEDEGAARD, M SECHER, NJ WILCOX, AJ TI STANDING AT WORK AND PRETERM DELIVERY SO BRITISH JOURNAL OF OBSTETRICS AND GYNAECOLOGY LA English DT Article ID LOW-BIRTH-WEIGHT; PHYSICAL-ACTIVITY; MATERNAL WORK; RISK-FACTORS; GESTATIONAL-AGE; FETAL GROWTH; FOLLOW-UP; PREGNANCY; CHILDREN; PREMATURITY AB Objective Guidelines in some European countries and the United States suggest that pregnant women should avoid prolonged standing and heavy lifting in the workplace during the second and third trimester of pregnancy. However, results from epidemiological studies on this topic are ambiguous. The aim of this study was to evaluate the influence of standing and walking at work in the second trimester on preterm delivery in a population with a low frequency of other workplace hazards. Subjects and design A prospective cohort of 8711 women with singleton pregnancies was established during 1989 through 1991. Information was collected during the 16th week of pregnancy about medical and obstetrical history, general lifestyle factors and exposures at work. The analyses were restricted to 4259 respondents who worked at the 16th week. Potential confounders and effect modifiers were evaluated by stratification and multivariate analyses. Results After adjustment for confounders, women standing more than five hours per work day had an odds ratio (OR) for preterm delivery of 1.2 (95% CI 0.6 to 2.4) compared with women standing two hours or less. For walking, the OR was 1.4 (95% CI 0.7 to 2.5). Many women were unable to separate periods of standing from periods of walking; a combined measure of these two exposures was created to reflect exposure intensity. Women who reported more than five hours of both standing and walking had an adjusted OR of 3.3 (95% CI 1.4 to 8.0) compared with women who reported two hours or less on either of the exposures. No adverse effects were seen for lifting or other types of physical exertion. Conclusions Our findings suggest that standing and walking at work during the second trimester may present a particular risk for preterm delivery, and workplace guidelines are justified. Further research is needed to address the specific mechanisms by which physical exertion, including standing and walking might cause preterm delivery. C1 NIEHS,EPIDEMIOL BRANCH,RES TRIANGLE PK,NC. RP HENRIKSEN, TB (reprint author), AARHUS UNIV HOSP,DEPT OBSTET & GYNAECOL,PERINATAL EPIDEMIOL RES UNIT,DK-8000 AARHUS C,DENMARK. OI Wilcox, Allen/0000-0002-3376-1311 NR 51 TC 66 Z9 68 U1 0 U2 11 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0306-5456 J9 BRIT J OBSTET GYNAEC JI Br. J. Obstet. Gynaecol. PD MAR PY 1995 VL 102 IS 3 BP 198 EP 206 DI 10.1111/j.1471-0528.1995.tb09094.x PG 9 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA QL346 UT WOS:A1995QL34600006 PM 7794843 ER PT J AU INABA, T NEBERT, DW BURCHELL, B WATKINS, PB GOLDSTEIN, JA BERTILSSON, L TUCKER, GT AF INABA, T NEBERT, DW BURCHELL, B WATKINS, PB GOLDSTEIN, JA BERTILSSON, L TUCKER, GT TI PHARMACOGENETICS IN CLINICAL-PHARMACOLOGY AND TOXICOLOGY SO CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY LA English DT Editorial Material DE PHARMACOLOGY; TOXICOLOGY; DRUG METABOLISM; PHARMACOGENETIC POLYMORPHISM ID S-MEPHENYTOIN; POLYMORPHIC HYDROXYLATION; DEBRISOQUINE; SPARTEINE; CHINESE; CYTOCHROME-P-450; IDENTIFICATION; CYCLOSPORINE; METABOLISM; OXIDATION AB An international symposium entitled Pharmacogenetics in clinical pharmacology and toxicology: a tribute to Werner Kalow was held in Toronto, Ontario, July 20, 1994. This subject was particularly important to discuss in the presence of Werner Kalow, 77 years young, who is considered as one of the grandfathers of this unique combination of medical research fields. It has become increasingly appreciated that dozens of human drug metabolism polymorphisms exist. The interindividual variabilities in drug metabolism discussed at this symposium do not represent small differences such as 50% or 3-fold but, rather, represent 10- to greater than 1000-fold differences. When attributed to a single gene, dramatic differences can be seen among family members, just as blue and brown eyes can occur in siblings. These differences can result in acute drug toxicity. In addition, there are chronic effects: over one's lifetime, striking differences in the metabolism of drugs, occupationally hazardous chemicals, and other environmental pollutants can lead to interindividual differences in the buildup of DNA damage (e.g., mutations, chromosomal breaks, rearrangements) leading to toxicity and tumor initiation, as well as leading to a buildup in nongenotoxic signals (signal transduction pathways without DNA damage) important for toxicity, tumor promotion, and tumor progression. The human UDP glucuronosyltransferase (UGT superfamily is known to comprise more than 10 genes in humans, and probably in other mammalian species. Breakthroughs in UGT gene mutations responsible for the Crigler-Najjar syndrome and Gilbert's disease have recently been reported. The human cytochrome P450 termed CYP3A4 is a major P450 enzyme in the liver and gastrointestinal tract, and the full impact of the CYP3A4 polymorphism has yet to be fully appreciated. CYP3A4 metabolism of cyclosporin A, commonly prescribed to organ transplant recipients, the induction of CYP3A4 by rifampicin, and inhibition of CYP3A4 metabolism by erythromycin or ketoconazole are now quite well understood. The field of ethnopharmacology, or pharmacoanthropology, has recently emerged, pioneered at least in part by Kalow. Differences in debrisoquine-sparteine metabolism, S-mephenytoin hydroxylation, diazepam clearance, and omeprazole clearance in various Caucasian and Oriental subpopulations in a number of countries have been extensively reported. After a number of inconclusive studies, it has now been ;shown unequivocally that the human S-mephenytoin 4'-hydroxylase polymorphism represents at least two distinct mutations (one involving a splice site) in the CYP2C19 gene. Finally, the implications and clinical significance of a number of human polymorphisms (CYP2D6, CYP2C19, N-acetylation (NAT2), S-methylation by thiopurine methyltransferase (TPMT), and ester hydrolysis by plasma cholinesterase) were carefully reviewed at this symposium. C1 UNIV CINCINNATI, MED CTR, CTR ENVIRONM GENET, CINCINNATI, OH 45267 USA. UNIV DUNDEE, NINEWELLS MED SCH, DEPT BIOCHEM MED, DUNDEE, SCOTLAND. UNIV MICHIGAN, SCH MED, ANN ARBOR, MI 48109 USA. NIEHS, RES TRIANGLE PK, NC 27709 USA. HUDDINGE UNIV HOSP, KAROLINSKA INST, DEPT MED LAB SCI & TECHNOL, DIV CLIN PHARMACOL, S-14186 HUDDINGE, SWEDEN. UNIV SHEFFIELD, ROYAL HALLAMSHIRE HOSP, DEPT MED & PHARMACOL, SHEFFIELD S10 2JF, S YORKSHIRE, ENGLAND. RP INABA, T (reprint author), UNIV TORONTO, FAC MED, DEPT PHARMACOL, TORONTO, ON M5S 1A8, CANADA. RI Goldstein, Joyce/A-6681-2012 NR 38 TC 29 Z9 30 U1 0 U2 2 PU CANADIAN SCIENCE PUBLISHING, NRC RESEARCH PRESS PI OTTAWA PA 65 AURIGA DR, SUITE 203, OTTAWA, ON K2E 7W6, CANADA SN 0008-4212 EI 1205-7541 J9 CAN J PHYSIOL PHARM JI Can. J. Physiol. Pharmacol. PD MAR PY 1995 VL 73 IS 3 BP 331 EP 338 PG 8 WC Pharmacology & Pharmacy; Physiology SC Pharmacology & Pharmacy; Physiology GA QY488 UT WOS:A1995QY48800001 PM 7648512 ER PT J AU HAHN, SM LEPINSKI, DL DELUCA, AM MITCHELL, JB PELLMAR, TC AF HAHN, SM LEPINSKI, DL DELUCA, AM MITCHELL, JB PELLMAR, TC TI NEUROPHYSIOLOGICAL CONSEQUENCES OF NITROXIDE ANTIOXIDANTS SO CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY LA English DT Article DE NITROXIDES; BRAIN; NEUROPHYSIOLOGY; TOXICITY; ANTIOXIDANTS ID LONG-TERM POTENTIATION; HIPPOCAMPAL SLICES; DAMAGE; TEMPOL AB Nitroxides are antioxidant compounds that have been shown to provide radioprotection in vivo and in vitro. Radioprotection in vivo is limited by toxicity, which appears to be neurologic in nature. To further evaluate the toxicity of these compounds, three representative nitroxides, Tempol, Tempamine, and Tempo, were examined in slices of guinea pig hippocampus. Each nitroxide increased the population spike and caused potentiation of excitatory postsynaptic potential - spike coupling. Repetitive activity and epileptiform activity were observed at the highest concentrations of Tempo and Tempamine. Tempol was the least toxic compound in this system, followed by Tempamine and Tempo. Additional studies are necessary to further define the effects of nitroxides on the central nervous system and to develop strategies to mitigate these effects. C1 ARMED FORCES RADIOBIOL RES INST,DEPT PHYSIOL,BETHESDA,MD 20889. RP HAHN, SM (reprint author), NCI,DIV CANC TREATMENT,RADIAT BIOL BRANCH,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 23 TC 20 Z9 20 U1 0 U2 1 PU NATL RESEARCH COUNCIL CANADA PI OTTAWA PA RESEARCH JOURNALS, MONTREAL RD, OTTAWA ON K1A 0R6, CANADA SN 0008-4212 J9 CAN J PHYSIOL PHARM JI Can. J. Physiol. Pharmacol. PD MAR PY 1995 VL 73 IS 3 BP 399 EP 403 PG 5 WC Pharmacology & Pharmacy; Physiology SC Pharmacology & Pharmacy; Physiology GA QY488 UT WOS:A1995QY48800009 PM 7648519 ER PT J AU WUN, LM FEUER, EJ MILLER, BA AF WUN, LM FEUER, EJ MILLER, BA TI ARE INCREASES IN MAMMOGRAPHIC SCREENING STILL A VALID EXPLANATION FOR TRENDS IN BREAST-CANCER INCIDENCE IN THE UNITED-STATES SO CANCER CAUSES & CONTROL LA English DT Article DE AGE-COHORT MODEL; BREAST CANCER INCIDENCE; LEAD-TIME EFFECT; SECULAR TREND; SCREENING-MAMMOGRAPHY; UNITED STATES ID DETECTION DEMONSTRATION PROJECT; CONNECTICUT; PROGRAMS; MODEL AB A number of studies have attributed much of the sharp increase in breast cancer incidence in the United States during the 1980s to the increased detection through mammography. The most recent breast cancer data from the US National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program show that the incidence trend has slowed, while results from the National Health Interview Survey (NHIS) of 1987 and 1990 indicate that the percentage of women receiving mammograms continues to increase. This phenomenon suggested the need to reassess the relationship between increasingly early detection of breast cancer and overall incidence trends. A polynomial age-cohort model was used to establish the secular trend in incidence rates excluding the impact of recent increases in detection due to the rising use of mammography. Based on the model, the incidence trend in the youngest age group (40 to 49 years) would peak and then begin to decline in the early 1980s, This pattern would manifest itself later in successively older age groups as these younger cohorts age. Breast cancer trends are seen to be generally consistent with the impact of the increased use of mammography when its effect is superimposed upon the background of declining or slowing secular trends. These results support previous reports linking incidence rates with the increase in screening-mammography. RP WUN, LM (reprint author), NCI,SURVEILLANCE PROGRAM,EPN 313,900 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 27 TC 34 Z9 35 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 MAR PY 1995 VL 6 IS 2 BP 135 EP 144 DI 10.1007/BF00052774 PG 10 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA QL730 UT WOS:A1995QL73000007 PM 7749053 ER PT J AU WHYATT, RM GARTE, SJ COSMA, G BELL, DA JEDRYCHOWSKI, W WAHRENDORF, J RANDALL, MC COOPER, TB OTTMAN, R TANG, DL TSAI, WY DICKEY, CP MANCHESTER, DK CROFTS, F PERERA, FP AF WHYATT, RM GARTE, SJ COSMA, G BELL, DA JEDRYCHOWSKI, W WAHRENDORF, J RANDALL, MC COOPER, TB OTTMAN, R TANG, DL TSAI, WY DICKEY, CP MANCHESTER, DK CROFTS, F PERERA, FP TI CYP1A1 MESSENGER-RNA LEVELS IN PLACENTAL TISSUE AS A BIOMARKER OF ENVIRONMENTAL EXPOSURE SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID ARYL-HYDROCARBON HYDROXYLASE; LUNG-CANCER; DNA ADDUCTS; PASSIVE SMOKERS; AIR-POLLUTION; GENE; SMOKING; METABOLISM; EXPRESSION; SUSCEPTIBILITY AB The human CYP1A1 gene codes for an inducible enzyme system involved in biotransformation of certain xenobiotics, including polycyclic aromatic hydrocarbons; some of the metabolites are carcinogenic and mutagenic. Effects of environmental exposures (smoking, air pollution, and diet) on CYP1A1 gene induction in placental tissue and the modulation of induction by the CYP1A1 Mspl RFLP were evaluated in two groups from Poland: 70 mother-child pairs from Krakow, a city with elevated air pollution; and 90 pairs from Limanowa, a less polluted area. Compared to placentas from nonsmoking women, CYP1A1 mRNA levels were significantly increased in placentas from current smokers (P < 0.001). Ex-smokers also had significantly higher placental mRNA levels, including women who quit smoking prior to pregnancy (P < 0.01). A marginal increase in CYP1A1 mRNA with environmental tobacco smoke exposure was evident. Within Krakow, there was an increase in CYP1A1 mRNA with ambient pollution at the place of residence for each woman, which was significant among women who were not employed away from the home (P < 0.05 controlling for smoking status, diet, and use of coal for heating). Significant increases in mRNA were associated with dietary consumption of smoked meat, cheese, and fish (P < 0.01). The CYP1A1 Mspl RFLP was not a significant determinant of CYP1A1 mRNA levels after controlling for smoking and other variables. Human placenta provides a readily available and responsive system that can serve as a model for evaluating environmental and genetic determinants of CYP1A1 induction. C1 COLUMBIA UNIV, SCH PUBL HLTH, DIV ENVIRONM HLTH SCI, NEW YORK, NY 10032 USA. NYU, MED CTR, NEW YORK, NY 10003 USA. COLORADO STATE UNIV, FT COLLINS, CO 80523 USA. NIEHS, RES TRIANGLE PK, NC 27709 USA. KRAKOW TECH UNIV, SCH MED, PL-31155 KRAKOW, POLAND. GERMAN CANC RES CTR, D-69720 HEIDELBERG, GERMANY. NEW YORK STATE PSYCHIAT INST & HOSP, NEW YORK, NY 10032 USA. UNIV COLORADO, DENVER, CO 80202 USA. RI Ottman, Ruth/O-2371-2013 FU NIEHS NIH HHS [R01-ES06722] NR 37 TC 47 Z9 47 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 EI 1538-7755 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAR PY 1995 VL 4 IS 2 BP 147 EP 153 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA QK538 UT WOS:A1995QK53800011 PM 7742722 ER PT J AU STRUEWING, JP LERMAN, C KASE, RG GIAMBARRESI, TR TUCKER, MA AF STRUEWING, JP LERMAN, C KASE, RG GIAMBARRESI, TR TUCKER, MA TI ANTICIPATED UPTAKE AND IMPACT OF GENETIC TESTING IN HEREDITARY BREAST AND OVARIAN-CANCER FAMILIES SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID HUNTINGTONS-DISEASE; SUSCEPTIBILITY; LINKAGE; RISKS AB In anticipation of the identification of the BRCA1 gene, we studied the interest in and anticipated reaction to DNA testing for mutations in this gene in members of high-risk families. We surveyed 91 female and 49 male subjects using a structured interview by study nurses. All subjects were members of inherited breast-ovarian cancer families participating in a genetic linkage study at the National Cancer Institute. The main outcomes of the study were interest in genetic testing and anticipated impact of test results. Seventy nine % of subjects indicated that they would ''definitely'' want to be tested, and 16% would ''probably'' want to be tested for mutations in the BRCA1 gene. Subjects with a high self-perceived risk of having an altered BRCA1 gene were more likely to definitely want testing (P = 0.02), while estimated true genetic risk did not predict interest in the test. Females were significantly more likely to definitely want testing (P = 0.005) and had a significantly greater mean anticipated negative-impact score (2.3) compared to males (1.0) (P < 0.001). We found a high level of interest in genetic testing for BRCA1 among members of inherited breast-ovarian cancer families participating in a genetic linkage study. While utilization may fall below levels of interest reported in this and other preliminary surveys, given the potential for early detection and treatment of breast and ovarian cancer, interest in BRCA1 testing may translate into high rates of uptake. These results indicate that it will be critical to incorporate follow-up counseling and support into BRCA1 testing programs. C1 GEORGETOWN UNIV,MED CTR,VINCENT T LOMBARDI CANC RES CTR,WASHINGTON,DC 20057. WESTAT RES INC,ROCKVILLE,MD 20850. RP STRUEWING, JP (reprint author), NCI,GENET EPIDEMIOL BRANCH,BLDG EPN,ROOM 439,6130 EXECUT BLVD,MSC 7372,BETHESDA,MD 20892, USA. RI Struewing, Jeffery/C-3221-2008; Tucker, Margaret/B-4297-2015; Struewing, Jeffery/I-7502-2013 OI Struewing, Jeffery/0000-0002-4848-3334 NR 15 TC 160 Z9 160 U1 3 U2 12 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAR PY 1995 VL 4 IS 2 BP 169 EP 173 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA QK538 UT WOS:A1995QK53800014 PM 7742725 ER PT J AU PATEL, AR OBRAMS, GI AF PATEL, AR OBRAMS, GI TI ADENOCARCINOMA OF THE LUNG SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Editorial Material ID NONSMOKING WOMEN; RISK-FACTORS; CANCER; SMOKING; SCAR RP PATEL, AR (reprint author), NCI, DEPT HLTH & HUMAN SERV, DIV CANC ETIOL, EPIDEMIOL & BIOSTAT PROGRAM, EXTRAMURAL PROGRAMS B, BETHESDA, MD 20892 USA. NR 20 TC 9 Z9 9 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAR PY 1995 VL 4 IS 2 BP 175 EP 180 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA QK538 UT WOS:A1995QK53800015 PM 7742726 ER PT J AU LIANG, BC MELTZER, PS GUAN, XY TRENT, JM AF LIANG, BC MELTZER, PS GUAN, XY TRENT, JM TI GENE AMPLIFICATION ELUCIDATED BY COMBINED CHROMOSOMAL MICRODISSECTION AND COMPARATIVE GENOMIC HYBRIDIZATION SO CANCER GENETICS AND CYTOGENETICS LA English DT Article ID MOLECULAR CYTOGENETIC ANALYSIS; INSITU HYBRIDIZATION; DNA-AMPLIFICATION; RAPID ANALYSIS; AMPLIFIED DNA; SOLID TUMORS; CELLS; CANCER AB Gene amplification is an important manifestation of genetic instability in cancer. Recently, the study of gene amplification has been greatly facilitated by the development of the molecular cytogenetic techniques of comparative genomic hybridization and chromosome microdissection. We describe in this brief overview a combined approach using both techniques, which allows the identification of chromosomal regions of gene amplification and provides entry point clones for target gene identification. This molecular/cytogenetic approach consisting of chromosome microdissection and comparative genomic hybridization should be valuable in identifying novel amplified genes important in neoplastic development and progression. RP LIANG, BC (reprint author), NIH,NATL CTR HUMAN GENOME RES,CANC GENET LAB,BLDG 49,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Guan, Xin-Yuan/A-3639-2009 OI Guan, Xin-Yuan/0000-0002-4485-6017 NR 27 TC 14 Z9 14 U1 0 U2 0 PU ELSEVIER SCIENCE PUBL CO INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0165-4608 J9 CANCER GENET CYTOGEN JI Cancer Genet. Cytogenet. PD MAR PY 1995 VL 80 IS 1 BP 55 EP 59 DI 10.1016/0165-4608(94)00153-3 PG 5 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA QQ230 UT WOS:A1995QQ23000011 PM 7697633 ER PT J AU MORENO, MB TITUS, JA COLE, MS TSO, JY LE, N PAIK, CH BAKACS, T ZACHARCHUK, CM SEGAL, DM WUNDERLICH, JR AF MORENO, MB TITUS, JA COLE, MS TSO, JY LE, N PAIK, CH BAKACS, T ZACHARCHUK, CM SEGAL, DM WUNDERLICH, JR TI BISPECIFIC ANTIBODIES RETARGET MURINE T-CELL CYTOTOXICITY AGAINST SYNGENEIC BREAST-CANCER IN-VITRO AND IN-VIVO SO CANCER IMMUNOLOGY IMMUNOTHERAPY LA English DT Article DE BISPECIFIC ANTIBODY; REDIRECTED LYSIS; TARGETED CYTOTOXICITY; MAMMARY TUMOR; MOUSE MODEL ID MAMMARY-TUMOR VIRUS; PERIPHERAL-BLOOD LYMPHOCYTES; HUMAN OVARIAN-CARCINOMA; MONOCLONAL-ANTIBODIES; NECROSIS-FACTOR; RECEPTOR ANTIBODIES; EXPRESSION; GROWTH; MICE; NEUTRALIZATION AB Bispecific antibodies with specificity for CD3 and a tumor antigen can redirect cytolytic T cells to kill tumor targets, regardless of their natural specificity, To assess the clinical potential of bispecific antibodies for treatment of human cancers we have, in the present study, adapted a totally syngeneic mouse model to the targeting of mouse T cells against mouse tumors in immunocompetent mice. We show that gp52 of the mouse mammary tumor virus (MTV) can serve as a tumor-specific antigen for redirected cellular cytotoxicity. Chemically crosslinked and genetically engineered bispecific antibodies with specificities for gp52 and murine CD3 epsilon-chain induced activated mouse T cells to specifically lyse mouse mammary tumor cells from cultured lines and primary tumors from C3H-MTV(+) mice. Retargeted T cells also blocked the growth of mammary tumors in vitro as well as their growth in syngeneic mice, These findings identify murine MTV-induced mammary adenocarcinomas as a solid-tumor, animal model for retargeting T cells with bispecific antibodies against syngeneic breast cancer. C1 NIH,CTR CLIN,DEPT NUCL MED,BETHESDA,MD 20892. NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892. NCI,IMMUNE CELL BIOL LAB,BETHESDA,MD 20892. PROT DESIGN LABS INC,MT VIEW,CA 94043. NR 44 TC 10 Z9 10 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 MAR PY 1995 VL 40 IS 3 BP 182 EP 190 DI 10.1007/BF01517350 PG 9 WC Oncology; Immunology SC Oncology; Immunology GA QV272 UT WOS:A1995QV27200006 PM 7728777 ER PT J AU SPEICHER, MR HOWE, C CROTTY, P DUMANOIR, S COSTA, J WARD, DC AF SPEICHER, MR HOWE, C CROTTY, P DUMANOIR, S COSTA, J WARD, DC TI COMPARATIVE GENOMIC HYBRIDIZATION DETECTS NOVEL DELETIONS AND AMPLIFICATIONS IN HEAD AND NECK SQUAMOUS-CELL CARCINOMAS SO CANCER RESEARCH LA English DT Note ID MOLECULAR CYTOGENETIC ANALYSIS; FINGER ENCODING GENE; SOLID TUMORS; IDENTIFICATION AB To gain a better understanding of genetic changes in squamous cell carcinomas of the head and neck we used comparative genomic hybridization for the analysis of 13 primary tumors. Copy number increases were most frequently observed on chromosomes 3q (10 cases) and 5p (8 cases) and less frequently on 1q (4 cases), 2 (1 case), 7 (2 cases), 8q (2 cases), 9 (1 case), 10p (2 cases), 13q (2 cases), 14q (1 case), 16 (1 case), 17 (2 cases), 20p (2 cases), 21q (1 case) and 22q (1 case). Copy number decreases occurred most frequently at 3p (5 cases), 5q (4 cases), 19p (6 cases), and 19q (5 cases). Copy number decreases also were observed on 1p (2 cases), 2q (2 cases), 4p (2 cases), 4q (2 cases), 7q (2 cases), 8p (1 case), 10q (1 case), 11p (2 cases), 11q (3 cases), 13q (3 cases), 14q (1 case), 16p (1 case), 17p (3 cases), 17q (1 case), 18q (1 case), and 22 (2 cases). Eight sites exhibiting significant sequence amplification were mapped to 3q26-->qter (3 cases), 11q13 (2 cases), 12p (2 cases), 2q33-36 (1 case), 7q21-22 (1 case), 7q33-->qter (1 case), 9p (1 case), and 13q32-->qter (1 case). Our data suggest that the regions 3q26-->qter and 5p mag harbor oncogenes important for initiation or progression of squamous cell carcinomas of the head and neck. In addition, comparative genomic hybridization defines a subgroup of tumors with 11q13 involvement, the location of the PRAD1/(CCND1/cyclin D1 gene. C1 YALE UNIV,SCH MED,DEPT PATHOL,NEW HAVEN,CT 06510. NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. RP SPEICHER, MR (reprint author), YALE UNIV,SCH MED,DEPT GENET,333 CEDAR ST,NEW HAVEN,CT 06510, USA. RI Speicher, Michael/B-5362-2013 OI Speicher, Michael/0000-0003-0105-955X NR 22 TC 161 Z9 163 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 MAR 1 PY 1995 VL 55 IS 5 BP 1010 EP 1013 PG 4 WC Oncology SC Oncology GA QJ600 UT WOS:A1995QJ60000010 PM 7866983 ER PT J AU ROBERTSTHOMSON, SJ MCMANUS, ME TUKEY, RH GONZALEZ, FJ HOLDER, GM AF ROBERTSTHOMSON, SJ MCMANUS, ME TUKEY, RH GONZALEZ, FJ HOLDER, GM TI METABOLISM OF POLYCYCLIC AZA-AROMATIC CARCINOGENS CATALYZED BY 4 EXPRESSED HUMAN CYTOCHROMES-P450 SO CANCER RESEARCH LA English DT Article ID LIVER MICROSOMAL METABOLITES; RAT-LIVER; K-REGION; TRANS-DIHYDRODIOLS; EPOXIDE HYDROLASE; 7-METHYLBENZACRIDINE; DIBENZACRIDINE; IDENTIFICATION; BENZOPYRENE; DERIVATIVES AB The role of human cytochromes P4501A1, -1A2, -3A4, and -3A5 in the metabolism of the polycyclic aza-aromatic hydrocarbons 7-methylbenz(c)acridine and dibenz(a,j)acridine was investigated. The regioselectivity of the reactions was determined, as well as the associated stereoselectivity in the production of dihydrodiol metabolites and K-region oxides. Metabolite distributions were also examined in the presence of the epoxide hydrolase inhibitor 1,1,1-trichloropropylene-2,3-oxide and the P450 modulator Lu-naphthoflavone. P4501A2 was most regioselective for the production of the proximate carcinogen; the 3,4-dihydrodiol of 7-methylbenz(c)acridine and P4503A4 showed the highest regioselectivity for K-region oxidation. In contrast, the analogous putative proximate carcinogen of dibenz(a,j)acridine was formed with the highest relative abundance by P4503A4, while P4501A2 was most regioselective for K-region oxidation. For both compounds the proximate carcinogens possessed predominantly the 3R,4R-absolute configuration, independent of the P450 catalyzing the reaction. The K-region dihydrodiols of 7-methylbenz (c)acridine were formed with no stereoselectivity, except with P1501A2 which favored production of the S,S isomer. In contrast the K-region dihydrodiol of dibenz(n,j)acridine was formed by P4501A1 and P4501A2 as the R,R isomer with almost 100% optical purity. P4501A2 and 3A4 showed no stereoselectivity in the formation of the K-region oxide of 7-methylbenz(c)acridine, while P4501A1 produced the 5R,6S-oxide with low optical purity. For dibenz(a,j)acridine 5,6-oxide, P4501A1 predominantly formed 5S,6R-oxide (80% pure). These results emphasize the importance of the composition and levels of expressed P450s of an individual in relation to the activation and detoxification of toxicants. C1 UNIV SYDNEY,DEPT PHARM,SYDNEY,NSW 2006,AUSTRALIA. UNIV QUEENSLAND,DEPT PHYSIOL & PHARMACOL,BRISBANE,QLD 4072,AUSTRALIA. UNIV CALIF SAN DIEGO,CTR CANC,DEPT PHARMACOL,LA JOLLA,CA 92093. NIH,MOLEC CARCINOGENESIS LAB,BETHESDA,MD 20892. RI Roberts-Thomson, Sarah/B-4282-2011 OI Roberts-Thomson, Sarah/0000-0001-8202-5786 FU NIGMS NIH HHS [GM36590] NR 59 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 0008-5472 J9 CANCER RES JI Cancer Res. PD MAR 1 PY 1995 VL 55 IS 5 BP 1052 EP 1059 PG 8 WC Oncology SC Oncology GA QJ600 UT WOS:A1995QJ60000016 PM 7866988 ER PT J AU CARDARELLI, CO AKSENTIJEVICH, I PASTAN, I GOTTESMAN, MM AF CARDARELLI, CO AKSENTIJEVICH, I PASTAN, I GOTTESMAN, MM TI DIFFERENTIAL-EFFECTS OF P-GLYCOPROTEIN INHIBITORS ON NIH3T3 CELLS TRANSFECTED WITH WILD-TYPE (G185) OR MUTANT (V185) MULTIDRUG TRANSPORTERS SO CANCER RESEARCH LA English DT Article ID RESISTANT TUMOR-CELLS; TRANSGENIC MICE; BONE-MARROW; DRUG-RESISTANCE; MDR1 CDNA; GENE; VINBLASTINE; EXPRESSION; IDENTIFICATION; COLCHICINE AB Multidrug resistance (MDR) may be associated with the expression of the MDR1 gene which encodes the 170-kDa cell surface P-glycoprotein (PGP) acting as an energy-dependent multidrug efflux pump. This pump can be inhibited by a variety of drugs including cyclosporin A, quinidine, and verapamil. Substrate specificity of the MDR1 gene product can be altered by a point mutation at amino acid residue 185 in which valine is substituted for glycine, but the effect of this mutation on inhibition of PGP is unknown. Multidrug-resistant NIH3T3 cells transfected with the MDR1 retroviral vector pHaMDR-1/A (G185) or pHaMDR1/A (V185) expressing comparable levels of PGP were compared for patterns of drug resistance and inhibition of drug resistance by MDR reversing agents. The NIH-MDR-G185 transfectants were somewhat preferentially resistant to daunorubicin, taxol, and vinblastine. The mutant (V185) conferred increased resistance to colchicine. This MDR phenotype in both NIH-MDR-G185- and NIH-MDR-V185-transfected NIH3T3 cells was overcome by the addition of cyclosporin A, quinidine, or verapamil. Verapamil was the most potent of the three agents affecting wild-type PGP. However, specific inhibitors showed different potency with wild-type or mutant transporters, depending on the cytotoxic drug whose resistance was being reversed. For example, cyclosporin A at a concentration of 1 mu g/ml was a powerful reverser of taxol and colchicine resistance for the mutant drug transporter, but was much less effective for the wild-type transporter. In contrast, verapamil reversed resistance to vinblastine more efficiently for the wild-type transporter than for the mutant transporter. These results suggest that the sensitivity of a multidrug transporter to a reversing agent will depend on the reversing agent, the cytotoxic drug, and the presence or absence of mutations which alter substrate specificity. C1 NCI,DIV CANC BIOL DIAG & CTR,CELL BIOL LAB,BETHESDA,MD 20892. NCI,DIV CANC BIOL DIAG & CTR,MOLEC BIOL LAB,BETHESDA,MD 20892. NR 47 TC 92 Z9 93 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAR 1 PY 1995 VL 55 IS 5 BP 1086 EP 1091 PG 6 WC Oncology SC Oncology GA QJ600 UT WOS:A1995QJ60000021 PM 7866993 ER PT J AU WALMER, DK PADIN, CJ WRONA, MA HEALY, BE BENTLEY, RC TSAO, MS KOHLER, MF MCLACHLAN, JA GRAY, KD AF WALMER, DK PADIN, CJ WRONA, MA HEALY, BE BENTLEY, RC TSAO, MS KOHLER, MF MCLACHLAN, JA GRAY, KD TI MALIGNANT TRANSFORMATION OF THE HUMAN ENDOMETRIUM IS ASSOCIATED WITH OVEREXPRESSION OF LACTOFERRIN MESSENGER-RNA AND PROTEIN SO CANCER RESEARCH LA English DT Article ID HUMAN-BREAST-CANCER; MOUSE UTERUS; HER-2 NEU; CELL-PROLIFERATION; GENE-EXPRESSION; OVARIAN-CANCER; MAMMARY-GLAND; S-PHASE; RECEPTOR; IDENTIFICATION AB In the mouse uterus, lactoferrin is a major estrogen-inducible uterine secretory protein, and its expression correlates directly with the period of peak epithelial cell proliferation. In this study, we examine the expression of lactoferrin mRNA and protein in human endometrium, endometrial hyperplasias, and adenocarcinomas using immunohistochemistry, Western immunoblotting, and Northern and in situ RNA hybridization techniques. Our results reveal that lactoferrin is expressed in normal cycling endometrium by a restricted number of glandular epithelial cells located deep in the zona basalis. Two thirds (8 of 12) of the endometrial adenocarcinomas examined overexpress lactoferrin. This tumor-associated increase in lactoferrin expression includes an elevation in the mRNA and protein of individual cells and an increase in the number of cells expressing the protein. In comparison, only 1 of the 10 endometrial hyperplasia specimens examined demonstrates an increase in lactoferrin. We also observe distinct cytoplasmic and nuclear immunostaining patterns under different fixation conditions in both normal and malignant epithelial cells, similar to those previously reported in the mouse reproductive tract. Serial sections of malignant specimens show a good correlation between the localization of lactoferrin mRNA and protein in individual epithelial cells by in situ RNA hybridization and immunohistochemistry. Although the degree of lactoferrin expression in the adenocarcinomas did not correlate with the tumor stage, grade, or depth of invasion in these 12 patients, there was a striking inverse correlation between the presence of progesterone receptors and lactoferrin in all 8 lactoferrin-positive adenocarcinomas. In summary, lactoferrin is expressed in a region of normal endometrium known as the zona basalis which is not shed with menstruation and is frequently overexpressed by progesterone receptor-negative cells in endometrial adenocarcinomas. C1 UNIV MICHIGAN,DEPT OBSTET & GYNECOL,ANN ARBOR,MI 48109. UNIV MARYLAND,SCH MED,BALTIMORE,MD 21201. DUKE UNIV,MED CTR,DEPT PATHOL,DURHAM,NC 27710. MONTREAL GEN HOSP,DEPT PATHOL,MONTREAL,PQ H3G 1A4,CANADA. NIEHS,REPROD & DEV TOXICOL LAB,RES TRIANGLE PK,NC 27709. UNIFORMED SERV UNIV HLTH SCI,DEPT OBSTET & GYNECOL,BETHESDA,MD 20814. RP WALMER, DK (reprint author), DUKE UNIV,MED CTR,DEPT OBSTET & GYNECOL,BOX 3143,DURHAM,NC 27710, USA. NR 47 TC 30 Z9 32 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 MAR 1 PY 1995 VL 55 IS 5 BP 1168 EP 1175 PG 8 WC Oncology SC Oncology GA QJ600 UT WOS:A1995QJ60000033 PM 7867003 ER PT J AU WIENER, F COLEMAN, A MOCK, BA POTTER, M AF WIENER, F COLEMAN, A MOCK, BA POTTER, M TI NONRANDOM CHROMOSOMAL CHANGE (TRISOMY-11) IN MURINE PLASMACYTOMAS INDUCED BY AN ABL-MYC RETROVIRUS SO CANCER RESEARCH LA English DT Article ID T-CELL LEUKEMIA; V-ABL; C-MYC; MOUSE CHROMOSOME-11; RAPID INDUCTION; TRANSLOCATION; PRISTANE; MICE; ONCOGENES; SEGMENT AB Trisomy of chromosome 11 (Ts11) is the second most frequent nonrandom chromosomal change in murine plasmacytomas (PCTs). The frequency of Ts11 is significantly higher in PCTs induced in pristane-conditioned mice infected by Abelson-murine leukemia virus (52%) compared to those induced by pristane alone (8.1%). Although the significance of Ts11 in mouse plasmacytomagenesis is not clearly understood it is hypothesized that a gene or genes located on chromosome (Chr) 11 may specifically promote the development of PCTs in which both oncogenes, c-myc and v-abl, are abundantly expressed. To test this assumption we induced PCTs by three highly effective plasmacytomagenic retroviruses: ABL-MYC, J3V1, and RIM. Nearly 90% of PCTs that arose in BALB/c, (BALB/c x DBA/2N)F-1, BALB/c-nu/nu, and 5-month-old SCID mice infected with ABL-MYC virus were trisomic for Chr 11. In contrast, <10% of PCTs induced by J3V1 or RIM retroviral constructs encompassing either v-myc and v-raf or c-myc and v-Ha-ras oncogenes, respectively, contained Ts11. We have also investigated whether the entire Chr 11 or any particular subregion is preferentially duplicated in the process of ABL-MYC plasmacytomagenesis. By inducing PCTs in F1 heterozygous mice that are carriers of reciprocal translocations involving Chr 11 we found that the duplicated chromosomal region is located distal to the T4Dn breakpoint (11B5 band) on the telomeric segment of Chr 11. The regular duplication of this chromosomal segment strongly suggests the presence of a gene or genes whose amplification is of critical importance for v-abl associated murine plasmacytomagenesis. C1 NCI,GENET LAB,BETHESDA,MD 20892. KAROLINSKA INST,CTR MICROBIOL & TUMORBIOL,S-17177 STOCKHOLM,SWEDEN. NR 46 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 0008-5472 J9 CANCER RES JI Cancer Res. PD MAR 1 PY 1995 VL 55 IS 5 BP 1181 EP 1188 PG 8 WC Oncology SC Oncology GA QJ600 UT WOS:A1995QJ60000035 PM 7867005 ER PT J AU PETRAKOVA, E GLAUDEMANS, CPJ AF PETRAKOVA, E GLAUDEMANS, CPJ TI SYNTHESIS OF METHYL GLYCOSIDES OF SOME ALPHA-ISOMALTO OLIGOSACCHARIDES SPECIFICALLY DEOXYGENATED AT POSITION C-2 SO CARBOHYDRATE RESEARCH LA English DT Article DE SYNTHESIS; METHYL GLYCOSIDES; ALPHA-ISOMALTO OLIGOSACCHARIDES; DEOXYGENATED ID STEREOSELECTIVE SYNTHESIS; ANTHRACYCLINE OLIGOSACCHARIDES; CANCER-THERAPY; RHODOMYCINS; ANTIBODIES; ANALOGS AB Methyl alpha-isomaltoside and methyl alpha-isomaltotrioside analogues specifically deoxygenated at position C-2 of various glucopyranosyl units were synthesized by condensation of either 6-O-acetyl-3-O-benzoyl-4-O-benzyl-1-O-tert-butyldimethylsilyl-2-deoxy-beta-D-arabino-hexopyranose (trimethylsilyl triflate mediated) or 6-O-acetyl-2,3,4-tri-O-benzyl-alpha-D-glucpyranosyl chloride (mediated by silver carbonate and silver triflate) with suitably blocked derivatives of methyl alpha-D-glucopyranoside, its 2-deoxy analogue, or methyl 2'-deoxy-alpha-isomaltoside. C1 NIDDK,BETHESDA,MD 20892. NR 21 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0008-6215 J9 CARBOHYD RES JI Carbohydr. Res. PD MAR 1 PY 1995 VL 268 IS 1 BP 35 EP 46 DI 10.1016/0008-6215(94)00314-6 PG 12 WC Biochemistry & Molecular Biology; Chemistry, Applied; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA QK275 UT WOS:A1995QK27500003 PM 7736465 ER PT J AU GOTOH, M KOVAC, P AF GOTOH, M KOVAC, P TI SYNTHESIS OF SPECIFICALLY DEOXYGENATED ANALOGS OF THE METHYL ALPHA-GLYCOSIDE OF THE INTRACATENARY MONOSACCHARIDE REPEATING UNIT OF THE O-POLYSACCHARIDE OF VIBRIO-CHOLERAE O/1 SO CARBOHYDRATE RESEARCH LA English DT Article DE DEOXYGENATED ANALOGS; METHYL ALPHA-GLYCOSIDE; MONOSACCHARIDE REPEATING UNIT; O-POLYSACCHARIDE; VIBRIO CHOLERAE 0, 1 ID ANTIGENIC DETERMINANTS; BLOCK SYNTHESIS; PENTASACCHARIDE; THIOGLYCOSIDE; DERIVATIVES AB Treatment of methyl alpha-D-perosaminide (1) with gamma-butyrolactone gave the 2'-deoxy analogue of methyl 4,6-dideoxy-4-(3-deoxy-1-glycero-tetronamido)-alpha-D-mannopyranoside (13), the methyl alpha-glycoside of the intracatenary monosaccharide repeating unit of the O-polysaccharide of Vibrio cholerae O:1. The analogous Q-deoxy derivative was obtained by hydrogenolysis of a 4'-chlorodeoxy precursor, obtained by chlorination of methyl 2,3-di-O-benzyl-4-(2-O-benzyl-3-deoxy-L-glycero-tetronamido)-4,6-dideoxy-alpha-D-mannopyranoside with methanesulfonyl chloride in DMF. To obtain the 3-deoxy analogue of 13, methyl 4-amino-2-O-benzyl-4,6-dideoxy-3-O-p-methoxy-benzyl-alpha-D-mannopyranoside was converted into methyl 2-O-benzyl-4,6-dideoxy-4-(2,4-di-O-benzyl-3-deoxy-L-glycero-tetronamido)-alpha-D-mannopyranoside, which was deoxygenated via the corresponding 3-O-(imidazol-1-ylthiocarbonyl) derivative. Subsequent catalytic debenzylation gave the deoxy compound (24). In an alternative synthesis, which is also generally useful for the preparation of 4-N-acyl-3-deoxy derivatives of 1, methyl 4-azido-4,6-dideoxy-alpha-D-mannopyranoside was converted through a series of transformations into methyl 4-amino-2-O-benzyl-3,4,6-trideoxy-alpha-D-mannopyranoside. Subsequent reaction with 2-O-benzyl-3-deoxy-L-glycero-tetronolactone, followed by hydrogenolysis of the formed tetronamido derivative, gave 24. C1 NIDDK,LMC,CARBOHYDRATES SECT,BETHESDA,MD 20892. NR 17 TC 14 Z9 14 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0008-6215 J9 CARBOHYD RES JI Carbohydr. Res. PD MAR 1 PY 1995 VL 268 IS 1 BP 73 EP 84 DI 10.1016/0008-6215(94)00319-B PG 12 WC Biochemistry & Molecular Biology; Chemistry, Applied; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA QK275 UT WOS:A1995QK27500006 PM 7537627 ER PT J AU PETRAKOVA, E GLAUDEMANS, CPJ AF PETRAKOVA, E GLAUDEMANS, CPJ TI ANOMALOUS ZEMPLEN DEACYLATION OF PROTECTED METHYL 2-DEOXY-ALPHA-D-ARABINO-HEXOPYRANOSIDES AND RELATED METHYL ALPHA-ISOMALTOSIDES AND ALPHA-ISOMALTOTRIOSIDES SO CARBOHYDRATE RESEARCH LA English DT Note DE ZEMPLEN DEACYLATION; PROTECTED METHYL 2-DEOXY-ALPHA-D-ARABINO-HEXOPYRANOSIDES; METHYL ALPHA-ISOMALTOSIDES; ALPHA-ISOMALTOTRIOSIDES ID SUGAR CHEMISTRY C1 NIDDK,BETHESDA,MD 20892. NR 14 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0008-6215 J9 CARBOHYD RES JI Carbohydr. Res. PD MAR 1 PY 1995 VL 268 IS 1 BP 135 EP 141 DI 10.1016/0008-6215(94)00315-7 PG 7 WC Biochemistry & Molecular Biology; Chemistry, Applied; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA QK275 UT WOS:A1995QK27500012 PM 7736462 ER PT J AU DIPPLE, A AF DIPPLE, A TI DNA-ADDUCTS OF CHEMICAL CARCINOGENS SO CARCINOGENESIS LA English DT Article ID REGION 3,4-DIOL 1,2-EPOXIDES; GUANINE RESIDUES; CYTOSINE BASES; ARALKYLATION; SELECTIVITY; ALKYLATION; ADENINE; ACID RP DIPPLE, A (reprint author), NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,CHEM CARCINOGENESIS LAB,POB B,FREDERICK,MD 21702, USA. FU NCI NIH HHS [N01-CO-46000] NR 25 TC 213 Z9 218 U1 1 U2 15 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 MAR PY 1995 VL 16 IS 3 BP 437 EP 441 DI 10.1093/carcin/16.3.437 PG 5 WC Oncology SC Oncology GA QP093 UT WOS:A1995QP09300001 PM 7697795 ER PT J AU MUDERS, F KROMER, EP BAHNER, U ELSNER, D ACKERMANN, B SCHUNKERT, H PALKOVITS, M RIEGGER, GAJ AF MUDERS, F KROMER, EP BAHNER, U ELSNER, D ACKERMANN, B SCHUNKERT, H PALKOVITS, M RIEGGER, GAJ TI CENTRAL VASOPRESSIN IN EXPERIMENTAL AORTIC-STENOSIS IN THE RAT SO CARDIOVASCULAR RESEARCH LA English DT Article DE VASOPRESSIN; CARDIOVASCULAR REGULATION; BRAIN NUCLEI; AORTIC STENOSIS ID CONGESTIVE HEART-FAILURE; RENIN-ANGIOTENSIN SYSTEM; CARDIOVASCULAR REGULATION; LOCUS COERULEUS; BRAIN; NEURONS; RELEASE; OSMORECEPTORS; BARORECEPTORS; HORMONE AB Objective: In several forms of heart disease characterised by low cardiac output, activated neurohumoral systems including increased vasopressin plasma levels play a key role in the changes in cardiovascular function. The aim of this study was to test the hypothesis that under such conditions the central vasopressin system might also be altered, which could contribute to deranged cardiovascular control. Methods: Aortic stenosis was produced in 22 rats by placing a Silver clip (inner diameter 0.6 mm) on the ascending aorta. After 12 weeks, haemodynamic and hormonal measurements were performed, and vasopressin content was determined in 20 microdissected brain areas (micropunch technique). Twenty two sham operated rats served as controls. Results: Twelve weeks after placing the supravalvular clip, significant aortic stenosis was documented by left ventricular myocardial hypertrophy. Cardiac index was significantly reduced and the peripheral vascular resistance index was increased, while poststenotic aortic pressure was non-significantly decreased. Plasma renin concentration [6.8(SEM 0.9) v 2.1(0.2) ngAI.ml(-1).h(-1) in controls] and plasma vasopressin [32.9(12.5) v 18.4(6.0) pg.ml(-1)] were significantly increased, while plasma and urinary noradrenaline remained unaltered. The vasopressin content was significantly altered in eight out of 20 brain areas investigated. Concerning the vasopressin producing hypothalamic nuclei, concentrations were increased in the paraventricular [7494(360) v 4744(237) pg.mg(-1) protein, P<0.05] and suprachiasmatic [3613(170) v 1784(197) pg.mg(-1) protein, P<0.01], but not in the supraoptic nuclei. Rats with aortic stenosis showed significantly raised vasopressin concentrations in the median eminence [25 186(1682) v 37 367(1345) pg.mg(-1) protein, P< 0.01], where the hormone is mainly concentrated in the hypothalamo-hypophysial tract. Vasopressin content was significantly decreased in locus coeruleus [49(5) v 89(6) pg.mg(-1) protein], which is known to be involved in modulation of sympathetic activity. Conclusions: As well as showing increased secretion of vasopressin into the blood with consecutive peripheral antidiuretic and vasoconstrictive effects, these data suggest an alteration in the central vasopressin system in aortic stenosis which might transmit cardiovascular effects by neuromodulation and neuroregulation. C1 UNIV REGENSBURG,INNERE MED KLIN POLIKLIN 2,D-93053 REGENSBURG,GERMANY. UNIV WURZBURG,MED KLIN,W-8700 WURZBURG,GERMANY. NIMH,CELL BIOL LAB,BETHESDA,MD 20892. RI Palkovits, Miklos/F-2707-2013; OI Palkovits, Miklos/0000-0003-0578-0387 NR 44 TC 12 Z9 12 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0008-6363 J9 CARDIOVASC RES JI Cardiovasc. Res. PD MAR PY 1995 VL 29 IS 3 BP 416 EP 421 DI 10.1016/S0008-6363(96)88600-7 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA QP174 UT WOS:A1995QP17400016 PM 7781015 ER PT J AU MINNITI, CP LUAN, D OGRADY, C ROSENFELD, RG OH, Y HELMAN, LJ AF MINNITI, CP LUAN, D OGRADY, C ROSENFELD, RG OH, Y HELMAN, LJ TI INSULIN-LIKE GROWTH-FACTOR-II OVEREXPRESSION IN MYOBLASTS INDUCES PHENOTYPIC CHANGES TYPICAL OF THE MALIGNANT PHENOTYPE SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID IGF-I; MESSENGER-RNA; MUSCLE DIFFERENTIATION; CELL-LINE; EXPRESSION; PROTEIN; GENE; INHIBITION; MYOGENESIS; RECEPTORS AB The objective of this study was to examine the role of insulin-like growth factor it (IGF-II) in the pathogenesis of human rhabdomyosarcomas (RMS). We have demonstrated previously that RMS express high levels of lGF-II mRNA, secrete IGF-II peptide, and express both IGF-I and IGF-II receptors. Moreover, we showed that IGF-II functions as an autocrine growth and motility factor in RMS. Since IGF-II is expressed at high levels in fetal muscle cells and RMS are tumors thought to derive from skeletal myoblasts arrested along the normal myogenic pathway, autocrine production of IGF-II by RMS may be an etiological event in the development of this tumor. We have developed a model system which enabled us to study the effects of endogenous IGF-II overprotection in muscle myoblasts. Human cDNA for pre-prohormone IGF-II was transfected into mouse myoblasts in order to achieve high, constant expression of this growth factor, which is normally down-regulated at the end of the differentiation process. Expression of high IGF-II levels resulted in: (a) an increased proliferative rate; (b) impairment of the ability to differentiate into myoblasts; and (c) acquisition of the capability of anchorage-independent growth. No changes in the expression of IGF-I receptors were noted. We conclude that IGF-II overexpression in muscle myoblasts induces morphological and biological changes typical of the malignant phenotype and represents a fundamental event in the pathogenesis of RMS and possibly of other embryonal tumors. C1 OREGON HLTH SCI UNIV,DEPT PEDIAT,PORTLAND,OR 97201. NCI,PEDIAT BRANCH,BETHESDA,MD 20892. RP MINNITI, CP (reprint author), GEORGETOWN UNIV,SCH MED,LOMBARDI CANC CTR,WASHINGTON,DC 20007, USA. NR 35 TC 32 Z9 33 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 MAR PY 1995 VL 6 IS 3 BP 263 EP 269 PG 7 WC Cell Biology SC Cell Biology GA QK966 UT WOS:A1995QK96600005 PM 7794794 ER PT J AU ROBERTS, JL SHARROW, SO SINGER, A AF ROBERTS, JL SHARROW, SO SINGER, A TI DISRUPTION OF INTRATHYMIC CD4-IA INTERACTIONS ON IMMATURE CD4(+)CD8(+) THYMOCYTES RESULTS IN DIMINISHED TCR EXPRESSION ON MATURE CD8(+) T-CELL PROGENY SO CELLULAR IMMUNOLOGY LA English DT Article ID RECEPTOR TRANSGENIC MICE; MONOCLONAL-ANTIBODY; NEGATIVE SELECTION; POSITIVE SELECTION; ANTIGEN RECEPTOR; CD4+8+ THYMOCYTES; CD4+CD8+ CELLS; MOLECULES; DELETION; DIFFERENTIATION AB Cell surface TCR expression by developing thymocytes is actively regulated during ontogeny. Whereas most immature CD4(+)CD8(+) thymocytes express low levels of TCR alpha beta, mature CD4(+) and CD8(+) thymocytes express significantly higher levels of surface TCR. Low TCR expression on CD4(+)CD8(+) thymocytes is due, at least in part, to inhibitory signals generated by CD4 interactions with MHC class II ligands in the thymus. In the present study we wished to determine whether levels of TCR expressed on mature thymocytes were also influenced by CD4-Ia interactions that had occurred on their CD4(+)CD8(+) precursors. To do so, we examined TCR expression on mature CD8(+) T cells from animals in which CD4-ligand interactions had been disrupted experimentally by in vivo administration of anti-CD4 mAb or by targeted disruption of an MHC class II gene. We found that TCR expression was significantly diminished on all mature CD8(+) T cells from both anti-CD4 mAb-treated mice and MHC class II-deficient animals. These results demonstrate that TCR expression by mature CD8(+) T cells, as well as that of immature CD4(+)CD8(+) thymocytes, is regulated by CD4-mediated signals acting on CD4(+)CD8(+) thymocytes. Because the effects of disrupting CD4-Ia interactions on TCR expression by CD8(+) T cells were independent of TCR specificity, these findings directly support the concept that CD4(-)CD8(+) T cells arise from precursor CD4(+)CD8(+) cells. (C) 1995 Academic Press, Inc. C1 NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892. NR 34 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD MAR PY 1995 VL 161 IS 1 BP 22 EP 27 DI 10.1006/cimm.1995.1004 PG 6 WC Cell Biology; Immunology SC Cell Biology; Immunology GA QK252 UT WOS:A1995QK25200004 PM 7867081 ER PT J AU AHEARNE, PM MORGAN, RA SEBASTIAN, MW BOLOGNESI, DP WEINHOLD, KJ AF AHEARNE, PM MORGAN, RA SEBASTIAN, MW BOLOGNESI, DP WEINHOLD, KJ TI MULTIPLE CTL SPECIFICITIES AGAINST AUTOLOGOUS HIV-1-INFECTED BLCLS SO CELLULAR IMMUNOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; TOXIC LYMPHOCYTES-T; EPSTEIN-BARR VIRUS; RECOMBINANT VACCINIA VIRUS; HTLV-III INFECTION; B-CELL LINES; HIV-INFECTION; PERSISTENT; AIDS; EXPRESSION AB The cellular immune response to HIV-1 has been well studied but, in many respects, remains incompletely defined. Although CTL specificities against highly conserved HIV-1 determinants as dictated by vaccinia/HIV-1 vector constructs have been described, much less is known regarding patient cellular reactivities against autologous cells infected with HIV-1. One of the main obstacles in characterizing this cellular reactivity has been the absence of a targeting system which accurately represents the HIV infected cell in vivo and is, at the same time, adaptable for in vitro assays. Through the use of two separate strategies aimed at increasing cellular CD4 expression, we were able to infect B-lymphocyte cell lines (BLCLs) with multiple strains of HIV-1. HIV-1-infected BLCLs were recognized by autologous effector cells with cytolytic specificities against env, gag, or pol determinants. In addition, HIV-1-infected BLCLs were capable of eliciting in vitro CTL reactivities directed against env-, gag-, and pol-expressing targets. This cellular reactivity was mediated by CD8(+) cells and was MHC Class I restricted, suggesting a classical CTL response. Since multiple antigens are recognized, an HIV-1-infected BLCL is a more natural representation of an in vivo cellular target than other available testing systems and should permit a more representative analysis of CTL responses during infection or following vaccination. (C) 1995 Academic Press, Inc. C1 DUKE UNIV,MED CTR,DEPT SURG,DURHAM,NC 27710. NHLBI,MOLEC HEMATOL BRANCH,BETHESDA,MD 20892. FU NHLBI NIH HHS [5232-HL07671]; NIAID NIH HHS [5-P30-AI28662, R01-AI29852] NR 19 TC 6 Z9 7 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD MAR PY 1995 VL 161 IS 1 BP 34 EP 41 DI 10.1006/cimm.1995.1006 PG 8 WC Cell Biology; Immunology SC Cell Biology; Immunology GA QK252 UT WOS:A1995QK25200006 PM 7867083 ER PT J AU HOUK, JC WISE, SP AF HOUK, JC WISE, SP TI DISTRIBUTED MODULAR ARCHITECTURES LINKING BASAL GANGLIA, CEREBELLUM, AND CEREBRAL-CORTEX - THEIR ROLE IN PLANNING AND CONTROLLING ACTION SO CEREBRAL CORTEX LA English DT Review ID MONKEY DOPAMINE NEURONS; CAT VISUAL-CORTEX; MOTOR CORTEX; RHESUS-MONKEY; INTERMEDIATE CEREBELLUM; PARKINSONS-DISEASE; GLOBUS-PALLIDUS; PRIMATE PUTAMEN; ARM MOVEMENTS; CORTICOSTRIATAL PROJECTIONS AB The motor system includes structures distributed widely through the CNS, and in this feature article we present a scheme for how they might cooperate in the control of action. Distributed modules, which constitute the basic building blocks of our model, include recurrent leaps connecting distant brain structures, as well as local circuitry that modulates loop activity. We consider interconnections among the basal ganglia, cerebellum, and cerebral cortex and the specialized properties of certain cell types within each of those structures, namely, striatal spiny neurons, cerebellar Purkinje cells, and neocortical pyramidal cells. In our model, striatal spiny neurons of the basal ganglia function in contextual pattern recognition under the training influence of reinforcement signals transmitted in dopamine fibers. Cerebellar Purkinje cells also function in pattern recognition, in their case to select and execute actions through training supervised by climbing fibers, which signal discoordination. Neocortical pyramidal cells perform collective computations learned through a local training mechanism and also function as information stores for other modular operations. We discuss how distributed modules might function in a parallel, cooperative manner to plan, modulate, and execute action. C1 NIMH, NEUROPHYSIOL LAB, POOLESVILLE, MD 20837 USA. RP NORTHWESTERN UNIV, MED CTR, SCH MED, DEPT PHYSIOL, 303 E CHICAGO AVE, CHICAGO, IL 60611 USA. FU NIMH NIH HHS [P50 MH 48185] NR 165 TC 333 Z9 337 U1 1 U2 21 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 MAR-APR PY 1995 VL 5 IS 2 BP 95 EP 110 DI 10.1093/cercor/5.2.95 PG 16 WC Neurosciences SC Neurosciences & Neurology GA QP100 UT WOS:A1995QP10000001 PM 7620294 ER PT J AU MURPHY, E GLASGOW, W FRALIX, T STEENBERGEN, C AF MURPHY, E GLASGOW, W FRALIX, T STEENBERGEN, C TI ROLE OF LIPOXYGENASE METABOLITES IN ISCHEMIC PRECONDITIONING SO CIRCULATION RESEARCH LA English DT Article DE LIPOXYGENASE; ISCHEMIC PRECONDITIONING; HYDROXYEICOSATETRAENOIC ACID ID ARACHIDONIC-ACID METABOLITES; PERFUSED RAT-HEART; PROTEIN-KINASE-C; SIGNAL TRANSDUCTION; MYOCARDIAL-ISCHEMIA; CARDIAC MYOCYTES; K+ CHANNELS; POSTISCHEMIC RECOVERY; VENTRICULAR MYOCYTES; REPORTED OBSERVATION AB Preconditioning with brief intermittent periods of ischemia before a sustained period of ischemia has been shown to reduce infarct size and improve recovery of function in rat hearts. The mediators of this protective response are unknown in rats. We tested the hypothesis that a lipoxygenase metabolite might be involved in preconditioning, since lipoxygenase metabolites such as 12-hydroperoxyeicosatetraenaic acid have been shown to increase K+ channel activity and to decrease Ca2+ channel activity, which could have a protective effect on ischemic injury. In support of this hypothesis, we report that the lipoxygenase inhibitors nordihydroguaiaretic acid (NDGA, 5 mu mol/L) and eicosatetraynoic acid (7 mu mol/L) added just before and during preconditioning blocked the protective effects of preconditioning on recovery of function during reflow after 30 minutes of global ischemia. In addition, these lipoxygenase inhibitors partially blocked the ability of preconditioning to attenuate the rise in cytosolic free calcium during sustained ischemia. We also investigated the effects of preconditioning on eicosanoid metabolism by using high-performance liquid chromatography and found that 12-hydroxyeicosatetraenoic acid (12-HETE), the stable product of the lipoxygenase pathway, was made during the preconditioning protocol and that 12-HETE accumulation was blocked by NDGA. Thus, there is a correlation between functional recovery after ischemia and stimulation of the lipoxygenase pathway of arachidonic acid metabolism before the sustained period of ischemia; inhibition of the lipoxygenase pathway eliminates the protective effect of preconditioning on recovery of function after ischemia. C1 DUKE UNIV,MED CTR,DEPT PATHOL,DURHAM,NC 27710. RP MURPHY, E (reprint author), NIEHS,MOLEC BIOPHYS LAB,POB 12233,RES TRIANGLE PK,NC 27709, USA. FU NHLBI NIH HHS [HL-39752, R01 HL039752] NR 75 TC 51 Z9 52 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7330 J9 CIRC RES JI Circ.Res. PD MAR PY 1995 VL 76 IS 3 BP 457 EP 467 PG 11 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA QP859 UT WOS:A1995QP85900016 PM 7859391 ER PT J AU RABKIN, CS BEDI, G MUSABA, E SUNKUTU, R MWANSA, N SIDRANSKY, D BIGGAR, RJ AF RABKIN, CS BEDI, G MUSABA, E SUNKUTU, R MWANSA, N SIDRANSKY, D BIGGAR, RJ TI AIDS-RELATED KAPOSIS-SARCOMA IS A CLONAL NEOPLASM SO CLINICAL CANCER RESEARCH LA English DT Note ID POLYMORPHISMS; PATHOGENESIS; ORIGIN; CANCER AB Kaposi's sarcoma is generally believed to be a nonneoplastic hyperproliferation because it may regress spontaneously and its spindle cells lack features of typical tumor cells, such as aneuploidy, nuclear atypia, and permissive growth in cell culture. A fundamental characteristic of neoplasms is clonality, in that they arise from clonal replication of a single cell whereas reactive processes are derived from polyclonal proliferation. We used an X chromosome inactivation assay to determine the clonality of Kaposi's sarcoma nodules from patients with AIDS-related disease. The assay is based on a methyl-sensitive restriction digest followed by PCR amplification of the highly polymorphic androgen receptor gene. Two of three evaluable cases had a monoclonal pattern of inactivation, and the third case had a clonal expansion of cells with an altered microsatellite repeat sequence. These data suggest that Kaposi's sarcoma (at least in the AIDS setting) is a clonal neoplasm. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT OTOLARYNGOL,BETHESDA,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT HEAD & NECK SURG,BETHESDA,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT ONCOL,BETHESDA,MD 21205. NCI,VIRAL EPIDEMIOL BRANCH,BETHESDA,MD 20892. UNIV LUSAKA,TEACHING HOSP,DEPT DERMATOVENEREOL,LUSAKA,ZAMBIA. NR 19 TC 49 Z9 49 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAR PY 1995 VL 1 IS 3 BP 257 EP 260 PG 4 WC Oncology SC Oncology GA RJ527 UT WOS:A1995RJ52700002 PM 9815980 ER PT J AU CHEN, CC PREMKUMAR, A HILL, SC SKARULIS, MC SPIEGEL, AM AF CHEN, CC PREMKUMAR, A HILL, SC SKARULIS, MC SPIEGEL, AM TI TC-99M SESTAMIBI IMAGING OF A HYPERFUNCTIONING PARATHYROID AUTOGRAFT WITH DOPPLER ULTRASOUND AND MRI CORRELATION SO CLINICAL NUCLEAR MEDICINE LA English DT Article ID TECHNETIUM 99M SESTAMIBI; GLANDS; HYPERPARATHYROIDISM; TRANSPLANTATION; LOCALIZATION; SCINTIGRAPHY; TISSUE AB The authors describe a case in which Tc-99m sestamibi demonstrated increased vascularity and uptake in a hyperfunctioning autograft in a patient with recurrent hyperparathyroidism and multiple endocrine neoplasia type 1. Findings were confirmed by differential parathyroid hormone levels in antecubital venous blood samples, ultrasound with color Doppler, MRI, and surgery. C1 WARREN G MAGNUSON CLIN CTR,DEPT RADIOL,BETHESDA,MD. NATL INST DIABET DIGEST & KIDNEY DIS,BETHESDA,MD. RP CHEN, CC (reprint author), WARREN G MAGNUSON CLIN CTR,DEPT NUCL MED,BETHESDA,MD, USA. NR 15 TC 11 Z9 12 U1 1 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0363-9762 J9 CLIN NUCL MED JI Clin. Nucl. Med. PD MAR PY 1995 VL 20 IS 3 BP 222 EP 225 DI 10.1097/00003072-199503000-00007 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA QL189 UT WOS:A1995QL18900007 PM 7750215 ER PT J AU JUNE, HL STITZER, ML CONE, E AF JUNE, HL STITZER, ML CONE, E TI ACUTE PHYSICAL-DEPENDENCE - TIME-COURSE AND RELATION TO HUMAN PLASMA MORPHINE CONCENTRATIONS SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID NALOXONE-PRECIPITATED WITHDRAWAL; METHADONE; EXPOSURE; INTERVAL; MONKEY; RATS AB Objectives: To characterize the postmorphine time course of precipitated withdrawal responses in comparison with the time course of opioid agonist effects and of plasma morphine concentrations. Background: The study provides a more detailed and comprehensive assessment of the postagonist time course of acute dependence effects in humans than previously available. Design: Opioid agonist effects, morphine plasma levels, and withdrawal effects precipitated by naloxone (10 mg/70 kg, administered intramuscularly) were examined at 1, 3, 6, 12, 18, 24, 30, 36, and 42 hours after a single dose of morphine (18 mg/70 kg, administered intramuscularly) in 10 nondependent opioid-experienced subjects. Results: The intensity of subjectively reported precipitated withdrawal effects was greatest when testing was conducted at 6 hours after morphine administration, whereas peak intensity of agonist effects (pupil constriction and subjective ratings) and highest plasma morphine concentrations (57.3 ng/ml) were observed at the shortest test interval (1 hour) after morphine. Offset time course of naloxone-precipitated effects differed across specific measures, with hot and cold feelings elevated for the longest time after morphine (36 hrs), but significant effects were generally apparent for up to 24 hours after morphine pretreatment. Agonist effects lasted through only 12 hours; trace amounts of morphine were detected in plasma for up to 30 hours after administration. Conclusions: Results show that acute physical dependence engendered by a single dose of morphine peaks later and persists over a longer duration after morphine administration than do other agonist effects. This suggests that neuronal adaptations underlying physical dependence develop and decay gradually over time during a single episode of receptor occupancy. The presence of detectable morphine in plasma is consistent with a competitive displacement mechanism of precipitated effects, although noncompetitive actions of morphine or its metabolites are not ruled out. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT PSYCHIAT & BEHAV SCI,BEHAV PHARMACOL RES UNIT,BALTIMORE,MD 21218. NIDA,ADDICT RES CTR,BALTIMORE,MD 21224. FU NIDA NIH HHS [DA-07209, DA-04011] NR 29 TC 36 Z9 37 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 MAR PY 1995 VL 57 IS 3 BP 270 EP 280 DI 10.1016/0009-9236(95)90152-3 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA QP664 UT WOS:A1995QP66400003 PM 7697945 ER PT J AU MUMFORD, GK EVANS, SM FLEISHAKER, JC GRIFFITHS, RR AF MUMFORD, GK EVANS, SM FLEISHAKER, JC GRIFFITHS, RR TI ALPRAZOLAM ABSORPTION KINETICS AFFECTS ABUSE LIABILITY SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID DIAZEPAM; HUMANS; PHARMACOKINETICS; CHOICE; PHARMACODYNAMICS; REINFORCEMENT; PREFERENCE; TRIAZOLAM; LORAZEPAM; OXAZEPAM AB Objective: To evaluate the behavioral, subjective, and reinforcing effects of immediate-release (IR) alprazolam and extended-release (XR) alprazolam to assess the effect of release rate on laboratory measures of abuse liability. Methods: Fourteen healthy men with histories of sedative abuse participated as subjects in a double-blind crossover study. All subjects received placebo, 1 and 2 mg immediate-release alprazolam, and 2 and 3 mg extended-release alprazolam in random order. Behavioral performance, subjective effects, and alprazolam plasma concentrations were assessed repeatedly 1/2 hour before and 1/2, 1, 3, 5, 7, 9, 12, and 24 hours after drug administration. Results: Mean peak alprazolam plasma concentrations occurred 1.7 and 9.2 hours after immediate-release alprazolam and extended-release alprazolam, respectively. Compared to placebo, 2 mg immediate-release alprazolam impaired all measures of psychomotor and cognitive performance (Digit Symbol Substitution Test), motor coordination (circular lights and balance), and memory (digit entry and recall); 2 mg extended-release alprazolam did not aged any of these measures and 3 mg extended-release alprazolam impaired circular lights only. Immediate-release alprazolam, 2 mg, increased all six measures of positive drug effects (e.g., ratings of liking or good effects); none of these measures were increased by 2 mg extended-release alprazolam and only three of the six measures were increased by 3 mg extended-release alprazolam. A drug versus money multiple-choice procedure designed to assess the relative reinforcing effects of each condition was administered 24 hour after the drug. The amount of money subjects were willing to ''pay'' to take the drug was significantly greater than placebo for both doses of immediate-release alprazolam but for neither dose of extended-release alprazolam. Conclusions: These data indicate that extended-release alprazolam has less potential for abuse than immediate-release alprazolam. C1 NIDA,ADDICT RES CTR,CLIN PHARMACOL BRANCH,BALTIMORE,MD 21224. UPJOHN CO,CLIN PHARMACOKINET UNIT,KALAMAZOO,MI 49007. JOHNS HOPKINS UNIV,SCH MED,BEHAV BIOL RES CTR,DEPT PSYCHIAT & BEHAV SCI,BALTIMORE,MD. JOHNS HOPKINS UNIV,SCH MED,BEHAV BIOL RES CTR,DEPT NEUROSCI,BALTIMORE,MD. FU NIDA NIH HHS [DA-03889] NR 31 TC 54 Z9 55 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 MAR PY 1995 VL 57 IS 3 BP 356 EP 365 DI 10.1016/0009-9236(95)90162-0 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA QP664 UT WOS:A1995QP66400013 PM 7697954 ER PT J AU DAWID, IB TOYAMA, R TAIRA, M AF DAWID, IB TOYAMA, R TAIRA, M TI LIM DOMAIN PROTEINS SO COMPTES RENDUS DE L ACADEMIE DES SCIENCES SERIE III-SCIENCES DE LA VIE-LIFE SCIENCES LA English DT Review DE HOMEODOMAIN; ZINC-BINDING PROTEIN; DIMERIZATION DOMAIN; PROTEIN INTERACTION; CYTOSKELETON; TRANSCRIPTION FACTOR ID CYSTEINE-RICH PROTEIN; ELEGANS HOMEOPROTEINS UNC-86; VULVAL CELL LINEAGES; ZINC-FINGER MOTIF; CAENORHABDITIS-ELEGANS; INTESTINAL PROTEIN; INSULIN GENE; C-ELEGANS; HOMEODOMAIN; MEC-3 AB The LIM domain is a cysteine-rich domain composed of 2 special zinc fingers that are joined by a 2-amino acid spacer. Some proteins are constituted by LIM domains only while others contain a variety of different functional domains. LIM proteins form a diverse group which includes transcription factors and cytoskeletal proteins. The primary role of LIM domains appears to be in protein-protein interaction, through the formation of dimers with identical or different LIM domains or by binding distinct proteins. In LIM homeodomain proteins, LIM domains seem to function as negative regulatory domains. LIM homeodomain proteins are involved in the control of cell lineage determination and the regulation of differentiation, and LIM-only proteins may have similar roles. LIM-only proteins are also implicated in the control of cell proliferation since several genes encoding such proteins are associated with oncogenic chromosome translocations. In analyzing sequence relationships between LIM domains we suggest that they may be arranged into 5 groups which appear to correlate with the structural and functional properties of the proteins containing these domains. RP DAWID, IB (reprint author), NICHHD,MOLEC GENET LAB,BETHESDA,MD 20892, USA. NR 67 TC 212 Z9 219 U1 0 U2 5 PU JOHN LIBBEY EUROTEXT LTD PI MONTROUGE PA 127 AVE DE LA REPUBLIQUE, 92120 MONTROUGE, FRANCE SN 0764-4469 J9 CR ACAD SCI III-VIE JI Comptes Rendus Acad. Sci. Ser. III-Sci. Vie-Life Sci. PD MAR PY 1995 VL 318 IS 3 BP 295 EP 306 PG 12 WC Biology; Multidisciplinary Sciences SC Life Sciences & Biomedicine - Other Topics; Science & Technology - Other Topics GA QU538 UT WOS:A1995QU53800001 PM 7788499 ER PT J AU GIAMBRA, LM AF GIAMBRA, LM TI A LABORATORY METHOD FOR INVESTIGATING INFLUENCES ON SWITCHING ATTENTION TO TASK-UNRELATED IMAGERY AND THOUGHT SO CONSCIOUSNESS AND COGNITION LA English DT Article ID STRESS AB Thought-intrusions, automatic inferences, and other unintended thought are beginning to play an important role in the study of psychiatric disease as well as normal thought processes. We examine one method for the study of task-unrelated imagery and thought (TUIT). TUIT likelihood was shown to be reliably measured over a wide range of vigilance tasks, to have high short-term test-retest reliability, and to be sensitive to information processing demands. Likelihood of TUITs was shown to be different as a function of aging, hyperactivity, time of the day, and level of depression. Thus, we now can reliably measure the influence of endogenous and exogenous influences on TUITs. In addition, TUIT measurement was proposed as minimally interfering and natural second task for determining resource utilizing in a primary task. Finally, this method was offered as a reliable approach to quantification of such mental states as obsessions and drug craving and addiction. (C) 1995 Academic Press, Inc. RP GIAMBRA, LM (reprint author), NIA,GERONTOL RES CTR,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. NR 32 TC 153 Z9 158 U1 1 U2 22 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 1053-8100 J9 CONSCIOUS COGN JI Conscious. Cogn. PD MAR PY 1995 VL 4 IS 1 BP 1 EP 21 DI 10.1006/ccog.1995.1001 PG 21 WC Psychology, Experimental SC Psychology GA QR311 UT WOS:A1995QR31100001 PM 7497092 ER PT J AU VOGEL, JL PARSELL, DA LINDQUIST, S AF VOGEL, JL PARSELL, DA LINDQUIST, S TI HEAT-SHOCK PROTEINS HSP104 AND HSP70 REACTIVE MESSENGER-RNA SPLICING AFTER HEAT INACTIVATION SO CURRENT BIOLOGY LA English DT Article ID PRE-MESSENGER-RNA; SACCHAROMYCES-CEREVISIAE; DNA-REPLICATION; ATP HYDROLYSIS; HELA-CELLS; YEAST; THERMOTOLERANCE; POLYMERASE; BINDING; GENE AB Background: The heat-shock protein Hsp104 plays a crucial role in the survival of cells exposed to high temperatures and other severe stresses, but its specific functions and the biological pathways on which it operates have been unclear. Indeed, very little is known about the specific cellular processes in which any of the heat-shock proteins acts to affect thermotolerance. One essential process that is particularly sensitive to heat in many organisms is the splicing of intervening sequences from mRNA precursors. Results: We have examined the role of Hsp104 in the repair of splicing after disruption by heat shock. When splicing in the budding yeast Saccharomyces cerevisiae was disrupted by a brief heat shock, it recovered much more rapidly in wild-type strains than in strains containing hsp104 mutations. Constitutive expression of Hsp104 promoted the recovery of heat-damaged splicing in the absence of other protein synthesis, but did not protect splicing from the initial disruption, suggesting that Hsp104 functions to repair splicing after heat damage rather than to prevent the initial damage. A modest reduction in the recovery of splicing after heat shock in an hsp70 mutant suggested that Hsp70 may also function in the repair of splicing. The roles of Hsp104 and Hsp70 were confirmed by the ability of the purified proteins to restore splicing in extracts that had been heat-inactivated in vitro. Together, these two proteins were able to restore splicing to a greater degree than could be accomplished by an optimal concentration of either protein alone. Conclusions: Our findings provide the first demonstration of the roles of heat-shock proteins in a biological process that is known to be particularly sensitive to heat in vivo. The results support previous genetic arguments that the Hsp104 and Hsp70 proteins have different, but related, functions in protecting cells from the toxic effects of high temperatures. Because Hsp104 and Hsp70 are able to function in vitro, after the heat-damaged substrate or substrates have been generated, neither protein is required to bind to its target(s) during heating in order to effect repair. C1 UNIV CHICAGO, DEPT MOLEC GENET & CELL BIOL, CHICAGO, IL 60637 USA. UNIV CHICAGO, HOWARD HUGHES MED INST, CHICAGO, IL 60637 USA. NIAID, VIRAL DIS LAB, BETHESDA, MD 20892 USA. CONNECT THERAPEUT INC, PALO ALTO, CA 94303 USA. NR 51 TC 79 Z9 82 U1 0 U2 5 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0960-9822 EI 1879-0445 J9 CURR BIOL JI Curr. Biol. PD MAR PY 1995 VL 5 IS 3 BP 306 EP 317 DI 10.1016/S0960-9822(95)00061-3 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA QM823 UT WOS:A1995QM82300019 PM 7780741 ER PT J AU HIKITA, N CHAN, CC WHITCUP, SM NUSSENBLATT, RB MOCHIZUKI, M AF HIKITA, N CHAN, CC WHITCUP, SM NUSSENBLATT, RB MOCHIZUKI, M TI EFFECTS OF TOPICAL FK506 ON ENDOTOXIN-INDUCED UVEITIS (EIU) IN THE LEWIS RAT SO CURRENT EYE RESEARCH LA English DT Article DE FK506; ENDOTOXIN-INDUCED UVEITIS; CYTOKINES; T LYMPHOCYTE; ADHESION MOLECULES; RAT ID EXPERIMENTAL AUTOIMMUNE UVEORETINITIS; ADHESION MOLECULE EXPRESSION; TUMOR-NECROSIS-FACTOR; TNF-ALPHA; FK-506; IMMUNOSUPPRESSANT; INVITRO; CELLS; DISEASE; THERAPY AB FK506 is a macrolide antibiotic and a potent immunosuppressant, To investigate the effect of topical FK506 on acute ocular inflammation, we evaluated its action on the development of endotoxin-induced uveitis (EIU). At two different concentrations of 0.05% and 0.3%, topical FK506 was applied to Lewis rats with EIU. In aqueous, the mean number of inflammatory cells per microliter +/- SEM was 2,389+/-1,277, 1,571+/-1,562, 898+/-882, and 69+/-152 fir rats treated with vehicle alone, 0.05%, 0.3% FK506, and 1% prednisolone acetate. The median of histological grades was 2, 1.5, 0.8, and 0.5 for animals treated with these 4 different regimens respectively. Analysis of aqueous protein showed a small reduction in FK506-treated animals. Mean blood levels of FK506 were low in rats treated with topical FK506 (0.05%, 0.84 ng/ml; 0.3%, 2.0 ng/ml) suggesting that its therapeutic effect was not secondary to the systemic absorption of the drug. Although FK506 is not as effective as prednisolone, 0.3% FK506 produced significant decreases in the mean aqueous inflammatory cell number and histological inflammatory score as compared to control vehicle alone. We conclude that topical FK506 can suppress EIU in a dose-dependent fashion and may be an alternative medication for patients with anterior uveitis and contra-indication to topical steroid. C1 NEI,IMMUNOL LAB,BETHESDA,MD 20892. KURUME UNIV,DEPT OPHTHALMOL,KURUME,FUKUOKA 830,JAPAN. NR 27 TC 19 Z9 19 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0271-3683 J9 CURR EYE RES JI Curr. Eye Res. PD MAR PY 1995 VL 14 IS 3 BP 209 EP 214 DI 10.3109/02713689509033516 PG 6 WC Ophthalmology SC Ophthalmology GA QR509 UT WOS:A1995QR50900006 PM 7540967 ER PT J AU KAELBER, CT REGIER, DA AF KAELBER, CT REGIER, DA TI DIRECTIONS IN PSYCHIATRIC EPIDEMIOLOGY SO CURRENT OPINION IN PSYCHIATRY LA English DT Article ID CATCHMENT-AREA; ADDICTIVE-DISORDERS; MAJOR DEPRESSION; UNITED-STATES; PREVALENCE; SYSTEM AB Recently published revisions of the international classification of diseases by the world health organization and the diagnostic and statistical manual of mental disorders by the american psychiatric association have provided further impetus to improve diagnostic reliability by emphasizing more objective criteria for case definitions. The value of these efforts to improve diagnostic reliability continues to be well documented by the reporting of more reliable estimates of the occurrence of mental and behavioral disorders in clinical, community, national, and international surveys. Valuable efforts have also been provided by innovative studies designed to sharpen case definitions, identify new syndromes, clarify relationships among comorbid conditions, and estimate the use of and need for mental health services. RP KAELBER, CT (reprint author), NIMH,DIV EPIDEMIOL & SERV RES,5600 FISHERS LANE,ROCKVILLE,MD 20857, USA. NR 42 TC 5 Z9 5 U1 10 U2 10 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0951-7367 J9 CURR OPIN PSYCHIATR JI Curr. Opin. Psychiatr. PD MAR PY 1995 VL 8 IS 2 BP 109 EP 115 DI 10.1097/00001504-199503000-00011 PG 7 WC Psychiatry SC Psychiatry GA QM150 UT WOS:A1995QM15000010 ER PT J AU LICHT, T GOTTESMAN, MM PASTAN, I AF LICHT, T GOTTESMAN, MM PASTAN, I TI TRANSFER OF THE MDR1 (MULTIDRUG-RESISTANCE) GENE - PROTECTION OF HEMATOPOIETIC-CELLS FROM CYTOTOXIC CHEMOTHERAPY, AND SELECTION OF TRANSDUCED CELLS IN-VIVO SO CYTOKINES AND MOLECULAR THERAPY LA English DT Review DE BONE MARROW; GENE THERAPY; HEMATOPOIETIC STEM CELLS; P-GLYCOPROTEIN; RETROVIRUS ID MULTIPLE-DRUG RESISTANCE; BONE-MARROW CELLS; BACTERIAL TRANSPORT PROTEINS; P-GLYCOPROTEIN GENE; TRANSGENIC MICE; STEM-CELLS; MONOCLONAL-ANTIBODY; GROWTH-FACTORS; RETROVIRAL TRANSFER; COMPLEMENTARY-DNA AB Expression of the drug efflux pump P-glycoprotein, encoded by the multidrug resistance (MDR1) gene, has been identified as an impediment to successful chemotherapy of neoplastic diseases. More recently, its potential use for gene therapy has been analyzed. Expression of a full-length MDR1 cDNA in hematopoietic cells renders them resistant to various anticancer drugs, as first shown in a transgenic mouse model. Similarly, mouse hematopoietic progenitor cells in bone marrow or peripheral blood are protected from the toxicity of anticancer chemotherapy by retroviral transduction of the MDR1 gene. Furthermore, cells engineered to express P-glycoprotein survived after the administration of cytotoxic drugs, indicating that the gene could function as a selectable marker in vivo. Recently, MDR1 transduction into isolated pluripotent hematopoietic stem cells has been demonstrated. Clinical studies on MDR1 gene transfer into hematopoietic cells of cancer patients are being planned. Transfer of the MDR1 gene into hematopoietic precursor cells may allow the introduction and selection of otherwise non-selectable genes in bone marrow. The ability to select transduced cells can circumvent the low transduction efficiency that has hampered efficient gene therapy. Recently, fusion genes in which the MDR1 cDNA is fused to genes that correct genetic disorders have been constructed to facilitate gene therapy of inherited metabolic disorders. C1 NCI,DIV CANC BIOL DIAG & CTR,MOLEC BIOL LAB,BETHESDA,MD 20892. NCI,DIV CANC BIOL DIAG & CTR,CELL BIOL LAB,BETHESDA,MD 20892. NR 88 TC 20 Z9 21 U1 0 U2 1 PU MARTIN DUNITZ LTD PI LONDON PA 7-9 PRATT ST, LONDON, ENGLAND NW1 0AE SN 1355-6568 J9 CYTOKINES MOL THER JI Cytokines Mol. Ther. PD MAR PY 1995 VL 1 IS 1 BP 11 EP 20 PG 10 WC Biotechnology & Applied Microbiology; Cell Biology; Hematology; Immunology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Cell Biology; Hematology; Immunology; Research & Experimental Medicine GA TF514 UT WOS:A1995TF51400003 PM 9384659 ER PT J AU EIBL, B GREITER, E GRUNEWALD, K GASTL, G WEYRER, K THALER, J AULITZKY, W HERRMANN, F RAPP, U HUBER, C AF EIBL, B GREITER, E GRUNEWALD, K GASTL, G WEYRER, K THALER, J AULITZKY, W HERRMANN, F RAPP, U HUBER, C TI EXPRESSION OF C-FOS CORRELATES WITH IFN-ALPHA RESPONSIVENESS IN PHILADELPHIA-CHROMOSOME-POSITIVE CHRONIC MYELOGENOUS LEUKEMIA SO CYTOKINES AND MOLECULAR THERAPY LA English DT Article DE CML; ONCOGENES; MESSENGER-RNA LEVELS; IFN-ALPHA; IFN-ALPHA SENSITIVITY ID BCR-GENE; DIFFERENTIATION; INDUCTION; CDNA; PROTEIN; ACID; MYC AB This study evaluates (i) constitutive levels of oncogene and p53 transcripts in chronic phase CML patients and (ii) their modulations subsequent to in vivo therapy with rIFN-alpha 2c. Peripheral blood mononuclear cells (pbmc) and bone marrow cells of 26 patients were examined for c-fos, c-myc, p53 and the hybrid bcr/abl mRNA levels. Results indicated that (i) constitutive c-fos transcript levels are significantly higher in patients subsequently responding to IFN-alpha therapy (p < 0.01) and are positively correlated with the proportion of lymphocytes (r = 0.6895, p < 0.01) and negatively with the proportion of immature cells (r = -0.568, p < 0.01) contained in the pbmc preparations tested, (ii) constitutive mRNA levels of the hybrid bcr/abl, c-myc and p53 are positively correlated with each other, but failed to relate to disease parameters, and (iii) acute and chronic in vivo exposure to IFN-alpha is accompanied by upregulation of c-fos and downregulation of c-myc mRNA levels in responder patients. C1 UNIV INNSBRUCK HOSP,DEPT INTERNAL MED,MOLEC GENET & DIAGNOST LAB,A-6020 INNSBRUCK,AUSTRIA. UNIV INNSBRUCK HOSP,DEPT INTERNAL MED,DIV CLIN IMMUNOBIOL,A-6020 INNSBRUCK,AUSTRIA. TUMOR BIOL CTR,FREIBURG,GERMANY. UNIV MAINZ,DEPT HEMATOL,W-6500 MAINZ,GERMANY. UNIV HOSP RUDOLF VIRCHOW,DEPT HEMATOL ONCOL & MOLEC BIOL,BERLIN,GERMANY. NATL CANC INST,FCRF,VIRAL PATHOL SECT,FREDERICK,MD. NR 22 TC 5 Z9 5 U1 0 U2 0 PU MARTIN DUNITZ LTD PI LONDON PA 7-9 PRATT ST, LONDON, ENGLAND NW1 0AE SN 1355-6568 J9 CYTOKINES MOL THER JI Cytokines Mol. Ther. PD MAR PY 1995 VL 1 IS 1 BP 29 EP 38 PG 10 WC Biotechnology & Applied Microbiology; Cell Biology; Hematology; Immunology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Cell Biology; Hematology; Immunology; Research & Experimental Medicine GA TF514 UT WOS:A1995TF51400005 PM 9384661 ER PT J AU OLIVER, G WEHR, R JENKINS, NA COPELAND, NG CHEYETTE, BNR HARTENSTEIN, V ZIPURSKY, SL GRUSS, P AF OLIVER, G WEHR, R JENKINS, NA COPELAND, NG CHEYETTE, BNR HARTENSTEIN, V ZIPURSKY, SL GRUSS, P TI HOMEOBOX GENES AND CONNECTIVE-TISSUE PATTERNING SO DEVELOPMENT LA English DT Article DE CONNECTIVE TISSUE; TENDONS; MUSCLE; HOMEOBOX; EMBRYOGENESIS; MURINE; LIMB; SPLOTCH ID LIMB; MAP AB In vertebrates, limb tendons are derived from cells that migrate from the lateral plate mesoderm during early development. While some of the developmental steps leading to the formation of these tissues are known, little is known about the molecular mechanisms controlling them, We have identified two murine homeobox-containing genes, Six 1 and Six 2, which are expressed in a complementary fashion during the development of limb tendons. Transcripts for both genes are found in different sets of phalangeal tendons. Six 1 and Six 2 also are expressed in skeletal and smooth muscle, respectively. These genes may participate in the patterning of the distal tendons of the limb phalanges by setting positional values along the limb axes. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. UNIV CALIF LOS ANGELES,DEPT BIOL CHEM,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,HOWARD HUGHES MED INST,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,SCH MED,DEPT BIOL,LOS ANGELES,CA 90024. RP OLIVER, G (reprint author), MAX PLANCK INST BIOPHYS CHEM,DEPT MOLEC CELL BIOL,AM FASSBERG,D-37077 GOTTINGEN,GERMANY. RI Cheyette, Benjamin/K-5535-2014 OI Cheyette, Benjamin/0000-0001-9934-7941 FU NCI NIH HHS [N01-CO-74101] NR 27 TC 246 Z9 249 U1 0 U2 2 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 MAR PY 1995 VL 121 IS 3 BP 693 EP 705 PG 13 WC Developmental Biology SC Developmental Biology GA QN067 UT WOS:A1995QN06700008 PM 7720577 ER PT J AU WITTA, SE AGARWAL, VR SATO, SM AF WITTA, SE AGARWAL, VR SATO, SM TI XIPOU 2, A NOGGIN-INDUCIBLE GENE, HAS DIRECT NEURALIZING ACTIVITY SO DEVELOPMENT LA English DT Article DE XIPOU 2; NEURAL INDUCTION; POU; NOGGIN; XENOPUS; BLASTOMERE; CELL FATE DETERMINATION ID DOMAIN TRANSCRIPTION FACTORS; HOMEO-BOX GENE; XENOPUS-EMBRYOS; CELL IDENTITY; NERVOUS-SYSTEM; EXPRESSION; INDUCTION; ORGANIZER; LAEVIS; DROSOPHILA AB XlPOU2, a member of the class III POU domain family, is expressed initially in Spemann's organizer, and later, in discrete regions of the developing nervous system in Xenopus laevis, XlPOU 2 may act downstream from initial neural induction events, since it is activated by the neural inducer, noggin. To determine if XlPOU 2 participates in the early events of neurogenesis, synthetic mRNA was microinjected into specific blastomeres of the 32-cell stage embryo, Misexpression of XlPOU 2 in the epidermis causes a direct switch in cell fate from an epidermal to a neuronal phenotype, In the absence of mesoderm induction, XlPOU 2 has the ability to induce a neuronal phenotype in uncommitted ectoderm. These data demonstrate the potential of XlPOU 2 to act as a master regulator of neurogenesis. C1 NIDDK,GENET & BIOCHEM BRANCH,BETHESDA,MD 20892. CORNELL UNIV MED COLL,N SHORE UNIV HOSP,BIOMED SCI RES CTR,MANHASSET,NY 11030. NR 60 TC 61 Z9 63 U1 0 U2 0 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0950-1991 J9 DEVELOPMENT JI Development PD MAR PY 1995 VL 121 IS 3 BP 721 EP 730 PG 10 WC Developmental Biology SC Developmental Biology GA QN067 UT WOS:A1995QN06700010 PM 7720579 ER PT J AU RYAN, G STEELEPERKINS, V MORRIS, JF RAUSCHER, FJ DRESSLER, GR AF RYAN, G STEELEPERKINS, V MORRIS, JF RAUSCHER, FJ DRESSLER, GR TI REPRESSION OF PAX-2 BY WT1 DURING NORMAL KIDNEY DEVELOPMENT SO DEVELOPMENT LA English DT Article DE PAX-2; WT1; KIDNEY DEVELOPMENT; WILMS TUMOR; TRANSCRIPTION REPRESSION; MOUSE ID WILMS-TUMOR GENE; EXPRESSION; PRODUCT; GROWTH; MODULATION; PROMOTER; BINDING; LOCUS; CELLS; MICE AB The developmental, regulatory gene Pax-2 is activated during early kidney morphogenesis and repressed in mature renal epithelium. Persistent Pax-2 expression is also observed in a variety of kidney tumors. Yet, little is known about the signals regulating this transient expression pattern in the developing kidney. We have examined the spatial and temporal expression patterns of Pax-2 and the Wilms' tumor suppresser protein WT1 with specific antibodies in developing mouse kidneys. A marked increase in WT1 protein levels coincided precisely with down-regulation of the Pax-2 gene in the individual precursor cells of the visceral glomerular epithelium, suggesting a direct effect of the WT1 repressor protein on Pax-2 regulatory elements. To examine whether WT1 could directly repress Pax-2 transcription, binding of WT1 to three high affinity sites in the 5' untranslated Pax-2 leader sequence was demonstrated by DNAseI footprinting analysis, Furthermore, co-transfection assays using CAT reporter constructs under the control of Pax-2 regulatory sequences demonstrated WT1-dependent transcriptional repression. These three WT1 binding sites were also able to repress transcription, in a WT1-dependent manner, when inserted between a heterologous promoter and the reporter gene. The data indicate that Pax-2 is a likely target gene for WT1 and suggest a direct link, at the level of transcriptional regulation, between a developmental control gene, active in undifferentiated and proliferating cells, and a known tumor suppresser gene. C1 UNIV MICHIGAN,HOWARD HUGHES MED INST,ANN ARBOR,MI 48109. UNIV MICHIGAN,DEPT PATHOL,ANN ARBOR,MI 48109. NICHHD,MAMMALIAN GENES & DEV LAB,BETHESDA,MD 20892. WISTAR INST ANAT & BIOL,PHILADELPHIA,PA 19104. FU NCI NIH HHS [CA10815, CA47983, CA52009] NR 37 TC 209 Z9 213 U1 0 U2 2 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 MAR PY 1995 VL 121 IS 3 BP 867 EP 875 PG 9 WC Developmental Biology SC Developmental Biology GA QN067 UT WOS:A1995QN06700022 PM 7720589 ER PT J AU RADKEYARROW, M MCCANN, K DEMULDER, E BELMONT, B MARTINEZ, P RICHARDSON, DT AF RADKEYARROW, M MCCANN, K DEMULDER, E BELMONT, B MARTINEZ, P RICHARDSON, DT TI ATTACHMENT IN THE CONTEXT OF HIGH-RISK CONDITIONS SO DEVELOPMENT AND PSYCHOPATHOLOGY LA English DT Article ID MOTHER-CHILD INTERACTION; PARENTAL DEPRESSION; 2ND YEAR; COMPETENCE; PRESCHOOL; BEHAVIOR; PSYCHOPATHOLOGY; PEER; ADAPTATION; PREDICTORS AB The role of attachment in interaction with other relationships and conditions was investigated in relation to children's later psychosocial development (at ages 6 and 9). Thirty-nine unipolar depressed mothers, 24 bipolar mothers, and 32 normal control mothers and their children were studied. The network of conditions defining early experience included, in addition to attachment, maternal psychopathology, marital discord, other disordered relationships in the family, and recent losses of significant persons. Patterns of mother-child interaction were also examined. Assessments of children's problems were based on psychiatric evaluations of depressive affect, anxiety, and disruptive-oppositional behavior. The findings support the conclusion that attachment enters into development in interaction with other relationships and conditions. Maternal psychopathology, in particular, in interaction with the attachment relationship, is linked to later developmental outcomes. The importance of considering mother-child interactional and dispositional characteristics is indicated. The early attachment relationship together with the ways in which the mother's depression is expressed with her child, and the child's style of coping with the mother's functioning establish patterns of behavior that influence the child's vulnerability to later problems. Multiple pathways of transmission of affective problems are discussed. RP RADKEYARROW, M (reprint author), NIMH,DEV PSYCHOL LAB,15K,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 67 TC 40 Z9 41 U1 1 U2 9 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0954-5794 J9 DEV PSYCHOPATHOL JI Dev. Psychopathol. PD SPR PY 1995 VL 7 IS 2 BP 247 EP 265 PG 19 WC Psychology, Developmental SC Psychology GA QW982 UT WOS:A1995QW98200003 ER PT J AU KORDON, EC MCKNIGHT, RA JHAPPAN, C HENNIGHAUSEN, L MERLINO, G SMITH, GH AF KORDON, EC MCKNIGHT, RA JHAPPAN, C HENNIGHAUSEN, L MERLINO, G SMITH, GH TI ECTOPIC TGF-BETA-1 EXPRESSION IN THE SECRETORY MAMMARY EPITHELIUM INDUCES EARLY SENESCENCE OF THE EPITHELIAL STEM-CELL POPULATION SO DEVELOPMENTAL BIOLOGY LA English DT Article ID GROWTH-FACTOR-BETA; TRANSGENIC MICE; BRANCHING MORPHOGENESIS; ALVEOLAR DEVELOPMENT; PROTEIN GENE; GLAND; FACTOR-BETA-1; INHIBITION; DEATH; PROLIFERATION AB An important feature of the mammary gland is the regenerative capacity of its epithelium which is demonstrated upon successive cycles of lactation and involution. Pregnant mice expressing a whey-acidic protein (WAP) promoter-driven transforming growth factor-beta 1 (TGF beta 1) cDNA are unable either to generate a secretory mammary epithelium or to lactate. Here we investigate whether ectopic TGF beta 1 induces this phenotype by affecting the transgenic epithelium directly or in trans. Reciprocal transplantation of mammary tissue between normal and transgenic hosts resulted in the development of the respective phenotypes of the transplants within the same mammary fat pad. When isolated mammary epithelial cells from both were mixed before implantation so that transgenic and normal epithelium would develop together more proximately, both phenotypes were simultaneously observed in the resultant chimeric mammary outgrowths. Since no trans effect was detectable, we hypothesize that early expression of the transgene results in compromised lobular progenitor cells through an intracrine mechanism. Consistent with this posit, WAP promoter-driven protein expression was detected in individual cells of the subtending ducts of immature females at estrus. Transplantation of WAP-TGF beta 1 mammary gland into nonpregnant hosts revealed that transgenic implants, even those from young postpubertal virgin females, had a diminished ability to repopulate epithelium-free mammary fat pads. Accordingly, the ectopic expression of WAP-TGF beta 1 not only impairs lobular progenitors, but also promotes an early senescence of the regenerative capacity of the mammary ductal epithelium. This leads us to propose that mammary epithelial stem cells give rise to two functionally distinct progenitor cells in the mammary gland epithelium: one capable of producing daughters committed to ductal formation, the other capable only of producing daughters committed to lobular function. (C) 1995 Academic Press, Inc. C1 NCI,TUMOR IMMUNOL & BIOL LAB,BETHESDA,MD 20892. NCI,MOLEC BIOL LAB,BETHESDA,MD 20892. NIDDKD,BIOCHEM & METAB LAB,BETHESDA,MD 20892. NR 42 TC 147 Z9 151 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD MAR PY 1995 VL 168 IS 1 BP 47 EP 61 DI 10.1006/dbio.1995.1060 PG 15 WC Developmental Biology SC Developmental Biology GA QK991 UT WOS:A1995QK99100005 PM 7883078 ER PT J AU HANSON, RL NARAYAN, KMV MCCANCE, DR PETTITT, DJ JACOBSSON, LTH BENNETT, PH KNOWLER, WC AF HANSON, RL NARAYAN, KMV MCCANCE, DR PETTITT, DJ JACOBSSON, LTH BENNETT, PH KNOWLER, WC TI RATE OF WEIGHT-GAIN, WEIGHT FLUCTUATION, AND INCIDENCE OF NIDDM SO DIABETES LA English DT Article ID BODY-FAT DISTRIBUTION; DEPENDENT DIABETES-MELLITUS; NONDIABETIC PIMA-INDIANS; FOLLOW-UP; RISK-FACTORS; OBESITY; INSULIN; MEN; WOMEN; ASSOCIATION AB The relationships of rate of weight gain and weight fluctuation to incidence of non-insulin-dependent diabetes mellitus (NIDDM) were examined in Pima Indians. The 1,458 subjects were participants in a prospective study with examinations approximately every 2 years, Rate of weight gain was defined as the slope of the regression line of weight with time for two or more consecutive examinations greater than or equal to 2 years apart and weight fluctuation as the root-mean-square departure from this line for four examinations, Among men, incidence of NIDDM was strongly and significantly related to rate of weight gain (e.g., age-adjusted incidence = 56.7/1,000 person-years in those with weight gain greater than or equal to 3 kg/year and 16.9/1,000 person-years for those losing weight [P-trend < 0.01]). In women, weight gain was significantly related to diabetes incidence only in those who were not initially overweight (body mass index < 27.3 kg/m(2)). In contrast to the relationship with weight gain, weight fluctuation was not associated with incidence of diabetes in either sex. These findings suggest that weight control in overweight individuals may be a more effective strategy for prevention of NIDDM in men than in women, whereas prevention of obesity may prevent diabetes in both sexes. Concern about a diabetogenic effect of weight fluctuation should not deter weight control efforts. C1 NIDDKD,PHOENIX EPIDEMIOL & CLIN RES BRANCH,PHOENIX,AZ 85014. NIAMSD,PHOENIX,AZ. RP HANSON, RL (reprint author), NIDDKD,DIABET & ARTHRITIS EPIDEMIOL SECT,1550 E INDIAN SCH RD,PHOENIX,AZ 85014, USA. RI Narayan, K.M. Venkat /J-9819-2012; Hanson, Robert/O-3238-2015 OI Narayan, K.M. Venkat /0000-0001-8621-5405; Hanson, Robert/0000-0002-4252-7068 NR 37 TC 65 Z9 66 U1 1 U2 3 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0012-1797 J9 DIABETES JI Diabetes PD MAR PY 1995 VL 44 IS 3 BP 261 EP 266 DI 10.2337/diabetes.44.3.261 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA QZ334 UT WOS:A1995QZ33400003 PM 7883111 ER PT J AU DOMENE, HM CASSORLA, F WERNER, H ROBERTS, CT LEROITH, D AF DOMENE, HM CASSORLA, F WERNER, H ROBERTS, CT LEROITH, D TI RAT GROWTH-HORMONE RECEPTOR GROWTH HORMONE-BINDING PROTEIN MESSENGER-RNAS WITH DIVERGENT 5'-UNTRANSLATED REGIONS ARE EXPRESSED IN A TISSUE-SPECIFIC MANNER SO DNA AND CELL BIOLOGY LA English DT Article ID MESSENGER-RNA; FACTOR-I; RIBONUCLEIC-ACID; GENE-EXPRESSION; INSULIN; CLONING; LIVER; SERUM; AMPLIFICATION; PURIFICATION AB In the rat, the growth hormone receptor (GH-R) gene generates two transcripts, one encoding the transmembrane GH-R, and a shorter one encoding the GH-binding protein (GH-BP). These transcripts exhibit a high degree of heterogeneity in their 5'-untranslated regions (5'-UTRs). Some of the exons encoding these 5'-UTR variants may be flanked by distinct promoter regions whose activity would result in the tissue-specific expression of the GH-R gene. To assess this possibility, we used single-sided polymerase chain reaction (PCR) amplification to characterize 5'-UTR variants in rat GH-R cDNAs, and by using 5'-UTR-specific probes, we determined their pattern of expression in several tissues. Besides two previously described variants (V1 and V2), three new 5'-UTR variants were identified, extending 56 nucleotides (V3), 135 nucleotides (V4), and 209 nucleotides (V5) upstream of the ATG translation initiation codon. The expression of GH-R and GH-BP transcripts was clearly tissue specific. In the liver, GH-BP mRNA was the predominant transcript, whereas in other tissues, there was equivalent expression of both transcripts or predominant expression of GH-R mRNA. With respect to the tissue distribution of the 5'-UTR variants in particular, variants V1 and V5 exhibited a pattern of expression closely resembling that seen with an exon 2 probe, with the overall expression of variant V1 being much higher than that of variant V5. The V2 species was exclusively expressed in liver. Variant V3 was expressed at low levels in liver, muscle, heart, and kidney; in muscle and heart, it was preferentially associated with GH-BP transcripts. Variant V4, although present in liver, was more abundant in extrahepatic tissues and predominantly found in GH-R mRNA transcripts. Southern blot analyses were consistent with exon 2 and the exons encoding the V1 and V2 sequences being in proximity, with the other 5'-UTR sequences being encoded by exons located further upstream of exon 2. These findings support the concept that different 5'-UTR variants are the result of the different promoters acting in a tissue-specific manner. The association of specific 5'-UTR variants with either GH-R or GH-BP transcripts raises the possibility that the alternative splicing process that generates GH-BP mRNA in the rat might be controlled by the 5'-flanking region regulating the expression of specific leader exons. C1 NIDDKD,DIABET BRANCH,BETHESDA,MD 20892. NICHHD,DEV ENDOCRINOL BRANCH,BETHESDA,MD 20892. NR 38 TC 32 Z9 32 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1044-5498 J9 DNA CELL BIOL JI DNA Cell Biol. PD MAR PY 1995 VL 14 IS 3 BP 195 EP 204 DI 10.1089/dna.1995.14.195 PG 10 WC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity GA QN065 UT WOS:A1995QN06500002 PM 7880440 ER PT J AU HATCH, CL BONNER, WM AF HATCH, CL BONNER, WM TI CHARACTERIZATION OF THE PROXIMAL PROMOTER OF THE HUMAN HISTONE H2A.Z GENE SO DNA AND CELL BIOLOGY LA English DT Article ID BOX-BINDING PROTEINS; CHLORAMPHENICOL ACETYLTRANSFERASE; DNA METHYLATION; TRANSCRIPTION; SEQUENCE; VARIANT; EXPRESSION; POLYMERASE; CHROMATIN; ISLANDS AB Histone H2A.Z is a distinct and evolutionarily conserved member of the histone H2A family whose synthesis, in contrast to that of most other histone species, is not dependent on DNA replication. The gene for H2A.Z lacks the signals involved in the 3' processing of replication-linked histone mRNA species and contains introns as well as polyadenylation signals. The H2A.Z gene proximal promoter, a 200-bp region upstream of the transcription start site that provides maximal activity in CAT reporter studies, contains three CCAAT and two GGGCGG elements as well as a consensus TATA element. In vitro DNase I footprint analysis of this region indicated that the central CCAAT and the distal GGGCGG elements were protected by factors present in HeLa nuclear extract. Site-directed mutations of selected promoter elements were generated in the H2A.Z gene promoter region of a CAT reporter construct by a novel one-step PCR procedure. Of the elements examined, the central CCAAT element was found to be the most important determinant of promoter activity; its disruption decreased CAT reporter activity by 65%. Disruption of the proximal CCAAT or the distal GGGCGG elements led to decreases in activity of 40%, while disruption of any of the other examined led to smaller decreases. Gel-mobility shift analysis showed that the three CCAAT elements had overlapping but not identical binding specificities for nuclear factors. The two GGGCGG elements both were found to bind transcription factor Spl, but the distal element bound Spl with higher affinity. The findings show that the central and proximal CCAAT elements and the distal GGGCGG element appear to be the major determinants of the transcriptional activity of the H2A.Z gene. C1 NCI, DIV CANC TREATMENT, DEV THERAPEUT PROGRAM, MOLEC PHARMACOL LAB, BETHESDA, MD 20892 USA. NR 52 TC 11 Z9 12 U1 1 U2 2 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1044-5498 EI 1557-7430 J9 DNA CELL BIOL JI DNA Cell Biol. PD MAR PY 1995 VL 14 IS 3 BP 257 EP 266 DI 10.1089/dna.1995.14.257 PG 10 WC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity GA QN065 UT WOS:A1995QN06500009 PM 7880446 ER PT J AU SCHINDLER, CW GOLDBERG, SR AF SCHINDLER, CW GOLDBERG, SR TI CARDIOVASCULAR EFFECTS OF COCAINE - UNDERLYING MECHANISMS - INTRODUCTION SO DRUG AND ALCOHOL DEPENDENCE LA English DT Editorial Material RP SCHINDLER, CW (reprint author), NIDA,ADDICT RES CTR,INTRAMURAL RES PROGRAM,PRECLIN PHARMACOL LAB,BEHAV PHARMACOL & GENET SEC,BALTIMORE,MD 21122, USA. NR 6 TC 3 Z9 3 U1 1 U2 1 PU ELSEVIER SCI PUBL IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD MAR PY 1995 VL 37 IS 3 BP 181 EP 182 DI 10.1016/0376-8716(94)01084-X PG 2 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA QP207 UT WOS:A1995QP20700001 ER PT J AU SCHINDLER, CW TELLA, SR ERZOUKI, HK GOLDBERG, SR AF SCHINDLER, CW TELLA, SR ERZOUKI, HK GOLDBERG, SR TI PHARMACOLOGICAL MECHANISMS IN COCAINE CARDIOVASCULAR EFFECTS SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE COCAINE; CARDIOVASCULAR; ADRENOCEPTOR; DOPAMINE; BEHAVIOR ID DOPAMINE-D2 RECEPTOR AGONIST; CALCIUM-CHANNEL ANTAGONIST; CONSCIOUS SQUIRREL-MONKEYS; CENTRAL-NERVOUS-SYSTEM; INTRAVENOUS COCAINE; URINARY-EXCRETION; CORONARY-ARTERY; RAT-BRAIN; METABOLITES; DOGS AB The squirrel monkey is a reliable model for the cardiovascular effects of cocaine in that it mimics the human response to cocaine; low to moderate doses of cocaine produce a sustained pressor effect and tachycardia. Pretreatment experiments have indicated the importance of alpha-1 and beta-1 adrenoceptor mechanisms in mediating the pressor and tachycardiac effects of cocaine, respectively. Little support for a role of dopaminergic mechanisms in the hemodynamic effects of cocaine has been found. Toxicity to cocaine is often observed hours after its administration, pointing to a potential role of the cocaine metabolites. Studies on the direct effects and therefore these differing effects of the metabolites should be considered when evaluating the cardiovascular toxicity of cocaine. Further, as these metabolites are present in the body for long periods of time, these results suggest a role of the metabolites in producing toxicity long after cocaine administration. Finally, studies using both dopaminergic and calcium channel antagonists indicate that the pharmacological mechanisms involved in the cardiovascular effects of cocaine are not the same as those involved in its behavioral effects. C1 GEORGETOWN UNIV,SCH MED,DEPT PHARMACOL,WASHINGTON,DC 20007. RP SCHINDLER, CW (reprint author), NIDA,ADDICT RES CTR,DIV INTRAMURAL RES,PRECLIN PHARMACOL LAB,BEHAV PHARMACOL & GENET SECT,BALTIMORE,MD 21122, USA. NR 70 TC 39 Z9 40 U1 1 U2 2 PU ELSEVIER SCI PUBL IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD MAR PY 1995 VL 37 IS 3 BP 183 EP 191 DI 10.1016/0376-8716(94)01083-W PG 9 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA QP207 UT WOS:A1995QP20700002 PM 7796713 ER PT J AU NEWLIN, DB AF NEWLIN, DB TI EFFECT OF COCAINE ON VAGAL TONE - A COMMON FACTORS APPROACH SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE COCAINE; PARASYMPATHETIC; SYMPATHETIC; COMMON FACTORS; ABUSE LIABILITY; TACHYCARDIA; VAGAL TONE; CARDIOVASCULAR ID HEART PERIOD; ALCOHOL AB This paper discusses a distinct cardiovascular pattern that is common to a wide variety of abused substances. The pattern consists of tachycardia that appears mediated by withdrawal of vagal inhibition, as indicated by decreases in cardiac vagal tone. This decrease in vagal tone was particularly robust with i.v. cocaine given to experienced cocaine abusers in a residential research setting. Following 40 mg i.v. cocaine, heart rate increased by approximately 30 beats/min at the same time that vagal tone decreased by approximately 2 log units. The theoretical significance of these findings is based on evidence that the results reflect a common factor among many abused drugs, but not the few aversive drugs that have been studied in this paradigm. RP NEWLIN, DB (reprint author), NIDA,INTRAMURAL RES PROGRAM,BALTIMORE,MD, USA. NR 26 TC 15 Z9 15 U1 2 U2 2 PU ELSEVIER SCI PUBL IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD MAR PY 1995 VL 37 IS 3 BP 211 EP 216 DI 10.1016/0376-8716(94)01086-Z PG 6 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA QP207 UT WOS:A1995QP20700004 PM 7796715 ER PT J AU INOUE, K CREVELING, CR AF INOUE, K CREVELING, CR TI INDUCTION OF CATECHOL-O-METHYLTRANSFERASE IN THE LUMINAL EPITHELIUM OF RAT UTERUS BY PROGESTERONE - INHIBITION BY RU-486 SO DRUG METABOLISM AND DISPOSITION LA English DT Note ID LOCALIZATION; RECEPTOR C1 NIDDK,BIOORGAN CHEM LAB,BETHESDA,MD 20892. MATSUMOTO DENT COLL,INST DENT SCI,MATSUMOTO,NAGANO,JAPAN. NR 11 TC 2 Z9 2 U1 0 U2 0 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 MAR PY 1995 VL 23 IS 3 BP 430 EP 432 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA QM299 UT WOS:A1995QM29900021 PM 7628311 ER PT J AU BITTON, RJ FIGG, WD REED, E AF BITTON, RJ FIGG, WD REED, E TI A PRELIMINARY RISK-BENEFIT ASSESSMENT OF PACLITAXEL SO DRUG SAFETY LA English DT Review AB Paclitaxel is an antineoplastic agent, first isolated and described in 1971. Despite its novel structure and apparent activity in vitro, little interest was shown in developing the compound because of its scarcity, problems with its formulation and the mistaken assumption that its mechanism of action was similar to that of the vinca alkaloids. Approximately 10 years later, the unique mechanism of action of paclitaxel, its ability to stabilise microtubules, was discovered, and its activity against human tumour xenografts was demonstrated. Interest in the drug was reignited and clinical testing began. Severe hypersensitivity reactions were controlled in the phase II programme with a premedication regimen consisting of dexamethasone, histamine H-1-antagonists and H-2-antagonists. Neutropenia was dose limiting in all studies conducted in patients with solid tumours. This toxicity was schedule-dependent, and less severe when paclitaxel was administered as a 3-hour infusion regimen. Peripheral neuropathy was mild to moderate in the initial experience, and dose-dependent. However, when bone marrow support with haemopoietic growth factors was used to allow paclitaxel dose intensification, neurotoxicity became dose limiting. To date, substantial clinical efficacy has been demonstrated in ovarian, breast, non-small-cell lung, and head and neck cancers. Response rates were low in initial studies in melanoma, prostate, colon, cervix and renal cancer. In December 1992, US Food and Drug Administration approval was granted for the use of paclitaxel as second-line therapy in ovarian cancer patients. More recently, similar approval was granted for use in recurrent breast cancer. Nevertheless, important questions remain. Such questions include: (a) the optimal dosage and schedule; (b) the use of paclitaxel as initial therapy; (c) its role in other malignancies; and (d) the development of suitable combination chemotherapy regimens. C1 NCI,CLIN PHARMACOL BRANCH,BETHESDA,MD 20892. RI Figg Sr, William/M-2411-2016 NR 0 TC 15 Z9 15 U1 0 U2 0 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND SN 0114-5916 J9 DRUG SAFETY JI Drug Saf. PD MAR PY 1995 VL 12 IS 3 BP 196 EP 208 DI 10.2165/00002018-199512030-00005 PG 13 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology GA QL674 UT WOS:A1995QL67400005 PM 7619331 ER PT J AU YARMOLA, E CHRAMBACH, A AF YARMOLA, E CHRAMBACH, A TI BAND-WIDTH MEASUREMENT IN AUTOMATED GEL-ELECTROPHORESIS APPARATUS - DNA DISPERSION IN A DISCONTINUOUS SYSTEM AND IN A SINGLE BUFFER SO ELECTROPHORESIS LA English DT Article DE AUTOMATED GEL ELECTROPHORESIS; BAND WIDTH; DISPERSION COEFFICIENT; DISCONTINUOUS BUFFER SYSTEM ID DIFFUSION-COEFFICIENTS; POLYACRYLAMIDE; FRAGMENTS AB Recent commercial introduction of automated gel electrophoresis apparatus allows for band width measurements during electrophoresis and therefore promises to open up the exploitation of band width and shape for the physical characterization of charged macromolecules in the same manner in which to date quantitative gel electrophoresis had exploited electrophoretic mobility at multiple gel concentrations. The measurements demonstrate decreased band width and therefore increased resolving power for a discontinuous buffer system compared to Tris-borate EDTA buffer. The dispersion coefficients (D' = (sigma(2) -sigma(0)(2))/t) of homogeneous DNA components appear to decrease with gel concentration when either the field strength or the DNA length is small, and increase with gel concentration when these are large. This contrasting response of D' to increasing gel concentration is presumably due to DNA stretching, which increases in proportion to DNA length and field strength, and to the progressive orientation of agarose with increasing field strength. C1 NICHHD,THEORET & PHYS BIOL LAB,MACROMOLEC ANAL SECT,BETHESDA,MD 20892. NR 17 TC 22 Z9 22 U1 0 U2 3 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0173-0835 J9 ELECTROPHORESIS JI Electrophoresis PD MAR PY 1995 VL 16 IS 3 BP 345 EP 349 DI 10.1002/elps.1150160158 PG 5 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA QV450 UT WOS:A1995QV45000012 PM 7607167 ER PT J AU YARMOLA, E CHRAMBACH, A AF YARMOLA, E CHRAMBACH, A TI NONLINEAR FERGUSON-CURVES BY 2 RUNS OF THE COMMERCIAL AUTOMATED HPGE-1000 GEL-ELECTROPHORESIS APPARATUS WITH INTERMITTENT SCANNING OF FLUORESCENCE SO ELECTROPHORESIS LA English DT Article DE AUTOMATED APPARATUS; FERGUSON PLOT ANALYSIS; NONLINEAR CURVE FIT; PRECISION OF MOBILITY DETERMINATION; SIMULTANEOUS ANALYSIS AT 8 GEL CONCENTRATIONS ID DNA AB The exploitation of gel electrophoretic migration distance to gain information of molecular and gel fiber properties depends on the functions relating mobility with gel concentration. To the degree that these are nonlinear, the definition of those functions by past methods has been excessively laborious or, in application of gel concentration gradients, based on a number of assumptions. The recent commercial introduction of gel electrophoresis apparatus capable of intermittent scanning of the pattern promised to solve these problems. The present study shows that such apparatus allows for a precise definition of a nonlinear ''Ferguson curve'' (mobility vs. gel concentration) in two experiments, using different gel concentrations in the eight channels of the HPGE-1000 apparatus and 5-29 scans in each during the course of an electrophoretic run. Simultaneously, these Ferguson curves are obtained for five components of a DNA ladder ranging in DNA length from 121 to 1857 bp. RP YARMOLA, E (reprint author), NICHHD,THEORET & PHYS BIOL LAB,MACROMOLEC ANAL SECT,BLDG 10,RM 6C-215,BETHESDA,MD 20892, USA. NR 7 TC 6 Z9 6 U1 0 U2 1 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 MAR PY 1995 VL 16 IS 3 BP 350 EP 353 DI 10.1002/elps.1150160159 PG 4 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA QV450 UT WOS:A1995QV45000013 PM 7607168 ER PT J AU RAY, JM STETLERSTEVENSON, WG AF RAY, JM STETLERSTEVENSON, WG TI GELATINASE-A ACTIVITY DIRECTLY MODULATES MELANOMA CELL-ADHESION AND SPREADING SO EMBO JOURNAL LA English DT Article DE ADHESION; GELATINASE A; INVASION; METASTASIS; TIMP-2 ID TISSUE INHIBITOR; IV COLLAGENASE; TUMOR INVASION; MATRIX METALLOPROTEINASES; PLASMINOGEN-ACTIVATOR; FIBRONECTIN RECEPTOR; AMNIOTIC MEMBRANE; EXPRESSION; METASTASIS; TIMP-2 AB Interaction of cells with the extracellular matrix (ECM) plays an important role in the regulation of cell behavior. Formation of adhesive contacts leads to transduction of signals into the cell and results in altered gene expression and modulation of the cellular phenotype. Specific adhesive interactions of the fibronectin and vitronectin receptors with their ligands in the matrix modulates expression of ECM-degrading metalloproteases. These proteases are involved in the acquisition of the invasive phenotype by a number of cell types. The activity of matrix metalloproteases (MMPs) is reduced by endogenous inhibitors referred to as tissue inhibitors of metalloproteases (TIMPs). Alterations in the balance between the activity of MMPs and TIMPs alters cellular invasion through effects on matrix degradation. In this study we demonstrate that inhibition of endogenous gelatinase A activity in A2058 human melanoma cells results in enhanced cellular adhesion. To further explore this phenomenon, we have used retroviral infection vectors to control the amount of the MMP inhibitor TIMP-2 in human melanoma A2058 cells. Altering the production of TIMP-2 modulates not only proteolysis of the extracellular matrix, but also the adhesive and spreading properties of the cells and results in altered cell morphology. These effects of TIMP-2 appear to be mediated by inhibition of gelatinase A activity. We conclude that gelatinase A, in addition to contributing to proteolysis of ECM components, also functions to proteolyse cell surface components that mediate attachment of A2058 cells to the ECM. Thus, gelatinase A may function to modulate cell attachment and facilitate cell migration and invasion. RP RAY, JM (reprint author), NCI,PATHOL LAB,EXTRACELLULAR MATRIX PATHOL SECT,BLDG 10,ROOM 2A33,BETHESDA,MD 20892, USA. RI Stetler-Stevenson, William/H-6956-2012 OI Stetler-Stevenson, William/0000-0002-5500-5808 NR 56 TC 158 Z9 162 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD MAR 1 PY 1995 VL 14 IS 5 BP 908 EP 917 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA QM733 UT WOS:A1995QM73300006 PM 7534227 ER PT J AU ROUVIERE, PE PENAS, ADL MECSAS, J LU, CZ RUDD, KE GROSS, CA AF ROUVIERE, PE PENAS, ADL MECSAS, J LU, CZ RUDD, KE GROSS, CA TI RPOE, THE GENE ENCODING THE 2ND HEAT-SHOCK SIGMA-FACTOR, SIGMA(E), IN ESCHERICHIA-COLI SO EMBO JOURNAL LA English DT Article DE HEAT SHOCK; OUTER MEMBRANE PROTEINS; SIGMA E; SIGMA FACTOR; THERMOTOLERANCE ID RNA-POLYMERASE; SEQUENCE-ANALYSIS; PROTEIN-DEGRADATION; STATIONARY-PHASE; HIGH-TEMPERATURE; HTRA GENE; DNAJ; EXPRESSION; TRANSCRIPTION; TRANSLOCATION AB In Escherichia coli, the heat shock response is under the control of two alternative sigma factors: sigma(32) and sigma(E). The sigma(32)-regulated response is well understood, whereas little is known about that of sigma(E), except that it responds to extracytoplasmic immature outer membrane proteins. To further understand this response, we located the rpoE gene at 55.5' and analyzed the role of sigma(E). sigma(E) is required at high temperature, and controls the transcription of at least 10 genes. Some of these might contribute to the integrity of the cell since Delta poE cells are more sensitive to SDS plus EDTA and crystal violet. sigma(E) controls its own transcription from a sigma(E)-dependent promoter, indicating that rpoE transcription plays a role in the regulation of E sigma(E) activity. Indeed, under steady-state conditions, the transcription from this promoter mirrors the levels of E sigma(E) activity in the cell. However, it is unlikely that the rapid increase in E sigma(E) activity following induction can be accounted for solely by increased transcription of rpoE. Based upon homology arguments, we suggest that a gene encoding a negative regulator of sigma(E) activity is located immediately downstream of rpoE and mag function as the target of the E sigma(E) inducing signal. C1 UNIV CALIF SAN FRANCISCO,DEPT STOMATOL,SAN FRANCISCO,CA 94143. UNIV CALIF SAN FRANCISCO,DEPT MICROBIOL,SAN FRANCISCO,CA 94143. STANFORD UNIV,DEPT MICROBIOL & IMMUNOL,STANFORD,CA 94305. NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,BETHESDA,MD 20894. UNIV WISCONSIN,DEPT BACTERIOL,MADISON,WI 53706. FU NIGMS NIH HHS [GM36278-06] NR 60 TC 232 Z9 236 U1 0 U2 10 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD MAR 1 PY 1995 VL 14 IS 5 BP 1032 EP 1042 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA QM733 UT WOS:A1995QM73300018 PM 7889934 ER PT J AU BLITHE, DL ILES, RK AF BLITHE, DL ILES, RK TI THE ROLE OF GLYCOSYLATION IN REGULATING THE GLYCOPROTEIN HORMONE FREE ALPHA-SUBUNIT AND FREE BETA-SUBUNIT COMBINATION IN THE EXTRAEMBRYONIC CELOMIC FLUID OF EARLY-PREGNANCY SO ENDOCRINOLOGY LA English DT Article ID HUMAN CHORIONIC-GONADOTROPIN; N-LINKED OLIGOSACCHARIDES; MATERNAL SERUM; LUTEINIZING-HORMONE; CELLS; HCG; EXPRESSION; MOLECULES; SECRETION; DIMER AB The extraembryonic coelomic fluid (EECF) represents a major compartment in the fetal-placental unit during the first trimester of pregnancy. The compartment is composed of the fluid contained between the chorionic and amniotic membranes. The levels of glycoprotein hormone free alpha-subunit and free beta-subunit in the EECF far exceed those in the amniotic fluid or maternal serum. Furthermore, the level of free alpha in this compartment is twice that of intact hCG. We purified the glycoprotein hormone free alpha-subunit from a pool of EECF. This free alpha-subunit was found to be larger in size than the alpha-subunit of intact hCG. The size difference was observed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis under reduced and denatured conditions. The carbohydrate composition of the EECF free alpha-subunit indicated a higher degree of oligosaccharide branching, as evidenced by larger amounts of fucose, sialic acid, galactose, and N-acetylglucosamine than were present on combined hCG alpha. These differences in size and carbohydrate composition argue strongly against the concept that free alpha-subunits might originate from dissociation of intact hCG or ''nicked'' hCG. The free subunits of the EECF were evaluated for their ability to combine with the corresponding subunit obtained by dissociation of intact hCG. EECF free beta was able to combine with hCG alpha to form intact hCG. In contrast, EECF free alpha was unable do combine with hCG beta to form intact hCG. However, after removal of the asparagine-linked glycans by treatment with N-glycanase, most of the previously uncombinable free alpha-subunits were able to combine with hCG beta. These data demonstrate that the N-linked oligosaccharide(s) of EECF free alpha function to prevent the molecule from combining with the available and combinable free beta-subunits that coexist in the same physiological compartment during early pregnancy. In view of the large amount of free alpha that is present in the EECF and the observation that, in vitro, free alpha can stimulate uterine decidual cell PRL secretion, together with the close apposition of free alpha-producing cells to decidual cells, it is likely that EECF free alpha has a function in early pregnancy. Carbohydrate modifications generated during the biosynthesis of EECF free alpha-subunit ensure that a population of free alpha molecules can exist in the presence of substantial quantities of free beta-subunits, and correspondingly, these same carbohydrate modifications function to permit the existence of free beta-subunits in the same gestational compartment with Gee alpha molecules. Whether there is a function for free beta-subunits in early pregnancy remains to be demonstrated. C1 ST BARTHOLOMEWS HOSP,COLL MED,JOINT ACAD DEPT REPROD PHYSIOL,WILLIAMSON LAB MOLEC ONCOL,LONDON EC1 7BE,ENGLAND. ST BARTHOLOMEWS HOSP,COLL MED,JOINT ACAD DEPT OBSTET & GYNECOL,WILLIAMSON LAB MOLEC ONCOL,LONDON EC1 7BE,ENGLAND. RP BLITHE, DL (reprint author), NICHHD,DEV ENDOCRINOL BRANCH,GLYCOBIOL UNIT,BLDG 10,ROOM 10N262,BETHESDA,MD 20892, USA. RI Iles, Ray/H-1617-2012 OI Iles, Ray/0000-0003-0573-9739 NR 40 TC 30 Z9 30 U1 0 U2 0 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD MAR PY 1995 VL 136 IS 3 BP 903 EP 910 DI 10.1210/en.136.3.903 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA QJ179 UT WOS:A1995QJ17900012 PM 7532582 ER PT J AU ZHENG, LX PAIK, WY CESNJAJ, M BALLA, T TOMIC, M CATT, KJ STOJILKOVIC, SS AF ZHENG, LX PAIK, WY CESNJAJ, M BALLA, T TOMIC, M CATT, KJ STOJILKOVIC, SS TI EFFECTS OF THE PHOSPHOLIPASE-C INHIBITOR, U73122, ON SIGNALING AND SECRETION IN PITUITARY GONADOTROPHS SO ENDOCRINOLOGY LA English DT Article ID GTP-BINDING PROTEIN; THYROTROPIN-RELEASING-HORMONE; INOSITOL PHOSPHATE PRODUCTION; CYTOSOLIC FREE CALCIUM; GUANOSINE TRIPHOSPHATE; CA2+ OSCILLATIONS; LH-RELEASE; CELL-LINE; EXOCYTOSIS; RECEPTOR AB The effects of inhibition of phosphoinositide hydrolysis by U73122 [1-(6-[17 beta-3-methoxyestra-1,3,5-(10)triene-17-yl]amino/hexyl) 1H-pyrroledione] and neomycin on agonist-stimulated intracellular signaling and secretory responses were analyzed in cultured pituary cells and alpha T3-1 gonadotrophs. GnRH (100 nM)- and endothelin-1 (ET-1; 100 nM)-induced inositol (1,4,5)-trisphosphate and diacylglycerol formation in normal cells and immortalized gonadotrophs were reduced by U73122 in a concentration-dependent manner, with IC50 values of about 2 mu M and complete inhibition at 10 mu M U73122. Neomycin also reduced GnRH- and ET-induced inositol phosphate production in both cell types. Agonist-induced intracellular Ca2+ responses were also inhibited in both cell types by U73122 and neomycin at the same concentrations that inhibited their inositol phosphate responses. In cultured pituitary cells, agonist-induced LH release was inhibited by U73122 and neomycin in a dose-dependent manner. In perifused pituitary cells, U73122 completely inhibited GnRH- and substantial increase in basal LH release. In static cultures, U73122 inhibited agonist-induced LH response at low concentrations (up to 3 mu M), but stimulated LH release at higher concentrations due to direct activation of exocytosis by the compound. When added alone, U73122 caused a concentration-dependent increase in LH release with an EC(50) of about 7 mu M and a maximum response similar to that elicited by GnRH. The stimulatory action of U73122 on LH release was not reduced in the absence of extracellular Ca2+. In contrast to cultured pituitary cells, alpha T3-1 gonadotrophs showed only constitutive exocytosis that was not affected by either neomycin or U73122. These results demonstrate that GnRH and ET(A) receptors are coupled to the phosphoinositide/Ca2+ transduction system in pituitary gonadotrophs, and provide evidence for the dependence of agonist-regulated exocytosis on this signaling pathway. The ability of U73122 to stimulate LH release could reflect an additional action of the compound at late steps in the exocytic pathway. C1 NICHHD,ENDOCRINOL & REPROD RES BRANCH,BETHESDA,MD 20892. RI Tomic, Melanija/C-3371-2016; OI Balla, Tamas/0000-0002-9077-3335 NR 45 TC 42 Z9 42 U1 0 U2 0 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD MAR PY 1995 VL 136 IS 3 BP 1079 EP 1088 DI 10.1210/en.136.3.1079 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA QJ179 UT WOS:A1995QJ17900034 PM 7867562 ER PT J AU HOOPER, K CLARK, GC AF HOOPER, K CLARK, GC TI WORKSHOP ON PERINATAL EXPOSURE TO DIOXIN-LIKE COMPOUNDS .6. ROLE OF BIOMARKERS SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE PCB; PCDD; PCDF; PERINATAL; TRANSPLACENTAL; LACTATIONAL; BIOMARKER; MECHANISM; REPRODUCTION; ENDOCRINOLOGY; NEUROBEHAVIOR; IMMUNOLOGY ID PRIMATE CALLITHRIX-JACCHUS; PERIPHERAL LYMPHOCYTE SUBPOPULATIONS; DIBENZO-PARA-DIOXINS; IMMUNE-SYSTEM; 2,3,7,8-TETRACHLORODIBENZO-PARA-DIOXIN TCDD; POLYCHLORINATED-BIPHENYLS; PCBS; CHILDREN; PHOSPHORYLATION; CONTAMINANTS AB Studies of perinatal exposures to dioxin-like compounds (DLCs), coplanar polycyclic halogenated aromatics whose prototype is 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), have employed a variety of outcome measures to investigate effects on the reproductive/developmental, endocrine, immune, and neurobehavioral systems. The effects include infertility, growth retardation, fetal loss, changed sexual differentiation, reduced cognitive/motor function, dermatologic and other ectodermal effects, and decreased immune response. Significant biomarkers have included sperm count; CD4/CD8 ratio; and levels of testosterone, T4, and dopamine. Using specific dioxin or PCB congeners, these and other markers were used to investigate the mechanisms of the observed effects. The DLCs, which include some PCB congeners, are characterized by high-affinity binding to the Ah receptor; most biological effects are thought to be mediated by the ligand-Ah receptor complex. Other PCB congeners have low affinity for the Ah receptor, and operate by non-Ah receptor mechanisms. The biologic activity of a PCB mixture is the sum of the agonist and antagonist activities of the different constituents in the mixture. Animal studies with specific PCB congeners can help to clarify these activities. With similar approaches, biologic markers of effect can be developed and applied in epidemiologic studies to monitor for, and predict, adverse effects in humans. C1 NATL INST ENVIRONM HLTH SCI,RES TRIANGLE PK,NC. RP HOOPER, K (reprint author), CAL ENV PROTECT AGCY,HAZARDOUS MAT LAB 1,2151 BERKELEY WAY,BERKELEY,CA 94707, USA. NR 52 TC 10 Z9 11 U1 2 U2 2 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 MAR PY 1995 VL 103 SU 2 BP 161 EP 167 DI 10.2307/3432464 PG 7 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA QW127 UT WOS:A1995QW12700022 PM 7614941 ER PT J AU BARRETT, JC AF BARRETT, JC TI REVAMP THE NTP BIOASSAY - RESPONSE SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Letter RP BARRETT, JC (reprint author), NIEHS,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 0 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 MAR PY 1995 VL 103 IS 3 BP 220 EP 220 PG 1 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA RF756 UT WOS:A1995RF75600003 ER PT J AU CASTONGUAY, A OVERBY, L NETTESHEIM, P CLARK, GC PHILPOT, RM AF CASTONGUAY, A OVERBY, L NETTESHEIM, P CLARK, GC PHILPOT, RM TI EXPRESSION OF XENOBIOTIC-METABOLIZING ENZYMES IN CULTURED RAT TRACHEAL EPITHELIAL-CELLS SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article ID MECHANICAL INJURY; S-TRANSFERASES; GLUTATHIONE; CYTOCHROME-P-450; MONOOXYGENASE; REGENERATION; CONJUGATION; HEPATOCYTES; SYSTEM AB Rat tracheal epithelial (RTE) cells were cultured on membrane support with and without retinoic acid (RA). In early (6-day-old) cultures, the epithelium is a monolayer or bilayer of undifferentiated cells and secretes little mucuslike product either in the absence or presence of RA. In late (12- to 15-day-old) cultures, the epithelium differentiates as a mucocilary epithelium in the presence of RA and as I squamous epithelium in the absence of RA. The purpose of our study was to determine whether a number of: xenobiotic enzymes are expressed in these cultures and whether their expression depends on the state of differentiation. Enzyme expression was characterized by electrophoresis and immunoblotting as a function of time in culture and phenotypic differentiation. Cytochrome P450 1A1 was not expressed in freshly harvested RTE cells. This isoenzyme was induced in mts by gavage with 2,3,7,8-teuachlorodibenzo-p-dioxin (TCDD) or by exposure of early RTE cell cultures to TCDD, provided RA was also added to the cultures. Cytochrome P450 observed in freshly isolated RTE cells, bur not in early or late RTE cultures. In contrast, expression of NADPH-cytochrome P450 reductase was decreased in early cultures, but was increased in well-differentiated cultures. Flavin-containing monooxygenase was detected in lung tissue, but hot in freshly harvested or cultured RTE cells. Glutathione s-transferases (GST) mu and pi were expressed in freshly harvested RTE cells. GST pi was expressed in early and late cultures, whereas GST mu was expressed in late cultures, bur could not be found in early cultured RTE cells. Levels of GST isoenzymes were unaffected by RA. These results parallel the expression of enzymes observed in proliferating and differentiating epithelium induced by mechanical injury in vivo. Induction of monooxygenases by polycyclic aromatic hydrocarbons results in RTE cells with metabolic activating and deactivating enzymes and constitutes a system suited for some toxicological studies. C1 NIEHS,RES TRIANGLE PK,NC 27606. RP CASTONGUAY, A (reprint author), UNIV LAVAL,SCH PHARM,CANC ETIOL & CHEMOPREVENT LAB,QUEBEC CITY,PQ G1K 7P4,CANADA. NR 30 TC 2 Z9 2 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 MAR PY 1995 VL 103 IS 3 BP 254 EP 258 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA RF756 UT WOS:A1995RF75600015 PM 7768226 ER PT J AU WACHOLDER, S AF WACHOLDER, S TI WHEN MEASUREMENT ERRORS CORRELATE WITH TRUTH - SURPRISING EFFECTS OF NONDIFFERENTIAL MISCLASSIFICATION SO EPIDEMIOLOGY LA English DT Article DE BIAS; BIOMETRY; ENVIRONMENTAL EXPOSURE; EPIDEMIOLOGIC METHODS; OCCUPATIONAL EXPOSURE; ODDS RATIO; SENSITIVITY AND SPECIFICITY; REGRESSION ANALYSIS; STATISTICS AB Most of the literature on the effect of nondifferential misclassification and errors in variables either addresses binary exposure variables or discusses continuous variables in the classical error model, where the error is assumed to be uncorrelated with the true value. In both of these situations, an imperfectly measured exposure always attenuates the relation, at least in the univariate setting. Furthermore, measuring a confounder with error independent of the exposure, even while measuring the exposure of interest perfectly, leads to partial control of the confounding. For many variables measured in epidemiology, particularly those based on self-report, however, errors are often correlated with the true value, and these rules may not apply. Epidemiologists need to be wary of deviations from the classical error model, since poor measurement might occasion ally explain a positive finding even when the error does not differ by disease status. RP WACHOLDER, S (reprint author), NCI,BIOSTAT BRANCH,6130 EXECUT BLVD,EPN 403,ROCKVILLE,MD 20852, USA. NR 0 TC 85 Z9 86 U1 1 U2 9 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD MAR PY 1995 VL 6 IS 2 BP 157 EP 161 DI 10.1097/00001648-199503000-00012 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA QJ259 UT WOS:A1995QJ25900012 PM 7742402 ER PT J AU SORKIN, JD BOLTON, PA GREENBLATT, J SITHISARANKUL, P VLAHOV, D GRAHAM, NMH AF SORKIN, JD BOLTON, PA GREENBLATT, J SITHISARANKUL, P VLAHOV, D GRAHAM, NMH TI AGE, GENDER, AND OTHER PREDICTORS OF THE WASTING SYNDROME AMONG HIV-1-INFECTED INJECTING DRUG-USERS SO EPIDEMIOLOGY LA English DT Article DE ACQUIRED IMMUNE DEFICIENCY SYNDROME; NUTRITION; WASTING SYNDROME; SUBSTANCE ABUSE; BETA(2)-MICROGLOBULIN AB We conducted a study to identify predictors of the wasting syndrome among human immunodeficiency virus 1 (HIV-1)-seropositive injecting drug users. We enrolled 113 cases (defined as an unexplained loss of >10% baseline weight) and 226 controls (defined as <5% weight loss or any weight gain) from a HIV-1 seropositive cohort of injecting drug users (N = 630) into a nested case-control study. Crude predictors of wasting included: older age [odds ratio (OR) for a 1-year difference = 1.06], female gender (OR = 1.66), more years spent injecting drugs (OR for 1-year difference = 1.05), presence of diarrhea (OR = 3.78), lower percentage of CD4 T-lymphocytes (OR for 10-unit difference = 0.73), and higher log beta(2)-microglobulin concentration (OR for 1 log difference = 11.3). After adjusting for CD4 cell level, beta(2)-microglobulin concentration, diarrhea, gender, length and frequency of drug use, age, the presence of thrush, and education, independent predictors of weight loss in HIV-seropositive injecting drug users were female gender (OR = 2.23) and increasing age (OR for 1-year difference = 1.06). Frequency and duration of drug use were not strongly associated with the odds of developing wasting syndrome in this HIV-1-seropositive cohort. These data indicate that HIV wasting syndrome in injecting drug users is distinct from complications of drug use. RP SORKIN, JD (reprint author), NIA,EPIDEMIOL DEMOG & BIOMETRY PROGRAM,GATEWAY BLDG ROOM 3C309,BETHESDA,MD 20892, USA. FU NIDA NIH HHS [DA 04334] 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 MAR PY 1995 VL 6 IS 2 BP 172 EP 177 DI 10.1097/00001648-199503000-00015 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA QJ259 UT WOS:A1995QJ25900015 PM 7742405 ER PT J AU POTISCHMAN, N BRINTON, LA COATES, RJ MALONE, KE SCHOENBERG, JB AF POTISCHMAN, N BRINTON, LA COATES, RJ MALONE, KE SCHOENBERG, JB TI EXPOSURE TO BREAST-MILK AND RISK OF BREAST-CANCER SO EPIDEMIOLOGY LA English DT Letter RP POTISCHMAN, N (reprint author), NCI,DIV CANC ETIOL,ENVIRONM EPIDEMIOL BRANCH,EXECUT PLAZA N 443,BETHESDA,MD 20892, USA. RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 NR 0 TC 4 Z9 4 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD MAR PY 1995 VL 6 IS 2 BP 198 EP 199 DI 10.1097/00001648-199503000-00025 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA QJ259 UT WOS:A1995QJ25900023 PM 7742412 ER PT J AU WESTERHOFF, HV ZASLOFF, M ROSNER, JL HENDLER, RW DEWAAL, A GOMES, AV JONGSMA, APM RIETHORST, A JURETIC, D AF WESTERHOFF, HV ZASLOFF, M ROSNER, JL HENDLER, RW DEWAAL, A GOMES, AV JONGSMA, APM RIETHORST, A JURETIC, D TI FUNCTIONAL SYNERGISM OF THE MAGAININS PGLA AND MAGAININ-2 IN ESCHERICHIA-COLI, TUMOR-CELLS AND LIPOSOMES SO EUROPEAN JOURNAL OF BIOCHEMISTRY LA English DT Article DE ANTIMICROBIAL PEPTIDES; BINARY TOXINS; COOPERATIVITY; XENOPUS LAEVIS; PEPTIDE-BASED IMMUNITY ID REAL-TIME MEASUREMENTS; ANTIMICROBIAL ACTIVITY; XENOPUS-LAEVIS; ION CHANNELS; SARCOPHAGA-PEREGRINA; RESPIRATORY CONTROL; GRANULAR GLAND; CDNA SEQUENCE; FROG-SKIN; DELTA-PH AB Xenopus laevis skin secretion contains a mixture of magainins, which are small positively charged oligopeptides with antimicrobial activity. In this study, we show that two of these peptides, i.e. magainin-2 and PGLa, are much more active in biological functions when added together than when added alone. This synergy applies for the antimicrobial activity of these peptides, and for the toxic effects on tumor cells. We show that this peptide combination is also synergistic when permeabilizing protein-free liposomes for glucose, when dissipating the membrane potential in cytochrome oxidase liposomes and Escherichia coli, and, reversibly, when stimulating respiration in the liposomes. The occurrence of synergy in these diverse systems (complex and simple) suggests that the biological synergy results from synergy in the primary activity of the magainin. peptides, namely the permeabilization of free-energy transducing membranes, possibly by forming a multimeric transmembrane pore of mixed peptide composition. The antimicrobial activity of X. laevis skin secretions may be greatly enhanced by the application of this binary weapon. C1 NETHERLANDS CANC INST,ANTONI VAN LEEUWENHOEK HOSP,DIV MOLEC BIOL,AMSTERDAM,NETHERLANDS. UNIV AMSTERDAM,BIOCTR,EC SLATER INST,AMSTERDAM,NETHERLANDS. CHILDRENS HOSP PHILADELPHIA,DEPT PEDIAT,PHILADELPHIA,PA 19104. CHILDRENS HOSP PHILADELPHIA,DEPT GENET,DIV HUMAN GENET,PHILADELPHIA,PA 19104. NIDDKD,MOLEC BIOL LAB,BETHESDA,MD 20892. NHLBI,CELL BIOL LAB,MEMBRANE ENZYMOL SECT,BETHESDA,MD 20892. UNIV SPLIT,FAC NAT SCI & ARTS,SPLIT,CROATIA. RI Westerhoff, Hans/I-5762-2012 OI Westerhoff, Hans/0000-0002-0443-6114 NR 53 TC 101 Z9 105 U1 0 U2 10 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 MAR 1 PY 1995 VL 228 IS 2 BP 257 EP 264 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QK722 UT WOS:A1995QK72200007 PM 7705337 ER PT J AU WOLLMAN, SH AF WOLLMAN, SH TI THYROID RADIOIODIDE TRANSPORT - MODELS, RATE-LIMITING STEPS, AND RELATION TO FORMATION OF IODOPROTEIN SO EUROPEAN JOURNAL OF CELL BIOLOGY LA English DT Review DE THYROCYTE MONOLAYER; RADIOIODIDE TRANSPORT; PROTEIN IODINATION ID APICAL PLASMA-MEMBRANE; IODIDE TRANSPORT; ION-TRANSPORT; ULTRASTRUCTURAL LOCALIZATION; CELL MONOLAYERS; EPITHELIAL-CELL; IODINATION; THYROTROPIN; FOLLICLES; FRTL-5 RP WOLLMAN, SH (reprint author), NCI,MOLEC BIOL LAB,37 CONVENT DR MSC 4255,BETHESDA,MD 20892, USA. NR 46 TC 6 Z9 6 U1 0 U2 1 PU WISSENSCHAFTLICHE VERLAG GMBH PI STUTTGART 10 PA BIRKENWALDSTRASSE 44 POSTFACH 105339, W-7000 STUTTGART 10, GERMANY SN 0171-9335 J9 EUR J CELL BIOL JI Eur. J. Cell Biol. PD MAR PY 1995 VL 66 IS 3 BP 217 EP 225 PG 9 WC Cell Biology SC Cell Biology GA QM105 UT WOS:A1995QM10500001 PM 7774607 ER PT J AU CONLON, K OSBORNE, J MORIMOTO, C ORTALDO, JR YOUNG, HA AF CONLON, K OSBORNE, J MORIMOTO, C ORTALDO, JR YOUNG, HA TI COMPARISON OF LYMPHOKINE SECRETION AND MESSENGER-RNA EXPRESSION IN THE CD45RA(+) AND CD45RO(+) SUBSETS OF HUMAN PERIPHERAL-BLOOD CD4(+) AND CD8(+) LYMPHOCYTES SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE T CELLS; CD45RA(+); CD45RO(+); LYMPHOKINES ID T-CELL CLONES; TUMOR-NECROSIS-FACTOR; FUNCTIONAL SUBSETS; INTERFERON-GAMMA; MESSENGER-RNA; DIFFERENTIATION; PROFILES; CD4+CD45RA+; ACTIVATION; ANTIBODY AB Flow cytometric analysis of human peripheral blood T lymphocytes demonstrated that the majority of the CD4(+) cells were CD29(+) or CD45RO(+) ''mature'' cells while the CD8(+) cells were primarily CD45R4(+) ''naive'' cells. After an initial separation into CD4(+) and CD8(+) cells and a secondary separation into CD45 subsets, lymphokine secretion was assessed after phorbol 12-myristate 13-acetate and ionomycin or fixed anti-CD3 stimulation. Within the respective CD45 subsets, CD4(+) cells produced more interleukin (IL)-2, IL-4, and IL-6; but the CD8(+) cells secreted more interferon-gamma and granulocyte/macrophage-colony-stimulating factor. Tumor necrosis factor-alpha secretion was similar in the matched CD45 subsets. Northern analysis revealed a parallel pattern of lymphokine mRNA expression in the four lymphocyte subsets. These results suggest that human CD8(+) peripheral blood lymphocytes have a significant capacity to secrete lymphokines, and that the low lymphokine production observed in unseparated CD8(+) cells reflects the higher percentage of less functional CD45RA(+) cells. C1 NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,EXPTL IMMUNOL LAB,FREDERICK,MD 21702. PROGRAM RESOURCES INC DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD. DANA FARBER CANC INST,DIV TUMOR IMMUNOL,CAMBRIDGE,MA. NR 31 TC 49 Z9 51 U1 0 U2 3 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 MAR PY 1995 VL 25 IS 3 BP 644 EP 648 DI 10.1002/eji.1830250303 PG 5 WC Immunology SC Immunology GA QY507 UT WOS:A1995QY50700002 PM 7705392 ER PT J AU FERNANDEZBOTRAN, R WYNN, TA HIENY, S CASPAR, P CHILTON, PM SHER, A AF FERNANDEZBOTRAN, R WYNN, TA HIENY, S CASPAR, P CHILTON, PM SHER, A TI LINKED IN-VIVO EXPRESSION OF SOLUBLE INTERLEUKIN-4 RECEPTOR AND INTERLEUKIN-4 IN MURINE SCHISTOSOMIASIS SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE SOLUBLE INTERLEUKIN-4 RECEPTOR; IMMUNOREGULATION; SCHISTOSOMA MANSONI; INTERLEUKIN-4 ID TUMOR-NECROSIS-FACTOR; STIMULATORY FACTOR-I; RESTING B-CELLS; INTERFERON-GAMMA; IL-4 RECEPTOR; T-CELLS; CYTOKINE RECEPTORS; MONOCLONAL-ANTIBODY; PROTECTIVE IMMUNITY; GRANULOMA-FORMATION AB Soluble interleukin-4 receptors (sIL-4R) are truncated IL-4R molecules that are secreted into biological fluids. To gain an insight into the mechanisms that control sIL-4R synthesis in vivo and their role in the regulation of immune responses, the expression and secretion of sIL-4R in mice infected with Schistosoma mansoni was studied. Splenocytes from infected animals responded to schistosomal antigen preparations with increased production of both IL-4 and sIL-4R. The synthesis of sIL-4R by spleen cells peaked at 8 weeks following infection and coincided with maximum levels of sIL-4R in serum and sIL-4R-specific mRNA in the liver of infected mice. The expression of IL-4-specific mRNA in the liver was different from that of IL-4R, reaching its peak approximately 2 weeks earlier. A relationship between sIL-4R production and the development and activation of Th2 cells was suggested by the findings that: (a) in vivo administration of anti-IL-4 antibodies (11B11) impaired the ability of splenic cells to secrete either IL-4 or sIL-4R; and (b) splenic cells from mice vaccinated with irradiated cercariae,which tend to develop much weaker Th2 responses than mice injected with live cercariae, expressed reduced levels of sIL-4R when challenged with schistosomal antigens. Moreover, a direct role for IL-4 in regulating the expression of sIL-4R was suggested by the ability of anti-IL-4 antibodies to inhibit sIL-4R synthesis in vitro. These data provide the first evidence demonstrating that the production of sIL-4R in vivo is up-regulated during immune responses, especially during those characterized by the development and activation of Th2 cells and IL-4 secretion. The association between sIL-4R and IL-4 syntheses is consistent with a potential role for sIL-4R in the regulation of IL-4 activity in vivo. C1 UNIV LOUISVILLE, SCH MED, DEPT MICROBIOL & IMMUNOL, LOUISVILLE, KY 40292 USA. NIAID, PARASIT DIS LAB, IMMUNOL & CELL BIOL SECT, BETHESDA, MD 20892 USA. RP FERNANDEZBOTRAN, R (reprint author), UNIV LOUISVILLE, SCH MED, DEPT PATHOL, DIV IMMUNOPATHOL, LOUISVILLE, KY 40292 USA. RI Wynn, Thomas/C-2797-2011; Fernandez-Botran, Rafael/J-3659-2016; OI Fernandez-Botran, Rafael/0000-0001-8138-8745; Chilton, Paula/0000-0002-8749-0975 NR 47 TC 17 Z9 17 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 MAR PY 1995 VL 25 IS 3 BP 649 EP 656 DI 10.1002/eji.1830250304 PG 8 WC Immunology SC Immunology GA QY507 UT WOS:A1995QY50700003 PM 7705393 ER PT J AU FITTS, MG MAGE, RG AF FITTS, MG MAGE, RG TI SECONDARY REARRANGEMENTS AND POST-REARRANGEMENT SELECTION CONTRIBUTE TO RESTRICTED IMMUNOGLOBULIN DJ(H) EXPRESSION IN YOUNG-RABBIT BONE-MARROW SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE RABBIT; IMMUNOGLOBULIN; RECOMBINATION; SELECTION; BONE MARROW ID B-CELL DEVELOPMENT; LIGHT CHAIN GENES; JUNCTIONAL DIVERSITY; V(D)J RECOMBINATION; SEQUENCE HOMOLOGIES; PREFERENTIAL USAGE; REGION GENE; VH; JH; SEGMENTS AB Extrachromosomal circular DNA purified from bone marrow cells of 2-weeks-old rabbits was assayed by polymerase chain reaction to determine the relative rearrangement frequencies of immunglobulin D-H to J(H) genes in vivo. D-H genes rearranged to individual J(H) genes with different frequencies. This bias did not correlate with potential sequence overlaps in the D-H or J(H) coding sequences. The J(H)2 and J(H)4 genes were the preferred targets of recombination in primary rearrangements. Although primary rearrangements to J(H)6 were relatively infrequent, secondary rearrangements were detected. This assay also revealed previously undescribed J(H) pseudogenes with functional recombination signal sequences. Analyses of genomic VDJ(H) indicated that B cells expressing VDJ(H)4 heavy chains survived and dominated in the bone marrow environment due to secondary rearrangements and/or post-rearrangement selection. RP FITTS, MG (reprint author), NIAID,IMMUNOL LAB,BLDG 10,ROOM 11N311,10 CTR DR MSC 1892,BETHESDA,MD 20892, USA. NR 38 TC 6 Z9 6 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 MAR PY 1995 VL 25 IS 3 BP 700 EP 707 DI 10.1002/eji.1830250311 PG 8 WC Immunology SC Immunology GA QY507 UT WOS:A1995QY50700010 PM 7705399 ER PT J AU RIZZO, LV DEKRUYFF, RH UMETSU, DT CASPI, RR AF RIZZO, LV DEKRUYFF, RH UMETSU, DT CASPI, RR TI REGULATION OF THE INTERACTION BETWEEN TH1 AND TH2 T-CELL CLONES TO PROVIDE HELP FOR ANTIBODY-PRODUCTION IN-VIVO SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE T CELL; B CELL; IMMUNOGLOBULIN; INTERLEUKIN-4; INTERFERON-GAMMA ID TRANSFORMING GROWTH FACTOR-BETA-1; MURINE B-CELLS; IFN-GAMMA; DIFFERENTIAL REGULATION; LYMPHOKINE ACTIVITIES; ANTIGEN CONCENTRATION; IMMUNE-RESPONSES; INTERFERON GAMMA; SUBSETS; IGE AB On the premise that an individual with an intact immune system has the capability to develop both cellular and antibody immune responses supported by the balance between the lymphokines secreted by Thelper (Th) cells, we studied the interaction between different types of Th cell clones in vivo and the parameters that may affect this interaction. We used an adoptive transfer system in which nude or lethally irradiated mice were reconstituted with histocompatible CD4(+) keyhole limpet hemocyanin (KLH)-specific T cell clones with defined lymphokine profiles. This approach allowed us to study the effects of the cognate interaction between T and B cells in the presence of a defined set of lymphokines. We demonstrated that the co-transfer of both subsets of Th cells resulted in increased production of IgA, and decreased production of IgE and IgG2a. The concomitant presence of both cell types also increases their functional survival in vivo. We have shown that in the presence of a Th2 clone, higher immunization doses (above 100 mu g trinitrophenol (TNP)-KLH/mouse) result in increased production of IgE and IgG1. In contrast, when a Th1 clone is present, low immunization doses (less than 50 mu g TNP-KLH/mouse) resulted in increased production of IgG2a. We were also able to show that the neutralization of interleukin-4 (IL-4) and or interferon-gamma (IFN-gamma) was sufficient to abrogate most of the regulatory effects caused by the Th2 or the Th1 clone respectively. Our results indicate that the subset of T cell(s) transferred determines the type of response obtained. In addition, the data presented indicate that the antigen dose used for immunization can modulate the quantitative parameters of the response. Furthermore, we have shown that the interaction between the two subsets of T cells in vivo is characterized by both antagonistic and agonistic effects and that most of the regulatory effects exerted by one subset over the other are mediated by IL-4 or IFN-gamma. C1 STANFORD UNIV,DEPT PEDIAT,STANFORD,CA 94305. LUCILLE PACKARD CHILDRENS HOSP,STANFORD,CA. RP RIZZO, LV (reprint author), NEI,IMMUNOL LAB,BLDG 10,ROOM 10N202,BETHESDA,MD 20892, USA. RI Rizzo, Luiz Vicente/B-4458-2009 FU NIAID NIH HHS [R07AI01026, R01AI24571, R01AI26322] NR 60 TC 53 Z9 54 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 MAR PY 1995 VL 25 IS 3 BP 708 EP 716 DI 10.1002/eji.1830250312 PG 9 WC Immunology SC Immunology GA QY507 UT WOS:A1995QY50700011 PM 7705400 ER PT J AU CONLON, K LLOYD, A CHATTOPADHYAY, U LUKACS, N KUNKEL, S SCHALL, T TAUB, D MORIMOTO, C OSBORNE, J OPPENHEIM, J YOUNG, H KELVIN, D ORTALDO, J AF CONLON, K LLOYD, A CHATTOPADHYAY, U LUKACS, N KUNKEL, S SCHALL, T TAUB, D MORIMOTO, C OSBORNE, J OPPENHEIM, J YOUNG, H KELVIN, D ORTALDO, J TI CD8(+) AND CD45RA(+) HUMAN PERIPHERAL-BLOOD LYMPHOCYTES ARE POTENT SOURCES OF MACROPHAGE INFLAMMATORY PROTEIN 1-ALPHA, INTERLEUKIN-8 AND RANTES SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE MACROPHAGE INFLAMMATORY PROTEIN 1-ALPHA; RANTES; INTERLEUKIN-8; CD45RA; CD45RO ID TUMOR-NECROSIS-FACTOR; T-CELL CLONES; MOLECULAR-CLONING; CYTOKINE FAMILY; GENE-EXPRESSION; HUMAN CD4+; ACTIVATION; IDENTIFICATION; MIP-1-ALPHA; MIP-1-BETA AB The chemokines macrophage inflammatory protein 1 alpha. (MIP 1 alpha), interleukin-8 (IL-8) and RANTES are potent regulators of leukocyte trafficking. Examination of chemokine secretion by human peripheral blood lymphocytes after stimulation with anti-CD3 or phorbol 12, 13 myristate acetate and ionomycin showed CD8(+) cells were the dominant source of MIP 1 alpha and RANTES. Although production of MLP 1 alpha and IL-8 were similar in pharmacologically stimulated CD4(+) CD45RA(+), CD4(+) CD45RO(+), and CD8(+) CD45RA(+) cells, the largest amounts of MIP 1 alpha and RANTES were secreted by CD8(+) CD45RO(+) lymphocytes. A parallel pattern of prolonged chemokine mRNA expression for at least 18 h after activation was observed in the T cell subsets. These results confirm that human T lymphocytes have a unique capacity for secretion of these three chemokines. In addition, CD8(+) cells have an unrecognized role in recruiting cells to sites of inflammation, and adult human CD45RA(+) cells have a physiologically significant secretory capacity. C1 NCI,FREDERICK CANC RES & DEV CTR,EXPTL IMMUNOL LAB,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,MOLEC IMMUNOREGULAT LAB,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21702. PRINCE HENRY HOSP,DEPT INFECT DIS,LITTLE BAY,NSW 2036,AUSTRALIA. UNIV MICHIGAN,DEPT PATHOL,ANN ARBOR,MI 48109. GENENTECH CORP,DEPT IMMUNOL,S SAN FRANCISCO,CA 94080. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR IMMUNOL,BOSTON,MA 02115. NCI,FREDERICK CANC RES & DEV CTR,DYNCORP,PRI,FREDERICK,MD 21702. NR 28 TC 106 Z9 107 U1 0 U2 1 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 MAR PY 1995 VL 25 IS 3 BP 751 EP 756 DI 10.1002/eji.1830250319 PG 6 WC Immunology SC Immunology GA QY507 UT WOS:A1995QY50700018 PM 7535702 ER PT J AU ECKELMAN, WC AF ECKELMAN, WC TI RADIOLABELING WITH TC-99M TO STUDY HIGH-CAPACITY AND LOW-CAPACITY BIOCHEMICAL SYSTEMS SO EUROPEAN JOURNAL OF NUCLEAR MEDICINE LA English DT Review DE TC-99; BIOCHEMICAL SYSTEMS; CHELATING AGENTS ID RED BLOOD-CELLS; MONOCLONAL-ANTIBODIES; AMINE OXIME; N-(2,6-DIMETHYLPHENYLCARBAMOYLMETHYL)IMINODIACETIC ACID; CORONARY ANATOMY; CHELATING AGENT; IMAGING AGENT; TC-99M; COMPLEXES; PERFUSION AB After a brief review of the history of the development of technetium-99m-labeled radiopharmaceuticals, the use of technetium chelates in high-capacity systems is discussed. The latter are used in the study of five organ systems, the kidneys, liver, bone, brain, and heart. The chemical characterization of Tc-99m complexes is also reviewed, followed by discussion of the various approaches to the labeling of proteins with direct labeling, the preformed chelate approach, and the antibody chelator conjugate approach. Thereafter, the labeling of biochemicals with Tc-99m for use with easily saturated sites, e.g., receptors and enzymes, is considered. Finally, attention is given to factors that affect the preparation of high specific activity, high affinity Tc-99m-labeled biochemicals. RP ECKELMAN, WC (reprint author), NIH,DEPT PET,BLDG 10,RM 1C495,ROCKVILLE,MD 20892, USA. NR 172 TC 100 Z9 100 U1 1 U2 6 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0340-6997 J9 EUR J NUCL MED JI Eur. J. Nucl. Med. PD MAR PY 1995 VL 22 IS 3 BP 249 EP 263 DI 10.1007/BF01081522 PG 15 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA QN650 UT WOS:A1995QN65000011 PM 7789399 ER PT J AU HEINRICHS, C TSIGOS, C DESCHEPPER, J DREWS, R COLLU, R DUGARDEYN, C GOYENS, P GHANEM, GE BOSSON, D CHROUSOS, GP VANVLIET, G AF HEINRICHS, C TSIGOS, C DESCHEPPER, J DREWS, R COLLU, R DUGARDEYN, C GOYENS, P GHANEM, GE BOSSON, D CHROUSOS, GP VANVLIET, G TI FAMILIAL ADRENOCORTICOTROPIN UNRESPONSIVENESS ASSOCIATED WITH ALACRIMA AND ACHALASIA - BIOCHEMICAL AND MOLECULAR STUDIES IN 2 SIBLINGS WITH CLINICAL HETEROGENEITY SO EUROPEAN JOURNAL OF PEDIATRICS LA English DT Article DE FAMILIAL ACTH UNRESPONSIVENESS; ISOLATED GLUCOCORTICOID DEFICIENCY; ACHALASIA; ALACRIMA; TRIPLE A SYNDROME ID ISOLATED GLUCOCORTICOID DEFICIENCY; SELECTIVE ACTH INSENSITIVITY; INSUFFICIENCY; RECEPTOR; HORMONE; ABNORMALITIES; DISORDERS; MUTATION; DISEASE; CARDIA AB The syndrome of familial adrenocorticotropin (ACTH) unresponsiveness is a rare form of primary adrenal insufficiency, usually without mineralocorticoid deficiency. It is characterized by elevated plasma ACTH concentrations and undetectable plasma cortisol levels not responding to exogenous ACTH. Alacrima and achalasia have also been occasionally associated with adrenal insufficiency (triple A syndrome). Pathogenetic mutations have been identified in the ACTH receptor gene in families with isolated familial ACTH unresponsiveness. Whether the ACTH receptor represents the locus of the defect for the triple A syndrome is not known. Here we report two siblings with familial ACTH unresponsiveness who were discrepant for skin pigmentation and mineralocorticoid function. In addition, achalasia and alacrima were documented only in the older sibling. The boy, studied at the age of 2 years, was hyperpigmented, in contrast to his normally pigmented sister, studied at the age of 9 years; basal plasma a-melanocyte stimulating hormone immunureactivity levels were 79 and 38 pg/ml, respectively (normal <40 pg/ml). Furosemide-induced diuresis resulted in normal rises of plasma renin activity in both patients; however, plasma aldosterone levels increased only in the boy and not in his sister. Screening for abnormalities of the ACTH receptor gene by single strand conformation polymorphism analysis revealed no abnormality. Direct sequencing of the entire coding area of the ACTH receptor gene was also normal. Conclusion The syndrome of familial ACTH unresponsiveness can vary clinically and biologically within the same family. In contrast to results from some families with isolated familial ACTH unresponsiveness, the ACTH receptor gene does not appear to be the locus of the defect in this pedigree, suggesting a different molecular aetiology for the triple A syndrome which associates adrenal insufficiency, alacrima and achalasia. C1 FREE UNIV BRUSSELS,DEPT PAEDIAT,BRUSSELS,BELGIUM. FREE UNIV BRUSSELS,DEPT RADIOL,BRUSSELS,BELGIUM. FREE UNIV BRUSSELS,DEPT EXPTL SURG,BRUSSELS,BELGIUM. FREE UNIV BRUSSELS,DEPT CLIN BIOCHEM,BRUSSELS,BELGIUM. NICHHD,DEV ENDOCRINOL BRANCH,BETHESDA,MD. UNIV MONTREAL,MONTREAL,PQ,CANADA. RP HEINRICHS, C (reprint author), HOP UNIV ENFANTS REINE FABIOLA,15 AVE J J CROCQ,B-1020 BRUSSELS,BELGIUM. NR 45 TC 20 Z9 21 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0340-6199 J9 EUR J PEDIATR JI Eur. J. Pediatr. PD MAR PY 1995 VL 154 IS 3 BP 191 EP 196 DI 10.1007/BF01954269 PG 6 WC Pediatrics SC Pediatrics GA QH204 UT WOS:A1995QH20400006 PM 7758515 ER PT J AU MARTIN, PR ADINOFF, B LANE, E STAPLETON, JM BONE, GAH WEINGARTNER, H LINNOILA, M ECKARDT, MJ AF MARTIN, PR ADINOFF, B LANE, E STAPLETON, JM BONE, GAH WEINGARTNER, H LINNOILA, M ECKARDT, MJ TI FLUVOXAMINE TREATMENT OF ALCOHOLIC AMNESTIC DISORDER SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Article DE KORSAKOFFS SYNDROME; FLUVOXAMINE; SEROTONIN; MEMORY; TREATMENT ID MEMORY; IMPAIRMENTS; MECHANISMS; SEROTONIN; DISEASE AB The serotonin uptake inhibitor fluvoxamine was assessed in treatment of alcohol-induced Korsakoff's syndrome (KS) using fixed (4 weeks, 200 mg/day) or individualized (6 weeks, plasma concentration greater than or equal to 400 ng/ml) dosing in randomized placebo-controlled double-blind crossover studies. Cognitive functions and concentrations of the major cerebrospinal fluid (CSF) metabolites of serotonin (5-HIAA), norepinephrine (MHPG), and dopamine (HVA) were determined in abstinent, nondepressed KS patients (aged 45-75), at baseline and placebo (3-4 weeks), and after 3-4 (n = 10) or 6 (n = 4) weeks of fluvoxamine administration. Fluvoxamine decreased CSF 5-HIAA compared to placebo (P < 0.003) without consistent changes in HVA or MHPG. Reductions in 5-HIAA correlated with improvements on the Wechsler Memory Scale Memory Quotient (P < 0.05), independent of effects on attention/vigilance or Beck Depression Inventory scores. Reductions in 5-HIAA correlated with plasma fluvoxamine (P < 0.03) only for fluvoxamine concentrations below 450 ng/ml. These findings suggest improvement of memory consolidation and/or retrieval in patients with Korsakoff's syndrome by fluvoxamine via serotonergic mechanisms. C1 NIAAA,CLIN STUDIES LAB,INTRAMURAL RES PROGRAM,BETHESDA,MD 20892. RI Martin, Peter/A-7738-2008 NR 45 TC 23 Z9 24 U1 3 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD MAR PY 1995 VL 5 IS 1 BP 27 EP 33 DI 10.1016/0924-977X(94)00129-Y PG 7 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA QP379 UT WOS:A1995QP37900006 PM 7542052 ER PT J AU SHAHABUDDIN, M CRISCIO, M KASLOW, DC AF SHAHABUDDIN, M CRISCIO, M KASLOW, DC TI UNIQUE SPECIFICITY OF IN-VITRO INHIBITION OF MOSQUITO MIDGUT TRYPSIN-LIKE ACTIVITY CORRELATES WITH IN-VIVO INHIBITION OF MALARIA PARASITE INFECTIVITY SO EXPERIMENTAL PARASITOLOGY LA English DT Article DE INHIBITION; TRYPSIN-LIKE ACTIVITY; MALARIA; PARASITE INFECTIVITY; MOSQUITO MIDGUT; AEDES AEGYPTI; PLASMODIUM GALLINACEUM; PERITROPHIC MATRIX ID AEDES-AEGYPTI; PLASMODIUM-GALLINACEUM; TRANSMISSION; CULICIDAE; DIPTERA AB Synchrony in the egress of Plasmodium ookinetes from the food bolus and enzymatic digestion of the blood meal in the mosquito midgut suggests that digestive enzymes play a role in the successful transmission of malaria parasites. Previously, we found that parasite-produced chitinase is essential for parasite transmission and can be activated by mosquito midgut protease. To determine the suitability of developing a transmission-blocking vaccine directed against mosquito trypsinlike enzyme(s), Aedes aegypti midgut trypsin-like proteases were characterized biochemically and compared to a mammalian trypsin. Mosquito trypsin is more sensitive to inhibition by aprotinin and less sensitive to egg white trypsin inhibitor than is bovine pancreatic trypsin. Soybean trypsin inhibitor and leupeptin inhibit both enzymes to similar extent. Membrane-feeding assays with aprotinin, leupeptin, and egg white trypsin inhibitor revealed a correlation between in vitro inhibition of mosquito trypsin-like activity and transmission-blocking activity; The results suggest a role for mosquito midgut trypsin(s) in malaria parasite development and indicate that the protease(s) is a potential target for blocking malaria transmission. (C) 1995 Academic Press, Inc. RP SHAHABUDDIN, M (reprint author), NIAID,MALARIA RES LAB,MOLEC VACCINE SECT,BETHESDA,MD 20892, USA. NR 17 TC 23 Z9 23 U1 0 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0014-4894 J9 EXP PARASITOL JI Exp. Parasitol. PD MAR PY 1995 VL 80 IS 2 BP 212 EP 219 DI 10.1006/expr.1995.1026 PG 8 WC Parasitology SC Parasitology GA QP934 UT WOS:A1995QP93400006 PM 7534722 ER PT J AU COHN, RG WILLIAMS, M SHER, A CAULFIELD, JP AF COHN, RG WILLIAMS, M SHER, A CAULFIELD, JP TI SCHISTOSOMA-MANSONI - CHARACTERIZATION OF AN FC-EPSILON-R(+) POPULATION OF GRANULE-CONTAINING SPLENOCYTES ISOLATED FROM INFECTED MICE SO EXPERIMENTAL PARASITOLOGY LA English DT Note ID BONE-MARROW; MAST-CELLS; BASOPHILS C1 NIAID,PARASIT DIS LAB,IMMUNOL & CELL BIOL SECT,BETHESDA,MD 20892. RP COHN, RG (reprint author), SYNTEX DISCOVERY RES,INST IMMUNOL & BIOL SCI,PALO ALTO,CA, USA. FU NIAID NIH HHS [AI-23083] NR 8 TC 7 Z9 7 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0014-4894 J9 EXP PARASITOL JI Exp. Parasitol. PD MAR PY 1995 VL 80 IS 2 BP 339 EP 341 DI 10.1006/expr.1995.1042 PG 3 WC Parasitology SC Parasitology GA QP934 UT WOS:A1995QP93400022 PM 7895845 ER PT J AU BASILE, AS SAITO, K ALMARDINI, H RECORD, CO HUGHES, RD HARRISON, P WILLIAMS, R LI, Y HEYES, MP AF BASILE, AS SAITO, K ALMARDINI, H RECORD, CO HUGHES, RD HARRISON, P WILLIAMS, R LI, Y HEYES, MP TI THE RELATIONSHIP BETWEEN PLASMA AND BRAIN QUINOLINIC ACID LEVELS AND THE SEVERITY OF HEPATIC-ENCEPHALOPATHY SO GASTROENTEROLOGY LA English DT Article ID CEREBROSPINAL-FLUID; AMINO-ACIDS; FAILURE; METABOLITES; TRYPTOPHAN; KYNURENINES; INCREASES; CYTOKINES; REGIONS; DEATH AB Background/Aims: Quinolinic acid is an endogenous neuroexcitant derived from tryptophan. Brain quinolinic acid concentrations ave reportedly elevated in chronic liver failure. The aim of this study was to determine if brain quinolinic acid levels correlate with the severity of hepatic encephalopathy. Methods: Postmortem samples of selected brain regions and plasma samples taken at several stages of encephalopathy were obtained from patients with acute and chronic liver failure. Quinolinic acid levels were measured by mass spectroscopy using [O-18]quinolinic acid. Results: Plasma quinolinic acid levels were significantly increased by stage I encephalopathy in patients with acute liver failure and by stages II and Ill in patients with chronic liver failure. Brain quinolinic acid levels were elevated only in patients with acute liver failure and were uniformly distributed at concentrations below those observed in plasma. Conclusions: The uniform distribution of quinolinic acid at subplasma concentrations in the brains of patients with acute liver failure suggests that it is synthesized peripherally and enters the brain across a permeabilized blood-brain barrier. Whereas the elevation of brain quinolinic acid levels in patients who died of acute but not chronic liver failure suggests that the involvement of quinolinic acid in the pathogenesis of hepatic encephalopathy is minimal, it could predispose these patients to seizures. C1 NIMH,CLIN SCI LAB,ANALYT BIOCHEM SECT,BETHESDA,MD 20892. ROYAL VICTORIA INFIRM,GASTROENTEROL UNIT,NEWCASTLE TYNE NE1 4LP,TYNE & WEAR,ENGLAND. UNIV LONDON KINGS COLL,SCH MED,INST LIVER STUDIES,LONDON,ENGLAND. RP BASILE, AS (reprint author), NIDDKD,NEUROSCI LAB,BLDG 8,ROOM 111,BETHESDA,MD 20892, USA. RI Harrison, Phillip/D-5374-2009 NR 33 TC 20 Z9 20 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD MAR PY 1995 VL 108 IS 3 BP 818 EP 823 DI 10.1016/0016-5085(95)90456-5 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA QK572 UT WOS:A1995QK57200025 PM 7875484 ER PT J AU BRODY, DS THOMPSON, TL LARSON, DB FORD, DE KATON, WJ MAGRUDER, KM AF BRODY, DS THOMPSON, TL LARSON, DB FORD, DE KATON, WJ MAGRUDER, KM TI RECOGNIZING AND MANAGING DEPRESSION IN PRIMARY-CARE SO GENERAL HOSPITAL PSYCHIATRY LA English DT Article ID GENERAL HEALTH QUESTIONNAIRE; NATURALISTIC FOLLOW-UP; SELF-REPORT SCALE; COGNITIVE THERAPY; PSYCHIATRIC-DISORDERS; MEDICAL-CARE; RECURRENT DEPRESSION; NEGOTIATED APPROACH; FAMILY-PRACTICE; SOCIAL SUPPORT AB Depression is a common disorder in the primary care setting; it is associated with considerable distress and dysfunction. The management of depressed primary care patients can be complicated by the fact that these patients may lack insight into the cause of their symptoms and report only the somatic manifestations of their disorder to their physicians. Primary care patients may also be reluctant to accept a diagnosis of depression or referral to a mental health specialist. Primary care physicians may feel thy lack the time or the training to adequately address their patients' depressive disorders. This paper presents a model for identifying, evaluating, and treating depression which has been specifically developed to help primary care physicians overcome these barriers. C1 THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,DEPT PSYCHIAT,DEPT HLTH HUMAN SERV,PHILADELPHIA,PA 19107. JOHNS HOPKINS UNIV HOSP,DEPT MED,BALTIMORE,MD 21205. WASHINGTON UNIV,SCH MED,DEPT PSYCHIAT & BEHAV SCI,ST LOUIS,MO 63130. NIMH,DIV APPL & SCI RES,BETHESDA,MD 20892. RP BRODY, DS (reprint author), MERCY CATHOLIC MED CTR,DEPT MED,1500 LANSDOWNE AVE,DARBY,PA 19023, USA. NR 76 TC 38 Z9 39 U1 4 U2 4 PU ELSEVIER SCIENCE PUBL CO INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0163-8343 J9 GEN HOSP PSYCHIAT JI Gen. Hosp. Psych. PD MAR PY 1995 VL 17 IS 2 BP 93 EP 107 DI 10.1016/0163-8343(94)00093-S PG 15 WC Psychiatry SC Psychiatry GA QP239 UT WOS:A1995QP23900005 PM 7789790 ER PT J AU HAVERKOS, HW DROTMAN, DP AF HAVERKOS, HW DROTMAN, DP TI MEASURING INHALANT NITRITE EXPOSURE IN GAY MEN - IMPLICATIONS FOR ELUCIDATING THE ETIOLOGY OF AIDS-RELATED KAPOSIS-SARCOMA SO GENETICA LA English DT Article ID ACQUIRED IMMUNODEFICIENCY SYNDROME; HOMOSEXUAL MEN; BISEXUAL MEN; GENERALIZED LYMPHADENOPATHY; COFACTORS; COHORT; RISK; EPIDEMIOLOGY AB We reviewed 12 epidemiologic studies conducted among gay men with AIDS to examine the role of potential 'cofactors' in the development of KS. Aspects of the studies reviewed include basic study design, wording of the questionnaires, and published results comparing KS patients with those who developed opportunistic infections indicative of AIDS. The studies included questions about sociodemographics, medical history, use of drugs, travel, and sexual behaviors. Patients were invited to provide blood and/or other specimens for laboratory analysis. The results of the review of epidemiologic studies are inconclusive. Nitrite inhalant use was a variable often associated with KS (five studies). The differences in outcomes of these studies may reflect differences in study designs, sample sizes, timing, quality, and content of interviews regarding nitrites, sexual behaviours and other potential cofactors. Epidemiologic study with careful consideration to content of questionnaires and laboratory testing may yet reveal the causes or cofactors for this tumor. C1 CTR DIS CONTROL & PREVENT,ATLANTA,GA 30341. RP HAVERKOS, HW (reprint author), NIDA,5600 FISHERS LANE,ROOM 10A-38,ROCKVILLE,MD 20857, USA. NR 23 TC 9 Z9 9 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0016-6707 J9 GENETICA JI Genetica PD MAR PY 1995 VL 95 IS 1-3 BP 157 EP 164 DI 10.1007/BF01435007 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA QV294 UT WOS:A1995QV29400011 PM 7744258 ER PT J AU AMADOU, C RIBOUCHON, MT MATTEI, MG JENKINS, NA GILBERT, DJ COPELAND, NG AVOUSTIN, P PONTAROTTI, P AF AMADOU, C RIBOUCHON, MT MATTEI, MG JENKINS, NA GILBERT, DJ COPELAND, NG AVOUSTIN, P PONTAROTTI, P TI LOCALIZATION OF NEW GENES AND MARKERS TO THE DISTAL PART OF THE HUMAN MAJOR HISTOCOMPATIBILITY COMPLEX (MHC) REGION AND COMPARISON WITH THE MOUSE - NEW INSIGHTS INTO THE EVOLUTION OF MAMMALIAN GENOMES SO GENOMICS LA English DT Article ID CLASS-I REGION; T-COMPLEX; LINKAGE MAP; TRANSCRIPTION FACTOR; BEIGE BG; HLA; CHROMOSOME-13; ORGANIZATION; IDENTIFICATION; GLYCOPROTEIN AB We have refined and extended the map of the distal half of the human major histocompatibility complex. The map is continuous from HLA-E to 1000 kb telomeric of HLA-F and includes six new markers and genes. In addition, the corresponding sequences that were not previously mapped in the mouse genome have been located. The human and the mouse organizations have therefore been compared. This comparison allows us to demonstrate that the structure of the distal part of the MHC is similar in the two species. In addition, this comparison shows the presence of a breakpoint of synteny telomeric of the distal part of the H-2 region. Indeed, the region telomeric of HLA in human is found on a chromosome different from that carrying H-2 in mouse. The mapping analysis of paralogous genes (structurally related genes) around the breakpoint shows that the human organization probably represents the putative human/mouse ancestral one. This evolutionary breakpoint was precisely mapped in human, and the surrounding region was cloned into yeast artificial chromosomes. Finally, we show that the region found around the breakpoint was involved several times in chromosome recombinations in the mouse lineage, as it seems to correspond also to the t-complex distal inversion point. (C) 1995 Academic Press, Inc. C1 CHU PURPAN,CNRS,UPR 8291,F-31300 TOULOUSE,FRANCE. HOP ENFANTS LA TIMONE,INSERM,U406,F-13385 MARSEILLE 5,FRANCE. NCI,FREDERICK CANC RES & DEV CTR,MAMMALIAN GENET LAB,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. OI Pierre, Pontarotti/0000-0001-7202-3648 FU NCI NIH HHS [N01-CO-74101] NR 45 TC 73 Z9 74 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD MAR 1 PY 1995 VL 26 IS 1 BP 9 EP 20 DI 10.1016/0888-7543(95)80077-Y PG 12 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA QN568 UT WOS:A1995QN56800002 PM 7782091 ER PT J AU IWATA, T POPESCU, NC ZIMONJIC, DB KARLSSON, C HOOG, JO VACA, G RODRIGUEZ, IR CARPER, D AF IWATA, T POPESCU, NC ZIMONJIC, DB KARLSSON, C HOOG, JO VACA, G RODRIGUEZ, IR CARPER, D TI STRUCTURAL ORGANIZATION OF THE HUMAN SORBITOL DEHYDROGENASE GENE (SORD) SO GENOMICS LA English DT Article ID ALCOHOL-DEHYDROGENASE; ALDOSE REDUCTASE; HEREDITARY CATARACTS; FAMILY; PURIFICATION; PROTEIN; LENS; COMPLICATIONS; PROMOTER; PATHWAY AB The primary structure of human sorbitol dehydrogenase (SORD) was determined by cDNA and genomic cloning. The nucleotide sequence of the mRNA covers 2471 bp including an open reading frame that yields a protein of 356 amino acid residues. The gene structure of SORD spans approximately 30 kb divided into 9 exons and 8 introns. The gene was localized to chromosome 15q21.1 by in situ hybridization. Two transcription initiation sites were detected. Three Spl sites and a repetitive sequence (CAAA)(5) were observed in the 5' noncoding region; no classical TATAA or CCAAT elements were found. The related alcohol dehydrogenases and zeta-crystallin have the same gene organization split by 8 introns, but no splice points coincide between SORD and these gene types. The deduced amino acid sequence of the SORD structure differs at a few positions from the directly determined protein sequence, suggesting allelic forms of the enzyme. High levels of SORD transcripts were observed in lens and kidney, as judged from Northern blot analysis. (C) 1995 Academic Press, Inc. C1 NEI,MECHANISMS OCULAR DIS LAB,BETHESDA,MD 20892. NEI,RETINAL CELL & MOLEC BIOL LAB,BETHESDA,MD 20892. NCI,DIV CANC ETIOL,BIOL LAB,BETHESDA,MD 20892. KAROLINSKA INST,DEPT MED BIOCHEM & BIOPHYS,STOCKHOLM,SWEDEN. CTR INVEST BIOMED OCCIDENTE,INST MEXICANO SEGURO SOCIAL,GUADALAJARA,JALISCO,MEXICO. NR 42 TC 20 Z9 21 U1 0 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD MAR 1 PY 1995 VL 26 IS 1 BP 55 EP 62 DI 10.1016/0888-7543(95)80082-W PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA QN568 UT WOS:A1995QN56800007 PM 7782086 ER PT J AU BLITHE, D AF BLITHE, D TI EXPERTISE IN GLYCOBIOLOGY - THE INVISIBLE CATEGORY SO GLYCOBIOLOGY LA English DT Letter RP BLITHE, D (reprint author), NICHHD,GLYCOBIOL UNIT,BLDG 10,ROOM 10N262,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD MAR PY 1995 VL 5 IS 2 BP 155 EP 156 DI 10.1093/glycob/5.2.155 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QQ100 UT WOS:A1995QQ10000003 PM 7780188 ER PT J AU VANWAES, C AF VANWAES, C TI CELL-ADHESION AND REGULATORY MOLECULES INVOLVED IN TUMOR-FORMATION, HEMOSTASIS, AND WOUND-HEALING SO HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK LA English DT Review ID INTEGRIN ALPHA-6-BETA-4; SQUAMOUS CARCINOMA; EXPRESSION; RECEPTORS; ANTIBODY; LAMININ; BETA; A9 AB Background. Dynamic changes in cell adhesion and migration are fundamental properties of the cells that are important in hemostasis, vascularization, and wound repair. Changes in cell adhesion and migration are very important in the formation of tumors, and invasion and metastasis by neoplasms. Methods. Using immunolocalization and immunopurification techniques, expression of integrin molecules involved in cell adhesion has been characterized during tumor development and wound healing. The ability of cytokines to regulate expression and antibody and peptide inhibitors to inhibit function of integrins has been explored to better understand the role of integrins in pathogenesis. Results. Increased suprabasilar expression or the integrins alpha 6 beta 4, alpha 2 beta 1, and alpha 3 beta 1 accompanies development of squamous cell neoplasms of the head and neck. Integrin alpha II beta 3 is an integrin receptor which is important in platelet aggregation in hemostasis and formation of tumor metastases. Increased expression of integrin alpha v beta 3 has been identified in angiogenesis in response to growth factors and tumor angiogenic factors. Cytokine TGF-beta and arachadonic acid metabolite 12(S)-HETE are important signals in regulation of integrins and affect cell aggregation and migration in these processes. Ligands and inhibitors for some of these receptors have been identified which will be useful in determining their role during tumor development and progression. Conclusions. Recent advances in understanding the functions of the integrin cell adhesion molecules may soon add new diagnostic methods and therapies to the armamentarium of the head and neck oncologic, microvascular, plastic, and reconstructive surgeon. Therapies directed at controlling integrin cell-adhesion molecule expression and function are being explored to improve scar formation, bone synthesis, inhibition of vascular occlusion, and inhibition of tumor invasion and metastasis. (C) 1995 John Wiley and Sons, Inc. RP VANWAES, C (reprint author), NIDCD,TUMOR BIOL SECT,HEAD & NECK SURG BRANCH,5 RES COURT,ROOM 2B46,ROCKVILLE,MD 20850, USA. FU NIDCD NIH HHS [Z01-DC-00017] NR 18 TC 36 Z9 36 U1 0 U2 1 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0148-6403 J9 HEAD NECK-J SCI SPEC JI Head Neck-J. Sci. Spec. Head Neck PD MAR-APR PY 1995 VL 17 IS 2 BP 140 EP 147 DI 10.1002/hed.2880170212 PG 8 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA QH631 UT WOS:A1995QH63100011 PM 7558812 ER PT J AU PETTIT, GR XU, JP CICHACZ, Z SCHMIDT, JM DORSAZ, AC BOYD, MR CERNY, RL AF PETTIT, GR XU, JP CICHACZ, Z SCHMIDT, JM DORSAZ, AC BOYD, MR CERNY, RL TI ISOLATION AND STRUCTURE OF THE HUMAN CANCER CELL-GROWTH INHIBITORY PHAKELLISTATIN-4 FROM THE WESTERN PACIFIC SPONGE PHAKELLIA-COSTATA SO HETEROCYCLES LA English DT Article ID ANTINEOPLASTIC AGENTS; MARINE AB Structural elucidation by high field 2D nmr and FAB-ms/ms techniques led to cyclo-(Pro-Thr-Pro-Phe-Ile-Phe-Ser) as the assignment for phakellistatin(4)a new cell growth inhibitory peptide from the Chuuk Archipelago marine sponge Phakellia costata. C1 ARIZONA STATE UNIV,DEPT CHEM,TEMPE,AZ 85287. NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,FREDERICK,MD 21702. UNIV NEBRASKA,DEPT CHEM,MIDWEST CTR MASS SPECT,LINCOLN,NE 68588. RP PETTIT, GR (reprint author), ARIZONA STATE UNIV,CANC RES INST,TEMPE,AZ 85287, USA. NR 11 TC 15 Z9 15 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0385-5414 J9 HETEROCYCLES JI Heterocycles PD MAR 1 PY 1995 VL 40 IS 2 BP 501 EP 506 PG 6 WC Chemistry, Organic SC Chemistry GA QN351 UT WOS:A1995QN35100001 ER PT J AU GUBERNICK, DJ WINSLOW, JT JENSEN, P JEANOTTE, L BOWEN, J AF GUBERNICK, DJ WINSLOW, JT JENSEN, P JEANOTTE, L BOWEN, J TI OXYTOCIN CHANGES IN MALES OVER THE REPRODUCTIVE-CYCLE IN THE MONOGAMOUS, BIPARENTAL CALIFORNIA MOUSE, PEROMYSCUS-CALIFORNICUS SO HORMONES AND BEHAVIOR LA English DT Article ID MATERNAL-BEHAVIOR; SEXUAL-BEHAVIOR; PRAIRIE VOLES; MICROTUS-OCHROGASTER; PARENTAL BEHAVIOR; PATERNAL BEHAVIOR; MATING SYSTEM; RATS; VASOPRESSIN; PROLACTIN AB Levels of plasma oxytocin in male Peromyscus californicus were assessed across the reproductive cycle to provide a foundation for subsequent studies of the hormonal basis of paternal behavior and pair bonds. In Experiment 1, plasma oxytocin levels were significantly higher in expectant fathers than in virgin males or fathers. Plasma oxytocin increased in expectant fathers 1 day postcopulation and remained elevated for the first 15 days of gestation. Plasma oxytocin declined by Day 20 of gestation and oxytocin levels remained low in fathers throughout the lactational period. Oxytocin levels among expectant fathers did not differ between parental and nonparental males or between infanticidal and noninfanticidal males, suggesting that plasma oxytocin may not be involved in the prepartum onset of paternal behavior or the inhibition of infanticide. In Experiment 2, plasma oxytocin levels also did not differ between males that were parental or non-parental prepartum or postpartum. However, males separated from their mate and pups on the day of birth had elevated oxytocin levels on Day 3 postpartum compared to males that remained with their family, suggesting that disruption of the pair bond and/or absence of the young affects plasma oxytocin levels in males. This possibility remains to be determined. (C) 1995 Academic Press, Inc. C1 NIMH,NEUROPHYSIOL LAB,POOLESVILLE,MD 20837. RP GUBERNICK, DJ (reprint author), UNIV WISCONSIN,DEPT PSYCHOL,MADISON,WI 53706, USA. NR 45 TC 45 Z9 45 U1 1 U2 5 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0018-506X J9 HORM BEHAV JI Horm. Behav. PD MAR PY 1995 VL 29 IS 1 BP 59 EP 73 DI 10.1006/hbeh.1995.1005 PG 15 WC Behavioral Sciences; Endocrinology & Metabolism SC Behavioral Sciences; Endocrinology & Metabolism GA QN960 UT WOS:A1995QN96000005 PM 7782063 ER PT J AU JANINI, GM MUSCHIK, GM ISSAQ, HJ AF JANINI, GM MUSCHIK, GM ISSAQ, HJ TI MICELLAR ELECTROKINETIC CHROMATOGRAPHY IN COATED CAPILLARIES - DETERMINATION OF MICELLE-AQUEOUS PARTITION-COEFFICIENTS SO HRC-JOURNAL OF HIGH RESOLUTION CHROMATOGRAPHY LA English DT Article DE MICELLAR ELECTROKINETIC CHROMATOGRAPHY (MEKC); MICELLE-AQUEOUS PARTITION COEFFICIENTS; HYDROPHOBIC SOLUTES; POLYACRYLAMIDE-COATED COLUMNS ID LIQUID-CHROMATOGRAPHY; SOLUTES; BEHAVIOR AB A micellar electrokinetic chromatography method is presented for the determination of the partition coefficient for the distribution nonpolar and moderately polar solutes between the micelle and the aqueous phases in aqueous micellar solutions. In comparison with the literature the method is, theoretically and experimentally, the most straightforward for this application. An equation is derived for the determination of the partition coefficient in a coated fused silica capillary, with negligible electroosmotic flow, from simple measurements of the migration times of solutes and a marker for micelle migration. The advantages and limitations of this method are discussed. The method is tested by using sodium dodecylsulfate (SDS) surfactant and naphthalene, benzene, toluene, and phenol solutes. Micellar electrokinetic chromatography in coated columns is ideally suited for the separation of hydrophobic solutes in aqueous samples. RP JANINI, GM (reprint author), NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,POB B,FREDERICK,MD 21702, USA. NR 18 TC 11 Z9 11 U1 2 U2 4 PU DR ALFRED HUTHIG VERLAG GMBH PI HEIDELBERG 1 PA POSTFACH 102869, W-69018 HEIDELBERG 1, GERMANY SN 0935-6304 J9 HRC-J HIGH RES CHROM JI HRC-J. High Resolut. Chromatogr. PD MAR PY 1995 VL 18 IS 3 BP 171 EP 174 PG 4 WC Chemistry, Analytical SC Chemistry GA QV369 UT WOS:A1995QV36900006 ER PT J AU KORST, RJ BEWIG, B CRYSTAL, RG AF KORST, RJ BEWIG, B CRYSTAL, RG TI IN-VITRO AND IN-VIVO TRANSFER AND EXPRESSION OF HUMAN SURFACTANT SP-A-ASSOCIATED AND SP-B-ASSOCIATED PROTEIN CDNAS MEDIATED BY REPLICATION-DEFICIENT, RECOMBINANT ADENOVIRAL VECTORS SO HUMAN GENE THERAPY LA English DT Article ID PULMONARY ALVEOLAR PROTEINOSIS; RESPIRATORY-DISTRESS SYNDROME; II CELLS; BIOPHYSICAL ACTIVITY; LUNG SURFACTANT; ESCHERICHIA-COLI; GENE; MACROPHAGES; INVIVO; RECONSTITUTION AB Congenital pulmonary alveolar proteinosis (CPAP) is a fatal disease of full-term infants that is unresponsive to current medical therapy. It is now recognized that at least some forms of this disorder are associated with a deficiency of SP-B, one of the surfactant-associated proteins, as well as probable aberrations in the surfactant-associated proteins SP-A and SP-C. Given these developments, it is logical to hypothesize that CPAP may be amenable to gene therapy, in which the human SP-B cDNA, and possibly the cDNAs of the other surfactant associated proteins, are transferred to the epithelium of the lower respiratory tract. We constructed replication-deficient, recombinant adenovirus vectors in which a constitutive viral promoter drives the expression of the DNAs for the surfactant-associated proteins, SP-B (AdCMV.SP-B) and SP-A (AdCMV.SP-A). Following infection of the human lung A549 epithelial cell line with these vectors in vitro, the appropriately sized mRNAs for these cDNAs were detected, whereas cells infected with a control virus or uninfected cells produced none. Western blots demonstrated expression of these proteins, including appropriate processing of the hydrophobic protein, SP-B. Following in vivo intratracheal infection of rats with these vectors, Northern analysis of the lungs revealed appropriately sized mRNAs for these cDNAs whereas rats infected with control virus or uninfected rats show no hybridization with the human surfactant-associated protein probes. In the AdCMV.SP-A-infected rats. Western blots confirmed the overproduction of the human SP-A protein in both the bronchoalveolar lavage and lung homogenates compared to controls. Thus, it is feasible to utilize adenovirus vectors to transfer and express the human surfactant associated protein cDNAs in vitro and in vivo, presenting a possible mode of therapy for CPAP, as well as other surfactant deficiency states such as the neonatal respiratory distress syndrome and possibly the adult respiratory distress syndrome. C1 NHLBI,PULM BRANCH,BETHESDA,MD 20892. CORNELL UNIV,COLL MED,DIV PULM & CRIT CARE MED,NEW YORK,NY 10021. NR 57 TC 54 Z9 57 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD MAR PY 1995 VL 6 IS 3 BP 277 EP 287 DI 10.1089/hum.1995.6.3-277 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA QN706 UT WOS:A1995QN70600002 PM 7779911 ER PT J AU ZIMMERMAN, PA PHADKE, PM LEE, A ELSON, LH ARUAJO, E GUDERIAN, R NUTMAN, TB AF ZIMMERMAN, PA PHADKE, PM LEE, A ELSON, LH ARUAJO, E GUDERIAN, R NUTMAN, TB TI MIGRATION OF A NOVEL DQA1-ASTERISK ALLELE (DQA1-ASTERISK-0502) FROM AFRICAN ORIGIN TO NORTH AND SOUTH-AMERICA SO HUMAN IMMUNOLOGY LA English DT Article ID HLA-B ALLELES; T-CELLS; MOLECULES; POLYMORPHISM; EVOLUTION; RESIDUES; BINDING; HLA-DR1 AB A PCR-based strategy termed DHDA has recently been developed which reveals DQA1 and DQB1 allelic polymorphism through gel retardation following electrophoresis. This HLA-typing strategy improves the efficiency of identifying previously undetected DNA sequence polymorphisms. DHDA has been utilized to perform DQA1 genotypic analysis in non-Caucasian populations and has resulted in the identification of a novel allele, DQA1*0502 (designated by the WHO nomenclature committee). This new allele has been found in Africans and South and North Americans of black racial ancestry and is geographically consistent with the African diaspora during the 15th-19th centuries. DQA1*0502 represents a single C-to-G transversion in codon 59 (exon 2) and results in an amino acid change from proline to arginine. Although MHC genes are highly polymorphic, this DQA1*0502 substitution is unique, as it represents an amino acid change at a position assessed previously to be conserved in the human DQ alpha polypeptides. C1 AMER RED CROSS,HOLLAND LAB,HLA,TYPING LAB,ROCKVILLE,MD. VOZANDES HOSP,QUITO,ECUADOR. RP ZIMMERMAN, PA (reprint author), NIAID,PARASIT DIS LAB,BLDG 4,ROOM 126,BETHESDA,MD 20892, USA. NR 33 TC 17 Z9 17 U1 0 U2 0 PU ELSEVIER SCIENCE PUBL CO INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PD MAR PY 1995 VL 42 IS 3 BP 233 EP 240 DI 10.1016/0198-8859(94)00107-2 PG 8 WC Immunology SC Immunology GA QL393 UT WOS:A1995QL39300007 PM 7759311 ER PT J AU MASCI, AM SCALA, S RACIOPPI, L ZAPPACOSTA, S AF MASCI, AM SCALA, S RACIOPPI, L ZAPPACOSTA, S TI CELL-SURFACE EXPRESSION OF MAJOR HISTOCOMPATIBILITY CLASS-I ANTIGENS IS MODULATED BY P-GLYCOPROTEIN TRANSPORTER SO HUMAN IMMUNOLOGY LA English DT Article ID MULTIDRUG-RESISTANCE GENE; HEAVY-CHAINS; MONOCLONAL-ANTIBODIES; LYMPHOCYTES-T; HLA; BETA-2-MICROGLOBULIN; PEPTIDE; LINES; CONFORMATION; REGION AB P-glycoprotein (Mdr1), a member of the ABC superfamily, is a pump able to transport several compounds across plasma membranes. It displays a high level of similarity with the MHC-linked transporters TAP1 and TAP2 which are involved in the delivery of immunogenic peptides across the endoplasmic reticulum. In the present study we analyze the P-glycoprotein's ability to interfere with the biosynthetic pathway of the MHC class I molecules. Our results show that P-glycoprotein is involved in the modulation of the MHC class I expression in multidrug-resistant tumor cell lines, COS1 cells transfected with mdr1 gene, and human T lymphocytes. Epitope screening evokes the possibility that P-glycoprotein induces a modulation of the different MHC class I forms expressed on the cell surface. We propose that P-glycoprotein is involved in the transport of antigenic protein fragments from the cytosol into the endoplasmic reticulum. The suggested mechanism could be physiologically relevant in tissues displaying a high Mdr1 activity, where this transporter could contribute to the regulation of locoregional immune responses. C1 UNIV NAPLES FEDERICO II,DIPARTIMENTO BIOL & PATOL CELLULARE & MOLEC,I-80131 NAPLES,ITALY. UNIV ROMA LA SAPIENZA,DEPT EXPTL MED,I-00185 ROME,ITALY. NCI,MED BRANCH,BETHESDA,MD 20892. RI Scala, Stefania/K-1380-2016; OI Scala, Stefania/0000-0001-9524-2616; racioppi, luigi/0000-0002-9207-6752; Masci, Anna Maria/0000-0003-1940-6740 NR 49 TC 9 Z9 9 U1 0 U2 1 PU ELSEVIER SCIENCE PUBL CO INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PD MAR PY 1995 VL 42 IS 3 BP 245 EP 253 DI 10.1016/0198-8859(94)00096-9 PG 9 WC Immunology SC Immunology GA QL393 UT WOS:A1995QL39300009 PM 7759313 ER PT J AU MARTIN, M MANN, D CARRINGTON, M AF MARTIN, M MANN, D CARRINGTON, M TI RECOMBINATION RATES ACROSS THE HLA COMPLEX - USE OF MICROSATELLITES AS A RAPID SCREEN FOR RECOMBINANT CHROMOSOMES SO HUMAN MOLECULAR GENETICS LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; CLASS-II REGION; LINKAGE DISEQUILIBRIUM; HUMAN INSULIN; BETA GENE; HUMAN MHC; HOT SPOT; DNA; POLYMORPHISM; HAPLOTYPES AB Meiotic recombination does not appear to occur randomly across chromosomes, but rather seems to be restricted to specific regions. A striking example of this phenomenon is illustrated by the HLA class II region. No recombination within the 100 kb encompassing the DRB1-DQA1-DQB1 loci has been reported, whereas the random association of TAP1 with TAP2 alleles suggests the presence of a hotspot for recombination within the 15 kb separating the closest variant sites of these two loci. Recombination rates between loci may provide clues to the functional properties of haplotypes. Absence of recombination may suggest the necessity to keep alleles of certain genes in phase and, alternatively, high recombination rates may suggest selective pressure to diversify haplotypes within the population. To address this issue, recombination rates across the HLA complex were determined using the 59 Centre d'Etude Polymorphisme Humain (CEPH) pedigrees. The allele frequencies of four microsatellite markers which map at sites ranging from the telomeric to centromeric ends of the complex were determined and the markers were used as a rapid means for identification of recombinant chromosomes. Typing these as well as other polymorphic loci within the HLA class I, II and III regions allowed assignment of the segments where recombination occurred. Recombination rates within the class II region (defined here as DRB1 to DPB1) and class III region (defined here as HLA-B to DRB1) regions were 0.74% and 0.94%, respectively, both of which are within an expected range given the standard of 1% recombination rate per megabase of DNA per meiosis. The recombination rate of 0.31% determined within the class I region extending from the HLA-A to HLA-B loci (1.4 Mb), however, was significantly lower than that expected. C1 NCI, FREDERICK CANC RES & DEV CTR, PRI DYNCORP, VIRAL CARCINOGENESIS LAB, FREDERICK, MD 21702 USA. NCI, FREDERICK CANC RES & DEV CTR, PRI DYNCORP, BIOL CARCINOGENESIS & DEV PROGRAM, FREDERICK, MD 21702 USA. NR 34 TC 108 Z9 111 U1 0 U2 3 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 MAR PY 1995 VL 4 IS 3 BP 423 EP 428 DI 10.1093/hmg/4.3.423 PG 6 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA QQ070 UT WOS:A1995QQ07000015 PM 7795597 ER PT J AU ABATI, A SKARULIS, MC SHAWKER, T SOLOMON, D AF ABATI, A SKARULIS, MC SHAWKER, T SOLOMON, D TI ULTRASOUND-GUIDED FINE-NEEDLE ASPIRATION OF PARATHYROID LESIONS - A MORPHOLOGICAL AND IMMUNOCYTOCHEMICAL APPROACH SO HUMAN PATHOLOGY LA English DT Article DE PARATHYROID; ULTRASOUND-GUIDED FINE-NEEDLE ASPIRATION; CYTOLOGY; CHROMOGRANIN ID TUMORS; BIOPSY; ULTRASONOGRAPHY; CYTOLOGY; GLANDS; LOCALIZATION; CARCINOMA; GUIDANCE; ADENOMA; ASSAY AB Ultrasound-guided (US) fine-needle aspiration (Fn;A) can successfully localize abnormal parathyroid tissue (PT) preoperatively in hyperparathyroid patients. Samples from 12 patients with primary hyperparathyroidism evaluated using this technique since 1990 at the National Institutes of Health form the basis of this report. Eleven patients had undergone previous parathyroid surgery that failed to correct their hyperparathyroidism. Cytological evaluation and C-terminal (midmolecule) parathyroid hormone radioimmunoassay (PTH RIA) were performed on all samples. When sufficient material was available, immunocytochemical stains for chromogranin and thyroglobulin were performed. All cytological diagnoses were made without knowledge of the PTH RIA results. Using a combined approach of cytology and immunocytochemistry, six of 12 of the samples (50%) were diagnosed as PT. Follow-up on these six patients was confirmatory. Four of 12 samples (33%) were identified as thyroid; one of these patients had a PT adenoma identified in another location (the remaining three patients await further localization studies). Two of 12 samples (17%) could not be diagnosed because of insufficient cellularity; in both patients PT lesions were found in other locations. Morphological features of PT in FNA include the presence of cellular tissue fragments with epithelial cells arranged perivascularly around capillary cores, an overall organoid or trabecular architecture, and frequent microacini. Parathyroid tissue cells have round, fairly uniform nuclei measuring 6 to 8 mu m. Clusters of larger oxyphil cells may show considerable anisonucleosis. The absence of features of thyroid tissue such as hemosiderin-laden macrophages, abundant colloid, and paravacuolar granules is significant. However, in cases of intrathyroidal PT, admired thyroid material included in the aspiration tract may be present. Immunocytochemical stains for chromogranin, which is present in parathyroid tissue but not thyroid follicular cells, were positive in six of six samples interpreted as PT by cytology. No thyroglobulin staining was observed in any of the four of six PT samples for which material was available. C-terminal (midmolecule) PTH RIA correlated with cytological diagnoses in 100% of samples. Parathyroid hormone levels ranged from 1,300 to 262,000 pg/mL (normal blood level, 50 to 340 pg/mL) in the six samples diagnosed as PT by cytology. Parathyroid hormone RIA levels in the six non-PT samples were below normal blood values. The combined approach of cytology and immunocytochemistry provides high diagnostic accuracy in the interpretation of US-guided FNA for preoperative localization of parathyroid tissue. Copyright (C) 1995 by W.B. Saunders Company C1 NIDDKD,METAB DIS BRANCH,BETHESDA,MD 20892. RP ABATI, A (reprint author), NCI,DEPT DIAGNOST RADIOL,PATHOL LAB,CYTOPATHOL SECT,BLDG 10,ROOM 2A19,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 26 TC 38 Z9 41 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 MAR PY 1995 VL 26 IS 3 BP 338 EP 343 DI 10.1016/0046-8177(95)90068-3 PG 6 WC Pathology SC Pathology GA QL005 UT WOS:A1995QL00500016 PM 7890288 ER PT J AU BURT, VL WHELTON, P ROCCELLA, EJ BROWN, C CUTLER, JA HIGGINS, M HORAN, MJ LABARTHE, D AF BURT, VL WHELTON, P ROCCELLA, EJ BROWN, C CUTLER, JA HIGGINS, M HORAN, MJ LABARTHE, D TI PREVALENCE OF HYPERTENSION IN THE US ADULT-POPULATION - RESULTS FROM THE 3RD NATIONAL-HEALTH AND NUTRITION EXAMINATION SURVEY, 1988-1991 SO HYPERTENSION LA English DT Article DE HYPERTENSION, ESSENTIAL; BLOOD PRESSURE; PREVALENCE; CROSS-SECTIONAL STUDIES; NHANES ID BLOOD-PRESSURE; UNITED-STATES; DISEASE AB The purpose of this study was to estimate the current prevalence and distribution of hypertension and to determine the status of hypertension awareness, treatment, and control in the US adult population. The study used a cross-sectional survey of the civilian, noninstitutionalized population of the United States, including an in-home interview and a clinic examination, each of which included measurement of blood pressure. Data for 9901 participants 18 years of age and older from phase 1 of the third National Health and Nutrition Examination Survey, collected from 1988 through 1991, were used. Twenty-four percent of the US adult population representing 43 186 000 persons had hypertension. The age-adjusted prevalence in the non-Hispanic black, non-Hispanic white, and Mexican American populations was 32.4%, 23.3%, and 22.6%, respectively. Overall, two thirds of the population with hypertension were aware of their diagnosis (69%), and a majority were taking prescribed medication (53%). Only one third of Mexican Americans with hypertension were being treated (35%), and only 14% achieved control in contrast to 25% and 24% of the non-Hispanic black and non-Hispanic white populations with hypertension, respectively. Almost 13 million adults classified as being normotensive reported being told on one or more occasions that they had hypertension; 51% of this group reported current adherence to lifestyle changes to control their hypertension. Hypertension continues to be a common finding in the general population. Awareness, treatment, and control of hypertension have improved substantially since the 1976-1980 National Health and Nutrition Examination Survey but continue to be suboptimal, especially in Mexican Americans. Consideration should be given to revision of the criteria for classification of hypertension to reflect the widespread use of lifestyle modification for treatment of hypertension. C1 CTR DIS CONTROL & PREVENT,NATL CTR HLTH STAT,HYATTSVILLE,MD. JOHNS HOPKINS MED INST,BALTIMORE,MD. UNIV TEXAS,HLTH SCI CTR,SCH PUBL HLTH,HOUSTON,TX. RP BURT, VL (reprint author), NHLBI,NATL HIGH BLOOD PRESSURE EDUC PROGRAM,BLDG 31,ROOM 4A-05,BETHESDA,MD 20892, USA. NR 20 TC 1945 Z9 2001 U1 5 U2 29 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0194-911X J9 HYPERTENSION JI Hypertension PD MAR PY 1995 VL 25 IS 3 BP 305 EP 313 PG 9 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA QK786 UT WOS:A1995QK78600002 PM 7875754 ER PT J AU UNSER, M ALDROUBI, A EDEN, M AF UNSER, M ALDROUBI, A EDEN, M TI ENLARGEMENT OR REDUCTION OF DIGITAL IMAGES WITH MINIMUM LOSS OF INFORMATION SO IEEE TRANSACTIONS ON IMAGE PROCESSING LA English DT Article ID INTERPOLATION; DESIGN AB The purpose of this paper is to derive optimal spline algorithms for the enlargement or reduction of digital images by arbitrary (noninteger) scaling factors, In our formulation, the original and rescaled signals are each represented by an interpolating polynomial spline of degree n with step size one and Delta, respectively, The change of scale is achieved by determining the spline with step size Delta that provides the closest approximation of the original signal in the L(2)-norm. We show that this approximation can be computed in three steps: i) a digital prefilter that provides the B-spline coefficients of the input signal, ii) a resampling using an expansion formula with a modified sampling kernel that depends explicitly on Delta, and iii) a digital postfilter that maps the result back into the signal domain, We provide explicit formulas for n = 0, 1, and 3 and propose solutions for the efficient implementation of these algorithms, We consider image processing examples and show that the present method compares favorably with standard interpolation techniques, Finally, we discuss some properties of this approach and its connection with the classical technique of bandlimiting a signal, which provides the asymptotic limit of our algorithm as the order of the spline tends to infinity. C1 INSERM,PARIS,FRANCE. MIT,CAMBRIDGE,MA 02139. RP UNSER, M (reprint author), NIH,NATL CTR RES RESOURCES,BIOMED ENGN & INSTRUMENTAT PROGRAM,BETHESDA,MD 20892, USA. RI Unser, Michael/A-1550-2008; Aldroubi, Akram/J-7186-2012 NR 29 TC 142 Z9 153 U1 0 U2 1 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 SN 1057-7149 J9 IEEE T IMAGE PROCESS JI IEEE Trans. Image Process. PD MAR PY 1995 VL 4 IS 3 BP 247 EP 258 DI 10.1109/83.366474 PG 12 WC Computer Science, Artificial Intelligence; Engineering, Electrical & Electronic SC Computer Science; Engineering GA QP140 UT WOS:A1995QP14000002 PM 18289976 ER PT J AU CAO, XQ SHORES, EW HULI, J ANVER, MR KELSALL, BL RUSSELL, SM DRAGO, J NOGUCHI, M GRINBERG, A BLOOM, ET PAUL, WE KATZ, SI LOVE, PE LEONARD, WJ AF CAO, XQ SHORES, EW HULI, J ANVER, MR KELSALL, BL RUSSELL, SM DRAGO, J NOGUCHI, M GRINBERG, A BLOOM, ET PAUL, WE KATZ, SI LOVE, PE LEONARD, WJ TI DEFECTIVE LYMPHOID DEVELOPMENT IN MICE LACKING EXPRESSION OF THE COMMON CYTOKINE RECEPTOR-GAMMA CHAIN SO IMMUNITY LA English DT Article ID SEVERE COMBINED IMMUNODEFICIENCY; EPIDERMAL T-CELLS; IL-2 RECEPTOR; BETA-CHAIN; FUNCTIONAL COMPONENT; MONOCLONAL-ANTIBODY; GENE; DISEASE; REQUIREMENT; ACTIVATION AB The common gamma chain (gamma(c)) of the IL-2, IL-4, IL-7, IL-9, and IL-15 receptors is defective in hu mans with XSCID. Mice lacking gamma(c) expression had hypoplastic thymuses; the thymocytes responded to gamma(c)-independent mitogens, but not gamma(c)-dependent stimuli. Splenic T cells were diminished at 3 weeks of age, but CD4+ T cells markedly increased by 4 weeks. B cells were greatly diminished, in contrast with the situation in XSCID. NK cells, gamma delta intestinal intraepithelial lymphocytes, dendritic epidermal T cells, peripheral lymph nodes, and gut-associated lymphoid tissue were absent. These findings underscore the importance of gamma(c) in lymphoid development. Moreover, differences in humans and mice lacking ye expression indicate species-specific differences in the roles of gamma(c)-dependent cytokines or in the existence of redundant pathways. These mice provide an important model for studying the pathophysiology of and gene therapy for human XSCID. C1 NIAID,IMMUNOL LAB,BETHESDA,MD 20892. NIAID,MUCOSAL IMMUN SECT,BETHESDA,MD 20892. NIAID,CLIN INVEST LAB,BETHESDA,MD 20892. NICHHD,MAMMALIAN GENES & DEV LAB,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT & RES,DIV CELLULAR & GENE THERAPIES,DIV HEMATOL PROD,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT & RES,DIV CELLULAR & GENE THERAPIES,CELLULAR IMMUNOL LAB,BETHESDA,MD 20892. NCI,FREDERICK CANC RES & DEV CTR,DYNCORP INC,PROGRAM RESOURCES,PATHOL HISTOTECHNOL LAB,FREDERICK,MD 21702. NCI,DERMATOL BRANCH,BETHESDA,MD 20892. RP CAO, XQ (reprint author), NHLBI,MOLEC IMMUNOL LAB,BETHESDA,MD 20892, USA. RI Russell, Sarah/B-9341-2009 OI Russell, Sarah/0000-0001-5826-9641 NR 62 TC 683 Z9 691 U1 1 U2 9 PU CELL PRESS PI CAMBRIDGE PA 50 CHURCH ST CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 1074-7613 J9 IMMUNITY JI Immunity PD MAR PY 1995 VL 2 IS 3 BP 223 EP 238 DI 10.1016/1074-7613(95)90047-0 PG 16 WC Immunology SC Immunology GA QP276 UT WOS:A1995QP27600002 PM 7697543 ER PT J AU KURUCZ, I BRINKMANN, U LEE, B SEGAL, DM REITER, Y JUNG, SH PASTAN, I AF KURUCZ, I BRINKMANN, U LEE, B SEGAL, DM REITER, Y JUNG, SH PASTAN, I TI CONSTRUCTION OF A FUNCTIONAL DISULFIDE-STABILIZED TCR FV INDICATES THAT ANTIBODY AND TCR FV FRAMEWORKS ARE VERY SIMILAR IN STRUCTURE SO IMMUNITY LA English DT Article ID T-CELL RECEPTOR; ANTIGEN RECEPTOR; ESCHERICHIA-COLI; FUSION PROTEINS; HETERODIMERS; RECOGNITION; EXPRESSION; SECRETION; FRAGMENTS; CHAINS AB Disulfide-stabilized Fvs (dsFv) are recombinant Fv fragments of antibodies in which the inherently unstable V-H-V-L heterodimer is stabilized by an interchain disulfide bond engineered between structurally conserved framework positions. We now design and produce a disulfide-stabilized Fv of a T cell receptor. It is composed of V alpha and V beta variable domains of the 2B4 TCR stabilized by a disulfide bond between framework residues of the TCR Fv at a site corresponding to that used for disulfide stabilization of antibody Fvs. For ease of production and detection, the TCRdsFv was fused to a truncated form of Pseudomonas exotoxin (PE38). The TCR(dsFv) retains its native conformation and is much more stable than a TcR scFv. Moreover, it is functional in biological assays. Because successful disulfide stabilization of the TCR Fv by the positions used for antibody Fv stabilization would not occur unless the mutated residues in TCR Fv are at positions closely similar to those in antibody Fvs, most likely within less than 1.5 Angstrom, these results provide very strong experimental evidence for the structural similarity between immunoglobulin and TCR antigen-binding variable domains. C1 NCI, DIV CANC BIOL DIAG & CTR, EXPTL IMMUNOL BRANCH, BETHESDA, MD 20892 USA. RP KURUCZ, I (reprint author), NCI, DIV CANC BIOL DIAG & CTR, MOLEC BIOL LAB, BETHESDA, MD 20892 USA. RI Lee, Byungkook/E-4564-2011 OI Lee, Byungkook/0000-0002-3339-4582 NR 31 TC 14 Z9 14 U1 0 U2 3 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-7613 EI 1097-4180 J9 IMMUNITY JI Immunity PD MAR PY 1995 VL 2 IS 3 BP 281 EP 287 PG 7 WC Immunology SC Immunology GA QP276 UT WOS:A1995QP27600007 ER PT J AU BIKOFF, EK GERMAIN, RN ROBERTSON, EJ AF BIKOFF, EK GERMAIN, RN ROBERTSON, EJ TI ALLELIC DIFFERENCES AFFECTING INVARIANT CHAIN DEPENDENCY OF MHC CLASS-II SUBUNIT ASSEMBLY SO IMMUNITY LA English DT Article ID CELL-SURFACE EXPRESSION; ALPHA-BETA-HETERODIMERS; HLA-DR MOLECULES; MONOCLONAL-ANTIBODIES; ENDOPLASMIC-RETICULUM; PEPTIDE-BINDING; IA ANTIGENS; T-CELL; B-CELL; HISTOCOMPATIBILITY ANTIGENS AB The conserved invariant chain associates with highly polymorphic alpha and beta subunits guiding class II transport through the secretory pathway. Early associations of these three polypeptides inside antigen-presenting cells are poorly understood. The present experiments provide a detailed picture of the structure and fate of class II alpha and beta subunits in invariant chain mutants possessing different MHC haplotypes. In the absence of invariant chain, A alpha(b)A beta(b) is predominantly expressed as free A alpha(b) and A beta(b) chains by both splenocytes and activated LPS/IL-4 blasts, confirming that A alpha(b)A beta(b) assembly is strongly dependent on invariant chain coexpression. A quite different situation exists with respect to other allelic products. In the absence of invariant chain, A alpha(a)A beta(b), E alpha(k)E beta(k), and A alpha(a)A beta(d) molecules assemble efficiently and are conformationally similar to mature wild-type heterodimers. The contribution of invariant chain to subunit assembly thus differs for allelic variants, suggesting that sequential associations of alpha, beta, and invariant chain may be affected by polymorphic differences. C1 NIAID,IMMUNOL LAB,BETHESDA,MD 20892. RP BIKOFF, EK (reprint author), HARVARD UNIV,DEPT MOLEC & CELLULAR BIOL,CAMBRIDGE,MA 02138, USA. FU NIAID NIH HHS [AI-19047] NR 92 TC 85 Z9 87 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 50 CHURCH ST CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 1074-7613 J9 IMMUNITY JI Immunity PD MAR PY 1995 VL 2 IS 3 BP 301 EP 310 DI 10.1016/1074-7613(95)90054-3 PG 10 WC Immunology SC Immunology GA QP276 UT WOS:A1995QP27600009 PM 7697546 ER PT J AU LEE, CGL JENKINS, NA GILBERT, DJ COPELAND, NG OBRIEN, WE AF LEE, CGL JENKINS, NA GILBERT, DJ COPELAND, NG OBRIEN, WE TI CLONING AND ANALYSIS OF GENE-REGULATION OF A NOVEL LPS-INDUCIBLE CDNA SO IMMUNOGENETICS LA English DT Article ID PROTEIN-KINASE-C; MURINE PERITONEAL-MACROPHAGES; 3' UNTRANSLATED REGION; TUMOR-NECROSIS-FACTOR; MESSENGER-RNA EXPRESSION; CYTOSOLIC FREE CALCIUM; HUMAN MONOCYTES; ENDOTHELIAL-CELLS; TYROSINE PHOSPHORYLATION; ADENYLATE-CYCLASE AB The expression of many genes is altered upon the activation of macrophages by bacterial LPS. These genes play a crucial role in the orchestration of various responses to protect the host against infection. A novel 2.3 kilobase (kb) cDNA, designated IRG1, was obtained from a cDNA library prepared with RNA isolated from RAW 264.7 following lipopolysaccharide stimulation. Sequence analysis of the clone revealed no identity to any known genes but showed the presence of many potential phosphorylation sites suggesting that IRG1 protein product may be regulated at this level. Furthermore, IRG1 contains the motif for glycosaminoglycan attachment site, implying that IRG1 may be a proteoglycan. By interspecific backcross analysis, Irg1 was mapped to mouse chromosome 14 linked to Tyrp2 and Rap2a. The IRG1 message appears 1.5 h following LPS exposure and its induction was not dependent on new protein synthesis. In fact, cycloheximide induced the expression of IRG1, suggesting that a protein repressor prevents the expression of IRG1 when uninduced. The role of the protein kinase A pathway in regulating the induction of IRG1 by LPS is questionable, because although forskolin inhibited its induction, neither dibutyrl-cAMP nor 8-(4-chlorophenylthio)-cAMP had much effect on its expression. In contrast, activation of protein kinase C potentiated the LPS response. Chelation of extracellular calcium inhibited IRG1 4 h after LPS induction, while increasing intracellular calcium had little effect on the levels of the IRG1 transcript. inhibiting tyrosine phosphorylation abrogated the induction of IRG1 by LPS. Hence, the induction of IRG1 by LPS is mediated by tyrosine kinase and protein kinase C pathway. C1 BAYLOR COLL MED,DEPT BIOCHEM,HOUSTON,TX 77030. BAYLOR COLL MED,DEPT MOLEC & HUMAN GENET,HOUSTON,TX 77030. NCI,FREDERICK CANC RES & DEV CTR,MAMMALIAN GENET LAB,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. NR 80 TC 36 Z9 39 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 MAR PY 1995 VL 41 IS 5 BP 263 EP 270 PG 8 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA QR444 UT WOS:A1995QR44400003 PM 7721348 ER PT J AU REMMERS, EF DU, Y ZHA, HB GOLDMUNTZ, EA WILDER, RL AF REMMERS, EF DU, Y ZHA, HB GOLDMUNTZ, EA WILDER, RL TI 10 POLYMORPHIC DNA LOCI, INCLUDING 5 IN THE RAT MHC (RT1) REGION, FORM A SINGLE LINKAGE GROUP ON RAT CHROMOSOME-20 SO IMMUNOGENETICS LA English DT Note ID MAJOR HISTOCOMPATIBILITY COMPLEX; GENETIC-MAP; MARKERS RP REMMERS, EF (reprint author), NIAMSD,ARTHRIT & RHEUMAT BRANCH,INFLAMMATORY JOINT DIS SECT,BLDG 10 ROOM 9N228,BETHESDA,MD 20892, USA. NR 18 TC 22 Z9 22 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 MAR PY 1995 VL 41 IS 5 BP 316 EP 319 PG 4 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA QR444 UT WOS:A1995QR44400010 PM 7721354 ER PT J AU MAITY, R MUKHERJEE, R SKOLNICK, P AF MAITY, R MUKHERJEE, R SKOLNICK, P TI MORPHINE INHIBITS THE DEVELOPMENT OF ALLOGENEIC IMMUNE-RESPONSES IN MOUSE LYMPH-NODE SO IMMUNOPHARMACOLOGY LA English DT Article DE MORPHINE; NALTREXONE; OPIATE RECEPTOR; POPLITEAL LYMPH NODE; ALLOANTIGEN; TISSUE REJECTION ID T-CELL SUBSETS; OPIATE-INDUCED IMMUNOSUPPRESSION; SKIN ALLOGRAFT-REJECTION; LYMPHOCYTES-T; OPIOID RECEPTORS; GRAFT-REJECTION; MHC CLASS; A INVIVO; CLASS-I; PEPTIDES AB Morphine and related opiates are often administered to relieve post-operative and chronic pain following transplantation surgery. Opiates have been shown to suppress a variety of immune parameters in both animal models and man. In the present study, we investigated whether morphine affects allogeneic immune responses by injecting C57BL/6 mice in the footpad with allogeneic spleen cells and examining changes in the draining popliteal lymph node (PLN). Morphine (administered as subcutaneous implants) had profound inhibitory effects on the development of alloreactivity manifested as a suppression of: (1) lymph node hyperplasia, (2) mixed lymphocyte reactivity (MLR) in PLN cells and (3) the number of CD4(+) and Thy 1.2 lymphoid subsets. These inhibitory effects of morphine were abolished or dramatically reduced by co-administration of the opiate antagonist, naltrexone, indicating that suppression of allo-sensitization was opiate receptor mediated. In toto, these findings demonstrate that morphine administration interferes with the development of allogeneic immune response in mouse lymph node through an opiate receptor mediated mechanism. C1 NIDDKD,NEUROSCI LAB,BETHESDA,MD 20892. NR 53 TC 7 Z9 7 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0162-3109 J9 IMMUNOPHARMACOLOGY JI Immunopharmacology PD MAR PY 1995 VL 29 IS 2 BP 175 EP 183 DI 10.1016/0162-3109(94)00058-N PG 9 WC Immunology; Pharmacology & Pharmacy SC Immunology; Pharmacology & Pharmacy GA QL224 UT WOS:A1995QL22400010 PM 7775160 ER PT J AU MARGOLIS, LB GLUSHAKOVA, SE BAIBAKOV, BA COLLIN, C ZIMMERBERG, J AF MARGOLIS, LB GLUSHAKOVA, SE BAIBAKOV, BA COLLIN, C ZIMMERBERG, J TI CONFOCAL MICROSCOPY OF CELLS IMPLANTED INTO TISSUE BLOCKS - CELL-MIGRATION IN LONG-TERM HISTOCULTURES SO IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL LA English DT Article DE TUMOR; INVASION; LUNG; TISSUE; IN VITRO ID GROWTH; INVITRO; TUMORS; SKIN AB In three-dimensional tissues in vivo, cells find themselves in a unique, heterogeneous microenvironment among various cellular and noncellular elements. Cells are greatly affected by and contribute to their physical and chemical microenvironments. However, live cells are currently studied predominantly in homogeneous monolayer cultures where newly established contacts might be fundamentally different from contacts in vivo. Several systems have been suggested to simulate the three-dimensional environment of real tissue. In this report, we describe a new system for studying cell behavior inside real tissues in vitro. By fluorescently labeling mouse tumor cells, then implanting them into cultured tissue blocks (histocultures), we have observed cellular location and followed their locomotion, within tissues in vitro for days. We discuss the potential of the described system for studying different aspects of cell behavior in a nativelike microenvironment. C1 MOSCOW MV LOMONOSOV STATE UNIV,BELOZERSKY INST PHYSICOCHEM BIOL,MOSCOW,RUSSIA. NINCDS,OFF DIRECTOR,BETHESDA,MD 20892. RP MARGOLIS, LB (reprint author), NICHHD,THEORET & PHYS BIOL LAB,9000 ROCKVILLE PIKE,BLDG 10,ROOM 10D14,BETHESDA,MD 20892, USA. NR 22 TC 6 Z9 6 U1 0 U2 0 PU SOC IN VITRO BIOLOGY PI COLUMBIA PA 8815 CENTRE PARK DRIVE SUITE 210, COLUMBIA, MD 21045 SN 1071-2690 J9 IN VITRO CELL DEV-AN JI In Vitro Cell. Dev. Biol.-Anim. PD MAR PY 1995 VL 31 IS 3 BP 221 EP 226 PG 6 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA QL756 UT WOS:A1995QL75600012 ER PT J AU SU, H CALDWELL, HD AF SU, H CALDWELL, HD TI KINETICS OF CHLAMYDIAL ANTIGEN-PROCESSING AND PRESENTATION TO T-CELLS BY PARAFORMALDEHYDE-FIXED MURINE BONE-MARROW-DERIVED MACROPHAGES SO INFECTION AND IMMUNITY LA English DT Article ID OUTER-MEMBRANE PROTEIN; SEQUENCE-ANALYSIS; GENITAL-INFECTION; PRESENTING CELLS; MURAMIC ACID; TRACHOMATIS; MICE; SALPINGITIS; BINDING; GROWTH AB Macrophages are potential candidates for antigen presentation to chlamydial-specific CD4(+) T cells. We have studied the kinetics of chlamydial antigen processing and presentation by using paraformaldehyde-fixed bone marrow-derived macrophages (BMDM) and splenic T cells isolated from chlamydia-infected mice. BMDM were inoculated,vith different multiplicities of heat-killed chlamydial elementary bodies, and at different times postingestion, the macrophages were fixed with paraformaldehyde and used as antigen-presenting cells in T-cell proliferation assays. T-cell proliferative responses were shown to be dependent on the chlamydial inoculum size, with a multiplicity of 10 chlamydiae per macrophage producing optimum T-cell proliferation. Temporal experiments showed that peak T-cell proliferative responses occurred between 4 and 12 h postingestion of chlamydiae by BMDM. T cells proliferated strongly to antigen when presented by H-2-matched BMDM but not when presented by H-2-disparate BMDM, demonstrating that T-cell recognition of processed chlamydial antigen was major histocompatibility complex restricted. BMDM inoculated with 10 chlamydiae per cell and fixed at 8 h postinoculation were shown to be as stimulatory to T cells as conventional splenic antigen-presenting cells. Because large numbers of BMDM can be propagated in vitro, and experimental conditions that provide optimum presentation of processed chlamydial antigen to chlamydia-specific CD4(+) T cells can be defined, BMDM may be a potentially useful source for the isolation of naturally processed parasite antigen from major histocompatibility complex class II molecules. C1 NIAID,ROCKY MT LABS,INTRACELLULAR PARASITES LAB,IMMUNOL SECT,HAMILTON,MT 59840. NR 38 TC 18 Z9 18 U1 0 U2 0 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 MAR PY 1995 VL 63 IS 3 BP 946 EP 953 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA QJ524 UT WOS:A1995QJ52400030 PM 7868267 ER PT J AU MURDIN, AD SU, H KLEIN, MH CALDWELL, HD AF MURDIN, AD SU, H KLEIN, MH CALDWELL, HD TI POLIOVIRUS HYBRIDS EXPRESSING NEUTRALIZATION EPITOPES FROM VARIABLE DOMAIN-I AND DOMAIN-IV OF THE MAJOR OUTER-MEMBRANE PROTEIN OF CHLAMYDIA-TRACHOMATIS ELICIT BROADLY CROSS-REACTIVE C-TRACHOMATIS-NEUTRALIZING ANTIBODIES SO INFECTION AND IMMUNITY LA English DT Note ID PROTECTIVE MONOCLONAL-ANTIBODIES; ANTIGENIC DETERMINANTS; T-HELPER; IMMUNOGENICITY; PATHOGENESIS; REINFECTION; INFECTIONS; DISEASE; TYPE-1 AB Trachoma and sexually transmitted diseases caused by Chlamydia trachomatis are major health problems worldwide. Epitopes from the variable domains of the major outer membrane protein are candidates for vaccine development. We have constructed hybrid polioviruses expressing sequences from major outer membrane protein variable domains I and IV. Antisera to the hybrids could, in combination, strongly neutralize 8 of the 12 C. trachomatis serovars most commonly associated with oculogenital infections and weakly neutralize the others. C1 NIAID,ROCKY MT LABS,INTRACELLULAR PARASITES LAB,HAMILTON,MT 59840. RP MURDIN, AD (reprint author), CONNAUGHT CTR BIOTECHNOL RES,1755 STEELES AVE W,N YORK,ON M2R 3T4,CANADA. NR 33 TC 28 Z9 29 U1 0 U2 0 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 MAR PY 1995 VL 63 IS 3 BP 1116 EP 1121 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA QJ524 UT WOS:A1995QJ52400055 PM 7532625 ER PT J AU GARDNER, SY BRODY, AR AF GARDNER, SY BRODY, AR TI INCORPORATION OF BROMODEOXYURIDINE AS A METHOD TO QUANTIFY CELL-PROLIFERATION IN BRONCHIOLAR-ALVEOLAR DUCT REGIONS OF ASBESTOS-EXPOSED MICE SO INHALATION TOXICOLOGY LA English DT Article ID RAT LUNG FIBROBLASTS; S-PHASE CELLS; GROWTH-FACTOR; CHRYSOTILE ASBESTOS; MONOCLONAL-ANTIBODY; MACROPHAGES; INHALATION; AUTORADIOGRAPHY; DEPOSITION; THYMIDINE AB Inhalation of asbestos fibers results in progressive interstitial pulmonary fibrosis in the bronchiolar-alveolar regions of humans and experimental animals. The fibrogenic lesions were described previously by morphometry in a rodent model of asbestos-induced pulmonary fibrosis in our laboratory. Our prior studies also showed that incorporation of tritiated thymidine (H-3-TdR) into nuclei of epithelial and interstitial cells of bronchiolar-alveolar regions correlates with this histopathologic response. The study presented here describes the early proliferative response in the bronchiolar-alveolar regions in mice after a brief exposure to chrysotile asbestos. Mice exposed to asbestos had significantly increased incorporation of bromodeoxyuridine (BrdU) in interstitial and epithelial cells of first alveolar duct bifurcations and terminal bronchioles at 48 h after exposure. The BrdU incorporation was similar at 24 h after exposure. This study confirms that BrdU provides information on asbestos-induced cell proliferation similar to that of H-3-TdR, but the technology is far safer and less time-consuming. C1 NIEHS,PULM PATHOBIOL LAB,RES TRIANGLE PK,NC 27709. NR 31 TC 16 Z9 16 U1 0 U2 1 PU TAYLOR & FRANCIS PI BRISTOL PA 1900 FROST ROAD, SUITE 101, BRISTOL, PA 19007-1598 SN 0895-8378 J9 INHAL TOXICOL JI Inhal. Toxicol. PD MAR PY 1995 VL 7 IS 2 BP 215 EP 224 DI 10.3109/08958379509029094 PG 10 WC Toxicology SC Toxicology GA QR948 UT WOS:A1995QR94800004 ER PT J AU PRODROMIDIS, M LAMB, ME STERNBERG, KJ HWANG, CP BROBERG, AG AF PRODROMIDIS, M LAMB, ME STERNBERG, KJ HWANG, CP BROBERG, AG TI AGGRESSION AND NONCOMPLIANCE AMONG SWEDISH CHILDREN IN CENTER-BASED CARE, FAMILY DAY-CARE, AND HOME CARE SO INTERNATIONAL JOURNAL OF BEHAVIORAL DEVELOPMENT LA English DT Article ID INFANT DAY-CARE; AGE; QUALITY; ATTACHMENT; PATTERNS AB The relations between individual, family, and child care characteristics and children's aggressive and noncompliant behaviours were examined in this study of 140 first-born Swedish children assessed at 16, 28, 40, and 80 months of age. All of the parents involved in the study had attempted to enrol their children in centre-based day care, but some were accepted instead into family day care settings, while others remained in the exclusive care of their parents. Composite measures of aggression and noncompliance were constructed using data obtained from multiple sources (i.e. mothers, teachers, observers). Child care arrangements and histories were not associated with levels of aggression or noncompliance. Multiple regression analyses suggested that the quality of home care was the best predictor of both aggressive and noncompliant behaviour. Boys were more aggressive than girls, and children with more controlling parents were more noncompliant. Individual differences in aggression (but not noncompliance) were moderately stable over time. C1 NICHHD,SOCIAL & EMOT DEV SECT,BETHESDA,MD 20814. UNIV MIAMI,SCH MED,MIAMI,FL. GOTHENBURG UNIV,GOTHENBURG,SWEDEN. NR 46 TC 19 Z9 19 U1 0 U2 0 PU LAWRENCE ERLBAUM ASSOC LTD PI HOVE PA 27 PALMEIRA MANSIONS CHURCH RD, HOVE, E SUSSEX, ENGLAND BN3 2FA SN 0165-0254 J9 INT J BEHAV DEV JI Int. J. Behav. Dev. PD MAR PY 1995 VL 18 IS 1 BP 43 EP 62 PG 20 WC Psychology, Developmental SC Psychology GA QP797 UT WOS:A1995QP79700003 ER PT J AU BORNSTEIN, MH MAITAL, SL TAL, J BARAS, R AF BORNSTEIN, MH MAITAL, SL TAL, J BARAS, R TI MOTHER AND INFANT ACTIVITY AND INTERACTION IN ISRAEL AND IN THE UNITED-STATES - A COMPARATIVE-STUDY SO INTERNATIONAL JOURNAL OF BEHAVIORAL DEVELOPMENT LA English DT Article ID COGNITIVE COMPETENCE; CHILD; STABILITY; FAMILY; EXPERIENCES; PREDICTION AB Activities and interactions of Israeli and US mothers and their 5-month-old infants were observed in the natural setting of their homes, This report examines infant visual and tactual exploration and vocalisation as well as maternal stimulation and speech. First, similarities and differences in activities between Israeli and US infants and mothers are assessed. Next, coherence in infant activities and in maternal activities within each society are evaluated, and resultant patterns of coherence between the two societies are compared, Last, correspondences between infant and maternal activities in each society are analysed, and resultant patterns of mother-infant interactions between the two societies are compared. Identification and description of activities, interactions, and developmental processes which are similar and different in comparable segments of Israeli and US society are discussed, and crosscultural tests of developmental issues related to coherence and to correspondence of activity in mother-infant dyads are evaluated. Israeli and US mothers may follow culture-specific paths in striving to meet infants' needs and in achieving socialisation goals. C1 UNIV HAIFA,IL-31999 HAIFA,ISRAEL. RP BORNSTEIN, MH (reprint author), NICHHD,BLDG 31,ROOM B2B15,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 91 TC 7 Z9 9 U1 0 U2 0 PU LAWRENCE ERLBAUM ASSOC LTD PI HOVE PA 27 PALMEIRA MANSIONS CHURCH RD, HOVE, E SUSSEX, ENGLAND BN3 2FA SN 0165-0254 J9 INT J BEHAV DEV JI Int. J. Behav. Dev. PD MAR PY 1995 VL 18 IS 1 BP 63 EP 82 PG 20 WC Psychology, Developmental SC Psychology GA QP797 UT WOS:A1995QP79700004 ER PT J AU SAEKI, T TAKAHASHI, T OKABE, M FURUYA, A HANAI, N YAMAGAMI, K MANDAI, K MORIWAKI, S DOIHARA, H TAKASHIMA, S SALOMON, DS AF SAEKI, T TAKAHASHI, T OKABE, M FURUYA, A HANAI, N YAMAGAMI, K MANDAI, K MORIWAKI, S DOIHARA, H TAKASHIMA, S SALOMON, DS TI IMMUNOHISTOCHEMICAL DETECTION OF RIBONUCLEOTIDE REDUCTASE IN HUMAN BREAST-TUMORS SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE RIBONUCLEOTIDE REDUCTASE (RNR); HUMAN BREAST CARCINOMAS; IMMUNOHISTOCHEMISTRY ID CELL-CYCLE; CALF THYMUS; EXPRESSION; SUBUNITS; LOCALIZATION AB Ribonucleotide reductase (RNR) consists of two non-identical subunits, R1 and R2 and is one of the key enzymes involved in DNA biosynthesis. RNR activity is considerably higher in malignant tumors than in normal tissues in the rat suggesting that RNR may play an important role in the pathogenesis of human tumors. In order to obtain immunological reagents to study the localization and level of expression of RNR in various human tissues, a synthetic peptide containing sequences corresponding to the COOH-terminal region of the human R2 subunit was used to generate rat monoclonal antibodies. The generated rat monoclonal antibodies (IgG) inhibited RNR enzymatic activity purified from murine P388 leukemia cells. These antibodies were used to immunohistochemically examine the distribution of RNR in a small panel of 8 malignant and 4 benign human breast tumors. Positive immunostaining for RNR was observed in the cytoplasm of human breast carcinoma cells in which a specific 44 kDa specific band of R2 subunit was also detected by Western blot analysis. The immunostaining was blocked by preabsorption of the antibody with an excess amount of the synthetic peptide immunogen. In 8 of 8 breast carcinomas, positive immunostaining for the R2 subunit was observed whereas noninvolved, adjacent breast tissue showed no staining with this antibody. In addition, few of the benign breast lesions exhibited staining with this antibody. These data indicate that these antibodies can immunohistochemically detect RNR in frozen or formalin-fixed, paraffin- embedded tissues and that there is a differential expression of RNR between breast tumors and non-involved breast tissue. Immunohistochemical detection of RNR using these antibodies may therefore be useful for the diagnosis of human breast tumors. C1 NCI,TUMOR GROWTH FACTOR SECT,TUMOR IMMUNOL & BIOL LAB,BETHESDA,MD 20892. KYOWA HAKKO KOGYO CO LTD,TOKYO RES LABS,TOKYO,JAPAN. KYOWA HAKKO KOGYO CO LTD,PHARMATHEUT RES LABS,SHIZUOKA,JAPAN. RP SAEKI, T (reprint author), NATL SHIKOKU CANC CTR HOSP,DEPT CLIN RES,ONCOGENE SECT,13 HORINOUCHI,MATSUYAMA,EHIME 790,JAPAN. NR 20 TC 8 Z9 9 U1 0 U2 1 PU INT JOURNAL ONCOLOGY PI ATHENS PA C/O PROFESSOR D A SPANDIDOS, EDITORIAL OFFICE, 1, S MERKOURI ST, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD MAR PY 1995 VL 6 IS 3 BP 523 EP 529 PG 7 WC Oncology SC Oncology GA QJ135 UT WOS:A1995QJ13500002 PM 21556566 ER PT J AU SHARFMAN, WH URBA, WJ SMITH, JW JANIK, JE CURTI, BD GAUSE, BL HOLMLUND, JT STEIS, RG BEAUCHAMP, AE LONGO, DL AF SHARFMAN, WH URBA, WJ SMITH, JW JANIK, JE CURTI, BD GAUSE, BL HOLMLUND, JT STEIS, RG BEAUCHAMP, AE LONGO, DL TI PHASE I/II TRIAL OF 5-FLUOROURACIL, LEUCOVORIN, ZIDOVUDINE AND DIPYRIDAMOLE FOR PATIENTS WITH METASTATIC COLORECTAL-CANCER, RENAL-CELL CARCINOMA AND MALIGNANT-MELANOMA SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE BIOCHEMICAL MODULATION; THYMIDYLATE SYNTHASE ID RANDOMIZED TRIAL; FOLINIC ACID; FLUOROURACIL; METHOTREXATE AB We conducted a phase I/II trial of 5-fluorouracil (5-FU), calcium leucovorin (LV), zidovudine (AZT) and dipyridamole (DP), (FLAP) in patients with metastatic colorectal cancer, renal cell carcinoma and malignant melanoma. AZT and DP were given to enhance the biochemical modulation and antitumor activity of 5-FU and LV. All patients received 5-FU (370 mg/m(2) i.v. bolus day 0-4), LV (50 mg/m(2) p.o. every 4 h day 0-4) and DP (50 mg/m(2) p.o. every 6 h days 0-27). In the phase I portion of the study, AZT was dose escalated in cohorts of 5 patients each, from 50 mg p.o. every 6 h days 0-27 to the MTD of 200 mg p.o. every 6 h days 0-27. Thirty-three patients received 200 mg of AZT in the phase II portion of the trial. Eleven patients developed grade III and 5 patients developed grade IV leukopenia. Four patients developed grade III and 21 patients developed grade IV neutropenia, with six febrile neutropenic episodes. Six patients experienced grade III anemia and four grade III thrombocytopenia. Diarrhea or stomatitis of greater than or equal to grade III occurred in six and four patients, respectively. Fifty-eight percent (19 of 33) of patients required dose reductions of AZT for hematologic toxicity (13 of 19 in the first treatment cycle). At the 200 mg AZT dose level, there were two partial responses in nine colorectal cancer patients (22%), no objective responses in 14 patients with renal cell carcinoma or in 14 patients with melanoma. FLAP does not have significant activity in melanoma, renal cell carcinoma or 5-FU-treated colorectal cancer patients, although it may have activity in untreated colon cancer. C1 NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,FREDERICK,MD 21702. FREDERICK MEM HOSP,FREDERICK,MD. NR 16 TC 3 Z9 3 U1 0 U2 0 PU INT JOURNAL ONCOLOGY PI ATHENS PA C/O PROFESSOR D A SPANDIDOS, EDITORIAL OFFICE, 1, S MERKOURI ST, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD MAR PY 1995 VL 6 IS 3 BP 579 EP 583 PG 5 WC Oncology SC Oncology GA QJ135 UT WOS:A1995QJ13500010 PM 21556574 ER PT J AU SHAPIRO, BA CHEN, JH BUSSE, T NAVETTA, J KASPRZAK, W MAIZEL, JV AF SHAPIRO, BA CHEN, JH BUSSE, T NAVETTA, J KASPRZAK, W MAIZEL, JV TI OPTIMIZATION AND PERFORMANCE ANALYSIS OF A MASSIVELY-PARALLEL DYNAMIC FROG RAM MING ALGORITHM FOR RNA SECONDARY STRUCTURE PREDICTION SO INTERNATIONAL JOURNAL OF SUPERCOMPUTER APPLICATIONS AND HIGH PERFORMANCE COMPUTING LA English DT Article ID TARGET SEQUENCE AB An optimized and parallelized form of a dynamic programming algorithm capable of generating optimal and suboptimal RNA secondary structures is presented, Implementation of this algorithm on a MasPar MP-2 with 16K processors is shown to perform extremely well for very large nucleic acid sequences such as HIV (AIDS) and Rhinovirus (common cold), These sequences are, respectively, 9,128 and 7,208 nucleotides in length. By taking advantage of the parallel nature of MasPar and also optimizing the communication requirements the implementation essentially reduced the algorithm from order O(n(3)) to O(n(2)). This reduction in complexity enables us to fold large RNA sequences in reasonable amounts of time, This capability has proven to be a valuable tool in studying the molecular structure and biological function of molecules this large. C1 NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,FREDERICK BIOMED SUPERCOMP CTR,FREDERICK,MD 21702. MASPAR COMP CORP,BETHESDA,MD 20817. RP SHAPIRO, BA (reprint author), NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT DIAG & CTR,IMAGE PROC SECT,MATH BIOL LAB,FREDERICK,MD 21702, USA. NR 13 TC 6 Z9 6 U1 0 U2 0 PU MIT PRESS PI CAMBRIDGE PA 55 HAYWARD ST JOURNALS DEPT, CAMBRIDGE, MA 02142 SN 1078-3482 J9 INT J SUPERCOMPUT AP JI Int. J. Supercomput. Appl. High Perform. Comput. PD SPR PY 1995 VL 9 IS 1 BP 29 EP 39 DI 10.1177/109434209500900103 PG 11 WC Computer Science, Hardware & Architecture; Computer Science, Interdisciplinary Applications SC Computer Science GA QQ387 UT WOS:A1995QQ38700003 ER PT J AU WILCOX, A SKJAERVEN, R BUEKENS, P KIELY, J AF WILCOX, A SKJAERVEN, R BUEKENS, P KIELY, J TI BIRTH-WEIGHT AND PERINATAL-MORTALITY - A COMPARISON OF THE UNITED-STATES AND NORWAY SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID VITAL-STATISTICS AB Objective.-To compare perinatal mortality in the United States and Norway, using a new analytic approach based on relative birth weight. Design.-Comparison of linked birth and perinatal death records for US and Norwegian births from 1986 through 1987, the most recently available 2-year period. Setting.-Norway and the United States. Participants.-A total of 7 445 914 US births and 105 084 Norwegian births. Interventions.-None. Main Outcome Measure.-Perinatal weight-specific mortality after adjustment for each country's own mean birth weight. Results.-The higher rate of perinatal death in the United States compared with Norway is due to an excess of preterm deliveries in the United States. Low-weight, preterm births comprise 2.9% of US births compared with 2.1% of Norwegian births. If the United States could eliminate this slight excess of preterm delivery, perinatal mortality in the United States would decrease to the level in Norway. Unexpectedly, the survival of newborns at any given birth weight is virtually the same in the United States and Norway when newborns' birth weights are considered relative to their own nation's mean weight. Conclusions.-Low rates of perinatal mortality in the Scandinavian countries have usually been attributed to the heavier weights of their newborns. Higher mortality among US infants is in fact due entirety to a small excess of preterm deliveries. The lighter weights of US newborns at term appear not to affect perinatal survival. Furthermore, the apparent survival advantage of low-weight US newborns (used by policymakers as evidence of superior US intensive neonatal care) may be at [east partly an artifact. When weight-specific mortality rates are adjusted to relative birth weight, low-weight newborns have the same survival in Norway as in the United States. The prevention of excess mortality among US infants depends on the prevention of preterm births, not on changes in mean birth weight. C1 UNIV BERGEN,MED INFORMAT & STAT SECT,BERGEN,NORWAY. FREE UNIV BRUSSELS,SCH PUBL HLTH,BRUSSELS,BELGIUM. CTR DIS CONTROL & PREVENT,NATL CTR HLTH STAT,HYATTSVILLE,MD 20782. RP WILCOX, A (reprint author), NIEHS,EPIDEMIOL BRANCH,POB 12233,RES TRIANGLE PK,NC 27709, USA. OI Wilcox, Allen/0000-0002-3376-1311 NR 19 TC 60 Z9 61 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAR 1 PY 1995 VL 273 IS 9 BP 709 EP 711 DI 10.1001/jama.273.9.709 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA QH814 UT WOS:A1995QH81400029 PM 7853628 ER PT J AU WALDMANN, TA AF WALDMANN, TA TI HUMAN T-CELL LYMPHOTROPIC VIRUS TYPE-I ASSOCIATED ADULT T-CELL LEUKEMIA - THE JOSEPH-GOLDBERGER-CLINICAL-INVESTIGATOR-LECTURE SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Discussion ID RECEPTOR GAMMA-CHAIN; ANTI-TAC-H; INTERLEUKIN-2 RECEPTOR; MONOCLONAL-ANTIBODY; PSEUDOMONAS EXOTOXIN; RADIOIMMUNOTHERAPY; LYMPHOMA; FEATURES; SURVIVAL; DOMAINS RP WALDMANN, TA (reprint author), NCI,METAB BRANCH,BLDG 10,ROOM 4N115,BETHESDA,MD 20892, USA. NR 24 TC 5 Z9 6 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAR 1 PY 1995 VL 273 IS 9 BP 735 EP 737 DI 10.1001/jama.273.9.735 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA QH814 UT WOS:A1995QH81400034 PM 7853633 ER PT J AU KARI, F BUCHER, J HASEMAN, J EUSTIS, S HUFF, J AF KARI, F BUCHER, J HASEMAN, J EUSTIS, S HUFF, J TI LONG-TERM EXPOSURE TO THE ANTIINFLAMMATORY AGENT PHENYLBUTAZONE INDUCES KIDNEY TUMORS IN RATS AND LIVER-TUMORS IN MICE SO JAPANESE JOURNAL OF CANCER RESEARCH LA English DT Article DE F344 RAT; B6C3F1 MOUSE; HEPATOCELLULAR TUMOR; TUBULAR CELL TUMOR ID ETHYL-N-HYDROXYETHYLNITROSAMINE; ANALGESIC NEPHROPATHY; STATISTICAL ISSUES; PAPILLARY NECROSIS; NEOPLASTIC LESIONS; CARCINOGENICITY; CHEMICALS; TESTS; CANCER; ACID AB Long-term toxicity and carcinogenicity of phenylbutazone, a nonsteroidal anti-inflammatory drug, were evaluated in F344/N rats and B6C3F1 mice. In 2-year studies, phenylbutazone was given in corn oil by gavage 5 days per week to groups of 50 rats of each sex at doses of 0, 50, or 100 mg/kg body weight, and to groups of 50 mice at doses of 0, 150, or 300 mg/kg body weight. Body weights and survival were similar among groups. Major target organs are kidneys in rats and liver in mice. Kidney: inflammation, papillary necrosis, and mineralization in both sexes of rats, and hyperplasia and dilatation of the pelvis epithelium, and cysts in female rats. Uncommon tubular cell. tumors of the kidney were found in 13 exposed rats: 5 in the 50 mg group and 4 in the 100 mg group of males; 4 in dosed female rats; none in controls. In female rats, dose-related increases in hyperplasia of the pelvis transitional epithelium, and 2 carcinomas were discovered. Urinary bladder: papillomas of the transitional epithelium were seen in 2 low-dose male and in 1 low-dose female rats. Forestomach: ulcers in rats, with acanthosis, hyperkeratosis, and basal cell hyperplasia in female rats; however, no neoplasms were associated with these lesions. Liver: primarily in male mice exposed to phenylbutazone, hemorrhage, centrilobular cytomegaly and karyomegaly, fatty metamorphosis, cellular degeneration, and coagulative necrosis were seen; clear cell foci were observed in male mice. In summary, under the conditions of these 2-year oral intubation studies, phenylbutazone is associated with renal carcinogenicity in rats, as evidenced by increases in tubular cell neoplasms in both sexes. Evidence of carcinogenicity for male mice was shown by increased incidences and multiplicity of liver tumors. No carcinogenic activity was found for female mice. RP KARI, F (reprint author), NIEHS,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 65 TC 29 Z9 29 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 MAR PY 1995 VL 86 IS 3 BP 252 EP 263 PG 12 WC Oncology SC Oncology GA QP083 UT WOS:A1995QP08300004 PM 7744695 ER PT J AU DORN, LD SUSMAN, EJ FLETCHER, JC AF DORN, LD SUSMAN, EJ FLETCHER, JC TI INFORMED CONSENT IN CHILDREN AND ADOLESCENTS - AGE, MATURATION AND PSYCHOLOGICAL STATE SO JOURNAL OF ADOLESCENT HEALTH LA English DT Article DE INFORMED CONSENT; CHILDREN; ADOLESCENTS; RESEARCH PARTICIPATION; ANXIETY ID PARTICIPATION AB Purpose: The purpose of this investigation was to examine the relationship of understanding of research participation to anxiety, control, and stage of cognitive development. Methods: Participants included 44 boys and girls ages 7 to 20 years. All were inpatients for the first time in pediatric units of a research hospital. Twenty participants were admitted for experimental treatment of pediatric cancers and 24 were admitted for a 3-week treatment of extreme obesity. An interview was conducted to assess 12 elements of knowledge of research participation of a medical protocol. The interview was coded for: 1) knowledge of research participation score, 2) weighted knowledge of participation in research score (based on physician ratings of what was most-to-least important for children and adolescents to know), and 3) global control (perceived control over life, illness and treatment). A measure of anxiety and one Piagetian task to measure stage of cognitive development also were administered. Results: Pearson correlations, significant at p less-than-or-equal-to .05, were as follows: knowledge of participation in research and global control, (r = .40) and weighted knowledge of participation in research score and global control (r = .38). Hierarchical regression showed that the best predictors of knowledge of research participation or the weighted knowledge of research participation score was global control alone or an interaction of global control with anxiety. Conclusions: Emotional factors were more frequently related to understanding of research participation than age or cognitive development. Providing medical environments that decrease anxiety and increase control may enhance children's and adolescent's understanding of the research process. C1 PENN STATE UNIV,UNIVERSITY PK,PA 16802. NIH,BETHESDA,MD 20892. UNIV VIRGINIA,MED CTR,SCH MED,CHARLOTTESVILLE,VA 22901. RP DORN, LD (reprint author), UNIV PITTSBURGH,SCH NURSING,440 VICTORIA BLDG,PITTSBURGH,PA 15261, USA. NR 23 TC 55 Z9 55 U1 2 U2 3 PU ELSEVIER SCIENCE PUBL CO INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 1054-139X J9 J ADOLESCENT HEALTH JI J. Adolesc. Health PD MAR PY 1995 VL 16 IS 3 BP 185 EP 190 DI 10.1016/1054-139X(94)00063-K PG 6 WC Psychology, Developmental; Public, Environmental & Occupational Health; Pediatrics SC Psychology; Public, Environmental & Occupational Health; Pediatrics GA QP516 UT WOS:A1995QP51600003 PM 7779827 ER PT J AU IGARASHI, Y GOLDRICH, MS KALINER, MA IRANI, AMA SCHWARTZ, LB WHITE, MV AF IGARASHI, Y GOLDRICH, MS KALINER, MA IRANI, AMA SCHWARTZ, LB WHITE, MV TI QUANTITATION OF INFLAMMATORY CELLS IN THE NASAL-MUCOSA OF PATIENTS WITH ALLERGIC RHINITIS AND NORMAL SUBJECTS SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE ALLERGIC RHINITIS; NASAL MUCOSA; IMMUNOHISTOCHEMISTRY; LYMPHOCYTE; MAST CELL; IGE ID HUMAN EOSINOPHILS; MAST-CELLS; INTERLEUKIN-2 RECEPTOR; MONOCLONAL-ANTIBODIES; ANTIGEN CHALLENGE; INTERFERON-GAMMA; 3T3 FIBROBLASTS; SECRETION; IMMUNOHISTOCHEMISTRY; IMMUNOHISTOLOGY AB Background: The role of inflammatory cells at the local site of allergic inflammation in the nose is unclear. Methods: nasal biopsy specimens were obtained from 10 patients with symptomatic seasonal allergic rhinitis and 10 normal subjects. Freeze-dried paraffin-embedded sections were stained for mononuclear cells and eosinophils. Tissues in Carnoy's fixative were stained for mast cells. Results: T cells were much more plentiful than B cells or macrophages, and no significant differences were found between the two groups in the number of T cells, T-cells subsets, B cells, and macrophages. However, the number of Cd25+ cells (lymphocyte activation markers) and the number of eosinophils were significantly higher in the allergic group than in the control group. There were no significant differences between the two groups in the total mast cell number. However, mucosal type mast cells were slightly increased, and a higher ratio of mast cells were costained for IgE in the allergic group. IgE+ cells mostly constained for mast cell tryptase and did not costain for J chain. Conclusion: These data suggest that unlike granulocytes, in some mononuclear cells qualitative, not quantitative, changes may be important in allergic rhinitis and that IgE may not be locally produced in the nasal mucosa. C1 NIAID,CLIN INVEST LAB,ALLERG DIS SECT,BETHESDA,MD 20892. VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,DEPT MED,RICHMOND,VA 23298. NR 40 TC 52 Z9 53 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD MAR PY 1995 VL 95 IS 3 BP 716 EP 725 DI 10.1016/S0091-6749(95)70177-X PG 10 WC Allergy; Immunology SC Allergy; Immunology GA QM017 UT WOS:A1995QM01700012 PM 7897155 ER PT J AU RICHARDSON, LL KLEINMAN, HK DYM, M AF RICHARDSON, LL KLEINMAN, HK DYM, M TI THE EFFECTS OF AGING ON BASEMENT-MEMBRANE IN THE TESTIS SO JOURNAL OF ANDROLOGY LA English DT Article DE MESSENGER-RNA; LAMININ; COLLAGEN IV; HEPARAN SULFATE PROTEOGLYCAN; FIBRONECTIN; NORTHERN BLOT ID BROWN-NORWAY RAT; HEPARAN-SULFATE PROTEOGLYCAN; GLYCOSYLATION END-PRODUCTS; TESTICULAR CELL-CULTURE; AGE-RELATED-CHANGES; COLLAGEN TYPE-IV; EXTRACELLULAR-MATRIX; DIABETES-MELLITUS; SERTOLI CELLS; MESSENGER-RNA AB Age-related increases in basement membrane thickness have been noted in many tissues, including the testis. The current investigation examined the morphology of the basement membrane in the aged Brown Norway rat and sought to determine whether the accumulation of basement membrane was the result of an increase in the expression of the basement membrane genes. The aged testis was characterized by atrophy of the seminiferous tubules. Closer examination of the degenerated tubules revealed that the seminiferous epithelium was completely devoid of germ cells and that the basement membrane of these tubules was thickened and highly convoluted. In some animals, there was a measurable increase in basement membrane thickness in tubules of normal diameter together with an apparently normal epithelium, suggesting that the thickening is not solely due to a shrinkage of the tubules. To determine whether an increase in basement membrane synthesis was responsible for the thickening, the expression of the genes for laminin, collagen IV, heparan sulfate proteoglycan, and fibronectin was analyzed by Northern blot. There were no changes in the expression of the genes for the laminin B1 and B2 chains, heparan sulfate proteoglycan, or fibronectin that could be correlated with increasing age. Surprisingly, however, the levels of mRNA for the laminin A chain and collagen IV decreased with age. Thus, it appears that the increased thickening of the basement membrane may not be due to increased synthesis of its components, although due to the chronic nature of the aging process, small or transient increases in gene expression may not have been detected. It is also possible that other mechanisms, such as decreased turnover, may play an important role in the age-related thickening of the basement membrane in the testis. C1 GEORGETOWN UNIV,MED CTR,DEPT CELL BIOL,WASHINGTON,DC 20007. NIDR,DEV BIOL LAB,BETHESDA,MD 20892. FU NICHD NIH HHS [HD16260] NR 61 TC 16 Z9 18 U1 0 U2 0 PU AMER SOC ANDROLOGY, INC PI LAWRENCE PA C/O ALLEN PRESS, INC PO BOX 368, LAWRENCE, KS 66044 SN 0196-3635 J9 J ANDROL JI J. Androl. PD MAR-APR PY 1995 VL 16 IS 2 BP 118 EP 126 PG 9 WC Andrology SC Endocrinology & Metabolism GA RA432 UT WOS:A1995RA43200005 PM 7559141 ER PT J AU ROSIEPEN, G CHAPIN, RE WEINBAUER, GF AF ROSIEPEN, G CHAPIN, RE WEINBAUER, GF TI THE DURATION OF THE CYCLE OF THE SEMINIFEROUS EPITHELIUM IS ALTERED BY ADMINISTRATION OF 2,5-HEXANEDIONE IN THE ADULT SPRAGUE-DAWLEY RAT SO JOURNAL OF ANDROLOGY LA English DT Article DE SPERMATOGENESIS; SPERMATOGENIC CYCLE; BROMODEOXYURIDINE; FSH; TESTOSTERONE ID SERTOLI-CELL CYTOSKELETON; GLYCOL MONOMETHYL ETHER; TESTICULAR ATROPHY; EXPOSURE ALTERS; VITAMIN-A; TESTIS; SPERMATOGENESIS; POLYMERIZATION; DEGENERATION; KINETICS AB The duration of the cycle of the seminiferous epithelium is believed to be under genetic control rather than being influenced by other factors. However, the frequencies of certain spermatogenic stages-reflecting their relative durations-can be altered under various conditions including treatment with the n-hexane metabolite, 2,5-hexanedione (HD). To investigate whether HD administration alters the duration of the spermatogenic process, adult Sprague-Dawley rats were exposed to vehicle (n = 20) or 1% HD dissolved in the drinking water (n = 40) throughout a period of 29 days. On day 17, 100 mg/kg of 5-bromodeoxyuridine (BrdU) was given intraperitoneally; 3 hours later one testis was removed, and the remaining testis was excised 12 days later. BrdU was localized in Bouin's-fixed, Paraplast-embedded testes using immunogold-silver-staining, and sections were counterstained with periodic acid-Schiff and hematoxylin to permit identification of the spermatogenic stages. HD treatment reduced weights of body, testis, and epididymis (P < 0.05) but had no effects on serum levels of follicle-stimulating hormone or testosterone. The seminiferous epithelium was vacuolized, and spermatogenesis was affected to various degrees. HD significantly reduced the frequency of stage VII tubules (P < 0.01) and increased the frequency of stage IX and stage X tubules (P < 0.05). Furthermore, HD reduced the stage-dependent progression of BrdU-labeled germ cells. By day 29, BrdU-positive germ cells were seen in 13% of stage IX control tubules, whereas in HD-treated animals BrdU-labeled germ cells were not present in stage IX tubules and were found in only 2-3% of stage VIII tubules; the calculated duration of the spermatogenic cycle was significantly increased (P < 0.01) in the HD-administered animals (13.43 +/- 0.10 vs. 12.37 +/- 0.05 days). These findings demonstrate (1) that the duration of the cycle of the seminiferous epithelium can be altered experimentally in the adult Sprague-Dawley rat and (2) that changes in the frequency of spermatogenic stages can be associated with a change in the duration of the spermatogenic process. C1 UNIV MUNSTER,INST REPROD MED,D-48149 MUNSTER,GERMANY. UNIV MUNSTER,INST SPECIAL ZOOL & COMPARAT EMBRYOL,D-48149 MUNSTER,GERMANY. NIEHS,NATL TOXICOL PROGRAM,REPROD TOXICOL GRP,RES TRIANGLE PK,NC 27709. OI Chapin, Robert/0000-0002-5997-1261 NR 33 TC 19 Z9 20 U1 0 U2 0 PU AMER SOC ANDROLOGY, INC PI LAWRENCE PA C/O ALLEN PRESS, INC PO BOX 368, LAWRENCE, KS 66044 SN 0196-3635 J9 J ANDROL JI J. Androl. PD MAR-APR PY 1995 VL 16 IS 2 BP 127 EP 135 PG 9 WC Andrology SC Endocrinology & Metabolism GA RA432 UT WOS:A1995RA43200006 PM 7559142 ER PT J AU WESTERGAARD, GC SUOMI, SJ AF WESTERGAARD, GC SUOMI, SJ TI THE PRODUCTION AND USE OF DIGGING TOOLS BY MONKEYS - A NONHUMAN PRIMATE MODEL OF A HOMINID SUBSISTENCE ACTIVITY SO JOURNAL OF ANTHROPOLOGICAL RESEARCH LA English DT Article ID CEBUS-APELLA; SENSORIMOTOR INTELLIGENCE; OBJECT MANIPULATION; CAPUCHIN; CHIMPANZEES; APES; FOOD AB This research examined the production and use of digging tools by tufted capuchin monkeys (Cebus apella). We provided groups of subjects with sticks and containers that held peanuts buried in hard-packed earth. Nine of the ten subjects used their fingers to loosen earth and their hands to scoop away soil. Four of these subjects used sticks as digging tools, and three of them produced tools for this purpose Similarities were noted between the digging behavior of capuchins and that of humans in modern hunter-gatherer societies. We hypothesize that Home habilis could have produced digging tools analogous to those produced by monkeys in this investigation and that the use of such implements would have provided evolutionary advantages in harsh prehistoric environments. RP WESTERGAARD, GC (reprint author), NICHHD,COMPARAT ETHOL LAB,POB 529,POOLESVILLE,MD 20837, USA. NR 30 TC 8 Z9 8 U1 1 U2 5 PU JOURNAL OF ANTHROPOLOGICAL RES PI ALBUQUERQUE PA UNIV NEW MEXICO, ANTHROPOLOGY DEPT, ALBUQUERQUE, NM 87111 SN 0091-7710 J9 J ANTHROPOL RES JI J. Anthropol. Res. PD SPR PY 1995 VL 51 IS 1 BP 1 EP 8 PG 8 WC Anthropology SC Anthropology GA QZ518 UT WOS:A1995QZ51800002 ER PT J AU BADEN, DG MELINEK, R SECHET, V TRAINER, VL SCHULTZ, DR REIN, KS TOMAS, CR DELGADO, J HALE, L AF BADEN, DG MELINEK, R SECHET, V TRAINER, VL SCHULTZ, DR REIN, KS TOMAS, CR DELGADO, J HALE, L TI MODIFIED IMMUNOASSAYS FOR POLYETHER TOXINS - IMPLICATIONS OF BIOLOGICAL MATRICES, METABOLIC STATES, AND EPITOPE RECOGNITION SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article; Proceedings Paper CT Symposium on Analytical Methods for Seafood Toxins, at the 107th AOAC International Annual Meeting CY JUL 26-29, 1993 CL WASHINGTON, DC SP ASSOC OFFICIAL ANALYT CHEMISTS ID ENZYME-IMMUNOASSAY; SODIUM-CHANNELS; BREVETOXINS; DINOFLAGELLATE; CIGUATOXIN; INHIBITION; BINDING AB Polyether marine toxins are responsible for the seafood intoxication phenomena known as neurotoxic shellfish poisoning (due to brevetoxins), ciguatera (due to ciguatoxin), and diarrheic shellfish poisoning (due to okadaic acid), Using traditional techniques of hapten (pure toxin) conjugation to protein to create complete antigen, animal immunization and antibody isolation, and specific antibody subpopulation purification, discriminating antibodies have been isolated that detect brevetoxins and ciguatoxin, but not okadaic acid, in a dose-dependent fashion, Using microorganic chemistry and purified toxins, a unique set of tools has been created for the study of polyether ladder toxin accumulation; depuration; and specific site localization in tissues, food sources, and clinical samples, Developed test protocols can detect toxin in dinoflagellate cells, in extracts from food sources, in seawater and culture media, and in human serum samples, Enzyme-linked immunosorbent assay protocols developed for eventual collaborative testing have been successful in limited applications within the laboratory (correlation coefficient of 0.92 excluding 2 outliers), and alternative formats are being developed to optimize the basic test for use in research laboratories, regulatory laboratories, and field inspections. RP BADEN, DG (reprint author), UNIV MIAMI,NIEHS,CTR MARINE & FRESHWATER BIOMED SCI,4600 RICKENBACKER CAUSEWAY,MIAMI,FL 33149, USA. FU NIEHS NIH HHS [R01 ES 06411, P 30 ES 05705, R01 ES 05853] NR 29 TC 21 Z9 22 U1 1 U2 3 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD MAR-APR PY 1995 VL 78 IS 2 BP 499 EP 508 PG 10 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA QN304 UT WOS:A1995QN30400038 PM 7538840 ER PT J AU POLI, MA REIN, KS BADEN, DG AF POLI, MA REIN, KS BADEN, DG TI RADIOIMMUNOASSAY FOR PBTX-2-TYPE BREVETOXINS - EPITOPE SPECIFICITY OF 2 ANTI-PBTX SERA SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article; Proceedings Paper CT Symposium on Analytical Methods for Seafood Toxins, at the 107th AOAC International Annual Meeting CY JUL 26-29, 1993 CL WASHINGTON, DC SP ASSOC OFFICIAL ANALYT CHEMISTS ID RED TIDE DINOFLAGELLATE; PTYCHODISCUS-BREVIS; GYMNODINIUM; ANTIBODIES; TOXINS AB Antiserum against PbTx-2-type brevetoxins was produced by immunizing rabbits with a PbTx-2-bovine serum albumin (BSA) conjugate, This serum had a higher affinity, but lower titer, than our current goat serum, Using 4 natural brevetoxins and 6 synthetic derivatives as competitors in our brevetoxin radioimmunoassay, we determined the epitope specificity of both sera. Modification of the backbone structure at C-42 on the K-ring had little or no effect on the antigen-binding capability of either serum, Reduction of the double bond between C-2 and C-3 on the A-ring by reduction of the lactone decreased binding 500 to 750-fold. Epoxidation of the double bond between C-27 and C-28 on the H-ring did not affect binding, which suggested that the goat serum is specific for the A-ring region of the brevetoxin backbone, In contrast, modifying the A-ring had no effect on rabbit serum binding. However, epoxidation of the H-ring decreased binding 5 to 20-fold, which suggested that the rabbit antiserum is specific for the H-ring region of the molecule, These results suggest that assays utilizing only one antibody may not adequately detect toxin metabolites if molecules are altered in the critical region of antibody recognition. C1 UNIV MIAMI,ROSENSTIEL SCH MARINE & ATMOSPHER SCI,NIEHS,CTR MARINE & FRESHWATER BIOMED SCI,MIAMI,FL 33101. RP POLI, MA (reprint author), USA,MED RES INST INFECT DIS,FREDERICK,MD 21702, USA. NR 17 TC 35 Z9 36 U1 0 U2 0 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD MAR-APR PY 1995 VL 78 IS 2 BP 538 EP 542 PG 5 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA QN304 UT WOS:A1995QN30400044 PM 7538841 ER PT J AU FLEG, JL OCONNOR, F GERSTENBLITH, G BECKER, LC CLULOW, J SCHULMAN, SP LAKATTA, EG AF FLEG, JL OCONNOR, F GERSTENBLITH, G BECKER, LC CLULOW, J SCHULMAN, SP LAKATTA, EG TI IMPACT OF AGE ON THE CARDIOVASCULAR-RESPONSE TO DYNAMIC UPRIGHT EXERCISE IN HEALTHY-MEN AND WOMEN SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE GENDER; CARDIOVASCULAR PERFORMANCE ID CORONARY-ARTERY DISEASE; LEFT-VENTRICULAR PERFORMANCE; EJECTION FRACTION; CARDIAC-OUTPUT; RADIONUCLIDE ANGIOGRAPHY; ATTENUATION CORRECTION; BICYCLE EXERCISE; SUPINE EXERCISE; BLOOD POOL; VOLUME AB To examine whether age differentially modifies the physiological response to exercise in men and women, we performed gated radionuclide ventriculography with measurement of left ventricular volumes at rest and during peak upright cycle exercise in 200 rigorously screened healthy sedentary volunteers (121 men and 79 women) aged 22-86 yr from the Baltimore Longitudinal Study of Aging. At rest in the sitting position, age-associated declines in heart rate (HR) and increases in systolic blood pressure occurred in both sexes. Whereas resting cardiac index (CI) and total systemic vascular resistance (TSVR) in men did not vary with age, in women resting CI decreased 16% and TSVR increased 46% over the six-decade age span. Men, but not women, demonstrated an age-associated increase of similar to 20% in sitting end-diastolic volume index (EDVI), end-systolic volume index (ESVI), and stroke volume index over this age span. Peak cycle work rate declined with age similar to 40% in both sexes, but at any age it was greater in men than in women even after normalization for body weight. At peak effort, ejection fraction (EF), HR, and CI were reduced similarly with age while ESVI and TSVR were increased in both sexes; EDVI increased 35% with age and stroke work index (SWI) rose 19% in men, but neither was related to age in women; and stroke volume index did not vary with age in either sex. When hemodynamics were expressed as the change from rest to peak effort as an index of cardiovascular reserve function, both sexes demonstrated age-associated increases in EDVI and ESVI and reductions in EF, HR, and CI. However, the exercise-induced reduction in ESVI and the increases in EF, CI, and SWI from rest were greater in men than in women. Thus, age and gender each have a significant impact on the cardiac response to exhaustive upright cycle exercise. C1 JOHNS HOPKINS UNIV,SCH MED,DIV CARDIOL,BALTIMORE,MD 21224. RP FLEG, JL (reprint author), NIA,GERONTOL RES CTR,CARDIOVASC SCI LAB,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. FU NIA NIH HHS [N01-AG-9-2116] NR 36 TC 243 Z9 252 U1 2 U2 19 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 MAR PY 1995 VL 78 IS 3 BP 890 EP 900 PG 11 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA QP826 UT WOS:A1995QP82600021 PM 7775334 ER PT J AU KULLIK, I TOLEDANO, MB TARTAGLIA, LA STORZ, G AF KULLIK, I TOLEDANO, MB TARTAGLIA, LA STORZ, G TI MUTATIONAL ANALYSIS OF THE REDOX-SENSITIVE TRANSCRIPTIONAL REGULATOR OXYR - REGIONS IMPORTANT FOR OXIDATION AND TRANSCRIPTIONAL ACTIVATION SO JOURNAL OF BACTERIOLOGY LA English DT Article ID ESCHERICHIA-COLI; SALMONELLA-TYPHIMURIUM; POSITIVE REGULATOR; INDUCIBLE GENES; NADH PEROXIDASE; RNA-POLYMERASE; SULFENIC ACID; PROTEIN; STRESS; PROMOTERS AB OxyR is a redox-sensitive transcriptional regulator of the LysR family which activates the expression of genes important for the defense against hydrogen peroxide in Escherichia coli and Salmonella typhimurium. OxyR is sensitive to oxidation and reduction, and only oxidized OxyR is able to activate transcription of its target genes, Using site-directed mutagenesis, we found that one cysteine residue (C-199) is critical for the redox sensitivity of OxyR, and a C-199-->S mutation appears to lock the OxyR protein in the reduced form. We also used a random mutagenesis approach to isolate eight constitutively active mutants. AIL of the mutations are located in the C-terminal half of the protein, and four of the mutations map near the critical C-199 residue. In vivo as well as in vitro transcription experiments showed that the constitutive mutant proteins were able to activate transcription under both oxidizing and reducing conditions, and DNase I footprints showed that this activation is due to the ability of the mutant proteins to induce cooperative binding of RNA polymerase. Unexpectedly, RNA polymerase was also found to reciprocally affect OxyR binding. C1 NICHHD,CELL BIOL & METAB BRANCH,BETHESDA,MD 20892. UNIV CALIF BERKELEY,DIV BIOCHEM & MOLEC BIOL,BERKELEY,CA 94720. OI Storz, Gisela/0000-0001-6698-1241 NR 43 TC 166 Z9 169 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 MAR PY 1995 VL 177 IS 5 BP 1275 EP 1284 PG 10 WC Microbiology SC Microbiology GA QJ439 UT WOS:A1995QJ43900021 PM 7868602 ER PT J AU KULLIK, I STEVENS, J TOLEDANO, MB STORZ, G AF KULLIK, I STEVENS, J TOLEDANO, MB STORZ, G TI MUTATIONAL ANALYSIS OF THE REDOX-SENSITIVE TRANSCRIPTIONAL REGULATOR OXYR - REGIONS IMPORTANT FOR DNA-BINDING AND MULTIMERIZATION SO JOURNAL OF BACTERIOLOGY LA English DT Article ID ESCHERICHIA-COLI; SALMONELLA-TYPHIMURIUM; OXIDATIVE STRESS; POSITIVE REGULATOR; INDUCIBLE GENES; METR PROTEIN; NOD BOX; PROMOTERS; PURIFICATION; REGULON AB OxyR is a LysR-type transcriptional regulator which negatively regulates its own expression and positively regulates the expression of proteins important for the defense against hydrogen peroxide in Eschericha coli and Salmonella typhimurium. Using random mutagenesis, we isolated six nonrepressing OxyR mutants that were impaired in DNA binding. Five of the mutations causing the DNA binding defect mapped near the N-terminal helix-turn-helix motif conserved among the LysR family members, confirming that this region is a DNA binding domain in OxyR. The sixth nonrepressing mutant (with E-225 changed to K [E225K]) was found to be predominantly dimeric, in contrast to the tetrameric wild-type protein, suggesting that a C-terminal region defined by the E225K mutation is involved in multimerization. C1 NICHHD,CELL BIOL & METAB BRANCH,BETHESDA,MD 20892. OI Storz, Gisela/0000-0001-6698-1241 NR 39 TC 88 Z9 92 U1 1 U2 3 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 MAR PY 1995 VL 177 IS 5 BP 1285 EP 1291 PG 7 WC Microbiology SC Microbiology GA QJ439 UT WOS:A1995QJ43900022 PM 7868603 ER PT J AU HOCHBERG, MC LETHBRIDGECEJKU, M SCOTT, WW REICHLE, R PLATO, CC TOBIN, JD AF HOCHBERG, MC LETHBRIDGECEJKU, M SCOTT, WW REICHLE, R PLATO, CC TOBIN, JD TI UPPER EXTREMITY BONE MASS AND OSTEOARTHRITIS OF THE KNEES - DATA FROM THE BALTIMORE LONGITUDINAL-STUDY OF AGING SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article ID OSTEO-ARTHRITIS; MINERAL DENSITY; 2ND METACARPAL; HIP; OSTEOPOROSIS; FEMUR; EPIDEMIOLOGY; HAND; END AB To examine the association of upper extremity bone mass with osteoarthritis (OA) of the knee, bilateral standing knee radiographs, taken between 1985 and 1991, in 430 Caucasian male and 266 Caucasian female subjects aged 40 years and above in the Baltimore Longitudinal Study of Aging, were read by one investigator for grade of OA using Kellgren-Lawrence scales, Several measures of upper extremity bone mass, size, and density, including combined cortical thickness (CCT), total width and percentage of cortical area of the second metacarpal, and bone mineral content (BMC), width, and density of the distal third of the left radius measured with single photon absorptiometry, were assessed at the same visit, In univariate analyses, men and women with definite knee OA were significantly older, men had significantly greater radial, width, and women had significantly lo,ver bone mass as measured by both CCT and BMC. After adjustment for age and body weight, however, men with knee OA had significantly higher BMC and radial width while neither of these measures of upper extremity bone mass and size was significantly associated with the presence of definite knee OA in women, Neither measure of upper extremity bone density was significantly associated with definite knee OA in either sex, These data suggest that, although men (but not women) with definite knee OA have significantly higher levels of adjusted radial bone mass and size, subjects with knee OA do not have significantly higher levels of adjusted bone mineral density at either upper extremity site. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT RADIOL,DIV SKELETAL RADIOL,BALTIMORE,MD 21205. NIA,GERONTOL RES CTR,APPL PHYSIOL SECT,BALTIMORE,MD 21224. RP HOCHBERG, MC (reprint author), UNIV MARYLAND,SCH MED,DIV CLIN IMMUNOL & RHEUMATOL,PROFESS BLDG,419 W REDWOOD ST,SUITE 620,BALTIMORE,MD 21201, USA. NR 47 TC 30 Z9 31 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD MAR PY 1995 VL 10 IS 3 BP 432 EP 438 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA QK780 UT WOS:A1995QK78000013 PM 7785465 ER PT J AU COSTA, PT MCCRAE, RR KAY, GG AF COSTA, PT MCCRAE, RR KAY, GG TI PERSONS, PLACES, AND PERSONALITY - CAREER ASSESSMENT USING THE REVISED NEO PERSONALITY-INVENTORY SO JOURNAL OF CAREER ASSESSMENT LA English DT Article ID 5-FACTOR MODEL; VOCATIONAL INTERESTS; FACET SCALES; DIMENSIONS; CONSCIENTIOUSNESS; AGREEABLENESS; SAMPLE AB The Revised NEO Personality Inventory (NEO PI-R; Costa & McCrae, 1992a) is a questionnaire measure of 30 traits that define the comprehensive five-factor model (FFM) of personality. Data from police selection, college student, and Hispanic American samples illustrate the psychometric properties of the instrument. In vocational counseling, the NEO PI-R can supplement measures of vocational interests and abilities, especially by calling attention to the client's strengths and weaknesses in adjustment and motivation. Use of the NEO Job Profiler, a tool designed to help identify the personality requirements of different occupations, is illustrated in the police selection sample. Together, the NEO Job Profiler and NEO PI-R can help determine the optimal match between person and occupation. C1 GEORGETOWN UNIV,WASHINGTON,DC 20057. RP COSTA, PT (reprint author), NIA,GERONTOL RES CTR,PERSONAL & COGNIT LAB,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. NR 45 TC 36 Z9 40 U1 3 U2 32 PU PSYCHOLOGICAL ASSESSMENT RESOURCES INC PI ODESSA PA PO BOX 998, ODESSA, FL 33556 SN 1069-0727 J9 J CAREER ASSESSMENT JI J. Career Assess. PD SPR PY 1995 VL 3 IS 2 BP 123 EP 139 DI 10.1177/106907279500300202 PG 17 WC Psychology, Applied SC Psychology GA QT710 UT WOS:A1995QT71000002 ER PT J AU SHARTAVA, A MONTEIRO, CA BENCSATH, EA SCHNEIDER, K CHAIT, BT GUSSIO, R CASORIASCOTT, LA SHAH, AK HEUERMAN, CA GOODMAN, SR AF SHARTAVA, A MONTEIRO, CA BENCSATH, EA SCHNEIDER, K CHAIT, BT GUSSIO, R CASORIASCOTT, LA SHAH, AK HEUERMAN, CA GOODMAN, SR TI A POSTTRANSLATIONAL MODIFICATION OF BETA-ACTIN CONTRIBUTES TO THE SLOW DISSOCIATION OF THE SPECTRIN-PROTEIN 4.1-ACTIN COMPLEX OF IRREVERSIBLY SICKLED CELLS SO JOURNAL OF CELL BIOLOGY LA English DT Article ID HUMAN-ERYTHROCYTE MEMBRANE; HEINZ BODY FORMATION; PAINFUL CRISIS; PARTIAL-PURIFICATION; MOLECULAR-STRUCTURE; BUNDLING PROTEIN; RED-CELLS; BINDING; DISEASE; IDENTIFICATION AB Irreversibly sickled cells (ISCs) remain sickled even under conditions where they are well oxygenated and hemoglobin is depolymerized. In our studies we demonstrate that triton extracted ISC core skeletons containing only spectrin, protein 4.1, and actin also retain their sickled shape; while reversibly sickled cell (RSC) skeletons remodel to a round or biconcave shape. We also demonstrate that these triton extracted ISC core skeletons dissociate more slowly upon incubation at 37 degrees C than do RSC or control (AA) core skeletons. This observation may supply the basis for the inability of the ISC core skeleton to remodel its shape. Using an in vitro ternary complex dissociation assay, we demonstrate that a modification in beta-actin is the major determinant of the slow dissociation of the spectrin-protein 4.1-actin complex isolated from the ISC core skeleton. We demonstrate that the difference between ISC and control beta-actin is the inaccessibility of two cysteine residues in ISC beta-actin to labeling by thiol reactive reagents; due to the formation of a disulfide bridge between cysteine(284) and cysteine(373) in ISC beta-actin, or alternatively another modification of cysteine(284) and cysteine(373) which is reversible with DTT and adds less than 100 D to the molecular weight of beta-actin. C1 UNIV SO ALABAMA,COLL MED,DEPT STRUCT & CELLULAR BIOL,MOBILE,AL 36688. UNIV SO ALABAMA,COLL MED,DEPT BIOCHEM,MOBILE,AL 36688. UNIV SO ALABAMA,COLL MED,DEPT MATH & STAT,MOBILE,AL 36688. UNIV SO ALABAMA,COLL MED,USA COMPREHENS SICKLE CELL CTR,MOBILE,AL 36688. ROCKEFELLER UNIV,MASS SPECTROMETRY LAB,NEW YORK,NY 10021. NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,FREDERICK BIOMED SUPERCOMP CTR,FREDERICK,MD 21702. RI Schneider, Klaus/N-6604-2014 OI Schneider, Klaus/0000-0002-3068-8681 FU NHLBI NIH HHS [3P60 HL38639] NR 63 TC 47 Z9 48 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD MAR PY 1995 VL 128 IS 5 BP 805 EP 818 DI 10.1083/jcb.128.5.805 PG 14 WC Cell Biology SC Cell Biology GA QK440 UT WOS:A1995QK44000008 PM 7876306 ER PT J AU ROH, JY STANLEY, JR AF ROH, JY STANLEY, JR TI INTRACELLULAR DOMAIN OF DESMOGLEIN-3 (PEMPHIGUS-VULGARIS ANTIGEN) CONFERS ADHESIVE FUNCTION ON THE EXTRACELLULAR DOMAIN OF E-CADHERIN WITHOUT BINDING CATENINS SO JOURNAL OF CELL BIOLOGY LA English DT Article ID CELL-CELL-ADHESION; CYTOPLASMIC DOMAIN; BETA-CATENIN; DESMOSOMAL GLYCOPROTEIN; POSSIBLE INVOLVEMENT; ALPHA-CATENIN; N-CADHERIN; PLAKOGLOBIN; MOLECULES; CALCIUM AB For the extracellular (EC) domain of E-cadherin to function in homophilic adhesion it is thought that its intracytoplasmic (IC) domain must bind alpha- and beta-catenins, which link it to the actin cytoskeleton. However, the IC domain of pemphigus vulgaris antigen (PVA or Dsg3), which is in the desmoglein subfamily of the cadherin gene superfamily, does not bind alpha- or beta-catenins. Because desmogleins have also been predicted to function in the cell adhesion of desmosomes, we speculated that the PVA IC domain might be able to act in a novel way in conferring adhesive function on the EC domain of cadherins. To test this hypothesis we studied aggregation of mouse fibroblast L cell clones that expressed chimeric cDNAs encoding the EC domain of E-cadherin with various IC domains. We show here that the full IC domain of PVA as well as an IC subdomain containing only 40 amino acids of the PVA intracellular anchor (IA) region confer adhesive function on the E-cadherin EC domain without catenin-like associations with cytoplasmic molecules or fractionation with the cell cytoskeleton. This IA region subdomain is evolutionarily conserved in desmogleins, but not classical cadherins. These findings suggest an important cell biologic function for the IA region of desmogleins and demonstrate that strong cytoplasmic interactions are not absolutely necessary for E-cadherin-mediated adhesion. C1 NCI, DERMATOL BRANCH, BETHESDA, MD 20892 USA. NR 53 TC 25 Z9 25 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD MAR PY 1995 VL 128 IS 5 BP 939 EP 947 DI 10.1083/jcb.128.5.939 PG 9 WC Cell Biology SC Cell Biology GA QK440 UT WOS:A1995QK44000019 PM 7876317 ER PT J AU PETERS, PJ HSU, VW OOI, CE FINAZZI, D TEAL, SB OORSCHOT, V DONALDSON, JG KLAUSNER, RD AF PETERS, PJ HSU, VW OOI, CE FINAZZI, D TEAL, SB OORSCHOT, V DONALDSON, JG KLAUSNER, RD TI OVEREXPRESSION OF WILD-TYPE AND MUTANT ARF1 AND ARF6 - DISTINCT PERTURBATIONS OF NONOVERLAPPING MEMBRANE COMPARTMENTS SO JOURNAL OF CELL BIOLOGY LA English DT Article ID ADP-RIBOSYLATION FACTOR; GTP-BINDING PROTEIN; COP-COATED VESICLES; GOLGI MEMBRANES; BREFELDIN-A; IMMUNOELECTRON MICROSCOPY; PERMEABILIZED CELLS; ADDITIONAL MEMBERS; ENDOCYTIC PATHWAY; DYNAMIN AB The ARF GTP binding proteins are believed to function as regulators of membrane traffic in the secretory pathway. While the ARF1 protein has been shown in vitro to mediate the membrane interaction of the cytosolic coat proteins coatomer (COPI) and gamma-adaptin with the Golgi complex, the functions of the other ARF proteins have not been defined. Here, we show by transient transfection with epitope-tagged ARFs, that whereas ARF1 is localized to the Golgi complex and can be shown to affect predictably the assembly of COPI and gamma-adaptin with Golgi membranes in cells, ARF6 is localized to the endosomal/plasma membrane system and has no effect on these Golgi-associated coat proteins. By immune-electron microscopy, the wild-type ARF6 protein is observed along the plasma membrane and associated with endosomes, and overexpression of ARF6 does not appear to alter the morphology of the peripheral membrane system. In contrast, overexpression of ARF6 mutants predicted either to hydrolyze or bind GTP poorly shifts the distribution of ARF6 and affects the structure of the endocytic pathway. The GTP hydrolysis-defective mutant is localized to the plasma membrane and its overexpression results in a profound induction of extensive plasma membrane vaginations and a depletion of endosomes. Conversely, the GTP binding-defective ARF6 mutant is present exclusively in endosomal structures, and its overexpression results in a massive accumulation of coated endocytic structures. C1 NICHHD,CELL BIOL & METAB BRANCH,BETHESDA,MD 20892. UNIV UTRECHT,FAC MED,DEPT CELL BIOL,3584 CX UTRECHT,NETHERLANDS. UNIV UTRECHT,INST BIOMEMBRANES,3584 CX UTRECHT,NETHERLANDS. OI Finazzi, Dario/0000-0001-5176-2839; Teal, Stephanie/0000-0002-0167-1071 NR 57 TC 299 Z9 299 U1 3 U2 10 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD MAR PY 1995 VL 128 IS 6 BP 1003 EP 1017 DI 10.1083/jcb.128.6.1003 PG 15 WC Cell Biology SC Cell Biology GA QN288 UT WOS:A1995QN28800002 PM 7896867 ER PT J AU SAITO, N KAWAI, K NOWAK, TS AF SAITO, N KAWAI, K NOWAK, TS TI REEXPRESSION OF DEVELOPMENTALLY-REGULATED MAP2C MESSENGER-RNA AFTER ISCHEMIA - COLOCALIZATION WITH HSP72 MESSENGER-RNA IN VULNERABLE NEURONS SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE HEAT SHOCK; ISCHEMIA; MICROTUBULE-ASSOCIATED; PROTEIN 2; STRESS PROTEIN ID MICROTUBULE-ASSOCIATED PROTEIN-2; TRANSIENT FOREBRAIN ISCHEMIA; COMPLETE CEREBRAL-ISCHEMIA; III BETA-TUBULIN; MESSENGER-RNA; TYROSINE PHOSPHORYLATION; RAT-BRAIN; ADULT-RAT; GERBIL BRAIN; HEAT-SHOCK AB Levels of mRNAs encoding the microtubule-associated proteins MAP2b and MAP2c as well as the 70-kDa stress protein [72-kDa heat shock protein (hsp72)] were evaluated in postischemic rat brain by in situ hybridization with oligonucleotide probes corresponding to the known rat sequences. Rats were subjected to 10-min cardiac arrest, produced by compression of major thoracic vessels, followed by resuscitation. The normally expressed MAP2b mRNA showed transient twofold elevations in all hippocampal neuron populations at 6-h recirculation, followed by a return to control levels by 24 h. MAP2b hybridization was progressively lost thereafter from the vulnerable CA1 and outer cortical layers, preceding both the fall in immunoreactive MAP2b and the eventual cell loss in these regions, The depletion of MAP2b mRNA coincided with an increase in the alternatively spliced MAP2c in vulnerable regions during 12-48 h of recirculation, precisely overlapping the late component of hsp72 expression that persisted in these cell populations. Previous studies have suggested that the initial induction of hsp72 provides an index of potential postischemic injury in neuron populations that may or may not be injured, while lasting hsp72 mRNA expression is associated with cell damage. In contrast, the present results demonstrate that MAP2c expression under these conditions occurs uniquely in neuron populations subject to injury. Available evidence suggests that MAP2c expression represents a plastic response in subpopulations of neurons that will survive in these regions, although it remains to be explicitly determined whether it may also be transiently expressed in dying cells. In any case, these observations demonstrate that reexpression of developmentally regulated MAP2c mRNA is a relatively late postischemic response in vulnerable cell populations, indicating that pathways regulating MAP2 splicing may be closely associated with mechanisms of neuron injury and/or recovery. C1 NIH, NINDS, STROKE BRANCH, BETHESDA, MD 20892 USA. NR 88 TC 12 Z9 12 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0271-678X EI 1559-7016 J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD MAR PY 1995 VL 15 IS 2 BP 205 EP 215 PG 11 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA QG023 UT WOS:A1995QG02300004 PM 7860654 ER PT J AU KAWAI, K PENIX, LP KAWAHARA, N RUETZLER, CA KLATZO, I AF KAWAI, K PENIX, LP KAWAHARA, N RUETZLER, CA KLATZO, I TI DEVELOPMENT OF SUSCEPTIBILITY TO AUDIOGENIC-SEIZURES FOLLOWING CARDIAC-ARREST CEREBRAL-ISCHEMIA IN RATS SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE CARDIAC ARREST CEREBRAL ISCHEMIA; AUDIOGENIC SEIZURES; INFERIOR COLLICULUS ID EPILEPSY-PRONE RAT; INFERIOR COLLICULUS; MODEL; PREDISPOSITION; DECREASE; DYNAMICS; NEURONS; DAMAGE; DRUGS; ACID AB Susceptibility to audiogenic seizures (AGS) was investigated in Sprague-Dawley rats subjected to cardiac arrest cerebral ischemia (CACI), produced by compression of the major cardiac vessels. The onset of AGS was regularly observed 1 day after CACI of >5 min duration, The duration of postischemic susceptibility to AGS was directly related to the density of cerebral ischemia, with 50% of more severely ischemic animals still showing AGS susceptibility 8 weeks after CACI, Lesioning of the inferior colliculi (IC) abolished the onset of AGS; no such effect was observed after lesioning the medial geniculate (MG). Glutamic acid decarboxylase (GAD) immunochemistry revealed similar to 50% loss of GAD-positive neurons in the IC, which was similar in animals with various durations of AGS susceptibility. Otherwise, there was a conspicuous sprouting of gamma-aminobutyric acid (GABA)-ergic terminals in the ventral thalamic nuclei, which peaked similar to 1 month after the CACI. Evaluation of GABA-A inhibitory function in the hippocampus by the paired pulse stimulation revealed changes indicating loss of GABA-A inhibition coinciding with the onset of AGS, acid its return in animals tested 2 months after CACI. Our observations suggest a potential role of GABA-ergic dysfunction in the postischemic development of AGS. C1 NIH,NINDS,STROKE BRANCH,BETHESDA,MD 20892. NR 29 TC 37 Z9 38 U1 0 U2 0 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 MAR PY 1995 VL 15 IS 2 BP 248 EP 258 PG 11 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA QG023 UT WOS:A1995QG02300009 PM 7860659 ER PT J AU MORESCO, RM CASATI, R LUCIGNANI, G CARPINELLI, A SCHMIDT, K TODDE, S COLOMBO, F FAZIO, F AF MORESCO, RM CASATI, R LUCIGNANI, G CARPINELLI, A SCHMIDT, K TODDE, S COLOMBO, F FAZIO, F TI SYSTEMIC AND CEREBRAL KINETICS OF 16-ALPHA[F-18]FLUORO-17-BETA-ESTRADIOL - A LIGAND FOR THE IN-VIVO ASSESSMENT OF ESTROGEN-RECEPTOR BINDING PARAMETERS SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE HORMONE RECEPTORS; BRAIN; ESTRADIOL; IMAGING AGENTS; PITUITARY; HYPOTHALAMUS ID TARGET TISSUES; HUMAN-BRAIN; STEROID-HORMONES; FEMALE RAT; PET; ESTRADIOL; CELLS; LOCALIZATION; METABOLISM; NEURONS AB Estrogen receptors are expressed in several brain areas of various animal species, and steroid hormones exert physiologic and biochemical effects on the central nervous system. The aim of the present study was to evaluate in female adult rats, the suitability of 16 alpha[F-18]fluoro-17 beta-estradiol ([F-18]FES), a selective estrogen receptor ligand, for the in vivo assessment of brain estrogen receptors, This was considered to be a preliminary step in evaluating the potential usefulness of [F-18]FES for studies of cerebral estrogen receptors with positron emission tomography (PET) in nonhuman primates and human subjects. We evaluated (a) the time course of the metabolic degradation of [F-18]FES in blood; Cbf the time course of distribution of the tracer in discrete cerebral areas; (c) the inhibitory effect of increasing doses of cold estradiol on cerebral [F-18]FES uptake; and (d) the possibility of in vivo quantification of estrogen receptor binding parameters using both equilibrium and dynamic kinetic analyses. We quantified [F-18]FES binding to estrogen receptors using both equilibrium and dynamic kinetic analyses. The results of this study indicate that [F-18]FES is a suitable tracer for the measurement of estrogen receptors in the pituitary and hypothalamus, using either the equilibrium or the kinetic analysis. However, [F-18]FES is inadequate for the in vivo investigation of estrogen binding sites in brain areas with low receptor density, such as the hippocampus. C1 UNIV MILAN,IST NEUROSCI & BIOIMMAGINI,DEPT NUCL MED,CNR,INST H SAN RAFFAELE,MILAN,ITALY. UNIV MILAN,IST NEUROSCI & BIOIMMAGINI,DEPT MED CHEM & BIOCHEM,CNR,INST H SAN RAFFAELE,MILAN,ITALY. US DEPT HLTH & HUMAN SERV,PUBL HLTH SERV,NIMH,CEREBRAL METAB LAB,BETHESDA,MD. RI Lucignani, Giovanni/C-6773-2008 NR 44 TC 10 Z9 10 U1 1 U2 2 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 MAR PY 1995 VL 15 IS 2 BP 301 EP 311 PG 11 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA QG023 UT WOS:A1995QG02300013 PM 7860663 ER PT J AU PEKAR, J SINNWELL, T LIGETI, L CHESNICK, AS FRANK, JA MCLAUGHLIN, AC AF PEKAR, J SINNWELL, T LIGETI, L CHESNICK, AS FRANK, JA MCLAUGHLIN, AC TI SIMULTANEOUS MEASUREMENT OF CEREBRAL OXYGEN-CONSUMPTION AND BLOOD-FLOW USING O-17 AND F-19 MAGNETIC-RESONANCE-IMAGING SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE CEREBRAL BLOOD FLOW; CEREBRAL METABOLIC RATE FOR OXYGEN; F-19; NUCLEAR MAGNETIC RESONANCE IMAGING; O-17; TRACER KINETICS ID CONTINUOUS INHALATION; GLUCOSE-UTILIZATION; CAT BRAIN; NMR; SPECTROSCOPY; METABOLISM; ISCHEMIA; RECOVERY; INFARCTS; H-1 AB O-17 and F-19 magnetic resonance (MR) imaging were used to determine simultaneously the concentrations of (H2O)-O-17 and CHF3 in 0.8-cc voxels in the cat brain during inhalation of a gas mixture containing both O-17(2) and CHF3. The arterial time course of CHF3 was determined by ''on-line'' mass spectrometer detection of expired CHF3, and the arterial time course of (H2O)-O-17 was determined by O-17 MR analysis of arterial samples withdrawn during the inhalation period. The brain data and the arterial data for the two tracers were combined to calculate the cerebral oxygen consumption (CMRO(2)) and the CBF. The protocol was repeated on seven cats, using pentobarbital anesthesia. The average values of CMRO(2) and CBF for a 0.8-cc voxel in the parietal cortex were 1.5 +/- 0.5 mmol kg(-1) min(-1) and 38 +/- 15 ml 100 g(-1) min(-1), respectively. In individual animals the average uncertainty in CMRO, and CBF, calculated from Monte Carlo approaches, was +/-9%. C1 NIAAA, MEMBRANE BIOCHEM & BIOPHYS LAB, BETHESDA, MD 20892 USA. OIR, DIAGNOST RADIOL RES LAB, BETHESDA, MD 20892 USA. NHLBI, CARDIAC ENERGET LAB, BETHESDA, MD 20892 USA. NIMH, CLIN BRAIN DISORDERS BRANCH, BETHESDA, MD 20892 USA. SEMMELWEIS UNIV MED, H-1085 BUDAPEST, HUNGARY. NR 30 TC 26 Z9 27 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0271-678X EI 1559-7016 J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD MAR PY 1995 VL 15 IS 2 BP 312 EP 320 PG 9 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA QG023 UT WOS:A1995QG02300014 PM 7860664 ER PT J AU PETTIGREW, K ORZI, F SCHMIDT, K SOKOLOFF, L AF PETTIGREW, K ORZI, F SCHMIDT, K SOKOLOFF, L TI EFFECT OF HYPERGLYCEMIA ON RCMR(GLC) IN RATS - REPLY SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Letter C1 UNIV ROMA LA SAPIENZA,DIPARTIMENTO SCI NEUROL,NEUROL CLIN,I-00185 ROME,ITALY. NIMH,CEREBRAL METAB LAB,BETHESDA,MD 20892. RP PETTIGREW, K (reprint author), NIMH,DIV EPIDEMIOL & SERV RES,BETHESDA,MD 20892, USA. NR 3 TC 0 Z9 0 U1 0 U2 0 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 MAR PY 1995 VL 15 IS 2 BP 350 EP 351 PG 2 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA QG023 UT WOS:A1995QG02300020 ER PT J AU JAFFE, K BLUM, MS FALES, HM MASON, RT CABRERA, A AF JAFFE, K BLUM, MS FALES, HM MASON, RT CABRERA, A TI ON INSECT ATTRACTANTS FROM PITCHER PLANTS OF THE GENUS HELIAMPHORA (SARRACENIACEAE) SO JOURNAL OF CHEMICAL ECOLOGY LA English DT Article DE HELIAMPHORA; CARNIVOROUS PLANTS; PITCHER PLANTS; SARRACENIN; INSECT ATTRACTANTS AB Examination of Heliamphora heterodoxa and H. tatei from the Guayana Highlands of Venezuela reveals that the enol diacetal monoterpene, sarracenin, is the major volatile compound present in the spoon-shaped structures of leaves of the pitchers. In addition, erucamide, phenol, cinerone, phenylacetaldehyde, and a series of methyl esters also occur in extracts of the spoon-shaped appendages of pitchers at the time during which they attract insects. C1 UNIV GEORGIA,DEPT ENTOMOL,ATHENS,GA 30602. NHLBI,PHYS CHEM LAB,BETHESDA,MD 20892. OREGON STATE UNIV,DEPT ZOOL,CORVALLIS,OR 97331. RP JAFFE, K (reprint author), UNIV SIMON BOLIVAR,DPTO BIOL ORGANISMOS,APARTADO 89000,CARACAS 1080,VENEZUELA. NR 14 TC 15 Z9 17 U1 2 U2 15 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0098-0331 J9 J CHEM ECOL JI J. Chem. Ecol. PD MAR PY 1995 VL 21 IS 3 BP 379 EP 384 DI 10.1007/BF02036725 PG 6 WC Biochemistry & Molecular Biology; Ecology SC Biochemistry & Molecular Biology; Environmental Sciences & Ecology GA QQ926 UT WOS:A1995QQ92600010 PM 24234068 ER PT J AU LEE, H DARDEN, TA PEDERSEN, LG AF LEE, H DARDEN, TA PEDERSEN, LG TI MOLECULAR-DYNAMICS SIMULATION STUDIES OF A HIGH-RESOLUTION Z-DNA CRYSTAL SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article ID HANDED Z-DNA; ATOMIC RESOLUTION; DOUBLE HELIX; FORCE-FIELD; COUNTERIONS; WATER; EWALD; RING C1 UNIV N CAROLINA,DEPT CHEM,CHAPEL HILL,NC 27599. RP LEE, H (reprint author), NIEHS,QUANTITAT & COMPUTAT BIOL LAB,POB 12233,RES TRIANGLE PK,NC 27709, USA. RI Pedersen, Lee/E-3405-2013 OI Pedersen, Lee/0000-0003-1262-9861 NR 33 TC 40 Z9 40 U1 0 U2 5 PU AMER INST PHYSICS PI WOODBURY PA CIRCULATION FULFILLMENT DIV, 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2999 SN 0021-9606 J9 J CHEM PHYS JI J. Chem. Phys. PD MAR 1 PY 1995 VL 102 IS 9 BP 3830 EP 3834 DI 10.1063/1.468564 PG 5 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA QH968 UT WOS:A1995QH96800034 ER PT J AU VITIELLO, B JENSEN, PS AF VITIELLO, B JENSEN, PS TI PSYCHOPHARMACOLOGY IN CHILDREN AND ADOLESCENTS - CURRENT PROBLEMS, FUTURE-PROSPECTS - SUMMARY NOTES ON THE 1995 NIMH-FDA CONFERENCE SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Editorial Material RP VITIELLO, B (reprint author), NIMH,CHILD & ADOLESCENT DISORDERS RES BRANCH,PEDIAT PSYCHOPHARMACOL PROGRAM,5600 FISHERS LANE,ROCKVILLE,MD 20857, USA. NR 0 TC 9 Z9 9 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1044-5463 J9 J CHILD ADOL PSYCHOP JI J. Child Adolesc. Psychopharmacol. PD SPR PY 1995 VL 5 IS 1 BP 5 EP 7 DI 10.1089/cap.1995.5.5 PG 3 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA QZ008 UT WOS:A1995QZ00800002 ER PT J AU ARAI, K TSIGOS, C SUZUKI, Y LISTWAK, S ZACHMAN, K ZANGENEH, F RAPAPORT, R CHANOINE, JP CHROUSOS, GP AF ARAI, K TSIGOS, C SUZUKI, Y LISTWAK, S ZACHMAN, K ZANGENEH, F RAPAPORT, R CHANOINE, JP CHROUSOS, GP TI NO APPARENT MINERALOCORTICOID RECEPTOR DEFECT IN A SERIES OF SPORADIC CASES OF PSEUDOHYPOALDOSTERONISM SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID GLUCOCORTICOID RESISTANCE; INHERITANCE; GENE; DEFICIENCY; UNRESPONSIVENESS; LYMPHOCYTES; EXPRESSION; FAMILIES; FORMS AB Pseudohypoaldosteronism (PHA) is characterized by congenital resistance of the kidney and/or other mineralocorticoid target tissues to aldosterone, resulting in excessive salt wasting. Although the mineralocorticoid receptor (MR) was suggested as a potential locus of the defect in this disease, no such abnormality was found in 3 recently reported cases, one of whom belongs to this series of 5 patients. Molecular studies of the MR complementary DNA and gene in this series of sporadic cases of pseudohypoaldosteronism are reported. Four of these patients had multiple mineralocorticoid target tissue resistance, whereas 1 had transient isolated resistance in the kidney. A nonconservative homozygous mutation (C-944-->T-944, Ala(241)-->Val(241)) was identified in the complementary DNA of 4 of the patients but was also found in 62 of 100 normal alleles. One of these 4 patients had an additional conservative heterozygous mutation (A(760)-->G(760), Ileu(180)-->Val(180), which was also present in 11 of 100 normal alleles. None of the patients had any abnormalities in the first untranslated exon and 0.9 kilobases of the 5'-regulatory region of the MR gene, which were fully sequenced and compared with the normal sequence. It is concluded that the mutations identified in 4 of these 5 patients with PHA are polymorphisms, which on their own have no apparent pathophysiological significance. It is hypothesized that the defect causing PHA might be in a post-MR step of aldosterone action or in an unsuspected nonclassic receptor for this hormone. C1 NIDDKD, DIABET BRANCH, BETHESDA, MD 20892 USA. NIMH, CLIN NEUROENDOCRINOL BRANCH, BETHESDA, MD 20892 USA. W VIRGINIA UNIV, ROBERT C BYRD HLTH SCI CTR, DEPT PEDIAT, CHARLESTON, WV 25302 USA. CHILDRENS HOSP NEW JERSEY, DEPT PEDIAT, NEWARK, NJ 07107 USA. HOP UNIV DES ENFANTS REINE FABIOLA, B-1020 BRUSSELS, BELGIUM. RP ARAI, K (reprint author), NICHHD, DEV ENDOCRINOL BRANCH, BLDG 10, ROOM 10N262, 9000 ROCKVILLE PIKE, BETHESDA, MD 20892 USA. NR 40 TC 36 Z9 36 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 MAR PY 1995 VL 80 IS 3 BP 814 EP 817 DI 10.1210/jc.80.3.814 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA QM008 UT WOS:A1995QM00800020 PM 7883835 ER PT J AU ANASTI, JN FLACK, MR FROEHLICH, J NELSON, LM AF ANASTI, JN FLACK, MR FROEHLICH, J NELSON, LM TI THE USE OF HUMAN RECOMBINANT GONADOTROPIN RECEPTORS TO SEARCH FOR IMMUNOGLOBULIN G-MEDIATED PREMATURE OVARIAN FAILURE SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID STIMULATING-HORMONE RECEPTOR; CHORIONIC-GONADOTROPIN; BINDING; ANTIBODIES; EXPRESSION; RADIOIMMUNOASSAY AB Anti-FSH receptor antibodies, detected using animal systems, have been reported in a few patients with premature ovarian failure (POF). However, assays based on animal receptors may be inappropriate for detecting inhibiting antibodies in humans. Accordingly, we tested for interfering antibodies in patients with POF using a recombinant system expressing human (h) FSH and LH receptors. A mouse adrenal cell Line transfected with the hFSH receptor (Y1-hFSHR) exhibits a dose-dependent increase in progesterone when exposed to hFSH. An embryonal kidney cell Line transfected with the hLH receptor gene (hLHR-293) exhibits a dose-dependent increase in cAMP when exposed to hLH. We isolated immunoglobulins G (IgG) from 38 patients with POF and 14 normal women. We stimulated Y1-hFSHR and hLHR-293 cells with hFSH or hLH in the presence of these IgG and determined the resulting progesterone or cAMP response. The progesterone and cAMP responses obtained in the presence of IgG from patients with POF did not differ significantly from the responses in the presence of IgG from normal women. In contrast, antigonadotropin polyclonal antibodies isolated in the same manner as the above IgGs caused a greater than 90% reduction in the response of the Y1-hFSHR and hLHR-293 cells. We did not detect inhibitory antibodies in any of our 38 patients with POF. Therefore, if blocking antibodies interfering with gonadotropin-receptor interaction are a mechanism for POF, they account for a small minority of cases (<8%). RP ANASTI, JN (reprint author), NICHHD, DEV ENDOCRINOL BRANCH, GYNECOL RES SECT, BLDG 10, ROOM 10N-262, BETHESDA, MD 20892 USA. NR 25 TC 48 Z9 48 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 MAR PY 1995 VL 80 IS 3 BP 824 EP 828 DI 10.1210/jc.80.3.824 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA QM008 UT WOS:A1995QM00800022 PM 7883837 ER PT J AU LATRONICO, AC REINCKE, M MENDONCA, BB ARAI, K MORA, P ALLOLIO, B WAJCHENBERG, BL CHROUSOS, GP TSIGOS, C AF LATRONICO, AC REINCKE, M MENDONCA, BB ARAI, K MORA, P ALLOLIO, B WAJCHENBERG, BL CHROUSOS, GP TSIGOS, C TI NO EVIDENCE FOR ONCOGENIC MUTATIONS IN THE ADRENOCORTICOTROPIN RECEPTOR GENE IN HUMAN ADRENOCORTICAL NEOPLASMS SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID CONSTITUTIVELY ACTIVATING MUTATION; LUTEINIZING-HORMONE RECEPTOR; GLUCOCORTICOID DEFICIENCY; PRECOCIOUS PUBERTY; TUMORS AB The mechanism(s) of tumorigenesis for the majority of adrenocortical neoplasms remain unknown. G-Protein-coupled receptors were recently proposed as candidate protooncogenes. That activating mutations of this class of receptors might be important for tumor induction or progression of endocrine neoplasms was strengthened by the recent identification of such mutations in hyperfunctioning thyroid adenomas. To examine whether the ACTH receptor (ACTH-R) gene could be an oncogene in human adrenocortical tumors, we amplified by the polymerase chain reaction and directly sequenced the entire exon of the ACTH-R gene in 25 adrenocortical tumors (17 adenomas and 8 carcinomas) and 2 adrenocortical cancer cell lines. We found no missense point mutations or even silent polymorphisms in any of the tumors and cell Lines studied. We conclude that activating mutations of the ACTH-R gene do not represent a frequent mechanism of human adrenocortical tumorigenesis. C1 UNIV WURZBURG, MED KLIN, WURZBURG, GERMANY. UNIV SAO PAULO, HOSP CLIN, SCH MED, DIV ENDOCRINOL, SAO PAULO, BRAZIL. RP LATRONICO, AC (reprint author), NICHHD, DEV ENDOCRINOL BRANCH, BLDG 10, ROOM 10N262, 9000 ROCKVILLE PIKE, BETHESDA, MD 20892 USA. RI Mendonca, Berenice/C-2827-2012; OI Latronico Xavier, Ana Claudia/0000-0001-6782-693X NR 15 TC 84 Z9 86 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAR PY 1995 VL 80 IS 3 BP 875 EP 877 DI 10.1210/jc.80.3.875 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA QM008 UT WOS:A1995QM00800032 PM 7883845 ER PT J AU BROWN, SL SALIVE, ME GURALNIK, JM PAHOR, M CHAPMAN, DP BLAZER, D AF BROWN, SL SALIVE, ME GURALNIK, JM PAHOR, M CHAPMAN, DP BLAZER, D TI ANTIDEPRESSANT USE IN THE ELDERLY - ASSOCIATION WITH DEMOGRAPHIC CHARACTERISTICS, HEALTH-RELATED FACTORS, AND HEALTH-CARE UTILIZATION SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Article DE ANTIDEPRESSANT; MEDICATION; DEPRESSION; AGING; EPIDEMIOLOGY ID DEPRESSION; PREVALENCE; DISORDERS; SYMPTOMS; SITES; BLACK AB The characteristics of antidepressant use and its correlates were assessed in the four Established Populations for Epidemiologic Study of the Elderly (EPESE) communities (n = 13,074). Women were significantly more likely to be treated with an antidepressant drug than men, and African-Americans were significantly less likely than whites to be using antidepressant medication. Of the health-related measures, poor self-perceived health, polypharmacy, disabilities in activities of daily living, and a history of stroke were associated with the use of antidepressants. Each utilization of health care variable, (number of doctors visits, overnight hospitalization in the past year, and use of a regular doctor), was associated with antidepressant use in at least two of the four communities. After entering variables in a multivariate regression model, higher antidepressant use was significantly associated with female gender, race, poor self-perceived health, and a greater number of contacts with doctors in the past year. C1 UNIV CATTOLICA SACRO CUORE,CATTEDRA GERONTOL,ROME,ITALY. CTR DIS CONTROL,DIV CHRON DIS CONTROL & COMMUNITY INTERVENT,ATLANTA,GA 30333. DUKE UNIV,MED CTR,SCH MED,DURHAM,NC 27710. RP BROWN, SL (reprint author), NIA,EPIDEMIOL DEMOG & BIOMETRY PROGRAM,7201 WISCONSIN AVE,SUITE 3C309,BETHESDA,MD 20892, USA. NR 21 TC 46 Z9 46 U1 4 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0895-4356 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD MAR PY 1995 VL 48 IS 3 BP 445 EP 453 DI 10.1016/0895-4356(94)00188-V PG 9 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA QM991 UT WOS:A1995QM99100013 PM 7897465 ER PT J AU FENG, LL XIA, YY YOSHIMURA, T WILSON, CB AF FENG, LL XIA, YY YOSHIMURA, T WILSON, CB TI MODULATION OF NEUTROPHIL INFLUX IN GLOMERULONEPHRITIS IN THE RAT WITH ANTIMACROPHAGE INFLAMMATORY PROTEIN-2 (MIP-2) ANTIBODY SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE MACROPHAGE INFLAMMATORY PROTEIN-2; ANTIGLOMERULAR BASEMENT MEMBRANE GLOMERULONEPHRITIS; ANTIMACROPHAGE INFLAMMATORY PROTEIN-2 ANTIBODY; NEUTROPHILS; CHEMOKINE ID HUMAN MESANGIAL CELLS; INTERCELLULAR-ADHESION MOLECULE-1; MONOCYTE CHEMOATTRACTANT PROTEIN-1; BASEMENT-MEMBRANE ANTIBODY; LEUKOCYTE ADHESION; STIMULATING FACTOR; ENDOTHELIAL-CELLS; ICAM-1 EXPRESSION; MESSENGER-RNA; CDNA CLONING AB The role of the chemokine, macrophage inflammatory protein-2 (MIP-2), during anti-glomerular basement membrane (GBM) antibody (Ab) glomerulonephritis (GN) was studied. Rat MIP-2 cDNA had been cloned previously. Recombinant rat MIP-2 (rMIP-2) from Escherichia coli exhibited neutrophil chemotactic activity and produced neutrophil influx when injected into the rat bladder wall. By using a riboprobe derived from the cDNA and an anti-rMIP-2 polyclonal Ab, MIP-2 was found to be induced in glomeruli with anti-GBM Ab GN as mRNA by 30 min and protein by 4 h, with both disappearing by 24 h. The expression of MIP-2 correlated with glomerular neutrophil influx. A single dose of the anti-MIP-2 Ab 30 min before anti-GBM Ab was effective in reducing neutrophil influx (40% at 4 h, P < 0.01) and periodic acid-Schiff deposits containing fibrin (54% at 24 h, P < 0.01). The anti-rMIP-2 Ab had no effect on anti-GBM Ab binding (paired-label isotope study). Functional improvement in the glomerular damage was evidenced by a reduction of abnormal proteinuria (P < 0.05). These results suggest that MIP-2 is a major neutrophil chemoattractant contributing to influx of neutrophils in AB-induced glomerular inflammation in the rat. C1 Scripps Res Inst, DEPT IMMUNOL IMM5, LA JOLLA, CA 92037 USA. NCI, FREDERICK CANC RES & DEV CTR, IMMUNOL LAB, IMMUNOPATHOL SECT, FREDERICK, MD 21702 USA. FU NCRR NIH HHS [MO1 RR00833]; NIDDK NIH HHS [DK-20043, DK-42717] NR 78 TC 143 Z9 147 U1 0 U2 1 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAR PY 1995 VL 95 IS 3 BP 1009 EP 1017 DI 10.1172/JCI117745 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA QM012 UT WOS:A1995QM01200015 PM 7883948 ER PT J AU SCHMALSTIEG, FC LEONARD, WJ NOGUCHI, M BERG, M RUDLOFF, HE DENNEY, RM DAVE, SK BROOKS, EG GOLDMAN, AS AF SCHMALSTIEG, FC LEONARD, WJ NOGUCHI, M BERG, M RUDLOFF, HE DENNEY, RM DAVE, SK BROOKS, EG GOLDMAN, AS TI MISSENSE MUTATION IN EXON-7 OF THE COMMON GAMMA-CHAIN GENE CAUSES A MODERATE FORM OF X-LINKED COMBINED IMMUNODEFICIENCY SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE T LYMPHOCYTE; IMMUNODEFICIENCY; IL-2R; X CHROMOSOME; GENETICS ID CHROMOSOME INACTIVATION PATTERNS; B-CELLS; TYROSINE KINASE; IL-2 RECEPTOR; AGAMMAGLOBULINEMIA; REPEAT; LOCI; POLYMORPHISMS; EXPRESSION; CARRIERS AB Clinical and immunologic features of a recently recognized X-linked combined immunodeficiency disease (XCID) suggested that XCID and X-linked severe combined immunodeficiency (XSCID) might arise from different genetic defects. The recent discovery of mutations in the common gamma chain (gamma(c)) gene, a constituent of several cytokine receptors, in XSCID provided an opportunity to test directly whether a previously unrecognized mutation in this same gene was responsible for XCID. The status of X chromosome inactivation in blood leukocytes from obligate carriers of XCID was determined from the polymorphic, short tandem repeats (GAG), in the androgen receptor gene, which also contains a methylation-sensitive HpaII site. As in XSCID, X-chromosome inactivation in obligate carriers of XCID was nonrandom in T and B lymphocytes. In addition, X chromosome inactivation in PMNs was variable. Findings from this analysis prompted sequencing of the gamma(c) gene in this pedigree. A missense mutation in the region coding for the cytoplasmic portion of the gamma(c) gene was found in three affected males but not in a normal brother. Therefore, this point mutation in the gamma(c) gene leads to a less severe degree of deficiency in cellular and humoral immunity than that seen in XSCID. C1 UNIV TEXAS,MED BRANCH,DEPT HUMAN BIOL CHEM & GENET,GALVESTON,TX 77555. UNIV TEXAS,MED BRANCH,DEPT MICROBIOL & IMMUNOL,GALVESTON,TX 77555. NHLBI,MOLEC IMMUNOL LAB,BETHESDA,MD 20892. RP SCHMALSTIEG, FC (reprint author), UNIV TEXAS,MED BRANCH,CHILDRENS HOSP,DEPT PEDIAT,DIV IMMUNOL ALLERGY,ROOM C-236,GALVESTON,TX 77555, USA. NR 33 TC 59 Z9 60 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAR PY 1995 VL 95 IS 3 BP 1169 EP 1173 DI 10.1172/JCI117765 PG 5 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA QM012 UT WOS:A1995QM01200035 PM 7883965 ER PT J AU CIZZA, G PACAK, K KVETNANSKY, R PALKOVITS, M GOLDSTEIN, DS BRADY, LS FUKUHARA, K BERGAMINI, E KOPIN, IJ BLACKMAN, MR CHROUSOS, GP GOLD, PW AF CIZZA, G PACAK, K KVETNANSKY, R PALKOVITS, M GOLDSTEIN, DS BRADY, LS FUKUHARA, K BERGAMINI, E KOPIN, IJ BLACKMAN, MR CHROUSOS, GP GOLD, PW TI DECREASED STRESS RESPONSIVITY OF CENTRAL AND PERIPHERAL CATECHOLAMINERGIC SYSTEMS IN AGED 344/N FISCHER RATS SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE MICRODIALYSIS; PVN; LOCUS CERULEUS; TYROSINE HYDROXYLASE; CATECHOLAMINE-METABOLITES ID CORTICOTROPIN-RELEASING HORMONE; HYPOTHALAMIC PARAVENTRICULAR NUCLEUS; HYDROXYLASE MESSENGER-RNA; TYROSINE-HYDROXYLASE; LOCUS COERULEUS; IMMOBILIZATION STRESS; PLASMA-LEVELS; INCREASES; NEURONS; NOREPINEPHRINE AB We investigated the effects of stress on central and peripheral sympatho-adrenal and sympatho-neural functions in healthy, intact young (3-4 mo) and aged (24 mo) male Fischer 344/N rats. Extracellular fluid (ECF) levels of the catecholamines norepinephrine (NE), dihydroxyphenylglycol (DHPG), methoxyhydroxyphenylglycol (MHPG), and dihydroxyphenylacetic acid (DOPAC) were obtained by microdialysis in the paraventricular nucleus (PVN) of the hypothalamus at baseline and during immobilization (IMMO). The baseline levels of these substances were similar in both age groups, and their concentrations increased significantly in response to IMMO. The IMMO-induced increases of NE and MHPG, however, were significantly smaller in old than in young rats. Plasma levels of the catecholamines NE, DHPG, MHPG, DOPAC, dihydroxyphenylalanine (DOPA), epinephrine (EPI), dopamine (DA), and HVA were also determined in young and old rats during IMMO. Basal levels of these substances were significantly higher in old than in young rats. The magnitude of the IMMO-induced increases in the majority of these compounds however, was significantly smaller in old than in young rats. We conclude that, at the basal state, aging in the Fischer rat is associated with normal PVN ECF, but high plasma catecholamine levels; at stress state, however, old rats have substantially lesser activation of their central and peripheral catecholaminergic systems than young rats. C1 NINCDS,CLIN NEUROSCI BRANCH,BETHESDA,MD 20892. NIMH,CELL BIOL LAB,BETHESDA,MD 20892. INST EXPTL ENDOCRINOL,BRATISLAVA,SLOVAKIA. NICHHD,DEV ENDOCRINOL BRANCH,BALTIMORE,MD 21224. FRANCIS SCOTT KEY MED CTR,DEPT MED,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,SCH MED,DEPT MED,BALTIMORE,MD 21224. UNIV PISA,IST PATOL GEN,I-56100 PISA,ITALY. RP CIZZA, G (reprint author), NIMH,CLIN NEUROENDOCRINOL BRANCH,BLDG 10,RM 3S-225,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Palkovits, Miklos/F-2707-2013; OI Palkovits, Miklos/0000-0003-0578-0387 NR 47 TC 40 Z9 40 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAR PY 1995 VL 95 IS 3 BP 1217 EP 1224 DI 10.1172/JCI117771 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA QM012 UT WOS:A1995QM01200041 PM 7883970 ER PT J AU BAIER, LJ SACCHETTINI, JC KNOWLER, WC EADS, J PAOLISSO, G TATARANNI, PA MOCHIZUKI, H BENNETT, PH BOGARDUS, C PROCHAZKA, M AF BAIER, LJ SACCHETTINI, JC KNOWLER, WC EADS, J PAOLISSO, G TATARANNI, PA MOCHIZUKI, H BENNETT, PH BOGARDUS, C PROCHAZKA, M TI AN AMINO-ACID SUBSTITUTION IN THE HUMAN INTESTINAL FATTY-ACID-BINDING PROTEIN IS ASSOCIATED WITH INCREASED FATTY-ACID-BINDING, INCREASED FAT OXIDATION, AND INSULIN-RESISTANCE SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE INSULIN RESISTANCE; FATTY ACID BINDING PROTEIN; NON-INSULIN-DEPENDENT DIABETES MELLITUS; FAT OXIDATION; GENETIC POLYMORPHISM ID PIMA-INDIANS; DIABETES-MELLITUS; GLUCOSE DISPOSAL; CARBOHYDRATE-METABOLISM; EXPRESSION; GLYCEMIA; LINKAGE; MUSCLE AB The intestinal fatty acid binding protein locus (FABP2) was investigated as a possible genetic factor in determining insulin action in the Pima Indian population. A polymorphism at codon 54 of FABP2 was identified that results in an alanine-encoding allele (frequency 0.71) and a threonine-encoding allele (frequency 0.29). Pimas who were homozygous or heterozygous for the threonine-encoding allele were found to have a higher mean fasting plasma insulin concentration, a lower mean insulin-stimulated glucose uptake rate, a higher mean insulin response to oral glucose and a mixed meal, and a higher mean fat oxidation rate compared with Pimas who were homozygous for the alanine-encoding allele. Since the FABP2 threonine-encoding allele was found to be associated with insulin resistance and increased fat oxidation in vivo, we further analyzed the FABP2 gene products for potential functional differences. Titration microcalorimetry studies with purified recombinant protein showed that the threonine-containing protein had a twofold greater affinity for long-chain fatty acids than the alanine-containing protein. We conclude that the threonine-containing protein may increase absorption and/or processing of dietary fatty acids by the intestine and thereby increase fat oxidation, which has been shown to reduce insulin action. C1 YESHIVA UNIV ALBERT EINSTEIN COLL MED,DEPT BIOCHEM,BRONX,NY 10461. RP BAIER, LJ (reprint author), NIDDKD,PHOENIX EPIDEMIOL & CLIN RES BRANCH,4212 N 16TH ST,PHOENIX,AZ 85016, USA. OI Paolisso, Giuseppe/0000-0002-2137-455X NR 28 TC 275 Z9 290 U1 0 U2 8 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAR PY 1995 VL 95 IS 3 BP 1281 EP 1287 DI 10.1172/JCI117778 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA QM012 UT WOS:A1995QM01200048 PM 7883976 ER PT J AU TAUB, DD PROOST, P MURPHY, WJ ANVER, M LONGO, DL VANDAMME, J OPPENHEIM, JJ AF TAUB, DD PROOST, P MURPHY, WJ ANVER, M LONGO, DL VANDAMME, J OPPENHEIM, JJ TI MONOCYTE CHEMOTACTIC PROTEIN-1 (MCP-1), PROTEIN-2, AND PROTEIN-3 ARE CHEMOTACTIC FOR HUMAN T-LYMPHOCYTES SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Note DE MCP-1; MCP-2; MCP-3; T LYMPHOCYTES; CHEMOKINES ID ACTIVATING FACTOR; CYTOKINE FAMILY; CHEMOKINES; CELLS; CHEMOATTRACTANT; MIP-1-ALPHA; MIP-1-BETA; CLONING; RANTES; CDNA AB Monocyte chemotactic protein (MCP)-1, -2, and -3 all have been shown to induce monocyte/macrophage migration in vitro and MCP-1, also known as MCAF, chemoattracts basophils and mast cells. We report here that natural MCP-1 as well as synthetic preparations of MCP-2 and MCP-3 stimulate significant in vitro chemotaxis of human peripheral blood T lymphocytes. This MCP-induced migration was dose-dependent and directional, but not chemokinetic. Phenotypic analysis of the T cell population responsive to MCP-1, MCP-2, and MCP-3 demonstrates that both CD4(+) and CD8(+) T cells migrated in response to these chemokines. Similar results were observed using human CD4(+) and CD8(+) T cell clones. Neutralizing antisera to MCAF or MCP-2 abrogated T cell migration in response to MCP-1 and MCP-2, respectively, but not to RANTES. Subcutaneous administration of purified MCP-1 into the hind flanks of SCID mice engrafted with human peripheral blood lymphocytes (PBL) induced significant human CD3(+) T cell infiltration into the site of injection at 4 h. These results demonstrate that MCP-1, MCP-2, and MCP-3 are inflammatory mediators that specifically stimulate the directional migration of T cells as well as monocytes and may play an important role in immune cell recruitment into sites of antigenic challenge. C1 NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,PATHOL HISTOTECHNOL LAB,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,MOLEC IMMUNOREGULAT LAB,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,OFF ASSOCIATE DIRECTOR,FREDERICK,MD 21702. UNIV LOUVAIN,REGA INST,MOLEC IMMUNOL LAB,LOUVAIN,BELGIUM. RP TAUB, DD (reprint author), NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,CLIN SERV PROGRAM,BLDG 560,RM 11-23,FREDERICK,MD 21702, USA. NR 24 TC 302 Z9 307 U1 1 U2 12 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAR PY 1995 VL 95 IS 3 BP 1370 EP 1376 DI 10.1172/JCI117788 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA QM012 UT WOS:A1995QM01200058 PM 7883984 ER PT J AU RADER, DJ MANN, WA CAIN, W KRAFT, HG USHER, D ZECH, LA HOEG, JM DAVIGNON, J LUPIEN, P GROSSMAN, M WILSON, JM BREWER, HB AF RADER, DJ MANN, WA CAIN, W KRAFT, HG USHER, D ZECH, LA HOEG, JM DAVIGNON, J LUPIEN, P GROSSMAN, M WILSON, JM BREWER, HB TI THE LOW-DENSITY-LIPOPROTEIN RECEPTOR IS NOT REQUIRED FOR NORMAL CATABOLISM OF LP(A) IN HUMANS SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Note DE APOLIPOPROTEIN; ATHEROSCLEROSIS; KINETICS; CHOLESTEROL; HYPERCHOLESTEROLEMIA ID FAMILIAL HYPERCHOLESTEROLEMIA; APOLIPOPROTEIN-B; LDL-RECEPTOR; SERUM LIPOPROTEIN(A); HEART-DISEASE; PLASMA; LP; GENE; ATHEROSCLEROSIS; CHOLESTYRAMINE AB Lipoprotein(a) [Lp(a)] is an atherogenic lipoprotein which is similar in structure to low density lipoproteins (LDL). The role of the LDL receptor in the catabolism of Lp(a) has been controversial. We therefore investigated the in vivo catabolism of Lp(a) and LDL in five unrelated patients with homozygous familial hypercholesterolemia (FH) who have little or no LDL receptor activity. Purified I-125-Lp(a) and I-131-LDL were simultaneously injected into the homozygous FH patients, their heterozygous FH parents when available, and control subjects. The disappearance of plasma radioactivity was followed over time. As expected, the fractional catabolic rates(FCR) of I-131-LDL were markedly decreased in the homozygous FH patients (mean LDL FCR 0.190 d(-1)) and somewhat decreased in the heterozygous FH parents (mean LDL FCR 0.294 d(-1)) compared with controls(mean LDL FCR 0.401 d(-1)). In contrast, the catabolism of I-125- Lp(a) was not significantly different in the homozygous FH patients (mean FCR 0.251 d(-1)), heterozygous FH parents (mean FCR 0.254 d(-1)), and control subjects (mean FCR 0.287 d(-1)). In summary, absence of a functional LDL receptor does not result in delayed catabolism of Lp(a), indicating that the LDL receptor is not a physiologically important route of Lp(a) catabolism in humans. C1 NHLBI,MOLEC DIS BRANCH,BETHESDA,MD 20892. UNIV DELAWARE,SCH LIFE & HLTH SCI,NEWARK,DE 19716. CLIN RES INST MONTREAL,DEPT LIPID METAB & ATHEROSCLEROSIS RES,MONTREAL,PQ H2W 1R7,CANADA. HOSP UNIV ST FOY,ST FOY,PQ,CANADA. RP RADER, DJ (reprint author), UNIV PENN,MED CTR,INST HUMAN GENE THERAPY,BRB-1,ROOM 409,422 CURIE BLVD,PHILADELPHIA,PA 19104, USA. RI Wilson, James/F-9220-2011 OI Wilson, James/0000-0002-9630-3131 NR 38 TC 128 Z9 131 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAR PY 1995 VL 95 IS 3 BP 1403 EP 1408 DI 10.1172/JCI117794 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA QM012 UT WOS:A1995QM01200064 PM 7883987 ER PT J AU LANKFORD, EB EPSTEIN, ND FANANAPAZIR, L SWEENEY, HL AF LANKFORD, EB EPSTEIN, ND FANANAPAZIR, L SWEENEY, HL TI ABNORMAL CONTRACTILE PROPERTIES OF MUSCLE-FIBERS EXPRESSING BETA-MYOSIN HEAVY-CHAIN GENE-MUTATIONS IN PATIENTS WITH HYPERTROPHIC CARDIOMYOPATHY SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Note DE CARDIOMYOPATHY, HYPERTROPHIC; MYOSIN, GENETICS; MUTATION, GENETICS; MUSCLE CONTRACTION; MYOCARDIAL CONTRACTION ID SKINNED RABBIT PSOAS; SKELETAL-MUSCLE; MISSENSE MUTATIONS AB Missense mutations in the beta-myosin heavy chain (beta-MHC) gene cause hypertrophic cardiomyopathy (HCM). As normal and mutant beta-MHCs are expressed in slow-twitch skeletal muscle of HCM patients, we compared the contractile properties of single slow-twitch muscle fibers from patients with three distinct beta-MHC gene mutations and normal controls. Fibers with the 741(Gly-->Arg) mutation (near the binding site of essential light chain) demonstrated decreased maximum velocity of shortening (39% of normal) and decreased isometric force generation (42% of normal). Fibers with the 403(Arg-->Gln) mutation (at the actin interface of myosin) showed lowered force/stiffness ratio (56% of normal) and depressed velocity of shortening (50% of normal). Both the 741(Gly-->Arg) and 403(Arg-->Gln) mutation-containing fibers displayed abnormal force-velocity relationships and reduced power output. Fibers with the 256(Gly-->Glu) mutation (end of ATP-binding pocket) had contractile properties that were indistinguishable from normal. Thus there is variability in the nature and extent of functional impairments in skeletal fibers containing different beta-MHC gene mutations, which may correlate with the severity and penetrance of the disease that results from each mutation. These functional alterations likely constitute the primary stimulus for the cardiac hypertrophy that is characteristic of this disease. C1 UNIV PENN,SCH MED,DEPT PHYSIOL,PHILADELPHIA,PA 19104. HOSP UNIV PENN,CARDIOVASC SECT,PHILADELPHIA,PA 19104. NHLBI,INHERITED CARDIAC DIS SECT,BETHESDA,MD 20892. RI Sweeney, H Lee/F-1862-2010 FU NHLBI NIH HHS [HL-15835] NR 32 TC 137 Z9 140 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAR PY 1995 VL 95 IS 3 BP 1409 EP 1414 DI 10.1172/JCI117795 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA QM012 UT WOS:A1995QM01200065 PM 7883988 ER PT J AU SCHIFFMAN, MH KIVIAT, NB BURK, RD SHAH, KV DANIEL, RW LEWIS, R KUYPERS, J MANOS, MM SCOTT, DR SHERMAN, ME KURMAN, RJ STOLER, MH GLASS, AG RUSH, BB MIELZYNSKA, I LORINCZ, AT AF SCHIFFMAN, MH KIVIAT, NB BURK, RD SHAH, KV DANIEL, RW LEWIS, R KUYPERS, J MANOS, MM SCOTT, DR SHERMAN, ME KURMAN, RJ STOLER, MH GLASS, AG RUSH, BB MIELZYNSKA, I LORINCZ, AT TI ACCURACY AND INTERLABORATORY RELIABILITY OF HUMAN PAPILLOMAVIRUS DNA TESTING BY HYBRID CAPTURE SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID CERVICAL INTRAEPITHELIAL NEOPLASIA; INFECTION; HYBRIDIZATION; DIAGNOSIS; TYPE-16; CANCER; COHORT; ASSAY; GRADE; WOMEN AB Epidemiologists and clinicians wishing to introduce human papillomavirus (HPV) testing into cervical cancer prevention programs need standardized, reliable, and accurate HPV DNA tests that can detect the full spectrum of pathogenic HPV types. The Hybrid Capture System assay from Digene (hybrid capture assay) is a nonradioactive kit designed to detect 14 HPV types in two groups: a mix of 9 high-risk types associated with anogenital cancer (HPV types 16, 18, 31, 33, 35, 45, 51, 52, and 56) and another group of 5 low-risk types associated with condyloma acuminatum (HPV types 6, 11, 42, 43, and 44). The assay yields quantitative data meant to reflect viral concentration. In a study of 199 cervical specimens from women with concurrent Pap smears, we assessed the reliability of the new assay by comparing the hybrid capture assay results from three laboratories. We assessed the accuracy of the hybrid capture assay in comparison with a reference standard of HPV DNA content (multiple testing by several methods in two reference laboratories). We also compared the hybrid capture assay results with the concurrent cytologic diagnoses on the basis of an independent review of each smear by five pathologists. Pairwise interlaboratory agreement rates on HPV positivity for either high-risk or low-risk types ranged from 87 to 94%, and kappa values ranged from 0.61 to 0.83. Among specimens positive for high-risk types (the most important clinical outcome), the interlaboratory correlations of the quantitative data ranged from 0.60 to 0.90. Test results from all three laboratories were strongly associated with those of the HPV DNA reference standard and with the concurrent cytopathologic diagnoses. The most common errors were sporadic, apparently false-positive results. C1 UNIV WASHINGTON,SEATTLE,WA 98195. YESHIVA UNIV ALBERT EINSTEIN COLL MED,BRONX,NY 10461. JOHNS HOPKINS MED INST,BALTIMORE,MD 21205. PORTLAND KAISER PERMANENTE,PORTLAND,OR. CLEVELAND CLIN,CLEVELAND,OH 44106. DIGENE DIAGNOST INC,SILVER SPRING,MD. RP SCHIFFMAN, MH (reprint author), NCI,EPIDEMIOL & BIOSTAT PROGRAM,EXECUT PLAZA N ROOM 443,BETHESDA,MD 20892, USA. NR 24 TC 102 Z9 106 U1 0 U2 1 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 MAR PY 1995 VL 33 IS 3 BP 545 EP 550 PG 6 WC Microbiology SC Microbiology GA QG830 UT WOS:A1995QG83000007 PM 7751355 ER PT J AU FYFE, G FISHER, RI ROSENBERG, SA SZNOL, M PARKINSON, DR LOUIE, AC AF FYFE, G FISHER, RI ROSENBERG, SA SZNOL, M PARKINSON, DR LOUIE, AC TI RESULTS OF TREATMENT OF 255 PATIENTS WITH METASTATIC RENAL-CELL CARCINOMA WHO RECEIVED HIGH-DOSE RECOMBINANT INTERLEUKIN-2 THERAPY SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ACTIVATED KILLER-CELLS; PROSPECTIVE RANDOMIZED TRIAL; PROGNOSTIC FACTORS; NATURAL-HISTORY; PROPHYLACTIC ANTIBIOTICS; INTERFERON-ALPHA; ADVANCED CANCER; HYPOTHYROIDISM; IMMUNOTHERAPY; THYROIDITIS AB Purpose: To determine the efficacy and toxicity of a high-dose interleukin-2 (IL-2) regimen in patients with metastatic renal cell carcinoma. Patients and Methods: Two hundred fifty-five assessable patients were entered onto seven phase II clinical trials. Proleukin (aldesleukin; Chiron Corp, Emeryville, CA) 600,000 or 720,000 IU/kg was administered by 15-minute intravenous (IV) infusion every 8 hours for up to 14 consecutive doses over 5 days as clinically tolerated with maximum support, including pressors. A second identical cycle of treatment was scheduled following 5 to 9 days of rest, and courses could be repeated every 6 to 12 weeks in stable or responding patients. Results: The overall objective response rate was 14% (90% confidence interval [CI], 10% to 19%), with 12 (5%) complete responses (CRs) and 24 (9%) partial responses (PRs). Responses occurred in all sites of disease, including bone, intact primary tumors, and visceral metastases, and in patients with large tumor burdens or bulky individual lesions. The median response duration for patients who achieved a CR has not been reached, but was 19.0 months for those who achieved a PR. Baseline Eastern Cooperative Oncology Group (ECOG) performance status (PS) was the only predictive prognostic factor for response to IL-2. While treatment was associated with severe acute toxicities, these generally reversed rapidly after therapy was completed. However, 4% of patients died of adverse events judged to be possibly or probably treatment-related. Conclusion: High-dose IL-2 appears to benefit some patients with metastatic renal cell carcinoma by producing durable CRs or PRs. Despite severe acute treatment-associated toxicities, IL-2 should be considered for initial therapy of patients with appropriately selected metastatic renal cell carcinoma. (C) 1995 by American Society of Clinical Oncology. C1 LOYOLA UNIV,MED CTR,CHICAGO,IL 60611. NCI,SURG BRANCH,BETHESDA,MD 20892. NCI,INVEST DRUG BRANCH,BETHESDA,MD 20892. PRO NEURON,ROCKVILLE,MD. RP FYFE, G (reprint author), CHIRON CORP,4560 HORTON ST,EMERYVILLE,CA 94608, USA. NR 38 TC 682 Z9 699 U1 1 U2 7 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR PY 1995 VL 13 IS 3 BP 688 EP 696 PG 9 WC Oncology SC Oncology GA QL034 UT WOS:A1995QL03400021 PM 7884429 ER PT J AU ROMANELLI, F VALENCA, M CONTE, D ISIDORI, A NEGROVILAR, A AF ROMANELLI, F VALENCA, M CONTE, D ISIDORI, A NEGROVILAR, A TI ARACHIDONIC-ACID AND ITS METABOLITES EFFECTS ON TESTOSTERONE PRODUCTION BY RAT LEYDIG-CELLS SO JOURNAL OF ENDOCRINOLOGICAL INVESTIGATION LA English DT Article DE ARACHIDONIC ACID; PROSTAGLANDINS; LEUKOTRIENES; HYDROXYEICOSATETRAENOIC ACIDS; TESTOSTERONE; LEYDIG CELLS ID PROTEIN-KINASE-C; STIMULATED STEROIDOGENESIS; LUTEINIZING-HORMONE; LIPOXYGENASE PRODUCTS; PROSTAGLANDIN-E; TESTIS; INVOLVEMENT; SECRETION; MECHANISM; INHIBITION AB Arachidonic acid (AA) seems to play an important role in testicular steroidogenesis, although controversial data exist in the literature. In the present study AA induced a dose related increase of testosterone (T) formation and, at the highest dose, stimulated the production of prostaglandin E(2) (PGE(2)), leukotrienes B-4 (LTB(4)) and C-4 (LTC(4)) by purified rat Leydig cells. The contemporary addition of the prostaglandin synthesis blocker, indomethacin (IND), and AA further increased T formation, decreased PGE(2) levels and did not modify LTB(4) and LTC(4) concentrations. The addition of a lipoxygenase inhibitor, nordihydroguaiaretic acid (NDGA, 5 mu M), did not influence the stimulatory effect of AA on T and PGE(2) formation while it decreased the output of LTB(4) and LTC(4). When 20 mu M NDGA was used in addition to AA the expected reduction of leukotrienes release was observed together with a surprising impairment of T and PGE(2) secretion. PGE(2) and PGF(2 alpha) did not modify basal T production but reduced HCG-stimulated T secretion at the 10nM dose. When 5-12-and 15-HETE were tested an enhancement of basal T formation was observed at the 10nM dose. 5-HETE (10nM) stimulated HCG-induced T production. LTA(4), LTB(4) and LTE(4) did not influence basal T output while LTC(4) and LTD(4) inhibited it. LTC(4) (10nM) induced a decrease of HCG-stimulated T production. These findings suggest that: 1) exogenous AA stimulates T secretion; 2) conversion of AA to cycloxygenated and lipoxygenated metabolites is not required for its steroidogenic effect; 3) cycloxygenated and lipoxygenated compounds play a diverse modulatory role on testicular steroidogenesis. C1 UNIV ROMA LA SAPIENZA,CATTEDRA ANDROL,ROME,ITALY. NIEHS,MOLEC & INTEGRAT NEUROSCI LAB,REPROD NEUROENDOCRINOL SECT,RES TRIANGLE PK,NC 27709. RP ROMANELLI, F (reprint author), UNIV ROMA LA SAPIENZA,POLICLIN UMBERTO 1,MED CLIN 5,CATTEDRA ANDROL,VIA POLICLIN,I-00161 ROME,ITALY. RI Romanelli, Francesco/A-7925-2012; Valenca, Marcelo/A-4302-2013 OI Valenca, Marcelo/0000-0003-0678-3782 NR 37 TC 46 Z9 47 U1 1 U2 6 PU EDITRICE KURTIS S R L PI MILANO PA VIA LUIGI ZOJA, 30-20153 MILANO, ITALY SN 0391-4097 J9 J ENDOCRINOL INVEST JI J. Endocrinol. Invest. PD MAR PY 1995 VL 18 IS 3 BP 186 EP 193 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA QV467 UT WOS:A1995QV46700003 PM 7615904 ER PT J AU NAKAJIMA, H PARK, HL HENKART, PA AF NAKAJIMA, H PARK, HL HENKART, PA TI SYNERGISTIC ROLES OF GRANZYME-A AND GRANZYME-B IN MEDIATING TARGET-CELL DEATH BY RAT BASOPHILIC LEUKEMIA MAST-CELL TUMORS ALSO EXPRESSING CYTOLYSIN PERFORIN SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID CYTOTOXIC LYMPHOCYTES-T; CYTO-TOXIC LYMPHOCYTES; SERINE PROTEASE; GENE CED-3; RESISTANCE; INDUCTION; APOPTOSIS; ANTIBODY; CLONING; DAMAGE AB We have studied the cytotoxic activity of rat basophilic leukemia (RBL) cells transfected with cDNAs for the cytotoxic T lymphocyte (CTL) granule components, cytolysin (perforin), granzyme A, and granzyme B. With red cell targets, cytolysin expression conferred potent hemolytic activity, which was not influenced by coexpression of granzymes. With tumor targets, RBL cells expressing cytolysin alone were weakly cytotoxic, but both cytolytic and nucleolytic activity were enhanced by coexpression of granzyme B. RBL cells expressing all three CTL granule components showed still higher cytotoxic activities, with apoptotic target death. Analysis of the cytotoxic activity of individual transfectant clones showed that cytolytic and nucleolytic activity correlated with granzyme expression but was independent of cytolysin expression within the range examined. A synergism between granzymes A and B was apparent when the triple transfectant was compared with RBL cells expressing cytolysin and one granzyme. These data implicate granzymes as the major mediators of tumor target damage by cytotoxic lymphocytes. C1 NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892. NR 31 TC 120 Z9 121 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD MAR 1 PY 1995 VL 181 IS 3 BP 1037 EP 1046 DI 10.1084/jem.181.3.1037 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA QH747 UT WOS:A1995QH74700020 PM 7869027 ER PT J AU REHERMANN, B FOWLER, P SIDNEY, J PERSON, J REDEKER, A BROWN, M MOSS, B SETTE, A CHISARI, FV AF REHERMANN, B FOWLER, P SIDNEY, J PERSON, J REDEKER, A BROWN, M MOSS, B SETTE, A CHISARI, FV TI THE CYTOTOXIC T-LYMPHOCYTE RESPONSE TO MULTIPLE HEPATITIS-B VIRUS POLYMERASE EPITOPES DURING AND AFTER ACUTE VIRAL-HEPATITIS SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID NUCLEOCAPSID ANTIGEN; BINDING PEPTIDES; EXPRESSION; PROTEIN; CELLS; RECOGNIZE; INFECTION AB Cytotoxic T lymphocytes (CTL) are thought to contribute to viral clearance and liver cell injury during hepatitis B virus (HBV) infection. Using a strategy involving the in vitro stimulation of peripheral blood mononuclear cells (PBMC) with HBV-derived synthetic peptides containing HLA-A2.1, -A31, and -Aw68 binding motifs, we have previously described CTL responses to several epitopes within the HBV nucleocapsid and envelope antigens in patients with acute hepatitis. In this study we define six HLA-A2-restricted CTL epitopes located in the highly conserved reverse transcriptase and RNase H domains of the viral polymerase protein, and we show that the CTL response to polymerase is polyclonal, multispecific, and mediated by CD8(+) T cells in patients with acute viral hepatitis, but that it is not detectable in patients with chronic HBV infection or uninfected healthy blood donors. Importantly, the peptide-activated CTL recognize target cells that express endogenously synthesized polymerase protein, suggesting that these peptides represent naturally processed viral epitopes. DNA sequence analysis of the viruses in patients who did not respond to peptide stimulation indicated that CTL nonresponsiveness was not due to infection by viral variants that differed in sequences from the synthetic peptides. CTL specific for one of the epitopes were unable to recognize several naturally occurring viral variants, except at high peptide concentration, underlining the HBV subtype specificity of this response. Furthermore, CTL responses against polymerase, core, and envelope epitopes were detectable for more than a year after complete clinical recovery and seroconversion, reflecting either the persistence of trace amounts of virus or the presence of long lived memory CTL in the absence of viral antigen. Finally, we demonstrated that wild type viral DNA and RNA can persist indefinitely, in trace quantities, in the serum and PBMC after complete clinical and serological recovery, despite a concomitant, vigorous, and sustained polyclonal CTL response. Since viral persistence is not due to escape from CTL recognition under these conditions, the data suggest that HBV may retreat into immunologically privileged sites from which it can seed the circulation and reach CTL-inaccessible tissues, thereby maintaining the CTL response in apparently cured individuals and, perhaps, prolonging the liver disease in patients with chronic hepatitis. C1 SCRIPPS RES INST, DEPT MOLEC & EXPTL MED, LA JOLLA, CA 92037 USA. CYTEL CORP, DEPT IMMUNOL, SAN DIEGO, CA 92121 USA. USN HOSP, DEPT GASTROENTEROL, SAN DIEGO, CA 92134 USA. UNIV SO CALIF, RANCHO LOS AMIGOS MED CTR, SCH MED, LIVER UNIT, DOWNEY, CA 90033 USA. NIAID, VIRAL DIS LAB, BETHESDA, MD 20892 USA. RI Chisari, Francis/A-3086-2008; OI Chisari, Francis/0000-0002-4832-1044 FU NCRR NIH HHS [RR-00833]; NIAID NIH HHS [AI-20001] NR 28 TC 351 Z9 367 U1 0 U2 6 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD MAR 1 PY 1995 VL 181 IS 3 BP 1047 EP 1058 DI 10.1084/jem.181.3.1047 PG 12 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA QH747 UT WOS:A1995QH74700021 PM 7532675 ER PT J AU MELAMED, I TURNER, CE AKTORIES, K KAPLAN, DR GELFAND, EW AF MELAMED, I TURNER, CE AKTORIES, K KAPLAN, DR GELFAND, EW TI NERVE GROWTH-FACTOR TRIGGERS MICROFILAMENT ASSEMBLY AND PAXILLIN PHOSPHORYLATION IN HUMAN B-LYMPHOCYTES SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID TYROSINE KINASE-ACTIVITY; TRK PROTOONCOGENE PRODUCT; SWISS 3T3 CELLS; FACTOR RECEPTORS; PC12 CELLS; EXTRACELLULAR-MATRIX; FOCAL ADHESIONS; PROTEIN; NGF; CYTOSKELETON AB Increasing evidence suggests that the nervous system is involved in allergic inflammation. One of the potential regulatory molecules of the neuroimmune system is nerve growth factor (NGF). Recent studies from our group demonstrated the presence of a functional NGF receptor (NGFR) on human B lymphocytes. Moreover, we showed that gp140(trk) tyrosine kinase, which serves as an NGFR, was involved in transduction of early signaling events in human B lymphocytes. The mechanisms by which NGF initiates the signaling cascade and the link between the neuroimmune systems are unknown. We have focused on the role of the cytoskeleton as a possible mediator for transduction of signals induced by NGE Polymerized actin (F-actin) content was determined by fluorescent staining and immunoblotting with antiactin antibody. Addition of NGF caused a time- and concentration-dependent increase in F-actin content, and maximum effects were noted after 1 min. These increases in F-actin content and NGF-induced thymidine incorporation could be blocked by incubating the cells with cytochalasin D and botulinum C-2 toxin before the addition of NGF. Incubation of human B lymphocytes with 10 nM K252a, an inhibitor of Trk kinase, decreased NGF-induced microfilament assembly by 75%. In immunoprecipitation experiments, addition of NGF to B cells induced a rapid increase in the tyrosine phosphorylation of paxillin, one of a group of focal adhesion proteins involved in linking actin filaments to the plasma membrane. Coimmunoprecipitation studies demonstrated the association between gp140(trk) kinase and paxillin. Together, these observations suggest that actin assembly is involved in NGF signaling in human B cells, and that paxillin may be essential in this pathway after phosphorylation by gp140(trk) kinase. C1 NATL JEWISH CTR IMMUNOL & RESP MED,DEPT PEDIAT,DIV BASIC SCI,DENVER,CO 80206. SUNY HLTH SCI CTR,DEPT ANAT & CELL BIOL,SYRACUSE,NY 13210. UNIV SAARLAND,INST PHARMAKOL & TOXIKOL,D-66421 HOMBURG,GERMANY. NCI,FREDERICK CANC RES & DEV CTR,EUKARYOT SIGNAL TRANSDUCT SECT,FREDERICK,MD 21702. FU NHLBI NIH HHS [P01-HL36577]; NIAID NIH HHS [R01-AI 29704]; NIGMS NIH HHS [GM47607] NR 38 TC 37 Z9 38 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD MAR 1 PY 1995 VL 181 IS 3 BP 1071 EP 1079 DI 10.1084/jem.181.3.1071 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA QH747 UT WOS:A1995QH74700023 PM 7869029 ER PT J AU HAMA, N PALIOGIANNI, F FESSLER, BJ BOUMPAS, DT AF HAMA, N PALIOGIANNI, F FESSLER, BJ BOUMPAS, DT TI CALCIUM/CALMODULIN-DEPENDENT PROTEIN-KINASE-II DOWN-REGULATES BOTH CALCINEURIN AND PROTEIN-KINASE C-MEDIATED PATHWAYS FOR CYTOKINE GENE-TRANSCRIPTION IN HUMAN T-CELLS SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Note ID INTERLEUKIN-2 GENE; PHORBOL ESTER; LYMPHOCYTES-T; ACTIVATION; ANERGY; GLUCOCORTICOIDS; IDENTIFICATION; INDUCTION; INVIVO; CLONES AB Engagement of the T cell receptor for antigen activates phospholipase C resulting in an increase in intracellular free calcium concentration ([Ca2+](i)) and activation of protein kinase C (PKC). Increased [Ca2+](i) activates Ca2+/calmodulin-dependent kinases including the multifunctional Ca2+/calmodulin-dependent protein kinase II (CaM-K II), as well as calcineurin, a type 2B protein phosphatase. Recent studies have identified calcineurin as a key enzyme for interleukin (IL)-2 and IL-4 promoter activation. However, the role of CaM-K II remains unknown. We have used mutants of these kinases and phosphatases (gamma(B)(*)CaM-K and Delta CaM-AI, respectively) to explore their relative role in cytokine gene transcription and their interactions with PKC-dependent signaling systems. gamma(B)(*)CaM-K and Delta CaM-AI, known to exhibit constitutive Ca2+-independent activity, were cotransfected (alone or in combination) in Jurkat T cells with a plasmid containing the intact IL-2 promoter driving the expression of the chloramphenicol acetyltransferase reporter gene. Cotransfection of gamma(B)(*)CaM-K with the IL-2 promoter construct downregulated its transcription in response to stimulation with ionomycin and phorbol myristate acetate (PMA). The inhibitory effect of CaM-K II on IL-2 promoter was associated with decreased transcription of its AP-1 and NF-AT transactivating pathways. Under the same conditions, Delta CaM-AI superinduced IL-2 promoter activity (approximately twofold increase). When both mutants were used in combination, gamma(B)(*)CaM-K inhibited the induction of the IL-2 promoter by Delta CaM-AI. Similar results were obtained when a construct containing the IL-4 promoter also was used. gamma(B)(*)CaM-K also downregulated the activation of AP-1 in response to transfection with a constitutively active mutant of PKC or stimulation with PMA. These results suggest that CaM-K II may exert negative influences on cytokine gene transcription in human T cells, and provide preliminary evidence for negative cross-talk with the calcineurin- and PKC-dependent signaling systems. RP HAMA, N (reprint author), NIDDKD,METAB DIS BRANCH,KIDNEY DIS SECT,BLDG 10,RM 3N112,BETHESDA,MD 20892, USA. NR 26 TC 34 Z9 35 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD MAR 1 PY 1995 VL 181 IS 3 BP 1217 EP 1222 DI 10.1084/jem.181.3.1217 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA QH747 UT WOS:A1995QH74700038 PM 7869038 ER PT J AU HENSON, JH CAPUANO, S NESBITT, D HAGER, DN NUNDY, S MILLER, DS BALLATORI, N BOYER, JL AF HENSON, JH CAPUANO, S NESBITT, D HAGER, DN NUNDY, S MILLER, DS BALLATORI, N BOYER, JL TI CYTOSKELETAL ORGANIZATION IN CLUSTERS OF ISOLATED POLARIZED SKATE HEPATOCYTES - STRUCTURAL AND FUNCTIONAL EVIDENCE FOR MICROTUBULE-DEPENDENT TRANSCYTOSIS SO JOURNAL OF EXPERIMENTAL ZOOLOGY LA English DT Article ID CANINE KIDNEY-CELLS; RAT HEPATOCYTES; CYTOPLASMIC DYNEIN; TAURINE TRANSPORT; IMMUNOGLOBULIN-A; CULTURED-CELLS; RAJA-ERINACEA; GAMMA-TUBULIN; PROTEINS; MEMBRANE AB Isolated hepatocytes from the marine vertebrate Raja erinacea (the little skate) retain their structural and functional integrity as clusters of cells formed around a single tubular bile canaliculus, and therefore can be used as a model of polarized hepatocytes in situ. In this study we used confocal and conventional epifluorescence microscopy in conjunction with fluorescent markers and immunocytochemistry to examine the structure and function of the cytoskeleton in these cells. Actin filaments in the hepatocyte clusters were found cortically and also concentrated in a pericanalicular array, while microtubules appeared to radiate away from a concentration near the apical membrane of the biliary pole towards the basolateral sinusoidal surfaces. Treatment of clusters with the microtubule disrupting agent, nocodazole, resulted in the microtubules depolymerizing from the basolateral surfaces towards the apical surface, indicating that the microtubules were oriented with their plus ends at the basolateral surface and their minus ends at the apical surface. Nocodazole was also found to disrupt the ability of clusters to transcytose a fluorescent bile salt derivative into their canalicular lumens. We detected cytoplasmic dynein in skate hepatocyte homogenates by Western blotting using an anti-dynein intermediate chain antibody, and immunofluorescent staining of intact hepatocytes revealed a punctate vesicular pattern. The polarized arrangement of microtubules, the presence of cytoplasmic dynein, and the inhibition of bile salt secretion by nocodozole are consistent with the microtubule cytoskeleton playing a fundamental role in the mediation of transcytosis, endocytosis, and bile excretory function in these hepatocytes. These polarized isolated skate hepatocytes represent an excellent experimental model for the in vitro study of hepatic transport, and allow for important comparative studies aimed at elucidating the evolutionarily conserved nature of various hepatocyte structures amongst the vertebrates. (C) 1995 Wiley-Liss, Inc. C1 YALE UNIV,SCH MED,DEPT MED,NEW HAVEN,CT 06510. YALE UNIV,SCH MED,CTR LIVER,NEW HAVEN,CT 06510. NIEHS,CELLULAR & MOLEC PHARMACOL LAB,RES TRIANGLE PK,NC 27709. UNIV ROCHESTER,SCH MED,DEPT ENVIRONM MED,ROCHESTER,NY 14642. MT DESERT ISL BIOL LAB,SALSBURY COVE,ME 04672. RP HENSON, JH (reprint author), DICKINSON COLL,DEPT BIOL,CARLISLE,PA 17013, USA. FU NIDDK NIH HHS [DK 34989, DK 25636]; NIEHS NIH HHS [ES 03828] NR 47 TC 15 Z9 15 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 0022-104X J9 J EXP ZOOL JI J. Exp. Zool. PD MAR 1 PY 1995 VL 271 IS 4 BP 273 EP 284 DI 10.1002/jez.1402710405 PG 12 WC Zoology SC Zoology GA QN691 UT WOS:A1995QN69100004 PM 7722471 ER PT J AU WIKSTROM, A VANDOORNUM, GJJ QUINT, WGV SCHILLER, JT DILLNER, J AF WIKSTROM, A VANDOORNUM, GJJ QUINT, WGV SCHILLER, JT DILLNER, J TI IDENTIFICATION OF HUMAN PAPILLOMAVIRUS SEROCONVERSIONS SO JOURNAL OF GENERAL VIROLOGY LA English DT Article ID OPEN READING FRAMES; LINEAR EPITOPES; CAPSID PROTEINS; TYPE-16; ANTIBODIES; INFECTION; VIRUS; L1; NEOPLASIA; PARTNERS AB The temporal relationship between primary genital human papillomavirus (HPV) infections and the induction of antibodies against viral antigens has not been established. In order to address this question we studied a cohort of 110 women and 48 men with multiple heterosexual partners, who were followed for 220 person-years during which they made 583 visits to the sexually transmitted diseases clinic of the Amsterdam Public Health Service. At each visit spatula or brush samples from multiple anogenital and oral sites were collected for HPV DNA analysis by PCR. Serum samples were also collected and analysed for serological reactivity to peptides derived from the L1, L2 and E2 regions of HPV types 6, 16 and 18 as well as to bovine papillomavirus and HPV-16 virus-like particles. Seroconversions for at least three antigens were found among 16/158 patients. Of these, 10/16 were HPV-positive and in 5/16 cases seroconversions occurred concomitantly with the detection of HPV DNA. Analysis of participants who were HPV-negative at entry, but became HPV DNA-positive during follow-up revealed that antibodies against several HPV antigens were regularly induced at the time of a new HPV infection, in particular the IgG responses against HPV-16 virus-like particles and against the HPV-16 E2-derived peptide 245. Whereas the responses induced among the women with new HPV-16 infection tended to continuously increase, the responses among the men with any type of new HPV infection were mostly transient and disappeared during follow-up. In conclusion, we find that antibody responses to multiple viral antigens are often induced following the detection of genital HPV infection, that the type-specificity of the response is limited and that transient responses are common. C1 KAROLINSKA INST,CTR MICROBIOL & TUMOR BIOL,STOCKHOLM,SWEDEN. KAROLINSKA HOSP,DEPT DERMATOVENEREOL,S-10401 STOCKHOLM,SWEDEN. MUNICIPAL HLTH SERV AMSTERDAM,DEPT PUBL HLTH,AMSTERDAM,NETHERLANDS. DIAGNOST CTR SSDZ,DIV MOLEC BIOL,DELFT,NETHERLANDS. NIH,CELLULAR ONCOL LAB,BETHESDA,MD. NR 27 TC 65 Z9 67 U1 0 U2 2 PU SOC GENERAL MICROBIOLOGY PI READING PA HARVEST HOUSE 62 LONDON ROAD, READING, BERKS, ENGLAND RG1 5AS SN 0022-1317 J9 J GEN VIROL JI J. Gen. Virol. PD MAR PY 1995 VL 76 BP 529 EP 539 DI 10.1099/0022-1317-76-3-529 PN 3 PG 11 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA QL246 UT WOS:A1995QL24600005 PM 7897345 ER PT J AU JAN, LR YANG, CS TRENT, DW FALGOUT, B LAI, CJ AF JAN, LR YANG, CS TRENT, DW FALGOUT, B LAI, CJ TI PROCESSING OF JAPANESE ENCEPHALITIS-VIRUS NONSTRUCTURAL PROTEINS - NS2B-NS3 COMPLEX AND HETEROLOGOUS PROTEASES SO JOURNAL OF GENERAL VIROLOGY LA English DT Article ID NONSTRUCTURAL PROTEINS; NUCLEOTIDE-SEQUENCE; ESCHERICHIA-COLI; VACCINIA VIRUS; POLYPROTEIN; CLEAVAGE; NS3; IDENTIFICATION; DOMAIN; FLAVIVIRUSES AB Processing of Japanese encephalitis (JE) virus nonstructural (NS) proteins expressed by recombinant vaccinia viruses was analysed to characterize the responsible viral protease. Analysis of the processing of polyprotein NS2A-2B-3' containing the N-terminal 322 amino acids of NS3 revealed products consistent with cleavages at the predicted intergenic junctions as well as at one or possibly two sites within NS2A, Cleavage at the alternate site(s) containing the cleavage sequence motif within NS2A could possibly explain the production of the NS1' protein in JE virus-infected cells. Polyprotein NS2A-d2B-3' containing a large deletion within NS2B was cleavage-defective, despite the presence of the proposed NS3 protease domain. Cleavage of NS2A-d2B-3' was restored if NS2B or NS2A-2B was supplied in trans, providing evidence that NS2B is strictly required for NS3 proteolytic activity. NS2B- or NS3-specific sera raised against the bacterial TrpE fusion protein co-precipitated NS2B and NS3 or NS3'from the lysate of JE virus or recombinant virus-infected cells. Thus both protease components are associated as a complex, presumably representing the active JE virus protease. JE virus and the analogous dengue 4 (DEN-4) protease components were employed to examine the activity of heterologous proteases. The defective cleavage of JE virus NS2A-d2B-3' was complemented by heterologous DEN-4 NS2B, whereas the defective cleavage of DEN-4 NS2A-d2B-3' was not corrected by heterologous JE virus NS2B. This suggests that the heterologous JE virus NS2B-DEN-4 NS3 protease is not active, despite the considerable sequence conservation of NS2B and NS3 between the two viruses. The cleavage activity was restored by replacement of the C-terminal 80 amino acids of JE virus NS2B with the corresponding DEN-4 sequence, consistent with the notion that the C-terminal region contains amino acid residues for interaction with DEN-4 NS3. C1 NIAID,INFECT DIS LAB,MOLEC VIRAL BIOL SECT,BETHESDA,MD 20892. NATL TAIWAN UNIV,COLL MED,INST MICROBIOL,TAIPEI 10764,TAIWAN. NATL INST PREVENT MED,TAIPEI 11513,TAIWAN. CTR DIS CONTROL & PREVENT,FT COLLINS,CO 80522. US FDA,CTR BIOL EVALUAT & RES,VECTOR BORNE DIS LAB,BETHESDA,MD 20892. NIAID,INFECT DIS LAB,MOLEC VIRAL BIOL SECT,BETHESDA,MD 20892. NR 28 TC 44 Z9 47 U1 0 U2 1 PU SOC GENERAL MICROBIOLOGY PI READING PA HARVEST HOUSE 62 LONDON ROAD, READING, BERKS, ENGLAND RG1 5AS SN 0022-1317 J9 J GEN VIROL JI J. Gen. Virol. PD MAR PY 1995 VL 76 BP 573 EP 580 DI 10.1099/0022-1317-76-3-573 PN 3 PG 8 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA QL246 UT WOS:A1995QL24600009 PM 7897348 ER PT J AU SIRACUSA, LD WASHBURN, LL SWING, DA ARGESON, AC JENKINS, NA COPELAND, NG AF SIRACUSA, LD WASHBURN, LL SWING, DA ARGESON, AC JENKINS, NA COPELAND, NG TI HYPERVARIABLE YELLOW (A(HVY)), A NEW MURINE AGOUTI MUTATION - A(HVY) DISPLAYS THE LARGEST VARIATION IN COAT COLOR PHENOTYPES OF ALL KNOWN AGOUTI ALLELES SO JOURNAL OF HEREDITY LA English DT Article ID MOLECULAR CHARACTERIZATION; MOUSE CHROMOSOME-2; LOCUS; PROTEIN; MICE; GENE AB A new coat color mutation, which occurred spontaneously in the C3H/HeJ strain, has been identified, The original C3H/HeJ male mouse carrying the mutation was unusual because its coat color appeared mostly yellow, in contrast to the wild-type agouti coat normally exhibited by mice of the C3H/HeJ strain, Genetic crosses showed that the mutant phenotype was inherited as a single autosomal dominant gene, The mutation was backcrossed onto a C57BL/6J background and tested for allelism with the agouti locus, The results showed that the mutation, named hypervariable yellow (A(hvy)), is a new allele of the agouti locus. A(hvy) is unique because mice carrying the mutation can display a range of coat color from pure yellow to almost pure black, The A(hvy) mutation is responsible for the largest range of coat color phenotypes yet identified for any single agouti mutation. C1 JACKSON LAB,BAR HARBOR,ME 04609. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD. RP SIRACUSA, LD (reprint author), THOMAS JEFFERSON UNIV,DEPT MICROBIOL & IMMUNOL,233 S 10TH ST,PHILADELPHIA,PA 19107, USA. FU NCRR NIH HHS [P01 RR01183]; PHS HHS [N01-C0-74101] NR 24 TC 9 Z9 9 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 SN 0022-1503 J9 J HERED JI J. Hered. PD MAR-APR PY 1995 VL 86 IS 2 BP 121 EP 128 PG 8 WC Evolutionary Biology; Genetics & Heredity SC Evolutionary Biology; Genetics & Heredity GA QQ220 UT WOS:A1995QQ22000007 PM 7751596 ER PT J AU JAMUR, MC FARACO, CD LUNARDI, LO SIRAGANIAN, RP OLIVER, C AF JAMUR, MC FARACO, CD LUNARDI, LO SIRAGANIAN, RP OLIVER, C TI MICROWAVE FIXATION IMPROVES ANTIGENICITY OF GLUTARALDEHYDE-SENSITIVE ANTIGENS WHILE PRESERVING ULTRASTRUCTURAL DETAIL SO JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY LA English DT Note DE MICROWAVE FIXATION; ELECTRON MICROSCOPY; IMMUNOCYTOCHEMISTRY; GLUTARALDEHYDE-SENSITIVE ANTIGENS; MAST CELLS ID POSTEMBEDDING IMMUNOGOLD TECHNIQUE; AFFINITY IGE RECEPTOR; ELECTRON-MICROSCOPY; HISTOLOGICAL FIXATION; ENERGY FIXATION; HUMAN-TISSUES; MAST-CELLS; LIGHT; IRRADIATION; LOCALIZATION AB Microwave fixation for electron microscopy has been used primarily for post-embedding immunocytochemistry. The present study examined the ability of microwave fixation to preserve the antigenicity of glutaraldehyde-sensitive antigens for pre-embedding immunocytochemistry. Five monoclonal antibodies (MAbs) directed against cell surface components of rat mast cells were tested. The MAbs failed to show any labeling of conventionally fixed rat bone marrow-derived mast cells even at glutaraldehyde concentrations as low as 0.1%. Strong staining of mast cell plasma membranes was seen when bone marrow was initially fixed with 2% formaldehyde and then refixed in 2% glutaraldehyde/2% formaldehyde after immunostaining. However, the ultrastructural preservation of the cells was poor, Antigenicity and morphological detail were both preserved when bone marrow was fixed in 0.05% glutaraldehyde/2% formaldehyde for 4 sec in a 550-W microwave oven, With this method, mast cells in various stages of maturation as well as cells that did not contain granules were immunoreactive. This method should prove useful with antigens from many different cell types that are sensitive to glutaraldehyde fixation. C1 OFF NAVAL RES,BIOMED SCI & TECHNOL PROGRAM,ARLINGTON,VA 22217. FED UNIV PARANA,DEPT BIOL CELULAR,CURITIBA,PARANA,BRAZIL. RIBEIRAO PRETO UNIV,FAC MED,DEPT MORFOL,RIBEIRAO PRET,BRAZIL. NIDR,IMMUNOL LAB,BETHESDA,MD 20892. RI Jamur, Maria Celia/L-5520-2016 OI Jamur, Maria Celia/0000-0001-7065-8543 NR 29 TC 22 Z9 23 U1 0 U2 1 PU HISTOCHEMICAL SOC INC PI NEW YORK PA MT SINAI MEDICAL CENTER 19 EAST 98TH ST SUTIE 9G, NEW YORK, NY 10029 SN 0022-1554 J9 J HISTOCHEM CYTOCHEM JI J. Histochem. Cytochem. PD MAR PY 1995 VL 43 IS 3 BP 307 EP 311 PG 5 WC Cell Biology SC Cell Biology GA QJ287 UT WOS:A1995QJ28700009 PM 7868860 ER PT J AU BRANDO, C SHEVACH, EM AF BRANDO, C SHEVACH, EM TI ENGAGEMENT OF THE VITRONECTIN RECEPTOR (ALPHA-V-BETA-3) ON MURINE T-CELLS STIMULATES TYROSINE PHOSPHORYLATION OF A 115-KDA PROTEIN SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INTEGRIN-ASSOCIATED PROTEIN; EXTRACELLULAR-MATRIX; MONOCLONAL-ANTIBODIES; SIGNAL TRANSDUCTION; MOLECULAR-CLONING; ENDOTHELIAL-CELLS; LIGAND-BINDING; FIBRONECTIN; ADHESION; PP125(FAK) AB The murine vitronectin receptor (VNR, alpha V beta 3) is expressed on T cell hybridomas expressing both the alpha beta and the gamma delta TCR as well as on TCR-alpha beta cells activated for prolonged periods of time by mitogens or alloantigens. The VNR functions as a costimulatory molecule for the activation of a subset of gamma delta T cells that express the V gamma 1.1 C gamma 4 V delta 6 TCR and that may recognize a ubiquitously expressed autoantigen. To characterize further some of the signal transduction parameters observed after engagement of the VNR in stimulated T lymphocytes, we have examined the effect of ligation of the VNR by RGDS-containing proteins on the pattern of protein phosphorylation. We demonstrate the appearance of a 115-kDa, tyrosine-phosphorylated protein (pp115) after engagement of the VNR with its ligand, RGDS. pp115 was shown to be immunologically distinct from focal adhesion kinase, did not possess inherent kinase activity, and may represent an as yet unidentified substrate in the integrin signal transduction pathway. Although induction of pp115 was independent of TCR expression, because it was seen in the TG40 hybridoma, which expresses neither the alpha beta nor the gamma delta TCR, pp115 could also be induced by cross-linking of the TCR in a murine TCR gamma delta hybridoma in the absence of any extracellular matrix proteins. This result raises the possibility that induction of pp115 is a common biochemical step in signal transduction by both the TCR and the VNR. C1 NIAID,IMMUNOL LAB,BETHESDA,MD 20892. NR 36 TC 20 Z9 20 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 MAR 1 PY 1995 VL 154 IS 5 BP 2005 EP 2011 PG 7 WC Immunology SC Immunology GA QH291 UT WOS:A1995QH29100001 PM 7532658 ER PT J AU RICOVARGAS, SA POTTER, M OSMOND, DG AF RICOVARGAS, SA POTTER, M OSMOND, DG TI PERTURBATION OF B-CELL GENESIS IN THE BONE-MARROW OF PRISTANE-TREATED MICE - IMPLICATIONS FOR PLASMACYTOMA INDUCTION SO JOURNAL OF IMMUNOLOGY LA English DT Article ID PEANUT AGGLUTININ BINDING; MYC TRANSGENIC MICE; CHAIN-BEARING CELLS; RED-BLOOD-CELLS; BALB/C MICE; C-MYC; CHROMOSOMAL TRANSLOCATIONS; PRECURSOR CELLS; LYMPHOCYTE-PRODUCTION; EXOGENOUS AGENTS AB A single injection of pristane was given i.p. to plasmacytoma-susceptible BALB/cAn mice. At intervals up to 6 mo thereafter, immunofluorescence labeling of intranuclear terminal deoxynucleotidyl transferase (TdT), cell surface B220 glycoprotein, cytoplasmic mu-chains of IgM (c mu), and surface mu-chains (s mu), together with mitotic arrest techniques, were used to quantitate the in vivo population dynamics of precursor B cells in the bone marrow. TdT-expressing pro-B cells (TdT(+)B220(-), TdT(+)B220(+)), before the expression of mu-chains, showed sustained increases in both population size and the number of cells flowing through mitosis per unit time. In contrast, populations of pre-B cells (c mu(+)s mu(-)) and B cells (s mu(+)) were consistently depressed for long periods of time, including the phase of plasmacytoma formation. Precursor B cells in DBA/2 mice, a plasmacytoma-resistant strain, showed similar responses to pristane treatment. The results demonstrate that a single injection of pristane, which greatly increases the demand for macrophage activity in the peritoneal space, causes sustained distant alterations in B cell lymphopoiesis in the bone marrow; specifically, a prolonged increased proliferation of pro-B cells coupled with a depression and a exaggerated loss of pre-B cells and B cells. The protracted stress on B cell lymphopoiesis may be a predisposing factor in the subsequent development of c-myc-activating chromosomal rearrangements that play a critical role in plasmacytomagenesis. C1 MCGILL UNIV,DEPT ANAT & CELL BIOL,MONTREAL,PQ H3A 2B2,CANADA. NCI,GENET LAB,BETHESDA,MD 20892. NR 68 TC 13 Z9 13 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 MAR 1 PY 1995 VL 154 IS 5 BP 2082 EP 2091 PG 10 WC Immunology SC Immunology GA QH291 UT WOS:A1995QH29100009 PM 7868885 ER PT J AU STURMHOFEL, K BRANDO, C MARTINON, F SHEVACH, EM COLIGAN, JE AF STURMHOFEL, K BRANDO, C MARTINON, F SHEVACH, EM COLIGAN, JE TI ANTIGEN-INDEPENDENT, INTEGRIN-MEDIATED T-CELL ACTIVATION SO JOURNAL OF IMMUNOLOGY LA English DT Article ID GAMMA-DELTA-LYMPHOCYTES; RECEPTOR ZETA-CHAIN; VITRONECTIN RECEPTOR; ALPHA-BETA; PROTEINS; ADHESION; SURFACE; SPECIFICITY; EXPRESSION; FAMILY AB The ''outside-in'' signals produced by the interaction of integrin molecules with the extracellular matrix (ECM) trigger a multitude of cellular events. The vitronectin receptor (VNR), an alpha(v) beta(3) heterodimer, functions as a costimulatory molecule for the activation of a subset of V gamma 1.1/C gamma 4-bearing gamma/delta T cells, which have been postulated to recognize a ubiquitous self-antigen. We addressed the question of whether stimulation of these T cells requires both engagement of the VNR by ECM proteins and engagement of the TCR by its Ag. We introduced into a TCR(-) but VNR(+) mutant T cell hybridoma, TG40 (derived from 2B4), a chimeric molecule that contains the cytoplasmic tail of the TCR zeta-chain fused to the cytoplasmic and transmembrane region of either human CD8 or human CD25. The transfectants expressing the chimeric molecules secreted IL-2 constitutively when the VNR was engaged with a ligand, e.g., provided by ECM proteins present in FCS. This constitutive cytokine secretion could be blocked with mAb directed against the VNR, with or the peptide RGD, or by growth in serum-free medium. VNR-mediated cell activation also induced the phosphorylation of the zeta-chain. Signaling through the zeta-chain was required, as cells transfected with a chimera containing only a 22 amino-acid long, truncated zeta-chain did not secrete IL-2 constitutively. Thus, we demonstrated that the binding of the VNR to ECM protein in the presence of the zeta-chain is sufficient to induce cytokine secretion by T cells and does not require the recognition of an Ag by the TCR. Such integrin-mediated, Ag-independent activation of T cells may play a critical role in the potentiation of inflammatory responses. C1 NIAID,IMMUNOL LAB,ROCKVILLE,MD 20852. RP STURMHOFEL, K (reprint author), NIAID,MOLEC STRUCT LAB,TWINBROOK II,ROOM 103,12441 PARKLAWN DR,ROCKVILLE,MD 20852, USA. NR 45 TC 34 Z9 34 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 MAR 1 PY 1995 VL 154 IS 5 BP 2104 EP 2111 PG 8 WC Immunology SC Immunology GA QH291 UT WOS:A1995QH29100011 PM 7532660 ER PT J AU WADSWORTH, SA CHANG, AC HONG, MJP HALVORSON, MJ OTTO, S COLIGAN, JE AF WADSWORTH, SA CHANG, AC HONG, MJP HALVORSON, MJ OTTO, S COLIGAN, JE TI EXPRESSION OF A NOVEL INTEGRIN BETA-1 CHAIN EPITOPE AND ANTI-BETA(1) ANTIBODY-MEDIATED ENHANCEMENT OF FIBRONECTIN-BINDING ARE DEPENDENT ON THE STAGE OF T-CELL DIFFERENTIATION SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CYTOPLASMIC DOMAIN; IMMATURE THYMOCYTES; INTERLEUKIN-2 RECEPTOR; REGULATED EXPRESSION; MONOCLONAL-ANTIBODY; LIGAND INTERACTIONS; ENDOTHELIAL-CELLS; MURINE THYMOCYTES; ADHESION; SUBUNIT AB beta(1) integrins are a family of alpha beta heterodimers that serve as cell surface receptors for extracellular matrix proteins. We demonstrate that the anti-mouse integrin beta(1) chain mAb KMI6 selectively recognizes a beta(1) epitope that is constitutively expressed by certain immature thymocytes and is induced only slightly on mature thymocytes and peripheral T cells by activation with Con A. Because virtually all cells examined expressed beta(1) integrins on their surface, expression of the KMI6 epitope is T cell differentiation stage specific. Most CD3(-)4(-)8(-) thymocytes were KMI6(+), with the lowest level of staining observed on the earliest CD44(+)IL-2R(-) cells within this subset. Expression was down-regulated during the CD3(-)4(-)8(-) to CD3(-)4(-)8(+) transition, and lost by the CD4(+)8(+) stage. Mature single positive thymocytes and resting peripheral T cells were also KMI6(-). In contrast with the loss of the epitope before TCR expression by other thymocytes, most CD3(+)4(-)8(-) and certain CD8(+) gamma delta TCR(+) thymocytes were KMI6(+) Addition of KMI6 to cell adhesion assays enhanced CD4(-)8(-) thymocyte, but not activated mature thymocyte or peripheral T cell, binding to fibronectin (via alpha(4) beta(1) and alpha(5) beta(1)), whereas laminin binding (via alpha(6) beta(1)) was unaffected. These properties distinguish the KMI6 epitope from other epitopes involved in beta(1) integrin activation in mice and other species. The unique selectivity of KMI6 recognition of beta(1) integrins, and its selective enhancement of ligand binding suggest that beta(1) integrin structure and factors that regulate beta(1) integrin binding are correlated with the stage of T cell differentiation. C1 NIAID,MOLEC STRUCT LAB,ROCKVILLE,MD 20852. NR 42 TC 3 Z9 3 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 MAR 1 PY 1995 VL 154 IS 5 BP 2125 EP 2133 PG 9 WC Immunology SC Immunology GA QH291 UT WOS:A1995QH29100013 PM 7532661 ER PT J AU RIVOLTINI, L KAWAKAMI, Y SAKAGUCHI, K SOUTHWOOD, S SETTE, A ROBBINS, PF MARINCOLA, FM SALGALLER, ML YANNELLI, YR APPELLA, E ROSENBERG, SA AF RIVOLTINI, L KAWAKAMI, Y SAKAGUCHI, K SOUTHWOOD, S SETTE, A ROBBINS, PF MARINCOLA, FM SALGALLER, ML YANNELLI, YR APPELLA, E ROSENBERG, SA TI INDUCTION OF TUMOR-REACTIVE CTL FROM PERIPHERAL-BLOOD AND TUMOR-INFILTRATING LYMPHOCYTES OF MELANOMA PATIENTS BY IN-VITRO STIMULATION WITH AN IMMUNODOMINANT PEPTIDE OF THE HUMAN-MELANOMA ANTIGEN MART-1 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID METASTATIC MELANOMA; MOLECULES; IMMUNOTHERAPY; HLA-A2.1 AB MART-1 is an Ag expressed on melanomas and melanocytes, and is recognized by the majority of HLA-A2-restricted tumor-specific tumor-infiltrating lymphocytes (TIL) from melanoma patients. In the present study we have analyzed 10 potential 9-mer epitopes containing the HLA-A2.1 binding motifs for their ability to induce melanoma-specific T cell lines. Antimelanoma CTL could be generated only with MART-1(27-35) peptide, which has been previously shown to be recognized by a majority of HLA-A2-restricted TIL. Anti-MART-1(35-43)-specific CTL could also be induced, but these T cells did not recognize melanoma cells. MART-1(27-35)-specific CTL could be effectively generated from a total of 11 of 12 PBL and from 3 of 3 TIL derived from HLA-A2(+) melanoma patients, as well as from 2 of 4 PBL from HLA-A2(+) healthy donors by in vitro stimulation with autologous PBMC pulsed with the synthetic MART-1(27-35) peptide. These CTL lines specifically lysed and release cytokines (TNF-alpha, IFN-gamma, and GM-CSF) in response to T2 cells pulsed with MART-1(27-35), as well as to HLA-A2(+) MART-1(+) melanoma cells. CTL generated with MART-1(27-35) also lysed uncultured HLA-A2(+) melanoma cells derived from tumor biopsies, indicating that this MART-1 epitope is likely to be expressed in association with HLA-A2 on the surface of tumor cells in vivo. CTL lines generated with MART-1(27-35) mediated 25- to 100-fold higher lytic activity than MART-1-reactive CTL grown from TIL in the presence of high dose IL-2. These results demonstrate that MART-1(27-35) peptide may represent an ideal candidate for Ag-specific immunotherapy in melanoma patients. C1 NCI,SURG BRANCH,BETHESDA,MD 20892. NCI,CELL BIOL LAB,BETHESDA,MD 20892. CYTEL CORP,SAN DIEGO,CA 92121. RI Kawakami, Yutaka /E-7429-2013; OI Kawakami, Yutaka /0000-0003-4836-2855; Rivoltini, Licia/0000-0002-2409-6225 NR 25 TC 280 Z9 282 U1 0 U2 6 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAR 1 PY 1995 VL 154 IS 5 BP 2257 EP 2265 PG 9 WC Immunology SC Immunology GA QH291 UT WOS:A1995QH29100026 PM 7868898 ER PT J AU TAUB, D DASTYCH, J INAMURA, N UPTON, J KELVIN, D METCALFE, D OPPENHEIM, J AF TAUB, D DASTYCH, J INAMURA, N UPTON, J KELVIN, D METCALFE, D OPPENHEIM, J TI BONE-MARROW-DERIVED MURINE MAST-CELLS MIGRATE, BUT DO NOT DEGRANULATE, IN RESPONSE TO CHEMOKINES SO JOURNAL OF IMMUNOLOGY LA English DT Article ID ENDOTHELIAL-CELLS; CYTOKINE FAMILY; HUMAN BASOPHILS; RANTES; CHEMOATTRACTANT; GRANULOCYTES; ACTIVATION; CHEMOTAXIS; HISTAMINE; RECEPTORS AB We have determined that several chemokines induce mast cell migration in vitro. This directed migration is dependent on the presence of particular extracellular matrix proteins and the activation status of the cells. Mast cell haptotactic responses were observed in response to various chemokines on vitronectin-, laminin-, and fibronectin-coated filters. Unstimulated mast cells were chemoattracted only by monocyte chemotactic protein-1 and RANTES on vitronectin-coated and, to a lesser extent, laminin-coated filters, whereas IgE-activated mast cells migrated in response to monocyte chemotactic protein-1, regulated on activation normal T expressed and secreted, platelet factor-4, and macrophage inflammatory protein-1 alpha on all three matrix proteins. No significant migration was observed on collagen type IV-coated or uncoated filters. Mast cell migration in response to chemokines on extracellular matrices and its enhancement by IgE-dependent activation provide a mechanism by which cells may be drawn to sites of inflammation. Chemokine-induced mast cell recruitment may be particularly relevant in host defense responses to parasitic infections, allergic reactions, Jones-Mote reactions, and in wound healing. C1 NCI,FREDERICK CANC RES & DEV CTR,MOLEC IMMUNOREGULAT LAB,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21702. NIAID,MAST CELL PHYSIOL SECT,CLIN INVEST LAB,BETHESDA,MD 20892. RP TAUB, D (reprint author), NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,CLIN SERV PROGRAM,POB B,FREDERICK,MD 21702, USA. NR 27 TC 112 Z9 112 U1 1 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 MAR 1 PY 1995 VL 154 IS 5 BP 2393 EP 2402 PG 10 WC Immunology SC Immunology GA QH291 UT WOS:A1995QH29100039 PM 7532669 ER PT J AU KINTER, AL POLI, G FOX, L HARDY, E FAUCI, AS AF KINTER, AL POLI, G FOX, L HARDY, E FAUCI, AS TI HIV REPLICATION IN IL-2-STIMULATED PERIPHERAL-BLOOD MONONUCLEAR-CELLS IS DRIVEN IN AN AUTOCRINE PARACRINE MANNER BY ENDOGENOUS CYTOKINES SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; NECROSIS-FACTOR-ALPHA; PHORBOL-MYRISTATE ACETATE; HUMAN T-CELLS; NF-KAPPA-B; HTLV-III; PROMONOCYTIC CELLS; CELLULAR TROPISM; MONOCYTIC CELLS; GENE-EXPRESSION AB Replication of HIV is regulated by virus-encoded regulatory proteins, as well as by a variety of cellular factors including cytokines. In the present study, we have investigated the autocrine/paracrine effects of endogenous cytokines on HIV replication in primary PBMCs of healthy HIV seronegative individuals. Addition of rIL-2 to cultures between 0 and 72 h after isolation of PBMCs allowed the replication of primary HIV isolates and laboratory-adapted HIV strains to levels comparable with or greater than those obtained in parallel cultures of autologous PHA-blasts. In this regard, both major cellular targets of HIV infection, CD4(+) T lymphocytes and mononuclear phagocytes, were maintained for several weeks in IL-2-stimulated PBMC cultures and virion production was observed in both cell lineages. The kinetics of secretion of several cytokines (such as TNF-alpha, IL-1 beta, IL-6, and IFN-gamma), as well as expression of cellular activation markers, paralleled HIV replication in IL-2-stimulated PBMCs. Endogenous pro-inflammatory cytokines and IFN-gamma played a major role in the regulation of HIV replication in IL-2-stimulated PBMCs, as determined by the ability of several anti-cytokine Abs or antagonists to suppress HIV production; this was not the case in parallel cultures of autologous PHA-blasts. Thus, IL-2-stimulated PBMCs may represent a more physiologic in vitro system than PHA-blasts for the study of HIV infection and replication, and should prove useful in investigating the role of cytokines and other host factors in the regulation of HIV production. RP KINTER, AL (reprint author), NIAID,IMMUNOREGULAT LAB,BLDG 10A,ROOM 6A33A,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 74 TC 125 Z9 126 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 MAR 1 PY 1995 VL 154 IS 5 BP 2448 EP 2459 PG 12 WC Immunology SC Immunology GA QH291 UT WOS:A1995QH29100045 PM 7868911 ER PT J AU ELSON, LH CALVOPINA, M PAREDES, W ARAUJO, E BRADLEY, JE GUDERIAN, RH NUTMAN, TB AF ELSON, LH CALVOPINA, M PAREDES, W ARAUJO, E BRADLEY, JE GUDERIAN, RH NUTMAN, TB TI IMMUNITY TO ONCHOCERCIASIS - PUTATIVE IMMUNE PERSONS PRODUCE A TH1-LIKE RESPONSE TO ONCHOCERCA-VOLVULUS SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID GUATEMALAN HUMAN ONCHOCERCIASIS; PARASITE-SPECIFIC ANERGY; ADULT WORM ANTIGENS; TH-CELL SUBSETS; SCHISTOSOMA-MANSONI; PROTECTIVE IMMUNITY; DIFFERENTIAL INDUCTION; TRICHINELLA-SPIRALIS; HUMAN FILARIASIS; DOWN-REGULATION AB Immunity to Onchocerca volvulus (Ov) infection is suggested by the presence of putatively immune (PI) subjects in a region of Ecuador in which Ov is endemic. PI subjects were identified by traditional diagnostic methods combined with a polymerase chain reaction-based assay for Ov DNA in skin snips. Responses of peripheral blood mononuclear cells (PBMC) from the PI group (n = 16) were compared with those of persons with active infection (microfiladermic [MF] subjects; n = 51). PBMC of PI subjects proliferated significantly more to Ov antigen (OvAg; P < .009) than did PBMC of MF persons but less to streptolysin-O (P < .001). Cytokine analysis of PBMC culture supernatants revealed that PI subjects (n = 11) produced significantly more interferon-gamma to OvAg than did those in the MF group (n = 18; P = .018), less interleukin (IL)-5 to nonparasite antigen (P = .003) and mitogen (P = .012), and less IL-10 spontaneously (P = .016). Thus, immunity to Ov may in part be mediated by an antigen-specific Th1-type response. C1 HOSP VOZANDES,INVEST CLIN,QUITO,ECUADOR. UNIV LONDON IMPERIAL COLL SCI TECHNOL & MED,DEPT PURE & APPL BIOL,LONDON,ENGLAND. RP ELSON, LH (reprint author), NIAID,PARASIT DIS LAB,BLDG 4,ROOM 126,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. OI Bradley, Janette/0000-0003-3973-7977 NR 37 TC 105 Z9 106 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 MAR PY 1995 VL 171 IS 3 BP 652 EP 658 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA QJ455 UT WOS:A1995QJ45500020 PM 7876612 ER PT J AU OTTESEN, EA AF OTTESEN, EA TI IMMUNE RESPONSIVENESS AND THE PATHOGENESIS OF HUMAN ONCHOCERCIASIS SO JOURNAL OF INFECTIOUS DISEASES LA English DT Review ID IMMUNOLOGICAL CROSS-REACTIVITY; OCULAR ONCHOCERCIASIS; GUATEMALAN ONCHOCERCIASIS; VOLVULUS INFECTION; PARASITE ANTIGEN; GENERALIZED FORM; RESPONSES; COMPLEXES; HYPERSENSITIVITY; DISEASE AB Prominent antibody but minimal cellular proliferative responses to parasite antigen typify the systemic immune response of patients with onchocerciasis. While components of this response are proinflammatory (and antiparasitic), the primary force driving the immune system is the need to contain or limit inflammation around microfilariae that die in the skin or elsewhere at rates up to hundreds of thousands per day. These dying parasites initiate local inflammatory reactions, with the result being ''bystander'' tissue damage, which cumulatively determines host pathology. Local and systemic immune mechanisms to contain inflammation (e.g., blocking antibodies, down-regulating cytokines) are prominent in infected patients, and their delineation is crucial to understanding the pathogenesis of onchocercal disease in the skin, eye, and elsewhere. The degree of pathology appears directly related to both microfilarial numbers and the intensity of proinflammatory responses to them and inversely related to the effectiveness of specific mechanisms to suppress this inflammation. RP OTTESEN, EA (reprint author), NIAID,PARASIT DIS LAB,BLDG 4,ROOM 126,BETHESDA,MD 20892, USA. NR 77 TC 124 Z9 125 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 MAR PY 1995 VL 171 IS 3 BP 659 EP 671 PG 13 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA QJ455 UT WOS:A1995QJ45500021 PM 7876613 ER PT J AU BRODINE, SK HYAMS, KC MOLGAARD, CA ITO, SI THOMAS, RJ ROBERTS, CR GOLBECK, AL OLDFIELD, EC BLATTNER, WA AF BRODINE, SK HYAMS, KC MOLGAARD, CA ITO, SI THOMAS, RJ ROBERTS, CR GOLBECK, AL OLDFIELD, EC BLATTNER, WA TI THE RISK OF HUMAN T-CELL LEUKEMIA-VIRUS AND VIRAL-HEPATITIS INFECTION AMONG US MARINES STATIONED IN OKINAWA, JAPAN SO JOURNAL OF INFECTIOUS DISEASES LA English DT Note ID UNITED-STATES-NAVY; SEXUAL TRANSMISSION; MILITARY PERSONNEL; DISEASES; ANTIBODY AB The prevalence and incidence of human T cell leukemia virus type I/II (HTLV-I/II) and hepatitis A, B, and C virus infection were determined among US Marines stationed in Okinawa, Japan. Of 2875 personnel, 2 (0.07%) had antibody to HTLV-I/II. After 1-3 years, no HTLV seroconversions were observed, although 23% reported sexual contact with Okinawans. Of 1010 hepatitis-tested marines, 121 (12%) had antibody to hepatitis A virus (anti-HAV), 26 (2.6%) had antibody to hepatitis B core antigen (anti-HBc), and 2 (0.2%) had antibody to hepatitis C virus (anti-HCV). On follow-up, 1 subject seroconverted to anti-HAV, 8 to anti-HBc, and none to anti-HCV. Most marines with recent hepatitis B infection were young, single, and enlisted and had been on short deployments to other countries in Southeast Asia. Marines stationed in Okinawa are not at high risk for HTLV infection but are at increased risk for hepatitis B infection and should be considered for vaccination. C1 USN,MED CTR,DEPT INTERNAL MED,DIV INFECT DIS,SAN DIEGO,CA 92152. NCI,NAVAL MED RES INST,DIV EPIDEMIOL,BETHESDA,MD. NCI,VIRAL EPIDEMIOL SECT,BETHESDA,MD. NAVAL HOSP OKINAWA,DEPT PREVENT MED,MARINE EXPEDITIONARY FORCE 3,OKINAWA,JAPAN. WALTER REED ARMY INST RES,DIV RETROVIROL,WASHINGTON,DC. RP BRODINE, SK (reprint author), SAN DIEGO STATE UNIV,NAVAL HLTH RES CTR,GRAD SCH PUBL HLTH,DEPT MATH SCI,SAN DIEGO,CA 92186, USA. NR 17 TC 5 Z9 6 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 MAR PY 1995 VL 171 IS 3 BP 693 EP 696 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA QJ455 UT WOS:A1995QJ45500028 PM 7876620 ER PT J AU HIRSCHFELD, S SCHIFFMAN, G TUDORWILLIAMS, G PIZZO, PA AF HIRSCHFELD, S SCHIFFMAN, G TUDORWILLIAMS, G PIZZO, PA TI PNEUMONIA AND BACTEREMIA BY PNEUMOCOCCAL SEROTYPE-16 IN A HUMAN IMMUNODEFICIENCY VIRUS-INFECTED CHILD WITH NORMAL SERUM ANTIBODY-RESPONSE TO 23-VALENT PNEUMOVAX VACCINE SO JOURNAL OF INFECTIOUS DISEASES LA English DT Letter ID GROWTH-HORMONE; MEN C1 SUNY HLTH SCI CTR,DEPT MICROBIOL & PATHOL,BROOKLYN,NY 11203. RP HIRSCHFELD, S (reprint author), NCI,PEDIAT BRANCH,BLDG 10,ROOM 13N240,BETHESDA,MD 20892, USA. RI Hirschfeld, Steven/E-2987-2016 OI Hirschfeld, Steven/0000-0003-0627-7249 NR 10 TC 1 Z9 1 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 MAR PY 1995 VL 171 IS 3 BP 761 EP 762 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA QJ455 UT WOS:A1995QJ45500048 PM 7876638 ER PT J AU DECOURTEN, MP KSIAZEK, TG ROLLIN, PE KHAN, AS DAILY, PJ KNOWLER, WC AF DECOURTEN, MP KSIAZEK, TG ROLLIN, PE KHAN, AS DAILY, PJ KNOWLER, WC TI SEROPREVALENCE STUDY OF HANTAVIRUS ANTIBODIES IN PIMA-INDIANS WITH RENAL-DISEASE SO JOURNAL OF INFECTIOUS DISEASES LA English DT Letter ID DEPENDENT DIABETES-MELLITUS C1 CTR DIS CONTROL & PREVENT,NATL CTR INFECT DIS,DIV VIRAL & RICKETTSIAL DIS,ATLANTA,GA. RP DECOURTEN, MP (reprint author), NIDDK,PHOENIX EPIDEMIOL & CLIN RES BRANCH,DIABET & ARTHRIT EPIDEMIOL SECT,1550 E INDIAN SCH RD,PHOENIX,AZ 85014, USA. RI de Courten, Maximilian/B-3300-2012 OI de Courten, Maximilian/0000-0001-9997-9359 NR 10 TC 4 Z9 4 U1 2 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 MAR PY 1995 VL 171 IS 3 BP 762 EP 763 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA QJ455 UT WOS:A1995QJ45500049 PM 7876639 ER PT J AU DHONDT, E PURCELL, RH EMERSON, SU WONG, DC SHAPIRO, M GOVINDARAJAN, S AF DHONDT, E PURCELL, RH EMERSON, SU WONG, DC SHAPIRO, M GOVINDARAJAN, S TI EFFICACY OF AN INACTIVATED HEPATITIS-A VACCINE IN PREEXPOSURE AND POSTEXPOSURE CONDITIONS IN MARMOSETS SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT Meeting on Overview of the Clinical Development of Hepatitis A Vaccine CY FEB 03-06, 1994 CL MARCO ISLAND, FL ID A VIRUS; CELL-CULTURE AB A two-part challenge study was done in marmoset monkeys to confirm the efficacy of an inactivated hepatitis A vaccine. In part 1 (preexposure), 7 marmosets received a single low dose of vaccine (360 ELISA units [EL.U.]) and were challenged orally with wild type hepatitis A virus (HAV) either 1 or 6 months later. In part 2 (postexposure), 8 marmosets were challenged orally with HAV and then half each were inoculated with a single dose of 360 or 1440 EL.U. of vaccine 2 days later, The suboptimal immune response elicited by the low vaccine dose in the preexposure group was sufficient to induce complete protection against oral challenge with heterologous HAV in all marmosets that had responded serologically, In the postexposure group, the 360-EL.U. dose of vaccine resulted in partial protection against hepatitis A disease, whereas the 1440-EL.U. dose of vaccine elicited complete protection against disease and virus excretion. C1 NIH,BETHESDA,MD. BIOQUAL INC,ROCKVILLE,MD. RANCHO LOS AMIGOS MED CTR,DOWNEY,CA. RP DHONDT, E (reprint author), SMITHKLINE BEECHAM BIOL,RUE INST 89,B-1330 RIXENSART,BELGIUM. NR 13 TC 14 Z9 15 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 MAR PY 1995 VL 171 SU 1 BP S40 EP S43 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA QK826 UT WOS:A1995QK82600009 PM 7876647 ER PT J AU SHIMIZU, H MASUNAGA, T ISHIKO, A MATSUMURA, K HASHIMOTO, T NISHIKAWA, T DOMLOGEHULTSCH, N LAZAROVA, Z YANCEY, KB AF SHIMIZU, H MASUNAGA, T ISHIKO, A MATSUMURA, K HASHIMOTO, T NISHIKAWA, T DOMLOGEHULTSCH, N LAZAROVA, Z YANCEY, KB TI AUTOANTIBODIES FROM PATIENTS WITH CICATRICIAL PEMPHIGOID TARGET DIFFERENT SITES IN EPIDERMAL BASEMENT-MEMBRANE SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE BULLOUS DISEASES; EPILIGRIN; AUTOIMMUNITY; ULTRA STRUCTURE ID IMMUNOELECTRON MICROSCOPY; EXTRACELLULAR LOCALIZATION; ANTIGEN; SKIN; IMMUNOFLUORESCENCE; HETEROGENEITY; AUTOIMMUNE; EPILIGRIN; COMPONENT; DISEASES AB Indirect immunogold electron microscopy studies of cryofixed, freeze-substituted, and post-embedded normal human skin were performed to localize precisely the ultrastructural binding site of circulating autoantibodies from two groups of patients with cicatricial pemphigoid, One group of patients had circulating IgG autoantibodies that bound the dermal side of 1 M NaCl-split skin and immunoprecipitated epiligrin. The other group of patients had circulating IgG autoantibodies directed against the epidermal side of 1 M NaCl-split skin and showed no specific reactivity to any keratinocyte polypeptide by immunoprecipitation. IgG autoantibodies from all patients with anti-epiligrin cicatricial pemphigoid bound the lowermost aspect of the lamina lucida at its interface with the lamina densa; the greatest staining was seen beneath and beside hemidesmosomes. In contrast, IgG from cicatricial pemphigoid patients whose autoantibodies bound the epidermal side of M NaCl-split skin localized to hemidesmosomes and the junction between hemidesmosomes and the plasma membranes of basal keratinocytes. Although the latter staining pattern is similar to that observed with anti-BPAG2 autoantibodies, sera from our patients with cicatricial pemphigoid did not bind BPAG2 in immunoprecipitation studies of radiolabeled human keratinocyte extracts or show immunoblot reactivity to a fusion protein corresponding to the immunodominant epitope of this polypeptide. These studies demonstrate the following: 1) Autoantibodies from patients with anti-epiligrin cicatricial pemphigoid consistently bind the lower lamina lucida at its interface with the lamina densa; and 2) other patients with the same phenotype may have IgG autoantibodies against yet-unknown epitopes in basal keratinocytes. C1 NCI,DERMATOL BRANCH,BETHESDA,MD 20892. KEIO UNIV,SCH MED,DEPT DERMATOL,TOKYO,JAPAN. UNIFORMED SERV UNIV HLTH SCI,DEPT DERMATOL,BETHESDA,MD 20814. RI Shimizu, Hiroshi/A-5193-2012 NR 27 TC 67 Z9 67 U1 0 U2 1 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAR PY 1995 VL 104 IS 3 BP 370 EP 373 DI 10.1111/1523-1747.ep12665840 PG 4 WC Dermatology SC Dermatology GA QJ121 UT WOS:A1995QJ12100013 PM 7861004 ER PT J AU JONES, AP WEBB, LMC ANDERSON, AO LEONARD, EJ ROT, A AF JONES, AP WEBB, LMC ANDERSON, AO LEONARD, EJ ROT, A TI NORMAL HUMAN SWEAT CONTAINS INTERLEUKIN-8 SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE CHEMOKINES; CHEMOTAXIS; LEUKOCYTES; MCP-1 ID RECEPTOR; CELLS; SPECIFICITY; CHEMOTAXIS; BINDING AB Sweating in humans is induced by physical or emotional stress, which raises the possibility that sweating may relate to host defense. We therefore asked whether human eccrine sweat attracts leukocytes and found that it is chemotactic for human neutrophils. This activity was due to several chemoattractants, one of which was interleukin-8 (IL-8). Using immunohistochemistry and in situ hybridization IL-8 and its mRNA have been detected in sweat gland epithelium, indicating that IL-8 is produced in situ. This establishes a pattern of physiological IL-8 secretion by exocrine glands and suggests that, in addition to its role as a major inflammatory mediator, IL-8 also has physiological homeostatic flunctions. C1 SANDOZ GMBH,FORSCHUNGSINST DERMATOL,A-1235 VIENNA,AUSTRIA. USA,MED RES INST INFECT DIS,FT DETRICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. NR 24 TC 24 Z9 24 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD MAR PY 1995 VL 57 IS 3 BP 434 EP 437 PG 4 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA QM410 UT WOS:A1995QM41000013 PM 7884315 ER PT J AU MURPHY, PM AF MURPHY, PM TI BLOOD, SWEAT, AND CHEMOTACTIC CYTOKINES SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Editorial Material ID ANTIBODY; CELLS C1 NIAID,HOST DEF LAB,BETHESDA,MD 20892. NR 14 TC 4 Z9 4 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD MAR PY 1995 VL 57 IS 3 BP 438 EP 439 PG 2 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA QM410 UT WOS:A1995QM41000014 PM 7884316 ER PT J AU ROSENBERG, HF TIFFANY, HL AF ROSENBERG, HF TIFFANY, HL TI MONOCLONAL-ANTIBODY EG2 REACTIVITY - THE NEED FOR CLARIFICATION SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Letter RP ROSENBERG, HF (reprint author), NIAID,HOST DEF LAB,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 3 TC 1 Z9 1 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD MAR PY 1995 VL 57 IS 3 BP 513 EP 514 PG 2 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA QM410 UT WOS:A1995QM41000026 ER PT J AU REMALEY, AT HOEG, JM AF REMALEY, AT HOEG, JM TI POLARIZED SECRETION OF APOA-I AND APOA-II BY TRANSFECTED MDCK CELLS SO JOURNAL OF LIPID RESEARCH LA English DT Article DE MDCK CELLS; APICAL SECRETION; BASOLATERAL SECRETION; APOLIPOPROTEINS ID APOLIPOPROTEIN-A-I; INTESTINAL EPITHELIAL-CELLS; CANINE KIDNEY-CELLS; APICAL SECRETION; GLYCOPROTEIN COMPLEX; CYTOPLASMIC DOMAIN; RAT HEPATOCYTES; SORTING SIGNAL; MESSENGER-RNA; LINE CACO-2 AB Apolipoproteins (apo) are secreted preferentially from the basolateral surface of hepatocytes and enterocytes. The polarized secretion of proteins is either mediated by a protein-dependent sorting signal or by a cell-dependent default pathway. In order to determine the mechanism for the polarized secretion of apolipoproteins, we examined the secretion of apoA-I and apoA-II in transfected Madin-Darby canine kidney (MDCK) cells. Transfected MDCK cells and Caco-2 cells were grown as a polarized monolayer on tissue culture inserts, which separate an upper apical compartment from the lower basolateral compartment, and the secretion of apoA-I and apoA-II into the apical and basolateral compartments was quantitated by immunoprecipitation. Caco-2 cells almost exclusively secreted apoA-I and apoA-II basolaterally, with an apical to basolateral ratio of 18:82 for apoA-I, and 11:89 for apoA-II. In contrast, transfected MDCK cells secreted significant amounts of apoA-I and apoA-II into both compartments, but with a bias toward apical secretion and an apical to basolateral ratio of 66:34 and 68:32, respectively. The polarized secretion of MDCK cells was not due to transcytosis, diffusion, or differential recovery. As assessed by density gradient ultracentrifugation, apoA-I and apoA-II secreted from either the apical or basolateral surface were relatively lipid-poor. Overall, these results suggest that the polarized secretion of apoA-I and apoA-II does not occur by a protein-dependent sorting signal, but by a cell-dependent default pathway that leads to preferential basolateral secretion by Caco-2 cells and both apical and basolateral secretion in MDCK cells, but with a bias toward apical secretion. RP REMALEY, AT (reprint author), NHLBI,BLDG 10-N117,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 42 TC 6 Z9 6 U1 0 U2 0 PU LIPID RESEARCH INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD MAR PY 1995 VL 36 IS 3 BP 407 EP 413 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QP345 UT WOS:A1995QP34500002 PM 7775853 ER PT J AU MCNELLIS, D AF MCNELLIS, D TI A VIEW FROM BETHESDA - NIH GUIDELINES ON THE INCLUSION OF WOMEN AND MINORITIES AS SUBJECTS IN CLINICAL RESEARCH SO JOURNAL OF MATERNAL-FETAL INVESTIGATION LA English DT Editorial Material RP MCNELLIS, D (reprint author), NICHHD,PREGNANCY & PERINATOL BRANCH,BETHESDA,MD 20892, USA. NR 1 TC 1 Z9 1 U1 1 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0939-6322 J9 J MATERN-FETAL INVES JI J. Matern.-Fetal Invest. PD SPR PY 1995 VL 5 IS 2 BP 64 EP 64 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA RD052 UT WOS:A1995RD05200002 ER PT J AU CHATTON, JY SPRING, KR AF CHATTON, JY SPRING, KR TI THE SODIUM CONCENTRATION OF THE LATERAL INTERCELLULAR SPACES OF MDCK CELLS - A MICROSPECTROFLUOROMETRIC STUDY SO JOURNAL OF MEMBRANE BIOLOGY LA English DT Article DE EPITHELIA; FLUID TRANSPORT; FLUORESCENCE MICROSCOPY; TISSUE CULTURE; NA+ TRANSPORT ID CANINE KIDNEY-CELLS; CYTOSOLIC FREE NA+; COLONIC CRYPTS; ABSORPTION; EPITHELIUM; EXCHANGE; FLUID AB MDCK cell monolayers grown on glass coverslips were used to examine the Na+ concentration in individual lateral intercellular spaces (LIS) by video fluorescence microscopy. The LIS was filled with the Na+-sensitive fluorescent dye SBFO by incubation of the monolayers for 75-90 min with 250 mu M Of the membrane impermeant form of the dye. After dye loading, the monolayers were perfused at 37 degrees C with solutions buffered with HEPES or bicarbonate/CO2 containing 142 mM Na+. Ratios of the fluorescence images after sequential excitation with 340 nm and 380 nm light were performed and in situ calibration of LIS Na+ was accomplished after blocking the Na+ pump with 5 x 10(-4) M ouabain. Measurements of Na+ along the basolateral-to-apical axis of the LIS at 1.0 or 1.5 mu m intervals did not reveal a Na+ gradient when the perfusate was either HEPES or bicarbonate/CO2 solutions. In bicarbonate solutions, the mean Na+ concentration (mM) was 157.2 +/- 2.3, similar to 15 mM higher than the bath Na+ concentration. In HEPES solutions, however, the Na+ concentration was not different from the bath concentration (142.7 +/- 3.1 mM). The time course of Na+ changes in LIS was investigated by rapidly switching the perfusate from 142 to 80 mM Na+ and measuring the Na+ changes at one focal plane. C1 NHLBI,KIDNEY & ELECTROLYTE METAB LAB,BETHESDA,MD 20892. NR 24 TC 25 Z9 25 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0022-2631 J9 J MEMBRANE BIOL JI J. Membr. Biol. PD MAR PY 1995 VL 144 IS 1 BP 11 EP 19 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Physiology SC Biochemistry & Molecular Biology; Cell Biology; Physiology GA QL019 UT WOS:A1995QL01900002 PM 7595938 ER PT J AU XIA, P PERSSON, BE SPRING, KR AF XIA, P PERSSON, BE SPRING, KR TI THE CHLORIDE CONCENTRATION IN THE LATERAL INTERCELLULAR SPACES OF MDCK CELL MONOLAYERS SO JOURNAL OF MEMBRANE BIOLOGY LA English DT Article DE EPITHELIA; FLUID TRANSPORT; CL TRANSPORT; ABQ; FLUORESCENCE MICROSCOPY ID CYTOPLASM AB We measured the Cl concentration of the lateral intercellular spaces (LIS) of MDCK cell monolayers, grown on glass coverslips, by video fluorescence microscopy. Monolayers were perfused at 37 degrees C either with HEPES-buffered solutions containing 137 mM Cl or bicarbonate/CO2-buffered solutions containing 127 mM Cl. A mixture of two fluorescent dyes conjugated to dextrans (MW 10,000) was microinjected into domes and allowed to diffuse into the nearby LIS. The Cl-sensitive dye, ABQ-dextran, was selected because of its responsiveness at high Cl concentrations; a Cl-insensitive dye, Cl-NERF-dextran, was used as a reference. Both dyes were excited at 325 nm, and ratios of the fluorescence intensity at spectrally distinct emission wavelengths were obtained from two intensified CCD cameras, one for ABQ-dextran the other for Cl-NERF-dextran. LIS Cl concentration was calibrated in situ by treating the monolayer with digitonin or ouabain and varying the perfusate Cl between 0 and 137 mM (HEPES buffer) or between 0 and 127 mM (bicarbonate/CO2 buffer). LIS Cl in HEPES-buffered solutions averaged 176 +/- 19 mM (n = 12), calibrated with digitonin, and 170 +/- 9 mM (n = 12), calibrated with ouabain. LIS Cl in bicarbonate/CO2-buffered solutions averaged 174 +/- 10 mM (n = 7) using the ouabain calibration. The Cl concentration of MDCK cell domes, measured with Cl-sensitive microelectrodes and by microspectrofluorimetry, did not differ significantly, Images of the LIS at 3 focal planes, near the tight junction, midway and basal, failed to reveal any gradients in Cl concentration along the LIS. LIS Cl changed rapidly in response to perfusate Cl with characteristic times of 0.8 +/- 0.1 min (n = 21) for Cl decrease and 0.3 +/- 0.04 min (n = 21) for CI increase. In conclusion, (i) Cl concentration is higher in the LIS than in the bathing medium, (ii) no gradients of Cl along the depth of LIS are detectable, (iii) junctional Cl permeability is high. RP XIA, P (reprint author), NHLBI,KIDNEY & ELECTROLYTE METAB LAB,BETHESDA,MD 20892, USA. NR 17 TC 12 Z9 12 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0022-2631 J9 J MEMBRANE BIOL JI J. Membr. Biol. PD MAR PY 1995 VL 144 IS 1 BP 21 EP 30 PG 10 WC Biochemistry & Molecular Biology; Cell Biology; Physiology SC Biochemistry & Molecular Biology; Cell Biology; Physiology GA QL019 UT WOS:A1995QL01900003 PM 7541081 ER PT J AU WANG, JB MORIWAKI, A UHL, GR AF WANG, JB MORIWAKI, A UHL, GR TI DOPAMINE TRANSPORTER CYSTEINE MUTANTS - 2ND EXTRACELLULAR LOOP CYSTEINES ARE REQUIRED FOR TRANSPORTER EXPRESSION SO JOURNAL OF NEUROCHEMISTRY LA English DT Note DE CYSTEINES; THIOL-MODIFYING REAGENTS; EXTRACELLULAR LOOP; COCAINE; PARKINSONISM ID PARKINSONS-DISEASE; COCAINE; CLONING; BINDING; NEUROTRANSMITTER; RECOGNITION; RECEPTORS; SITE AB Studies with thiol-modifying reagents have suggested that cysteines might play important roles in the function of the dopamine transporter (DAT). To identify DAT cysteines with important thiol groups, we have studied six mutant dopamine transporters in which cysteines were replaced by alanines. Substitutions of cysteines assigned to the DAT's second putative extracellular loop-positions 180 and 189-dramatically decreased the expression of the mutant transporters. Substitutions at positions 90, 242, 305, and 345 had no significant effect in decreasing dopamine uptake, MPP(+) uptake, or cocaine analogue binding. Immunostaining COS cells transfected with Cys(180) and Cys(189) to Ala mutants revealed reduced membrane staining and prominent staining in perinuclear regions consistent with Golgi apparatus. These results suggest that cysteines in the DAT second extracellular loop may provide sulfide residues crucial to full transporter expression, at least in part, through interference with membrane insertion. Conceivably, they might also provide the targets for the influences of thiol-modifying reagents in modifying the function of the wild-type DAT expressed in striatal membranes. C1 NIDA,ADDICT RES CTR,MOLEC NEUROBIOL BRANCH,BALTIMORE,MD 21224. NIDA,ADDICT RES CTR,DIV INTRAMURAL RES,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROL,BALTIMORE,MD. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROSCI,BALTIMORE,MD. NR 23 TC 62 Z9 62 U1 1 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 MAR PY 1995 VL 64 IS 3 BP 1416 EP 1419 PG 4 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA QG995 UT WOS:A1995QG99500061 PM 7861176 ER PT J AU OREN, DA TURNER, EH WEHR, TA AF OREN, DA TURNER, EH WEHR, TA TI ABNORMAL CIRCADIAN-RHYTHMS OF PLASMA MELATONIN AND BODY-TEMPERATURE IN THE DELAYED SLEEP PHASE SYNDROME SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY LA English DT Letter RP OREN, DA (reprint author), NIMH,CLIN PSYCHOBIOL BRANCH,BLDG 10,ROOM 4S-239,10 CTR DR,MSC 1390,BETHESDA,MD 20892, USA. RI Turner, Erick/A-4848-2008 OI Turner, Erick/0000-0002-3522-3357 NR 6 TC 18 Z9 18 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 0022-3050 J9 J NEUROL NEUROSUR PS JI J. Neurol. Neurosurg. Psychiatry PD MAR PY 1995 VL 58 IS 3 BP 379 EP 379 DI 10.1136/jnnp.58.3.379 PG 1 WC Clinical Neurology; Psychiatry; Surgery SC Neurosciences & Neurology; Psychiatry; Surgery GA QN142 UT WOS:A1995QN14200025 PM 7897427 ER PT J AU MELLEN, N KIEMEL, T COHEN, AH AF MELLEN, N KIEMEL, T COHEN, AH TI CORRELATIONAL ANALYSIS OF FICTIVE SWIMMING IN THE LAMPREY REVEALS STRONG FUNCTIONAL INTERSEGMENTAL COUPLING SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID CENTRAL PATTERN GENERATOR; SPINAL-CORD; SYNAPTIC-INTERACTIONS; OSCILLATORS; LOCOMOTION; COORDINATION; CHAINS; MODEL; INTERNEURONS; SIMULATIONS AB 1. Cycle-to-cycle fluctuations in cycle periods and intersegmental burst delays of ventral root activity were studied during stable fictive swimming in the adult lamprey spinal cord. High spatial resolution was obtained by recording from 16 ventral roots, 1/2 on each side of the spinal cord. For ipsilateral ventral roots, correlations between cycle periods on the same cycle were high (0.50 +/- 0.16, mean +/- SD), and autocorrelations of intersegmental delays with a shift of one cycle were low (0.03 +/- 0.06). Correlations between cycle periods tended to decrease with intersegmental spacing but remained positive over the range of spacings tested (1-4,7 segments). 2. Sinusoidal movement imposed on the caudal end of the spinal cordlnotochord was used to entrain the fictive swimming rhythm. When the phase between the movement and the rhythm was perturbed, several cycles were required for the phase to return to its preferred value, indicating that in these experiments the effect of the movement was weak. In the absence of external perturbations, autocorrelations of delays between the movement and ventral root bursts with a shift of one cycle were high. 3. Numerical simulations with a simple stochastic phase model of the lamprey central pattern generator (CPG) were conducted. High correlations of periods and low autocorrelations of delays, the pattern observed experimentally, emerged as intersegmental connection strengths were increased. Coupling including both long and short connections produced this pattern of correlations with an average connection strength less than that required by short connections alone. 4. It is concluded that functional intersegmental coupling in the lamprey CPG during stable fictive swimming is strong. Specifically, the low autocorrelations of intersegmental delays indicate that intersegmental coupling is sufficiently strong to ensure that perturbations are almost completely corrected within one cycle. C1 UNIV MARYLAND,DEPT ZOOL,COLLEGE PK,MD 20742. NIDDK,MATH RES BRANCH,BETHESDA,MD 20892. FU NIMH NIH HHS [MH-44809]; NINDS NIH HHS [NS-16803] NR 29 TC 32 Z9 32 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD MAR PY 1995 VL 73 IS 3 BP 1020 EP 1030 PG 11 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA QU736 UT WOS:A1995QU73600012 PM 7608752 ER PT J AU CHEN, LL WISE, SP AF CHEN, LL WISE, SP TI NEURONAL-ACTIVITY IN THE SUPPLEMENTARY EYE FIELD DURING ACQUISITION OF CONDITIONAL OCULOMOTOR ASSOCIATIONS SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID DORSOMEDIAL FRONTAL-CORTEX; ADJACENT CINGULATE CORTEX; INFERIOR TEMPORAL CORTEX; INITIATED HAND MOVEMENTS; MONKEY DOPAMINE NEURONS; SINGLE-JOINT MOVEMENTS; PREMOTOR CORTEX; MOTOR CORTEX; MACAQUE MONKEY; INTRACORTICAL MICROSTIMULATION AB 1. The supplementary eye field (SEF) has been viewed as a premotor cortical held for the selection and control of saccadic eye movements. Drawing on studies of the neighboring premotor cortex, we hypothesized that if the SEF participates in the selection of action based on arbitrary stimulus-response associations, then task-related activity in the SEF should change during the learning of such associations. 2. Rhesus monkeys were operantly conditioned to make a saccadic eye movement to one of four targets (7 deg up, down, left, and right from center) in response to a foveal instruction stimulus (IS). One and only one of those four possible responses was arbitrarily designated ''correct'' for each IS. The monkeys responded to familiar ISs, four stimuli that remained unchanged throughout training and recording, as well as to novel ISs, which the monkeys had not previously seen. The monkeys initially chose responses to novel stimuli by trial and error, with near chance levels of performance, but quickly learned to select the correct saccade. 3. We studied 186 SEF cells as monkeys learned new visuomotor associations. Neuronal activity was quantified in four task periods: during the presentation of the IS, during an instructed delay period (i.e., after the removal of the IS but before a trigger or ''go'' stimulus), just before the saccade, and after the saccade during fixation of the target location. The discharge rate in each task period was considered a separate case for analysis, compared with that in a reference period preceding the IS, and eliminated from Further analysis ii not significantly different. 4. We observed two main categories of activity change during learning, which we termed learning selective and learning dependent. Learning-selective cases showed a significant evolution in activity as the monkeys learned which saccade was instructed by a novel IS, but had no significant modulation during trials with familiar ISs. Many of these cells were virtually inactive on trials with familiar ISs. However, they initially showed dramatic modulation when tested with a novel IS. As the monkey chose the correct saccade (or target) with increasing reliability, the modulation often decremented until the cell was again relatively unmodulated, as observed during familiar-IS trials. These cells usually remained relatively inactive until the monkeys were challenged to start learning another new stimulus-response association. Learning-selective activity was observed in all task periods, and 33 (18%) of the 186 adequately tested SEF cells showed learning-selective activity in one or more task periods. 5. Learning-dependent cases, similar to learning-selective ones, significantly changed activity during the course of learning. Learning-dependent cases differed From learning-selective ones in showing task-related modulation for familiar-IS trials. Their activity was often lowest at the beginning of learning, but steadily incremented, trial by trial, in close correlation with the monkeys' improvement in selecting the correct response. In most costs, discharge rates on novel-IS trials converged on those for the familiar IS instructing the same saccade, Learning-dependent activity was observed in all task periods, and 68 (37%) of 186 adequately tested SEF cells showed significant learning-dependent activity in one or more task periods. 6. The present findings support the hypothesis that SEF plays a role in the selection of eye movements or saccade targets on the basis of arbitrary stimuli and suggest that it may be part of a neural network responsible for learning flexible nonspatial stimulus-response relations. C1 NIMH,NEUROPHYSIOL LAB,POOLESVILLE,MD 20837. NR 96 TC 195 Z9 195 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD MAR PY 1995 VL 73 IS 3 BP 1101 EP 1121 PG 21 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA QU736 UT WOS:A1995QU73600018 PM 7608758 ER PT J AU CHEN, LL WISE, SP AF CHEN, LL WISE, SP TI SUPPLEMENTARY EYE FIELD CONTRASTED WITH THE FRONTAL EYE FIELD DURING ACQUISITION OF CONDITIONAL OCULOMOTOR ASSOCIATIONS SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID ADJACENT CINGULATE CORTEX; NEURONAL-ACTIVITY; MACAQUE MONKEY; RHESUS-MONKEYS; INTRACORTICAL MICROSTIMULATION; SUPERIOR COLLICULUS; MESIAL AREA-6; PRIMATE; MOVEMENTS; MOTOR AB 1. The companion paper reported that a substantial proportion of cells in the supplementary eye field (SEF) of macaque monkeys show significant evolution of neuronal activity as subjects learn new and arbitrary stimulus-saccade associations. The purpose of the present study was to compare and contrast the activity of the SEF and the frontal eye field (FEF) during such conditional oculomotor learning. 2. In both SEF and FEF, we observed learning-dependent and learning-selective activity, defined as significant evolution of task-related activity as monkeys learned which of four saccades was instructed by a novel stimulus. By definition, in addition to changes as the monkeys learned the instructional significance of a novel instruction stimulus, learning-dependent activity also showed task-related modulation for trials instructed by familiar stimuli, whereas learning-selective activity did not. Of the 186 SEF neurons adequately tested, 81 (44%) showed one of these two categories of learning-related change. By contrast, of the 90 FEF neurons adequately tested, only 14 (16%) showed similar properties. This difference was highly statistically significant (chi(2) = 21.1; P < 0.001). 3. We also observed persistent differences in activity for trials with familiar versus novel instruction stimuli, which we termed learning-static effects. In some cases, the learning-static effect coexisted with learning-dependent or learning-selective changes in activity, although in others it did not. In the former cases, activity changed systematically during learning, but reached a level that differed from that for familiar stimuli instructing the same saccade. In the latter cases, the activity did not change significantly as the monkey learned new conditional oculomotor associations, but did show a significant difference depending upon whether a novel or familiar stimulus instructed a given saccade. Overall, 66 of 186 (35%) cells in the SEF and 17 of 90 (19%) cells in the FEF showed learning-static effects in one or more task periods. This difference was statistically significant (chi(2) = 7.9; P < 0.005). 4. The significant difference in the properties of SEF and FEF cells suggests a functional dissociation of the two areas during conditional oculomotor learning. In this respect, the FEF resembles the primary motor cortex, whereas the SEF resembles the premotor cortex. C1 NIMH,NEUROPHYSIOL LAB,POOLESVILLE,MD 20837. NR 35 TC 119 Z9 120 U1 2 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD MAR PY 1995 VL 73 IS 3 BP 1122 EP 1134 PG 13 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA QU736 UT WOS:A1995QU73600019 PM 7608759 ER PT J AU SHOLOMENKO, GN ODONOVAN, MJ AF SHOLOMENKO, GN ODONOVAN, MJ TI DEVELOPMENT AND CHARACTERIZATION OF PATHWAYS DESCENDING TO THE SPINAL-CORD IN THE EMBRYONIC CHICK SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID EXCITATORY AMINO-ACIDS; CENTRAL NERVOUS-SYSTEM; BRAIN-STEM INFUSION; MOTOR-ACTIVITY; NEUROTRANSMITTER AGONISTS; RETICULOSPINAL NEURONS; RETICULAR-FORMATION; HIND-LIMB; LOCOMOTION; PROJECTIONS AB 1. We used an isolated preparation of the embryonic chick brain stem and spinal cord to examine the origin, trajectory, and effects of descending supraspinal pathways on lumbosacral motor activity. The in vitro preparation remained viable for less than or equal to 24 h and was sufficiently stable for electrophysiological pharmacological, and neuroanatomic examination. In this preparation as in the isolated spinal cord, spontaneous episodes of both forelimb and hindlimb motor activity occur in the absence of phasic afferent input. Motor activity can also be evoked by brain stem electrical stimulation or modulated by the introduction of neurochemicals to the independently perfused brain stem. 2. At embryonic day (E)6, lumbosacral motor activity could be evoked by brain stem electrical stimulation. At E5, neither brain stem nor spinal cord stimulation evoked activity in the lumbosacral spinal cord, although motoneurons did express spontaneous activity. 3. Lesion and electrophysiological studies indicated that axons traveling in the ventral cord mediated the activation of lumbosacral networks by brain stem stimulation. 4. Partition of the preparation into three separately perfused baths, using a zero-Ca2+ middle bath that encompassed the cervical spinal cord, demonstrated that the brain stem activation of spinal networks could be mediated by long-axoned pathways connecting the brain stem and lumbosacral spinal cord. 5. Using retrograde tracing from the spinal cord combined with brain stem stimulation, we found that the brain stem regions from which spinal activity could be evoked lie in the embryonic reticular formation close to neurons that send long descending axons to the lumbosacral spinal cord. The cells giving rise to these descending pathways are found in the ventral pontine and medullary reticular formation, a region that is the source of reticulospinal neurons important for motor activity in adult vertebrates. 6. Electrical recordings from this region revealed that the activity of some brain stem neurons was synchronized with the electrical activity of lumbosacral motoneurons during evoked or spontaneous episodes of rhythmic motor activity. 7. Both brain stem and spinal cord activity could be modulated by selective application of the glutamate agonist N-methyl-D-aspartate to the brain stem, supporting the existence of Functionally active descending projections from the brain stem to the spinal cord. It is not yet clear what role the brain stem activity carried by these pathways has in the genesis and development of spinal cord motor activity. C1 NIH,NEURAL CONTROL LAB,DEV NEUROBIOL SECT,BETHESDA,MD 20892. RP SHOLOMENKO, GN (reprint author), SIMON FRASER UNIV,DEPT BIOL SCI,BURNABY,BC V5A 1S6,CANADA. NR 55 TC 19 Z9 19 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD MAR PY 1995 VL 73 IS 3 BP 1223 EP 1233 PG 11 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA QU736 UT WOS:A1995QU73600027 PM 7608767 ER PT J AU ZHANG, L RAVIPATI, A JOSEPH, J ROTH, GS AF ZHANG, L RAVIPATI, A JOSEPH, J ROTH, GS TI AGING-RELATED CHANGES IN RAT STRIATAL D-2 RECEPTOR MESSENGER-RNA-CONTAINING NEURONS - A QUANTITATIVE NONRADIOACTIVE IN-SITU HYBRIDIZATION STUDY SO JOURNAL OF NEUROSCIENCE LA English DT Article DE AGING; D-2 RECEPTOR MESSENGER-RNA-CONTAINING NEURONS; STRIATUM; NONRADIOACTIVE IN SITU HYBRIDIZATION; DIGOXIGENIN; COMPUTER-ASSISTED IMAGE ASSESSMENT ID MESSENGER-RNA; DOPAMINE-RECEPTORS; WISTAR RATS; RECOVERY; BLOCKADE AB In situ hybridization of a digoxigenin-labeled oligonucleotide probe combined with computer-assisted image assessment was used to directly visualize D-2 receptor mRNA-containing neurons in rat striata, and quantify age-related changes in the sizes and relative mRNA content of these neurons. It was found that: (1) numbers of D-2 mRNA-containing neurons appear to decrease in striata of aged rats, (2) relative amounts of D-2 receptor mRNA decrease in striatal neurons of aged rats, and (3) neurons of all sizes appear to be lost, with the greatest absolute decrease in those smaller than 90 mu m(2). These data confirm the well documented age-associated loss of D-2 dopamine receptors, and further suggest that both neuronal death and reduced transcription contribute to this decrement. C1 NIA,GERONTOL RES CTR,MOLEC PHYSIOL & GENET SECT,BALTIMORE,MD 21224. TUFTS UNIV,USDA,ARS,HUMAN NUTR RES CTR AGING,BOSTON,MA 02111. NR 17 TC 40 Z9 41 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD MAR PY 1995 VL 15 IS 3 BP 1735 EP 1740 PN 1 PG 6 WC Neurosciences SC Neurosciences & Neurology GA QM467 UT WOS:A1995QM46700010 PM 7891131 ER PT J AU SMITH, MA MAKINO, S KVETNANSKY, R POST, RM AF SMITH, MA MAKINO, S KVETNANSKY, R POST, RM TI STRESS AND GLUCOCORTICOIDS AFFECT THE EXPRESSION OF BRAIN-DERIVED NEUROTROPHIC FACTOR AND NEUROTROPHIN-3 MESSENGER-RNAS IN THE HIPPOCAMPUS SO JOURNAL OF NEUROSCIENCE LA English DT Article DE STRESS; BRAIN-DERIVED NEUROTROPHIC FACTOR; NEUROTROPHIN-3; HIPPOCAMPUS; GLUCOCORTICOIDS; PLASTICITY ID NERVE GROWTH-FACTOR; LONG-TERM POTENTIATION; FACTOR MESSENGER-RNA; TRANSIENT FOREBRAIN ISCHEMIA; RAT-BRAIN; FACTOR FAMILY; MOLECULAR-CLONING; PYRAMIDAL NEURONS; LIMBIC SEIZURES; TYROSINE KINASE AB Chronic stress produces structural changes and neuronal damage especially in the hippocampus. Because neurotrophic factors affect neuron survival, we questioned whether they might be relevant to the heightened vulnerability of hippocampal neurons following stress. To begin investigating this possibility, we examined the effects of immobilization stress (2 hr/d) on the expression of neurotrophic factors in rat brains using in situ hybridization. We found that single or repeated immobilization markedly reduced brain-derived neurotrophic factor (BDNF) mRNA levels in the dentate gyrus and hippocampus. In contrast, NT-3 mRNA levels were increased in the dentate gyrus and hippocampus in response to repeated but not acute stress. Stress did not affect the expression of neurotrophin-4, or tyrosine receptor kinases (trkB or C). Corticosterone negative feedback may have contributed in part to the stress-induced decreases in BDNF mRNA levels, but stress still decreased BDNF in the dentate gyrus in adrenalectomized rats suggesting that additional components of the stress response must also contribute to the observed changes in BDNF. However, corticosterone-mediated increases in NT-3 mRNA expression appeared to be primarily responsible for the effects of stress on NT-3. These findings demonstrate that BDNF and NT-3 are stress-responsive genes and raise the possibility that alterations in the expression of these or other growth factors might be important in producing some of the physiological and pathophysiological effects of stress in the hippocampus. C1 NIMH,CLIN NEUROENDOCRINOL BRANCH,BETHESDA,MD 20892. SLOVAK ACAD SCI,INST EXPTL ENDOCRINOL,BRATISLAVA,SLOVAKIA. RP SMITH, MA (reprint author), NIMH,BIOL PSYCHIAT BRANCH,BLDG 10,ROOM 3N212,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 57 TC 908 Z9 940 U1 1 U2 19 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD MAR PY 1995 VL 15 IS 3 BP 1768 EP 1777 PN 1 PG 10 WC Neurosciences SC Neurosciences & Neurology GA QM467 UT WOS:A1995QM46700013 PM 7891134 ER PT J AU MURRAY, AM HYDE, TM KNABLE, MB HERMAN, MM BIGELOW, LB CARTER, JM WEINBERGER, DR KLEINMAN, JE AF MURRAY, AM HYDE, TM KNABLE, MB HERMAN, MM BIGELOW, LB CARTER, JM WEINBERGER, DR KLEINMAN, JE TI DISTRIBUTION OF PUTATIVE D4 DOPAMINE-RECEPTORS IN POSTMORTEM STRIATUM FROM PATIENTS WITH SCHIZOPHRENIA SO JOURNAL OF NEUROSCIENCE LA English DT Article DE D4; DOPAMINE RECEPTORS; SCHIZOPHRENIA; AUTORADIOGRAPHY; POSTMORTEM; BRAIN ID POSITRON EMISSION TOMOGRAPHY; HUMAN-BRAIN; BINDING; CLONING; GENE; NEUROLEPTICS; PARKINSONS; DENSITY; D1 AB The identification of five dopamine receptor subtypes has given the dopamine hypothesis of schizophrenia new life. The D4 receptor is particularly intriguing because it binds clozapine with high affinity. Putative D4 receptors were labeled in postmortem human brain by subtracting the binding of a saturating concentration of H-3-raclopride (6 nM, which labels D2 and D3 receptors) from that labeled by a saturating concentration of [H-3]YM 09151-2 (1-1.3 nM, which labels D2, D3, and D4 receptors). In the control brain, putative D4 receptors show a homogenous distribution in striatum and nucleus accumbens. This is also true in schizophrenic brains, although the levels are significantly higher (twofold). These data are inconsistent with mRNA studies that have shown negligible amounts in striatum and accumbens, with modest amounts reported in most of cerebral cortex. These findings suggest that the putative D4 receptors are not synthesized in this region, but are presynaptically localized on striatal afferent terminals. Our findings confirm and extend the report of Seeman et al. (1993). Extension of these findings into the nucleus accumbens is important because of its extensive connections to the limbic system while the putamen is exclusively ''motor'' striatum. C1 OFF CHIEF MED EXAMINER,WASHINGTON,DC 20032. RP MURRAY, AM (reprint author), ST ELIZABETH HOSP,NIMH,CLIN BRAIN DISORDERS BRANCH,INTRAMURAL RES PROGRAM,WASHINGTON,DC 20032, USA. NR 35 TC 173 Z9 173 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD MAR PY 1995 VL 15 IS 3 BP 2186 EP 2191 PN 2 PG 6 WC Neurosciences SC Neurosciences & Neurology GA QM468 UT WOS:A1995QM46800009 PM 7891160 ER PT J AU NIEDZIELSKI, AS WENTHOLD, RJ AF NIEDZIELSKI, AS WENTHOLD, RJ TI EXPRESSION OF AMPA, KAINATE, AND NMDA RECEPTOR SUBUNITS IN COCHLEAR AND VESTIBULAR GANGLIA SO JOURNAL OF NEUROSCIENCE LA English DT Article DE GLUTAMATE RECEPTOR; IN SITU HYBRIDIZATION; IMMUNOCYTOCHEMISTRY; AUDITORY PERIPHERY; HAIR CELL; RAT ID GUINEA-PIG COCHLEA; SELECTIVE GLUTAMATE RECEPTORS; METHYL-D-ASPARTATE; MAMMALIAN COCHLEA; OPERATED CHANNELS; MOLECULAR-CLONING; NERVOUS-SYSTEM; MESSENGER-RNAS; HIGH-AFFINITY; RAT-BRAIN AB Glutamate is believed to be the principal afferent neurotransmitter in the peripheral auditory and vestibular systems. In this report, we present a comprehensive molecular analysis of ionotropic glutamate receptor gene expression in the cochlear and vestibular ganglia of the rat. Fourteen glutamate receptor subunits were studied: GluR1-4 (including flip and flop variants), GluR5-7, KA1&2, NR1, and NR2A-D. Reverse transcription of RNA followed by DNA amplification with the polymerase chain reaction was used for the initial analysis. Immunocytochemistry and in situ hybridization with subunit-specific oligonucleotides were subsequently used for cellular localization of receptor expression. AMPA (GluR2-4), kainate (GluR5&6 and KA1&2), and NMDA receptor (NR1 and NR2A-D) subunit expression was detected. Based on the relative amounts of mRNA detected by in situ hybridization, the predominant receptors expressed by cochlear and vestibular ganglion cells appear to be GluR2, GluR3, GluR4, GluR5, and NR1. At a moderate level were GluR6, NR2B, and NR2D. KA1, KA2, NR2A, and NR2C mRNAs were also expressed in ganglion cells, but at lower levels. Only the AMPA receptor subunit GluR1 and the kainate receptor subunit GluR7 were not found to be expressed in vestibulocochlear neurons. These studies suggest that functional AMPA, kainate, and NMDA receptors are present at the hair cell/vestibulocochlear nerve synapse. RP NIEDZIELSKI, AS (reprint author), NIDCD,NEUROCHEM LAB,BLDG 36,ROOM 5D08,BETHESDA,MD 20892, USA. NR 58 TC 118 Z9 119 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD MAR PY 1995 VL 15 IS 3 BP 2338 EP 2353 PN 2 PG 16 WC Neurosciences SC Neurosciences & Neurology GA QM468 UT WOS:A1995QM46800022 PM 7891171 ER PT J AU MAYAT, E PETRALIA, RS WANG, YX WENTHOLD, RJ AF MAYAT, E PETRALIA, RS WANG, YX WENTHOLD, RJ TI IMMUNOPRECIPITATION, IMMUNOBLOTTING, AND IMMUNOCYTOCHEMISTRY STUDIES SUGGEST THAT GLUTAMATE-RECEPTOR DELTA-SUBUNITS FORM NOVEL POSTSYNAPTIC RECEPTOR COMPLEXES SO JOURNAL OF NEUROSCIENCE LA English DT Article DE LIGAND BINDING; PURKINJE CELLS; PARALLEL FIBERS; CEREBELLUM; LONG-TERM DEPRESSION; METABOTROPIC GLUTAMATE RECEPTORS ID ACID BINDING-SITES; CENTRAL-NERVOUS-SYSTEM; RAT-BRAIN; FUNCTIONAL EXPRESSION; POSTNATAL-DEVELOPMENT; SIGNAL TRANSDUCTION; CEREBELLAR CORTEX; MOLECULAR-CLONING; PURKINJE-CELLS; KAINATE AB An antibody was made to a C-terminus peptide of the glutamate receptor delta 2 subunit and used to study the distribution, biochemical properties, and developmental expression of the delta receptor in rat brain. The antibody recognizes both delta 1 and delta 2 but not AMPA, kainate, NMDA, and mGluR1 alpha glutamate receptor subunits based on Western blot analysis of transfected HEK-293 cells. Western blot analysis of brain showed a single immunoreactive band, migrating at M(r) = 114,000. Immunoprecipitation of detergent-solubilized cerebellar membranes was done to determine if delta is associated with other glutamate receptor subunits and if it binds any of the common excitatory amino acid ligands. Based on results of these studies, AMPA, kainate, NMDA, and mGluR1 alpha subunits do not coassemble with delta subunits, and H-3-glutamate, H-3-AMPA and H-3-kainate do not bind to the delta receptor complex. Western blot and immunocytochemical analyses showed marked expression of delta in the cerebellum while lower levels were detected in other regions of the brain. A dramatic increase of delta 1/2 immunoreactivity was observed in the cerebellum between the ages of 10 and 15 d postnatal. Light and electron microscopy, respectively, demonstrated dense immunostaining in Purkinje cells and in postsynaptic densities of the adult parallel fiber-Purkinje spine synapse. The prominent delta 1/2 immunoreactivity found in the parallel fiber-Purkinje spine synapse, and the temporal correlation of the development of this synapse with the major increase in delta 1/2 immunoreactivity, suggest a major functional role for the delta subunits in cerebellar circuitry. RP MAYAT, E (reprint author), NIDCD,NEUROCHEM LAB,BLDG 36,ROOM 5D-08,BETHESDA,MD 20892, USA. NR 76 TC 88 Z9 89 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD MAR PY 1995 VL 15 IS 3 BP 2533 EP 2546 PN 2 PG 14 WC Neurosciences SC Neurosciences & Neurology GA QM468 UT WOS:A1995QM46800038 PM 7891187 ER PT J AU NIKODIJEVIC, B ASCHKENASY, M DICKENS, G LACHANCE, C GUROFF, G AF NIKODIJEVIC, B ASCHKENASY, M DICKENS, G LACHANCE, C GUROFF, G TI CHARACTERISTICS OF THE K-252A-INDUCED INCREASE IN CALCIUM-UPTAKE IN PC12 CELLS SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE PC12; CALCIUM; K-252A; NEUROTROPHIN ID NERVE GROWTH-FACTOR; INDUCED NEURITE OUTGROWTH; PROTEIN-KINASE INHIBITOR; GANGLION-CELLS; K-252A; PHOSPHORYLATION; SURVIVAL; NEURONS AB K-252a treatment produced a 30-50% increase in the uptake of radioactive calcium by PC12 cells within 3-4 minutes. The increase in uptake was partially blocked by inhibitors of voltage-operated calcium channels, such as nifedipine, but not by inhibitors of receptor-operated calcium channels, such as nickel or suramin. Introduction of phosphatase 2A into the cells completely blocked the effect of K-252a. Long-term treatment of the cells with either K-252a or with nerve growth factor blocked the subsequent actions of either K-252a or nerve growth factor on calcium uptake, but neither altered the subsequent action of the L-channel agonist Bay K 8644 on calcium uptake. Calcium uptake was not stimulated by K-252a in PC12nnr, cells that have little or no high-affinity nerve growth factor receptors; cells expressing increased levels of high-affinity nerve growth factor receptors showed a response to K-252a comparable to that seen in parent PC12. The data suggest that the increased uptake of radioactive calcium produced by K-252a is mediated by a mechanism very similar to that serving the increased calcium uptake produced by nerve growth factor. (C) 1995 Wiley-Liss, Inc. C1 NICHHD,GROWTH FACTORS SECT,BETHESDA,MD 20892. NR 23 TC 2 Z9 2 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD MAR 1 PY 1995 VL 40 IS 4 BP 494 EP 498 DI 10.1002/jnr.490400408 PG 5 WC Neurosciences SC Neurosciences & Neurology GA QL262 UT WOS:A1995QL26200007 PM 7616609 ER PT J AU STEELE, VE PEREIRA, MA SIGMAN, CC KELLOFF, GJ AF STEELE, VE PEREIRA, MA SIGMAN, CC KELLOFF, GJ TI CANCER CHEMOPREVENTION AGENT DEVELOPMENT STRATEGIES FOR GENISTEIN SO JOURNAL OF NUTRITION LA English DT Article; Proceedings Paper CT 1st International Symposium on the Role of Soy in Preventing and Treating Chronic Disease CY FEB 20-23, 1994 CL MESA, AZ SP UNITED SOYBEAN BOARD, PROTEIN TECHNOL INT DE CHEMOPREVENTION; GENISTEIN; DRUG DEVELOPMENT; CARCINOGENESIS; CANCER PREVENTION ID KINASE INHIBITOR; TYROSINE KINASE; CELLS; PHOSPHORYLATION; EXPRESSION; COLON AB Cancer chemoprevention refers to the reduction of cancer incidence by administration of agents or drugs that inhibit, reverse or retard the cancer process. Genistein has demonstrated a wide variety of biological activities that make it a good candidate for a chemopreventive agent. Many agents, such as genistein, are currently being tested with the goal of developing safe and effective chemopreventive drugs for human use. Genistein was investigated as a potential chemopreventive agent in an azoxymethane-induced colon carcinogenesis model. Genistein was tested for its ability to inhibit aberrant colon crypts in the colon of F344 rats that had been treated with azoxymethane. Genistein was administered in the diet from 1 wk before the carcinogen to 4 wk after the first carcinogen dose for a total of 5 wk. At both doses, 75 and 150 mg/kg, the mean number of foci per colon was significantly reduced. Further development of this agent includes demonstration of the preventive efficacy in an in vivo tumorigenesis model, followed by preclinical pharmacology and toxicology testing. Phase 1, 2 and 3 clinical chemoprevention trials would be then performed to determine pharmacokinetics, safe doses, and effectiveness for New Drug Approval. C1 NCI,DIV CANC PREVENT & CONTROL,CHEMOPREVENT BRANCH,BETHESDA,MD 20892. CCS ASSOCIATES,MT VIEW,CA 94043. MED COLL OHIO,DEPT PATHOL,TOLEDO,OH 43614. NR 21 TC 88 Z9 90 U1 1 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 MAR PY 1995 VL 125 IS 3 SU S BP S713 EP S716 PG 4 WC Nutrition & Dietetics SC Nutrition & Dietetics GA QM161 UT WOS:A1995QM16100024 PM 7884556 ER PT J AU KREBSSMITH, SM HEIMENDINGER, J SUBAR, AF PATTERSON, BH PIVONKA, E AF KREBSSMITH, SM HEIMENDINGER, J SUBAR, AF PATTERSON, BH PIVONKA, E TI USING FOOD FREQUENCY QUESTIONNAIRES TO ESTIMATE FRUIT AND VEGETABLE INTAKE - ASSOCIATION BETWEEN THE NUMBER OF QUESTIONS AND TOTAL INTAKES SO JOURNAL OF NUTRITION EDUCATION LA English DT Article AB The purpose of this study was to determine how estimates of fruit and vegetable intake, as determined from food frequency questionnaires, may be affected by the number of foods included. Three different national surveys of adults were used. Each of the surveys employed a food frequency questionnaire, but each included a different number of questions related to fruits and vegetables. Compared across surveys, values for median frequency of intake of individual fruits and vegetables were generally similar. However, values for median frequency of total fruit and vegetable intake, determined by summing across all fruits and vegetables included in the respective questionnaires, were very different and were associated with the number of questions asked: the 1987 National Health Interview Survey included 20 questions regarding fruits and vegetables, and the median frequency of intake was 23.8 times per week; the baseline survey for the national 5 A Day for Better Health Program included 33 questions, and the median intake was 34.6; and the 1982-1984 NHANES I Epidemiologic Follow-up Survey included 40 questions, and the median intake was 38.8. These findings suggest that summing across frequencies for individual foods may not be a valid way to assess intakes of total fruits and vegetables. Summary questions and/or adjustment factors may need to be employed to increase precision of the estimates. RP KREBSSMITH, SM (reprint author), NCI,DIV CANC PREVENT & CONTROL,EXECUT PLAZA N,ROOM 313,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 0 TC 81 Z9 82 U1 1 U2 4 PU DECKER PERIODICALS INC PI HAMILTON PA 4 HUGHSON ST, PO BOX 620, LCD 1, HAMILTON ON L8N 3K7, CANADA SN 0022-3182 J9 J NUTR EDUC JI J. Nutr. Educ. PD MAR-APR PY 1995 VL 27 IS 2 BP 80 EP 85 PG 6 WC Education, Scientific Disciplines; Nutrition & Dietetics SC Education & Educational Research; Nutrition & Dietetics GA QR210 UT WOS:A1995QR21000007 ER PT J AU HEINEMAN, EF GAO, YT DOSEMECI, M MCLAUGHLIN, JK AF HEINEMAN, EF GAO, YT DOSEMECI, M MCLAUGHLIN, JK TI OCCUPATIONAL RISK-FACTORS FOR BRAIN-TUMORS AMONG WOMEN IN SHANGHAI, CHINA SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article; Proceedings Paper CT International Conference on Womens Health - Occupation and Cancer CY NOV, 1993 CL BALTIMORE, MD ID CANCER; EXPOSURE; FARMERS; GLIOMAS; CARCINOGENS; MORTALITY; MENINGES; FIELDS AB The etiology of brain cancer is not well understood and few studies have evaluated occupational risk factors among women. We evaluated occupation and industry at time of diagnosis for 276 incident primary brain tumor cases among women in Shanghai, China, for the period 1980-1984, identified through the Shanghai Cancer Registry. Standardized incidence ratios (SIRs) and their 95% confidence intervals (CIs) were calculated for all occupations and industries with at least three female cases. SIRs compared observed to expected numbers of cases, based on incidence rates for Shanghai and the number of women in each occupation and industry according to the 1982 census. Statistically significant excesses of brain tumors were seen among grain farmers (SIR = 6.5, 95% CI = 1.3-19.1), rubber workers (SIR = 5.0, 95% CI = 1.6-11.6), and workers in transportation equipment manufacture and repair (SIR 2.3, 95% CI = 1.1-4.3). Risks among textile spinners and winders were of borderline significance (SIR CI = 1.0-2.8). Elevated but nonsignificant risks of 2.0 or greater were seen among nurses, plastic products workers, sanitation workers, painters, and workers in manufacture of equipment for electrical generation, transmission, and distribution. Results for farmers, rubber workers, and painters are consistent with previously reported excesses among these occupations in men. The increase among nurses is a new finding, although elevated risks have been observed among male medical professionals. Risks were elevated with likely exposure to pesticides, particularly among those thought to have a high probability and a high level of exposure (SIR = 3.6, 95% CI = 1.2-8.5). C1 SHANGHAI CANC INST,DEPT EPIDEMIOL,SHANGHAI,PEOPLES R CHINA. RP HEINEMAN, EF (reprint author), NCI,DIV CANC EPIDEMIOL,EPIDEMIOL & BIOSTAT PROGRAM,OCCUPAT STUDIES SECT,6130 EXECUT BLVD,ROCKVILLE,MD 20852, USA. NR 22 TC 23 Z9 23 U1 0 U2 2 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1076-2752 J9 J OCCUP ENVIRON MED JI J. Occup. Environ. Med. PD MAR PY 1995 VL 37 IS 3 BP 288 EP 293 DI 10.1097/00043764-199503000-00003 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA QM284 UT WOS:A1995QM28400003 PM 7796195 ER PT J AU DOODY, MM MANDEL, JS BOICE, JD AF DOODY, MM MANDEL, JS BOICE, JD TI EMPLOYMENT PRACTICES AND BREAST-CANCER AMONG RADIOLOGIC TECHNOLOGISTS SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article; Proceedings Paper CT International Conference on Womens Health - Occupation and Cancer CY NOV, 1993 CL BALTIMORE, MD ID CURRENT MORTALITY RATES; PHYSICIAN SPECIALISTS; X-RAYS; WORKERS; TUBERCULOSIS; IRRADIATION; RADIATION; HEALTH; DEATH; WOMEN AB A case-control study of breast cancer and employment practices among female radiologic technologists was conducted. The cohort from which cases and controls were derived included over 105,000 female medical radiation workers certified by the American Registry of Radiologic Technologists during 1926-1980. Breast cancer cases (n = 528) were individually matched to an average of five control subjects (n = 2628) based on year of birth, year of certification, and length of follow-up. Procedures most commonly performed by controls included fluoroscopy (93%), portable radiographs (92%), routine radiographs (92%), multifilm procedures (87%), dental x-rays (46%), radium therapy (31%), orthovoltage (23%), and cobalt-60 (21%). Breast cancer was not significantly increased with occupational experience with any of these procedures. Furthermore, risk was not related to number of years worked with a particular procedure. This study is reassuring in indicating that medical radiation workers are not at substantial risk for developing radiation-induced breast cancer. However, because only surrogate measures of radiation exposure were available, possibility of a small risk cannot be discounted. Ongoing follow-up of this cohort for incident cancers will incorporate detailed exposure assessment schemes, providing additional information on effects of long-term low-dose radiation, through occupation. C1 UNIV MINNESOTA,DEPT ENVIRONM & OCCUPAT HLTH,MINNEAPOLIS,MN 55455. RP DOODY, MM (reprint author), NCI,RADIAT EPIDEMIOL BRANCH,EXECUT PLAZA N,ROOM 408,BETHESDA,MD 20892, USA. FU NCI NIH HHS [N01-CP-85604, N01-CP-05609, N01-CP-95614] NR 30 TC 17 Z9 17 U1 4 U2 7 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1076-2752 J9 J OCCUP ENVIRON MED JI J. Occup. Environ. Med. PD MAR PY 1995 VL 37 IS 3 BP 321 EP 327 DI 10.1097/00043764-199503000-00009 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA QM284 UT WOS:A1995QM28400009 PM 7796200 ER PT J AU CANTOR, KP STEWART, PA BRINTON, LA DOSEMECI, M AF CANTOR, KP STEWART, PA BRINTON, LA DOSEMECI, M TI OCCUPATIONAL EXPOSURES AND FEMALE BREAST-CANCER MORTALITY IN THE UNITED-STATES SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article; Proceedings Paper CT International Conference on Womens Health - Occupation and Cancer CY NOV, 1993 CL BALTIMORE, MD ID RUBBER WORKERS; RISK; EPIDEMIOLOGY; HYPOTHESIS; COHORT; MATRIX AB Mortality records from 24 states, gathered from 1984 to 1989 and coded for occupation and industry, were used to develop leads to workplace exposures as possible breast cancer risk factors. A case-control approach was used, with separate analyses for blacks and whites. After excluding homemakers, 33,509 cases and 117,794 controls remained. A job exposure matrix was used to estimate the probability and level of 31 workplace exposures. After adjusting for socioeconomic status, suggestive associations for probability and level of exposure were found for styrene, several organic solvents (methylene chloride, carbon tetrachloride, formaldehyde), and several metals/metal oxides and acid mists. Because of the methodologic limitations of this study, its primary value is in suggesting hypotheses for further evaluation. The findings for styrene, selected solvents, and metals and metal-related exposures deserve additional study. RP CANTOR, KP (reprint author), NCI,DIV CANC ETIOL,ENVIRONM EPIDEMIOL BRANCH,443 EXECUT PLAZA N,BETHESDA,MD 20892, USA. RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 NR 37 TC 91 Z9 94 U1 1 U2 8 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1076-2752 J9 J OCCUP ENVIRON MED JI J. Occup. Environ. Med. PD MAR PY 1995 VL 37 IS 3 BP 336 EP 348 DI 10.1097/00043764-199503000-00011 PG 13 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA QM284 UT WOS:A1995QM28400011 PM 7796202 ER PT J AU SAVITZ, DA ANDREWS, KW BRINTON, LA AF SAVITZ, DA ANDREWS, KW BRINTON, LA TI OCCUPATION AND CERVICAL-CANCER SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article; Proceedings Paper CT International Conference on Womens Health - Occupation and Cancer CY NOV, 1993 CL BALTIMORE, MD ID UNITED-STATES; WHITE WOMEN; RISK; SMOKING; DIET AB Data collected for a multicenter case-control study of invasive cervical cancer and carcinoma in situ of the cervix were analyzed with regard to occupation. Odds ratios comparing 481 invasive cases and 293 carcinoma in situ cases to 801 controls were calculated and adjusted for potential confounding factors. Working women and homemakers had a similar risk of invasive cervical cancer, with several groups of service and industrial workers showing elevated risks (particularly maids, cleaners, and cooks). Risk of carcinoma in situ was slightly increased for working women, but no occupational groups had notable associations. The principal strengths of this analysis were the ability to address both invasive cervical cancer and carcinoma in situ and to control for multiple potential confounding factors. However, occupational information was limited and risk estimates for women in specific occupations were imprecise. C1 NCI,ENVIRONM EPIDEMIOL BRANCH,ENVIRONM STUDIES SECT,BETHESDA,MD 20892. RP SAVITZ, DA (reprint author), UNIV N CAROLINA,SCH PUBL HLTH,DEPT EPIDEMIOL,CB 7400,CHAPEL HILL,NC 27599, USA. RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 FU NIEHS NIH HHS [T32 ES 07018-16S1] NR 14 TC 11 Z9 11 U1 1 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1076-2752 J9 J OCCUP ENVIRON MED JI J. Occup. Environ. Med. PD MAR PY 1995 VL 37 IS 3 BP 357 EP 361 DI 10.1097/00043764-199503000-00013 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA QM284 UT WOS:A1995QM28400013 PM 7796204 ER PT J AU VIGANO, A PRINCIPI, N VILLA, ML RIVA, C CRUPI, L TRABATTONI, D SHEARER, GM CLERICI, M AF VIGANO, A PRINCIPI, N VILLA, ML RIVA, C CRUPI, L TRABATTONI, D SHEARER, GM CLERICI, M TI IMMUNOLOGICAL CHARACTERIZATION OF CHILDREN VERTICALLY INFECTED WITH HUMAN-IMMUNODEFICIENCY-VIRUS, WITH SLOW OR RAPID DISEASE PROGRESSION SO JOURNAL OF PEDIATRICS LA English DT Article ID T-HELPER-CELL; HIV-INFECTION; INFANTS BORN; SURVIVAL; TYPE-1; DYSFUNCTION; SUBSETS; SECRETE; WOMEN; TH1 AB Cytokine production of unstimulated and mitogen-stimulated peripheral blood mononuclear cells of 31 children vertically infected with human immunodeficiency virus type 1 (HIV) and with different patterns of disease progression was evaluated to establish possible correlations between the immunologic and the clinical findings, Production of interferon gamma and interleukin-2 (type 1 cytokines), and of interleukin-4 and interleukin-10 (type 2 cytokines), was analyzed in seven symptom-free patients (Centers for Disease Control and Prevention class P-1B), 10 patients with mild symptoms (class P-2A), and 14 patients with severe symptoms (class P-PB-F), Cytokine production was compared with that of 10 age- and sex-matched control subjects who were seronegative for HIV. The HIV-infected patients produced significantly fewer type 1 cytokines and significantly more type 2 cytokines than the uninfected control subjects, No differences in the production of interferon gamma and interleukin-2 were detected among the different clinical categories of HIV-infected patients, In contrast, interleukin-4 production was augmented in the patients with class P-2A (p <0.05) and class P-SB-F HIV infection (p <0.03), in comparison with the children with class P-1B infection, The increase in interleukin-4 production was paralleled by an increase in the number of children with hyperimmunoglobulinemia E in each of the clinical groups (0% in class P-1B; 40% in class P-2A; and 71% in class P-2 B-F infection), Similarly, interleukin-10 production was increased both in patients with class P-2A and in those with class P-2B-F infection, in comparison with the children with class P-1B disease (p <0.006 and <0.04, respectively), These data indicate (1) that vertically acquired HIV infection results in decreased production of type 1 cytokines and in increased production of type 2 cytokines, and (2) that an increased production of type 2 cytokines correlates with hyperimmuno-globulinemia E and is present in, and may be characteristic of, the symptomatic phases of childhood HIV infection. C1 UNIV MILAN, CATTEDRA IMMUNOL, I-20133 MILAN, ITALY. UNIV MILAN, MALATTIE INFETT CLIN, MILAN, ITALY. NCI, EXPTL IMMUNOL BRANCH, BETHESDA, MD 20892 USA. L SACCO HOSP VIALBA, CATTEDRA PEDIAT 4, MILAN, ITALY. RI Trabattoni, Daria/G-7424-2012 NR 42 TC 60 Z9 62 U1 0 U2 1 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 MAR PY 1995 VL 126 IS 3 BP 368 EP 374 DI 10.1016/S0022-3476(95)70450-7 PG 7 WC Pediatrics SC Pediatrics GA QL579 UT WOS:A1995QL57900006 PM 7869194 ER PT J AU FLORES, LR WAHL, SM BAYER, BM AF FLORES, LR WAHL, SM BAYER, BM TI MECHANISMS OF MORPHINE-INDUCED IMMUNOSUPPRESSION - EFFECT OF ACUTE MORPHINE ADMINISTRATION ON LYMPHOCYTE TRAFFICKING SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID GROWTH-FACTOR-BETA; PERIPHERAL-BLOOD; PROLIFERATION; NALTREXONE; DEPENDENCY; CELL; RATS AB These studies investigated the potential mechanisms by which acute morphine administration inhibits peripheral blood lymphocyte activity in the rat. As reported previously, blood lymphocyte proliferative responses to concanavalin A were found to be suppressed by 70% 2 hr after administration of morphine (10 mg/kg). In the present study, a more selective mu receptor agonist, fentanyl (0.05 mg/kg), was found to similarly inhibit blood lymphocyte proliferation. Pretreatment with the opioid receptor antagonist naltrexone (5 mg/kg) completely blocked the inhibitory actions of morphine (7 mg/kg). Several different approaches were undertaken to determine whether the depressed blood lymphocyte proliferative response after opioid receptor stimulation was due to an effect on circulating lymphocyte number. First, it was found that morphine administration was accompanied by a 30% decrease in the absolute number of circulating lymphocytes, Fluorescence-activated cell sorter analysis revealed that the decrease was not selective for any specific subpopulation of T lymphocyte. Furthermore, the relative distribution of circulating monocytes, neutrophils or eosinophils was not altered by morphine treatment. The morphine-induced lymphopenia was abolished in adrenalectomized rats, suggesting that this redistribution effect was mediated by the release of adrenal hormones, However, on correcting for the decrease in lymphocyte number by using Ficoll-separated lymphocyte cultures, the proliferative responses of blood lymphocytes remained significantly depressed compared with control values, Collectively, these data suggest that both an adrenal-dependent lymphopenia and an opioid-induced decrease in responsiveness to mitogenic stimulation contribute to the overall antiproliferative effect of morphine on blood lymphocytes. C1 GEORGETOWN UNIV,MED CTR,DEPT PHARMACOL,WASHINGTON,DC 20007. NIDR,IMMUNOL LAB,BETHESDA,MD 20892. FU NIDA NIH HHS [F31 DA05420, R01 DA04358] NR 22 TC 54 Z9 56 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 MAR PY 1995 VL 272 IS 3 BP 1246 EP 1251 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA QL995 UT WOS:A1995QL99500039 PM 7891340 ER PT J AU BENVENISTE, M MAYER, ML AF BENVENISTE, M MAYER, ML TI TRAPPING OF GLUTAMATE AND GLYCINE DURING OPEN-CHANNEL BLOCK OF RAT HIPPOCAMPAL NEURON NMDA RECEPTORS BY 9-AMINOACRIDINE SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID MOUSE CENTRAL NEURONS; D-ASPARTATE RECEPTORS; USE-DEPENDENT BLOCK; 3-DIMENSIONAL STRUCTURES; ACETYLCHOLINE-RECEPTOR; SYNAPTIC CURRENTS; ACID RECEPTORS; BINDING-SITES; ACTIVATION; MODULATION AB 1. N-methyl-D-aspartate (NMDA) receptor responses were recorded from rat hippocampal neurons grown in dissociated culture, using whole-cell, outside-out and nucleated patch recording techniques. Rapid perfusion was used to study voltage-dependent block of NMDA receptors by 9-aminoacridine (9-AA) and by Mg2+. 2. Large amplitude tail currents were evoked on depolarization to +60 mV after application at -100 mV of NMDA and 9-AA but not NMDA and Mg2+. These tail currents were resistant to block by competitive antagonists to the glutamate and glycine binding sites on NMDA receptors and were not evoked when either NMDA or 9-AA were applied alone. 3. The decay kinetics of the tail current were dependent on agonist affinity; the time required for 80% charge transfer was 10-fold briefer for NMDA than for glutamate and 7-fold briefer for L-alanine than for glycine. These results are in accord with a sequential model for block of NMDA receptors by 9-AA, in which neither glutamate nor glycine can dissociate from the open-blocked state of the receptor. 4. Tail current responses had amplitudes 2- to 4-fold larger than responses to maximally effective concentrations of glutamate and glycine, indicating that NMDA receptor channels accumulate in the open-blocked state during co-application of agonist and 9-AA. The rise time and decay kinetics of tail current responses were faster than the response to brief applications of a maximally effective concentration of glutamate. Together, these results suggest that at +60 mV recovery from block by 9-AA occurs faster than the rate of opening of NMDA receptors in response to glutamate. 5. Our experiments suggest that open channel block of NMDA receptors can provide a novel approach for measurement of both open probability and the first latency distribution for ion channel opening in response to the binding of agonists, and provide additional evidence suggesting that the delayed opening of NMDA receptor channels underlies slow activation and deactivation of responses to glutamate. C1 NICHHD,CELLULAR & MOLEC NEUROPHYSIOL LAB,BETHESDA,MD 20892. RI Mayer, Mark/H-5500-2013 NR 42 TC 78 Z9 80 U1 0 U2 1 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD MAR 1 PY 1995 VL 483 IS 2 BP 367 EP 384 PG 18 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA QL582 UT WOS:A1995QL58200006 PM 7650609 ER PT J AU SELWITZ, RH NOWJACKRAYMER, RE KINGMAN, A DRISCOLL, WS AF SELWITZ, RH NOWJACKRAYMER, RE KINGMAN, A DRISCOLL, WS TI PREVALENCE OF DENTAL-CARIES AND DENTAL FLUOROSIS IN AREAS WITH OPTIMAL AND ABOVE-OPTIMAL WATER FLUORIDE CONCENTRATIONS - A 10-YEAR FOLLOW-UP SURVEY SO JOURNAL OF PUBLIC HEALTH DENTISTRY LA English DT Article DE DENTAL CARIES; DENTAL FLUOROSIS; MOTTLED ENAMEL; FLUORIDE; FLUORIDATION ID PATTERNS; TRENDS; ENAMEL AB Objectives: This paper presents findings for dental caries and fluorosis from an October 1990 follow-up survey in Illinois and compares results with those obtained from two similar school-based examinations conducted in 1980 and 1985 within the same communities. Methods: The seven study sites were grouped into four categories according to the approximate relation of their water fluoride concentration to the recommended optimal fluoride level for the area. Tests for differences in dental caries and dental fluorosis across the four wafer fluoride groupings and three examinations were conducted. Results: DMFS scores for children who resided in communities with above-optimal wafer fluoride levels did not change significantly from 1980 through 1990. At the optimal wafer fluoride concentration, caries scores did not change substantially from 1980 to 1985; however, the mean DMFS score in 1990, 1.9, was significantly lower than caries levels observed during the two previous exams. In the optimally fluoridated area, the proportion of fluorosed tooth surfaces increased significantly from 1980 to 1985, but then declined by 1990 to the level observed in 1980 for both age groups. Conclusions: The results suggest that: (1) in the optimally fluoridated community, the apparent increase in the prevalence of dental fluorosis observed from 1980 to 1985 did not continue from 1985 to 1990; and (2) at above-optimal wafer fluoride concentrations, dental fluorosis either remained stable or demonstrated no sustained increase over the decade. RP SELWITZ, RH (reprint author), NIDR,DIV EPIDEMIOL & ORAL DIS PREVENT,NATCHER BLDG,ROOM 3AN-44J,45 CTR DR,MSC 6401,BETHESDA,MD 20892, USA. NR 29 TC 19 Z9 21 U1 0 U2 3 PU AAPHD NATIONAL OFFICE PI RICHMOND PA J PUBLIC HEALTH DENT 10619 JOUSTING LANE, RICHMOND, VA 23235 SN 0022-4006 J9 J PUBLIC HEALTH DENT JI J. Public Health Dent. PD SPR PY 1995 VL 55 IS 2 BP 85 EP 93 DI 10.1111/j.1752-7325.1995.tb02337.x PG 9 WC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health SC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health GA QZ263 UT WOS:A1995QZ26300004 PM 7643332 ER PT J AU FINTOR, L ALCIATI, MH FISCHER, R AF FINTOR, L ALCIATI, MH FISCHER, R TI LEGISLATIVE AND REGULATORY MANDATES FOR MAMMOGRAPHY QUALITY ASSURANCE SO JOURNAL OF PUBLIC HEALTH POLICY LA English DT Article ID SCREEN-FILM MAMMOGRAPHY; ACCREDITATION; EQUIPMENT AB The current practice of screening mammography in the United States has been the focus of numerous legislative and regulatory mandates at the state and federal levels, both in terms of increasing access to age-eligible women and elevating the quality of mammographic imaging. Several parameters have emerged as central to a comprehensive mammography quality assurance program: (I) equipment specifications, (2) equipment performance testing including radiation dose limits, (3) facility quality assurance procedures, and (4) personnel qualifications. In 1992, Congress enacted the Mammography Quality Standards Act (MQSA) (P. L. 102-539) to address the problem of differences in mandated standards across states. By October 1994, all facilities will be required to comply with interim MQSA regulations which were released in December 1993. However, depending upon the specific requirements of applicable state standards, the extent and nature of modifications of existing quality assurance procedures will differ for facilities across states as they attempt to come into compliance with uniform Federal standards. In addition, because some provisions within state standards are likely to be more stringent than Federal standards, some level of variation will persist. This paper reviews the components of mandated standards established by states and the standards established by other organizations, including the Federal Government, prior to the MQSA interim regulations. This review will provide an understanding of the highly technical and complicated requirements surrounding mammography quality assurance. C1 NCI,DIV CANC PREVENT & CONTROL,CANC CONTROL SCI PROGRAM,PUBL HLTH APPLICAT RES BRANCH,ROCKVILLE,MD 20892. US FDA,CTR DEVICES & RADIOL HLTH,DIV MAMMOG QUAL,ROCKVILLE,MD 20857. US FDA,CTR DEVICES & RADIOL HLTH,RADIAT PROGRAM,ROCKVILLE,MD 20857. RP FINTOR, L (reprint author), NCI,DIV CANC PREVENT & CONTROL,SURVEILLANCE PROGRAM,APPL RES BRANCH,EXECUT PLAZA N,BETHESDA,MD 20892, USA. OI Alciati, Marianne/0000-0001-6294-1090 NR 46 TC 8 Z9 8 U1 0 U2 0 PU JOURNAL PUBLIC HEALTH POLICY PI S BURLINGTON PA 208 MEADOWOOD DR, S BURLINGTON, VT 05403 SN 0197-5897 J9 J PUBLIC HEALTH POL JI J. Public Health Policy PD SPR PY 1995 VL 16 IS 1 BP 81 EP 107 DI 10.2307/3342978 PG 27 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA QR236 UT WOS:A1995QR23600005 PM 7738160 ER PT J AU CHEN, CC KERR, GS CARTER, CS READ, EJ CARRASQUILLO, JA LEITMAN, SF HOFFMAN, GS AF CHEN, CC KERR, GS CARTER, CS READ, EJ CARRASQUILLO, JA LEITMAN, SF HOFFMAN, GS TI LACK OF SENSITIVITY OF IN-111 MIXED LEUKOCYTE SCANS FOR ACTIVE DISEASE IN TAKAYASUS-ARTERITIS SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE TAKAYASUS ARTERITIS; IN-111; LEUKOCYTES ID PLATELET DEPOSITION; BIFURCATION GRAFTS; IN-111; INFECTION AB Objective. Currently, a reliable, noninvasive means of detecting the active vasculitic lesions of Takayasu's arteritis does not exist. Based on the cellular infiltrates seen in active lesions, we postulated that indium-lll labelled mixed leukocytes could be used to scintigraphically detect sites of active vasculitis. Methods. Fifteen In-111 mixed leukocyte scans were performed in 10 patients with Takayasu's arteritis and correlated with clinical, laboratory, and radiographic findings. Patients had either active, stable/smoldering, or inactive disease at the time when 8, 4, and 3 scans were performed, respectively. Results. Two of the 8 scans performed in patients with active disease were positive for increased vessel uptake (sensitivity = 25%). All other scans were interpreted as negative for active arteritis. Conclusion. We conclude that In-ill mixed leukocyte scans have a low sensitivity for detection of active Takayasu's arteritis. C1 NIAID,WARREN G MAGNUSON CLIN CTR,DEPT TRANSFUS MED,BETHESDA,MD 20892. NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. RP CHEN, CC (reprint author), NIAID,WARREN G MAGNUSON CLIN CTR,DEPT NUCL MED,BLDG 10,RM 1C-401,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Carrasquillo, Jorge/E-7120-2010 NR 21 TC 13 Z9 13 U1 0 U2 0 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO ON M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD MAR PY 1995 VL 22 IS 3 BP 478 EP 481 PG 4 WC Rheumatology SC Rheumatology GA QP817 UT WOS:A1995QP81700018 PM 7783065 ER PT J AU HOCHBERG, MC LETHBRIDGECEJKU, M SCOTT, WW REICHLE, R PLATO, CC TOBIN, JD AF HOCHBERG, MC LETHBRIDGECEJKU, M SCOTT, WW REICHLE, R PLATO, CC TOBIN, JD TI THE ASSOCIATION OF BODY-WEIGHT, BODY FATNESS AND BODY-FAT DISTRIBUTION WITH OSTEOARTHRITIS OF THE KNEE - DATA FROM THE BALTIMORE LONGITUDINAL-STUDY OF AGING SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE EPIDEMIOLOGY; ETIOLOGY; OSTEOARTHRITIS; OBESITY ID OSTEO-ARTHRITIS; CARDIOVASCULAR-DISEASE; NATIONAL-HEALTH; ADIPOSE-TISSUE; OBESITY; POPULATION; WOMEN; CLASSIFICATION; EPIDEMIOLOGY; PARTICIPANTS AB Objective. To examine the association of body weight, body fatness, and body fat distribution with osteoarthritis (OA) of the knee. Methods. Bilateral standing knee radiographs, taken between 1985 and 1991, of 465 Caucasian men and 275 Caucasian women subjects aged 40 and above in the Baltimore Longitudinal Study of Aging were read by one investigator for grade of OA using Kellgren-Lawrence scales. Measures of obesity, assessed at same visit as the last radiograph during this interval, included body mass index, percent body fat, and body fat distribution. Results, Both men and women with definite knee OA had higher age adjusted mean levels of body mass index, while women only had higher age adjusted mean levels of percent body fat. Both women and men in the highest tertile of body mass index had significantly increased odds of both definite and bilateral knee OA; women in the middle and highest tertile of percent body fat had significantly increased odds of both definite and bilateral knee OA, and men in the highest tertile of waist-hip ratio had significantly increased odds of bilateral knee OA. After adjusting for body mass index, however, the association of percent body fat and waist-hip ratio with knee OA in women and men, respectively, was no longer significant. Conclusion, These data further extend observations that body weight is associated with both definite and bilateral knee OA in both sexes, and support a stronger contribution of mechanical as opposed to systemic factors to explain this association. C1 UNIV MARYLAND,SCH MED,DEPT EPIDEMIOL & PREVENT MED,BALTIMORE,MD 21201. JOHNS HOPKINS UNIV,SCH MED,DEPT RADIOL,DIV SKELETAL RADIOL,BALTIMORE,MD 21205. NIA,GERONTOL RES CTR,APPL PHYSIOL SECT,BALTIMORE,MD 21224. RP HOCHBERG, MC (reprint author), UNIV MARYLAND,SCH MED,DEPT MED,DIV CLIN IMMUNOL & RHEUMATOL,PROFESS BLDG,419 W REDWOOD ST,BALTIMORE,MD 21201, USA. NR 34 TC 169 Z9 172 U1 0 U2 3 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO ON M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD MAR PY 1995 VL 22 IS 3 BP 488 EP 493 PG 6 WC Rheumatology SC Rheumatology GA QP817 UT WOS:A1995QP81700020 PM 7783067 ER PT J AU BUCZKO, E KOH, YC MIYAGAWA, Y DUFAU, ML AF BUCZKO, E KOH, YC MIYAGAWA, Y DUFAU, ML TI THE RAT 17-ALPHA-HYDROXYLASE-17,20-DESMOLASE (CYP17) ACTIVE-SITE - COMPUTERIZED HOMOLOGY MODELING AND SITE-DIRECTED MUTAGENESIS SO JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY LA English DT Article ID STEROID 17-ALPHA-HYDROXYLASE/17,20 LYASE; AMINO-ACID SEQUENCE; 3-BETA-HYDROXYSTEROID DEHYDROGENASE; CRYSTAL-STRUCTURE; SHORT-CHAIN; CDNA; EXPRESSION; CLONING; TESTIS; GENE AB A homology model of the rat 17 alpha-hydroxylase-17,20 desmolase (CYP17)dagger steroid binding domain was derived from the alpha/beta F supersecondary structural element of the 3 alpha/20 beta hydroxysteroid dehydrogenase (HSD) of Streptomyces hydrogenans that constitutes a major segment of the C19 steroid binding cavity. A CYP17 arginine-rich domain, including Arg346, Arg361 and Arg363, that has previously been shown to be important to CYP17 catalytic activity, is conserved in this HSD structural element between two HSD domains known to be important to C19 steroid binding. These two HSD motifs, in addition to a C-terminal domain at the apex of the steroid binding cavity, are also present in similar though not identical forms in the rat CYP17 sequence. The model was evaluated in terms of both hydroxylase/lyase activity and stability of CYP17 mutant proteins (Tyr334Phe, Phe343Ile, Arg357Ala, Arg361Ala, Asp345Ala), and further tested with mutagenesis of Glu353, Glu358, and Tyr431. Those amino acids located at folding junctions in the model steroid binding domain (Glu358, Arg361, and Tyr431) are each individually required to prevent degradation of the nascent protein, as well as for basic hydroxylase/lyase activity. Genomic analysis of the rat CYP17 gene reveals that this domain is contained in exon 6, and a correlation exists between the length of exon 6 and the boundaries of the HSD supersecondary element. These studies demonstrate that exon 6 of the rat CYP17 is essential for CYP17 activity, and may be structurally related to the NAD-linked prokaryote alpha/beta F supersecondary element. C1 NICHHD,MOLEC ENDOCRINOL SECT,ENDOCRINOL & REPROD RES BRANCH,BETHESDA,MD 20892. NR 37 TC 7 Z9 8 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0960-0760 J9 J STEROID BIOCHEM JI J. Steroid. Biochem. Mol. Biol. PD MAR PY 1995 VL 52 IS 3 BP 209 EP 218 DI 10.1016/0960-0760(94)00174-K PG 10 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA QN902 UT WOS:A1995QN90200001 PM 7696141 ER PT J AU MCLELLAN, AT GROSSMAN, DS BLAINE, JD HAVERKOS, HW AF MCLELLAN, AT GROSSMAN, DS BLAINE, JD HAVERKOS, HW TI REGARDING EVIDENCE FOR EFFECTIVENESS OF ACUPUNCTURE - RESPONSE SO JOURNAL OF SUBSTANCE ABUSE TREATMENT LA English DT Letter C1 NIDA,DIV CLIN RES,ROCKVILLE,MD. RP MCLELLAN, AT (reprint author), PENN VET ADM CTR STUDIES ADDICT,PHILADELPHIA,PA, 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 0740-5472 J9 J SUBST ABUSE TREAT JI J. Subst. Abus. Treat. PD MAR-APR PY 1995 VL 12 IS 2 BP 141 EP 141 PG 1 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA QV995 UT WOS:A1995QV99500010 PM 7623391 ER PT J AU CLIVE, RE OCWIEJA, KM KAMELL, L HOYLER, SS SEIFFERT, JE YOUNG, JL HENSON, DE WINCHESTER, DP OSTEEN, RT MENCK, HR FREMGEN, A AF CLIVE, RE OCWIEJA, KM KAMELL, L HOYLER, SS SEIFFERT, JE YOUNG, JL HENSON, DE WINCHESTER, DP OSTEEN, RT MENCK, HR FREMGEN, A TI A NATIONAL QUALITY IMPROVEMENT EFFORT - CANCER REGISTRY DATA SO JOURNAL OF SURGICAL ONCOLOGY LA English DT Article DE BENCHMARK; OUTCOME; ONCOLOGY; UNIFORM; STANDARDS AB Cancer registries are sources of epidemiological, patterns-of-care, and outcome data for local, regional, state, and national studies of patients with cancer. Since 1976, these registries have formed a voluntary network of contributors to annual patient care studies under the aegis of the National Cancer Data Committee of the Commission on Cancer. These annual studies provide timely clinical information that is widely disseminated to physicians, allied health personnel, administrators, health care planners, and public and private agencies. The use of the data has grown exponentially and has been the basis for more than 90 publications. Merging this activity with the National Cancer Data Base has further expanded the demand and use of registry data. This study was undertaken to respond to inquiries as to the validity of the data and the qualifications and competency of cancer registrars. It provides the baseline for cancer registry data quality and serves as a quality management tool to identify opportunities to enhance data quality. (C) 1995 Wiley-Liss, Inc. C1 UNIV IOWA HOSP & CLIN,IOWA CITY,IA. WASHINGTON HOSP,INST CANC,WASHINGTON,DC. N AMER ASSOC,CENT CANC REGISTRIES,SACRAMENTO,CA. CALIF DEPT HLTH SERV,CALIF CANC REGISTRY,SACRAMENTO,CA. NCI,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20892. BRIGHAM & WOMENS HOSP,BOSTON,MA. AMER COLL SURGEONS,COMMISS CANC,CHICAGO,IL. NR 5 TC 27 Z9 27 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 0022-4790 J9 J SURG ONCOL JI J. Surg. Oncol. PD MAR PY 1995 VL 58 IS 3 BP 155 EP 161 PG 7 WC Oncology; Surgery SC Oncology; Surgery GA QN640 UT WOS:A1995QN64000003 PM 7898110 ER PT J AU ALLEN, AJ LEONARD, HL SWEDO, SE AF ALLEN, AJ LEONARD, HL SWEDO, SE TI CASE-STUDY - A NEW INFECTION-TRIGGERED, AUTOIMMUNE SUBTYPE OF PEDIATRIC OCD AND TOURETTES-SYNDROME SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE AUTOIMMUNE; OBSESSIVE-COMPULSIVE DISORDER; TIC DISORDERS; STREPTOCOCCAL INFECTIONS; VIRAL INFECTIONS; TOURETTES SYNDROME ID SYDENHAM CHOREA; SYMPTOMS AB A review of clinical observations and literature reports leads to the hypothesis that, via a process analogous to Sydenham's chorea, infections with group A beta-hemolytic streptococci, among others, may trigger autoimmune responses that cause or exacerbate some cases of childhood-onset obsessive-compulsive disorder (OCD) or tic disorders (including Tourette's syndrome). If this hypothesis is correct, then immunological treatments should lead to decreased symptoms in some cases. Four cases with abrupt, severe onset or worsening of OCD or tics are presented from an open treatment study. All were boys aged 10 to 14 years. One had OCD, one had Tourette's syndrome, and two had both OCD and Tourette's syndrome. Clinically and on standardized rating scales, their symptoms were in the moderate to very severe range. Two had evidence of recent group A beta-hemolytic streptococci infections, and the others had histories of recent viral illnesses. Two were treated with plasmapheresis, one with intravenous immunoglobulin, and one with immunosuppressive doses of prednisone. All had a clinically significant response immediately after treatment. Diagnostic criteria are provided that describe these cases of pediatric, infection-triggered, autoimmune neuropsychiatric disorders (PITANDs). Suggestions are made regarding the evaluation and management of patients who may have this condition. C1 NIMH,CHILD PSYCHIAT BRANCH,PEDIAT NEUROPSYCHIAT DISORDERS UNIT,BETHESDA,MD 20892. RP ALLEN, AJ (reprint author), NIMH,CHILD PSYCHIAT BRANCH,BEHAV PEDIAT SECT,BLDG 10,ROOM 6N240,10 CTR DR,MSC 1600,BETHESDA,MD 20892, USA. NR 12 TC 201 Z9 201 U1 1 U2 6 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD MAR PY 1995 VL 34 IS 3 BP 307 EP 311 DI 10.1097/00004583-199503000-00015 PG 5 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA QK025 UT WOS:A1995QK02500015 PM 7896671 ER PT J AU CONRYCANTILENA, C VILAMIDOU, L MELPOLDER, JC VANRADEN, M ALTER, HJ AF CONRYCANTILENA, C VILAMIDOU, L MELPOLDER, JC VANRADEN, M ALTER, HJ TI PORPHYRIA-CUTANEA-TARDA IN HEPATITIS-C VIRUS-INFECTED BLOOD-DONORS SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Note ID ANTIBODIES C1 NIAID,DIV MICROBIOL & INFECT DIS,BIOMETRY SECT,BETHESDA,MD. RP CONRYCANTILENA, C (reprint author), NIH,WARREN GRANT MAGNUSON CLIN CTR,DEPT TRANSFUS MED,BLDG 10,IC711,BETHESDA,MD 20892, USA. NR 13 TC 5 Z9 5 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD MAR PY 1995 VL 32 IS 3 BP 512 EP 514 DI 10.1016/0190-9622(95)90090-X PG 3 WC Dermatology SC Dermatology GA QJ458 UT WOS:A1995QJ45800017 PM 7868725 ER PT J AU FREEMAN, BD YATSIV, I NATANSON, C SOLOMON, MA QUEZADO, ZMN DANNER, RL BANKS, SM HOFFMAN, WD AF FREEMAN, BD YATSIV, I NATANSON, C SOLOMON, MA QUEZADO, ZMN DANNER, RL BANKS, SM HOFFMAN, WD TI CONTINUOUS ARTERIOVENOUS HEMOFILTRATION DOES NOT IMPROVE SURVIVAL IN A CANINE MODEL OF SEPTIC SHOCK SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID MULTIPLE ORGAN FAILURE; ESCHERICHIA-COLI; SEPSIS; ENDOTOXIN; DYSFUNCTION; CHALLENGES; VOLUME; TRIAL; DOGS AB BACKGROUND: We examined whether or not continuous arteriovenous hemofiltration (CAVH), in the absence of renal failure, would improve either hemodynamic abnormalities or survival in a canine model of septic shock. STUDY DESIGN: Escherichia coli 0111, as an intraperitoneal clot, was surgically implanted into 21 one- to two-year-old purpose-bred beagles. The dogs were randomized to no CAVH (control group, n=7), shun CAVH (extracorporeal circulation without hemofiltration, n=7), or true CAVH (hemofiltration with removal of 600 mL/hour of ultrafiltrate, n=7). Hemofiltration began one hour after clot implantation and continued for six hours. All dogs received antibiotics and had serial hemodynamic and laboratory evaluations. RESULTS: During the first seven hours of the study, all dogs displayed a progressive, significant decrease in mean arterial pressure, cardiac index, left ventricular ejection fraction, and serum pH (all p<0.05). Two of seven dogs in the control group, one of seven dogs in the sham CAVH group, and one of seven dogs in the true CAVH group survived seven days after clot implantation. True CAVH, which included fluid replacement with lactated Ringer's solution, significantly increased serum lactate and decreased serum bicarbonate levels after six hours (both p<0.05). However, pH did not differ between the three treatment groups (p>0.20). Continuous arteriovenous hemofiltration therapy had no significant effect on cardiovascular abnormalities or survival. CONCLUSIONS: The results of this study suggest that CAVH would be unlikely to provide benefit to patients with gram-negative septic shock, in the absence of renal failure. RP FREEMAN, BD (reprint author), NIH,DEPT CRIT CARE MED,BLDG 10,ROOM 7D43,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Quezado, Zenaide/O-4860-2016 OI Quezado, Zenaide/0000-0001-9793-4368 NR 44 TC 31 Z9 31 U1 0 U2 0 PU AMER COLL SURGEONS PI CHICAGO PA 54 EAST ERIE ST, CHICAGO, IL 60611 SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD MAR PY 1995 VL 180 IS 3 BP 286 EP 292 PG 7 WC Surgery SC Surgery GA QK363 UT WOS:A1995QK36300004 PM 7874338 ER PT J AU LYNESS, JM COX, C CURRY, J CONWELL, Y KING, DA CAINE, ED AF LYNESS, JM COX, C CURRY, J CONWELL, Y KING, DA CAINE, ED TI OLDER AGE AND THE UNDERREPORTING OF DEPRESSIVE SYMPTOMS SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article; Proceedings Paper CT 147th Annual Meeting of the American-Psychiatric-Association CY MAY 21-27, 1994 CL PHILADELPHIA, PA SP Amer Psychiat Assoc ID ILLNESS RATING-SCALE; MAJOR DEPRESSION; MEDICAL ILLNESS; PRIMARY CARE; FOLLOW-UP; ASSESSMENTS; POPULATION; VALIDATION; VALIDITY; ADULTS AB OBJECTIVE: To determine whether older age is associated with a decrease in self-reported depressive symptoms, independent of examiner-rated symptoms, in inpatients with major depression. DESIGN: Survey study. SETTING: Inpatient psychiatric units at a university medical center. PATIENTS: Eligible subjects were those over 20 years of age with a primary diagnosis of DSM-III-R major depression. Participation was sought from all subjects over 60 years of age and from every second or every third younger subject, depending on rater availability. Of 137 eligible subjects, 97 completed all study measures. MEASUREMENTS: The Beck Depression Inventory (BDI), as a measure of self-reported depressive symptoms, was the dependent variable. The Hamilton Rating Scale for Depression (Ham-D) was used to assess examiner-rated symptoms. MAIN RESULTS: Older age (P = .03) was associated negatively and examiner-rated depressive symptoms (P = .0001) were associated positively with BDI score. Other variables, including gender, education, age of depression onset, and medical illness burden, were not independently associated with BDI. Examination of depressive symptom subtotals (psychologic/affective vs. somatic/neurovegetative) revealed that only the self-reported psychologic/affective subtotal was significantly associated with age (P = .0018). CONCLUSIONS: Some older patients with clinically significant depression underreport their symptoms. When asking older patients about depressive symptoms, clinicians should view negative responses only within larger clinical contexts and should obtain information from other sources as needed. Similar concerns must temper interpretation of research that relies on subject self-report to study depression in late life. C1 UNIV ROCHESTER,NIMH,CLIN RES CTR STUDY PSYCHOPATHOL ELDERLY,ROCHESTER,NY. UNIV ROCHESTER,SCH MED & DENT,DEPT PSYCHIAT,ROCHESTER,NY. UNIV ROCHESTER,SCH MED & DENT,DEPT BIOSTAT,ROCHESTER,NY. FU NIMH NIH HHS [P50 MH40381, T32 MH18911] NR 35 TC 110 Z9 112 U1 0 U2 4 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAR PY 1995 VL 43 IS 3 BP 216 EP 221 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA QK439 UT WOS:A1995QK43900002 PM 7884106 ER PT J AU ETTINGER, WH HARRIS, T VERDERY, RB TRACY, R KOUBA, E AF ETTINGER, WH HARRIS, T VERDERY, RB TRACY, R KOUBA, E TI EVIDENCE FOR INFLAMMATION AS A CAUSE OF HYPOCHOLESTEROLEMIA IN OLDER-PEOPLE SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Note ID CYTOKINE MEASUREMENTS; CHOLESTEROL LEVELS; SERUM-CHOLESTEROL; MORTALITY C1 WAKE FOREST UNIV,BOWMAN GRAY SCH MED,DEPT PUBL HLTH SCI,WINSTON SALEM,NC 27157. UNIV ARIZONA,ARIZONA CTR AGING,TUCSON,AZ 85721. NIA,EPIDEMIOL DEMOG & BIOMETRY PROGRAM,BETHESDA,MD. UNIV VERMONT,DEPT PATHOL,BURLINGTON,VT 05405. RP ETTINGER, WH (reprint author), WAKE FOREST UNIV,BOWMAN GRAY SCH MED,DEPT INTERNAL MED,MED CTR BLVD,WINSTON SALEM,NC 27157, USA. FU NHLBI NIH HHS [N01-HC85080]; NIA NIH HHS [K07-AG00421, P60-AG10484] NR 18 TC 64 Z9 64 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAR PY 1995 VL 43 IS 3 BP 264 EP 266 PG 3 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA QK439 UT WOS:A1995QK43900011 PM 7884115 ER PT J AU SMITH, PR GOTTESMAN, S JONES, WK AF SMITH, PR GOTTESMAN, S JONES, WK TI MANAGING THE ELECTRONIC NIH-GUIDE FOR GRANTS AND CONTRACTS SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Article ID DATABASE; GENBANK AB This article describes the implementation of a suite Of computer programs to manage and provide access to a database containing the electronic documents that constitute the NIH-Guide that is distributed by the NIH on a weekly basis. The software consists of a management program that reads, processes, and stores the incoming documents and performs erratum updates on existing documents; an alerting program that sends selected information to users who have registered their information needs; a viewer that can be used on the local computer to read these documents; and a World-Wide-Web (WWW) server that can distribute the guide to computers that run WWW client software. The design of the documentation annotations, the management software, and the WWW server are expected to constitute valuable models for similar projects in the future. C1 NIH,DIV COMP RES & TECHNOL,BETHESDA,MD 20892. RP SMITH, PR (reprint author), NYU,MED CTR,DEPT CELL BIOL,550 1ST AVE,NEW YORK,NY 10016, USA. FU NCRR NIH HHS [RR-00096-32] NR 13 TC 1 Z9 1 U1 0 U2 2 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PD MAR-APR PY 1995 VL 2 IS 2 BP 94 EP 101 PG 8 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Medical Informatics SC Computer Science; Information Science & Library Science; Medical Informatics GA QL256 UT WOS:A1995QL25600004 PM 7743321 ER PT J AU MORRELL, CH PEARSON, JD CARTER, HB BRANT, LJ AF MORRELL, CH PEARSON, JD CARTER, HB BRANT, LJ TI ESTIMATING UNKNOWN TRANSITION TIMES USING A PIECEWISE NONLINEAR MIXED-EFFECTS MODEL IN MEN WITH PROSTATE-CANCER SO JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION LA English DT Article DE AGING; LONGITUDINAL DATA; RANDOM EFFECTS; TUMOR GROWTH ID ANTIGEN; ADENOCARCINOMA; DISEASE AB It may be clinically useful to know when prostate-specific antigen (PSA) levels first begin to rise rapidly and to determine if the natural history of PSA progression is different in men with locally confined prostate cancers compared to men with metastatic tumors. This article uses a nonlinear mixed-effects model to describe longitudinal changes in PSA in men before their prostate cancers were detected clinically. Repeated measurements of PSA are available for 18 subjects with a diagnosis of prostate cancer based on prostate biopsy. PSA measurements were determined on repeated frozen serum samples collected from subjects with at least 10.0 years and up to 25.6 years of observation before the cancer was detected. A piecewise model is used to describe this data. The model is linear long before the cancer was detected and exponential nearer the time the cancer was detected. The time at which the PSA levels change from linear to exponential PSA progression is unknown but can be estimated by including random terms that allow each subject to have his own transition time. The model also accounts for two groups of patients-those with local or regional cancer and those with advanced cancer or whose cancer has metastasized. Various parameters are allowed to differ between these two groups. By backward elimination of statistically nonsignificant parameters, a model is found that adequately describes the data. The model represents a situation where local/regional and advanced/metastatic cancers have similar rates of PSA progression, but advanced/metastatic cancers are diagnosed later. Piecewise mixed-effects models may be useful in a variety of research settings where it is necessary to estimate the unknown time of an event. C1 NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,DEPT UROL,BALTIMORE,MD 21287. RP MORRELL, CH (reprint author), LOYOLA COLL,DEPT MATH SCI,BALTIMORE,MD 21210, USA. NR 15 TC 51 Z9 51 U1 1 U2 2 PU AMER STATIST ASSN PI ALEXANDRIA PA 1429 DUKE ST, ALEXANDRIA, VA 22314 SN 0162-1459 J9 J AM STAT ASSOC JI J. Am. Stat. Assoc. PD MAR PY 1995 VL 90 IS 429 BP 45 EP 53 DI 10.2307/2291128 PG 9 WC Statistics & Probability SC Mathematics GA QH030 UT WOS:A1995QH03000006 ER PT J AU TROENDLE, JF AF TROENDLE, JF TI A STEPWISE RESAMPLING METHOD OF MULTIPLE HYPOTHESIS-TESTING SO JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION LA English DT Article DE EXPERIMENTWISE; P VALUE; TEST STATISTIC; TYPE I ERROR ID BONFERRONI PROCEDURE AB This article introduces a method of multiple hypothesis testing that combines the idea of sequential multiple testing procedures with the structure of resampling methods. The method can be seen as an alternative to the analytic method of Dunnett and Tamhane, which requires a specific distributional form. Resampling incorporates the covariance structure of the data without the need for distributional assumptions. Recent work by Westfall and Young has shown that a step-down resampling method is asymptotically consistent when adjusted p values can be obtained exactly for continuous data. This article shows that in the case of a comparison of two groups on multiple outcomes, those results are generalizable to discrete data where exact adjusted p values are not available. It is shown that the method asymptotically attains the desired level for controlling the experimentwise probability of a type I error. RP TROENDLE, JF (reprint author), NICHHD,BETHESDA,MD 20892, USA. NR 11 TC 54 Z9 54 U1 0 U2 2 PU AMER STATIST ASSN PI ALEXANDRIA PA 1429 DUKE ST, ALEXANDRIA, VA 22314 SN 0162-1459 J9 J AM STAT ASSOC JI J. Am. Stat. Assoc. PD MAR PY 1995 VL 90 IS 429 BP 370 EP 378 DI 10.2307/2291163 PG 9 WC Statistics & Probability SC Mathematics GA QH030 UT WOS:A1995QH03000041 ER PT J AU LINEHAN, WM AF LINEHAN, WM TI INHIBITION OF PROSTATE-CANCER METASTASIS - A CRITICAL CHALLENGE AHEAD SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID PROLIFERATION; CARCINOMA; GENISTEIN; GROWTH; CELLS C1 NCI,DIV CANC TREATMENT,SURG BRANCH,UROL ONCOL SECT,BETHESDA,MD 20892. RP LINEHAN, WM (reprint author), NIH,BLDG 10,RM 2B47,BETHESDA,MD 20892, USA. NR 25 TC 5 Z9 5 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 MAR 1 PY 1995 VL 87 IS 5 BP 331 EP 332 DI 10.1093/jnci/87.5.331 PG 2 WC Oncology SC Oncology GA QH570 UT WOS:A1995QH57000001 PM 7853410 ER PT J AU GEORGIADIS, MS STEINBERG, SM HANKINS, LA IHDE, DC JOHNSON, BE AF GEORGIADIS, MS STEINBERG, SM HANKINS, LA IHDE, DC JOHNSON, BE TI OBESITY AND THERAPY-RELATED TOXICITY IN PATIENTS TREATED FOR SMALL-CELL LUNG-CANCER SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID UNITED-STATES; BODY-WEIGHT; CHEMOTHERAPY; PHARMACOKINETICS; OVERWEIGHT AB Background: Obese individuals have altered pharmacokinetics for many medications when compared with the non-obese. For the oncologist treating an obese cancer patient, these changes in drug disposition may potentially cause increased therapy-related toxicity. As a consequence, oncologists frequently treat obese patients with dose reductions in an effort to decrease chemotherapy toxicity. However, little clinical data exist to either support or refute this policy. Purpose: The clinical course of a cohort of patients treated for small-cell lung cancer (SCLC) was evaluated to determine if the obese patients had an increase in therapy-related toxicity. Methods: The study sample included 262 patients with histologically confirmed SCLC treated in clinical trials from 1977 through 1993. Before 1986, patients with limited stage SCLC were treated with a cyclophosphamide-based regimen with (n = 47) or without (n = 46) chest radiotherapy. Subsequent patients with limited stage disease (n = 54) received etoposide and cisplatin plus twice-daily chest radiotherapy. Patients with extensive stage SCLC were randomly treated with standard-dose (n = 46) or high-dose etoposide plus cisplatin (n = 44); poor-risk patients with extensive stage disease (n = 25) were assigned to standard dose etoposide plus cisplatin. For all patients, actual body weight was used when determining initial doses of chemotherapy. The measure of relative weight was the body mass index (BMI), which was calculated from the pretreatment height and weight data. The BMI was evaluated both on a continuum and with patients grouped into BMI levels (normal, obese, and severely obese). Toxicity parameters were collected during induction chemotherapy and were compared with the BMI. In addition, the overall survival of the entire cohort was evaluated, with patients divided into different groups based on their BMI level. Results: We performed 170 comparisons between the BMI as a continuum or the BMI level and the 15 toxicity parameters. There were no consistent associations of significance found between increasing BMI or BMI levels and increasing toxicity from therapy. When survival was evaluated, no statistically significant differences were found between the survival of patients within the different BMI levels. Conclusions: In this group of 262 patients with SCLC, obesity at the start of treatment was not associated with increased toxicity from treatment or a shortened survival. No support for empiric chemotherapy dose reductions based on ideal body weight was evident from this study. C1 NIH, BETHESDA, MD 20889 USA. UNIFORMED SERV UNIV HLTH SCI, BETHESDA, MD 20814 USA. NATL NAVAL MED CTR, BETHESDA, MD USA. NCI, DIV CANC TREATMENT, CLIN ONCOL PROGRAM, BIOSTAT & DATA MANAGEMENT SECT, BETHESDA, MD 20892 USA. NCI, NAVY MED ONCOL BRANCH, DIV CANC TREATMENT, BETHESDA, MD USA. NR 28 TC 56 Z9 56 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 MAR 1 PY 1995 VL 87 IS 5 BP 361 EP 366 DI 10.1093/jnci/87.5.361 PG 6 WC Oncology SC Oncology GA QH570 UT WOS:A1995QH57000009 PM 7853417 ER PT J AU DARBY, SC WHITLEY, E HOWE, GR HUTCHINGS, SJ KUSIAK, RA LUBIN, JH MORRISON, HI TIRMARCHE, M TOMASEK, L RADFORD, EP ROSCOE, RJ SAMET, JM YAO, SX AF DARBY, SC WHITLEY, E HOWE, GR HUTCHINGS, SJ KUSIAK, RA LUBIN, JH MORRISON, HI TIRMARCHE, M TOMASEK, L RADFORD, EP ROSCOE, RJ SAMET, JM YAO, SX TI RADON AND CANCERS OTHER THAN LUNG-CANCER IN UNDERGROUND MINERS - A COLLABORATIVE ANALYSIS OF 11 STUDIES SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID URANIUM MINERS; MORTALITY 1950-80; DAUGHTER EXPOSURE; COHORT; WORKERS; LEUKEMIA; RISK; PROGENY AB Background: Exposure to the radioactive gas radon and its progeny (Rn-222 and its radioactive decay products) has recently been linked to a variety of cancers other than lung cancer in geographic correlation studies of domestic radon exposure and in individual cohorts of occupationally exposed miners. Purpose: This study was designed to characterize further the risks for cancers other than lung cancer (i.e., non-lung cancers) from atmospheric radon. Methods: Mortality from non-lung cancer was examined in a collaborative analysis of data from 11 cohorts of underground miners in which radon-related excesses of lung cancer had been established. The study included 64 209 men who were employed in the mines for 6.4 years on average, received average cumulative exposures of 155 working-level months (WLM), and were followed for 16.9 years on average. Results: For all non-lung cancers combined, mortality was close to that expected from mortality rates in the areas surrounding the mines (ratio of observed to expected deaths [O/E] = 1.01; 95% confidence interval [CI] = 0.95-1.07, based on 1179 deaths), and mortality did not increase with increasing cumulative exposure. Among 28 individual cancer categories, statistically significant increases in mortality for cancers of the stomach (O/E = 1.33; 95% CI = 1.16-1.52) and liver (O/E = 1.73; 95% CI = 1.29-2.28) and statistically significant decreases for cancers of the tongue and mouth (O/E = 0.52; 95% CI = 0.26-0.93), pharynx (O/E = 0.35; 95% CI = 0.16-0.66), and colon (O/E = 0.77; 95% CI = 0.63-0.95) were observed. For leukemia, mortality was increased in the period less than 10 years since starting work (O/E = 1.93; 95% CI = 1.19-2.95) but not subsequently. For none of these diseases was mortality significantly related to cumulative exposure. Among the remaining individual categories of non-lung cancer, mortality was related to cumulative exposure only for cancer of the pancreas (excess relative risk per WLM = 0.07%; 95% CI = 0.01-0.12) and, in the period less than 10 years since the start of employment, for other and unspecified cancers (excess relative risk per WLM = 0.22%; 95% CI = 0.08-0.37). Conclusions: The increases in mortality from stomach and liver cancers and leukemia are unlikely to have been caused by radon, since they are unrelated to cumulative exposure. The association between cumulative exposure and pancreatic cancer seems likely to be a chance finding, while the association between cumulative exposure and other and unspecified cancers was caused by deaths certified as due to carcinomatosis (widespread disseminated cancer throughout the body) that were likely to have been due to lung cancers. This study, therefore, provides considerable evidence that high concentrations of radon in air do not cause a material risk of mortality from cancers other than lung cancer. Implications: Protection standards for radon should continue to be based on consideration of the lung cancer risk alone. C1 NATL CANC INST CANADA,TORONTO,ON,CANADA. HLTH & SAFETY EXECUT,BOOTLE,MERSEYSIDE,ENGLAND. ONTARIO MINIST LABOR,TORONTO,ON,CANADA. NCI,DIV CANC ETIOL,BETHESDA,MD 20892. HLTH & WELF CANADA,OTTAWA,ON,CANADA. CEN,INST PROTECT SURETE NUCL,FONTENAY ROSES,FRANCE. NATL INST PUBL HLTH,PRAGUE,CZECH REPUBLIC. NIOSH,CINCINNATI,OH 45226. UNIV NEW MEXICO,NEW MEXICO TUMOR REGISTRY,ALBUQUERQUE,NM 87131. RP DARBY, SC (reprint author), UNIV OXFORD,RADCLIFFE INFIRM,IMPERIAL CANC RES FUND,CANC EPIDEMIOL UNIT,GIBSON BLDG,OXFORD OX2 6HE,ENGLAND. NR 51 TC 139 Z9 145 U1 1 U2 9 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 MAR 1 PY 1995 VL 87 IS 5 BP 378 EP 384 DI 10.1093/jnci/87.5.378 PG 7 WC Oncology SC Oncology GA QH570 UT WOS:A1995QH57000012 PM 7853419 ER PT J AU TORETSKY, JA NECKERS, L WEXLER, LH AF TORETSKY, JA NECKERS, L WEXLER, LH TI DETECTION OF (11-22)(Q24-Q12) TRANSLOCATION-BEARING CELLS IN PERIPHERAL-BLOOD PROGENITOR CELLS OF PATIENTS WITH EWINGS-SARCOMA FAMILY OF TUMORS SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Note ID FUSION C1 NCI,DIV CANC TREATMENT,PEDIAT BRANCH,BETHESDA,MD 20892. NCI,DIV CANC TREATMENT,CLIN PHARMACOL BRANCH,BETHESDA,MD 20892. NR 5 TC 38 Z9 38 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 MAR 1 PY 1995 VL 87 IS 5 BP 385 EP 386 DI 10.1093/jnci/87.5.385 PG 2 WC Oncology SC Oncology GA QH570 UT WOS:A1995QH57000013 PM 7853420 ER PT J AU ZBAR, B GLENN, G LUBENSKY, I CHOYKE, P WALTHER, MM MAGNUSSON, G BERGERHEIM, USR PETTERSSON, S AMIN, M HURLEY, K LINEHAN, WM AF ZBAR, B GLENN, G LUBENSKY, I CHOYKE, P WALTHER, MM MAGNUSSON, G BERGERHEIM, USR PETTERSSON, S AMIN, M HURLEY, K LINEHAN, WM TI HEREDITARY PAPILLARY RENAL-CELL CARCINOMA - CLINICAL-STUDIES IN 10 FAMILIES SO JOURNAL OF UROLOGY LA English DT Article DE CARCINOMA, RENAL CELL; CARCINOMA, PAPILLARY; HEREDITARY DISEASES ID VONHIPPEL-LINDAU DISEASE; TRANSLOCATION; IDENTIFICATION; TUMORS AB We recently described a 3-generation family with members affected with papillary renal cell carcinoma, an uncommon histological type of renal cell carcinoma. Possibly family 150 is an isolated occurrence, a reflection of some as yet unknown environmental factor. Alternatively, family 150 may represent a distinct class of inherited cancer. To distinguish between these 2 possibilities we sought additional families with papillary renal cell carcinoma and we identified 9 with members affected with papillary renal cell carcinoma. There were 29 affected male and 12 affected female subjects (ratio 2.41:1), including affected members of family 150. Papillary renal cell carcinomas were often detected incidentally in asymptomatic individuals or during screening of asymptomatic members of renal cell carcinoma families. The penetrance, the proportion of obligate gene carriers that showed clinical evidence of the disease, was reduced. The median survival of affected individuals was 52 years. The results support the concept that the predisposition to develop papillary renal cell carcinomas may be inherited and that hereditary papillary renal cell carcinoma constitutes a distinct class of inherited cancer. C1 NCI,DEPT DIAGNOST RADIOL,CANC DIAG BRANCH,IMMUNOL & PATHOL LABS,BETHESDA,MD 20892. KAROLINSKA HOSP,DEPT SURG,S-10401 STOCKHOLM,SWEDEN. HUDDINGE HOSP,DEPT RENAL MED,S-14186 HUDDINGE,SWEDEN. SAHLGRENS UNIV HOSP,DEPT UROL,GOTHENBURG,SWEDEN. HENRY FORD HOSP,DEPT PATHOL,DETROIT,MI 48202. RP ZBAR, B (reprint author), NCI,DEPT DIAGNOST RADIOL,SURG BRANCH,IMMUNOL & PATHOL LABS,BETHESDA,MD 20892, USA. NR 29 TC 115 Z9 119 U1 1 U2 2 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-5347 J9 J UROLOGY JI J. Urol. PD MAR PY 1995 VL 153 IS 3 BP 907 EP 912 DI 10.1016/S0022-5347(01)67601-8 PN 2 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA QF634 UT WOS:A1995QF63400005 PM 7853572 ER PT J AU WALTHER, MM CHOYKE, PL WEISS, G MANOLATOS, C LONG, J REITER, R ALEXANDER, RB LINEHAN, WM AF WALTHER, MM CHOYKE, PL WEISS, G MANOLATOS, C LONG, J REITER, R ALEXANDER, RB LINEHAN, WM TI PARENCHYMAL SPARING SURGERY IN PATIENTS WITH HEREDITARY RENAL-CELL CARCINOMA SO JOURNAL OF UROLOGY LA English DT Article DE CARCINOMA, RENAL CELL; HEREDITARY DISEASES, SURGERY ID VONHIPPEL-LINDAU DISEASE; IDENTIFICATION; MANIFESTATIONS; NEPHRECTOMY; MANAGEMENT AB The von Hippel-Lindau syndrome is the most well known cause of familial renal cancer. Because affected individuals with renal lesions can have complex, multisystem manifestations of von Hippel-Lindau disease, our renal management strategy has included parenchymal sparing surgery whenever possible. From May 1988 to January 1993, 20 patients with hereditary renal cell carcinoma (19 with von Hippel-Lindau disease and 1 with hereditary papillary renal cancer) underwent renal exploration with the intent of performing parenchymal sparing surgery. A total of 7 nephrectomies and 27 parenchymal sparing procedures was performed. Additional procedures performed included 2 bilateral adrenalectomies for pheochromocytomas, 1 resection of a renal vein thrombus and 1 resection of a pancreatic islet cell tumor. Renal atrophy occurred in 3 of 27 kidneys (11%) treated by parenchymal sparing surgery. In 8 kidneys of 7 patients new solid lesions developed and in 14 kidneys of 12 patients no new solid lesions developed during a mean followup of 26 months (range 6 to 60 months). The use of parenchymal sparing surgery in patients with familial forms of kidney cancer is based on a desire to maintain renal function as long as possible while reducing the risk of metastases. The potential advantages and disadvantages of more ablative surgical treatment requiring subsequent dialysis or transplantation in patients with existing or potential central nervous system, eye, pancreas and/or adrenal tumors must be weighed against the possibility of renal cancer metastases or recurrence when deciding on the use of parenchymal sparing surgery. C1 NIH,WARREN GRANT MAGNUSON CLIN CTR,DEPT DIAGNOST RADIOL,BETHESDA,MD 20892. RP WALTHER, MM (reprint author), NCI,SURG BRANCH,UROL ONCOL SECT,BLDG 10,BETHESDA,MD 20892, USA. NR 28 TC 69 Z9 72 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 MAR PY 1995 VL 153 IS 3 BP 913 EP 916 DI 10.1016/S0022-5347(01)67602-X PN 2 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA QF634 UT WOS:A1995QF63400006 PM 7853573 ER PT J AU LYNCH, WP ROBERTSON, SJ PORTIS, JL AF LYNCH, WP ROBERTSON, SJ PORTIS, JL TI INDUCTION OF FOCAL SPONGIFORM NEURODEGENERATION IN DEVELOPMENTALLY RESISTANT MICE BY IMPLANTATION OF MURINE RETROVIRUS-INFECTED MICROGLIA SO JOURNAL OF VIROLOGY LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; NEUROTROPHIC FACTOR PREVENTS; LEUKEMIA-VIRUS; MONOCLONAL-ANTIBODIES; AMEBOID MICROGLIA; MONONUCLEAR PHAGOCYTES; MAMMALIAN BRAIN; ASTROGLIAL RESPONSE; ANTIGEN EXPRESSION; NEURONAL SURVIVAL AB FrCas(E) is a highly neurovirulent murine leukemia virus which causes a noninflammatory spongiform neurodegenerative disease after neonatal inoculation. The central nervous system (CNS) infection is widespread, involving several different cell types, whereas the lesions are localized to motor areas of the brain and spinal cord. Inoculation of FrCas(E) at 10 days of age (P10) results in viremia, but infection of the CNS is restricted and neurological disease is not observed (M. Czub, S. Czub, F. McAtee, and J. Portis, J. Virol. 65:2539-2544, 1991). In this study, we used this developmental resistance to restrict the extent and the distribution of FrCas(E) in the brain to examine whether the spongiform degeneration is a consequence of infection of cells in proximity to the lesions. Two approaches were used to infect the brain on or after P10. First, mice were inoculated with FrCas(E) at P10 to induce viremia and then at P17 were subjected to focal CNS injury within brain regions known to be susceptible to virus-induced spongiform degeneration. The injury resulted in local inflammation, glial activation, migration of inflammatory cells into the wound site, and high-level parenchymal infection about the wound site. However, no evidence of spongiform neurodegeneration was observed over a period of 3 months. The second approach involved the implantation of FrCas(E)-infected microglia into the CNS at greater than or equal to P10. This resulted in microglial engraftment and focal CNS infection unilaterally at the implantation sites and bilaterally along white matter tracts of the corpus callosum and pens and in cells of the subventricular layers of the lateral cerebral ventricles. Strikingly, focal spongiform degeneration colocalized with the sites of infection. In contrast to the wounding experiments, the implantation model was not associated with an inflammatory response or significant glial activation. Results of these studies suggest that (i) the developmental resistance of the CNS to infection lies at the blood-brain barrier and can be bypassed by direct introduction into the brain of virus-infected cells, (ii) the neuropathology induced by this virus is a consequence of local effects of the infection and does not appear to require endothelial or neuronal infection, and (iii) elements of the inflammatory response and/or glial activation may modulate the expression of neuropathology induced by neurovirulent retroviruses. C1 NIAID,ROCKY MT LABS,PERSISTENT VIRAL DIS LAB,HAMILTON,MT 59840. NR 69 TC 44 Z9 44 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 MAR PY 1995 VL 69 IS 3 BP 1408 EP 1419 PG 12 WC Virology SC Virology GA QG073 UT WOS:A1995QG07300004 PM 7853473 ER PT J AU BOUR, S SCHUBERT, U STREBEL, K AF BOUR, S SCHUBERT, U STREBEL, K TI THE HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 VPU PROTEIN SPECIFICALLY BINDS TO THE CYTOPLASMIC DOMAIN OF CD4 - IMPLICATIONS FOR THE MECHANISM OF DEGRADATION SO JOURNAL OF VIROLOGY LA English DT Article ID ENDOPLASMIC-RETICULUM; GLYCOPROTEIN PRECURSOR; RAPID DEGRADATION; MEMBRANE; HIV-1; RETENTION; CELLS; GENE; IDENTIFICATION; RETROVIRUS AB We have recently demonstrated that coexpression of Vpu and CD4 in HeLa cells results in the degradation of CD4 in the endoplasmic reticulum. The sensitivity of CD4 to Vpu-mediated degradation is conferred by the presence of specific sequences located between amino acids 402 and 420 in the CD4 cytoplasmic domain. Using an in vitro translation system, we also showed that degradation of CD4 by Vpu requires the two proteins to be present in the same membrane compartment. Although these results suggest that spatial proximity between CD4 and Vpu may be critical in triggering degradation, it remains unknown whether the two molecules have the ability to interact with each other. In order to better define the mechanisms involved in CD4 degradation, we investigated the existence and functional relevance of direct interactions between CD4 and Vpu. Coimmunoprecipitation experiments showed that Vpu specifically binds to the cytoplasmic tail of CD4. This phenomenon is relevant to the mechanism of CD4 degradation since the ability of CD8/CD4 chimeric molecules and various CD4 mutants to form complexes with Vpu correlates with their sensitivity to degradation. Accordingly, we found that amino acid residues in the CD4 cytoplasmic tail previously shown to be important for degradation are necessary for Vpu binding. We further demonstrate that a deletion mutant of Vpu as well as a phosphorylation mutant, both biologically inactive with regard to CD4 degradation, retained the capacity to interact with the CD4 cytoplasmic domain. Taken together, these results indicate that Vpu binding is necessary to trigger CD4 degradation. However, the binding to target molecules is not sufficient per se to cause degradation. Interaction between CD4 and Vpu is thus likely to be an early event critical in triggering a multistep process leading to CD4 degradation. RP BOUR, S (reprint author), NIAID,MOLEC MICROBIOL LAB,BLDG 4,ROOM 312,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 51 TC 167 Z9 172 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 MAR PY 1995 VL 69 IS 3 BP 1510 EP 1520 PG 11 WC Virology SC Virology GA QG073 UT WOS:A1995QG07300016 PM 7853484 ER PT J AU FURUTA, RA KUBOTA, S MAKI, M MIYAZAKI, Y HATTORI, T HATANAKA, M AF FURUTA, RA KUBOTA, S MAKI, M MIYAZAKI, Y HATTORI, T HATANAKA, M TI USE OF A HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 REV MUTANT WITHOUT NUCLEOLAR DYSFUNCTION AS A CANDIDATE FOR POTENTIAL AIDS THERAPY SO JOURNAL OF VIROLOGY LA English DT Article ID ENVELOPE GLYCOPROTEIN; RETROVIRAL VECTORS; HIV-1 REPLICATION; TARGETING SIGNAL; GENE-EXPRESSION; TRANS-ACTIVATOR; MESSENGER-RNA; PROTEIN; SEQUENCE; CELLS AB Applications of transdominant mutants of human immunodeficiency virus type 1 (HIV-1) regulatory proteins, especially Rev mutant, have been attempted for gene therapy against AIDS, because the Rev protein is essential for viral replication. We have previously reported that a mutant Rev protein (dRev) lacking its nucleolar targeting signal remained out of nuclei in expressed cells and strongly inhibited the function of Rev. To investigate the effects of dRev on HIV-1 replication, we established several dRev-expressing human cell lines with two different vector systems and examined virus production in these cells, An HIV-1-derived vector containing drev cDNA was constructed and introduced into CD4-positive HeLa cells and cells of the human T-cell line CCRF-CEM (CEM). In dRev-expressing HeLa cells, virus replication, syncytium formation, and cell death caused by HIV-1 infection were remarkably suppressed, and the same vector also conferred a resistant phenotype on CEM cells, The production was also suppressed in CEM cells containing the drev gene driven by a cytomegalovirus promoter. In addition, we found that dRev dia not cause nucleolar dysfunction in a transient assay, in contrast to other transdominant mutants and wild-type Rev, Since dRev cannot migrate into the nuclei, it is expected not to interfere with nuclear/nucleolar functions of the host cell, We conclude that dRev is one promising candidate as an antiviral molecule for gene therapy against AIDS, C1 KYOTO UNIV,INST VIRUS RES,DEPT MOLEC VIROL,KYOTO 606,JAPAN. KYOTO UNIV,IMMUNODEFICIENCY VIRUS RES CTR,INST VIRUS RES,KYOTO 606,JAPAN. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MOLEC VIROL & CARCINOGENESIS LAB,FREDERICK,MD 21702. NR 50 TC 25 Z9 25 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 MAR PY 1995 VL 69 IS 3 BP 1591 EP 1599 PG 9 WC Virology SC Virology GA QG073 UT WOS:A1995QG07300025 PM 7853493 ER PT J AU SEMMES, OJ JEANG, KT AF SEMMES, OJ JEANG, KT TI DEFINITION OF A MINIMAL ACTIVATION DOMAIN IN HUMAN T-CELL LEUKEMIA-VIRUS TYPE-I TAX SO JOURNAL OF VIROLOGY LA English DT Article ID LONG TERMINAL REPEAT; DNA-BINDING PROTEINS; HTLV-I; TRANSCRIPTIONAL ACTIVATION; MAMMALIAN-CELLS; GENE-EXPRESSION; MEDIATED TRANSACTIVATION; BASAL TRANSCRIPTION; INDUCIBLE ENHANCER; NUCLEAR FACTOR AB Fourteen mutants were used to delineate a minimal activation domain in the Tax protein of human T-celI leukemia virus type I, In an assay using a Gal4-Tax (GalTx) fusion protein and a responsive promoter containing Gal4 consensus binding sites, we found that activation was ''squelched'' by coexpression of wild-type Tax protein in trans. When Tax mutants were tested for squelching, many competed effectively against GalTx. However, those containing changes in amino acids 289 to 322 failed to inhibit activity. In particular, three mutants that were expressed stably, with changes at amino acids 289, 296, and 320 respectively, did not squelch GalTx activity. On the other hand, mutants with individual changes at amino acid 3, 9, 29, 41, 273, and 337 efficiently inhibited GalTx function. Three other mutants failed to be stably expressed. In separate experiments, when fused alone to the DNA-binding domain of Gal4, amino acids 289 to 322 of Tax conferred trans activation ability. This fusion protein was able to activate a core promoter. These findings suggest that amino acids 289 to 322 define a region that contacts an essential transcription factor and that this region is a modular activation domain. C1 NIAID,MOLEC MICROBIOL LAB,MOLEC VIROL SECT,BETHESDA,MD 20892. RI Jeang, Kuan-Teh/A-2424-2008 NR 79 TC 50 Z9 50 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 MAR PY 1995 VL 69 IS 3 BP 1827 EP 1833 PG 7 WC Virology SC Virology GA QG073 UT WOS:A1995QG07300055 PM 7853523 ER PT J AU STERN, TL REITZ, MS ROBERTGUROFF, M AF STERN, TL REITZ, MS ROBERTGUROFF, M TI SPONTANEOUS REVERSION OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 NEUTRALIZATION-RESISTANT VARIANT HXB2THR582 - IN-VITRO SELECTION AGAINST CYTOPATHICITY HIGHLIGHTS GP120-GP41 INTERACTIVE REGIONS SO JOURNAL OF VIROLOGY LA English DT Article ID GP41 ENVELOPE GLYCOPROTEIN; HUMAN MONOCLONAL-ANTIBODY; AIDS-RELATED COMPLEX; AMINO-ACID CHANGES; HTLV-III; TRANSMEMBRANE-PROTEIN; POINT MUTATION; SYNCYTIUM FORMATION; REPLICATIVE CAPACITY; GENOMIC DIVERSITY AB Spontaneous revertants of the immune-selected variant HXB2thr582, which resists neutralization by certain conformationally dependent antibodies specific for the CD4-binding site on gp120 (such as F105), appeared after long-term culture in the absence of immune-selecting serum, Molecular analysis showed some of the viruses in the revertant stock contained a simple back mutation, whereas others retained the Thr-582 codon but contained a substitution of serine for phenylalanine in gp41 at position 673. Neutralization sensitivity to the selecting serum and to F105 of infectious clones containing either the back mutation or the compensatory mutation, HXB2thr582ser673, was confirmed. HXB2thr582-infected cells have a greater propensity for syncytium formation and Single cell killing than do either the parental HXB2 or the revertant HXB2thr582ser673. This suggests that the revertant arose by selection in vitro for a less cytopathic virus. Our results link three envelope regions shown to influence virus-cell fusion as well as neutralization by antibody: the CD4-binding region, the leucine zipper domain, and a region hidden to antipeptide antibodies upon envelope oligomerization. Taken together they illustrate the functional importance of the gp120-gp41 interaction and emphasize the impact of the interplay between envelope regions on overall conformation and function and on recognition by neutralizing antibodies. C1 NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. NR 64 TC 10 Z9 10 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 MAR PY 1995 VL 69 IS 3 BP 1860 EP 1867 PG 8 WC Virology SC Virology GA QG073 UT WOS:A1995QG07300059 PM 7853527 ER PT J AU DERSE, D MIKOVITS, J POLIANOVA, M FELBER, BK RUSCETTI, F AF DERSE, D MIKOVITS, J POLIANOVA, M FELBER, BK RUSCETTI, F TI VIRIONS RELEASED FROM CELLS TRANSFECTED WITH A MOLECULAR CLONE OF HUMAN T-CELL LEUKEMIA-VIRUS TYPE-I GIVE RISE TO PRIMARY AND SECONDARY INFECTIONS OF T-CELLS SO JOURNAL OF VIROLOGY LA English DT Note ID TROPICAL SPASTIC PARAPARESIS; HUMAN-ENDOTHELIAL CELLS; LONG TERMINAL REPEAT; HTLV-I; TRANSCRIPTIONAL ACTIVATOR; LYMPHOMA VIRUS; SURFACE PHENOTYPE; INVITRO INFECTION; PERIPHERAL-BLOOD; LYMPHOCYTES-T AB The ability of molecular clones of human T-cell leukemia virus type I (HTLV-I) to direct the synthesis of infectious virions has not previously been demonstrated. An HTLV-I provirus originating from an adult T-cell leukemia patient was cloned into a plasmid vector and is designated pCS-HTLV. This molecular clone was shown to direct the synthesis of viral mRNAs and proteins in transiently transfected cells; in addition, virus structural proteins were released into the culture medium. Viral proteins were assembled into virions that sedimented at a buoyant density characteristic of retrovirus particles and whose morphology was verified by electron microscopy. Virions concentrated from transiently transfected cell supernatants were incubated with primary cord blood lymphocytes or with transformed T-cell lines to establish that these particles were infectious. Expression of spliced, viral mRNAs in the T-cell cultures after both primary and secondary infections with cell-free virus revealed that pCS-HTLV encodes an infectious provirus. C1 NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,HUMAN RETROVIRUS PATHOGENESIS GRP,FREDERICK,MD 21702. RP DERSE, D (reprint author), NCI,FREDERICK CANC RES & DEV CTR,LEUKOCYTE BIOL LAB,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21702, USA. FU PHS HHS [N01-C0-74102, N01-C0-74101] NR 40 TC 63 Z9 63 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 MAR PY 1995 VL 69 IS 3 BP 1907 EP 1912 PG 6 WC Virology SC Virology GA QG073 UT WOS:A1995QG07300065 PM 7853532 ER PT J AU MARCHETTI, A BUTTITTA, F MIYAZAKI, S GALLAHAN, D SMITH, GH CALLAHAN, R AF MARCHETTI, A BUTTITTA, F MIYAZAKI, S GALLAHAN, D SMITH, GH CALLAHAN, R TI INT-6, A HIGHLY CONSERVED, WIDELY EXPRESSED GENE, IS MUTATED BY MOUSE MAMMARY-TUMOR VIRUS IN MAMMARY PRENEOPLASIA SO JOURNAL OF VIROLOGY LA English DT Note ID TRANSGENIC MICE; PROTEIN; TUMORIGENESIS; ACTIVATION; INSERTION; KINASES; HOMOLOG; GENOME; REGION; SITES AB With a unique mouse mammary tumor model system in which mouse mammary tumor virus (MMTV) insertional mutations can be detected during progression from preneoplasia to frank malignancy, including metastasis, we have discovered a new common integration site (designated Int-6) for MMTV in mouse mammary tumors, MMTV was integrated into Int-6 in a mammary hyperplastic outgrowth line, its tumors and metastases, and two independent mammary tumors arising in unrelated mice, The Int-6 gene is ubiquitously expressed as a 1.4-kb RNA species in adult tissues and is detected beginning at day 8 of embryonic development, The nucleotide sequence of Int-6 is unrelated to any of the known genes in the GenBank database. MMTV integrates within introns of the gene in the opposite transcriptional orientation, In each tumor tested, this results in the expression of a truncated Int-6/long terminal repeat (LTR) chimeric RNA species which is terminated at a cryptic termination signal in the MMTV LTR Since the nonrearranged Int-6 alleles in these tumors contain no mutations, we favor the conclusion that truncation of the Int-6 gene product either biologically activates its function or represents a dominant-negative mutation. C1 NCI,TUMOR IMMUNOL & BIOL LAB,BETHESDA,MD 20892. NR 24 TC 133 Z9 134 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 MAR PY 1995 VL 69 IS 3 BP 1932 EP 1938 PG 7 WC Virology SC Virology GA QG073 UT WOS:A1995QG07300070 PM 7853537 ER PT J AU FREED, EO MARTIN, MA AF FREED, EO MARTIN, MA TI VIRION INCORPORATION OF ENVELOPE GLYCOPROTEINS WITH LONG BUT NOT SHORT CYTOPLASMIC TAILS IS BLOCKED BY SPECIFIC, SINGLE AMINO-ACID SUBSTITUTIONS IN THE HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 MATRIX SO JOURNAL OF VIROLOGY LA English DT Note ID INTRACELLULAR-TRANSPORT; MATURE VIRIONS; HOST-RANGE; ENV GENE; PROTEIN; INFECTIVITY; DOMAIN; HIV-1; RETROVIRUS; SEQUENCE AB Incorporation of envelope glycoproteins into a budding retrovirus is an essential step in the formation of an infectious virus particle. By using site-directed mutagenesis, we identified specific amino acid residues in the matrix domain of the human immunodeficiency virus type 1 (HIV-1) Gag protein that are critical to the incorporation of HIV-1 envelope glycoproteins into virus particles. Pseudotyping analyses were used to demonstrate that two heterologous envelope glycoproteins with short cytoplasmic tails (the envelope of the amphotropic murine leukemia virus and a naturally truncated HIV-2 envelope) are efficiently incorporated into HIV-1 particles bearing the matrix mutations. Furthermore, deletion of the cytoplasmic tail of HN-I transmembrane envelope glycoprotein gp41 from 150 to 7 or 47 residues reversed the incorporation block imposed by the matrix mutations. These results suggest the existence of a specific functional interaction between the HIV-1 matrix and the gp41 cytoplasmic tail. RP FREED, EO (reprint author), NIAID,MOLEC MICROBIOL LAB,BLDG 4,RM 307,BETHESDA,MD 20892, USA. NR 49 TC 234 Z9 235 U1 0 U2 5 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 MAR PY 1995 VL 69 IS 3 BP 1984 EP 1989 PG 6 WC Virology SC Virology GA QG073 UT WOS:A1995QG07300079 PM 7853546 ER PT J AU NORBURN, JEK BERNARD, SL KONRAD, TR WOOMERT, A DEFRIESE, GH KALSBEEK, WD KOCH, GG ORY, MG AF NORBURN, JEK BERNARD, SL KONRAD, TR WOOMERT, A DEFRIESE, GH KALSBEEK, WD KOCH, GG ORY, MG TI SELF-CARE AND ASSISTANCE FROM OTHERS IN COPING WITH FUNCTIONAL STATUS LIMITATIONS AMONG A NATIONAL SAMPLE OF OLDER ADULTS SO JOURNALS OF GERONTOLOGY SERIES B-PSYCHOLOGICAL SCIENCES AND SOCIAL SCIENCES LA English DT Article AB Using data front the first wave of a new longitudinal data set collected in the late fall and winter of 1990-1991, the National Survey of Self-Care and Aging (NSSCA), we examined older adults' self-care practices in coping with functional status limitations based on in-person interviews with a national probability sample of 3,485 noninstitutionalized adults aged 65 or older selected from Medicare beneficiary files. A composite score of functional status was calculated to reflect the presence and severity of disability in three dimensions: basic, mobility, and instrumental activities of daily living. Three types of self-care coping strategies were defined: use of equipment or devices, changes in behavior, and modifications in one's environment. National estimates of self-care practices, assistance from others, and functional status measures were presented. Data revealed that the likelihood of engaging in self-care coping strategies increased as the severity of disability increased, except among the most severely disabled. Generally, those receiving assistance from others were more likely to engage in self-care activities, suggesting that receiving assistance supplements, rather than supplants, self-care coping strategies. C1 UNIV N CAROLINA,CECIL G SHEPS CTR HLTH SERV RES,CHAPEL HILL,NC 27599. UNIV N CAROLINA,CURRICULUM PUBL HLTH NURSING,CHAPEL HILL,NC 27599. UNIV N CAROLINA,DEPT HLTH POLICY & ADM,CHAPEL HILL,NC 27599. UNIV N CAROLINA,DEPT SOCIAL MED,CHAPEL HILL,NC 27599. UNIV N CAROLINA,DEPT EPIDEMIOL,CHAPEL HILL,NC 27599. UNIV N CAROLINA,DEPT BIOSTAT,CHAPEL HILL,NC 27599. NIA,BETHESDA,MD 20892. FU NIA NIH HHS [AG07929-02] NR 26 TC 59 Z9 60 U1 1 U2 3 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 SN 1079-5014 J9 J GERONTOL B-PSYCHOL JI J. Gerontol. Ser. B-Psychol. Sci. Soc. Sci. PD MAR PY 1995 VL 50 IS 2 BP S101 EP S109 PG 9 WC Geriatrics & Gerontology; Gerontology; Psychology; Psychology, Multidisciplinary SC Geriatrics & Gerontology; Psychology GA RY948 UT WOS:A1995RY94800011 PM 7757838 ER PT J AU UTANI, A KOPP, JB KOZAK, CA MATSUKI, Y AMIZUKA, N SUGIYAMA, S YAMADA, Y AF UTANI, A KOPP, JB KOZAK, CA MATSUKI, Y AMIZUKA, N SUGIYAMA, S YAMADA, Y TI MOUSE KALININ B1 (LAMININ BETA-3 CHAIN) - CLONING AND TISSUE DISTRIBUTION SO LABORATORY INVESTIGATION LA English DT Article DE CDNA SEQUENCE; GENE MAP; IN SITU HYBRIDIZATION ID BASEMENT-MEMBRANE PROTEINS; NEUROMUSCULAR-JUNCTION; CELLS; EPILIGRIN; LIGAND; ALPHA-3-BETA-1; EXPRESSION; ASSIGNMENT; COMPONENT; RECEPTOR AB BACKGROUND: Kalinin, an anchoring filament-associated protein, is a member of the laminin family which is believed to play a role in the attachment of particular epithelial cells to the basement membrane. EXPERIMENTAL DESIGN: A newborn mouse lung cDNA library was screened under low stringency conditions using as a probe a murine laminin pi chain cDNA, an approach designed to identify novel laminin pi chain homologs. RESULTS: We have identified a novel cDNA sequence comprising 4049 base pahs, with an open reading frame that potentially codes for 1168 amino acids, including a presumptive signal peptide. The gene was mapped to mouse chromosome 1. The amino acid sequence is homologous to laminin beta 1 and beta 2 chains, but is distinguished from these molecules by having a truncated short arm region. The sequence has considerable similarity to the human kalinin B1 chain (laminin beta 3), suggesting that it is murine beta 3 chain. Northern blot analysis demonstrated a single 4.0-kilobase species in the mouse newborn skin, lung, and Pam 212 cells. Immunolocalization studies using the 14-day embryo and adult mouse tissues demonstrated that the murine beta 3 chain is located at the dermal-epidermal junction of the skin and the basement membrane of the oral mucosa, oropharynx, and upper portions of the tracheobronchial tree. In situ hybridization studies of the mammary gland showed that the beta 3 mRNA chain was produced by the epithelial cells of the gland but not by the mesenchymal cells. Western blotting under nonreducing conditions using the antibody to beta 3 chain detected molecules of 400 and 440 kilodaltons (kDa) in the conditioned medium of human foreskin keratinocytes, A431 cells, and Pam 212 cells. Western blotting under reducing conditions detected only a single 140-kDa species, suggesting that beta 3 chain is present within disulfide-linked complexes. This 140-kDa species was contained in the kalinin complex immunoprecipitated by anti-kalinin beta 2 (laminin gamma 2) antibody from the conditioned medium of HT1080 cells, suggesting that both the beta 3 and gamma 2 chains are present in the multimeric complex. CONCLUSIONS: Murine laminin beta 3 chain shows considerable homology to the human homolog and has a tightly restricted tissue distribution, confined to the basement membrane of cells in contact with the external environment. In vitro studies indicate that the beta 3 chain participates in trimer formation with the gamma 2 chain and possibly with other laminin chains as well. C1 NIDR,DEV BIOL LAB,BETHESDA,MD 20892. NIAID,MOLEC MICROBIOL LAB,BETHESDA,MD 20892. ROYAL VICTORIA HOSP,CALCIUM RES LAB,MONTREAL,PQ H3A 1A1,CANADA. NIDR,ORAL MED LAB,BETHESDA,MD 20892. NR 35 TC 29 Z9 30 U1 0 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 MAR PY 1995 VL 72 IS 3 BP 300 EP 310 PG 11 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA QN467 UT WOS:A1995QN46700007 PM 7898049 ER PT J AU PARSEGIAN, VA AF PARSEGIAN, VA TI STRENGTH OF VAN-DER-WAALS ATTRACTION BETWEEN MICA SURFACES ACROSS LIPID BILAYERS SO LANGMUIR LA English DT Note ID ENTROPY-DRIVEN TENSION; FORCES; PHOSPHATIDYLCHOLINE; ELECTROLYTE; DEFORMATION; MEMBRANES; ADHESION C1 NIDDK,DIR,MOLEC FORCES SECT,BETHESDA,MD 20892. RP PARSEGIAN, VA (reprint author), NIDDK,DCRT,STRUCT BIOL LAB,BETHESDA,MD 20892, USA. NR 17 TC 6 Z9 6 U1 1 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0743-7463 J9 LANGMUIR JI Langmuir PD MAR PY 1995 VL 11 IS 3 BP 1047 EP 1047 DI 10.1021/la00003a059 PG 1 WC Chemistry, Multidisciplinary; Chemistry, Physical; Materials Science, Multidisciplinary SC Chemistry; Materials Science GA QP595 UT WOS:A1995QP59500059 ER PT J AU WU, T RIEVES, RD LOGUN, C SHELHAMER, JH AF WU, T RIEVES, RD LOGUN, C SHELHAMER, JH TI PLATELET-ACTIVATING-FACTOR STIMULATES EICOSANOID PRODUCTION IN CULTURED FELINE TRACHEAL EPITHELIAL-CELLS SO LUNG LA English DT Article DE PLATELET-ACTIVATING FACTOR; ARACHIDONIC ACID; EICOSANOIDS; AIRWAY EPITHELIAL CELLS ID HUMAN AIRWAYS INVITRO; ARACHIDONIC-ACID; GUINEA-PIG; HUMAN-LUNG; MONOHYDROXYEICOSATETRAENOIC ACID; RESPIRATORY GLYCOCONJUGATE; BINDING-SITES; RELEASE; GENERATION; CYCLOOXYGENASE AB The effect of platelet-activating factor (PAF) on eicosanoid generation and release in cultured feline tracheal epithelial cells was investigated by measuring a wide range of lipoxygenase and cyclooxygenase pathway products. Subconfluent epithelial cell cultures were stimulated by PAF and eicosanoid production was determined by high performance liquid chromatography (HPLC) of [H-3]-labeled arachidonic acid (AA) metabolites and by radioimmunoassay (RIA) following HPLC separation. The HPLC chromatograms revealed that PAF augmented the release of prostaglandin (PG)E(2), PGF(2 alpha), 12-hydroxyeicosatetraenoic acid (HETE), and AA. Among these eicosanoids, PGE(2) predominated under baseline conditions and following PAF exposure. RIAs of the nonradiolabeled HPLC elution corresponding to various eicosanoid standards demonstrated that PAF increased the production of 6-keto-PGF(1 alpha), thromboxane B-2 (TXB(2)), PGD(2), 5-HETE, and 15-HETE, as well as PGE(2), PGF(2 alpha), and 12-HETE. The PAF-induced eicosanoid augmentation was dose-dependent and occurred within 1 hour with a prompt decline following termination of PAF exposure. This stimulating effect of PAF on eicosanoid release was blocked by two PAF receptor antagonists, Ro 19-3704 and WEB 2086. The PAF-induced increase in eicosanoid release was similar in magnitude to the increase caused by calcium ionophore (Ca-ionophore) A23187, a potent known stimulus for eicosanoid release. Cells of different culture durations (3 and 6 days) showed similar capacity for eicosanoid production. We conclude that PAF stimulates the production of cyclooxygenase and lipoxygenase pathway products from airway epithelial cells via PAF receptors, and that these epithelium-derived eicosanoids may be responsible for some of the PAF-induced respiratory physiological and pathophysiological effects. C1 NIH,DEPT CRIT CARE MED,BETHESDA,MD 20892. NR 43 TC 7 Z9 7 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0341-2040 J9 LUNG JI Lung PD MAR-APR PY 1995 VL 173 IS 2 BP 89 EP 103 DI 10.1007/BF02981469 PG 15 WC Respiratory System SC Respiratory System GA QB461 UT WOS:A1995QB46100003 PM 7715256 ER PT J AU BATTEY, JF BROWN, PH GRITZ, ER HONG, WK JOHNSON, BE KARP, DD MULSHINE, JL SHAW, GL SHOPLAND, DR SUNDAY, ME SZABO, E AF BATTEY, JF BROWN, PH GRITZ, ER HONG, WK JOHNSON, BE KARP, DD MULSHINE, JL SHAW, GL SHOPLAND, DR SUNDAY, ME SZABO, E TI PRIMARY AND SECONDARY PREVENTION OF LUNG-CANCER - AN INTERNATIONAL-ASSOCIATION-FOR-THE-STUDY-OF-LUNG-CANCER WORKSHOP SO LUNG CANCER LA English DT Editorial Material C1 NCI,DIV CANC PREVENT & CONTROL,BIOMARKERS & PREVENT RES BRANCH,ROCKVILLE,MD 20852. DIV DEV THERAPEUT PROGRAM,MOLEC STRUCT SECT,BETHESDA,MD 20892. UNIV TEXAS,MD ANDERSON CANC CTR,DEPT BEHAV SCI,HOUSTON,TX 77030. UNIV TEXAS,MD ANDERSON CANC CTR,DEPT THORAC HEAD & NECK MED ONCOL,HOUSTON,TX 77030. NCI,DIV CANC TREATMENT,NAVY MED ONCOL BRANCH,BETHESDA,MD 20897. TUFTS UNIV,SCH MED,DEPT HEMATOL & MED ONCOL,BOSTON,MA 02111. NCI,DIV CANC PREVENT & CONTROL,CANC CONTROL SCI PROGRAM,ROCKVILLE,MD 20852. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. NR 0 TC 5 Z9 5 U1 0 U2 1 PU ELSEVIER SCI PUBL IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0169-5002 J9 LUNG CANCER-J IASLC JI Lung Cancer PD MAR PY 1995 VL 12 IS 1-2 BP 91 EP 103 DI 10.1016/0169-5002(94)00412-G PG 13 WC Oncology; Respiratory System SC Oncology; Respiratory System GA QU650 UT WOS:A1995QU65000011 PM 7600036 ER PT J AU VANGELDEREN, P MOONEN, CTW DUYN, JH AF VANGELDEREN, P MOONEN, CTW DUYN, JH TI SUSCEPTIBILITY INSENSITIVE SINGLE-SHOT MRI COMBINING BURST AND MULTIPLE SPIN ECHOES SO MAGNETIC RESONANCE IN MEDICINE LA English DT Note DE MRI; BURST; MSE; GRASE AB A single shot MR imaging technique insensitive to magnetic susceptibility effects is introduced. The method allows multislice imaging in areas with poor magnetic field homogeneity, and can be implemented on standard clinical scanners. The design is based on the combination of a BURST excitation with multiple Rf refocusing pulses. Images were obtained at 1.5 T on phantoms and human brain with a matrix size of 64 x 54 and a resolution of 4 x 4 mm in 230 ms. C1 NIH,OIR,DIAGNOST RADIOL RES LAB,BETHESDA,MD 20892. NIH,NATL CTR RES RESOURCES,BIOMED ENGN & INSTRUMENTAT PROGRAM,IN VIVO NMR RES CTR,BETHESDA,MD 20892. RI Duyn, Jozef/F-2483-2010; Moonen, Chrit/K-4434-2016 OI Moonen, Chrit/0000-0001-5593-3121 NR 7 TC 9 Z9 9 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0740-3194 J9 MAGNET RESON MED JI Magn.Reson.Med. PD MAR PY 1995 VL 33 IS 3 BP 439 EP 442 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA QK086 UT WOS:A1995QK08600019 PM 7760714 ER PT J AU BYRNE, J FEARS, TR WHITNEY, C PARRY, DM AF BYRNE, J FEARS, TR WHITNEY, C PARRY, DM TI SURVIVAL AFTER RETINOBLASTOMA - LONG-TERM CONSEQUENCES AND FAMILY HISTORY OF CANCER SO MEDICAL AND PEDIATRIC ONCOLOGY LA English DT Article DE RETINOBLASTOMA; SURVIVORS; LATE EFFECTS ID UNITED-STATES; CHILDHOOD; TUMORS; ADULTS AB Retinoblastoma (Rb) is a rare childhood tumor of the eye. In the heritable form, tumors are often bilateral and survivors have a greatly increased risk both for a second malignancy and for having children with Rb. Familial patterns of both cancer and birth defects are poorly understood in families with a heritable cancer, and little is known of the ways that a heritable cancer affects the lives of long-term survivors. To find out more about these and other issues in the lives of long-term survivors of childhood and adolescent cancer, we interviewed 56 adult survivors of retinoblastoma (15 with the heritable form) and 84 brothers and sisters as controls, who formed part of a large retrospective cohort study. Rb survivors were interviewed between 1980 and 1983, when they were 30 years old on average. Types of employment and health problems did not differ between survivors and controls, regardless of sight, but the income of blind survivors was considerably less than that of partially sighted survivors. Despite similar marriage rates, fewer survivors than controls reported a pregnancy (RR = 0.45; 95% Cl; 0.24-0.83 for both sexes combined). Parents of children with heritable Rb seemed more likely to have had cancer than parents in families with nonheritable Rb (P = 0.06), and mothers were more likely than fathers to be affected (P = 0.01). This small series suggests that having retinoblastoma may have many long-term consequences, reaching beyond genetic and physical effects to touch family life and income attainment and the health of other family members. Follow-up of more modern cohorts and the use of molecular tools will clarify the long-term consequences of more recent therapies, and patterns of familiar cancer. (C) 1995 Wiley-Liss, Inc. C1 BOYNE RES INST,DROGHEDA,IRELAND. CHILDRENS RES INST,WASHINGTON,DC. NCI,EPIDEMIOL & BIOSTAT PROGRAM,BETHESDA,MD 20892. NR 19 TC 25 Z9 25 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0098-1532 J9 MED PEDIATR ONCOL JI Med. Pediatr. Oncol. PD MAR PY 1995 VL 24 IS 3 BP 160 EP 165 DI 10.1002/mpo.2950240304 PG 6 WC Oncology; Pediatrics SC Oncology; Pediatrics GA QE250 UT WOS:A1995QE25000003 PM 7838037 ER PT J AU BOLLINGER, RC TRIPATHY, SP QUINN, TC AF BOLLINGER, RC TRIPATHY, SP QUINN, TC TI THE HUMAN-IMMUNODEFICIENCY-VIRUS EPIDEMIC IN INDIA - CURRENT MAGNITUDE AND FUTURE PROJECTIONS SO MEDICINE LA English DT Review ID SEXUALLY-TRANSMITTED DISEASES; HIV-INFECTION; BLOOD-DONORS; PLASMA DONORS; UNITED-STATES; WESTERN INDIA; TAMIL-NADU; RISK GROUP; AIDS; DELHI C1 NIAID,BETHESDA,MD. INDIAN COUNCIL MED RES,NEW DELHI,INDIA. RP BOLLINGER, RC (reprint author), JOHNS HOPKINS UNIV,SCH MED,DIV INFECT DIS,ROSS RES BLDG,ROOM 1159,720 RUTLAND AVE,BALTIMORE,MD 21205, USA. FU NCRR NIH HHS [5M01RR00722]; NIAID NIH HHS [AI 33879-02] NR 101 TC 80 Z9 80 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0025-7974 J9 MEDICINE JI Medicine (Baltimore) PD MAR PY 1995 VL 74 IS 2 BP 97 EP 106 DI 10.1097/00005792-199503000-00005 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA QQ270 UT WOS:A1995QQ27000005 PM 7891548 ER PT J AU MCCRAY, AT SCHERRER, JR SAFRAN, C CHUTE, CG AF MCCRAY, AT SCHERRER, JR SAFRAN, C CHUTE, CG TI CONCEPTS, KNOWLEDGE, AND LANGUAGE IN HEALTH-CARE INFORMATION-SYSTEMS SO METHODS OF INFORMATION IN MEDICINE LA English DT Editorial Material C1 UNIV GENEVA,FAC MED,GENEVA,SWITZERLAND. HARVARD UNIV,BETH ISRAEL HOSP,SCH MED,CTR CLIN COMP,BOSTON,MA. MAYO CLIN & MAYO FDN,DEPT HLTH SCI RES,MED INFORMAT RESOURCES SECT,ROCHESTER,MN 55905. RP MCCRAY, AT (reprint author), NATL LIB MED,LISTER HILL CTR BIOMED COMMUN,EDUC TECHNOL BRANCH,BETHESDA,MD 20894, USA. NR 0 TC 25 Z9 25 U1 0 U2 1 PU F K SCHATTAUER VERLAG GMBH PI STUTTGART PA P O BOX 10 45 45, LENZHALDE 3, D-70040 STUTTGART, GERMANY SN 0026-1270 J9 METHOD INFORM MED JI Methods Inf. Med. PD MAR PY 1995 VL 34 IS 1-2 BP 1 EP 4 PG 4 WC Computer Science, Information Systems; Health Care Sciences & Services; Medical Informatics SC Computer Science; Health Care Sciences & Services; Medical Informatics GA QT068 UT WOS:A1995QT06800001 PM 9082118 ER PT J AU MCCRAY, AT NELSON, SJ AF MCCRAY, AT NELSON, SJ TI THE REPRESENTATION OF MEANING IN THE UMLS SO METHODS OF INFORMATION IN MEDICINE LA English DT Article; Proceedings Paper CT 3rd Working Conference of the International-Medical-Informatics-Association-Working-Group-6 CY MAY 29-JUN 01, 1994 CL VEVEY, SWITZERLAND SP INT MED INFORMAT ASSOC, WORKING GRP 6 DE UMLS; KNOWLEDGE REPRESENTATION AB The UMLS knowledge sources provide detailed information about biomedical naming systems and databases. The Metathesaurus contains biomedical terminology from an increasing number of biomedical thesauri, and the Semantic Network provides a structure that encompasses and unifies the thesauri that are included in the Metathesaurus. This paper addresses some fundamental principles underlying the design and development of the Metathesaurus and Semantic Network. It begins with a description of the formal properties of thesauri, including the Metathesaurus, and the formal properties of the Semantic Network, It continues with consideration of the principle of semantic locality and how this is reflected in the UMLS knowledge sources. The paper concludes with a discussion of the issues involved in attempting to re-use knowledge and the potential for re-use of the UMLS knowledge sources. C1 MED COLL GEORGIA,AUGUSTA,GA 30912. RP MCCRAY, AT (reprint author), NATL LIB MED,BETHESDA,MD 20894, USA. NR 15 TC 109 Z9 110 U1 0 U2 0 PU F K SCHATTAUER VERLAG GMBH PI STUTTGART PA P O BOX 10 45 45, LENZHALDE 3, D-70040 STUTTGART, GERMANY SN 0026-1270 J9 METHOD INFORM MED JI Methods Inf. Med. PD MAR PY 1995 VL 34 IS 1-2 BP 193 EP 201 PG 9 WC Computer Science, Information Systems; Health Care Sciences & Services; Medical Informatics SC Computer Science; Health Care Sciences & Services; Medical Informatics GA QT068 UT WOS:A1995QT06800024 PM 9082131 ER PT J AU Klein, DL AF Klein, DL TI Pneumococcal conjugate vaccines: Review and update SO MICROBIAL DRUG RESISTANCE-MECHANISMS EPIDEMIOLOGY AND DISEASE LA English DT Review ID INFLUENZAE TYPE-B; MEMBRANE PROTEIN COMPLEX; STREPTOCOCCUS-PNEUMONIAE; CAPSULAR POLYSACCHARIDE; ANTIBODY-RESPONSE; OTITIS-MEDIA; IMMUNE-RESPONSE; CHILDREN; IMMUNOGENICITY; IMMUNIZATION RP Klein, DL (reprint author), NIAID,NIH,6003 EXECUT BLVD,SOLAR BLDG,ROOM 3B03,BETHESDA,MD 20892, USA. NR 64 TC 36 Z9 36 U1 1 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1076-6294 J9 MICROB DRUG RESIST JI Microb. Drug Resist.-Mechan. Epidemiol. Dis. PD SPR PY 1995 VL 1 IS 1 BP 49 EP 58 DI 10.1089/mdr.1995.1.49 PG 10 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA TU493 UT WOS:A1995TU49300007 PM 9156384 ER PT J AU HOLCOMB, WF AF HOLCOMB, WF TI RADIATION SAFETY TRAINING-PROGRAM AT THE NATIONAL-INSTITUTES-OF-HEALTH SO MILITARY MEDICINE LA English DT Article AB At the U.S. Public Health Service's National Institutes of Health (NIH), one of the world's largest biomedical and clinical research institutions, 70 to 80% of all research is performed using radiation or radioactive materials. To maintain a safe environment and minimize risks to the health and safety of the employees, patients, visitors, and the surrounding community, a radiation protection program is required. Under U.S. Nuclear Regulatory Commission licenses and NIH policies, the Radiation Safety Branch (RSB), Division of Safety, administers a comprehensive radiation safety program covering over 3,500 NIH laboratories and some 7,000 laboratory and ancillary staff workers. The NIH radiation protection program provides for the effective supervision, control, and monitoring of all radioactive materials and radiation sources at NIH, This includes activities such as radiation exposure monitoring, laboratory inspections, waste management, consulting, environmental monitoring, and training, Training is considered an integral part of the radiation safety program, RSB offers an extensive training program with over 20 different training courses each year, For example, in 1993 some 6,700 employees attended 243 classes. RP HOLCOMB, WF (reprint author), NIH,DIV SAFETY,RADIAT SAFETY BRANCH,BLDG 10,BETHESDA,MD 20892, USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU ASSN MILITARY SURG US PI BETHESDA PA 9320 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0026-4075 J9 MIL MED JI Milit. Med. PD MAR PY 1995 VL 160 IS 3 BP 115 EP 120 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA QY950 UT WOS:A1995QY95000006 PM 7783932 ER PT J AU ALALAWI, N ROSE, DW BUCKMASTER, C AHN, N RAPP, U MEINKOTH, J FERAMISCO, JR AF ALALAWI, N ROSE, DW BUCKMASTER, C AHN, N RAPP, U MEINKOTH, J FERAMISCO, JR TI THYROTROPIN-INDUCED MITOGENESIS IS RAS DEPENDENT BUT APPEARS TO BYPASS THE RAF-DEPENDENT CYTOPLASMIC KINASE CASCADE SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID ACTIVATED PROTEIN-KINASE; EPIDERMAL GROWTH-FACTOR; HUMAN THYROID-TUMORS; SIGNAL-TRANSDUCTION; ADENYLATE-CYCLASE; DNA-SYNTHESIS; ZETA-ISOFORM; CELLS; PHOSPHORYLATION; INHIBITION AB Cellular growth control requires the coordination and integration of multiple signaling pathways which are likely to be activated concomitantly. Mitogenic signaling initiated by thyrotropin (TSH) in thyroid cells seems to require two distinct signaling pathways, a cyclic AMP (cAMP)-dependent signaling pathway and a Ras-dependent pathway. This is a paradox, since activated cAMP-dependent protein kinase disrupts Ras-dependent signaling induced by growth factors such as epidermal growth factor and platelet-derived growth factor. This inhibition may occur by preventing Raf-1 protein kinase from binding to Ras, an event thought to be necessary for the activation of Raf-1 and the subsequent activation of the mitogen-activated protein (MAP)/extracellular signal-regulated kinase (ERK) kinases (MEKs) and MAP kinase (MAPK)/ERKs. Here we report that serum-stimulated hyperphosphorylation of Raf-1 was inhibited by TSH treatment of Wister rat thyroid cells, indicating that in this cell line, as in other cell types, increases in intracellular cAMP levels inhibit activation of downstream kinases targeted by Ras. Ras-stimulated expression of genes containing AP-1 promoter elements was similarly inhibited by TSH. On the other hand, stimulation of thyroid cells with TSH resulted in stimulation of DNA synthesis which was Ras dependent but both Raf-1 and MEK independent. We also show that Ras-stimulated DNA synthesis required the use of this kinase cascade in untreated quiescent cells hut not in TSH-treated cells. These data suggest that in TSH-treated thyroid cells, Ras might be able to signal through effecters other than the well-studied cytoplasmic kinase cascade. C1 UNIV CALIF SAN DIEGO,DEPT PHARMACOL,LA JOLLA,CA 92093. UNIV CALIF SAN DIEGO,DEPT MED,LA JOLLA,CA 92093. UNIV CALIF SAN DIEGO,WHITTIER DIABET PROGRAM,LA JOLLA,CA 92093. UNIV COLORADO,DEPT CHEM & BIOCHEM,BOULDER,CO 80309. UNIV COLORADO,HOWARD HUGHES MED INST,BOULDER,CO 80309. NCI,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21702. NR 61 TC 60 Z9 60 U1 0 U2 0 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 MAR PY 1995 VL 15 IS 3 BP 1162 EP 1168 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA QH483 UT WOS:A1995QH48300004 PM 7862110 ER PT J AU DRYSDALE, CM DUENAS, E JACKSON, BM REUSSER, U BRAUS, GH HINNEBUSCH, AG AF DRYSDALE, CM DUENAS, E JACKSON, BM REUSSER, U BRAUS, GH HINNEBUSCH, AG TI THE TRANSCRIPTIONAL ACTIVATOR GCN4 CONTAINS MULTIPLE ACTIVATION DOMAINS THAT ARE CRITICALLY DEPENDENT ON HYDROPHOBIC AMINO-ACIDS SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID SACCHAROMYCES-CEREVISIAE; LEUCINE ZIPPER; FACTOR-TFIIB; TRANSLATIONAL ACTIVATION; MESSENGER-RNA; PROTEIN; YEAST; BINDING; VP16; DNA AB GCN4 is a transcriptional activator in the bZIP family that regulates amino acid biosynthetic genes in the yeast Saccharomyces cerevisiae, Previous work suggested that the principal activation domain of GCN4 is a highly acidic segment of approximately 40 amino acids located in the center of the protein, We conducted a mutational analysis of GCN4 with a single-copy allele expressed under the control of the native promoter and translational control elements, Our results indicate that GCN4 contains two activation domains of similar potency that can function independently to promote high-level transcription of the target genes HIS3 and HIS4. One of these domains is coincident with the acidic activation domain defined previously; the other extends over the N-terminal one-third of the protein, Both domains are partially dependent on the coactivator protein ADA2. Each domain appears to be composed of two or more small subdomains that have additive effects on transcription and that can cooperate in different combinations to promote high-level expression of HIS3 and HIS4. At least three of these subdomains are critically dependent on bulky hydrophobic amino acids for their function, Five of the important hydrophobic residues, Phe-97, Phe-98, Met-107, Tyr-110, and Leu-113, fall within a region of proposed sequence homology between GCN4 and the herpesvirus acidic activator VP16. The remaining three residues, Trp-120, Leu-123, and Phe-124, are highly conserved between GCN4 and its Neurospora counterpart, cpc-1. Because of the functional redundancy in the activation domain, mutations at positions 97 and 98 must be combined with mutations at positions 120 to 124 to observe a substantial reduction in activation by full-length GCN4, and substitution of all eight hydrophobic residues was required to inactivate full-length GCN4, These hydrophobic residues may mediate important interactions between GCN4 and one or more of its target proteins in the transcription initiation complex. C1 NICHHD,GENET MOLEC LAB,MOLEC GENET LOWER EUKARYOTES SECT,BETHESDA,MD 20892. UNIV ERLANGEN NURNBERG,INST MIKROBIOL BIOCHEM & GENET,D-91058 ERLANGEN,GERMANY. ETH ZURICH,INST MIKROBIOL,CH-8092 ZURICH,SWITZERLAND. RI Braus, Gerhard/G-3999-2012 OI Braus, Gerhard/0000-0002-3117-5626 NR 58 TC 112 Z9 113 U1 0 U2 4 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 MAR PY 1995 VL 15 IS 3 BP 1220 EP 1233 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA QH483 UT WOS:A1995QH48300011 PM 7862116 ER PT J AU WANG, G LEVY, DD SEIDMAN, MM GLAZER, PM AF WANG, G LEVY, DD SEIDMAN, MM GLAZER, PM TI TARGETED MUTAGENESIS IN MAMMALIAN-CELLS MEDIATED BY INTRACELLULAR TRIPLE-HELIX FORMATION SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID TRANSFER-RNA GENE; FORMING OLIGONUCLEOTIDE; BASE-PAIRS; SHUTTLE-VECTOR; CROSS-LINKING; DNA; RECOGNITION; INHIBITION; BINDING; TRANSCRIPTION AB As an alternative to standard gene transfer techniques for genetic manipulation, we have investigated the use of triple helix forming oligonucleotides to target mutations to selected genes within mammalian cells. By treating monkey COS cells with oligonucleotides linked to psoralen, we have generated targeted mutations in a simian virus 40 (SV40) vector contained within the cells via intracellular triple helix formation. Oligonucleotide entry into the cells and sequence-specific tripler formation within the SV40 DNA deliver the psoralen to the targeted site. Photoactivation of the psoralen by long wavelength UV light yields adducts and thereby mutations at that site. We engineered into the SV40 vector novel supF mutation reporter genes containing modified polypurine sites amenable to tripler formation. By comparing the abilities of a series of oligonucleotides to target these new sites, we show that targeted mutagenesis in vivo depends on the strength and specificity of the third strand binding. Oligonucleotides with weak target site binding affinity or with only partial target site homology were ineffective at inducing mutations in the SV40 vectors within the COS cells. We also show that the targeted mutagenesis is dependent on the oligonucleotide concentration and is influenced by the timing of the oligonucleotide treatment and of the UV irradiation of the cells. Frequencies of intracellular targeted mutagenesis in the range of 1 to 2% were observed, depending upon the conditions of the experiment. DNA sequence analysis revealed that most of the mutations were T.A-to-A.T transversions precisely at the targeted psoralen intercalation site. Several deletions encompassing that site were also seen. The ability to target mutations to selected sites within mammalian cells by using modified tripler-forming oligonucleotides may provide a new research tool and may eventually lead to therapeutic applications. C1 YALE UNIV,SCH MED,DEPT THERAPEUT RADIOL,NEW HAVEN,CT 06510. NCI,MOLEC CARCINOGENESIS LAB,BETHESDA,MD 20892. OTSUKA AMER PHARMACEUT INC,ROCKVILLE,MD 20850. FU NIEHS NIH HHS [ES05775] NR 41 TC 168 Z9 169 U1 0 U2 4 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 MAR PY 1995 VL 15 IS 3 BP 1759 EP 1768 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA QH483 UT WOS:A1995QH48300066 PM 7862165 ER PT J AU JOHN, S REEVES, RB LIN, JX CHILD, R LEIDEN, JM THOMPSON, CB LEONARD, WJ AF JOHN, S REEVES, RB LIN, JX CHILD, R LEIDEN, JM THOMPSON, CB LEONARD, WJ TI REGULATION OF CELL-TYPE-SPECIFIC INTERLEUKIN-2 RECEPTOR ALPHA-CHAIN GENE-EXPRESSION - POTENTIAL ROLE OF PHYSICAL INTERACTIONS BETWEEN ELF-1, HMG-I(Y), AND NF-KAPPA-B FAMILY PROTEINS SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID INDUCIBLE ENHANCER ELEMENTS; SEQUENCE-SPECIFIC BINDING; SERUM RESPONSE ELEMENT; ETS-RELATED PROTEIN; HUMAN LYMPHOCYTES-T; HUMAN IL-2 RECEPTOR; DNA-BINDING; HMG-I; GAMMA-CHAIN; C-FOS AB The interleukin 2 receptor alpha-chain (IL-2R alpha) gene is rapidly and potently induced in T cells in response to mitogenic stimuli. Previously, an inducible enhancer between nucleotides -299 and -228 that contains NF-kappa B and CArG motifs was identified. We now report the characterization of a second essential positive regulatory element located between nucleotides -137 and -64 that binds Elf-1 and HMG-I(Y). This element had maximal activity in lymphoid cells, paralleling the cell type specificity of Elf-1 expression. Transcription from the IL-2R alpha promoter was inhibited when either the Elf-1 or the HMG-I(Y) binding site was mutated. Coexpression of both proteins activated transcription of the -137 to -64 element in COS-7 cells. Elf-1 physically associated with HMG-I and with NF-kappa B p50 and c-Rel in vitro, suggesting that protein-protein interactions might functionally coordinate the actions of the upstream and downstream positive regulatory elements. This is the first report of a physical interaction between an Ets family member and NF-kappa B family proteins. These findings provide significant new insights into the protein-protein and protein-DNA interactions that regulate cell-type-specific and inducible IL-2R alpha gene expression and also have implications for other genes regulated by Elf-1 and NF-kappa B family proteins. C1 NHLBI,MOLEC IMMUNOL LAB,BETHESDA,MD 20892. WASHINGTON STATE UNIV,DEPT BIOCHEM & BIOPHYS,PULLMAN,WA 99164. WASHINGTON STATE UNIV,DEPT GENET & CELL BIOL,PULLMAN,WA 99164. UNIV CHICAGO,HOWARD HUGHES MED INST,DEPT MED,CHICAGO,IL 60637. UNIV CHICAGO,HOWARD HUGHES MED INST,DEPT PATHOL,CHICAGO,IL 60637. UNIV CHICAGO,DEPT MOLEC GENET & CELL BIOL,CHICAGO,IL 60637. FU NIAID NIH HHS [R01 AI29673] NR 81 TC 226 Z9 226 U1 0 U2 0 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 MAR PY 1995 VL 15 IS 3 BP 1786 EP 1796 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA QH483 UT WOS:A1995QH48300069 PM 7862168 ER PT J AU WEBBER, KO REITER, Y BRINKMANN, U KREITMAN, R PASTAN, I AF WEBBER, KO REITER, Y BRINKMANN, U KREITMAN, R PASTAN, I TI PREPARATION AND CHARACTERIZATION OF A DISULFIDE-STABILIZED FV FRAGMENT OF THE ANTI-TAC ANTIBODY - COMPARISON WITH ITS SINGLE-CHAIN ANALOG SO MOLECULAR IMMUNOLOGY LA English DT Article DE PROTEIN FOLDING; PROTEIN ENGINEERING; CANCER DETECTION; RADIOIMMUNOTHERAPY ID RECOMBINANT IMMUNOTOXIN; INTERLEUKIN-2 RECEPTOR; ESCHERICHIA-COLI; PROTEINS; CELLS AB Recombinant DNA techniques now allow the production of ''mini-antibodies'' called Fv fragments. These have been produced either as the independent variable domains of the heavy and light chains non-covalently associated in one-to-one stoichiometry or as single-chain gene products with the two domains linked by an intervening peptide sequence. Although Fv fragments can have excellent binding properties, they are often difficult to produce in good yield and lack the characteristic stability of whole antibodies. To improve the stability of the Fv molecule, we have introduced a cysteine residue into conserved framework regions of both the heavy and light variable domains from the anti-Tac antibody at positions compatible with the formation of an interdomain disulfide linkage (i.e. V-H-44 and V-L-99). The mutant subunits form a disulfide-bonded Fv molecule, which binds to the alpha-subunit of the IL2 receptor IL2R alpha) with an affinity identical to that of humanized anti-Tac IgG. This disulfide-stabilized Fv (dsFv) proved to be substantially more resistant to denaturation by heat or urea treatment than the single-chain Fv (scFv). Furthermore, the yield of dsFv is similar to four-fold higher than that of the single-chain analog. C1 NCI,DIAGNOSIS & CTR,DIV CANC BIOL,MOLEC BIOL LAB,BETHESDA,MD 20892. NR 27 TC 48 Z9 54 U1 0 U2 2 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 MAR PY 1995 VL 32 IS 4 BP 249 EP 258 DI 10.1016/0161-5890(94)00150-Y PG 10 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA QT368 UT WOS:A1995QT36800003 PM 7723770 ER PT J AU WONG, R ZHU, XG PINEDA, MA CHENG, SY WEINTRAUB, BD AF WONG, R ZHU, XG PINEDA, MA CHENG, SY WEINTRAUB, BD TI CELL TYPE-DEPENDENT MODULATION OF THE DOMINANT-NEGATIVE ACTION OF HUMAN MUTANT THYROID-HORMONE BETA-1 RECEPTORS SO MOLECULAR MEDICINE LA English DT Article ID RETINOID-X-RECEPTOR; LIGAND-BINDING DOMAIN; GENERALIZED RESISTANCE; RESPONSE ELEMENTS; AUXILIARY PROTEIN; ENHANCES BINDING; ACID RECEPTORS; T3 RECEPTOR; GENE; EXPRESSION AB Background: Mutations in the ligand-binding domain of the thyroid hormone receptor beta (TR beta) gene cause the syndrome of resistance to thyroid hormone (RTH). The clinical phenotype results from the antagonism of the normal TR alpha and the non-mutated TR beta alleles by the TR beta 1 mutants, via a dominant negative effect. There is, however, marked heterogeneity of organ resistance within and among kindreds with RTH. This study examines the potential role of cell type in modulating the dominant negative potency of human TR beta 1 (h-TR beta 1) mutants. Materials and Methods: Transient transfections were performed in HeLa and NIH3T3 cells, using a wild type (WT) and three naturally occurring mutant h-TR beta 1 constructs, and three natural thyroid hormone response elements (TREs). Immunocytochemistry was performed to detect levels of TR beta 1 expression in these two cell types. In order to determine how TR beta 1 interacts with other cellular partners, gel-shift analyses using HeLa and NM3T3 nuclear extracts were performed. Results: Transfection studies using WT h-TR beta 1 in HeLa and NM3T3 cells, showed that the 3,3',5-triiodothyronine (T-3)-induced transactivation of the different TREs varied between cell. types. Unlike the non-T-3-binding h-TR beta 1 mutant, PV, mutants ED and OK displayed the expected T-3-induced dose responsiveness in these two cell types. For each TRE examined, the magnitude of the dominant negative effect varied between the cell types. The levels of receptor expression in HeLa and NIH3T3 cells were identical, as determined by immunocytochemistry. Gel-shift analyses showed differences in the formation of hetero- and homodimers depending on both the cell type and TRE motif. Conclusions: The cell type in which a mutant receptor operates affects the relative amounts of hetero- and homodimers. Together with the nature of the mutation and the TRE-motif, this could modulate the dominant negative action of mutant receptors in different tissues, which, in turn, could contribute to the variable phenotypic characteristics of RTH. C1 NCI,MOLEC BIOL LAB,GENE REGULAT SECT,BETHESDA,MD 20892. NIDDK,MOLEC & CELLULAR ENDOCRINOL BRANCH,BETHESDA,MD 20892. NR 44 TC 14 Z9 14 U1 0 U2 1 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 1076-1551 J9 MOL MED JI Mol. Med. PD MAR PY 1995 VL 1 IS 3 BP 306 EP 319 PG 14 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA QX600 UT WOS:A1995QX60000009 PM 8529109 ER PT J AU KUMAR, S YADAVA, A KEISTER, DB TIAN, JH OHL, M PERDUEGREENFIELD, KA MILLER, LH KASLOW, DC AF KUMAR, S YADAVA, A KEISTER, DB TIAN, JH OHL, M PERDUEGREENFIELD, KA MILLER, LH KASLOW, DC TI IMMUNOGENICITY AND IN-VIVO EFFICACY OF RECOMBINANT PLASMODIUM-FALCIPARUM MEROZOITE SURFACE PROTEIN-1 IN AOTUS MONKEYS SO MOLECULAR MEDICINE LA English DT Article ID CARBOXYL-TERMINAL FRAGMENT; MICE; VACCINATION; ANTIBODIES; PRECURSOR; ANTIGENS; PARASITE; TARGET; GROWTH AB Background: The carboxy-terminus of the merozoite surface protein-1 (MSP1) of Plasmodium falciparum has been implicated as a target of protective immunity. Materials and Methods: Two recombinant proteins from the carboxy-terminus of MSP1, the 42 kD fused to GST (bMSP1(42)) and the 19 kD (yMSP1(19)), were expressed in Escherichia coli and secreted from Saccharomyces cerevisiae, respectively. To determine if vaccination with these recombinant proteins induces protective immunity, we conducted a randomized, blinded vaccine trial in two species of Aotus monkeys, A. nancymai and A. vociferans. After three injections using Freund's adjuvant, the monkeys were challenged with the virulent Vietnam Oak Knoll (FVO) strain of P. falciparum. Results: All three control monkeys required treatment by Day 19. Two of three monkeys vaccinated with bMSP1(42) required treatment by Day 17, whereas the third monkey controlled parasitemia for 28 days before requiring treatment. In contrast, both of the A. nancymai vaccinated with yMSP1(19) self-resolved an otherwise lethal infection. One of the two yMSP1(19)-vaccinated A. vaciferans had a prolonged prepatent period of >28 days before requiring treatment. No evidence of mutations were evident in the parasites recovered after the prolonged prepatent period. Sera from the two A. nancymai that self-cured had no detectable effect on in vitro invasion. Conclusions: Vaccination of A. nancymai with yMSP1(19) induced protective immune responses. The course of recrudescing parasitemias in protected monkeys suggested that immunity is not mediated by antibodies that block invasion. Our data indicate that vaccine trials with the highly adapted FVO strain of P. falciparum can be tested in A. nancymai and that MSP1(19) is a promising anti-blood-stage vaccine for human trials. C1 NIAID,MALARIA RES LAB,BETHESDA,MD 20892. NIH,HOWARD HUGHES MED INST,RES SCHOLAR PROGRAM,CHEVY CHASE,MD. NIH,NATL CTR RES RESOURCES,VET RESOURCES PROGRAM,BETHESDA,MD 20892. NR 20 TC 148 Z9 152 U1 0 U2 1 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 1076-1551 J9 MOL MED JI Mol. Med. PD MAR PY 1995 VL 1 IS 3 BP 325 EP 332 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA QX600 UT WOS:A1995QX60000011 PM 8529111 ER PT J AU MOWATT, MR LUJAN, HD COTTEN, DB BOWERS, B YEE, J NASH, TE STIBBS, HH AF MOWATT, MR LUJAN, HD COTTEN, DB BOWERS, B YEE, J NASH, TE STIBBS, HH TI DEVELOPMENTALLY-REGULATED EXPRESSION OF A GIARDIA-LAMBLIA CYST WALL PROTEIN GENE SO MOLECULAR MICROBIOLOGY LA English DT Article ID SECRETORY VESICLE FORMATION; PRIMITIVE EUKARYOTE; MONOCLONAL-ANTIBODY; ANIMAL INFECTIVITY; INVITRO; ANTIGENS; ENCYSTATION; IDENTIFICATION; EXCYSTATION; RESOLUTION AB The protozoan Giardia lamblia is an obligate parasite of the mammalian small intestine. We studied the expression of a gene that encodes a protein component of the cyst wall, a complex structure assembled during the differentiation of trophozoites to cysts and which is critical to survival of the parasite outside its mammalian host. Transcripts from the cyst wall protein gene increase more than 100-fold during encystation, reaching a maximum between 5 and 24 hours after induction. Cyst wall protein expression also increases dramatically during encystation, and, prior to its incorporation into the nascent cyst wall, the protein is contained within the encystation-specific vesicles of encysting trophozoites. The sequence of the cloned gene predicts an acidic, leucine-rich polypeptide of M(r) 26000 that contains 5.3 tandemly arranged copies of a degenerate 24-amino-acid repeat. A hydrophobic amino-terminal peptide probably serves as the initial signal that targets this protein to a secretory pathway involving vesicular localization during encystation and, ultimately, secretion to form the cyst wall. C1 TULANE UNIV,DEPT CELL & MOLEC BIOL,NEW ORLEANS,LA 70118. NHLBI,CELL BIOL LAB,BETHESDA,MD 20892. RP MOWATT, MR (reprint author), NIAID,PARASIT DIS LAB,BETHESDA,MD 20892, USA. NR 48 TC 123 Z9 125 U1 0 U2 2 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD MAR PY 1995 VL 15 IS 5 BP 955 EP 963 DI 10.1111/j.1365-2958.1995.tb02364.x PG 9 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA QN786 UT WOS:A1995QN78600016 PM 7596296 ER PT J AU ROSEBOOM, PH KLEIN, DC AF ROSEBOOM, PH KLEIN, DC TI NOREPINEPHRINE STIMULATION OF PINEAL CYCLIC-AMP RESPONSE ELEMENT-BINDING PROTEIN-PHOSPHORYLATION - PRIMARY ROLE OF A BETA-ADRENERGIC-RECEPTOR CYCLIC-AMP MECHANISM SO MOLECULAR PHARMACOLOGY LA English DT Article ID N-ACETYLTRANSFERASE ACTIVITY; TRANSCRIPTION FACTOR CREB; GUANOSINE 3',5'-MONOPHOSPHATE; THYROXINE 5'-DEIODINASE; SOMATOSTATIN GENE; CIRCADIAN-RHYTHM; RAT PINEALOCYTES; ORGAN-CULTURE; C-FOS; GLAND AB Norepinephrine (NE) regulates melatonin production and many other aspects of pineal function through actions involving cAMP. In the present study the effects of NE on the phosphorylation of the cAMP response element-binding protein (CREB) were studied to determine whether CREB phosphorylation might be involved in cAMP signal transduction in this tissue. CREB was detected using gel mobility-shift analysis with the radiolabeled Ca2+/cAMP response element of the c-fos promoter. CREB phosphorylation was estimated in the gel mobility-shift assay using an antiserum specific for phosphorylated CREB. This antiserum generates a supershifted CREB signal with protein extracts obtained from glands treated with NE (EC(50) congruent to 10 nM) in organ culture, demonstrating that NE stimulates CREB phosphorylation. CREB phosphorylation peaks 30-45 min after NE treatment is initiated and then gradually returns to base-line values. Pharmacological studies show that NE-stimulated CREB phosphorylation is mediated primarily through beta(1)-adrenergic receptor-stimulated increases in cAMP. Activation of alpha(1)-adrenergic receptors, which is known to elevate the intracellular free Ca2+ concentration, does not cause CREB phosphorylation. However, it is possible to produce CREB phosphorylation with certain pharmacological agents that elevate the intracellular free Ca2+ concentration. In vivo studies show that CREB phosphorylation can be induced by treatment with isoproterenol (1 mg/kg), demonstrating that phosphorylation of pineal CREB occurs in intact animals. These studies indicate that cAMP-dependent CREB phosphorylation could play a role in the adrenergic regulation of gene expression in pinealocytes. C1 NICHHD,DEV NEUROBIOL LAB,NEUROENDOCRINOL SECT,BETHESDA,MD 20892. NR 45 TC 140 Z9 141 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 MAR PY 1995 VL 47 IS 3 BP 439 EP 449 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA QP735 UT WOS:A1995QP73500003 PM 7700241 ER PT J AU FAN, P AF FAN, P TI NONOPIOID MECHANISM OF MORPHINE MODULATION OF THE ACTIVATION OF 5-HYDROXYTRYPTAMINE TYPE-3 RECEPTORS SO MOLECULAR PHARMACOLOGY LA English DT Article ID MYENTERIC PLEXUS; 5-HT3 RECEPTORS; GUINEA-PIG; RELEASE; RAT; PHARMACOLOGY; ANTAGONISTS; EXPRESSION AB The effect of morphine on the ion current mediated by 5-hydroxytryptamine (5-HT3) receptors was investigated in rat nodose ganglion neurons and in Xenopus oocytes expressing the cloned 5-HT3 receptor. Morphine reversibly inhibited the 5-HT-induced current and shifted the 5-HT concentration-response curve to the right in a parallel fashion, without reducing the maximal 5-HT response. IC50 values for morphine were 0.3 mu M in nodose neurons and 0.32 mu M in oocytes. The apparent K-d of morphine in nodose neurons was 0.903 mu M. This effect of morphine was immediate, not dependent on membrane potential, and not prevented by the opioid receptor antagonists naltrexone and beta-chlomaltrexamine. It is concluded that opioid receptors were not involved in the present study and that morphine acted at the agonist recognition site located on the 5-HT3 receptor. RP FAN, P (reprint author), NIAAA,MOLEC & CELLULAR NEUROBIOL LAB,12501 WASHINGTON AVE,ROCKVILLE,MD 20852, USA. NR 26 TC 23 Z9 23 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 MAR PY 1995 VL 47 IS 3 BP 491 EP 495 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA QP735 UT WOS:A1995QP73500010 PM 7535378 ER PT J AU LINK, CJ ROBBINS, JH BOHR, VA AF LINK, CJ ROBBINS, JH BOHR, VA TI GENE-SPECIFIC DNA-REPAIR OF DAMAGE-INDUCED IN FAMILIAL ALZHEIMER-DISEASE CELLS BY ULTRAVIOLET-IRRADIATION OR BY NITROGEN-MUSTARD SO MUTATION RESEARCH-DNA REPAIR LA English DT Article DE ALZHEIMER DISEASE; DNA REPAIR; CYCLOBUTANE PYRIMIDINE DIMER; UV RADIATION; NITROGEN MUSTARD ID XERODERMA-PIGMENTOSUM; LYMPHOCYTES; FIBROBLASTS; METHYLTRANSFERASE; HYPERSENSITIVITY; SEQUENCES AB We have measured gene specific DNA repair in a normal human fibroblast cell line, and in fibroblast lines from two patients with familial Alzheimer disease (AD). Cells were treated with either ultraviolet radiation (UV) or the chemotherapeutic alkylating agent, nitrogen mustard (HN2). DNA damage formation and repair were studied in the active dihydrofolate reductase (DHFR) gene for the main lesions introduced by each of these two types of DNA damaging agents. The gene specific repair of UV induced cyclobutane pyrimidine dimers in the human DHFR gene was 86% complete in the AD cells after 24 h of repair incubation. This repair efficiency was similar to what we and others have found in normal human fibroblasts. After treatment of the AD cells with HN2, we found the frequency of HN2 induced lesions in the DHFR gene to be similar to the frequency in the transcriptionally inactive delta-globin gene. The gene specific repair of HN2 induced lesions in the DHFR gene was completed within 8-24 h in the normal fibroblast line and in the familial AD line, and the repair kinetics were similar for both cell lines. These results indicate that familial AD fibroblasts have normal gene specific repair of both UV induced and HN2 induced DNA damage in active genes. C1 NCI,DIV CANC TREATMENT,MOLEC PHARMACOL LAB,BETHESDA,MD 20892. NCI,DIV CANC TREATMENT,RADIAT ONCOL BRANCH,BETHESDA,MD 20892. NCI,DCBDC,DERMATOL BRANCH,BETHESDA,MD 20892. NIA,GERONTOL RES CTR,MOLEC GENET LAB,BALTIMORE,MD 21224. NR 26 TC 7 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0921-8777 J9 MUTAT RES-DNA REPAIR JI Mutat. Res.-DNA Repair PD MAR PY 1995 VL 336 IS 2 BP 115 EP 121 DI 10.1016/0921-8777(94)00051-7 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA QL237 UT WOS:A1995QL23700002 PM 7885382 ER PT J AU DESERRES, FJ MALLING, HV AF DESERRES, FJ MALLING, HV TI TRIETHYLENEMELAMINE - INDUCTION OF SPECIFIC-LOCUS MUTATIONS IN THE AD-3 REGION OF HETEROKARYON-12 OF NEUROSPORA-CRASSA SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article DE HETEROKARYON 12; GENE POINT MUTATION; MULTIPLE-LOCUS MUTATION; MULTILOCUS DELETION MUTATION; AD-3 REGION; AD-3A LOCUS; AD-3B LOCUS; RECESSIVE LETHAL MUTATION; TRIETHYLENEMELAMINE; 2,4,6-TRIS(1-AZIRIDINYL)-1,3,5-TRIAZINE ID GENE POINT MUTATIONS; 2-COMPONENT HETEROKARYONS; RISK ASSESSMENT; ASSAY AB The mutagenicity of the trifunctional alkylating (or cross-linking) agent TEM (triethylenemelamine or 2,4,6-tris(1-aziridinyl)-1,3,5-triazine) in the adenine-3 (ad-3) region was studied with a two-component heterokaryon (H-12) of Neurospora crassa. The objective was to characterize the genetic damage produced by this chemical to determine the spectrum of specific-locus mutations induced in a lower eukaryotic organism and to compare this spectrum with that induced in the mouse. Specific-locus mutations in the ad-3 region of strain H-12 result from gene/point mutations, multiple-locus mutations, and multilocus deletion mutations at the closely linked ad-3A and ad-3B loci. These loci control two sequential biochemical reactions in the purine biosynthetic pathway. A 0.1 M solution of TEM was used to treat conidial suspensions of H-12 for 20, 40, 80, 120, or 170 min to obtain dose-response curves for (1) inactivation of conidia, and (2) the induction of specific-locus mutations in the ad-3 region. These experiments demonstrated that TEM is a strong mutagen (maximum forward-mutation frequency between 100 and 1000 ad-3 mutations per 10(6) survivors) for the induction of specific-locus mutations in the ad-3 region. Both biochemical and classical genetic tests were used to characterize the TEM-induced ad-3 mutations ! from each of the five treatment groups to distinguish between the different genotypic classes and subclasses. The overall data base from these genetic studies demonstrates that TEM-induced ad-3 mutations result predominantly (95.5% [769/805]) from gene/point mutations at the ad-3A and ad-3B loci, and from a low percentage (4.5% [36/805) of multilocus deletion mutations. In addition, TEM induces an unusually high frequency of multiple-locus mutations with sites of recessive lethal damage closely linked with the ad-3 region. Comparison of the dose-response curves for the major classes and subclasses of TEM-induced ad-3 mutations demonstrates (1) that gene/point mutations and multilocus deletion mutations increase as the 1.4 power of TEM treatment time, and (2) that the two classes of TEM-induced multiple-locus ad-3 mutations consisting of gene/point mutations with separate sites of recessive lethal damage increase at about the 1.96 power of TEM treatment time. When the data from the present specific-locus studies are compared with those in the mouse, we find, insofar as such comparisons are possible, that a similar spectrum of specific-locus mutations has been induced by TEM in each assay system. RP DESERRES, FJ (reprint author), NIEHS,DIV INTRAMURAL RES,ENVIRONM TOXICOL PROGRAM,TOXICOL BRANCH,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 22 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0027-5107 J9 MUTAT RES-FUND MOL M JI Mutat. Res.-Fundam. Mol. Mech. Mutagen. PD MAR PY 1995 VL 327 IS 1-2 BP 87 EP 111 DI 10.1016/0027-5107(94)00174-4 PG 25 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA QK550 UT WOS:A1995QK55000011 PM 7870102 ER PT J AU GHOSH, S AF GHOSH, S TI PROBABILITY AND COMPLEX DISEASE GENES SO NATURE GENETICS LA English DT Editorial Material ID DEPENDENT DIABETES-MELLITUS; LINKAGE DISEQUILIBRIUM; INSULIN; TWINS; CONCORDANCE; FINLAND; IDDM RP GHOSH, S (reprint author), NIH,NATL CTR HUMAN GENOME RES,BLDG 10,BETHESDA,MD 20892, USA. NR 16 TC 6 Z9 6 U1 0 U2 0 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 MAR PY 1995 VL 9 IS 3 BP 223 EP 224 DI 10.1038/ng0395-223 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA QL232 UT WOS:A1995QL23200004 PM 7773279 ER PT J AU DIETZ, H FRANCKE, U FURTHMAYR, H FRANCOMANO, C DEPAEPE, A DEVEREUX, R RAMIREZ, F PYERITZ, R AF DIETZ, H FRANCKE, U FURTHMAYR, H FRANCOMANO, C DEPAEPE, A DEVEREUX, R RAMIREZ, F PYERITZ, R TI THE QUESTION OF HETEROGENEITY IN MARFAN-SYNDROME SO NATURE GENETICS LA English DT Letter ID ECHOCARDIOGRAPHIC MEASUREMENTS; CONNECTIVE-TISSUE C1 JOHNS HOPKINS UNIV,SCH MED,DEPT MED,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT MOLEC BIOL & GENET,BALTIMORE,MD 21205. STANFORD UNIV,SCH MED,HOWARD HUGHES MED INST,STANFORD,CA 94305. STANFORD UNIV,SCH MED,DEPT PATHOL,STANFORD,CA 94305. NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. STATE UNIV GHENT,CTR MED GENET,B-9000 GHENT,BELGIUM. NEW YORK HOSP,CORNELL MED CTR,DEPT MED,NEW YORK,NY 10021. CUNY MT SINAI SCH MED,DEPT MOLEC BIOL,NEW YORK,NY 10029. ALLEGHENY SINGER RES INST,DEPT HUMAN GENET,PITTSBURGH,PA 15212. RP DIETZ, H (reprint author), JOHNS HOPKINS UNIV,SCH MED,DEPT PEDIAT,BALTIMORE,MD 21205, USA. RI Pyeritz, Reed/A-1364-2010; Furthmayr, Heinz/A-6295-2010 NR 18 TC 38 Z9 38 U1 0 U2 1 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 MAR PY 1995 VL 9 IS 3 BP 228 EP 229 DI 10.1038/ng0395-228 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA QL232 UT WOS:A1995QL23200007 PM 7773282 ER PT J AU GUILLEMOT, F CASPARY, T TILGHMAN, SM COPELAND, NG GILBERT, DJ JENKINS, NA ANDERSON, DJ JOYNER, AL ROSSANT, J NAGY, A AF GUILLEMOT, F CASPARY, T TILGHMAN, SM COPELAND, NG GILBERT, DJ JENKINS, NA ANDERSON, DJ JOYNER, AL ROSSANT, J NAGY, A TI GENOMIC IMPRINTING OF MASH2, A MOUSE GENE REQUIRED FOR TROPHOBLAST DEVELOPMENT SO NATURE GENETICS LA English DT Article ID GROWTH FACTOR-II; PATERNAL GENOMES; H19 GENE; EXPRESSION; CELLS; LINKAGE; ACHAETE; EMBRYOGENESIS; CHROMOSOME-7; DROSOPHILA AB The mouse gene Mash2 encodes a transcription factor required for development of trophoblast progenitors. Mash2- homozygous mutant embryos die at 10 days post-coitum from placental failure. Here we show that Mash2 is genomically imprinted. First, Mash2+/- embryos inheriting a wild-type allele from their father die at the same stage as appears almost completely repressed by 8.5 days post-coitum. Finally, we have genetically and physically mapped Mash2 to the distal region of chromosome 7, within a The mouse gene Mash2 encodes a transcription factor required for development of cluster of imprinted genes, including insulin-2, insulin-like growth factor-2 and H19. C1 MT SINAI HOSP,SAMUEL LUNENFELD RES INST,TORONTO,ON M5G 1X5,CANADA. PRINCETON UNIV,DEPT MOLEC BIOL,PRINCETON,NJ 08544. PRINCETON UNIV,HOWARD HUGHES MED INST,PRINCETON,NJ 08544. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. CALTECH,HOWARD HUGHES MED INST,DIV BIOL,PASADENA,CA 91106. UNIV TORONTO,DEPT MOLEC & MED GENET,TORONTO,ON M5S 1A8,CANADA. RP GUILLEMOT, F (reprint author), UNIV LOUIS PASTEUR STRASBOURG 1,CU STRASBOURG,INST GENET & BIOL MOLEC & CELLULAIRE,CNRS,INSERM,F-67404 ILLKIRCH GRAFFENS,FRANCE. RI Nagy, Andras/G-6465-2013 FU NCI NIH HHS [N0I-CO-46000]; NIGMS NIH HHS [GM51460] NR 50 TC 300 Z9 308 U1 0 U2 6 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 MAR PY 1995 VL 9 IS 3 BP 235 EP 242 DI 10.1038/ng0395-235 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA QL232 UT WOS:A1995QL23200011 PM 7773285 ER PT J AU RUSSELL, LJ DIGIOVANNA, JJ ROGERS, GR STEINERT, PM HASHEM, N COMPTON, JG BALE, SK AF RUSSELL, LJ DIGIOVANNA, JJ ROGERS, GR STEINERT, PM HASHEM, N COMPTON, JG BALE, SK TI MUTATIONS IN THE GENE FOR TRANSGLUTAMINASE-1 IN AUTOSOMAL RECESSIVE LAMELLAR ICHTHYOSIS SO NATURE GENETICS LA English DT Article ID FACTOR-XIII; SUBUNIT DEFICIENCY AB We recently mapped the disease locus for severe autosomal recessive lamellar ichthyosis (LI) to chromosome 14q11 and showed complete linkage with TGM1, the gene encoding transglutaminase 1. We have now identified point mutations in TGM1 in two of the multiplex Li families used in the linkage study. Each nucleotide change causes a non-conservative amino acid substitution of histidine for one of two adjacent arginine residues in exon 3 of the gene (Arg141His, Arg142His). Within the transglutaminase family, these arginines are invariant within a conserved region, distant from the catalytic site of the enzyme. We hypothesize that these mutations adversely affect formation of crosslinks essential in production of cornified cell envelopes and a normal stratum corneum layer of the skin. C1 NIAMSD,GENET STUDIES SECT,SKIN BIOL LAB,BETHESDA,MD 20892. NIAMSD,DERMATOL CLIN RES UNIT,BETHESDA,MD 20892. AIN SHAMS UNIV,CTR GENET MED,CAIRO,EGYPT. NR 19 TC 255 Z9 262 U1 0 U2 6 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 MAR PY 1995 VL 9 IS 3 BP 279 EP 283 DI 10.1038/ng0395-279 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA QL232 UT WOS:A1995QL23200018 PM 7773290 ER PT J AU FINNEGAN, LP ROSSOUW, J HARLAN, WR AF FINNEGAN, LP ROSSOUW, J HARLAN, WR TI A PEPPY RESPONSE TO PEPI RESULTS SO NATURE MEDICINE LA English DT Editorial Material ID ENDOMETRIAL CARCINOMA RP FINNEGAN, LP (reprint author), NIH,OFF DIS PREVENT,OFF RES WOMENS HLTH,BETHESDA,MD 20892, USA. NR 9 TC 1 Z9 1 U1 0 U2 0 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1078-8956 J9 NAT MED JI Nat. Med. PD MAR PY 1995 VL 1 IS 3 BP 205 EP 206 DI 10.1038/nm0395-205 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA QX559 UT WOS:A1995QX55900021 PM 7585031 ER PT J AU LEIKIN, S RAU, DC PARSEGIAN, VA AF LEIKIN, S RAU, DC PARSEGIAN, VA TI TEMPERATURE-FAVORED ASSEMBLY OF COLLAGEN IS DRIVEN BY HYDROPHILIC NOT HYDROPHOBIC INTERACTIONS SO NATURE STRUCTURAL BIOLOGY LA English DT Article ID PROTEIN-FOLDING THERMODYNAMICS; DNA DOUBLE HELICES; HYDRATION FORCES; MOLECULAR PACKING; FIBRILS; ENTHALPY; ENTROPY AB It has become almost axiomatic that protein folding and assembly are dominated by the hydrophobic effect. The contributions from this, and other, hydrophilic interactions can now be better distinguished by direct measurement of forces between proteins. Here we report the measurement of forces between triple helices of type I collagen at different temperatures, pH and solute concentrations. We separate repulsive and attractive components of the net force and analyze the origin of the attraction responsible for the collagen self-assembly. In this case the role of the hydrophobic effect appears to be negligible, Instead, water-mediated hydrogen bonding between polar residues is the most consistent explanation. C1 NIDDKD,DIV INTRAMURAL RES,BETHESDA,MD 20892. RP LEIKIN, S (reprint author), NIDDKD,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 38 TC 103 Z9 106 U1 2 U2 19 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 MAR PY 1995 VL 2 IS 3 BP 205 EP 210 DI 10.1038/nsb0395-205 PG 6 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA RF666 UT WOS:A1995RF66600009 PM 7773789 ER PT J AU BALDWIN, ET BHAT, TN LIU, BS PATTABIRAMAN, N ERICKSON, JW AF BALDWIN, ET BHAT, TN LIU, BS PATTABIRAMAN, N ERICKSON, JW TI STRUCTURAL BASIS OF DRUG-RESISTANCE FOR THE V82A MUTANT OF HIV-1 PROTEINASE SO NATURE STRUCTURAL BIOLOGY LA English DT Article ID SYMMETRICAL INHIBITORS; TYPE-1 PROTEASE; VARIANTS; TARGET; AIDS AB A major problem in the development of antiviral therapies for AIDS has keen the emergence of drug resistance, We report an analysis of the structure of a Val 82 to Ala mutant of HIV-1 proteinase complexed to A-77003, a C2 symmetry-based inhibitor, Modelling studies predicted that the V82A mutation would result in decreased van der Waals' interactions with the phenyl rings of A-77003 in both S1 and S1(1) subsites, Unexpected rearrangements of the protein backbone, however, resulted in favourable re-packing of inhibitor and enzyme atoms in the S1 but not the S1(1) subsite. This analysis reveals the importance of enzyme flexibility in accommodating alternate packing arrangements, and can be applied to the re-design of inhibitors targeted to drug resistant variants which emerge in the clinic. C1 NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,FREDERICK BIOMED SUPERCOMP CTR,STRUCT BIOCHEM PRO,FREDERICK,MD 21702. NR 22 TC 100 Z9 100 U1 0 U2 1 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 MAR PY 1995 VL 2 IS 3 BP 244 EP 249 DI 10.1038/nsb0395-244 PG 6 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA RF666 UT WOS:A1995RF66600014 PM 7773792 ER PT J AU BATTAINI, F ELKABES, S BERGAMASCHI, S LADISA, V LUCCHI, L DEGRAAN, PNE SCHUURMAN, T WETSEL, WC TRABUCCHI, M GOVONI, S AF BATTAINI, F ELKABES, S BERGAMASCHI, S LADISA, V LUCCHI, L DEGRAAN, PNE SCHUURMAN, T WETSEL, WC TRABUCCHI, M GOVONI, S TI PROTEIN-KINASE-C ACTIVITY, TRANSLOCATION, AND CONVENTIONAL ISOFORMS IN AGING RAT-BRAIN SO NEUROBIOLOGY OF AGING LA English DT Article DE PROTEIN KINASE C; AGING; WISTAR RAT; BRAIN B-50/GAP-43; PKC TRANSLOCATION; PKC ISOFORMS ID HIPPOCAMPAL PYRAMIDAL NEURONS; PHORBOL ESTER BINDING; CELLULAR-DISTRIBUTION; PHOSPHORYLASE-KINASE; B-50 GAP-43; CALCIUM; SUBSTRATE; ACTIVATION; EXPRESSION; MEMBRANES AB Protein kinase C was studied in various brain areas in aging Wistar rats. Histone-directed kinase activity from the cortex, hippocampus and cerebellum did not change with aging. Using purified protein B-50 as a substrate, between 3 and 8 months a decrease in in vitro phosphorylation was detected in the membrane fraction of the cortex but after this age values remained stable. In hippocampal membranes, B-50 phosphorylation was increased in aged rats. PKC translocation was impaired in aged rats in both the cortex and the hippocampus. PKC alpha and beta mRNA decreased in the cortex between 3 and 8 months with no further decline in aged animals. Hippocampal mRNA for calcium-dependent PKC isoforms was not modified during aging, as assessed by Northern and in situ hybridization. Western blot analysis revealed a change in PKC gamma protein only, which was increased in hippocampal membranes from aged rats. The data indicate that the key PKC function that is impaired in aged rats is enzyme translocation irrespective of the brain area investigated. C1 UNIV ROMA TOR VERGATA,DIPARTIMENTO MED SPERIMENTALE & SCI BIOCHIM,I-00187 ROME,ITALY. UNIV UTRECHT,RUDOLF MAGNUS INST,DEPT MED PHARMACOL,3508 TA UTRECHT,NETHERLANDS. DEPT NEUROBIOL,W-5000 COLOGNE 80,GERMANY. NIEHS,CELLULAR & MOLEC PHARMACOL LAB,RES TRIANGLE PK,NC 27709. RP BATTAINI, F (reprint author), UNIV MILAN,INST PHARMACOL SCI,VIA BALZARETTI 9,I-20133 MILAN,ITALY. RI Battaini , Fiorenzo/H-2617-2012; Govoni, Stefano/K-2965-2015 OI Govoni, Stefano/0000-0002-7243-6837 NR 75 TC 64 Z9 64 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD MAR-APR PY 1995 VL 16 IS 2 BP 137 EP 148 DI 10.1016/0197-4580(94)00154-5 PG 12 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA QL482 UT WOS:A1995QL48200003 PM 7777132 ER PT J AU VENDRELL, P JUNQUE, C PUJOL, J JURADO, MA MOLET, J GRAFMAN, J AF VENDRELL, P JUNQUE, C PUJOL, J JURADO, MA MOLET, J GRAFMAN, J TI THE ROLE OF PREFRONTAL REGIONS IN THE STROOP TASK SO NEUROPSYCHOLOGIA LA English DT Article DE PREFRONTAL; STROOP; ATTENTION ID CINGULATE GYRUS; FRONTAL-LOBE; ATTENTION; DEFICITS; MONKEY; CORTEX; SPEED AB The Stroop is a classical paradigm that presumably involves the inhibition of automatic responses and is frequently used to assess the frontal lobe functions. We investigated the effect of discrete prefrontal lesions in a Stroop task. A sample of 32 patients with frontal lesions were matched with normal controls by sex, age and years of education. Significant differences between patients and controls were found for errors but not for reaction time. Regression analysis showed that the region most related to errors was the right prefrontal lateral cortex. Left lobectomies did not impair the Stroop performance. Our results favour the role of the right prefrontal cortex in sustained attention, and disagree with the conception of the left prefrontal cortex having a role in the inhibition of verbal automatic responses. C1 CTR DIAGNOST PEBRALBES,BARCELONA,SPAIN. NICDS,MED NEUROL BRANCH,COGNIT NEUROSCI UNIT,BETHESDA,MD. RP VENDRELL, P (reprint author), UNIV BARCELONA,DEPT PSIQUIATRIA & PSICOBIOL,ADOLF FLORENSA S-N,E-08028 BARCELONA,SPAIN. RI Vendrell, Pere/B-4392-2011; Junque, Carme/B-4400-2011; JURADO, MARIA ANGELES/E-1745-2011; OI Vendrell, Pere/0000-0001-8918-5440; Junque, Carme/0000-0002-6381-3063; JURADO, MARIA ANGELES/0000-0002-9403-1670; Grafman, Jordan H./0000-0001-8645-4457 NR 24 TC 217 Z9 217 U1 2 U2 15 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0028-3932 J9 NEUROPSYCHOLOGIA JI Neuropsychologia PD MAR PY 1995 VL 33 IS 3 BP 341 EP 352 DI 10.1016/0028-3932(94)00116-7 PG 12 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA QP052 UT WOS:A1995QP05200007 PM 7792000 ER PT J AU REN, K RUDA, MA AF REN, K RUDA, MA TI NITRIC-OXIDE SYNTHASE-CONTAINING NEURONS IN SENSORY GANGLIA OF THE RAT ARE SUSCEPTIBLE TO CAPSAICIN-INDUCED CYTOTOXICITY SO NEUROSCIENCE LA English DT Article ID DORSAL-ROOT GANGLIA; NADPH-DIAPHORASE; SPINAL-CORD; MESSENGER-RNA; PERIPHERAL AXOTOMY; SCIATIC-NERVE; IMMUNOREACTIVITY; INCREASE; HYPERALGESIA; PROTEIN AB Nitric oxide synthase in lumbar dorsal root ganglia of neonatal rat was studied by reduced nicotinamide adenine dinucleotide phosphate diaphorase and in situ hybridization histochemistry. Induction of nitric oxide synthase in neonatal capsaicin-treated rats after sciatic axotomy was compared with the axotomy-induced nitric oxide synthase increase observed in vehicle-treated littermates. In neonatal capsaicin-treated animals, the number of neurons constitutively labeled by reduced nicotinamide adenine dinucleotide phosphate diaphorase was greatly reduced as compared to vehicle-treated littermates. Nitric oxide synthase messenger RNA was not readily identified constitutively in dorsal root ganglion neurons. Seven days after sciatic transection the induction of reduced nicotinamide adenine dinucleotide phosphate diaphorase and nitric oxide synthase messenger RNA found in the vehicle-treated group was not observed in the capsaicin group. The presence of nitric oxide synthase in dorsal, root ganglion neurons thus does not appear to protect against Ca2+-mediated capsaicin-induced cytotoxicity. However, since some nitric oxide synthase dorsal root ganglion neurons persist after the capsaicin neurotoxicity, nitric oxide synthase expression must occur in a neurochemically diverse subpopulation of small (< 1000 mu m(2)) neurons. The capsaicin sensitivity of most nitric oxide synthase dorsal root ganglion neurons indicates that they have unmyelinated axons and are likely to be involved in nociception. RP REN, K (reprint author), NIDR,NEUROBIOL & ANESTHESIOL BRANCH,BLDG 30,BETHESDA,MD 20892, USA. NR 33 TC 41 Z9 41 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD MAR PY 1995 VL 65 IS 2 BP 505 EP 511 DI 10.1016/0306-4522(94)00510-C PG 7 WC Neurosciences SC Neurosciences & Neurology GA QL039 UT WOS:A1995QL03900017 PM 7539899 ER PT J AU RHEE, HM SONG, BJ CUSHMAN, S SHOAF, SE AF RHEE, HM SONG, BJ CUSHMAN, S SHOAF, SE TI VASCULAR REACTIVITY IN ALCOHOLIC RAT AORTAS - IN-VITRO INTERACTIONS BETWEEN CATECHOLAMINES AND ALCOHOL SO NEUROTOXICOLOGY LA English DT Article DE ALCOHOL; NOREPINEPHRINE; VASCULAR REACTIVITY; DIABETES MELLITUS; AORTIC RINGS ID BLOOD-PRESSURE; HYPERTENSION; CONSUMPTION; ETHANOL AB To understand the nature of vascular problems of hypertensive and alcoholic subjects, an in vitro interaction between catecholamine and alcohol was investigated in male Sprague-Dawley rats. The decending aortas were isolated from either the control or alcohol treated rats. The aortic strips were cooled rapidly in ice-chilled Krebs-Henseleit (K-H)solution and the aorta was cut into a series of rings of approximately 1 mm width. The rings were fixed under 1 g of resting tension between a force-displacement transducer and anchoring electrodes at 37 degrees C. The rings were equilibrated for an hour with frequent changes of the K-H solution before testing. There was norepinephrine (NE) dose-dependent contraction of the rings, which showed the maximum tension with 1 mu M NE. Acetylcholine or carbachol produced slow relaxation. Pretreatment of the rings with 10 mu M prazocin prevent the contraction induced by 1 mu M NE. Even in the presence of prazocin, 60 mM KCI was able to generate the maximum tension. NE-induced contraction was analyzed in the control K-H solution or in the presence of 1.5, 3.0 and 5.0% of ethanol. Ethanol (1.5%) slowed the rate of rise of the aortic tension without a remarkable compromise of the maximum tension. But, there was a significant reduction in contraction with 3% ethanol. A complete inhibition of contraction was not-ed with 5% ethanol. However, the effect of ethanol was fully reversible upon washings the aortic rings with K-H solution. Aortic rings prepared from the rats that were fed with alcohol for 30 days were not able to generate the maximum tension with 1 mu M NE. The data suggest that alcohol modifies the vascular reactivity to sympathetic responses. (C) 1995 Intox Press, Inc. C1 NIAAA,ROCKVILLE,MD 20852. NIDDKD,BETHESDA,MD 20892. RP RHEE, HM (reprint author), US FDA,CTR DRUG EVALUAT & RES,DIV METAB & ENDOCRINE DRUG PROD,ROCKVILLE,MD 20857, USA. NR 22 TC 5 Z9 5 U1 0 U2 0 PU INTOX PRESS INC PI LITTLE ROCK PA PO BOX 24865, LITTLE ROCK, AR 72221 SN 0161-813X J9 NEUROTOXICOLOGY JI Neurotoxicology PD SPR PY 1995 VL 16 IS 1 BP 179 EP 185 PG 7 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA QV617 UT WOS:A1995QV61700020 PM 7603639 ER PT J AU COOPER, GS BAIRD, DD HULKA, BS WEINBERG, CR SAVITZ, DA HUGHES, CL AF COOPER, GS BAIRD, DD HULKA, BS WEINBERG, CR SAVITZ, DA HUGHES, CL TI FOLLICLE-STIMULATING-HORMONE CONCENTRATIONS IN RELATION TO ACTIVE AND PASSIVE SMOKING SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID NATURAL MENOPAUSE; CIGARETTE-SMOKING; AGE; GONADOTROPINS; TRANSITION; PROLACTIN AB Objective: To determine the association between various forms of tobacco exposure and ovarian status, as measured by FSH concentrations, in women 38-49 years old. Methods: Two hundred ninety women between 38-49 years old, who had not had hysterectomy or oophorectomy, completed a self-administered questionnaire that included information on tobacco exposure and had serum FSH levels measured on days 2-4 of the menstrual cycle. Linear regression was used to assess the relation between FSH and tobacco exposure. Results: Controlling for age and other factors, FSH concentrations were 66% higher among current smokers (geometric mean FSH 14.0 mIU/mL) and 39% higher among nonsmokers with passive smoke exposure (11.7 mIU/mL), compared to nonsmoking women without passive smoke exposure (8.4 mIU/mL). The estimated increase in FSH for each year of age was greater for current smokers than for nonsmokers (16 versus 6%, respectively). Ex-smokers did not have higher FSH concentrations, and there was no association between prenatal exposure to tobacco smoke and FSH. Conclusion: Both active and passive smoking are associated with elevated FSH concentrations in women 38-49 years old. The effect, limited to women with current exposure, is consistent with a shorter duration of the menopausal transition period. C1 NIEHS,STAT & BIOMATH BRANCH,RES TRIANGLE PK,NC 27709. UNIV N CAROLINA,DEPT EPIDEMIOL,CHAPEL HILL,NC. DUKE UNIV,MED CTR,DEPT OBSTET & GYNECOL,DURHAM,NC. RP COOPER, GS (reprint author), NIEHS,EPIDEMIOL BRANCH,MDA3-05,POB 12233,RES TRIANGLE PK,NC 27709, USA. OI Baird, Donna/0000-0002-5544-2653 FU NCRR NIH HHS [RR00046] NR 22 TC 65 Z9 67 U1 0 U2 3 PU ELSEVIER SCIENCE PUBL CO INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD MAR PY 1995 VL 85 IS 3 BP 407 EP 411 DI 10.1016/0029-7844(94)00381-M PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA QH305 UT WOS:A1995QH30500017 PM 7862381 ER PT J AU DABHOLKAR, M VIONNET, J PARKER, RJ BOSTICKBRUTON, F DOBBINS, A REED, E AF DABHOLKAR, M VIONNET, J PARKER, RJ BOSTICKBRUTON, F DOBBINS, A REED, E TI EXPRESSION OF AN ALTERNATIVELY SPLICED ERCC1 MESSENGER-RNA SPECIES, IS RELATED TO REDUCED DNA-REPAIR EFFICIENCY IN HUMAN T-LYMPHOCYTES SO ONCOLOGY REPORTS LA English DT Article DE ERCC1; XPA; ALTERNATIVE SPLICING; NONDRUG SELECTED T-CELLS ID A XERODERMA-PIGMENTOSUM; EXCISION REPAIR; CISPLATIN SENSITIVITY; CANCER-PATIENTS; GENE ERCC-1; HOMOLOGY; ADDUCTS; DOMAIN; YEAST; CELLS AB We have previously shown that in non-drug-selected human T lymphocytes, DNA repair is the primary determinant of cellular resistance to cisplatin (1). In this system, we have assessed mRNA levels of expression of the nucleotide excision repair (NER) genes ERCC1 and XPA, as well as the alternatively spliced species of ERCC1 which lacks exon VIII. The focus of these studies, was to try to identify the possible relative roles of normal XPA, full-length ERCC1, and alternatively spliced ERCC1, in a system where DNA repair is a clear determinant of cisplatin resistance. ERCC1 expression was directly related to cisplatin-DNA adduct repair capability, as well as directly related to cisplatin resistance, suggesting a primary role for ERCC1 in effecting DNA repair. XPA expression was approximately equivalent in each cell line, regardless of the level of DNA repair activity, suggesting a helper role for the product of this gene. The mRNA levels of the alternatively spliced species of ERCC1 were strongly inversely related to DNA repair activity, suggesting a possible inhibitory influence on the DNA repair process. This interpretation is consistent with alternative splicing of several known oncogenes, where the alternatively spliced species has an inhibitory effect on the full-length gene product. The NER pathway appears to be vitally important in effecting cisplatin resistance in non-drug-selected T lymphocytes. Further, it appears that NER may have at least one inhibitory regulatory component. C1 NCI,CLIN PHARMACOL BRANCH,MED OVARIAN CANC SECT,9000 ROCKVILLE PIKE,BLDG 10,RM 12N226,BETHESDA,MD 20892. NR 27 TC 13 Z9 13 U1 0 U2 1 PU NATL HELLENIC RES FOUNDATION PI ATHENS PA C/O D A SPANDIDOS 48 VAS CONSTANTINOU AVE, ATHENS 11635, GREECE SN 1021-335X J9 ONCOL REP JI Oncol. Rep. PD MAR-APR PY 1995 VL 2 IS 2 BP 209 EP 214 PG 6 WC Oncology SC Oncology GA QG815 UT WOS:A1995QG81500004 PM 21597714 ER PT J AU FIGG, WD MCCALL, NA REED, E SARTOR, O AF FIGG, WD MCCALL, NA REED, E SARTOR, O TI THE IN-VITRO RESPONSE OF 4 ANTISTEROID RECEPTOR AGENTS ON THE HORMONE-RESPONSIVE PROSTATE-CANCER CELL-LINE LNCAP SO ONCOLOGY REPORTS LA English DT Article DE LNCAP; TAMOXIFEN; FLUTAMIDE; CASODEX; RU486; MUTATED ANDROGEN RECEPTOR; BICALUTAMIDE; IN-VITRO; HYDROXYFLUTAMIDE ID FLUTAMIDE WITHDRAWAL; ANTI-ANDROGENS; CARCINOMA; TRIAL; ANTIANDROGENS; ORCHIECTOMY; CASODEX AB Previous reports indicate that flutamide withdrawal is associated with PSA declines and tumor shrinkage in selected patients with 'hormone-refractory' prostate cancer. Though the mechanisms underlying this effect are not clear, investigators have hypothesized that these effects are mediated by mutant androgen receptors recognizing hydroxy-flutamide as an androgenic agonist. Such receptors have been well described in the human prostate cancer cell line LNCaP. Despite the finding that the androgen receptor of LNCaP aberrantly recognizes a variety of steroids, including estrogen and progesterone, as androgenic agonists, there are no studies which examine the effect of estrogen antagonists and progesterone antagonist on baseline and androgen-stimulated LNCaP growth. In this report, LNCaP cells were cultured in phenol red-free media using charcoal-stripped sera. As previously reported, flutamide enhanced LNCaP growth and bicalutamide inhibited androgen-stimulated LNCaP proliferation. Neither tamoxifen nor RU486 influenced LNCaP growth (either in the presence or absence of exogenous androgens). From these data we conclude that antagonists of estrogen and progesterone action have no anti-proliferative effect on LNCaP cells and that the mutant androgen receptor expressed in these cells is quite restrictive in the recognition of compounds with antagonistic activity. The clinical implications of these findings are discussed. RP FIGG, WD (reprint author), NCI,DIV CANC TREATMENT,CLIN ONCOL PROGRAM,CLIN PHARMACOL BRANCH,BLDG 10,ROOM 5A-01,BETHESDA,MD 20892, USA. RI Figg Sr, William/M-2411-2016 NR 28 TC 8 Z9 8 U1 0 U2 0 PU NATL HELLENIC RES FOUNDATION PI ATHENS PA C/O D A SPANDIDOS 48 VAS CONSTANTINOU AVE, ATHENS 11635, GREECE SN 1021-335X J9 ONCOL REP JI Oncol. Rep. PD MAR-APR PY 1995 VL 2 IS 2 BP 295 EP 298 PG 4 WC Oncology SC Oncology GA QG815 UT WOS:A1995QG81500019 PM 21597729 ER PT J AU LASA, MSM DATILES, MB MAGNO, BV MAHURKAR, A AF LASA, MSM DATILES, MB MAGNO, BV MAHURKAR, A TI SCHEIMPFLUG PHOTOGRAPHY AND POSTCATARACT SURGERY POSTERIOR CAPSULE OPACIFICATION SO OPHTHALMIC SURGERY AND LASERS LA English DT Article ID LENS TRANSPARENCY; DISTURBANCES; CAMERA AB We describe a method to objectively document postcataract surgery posterior capsule opacification using Zeiss Scheimpflug photography and computerized image analysis. We examined 42 eyes with clear capsules (group A) and 27 with posterior capsule opacities (group B). The group A eyes had significantly better visual acuity (P < .05), lower mean capsular densitometry readings (0.03 +/- 0.03 optical density units versus 0.15 +/- 0.11 optical density units; P < .0001), and thinner capsules (0.03 +/- 0.4 mm versus 0.10 +/- 0.05 mm) than the group B eyes. This new objective method of documenting postoperative capsular haze may be useful for clinical studies such as clinical trials of drugs or surgical techniques being developed to prevent or minimize capsule opacification. C1 NEI,OPHTHALM GENET & CLIN SERV BRANCH,BLDG 10,RM 10N226,BETHESDA,MD 20892. OI Datiles, Manuel III B./0000-0003-4660-1664 NR 18 TC 19 Z9 21 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0022-023X J9 OPHTHALMIC SURG LAS JI Ophthalmic Surg. Lasers PD MAR-APR PY 1995 VL 26 IS 2 BP 110 EP 113 PG 4 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA QQ880 UT WOS:A1995QQ88000003 PM 7596535 ER PT J AU KLEIN, R ROWLAND, ML HARRIS, MI AF KLEIN, R ROWLAND, ML HARRIS, MI TI RACIAL/ETHNIC DIFFERENCES IN AGE-RELATED MACULOPATHY - 3RD NATIONAL-HEALTH AND NUTRITION EXAMINATION SURVEY SO OPHTHALMOLOGY LA English DT Article ID MACULAR DEGENERATION; PREVALENCE; DRUSEN AB Purpose: To investigate the prevalence of age-related maculopathy in three racial/ethnic groups, non-Hispanic whites, non-Hispanic blacks, and Mexican Americans. Methods: People 40 years of age or older who participated in a nationally representative population-based sample of the Third National Health and Nutrition Examination Survey were examined from 1988 to 1991, Age-related maculopathy was determined by grading of fundus photographs using a standardized protocol for a sample of 4007 persons. Results: The prevalence of any age-related maculopathy in the civilian noninstitutionalized United States population including those 40 years of age or older was 9.2% as estimated from the sample. Prevalence was higher in non-Hispanic whites (9.3%) compared with non-Hispanic blacks (7.4%) and Mexican Americans (7.1%), Before 60 years of age, Mexican Americans (odds ratio [OR], 1.53; 95% confidence interval [CI] 1.0-2.35) and non-Hispanic blacks (OR, 1.59; 95% CI, 0.86-2.95) had a greater chance of having any maculopathy than non-Hispanic whites; thereafter, Mexican Americans (OR, 0.63; 95% CI, 0.44-0.90) and non-Hispanic blacks (OR, 0.50; 95% CI, 0.37-0.68) had a lesser chance than non-Hispanic whites. Conclusion: These survey data indicate that age-related maculopathy is prevalent in all groups studied. Differences among the racial/ethnic groups vary by age and sex. C1 NATL CTR HLTH STAT,DIV HLTH EXAMINAT STAT,HYATTSVILLE,MD 20782. NIDDKD,BETHESDA,MD 20892. RP KLEIN, R (reprint author), UNIV WISCONSIN,SCH MED,DEPT OPHTHALMOL & VISUAL SCI,600 HIGHLAND AVE,CSC F4-336,MADISON,WI 53792, USA. FU NEI NIH HHS [U 10 EY06594]; PHS HHS [200-89-7004] NR 23 TC 107 Z9 110 U1 0 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD MAR PY 1995 VL 102 IS 3 BP 371 EP 381 PG 11 WC Ophthalmology SC Ophthalmology GA QL484 UT WOS:A1995QL48400008 PM 7891973 ER PT J AU BOYLE, P MACFARLANE, GJ BLOT, WJ CHIESA, F LEFEBVRE, JL AZUL, AM DEVRIES, N SCULLY, C AF BOYLE, P MACFARLANE, GJ BLOT, WJ CHIESA, F LEFEBVRE, JL AZUL, AM DEVRIES, N SCULLY, C TI EUROPEAN SCHOOL OF ONCOLOGY ADVISORY REPORT TO THE EUROPEAN-COMMISSION FOR THE EUROPE-AGAINST-CANCER PROGRAM - ORAL CARCINOGENESIS IN EUROPE SO ORAL ONCOLOGY LA English DT Review DE ORAL NEOPLASMS; EPIDEMIOLOGY; TREATMENT; CHEMOPREVENTION; SCREENING ID SQUAMOUS-CELL CARCINOMA; SERUM-VITAMIN-A; NUTRITION INTERVENTION TRIALS; DISEASE-SPECIFIC MORTALITY; HUMAN PAPILLOMAVIRUS DNA; HERPES-SIMPLEX VIRUSES; 2ND PRIMARY TUMORS; PHARYNGEAL CANCER; BETA-CAROTENE; CHANGING INCIDENCE AB European School of Oncology Advisory Group has reviewed current knowledge on the epidemiology, treatment and prevention of cancer of the oral cavity. While the major factors in the aetiology of such cancers are thought to be well understood, i.e. tobacco and alcohol consumption, current increases in the occurrence of the disease, especially in young adults throughout Europe, are cause for concern. The reasons for such increases are not clearly evident and the Advisory Group has suggested further work which is required to be carried out to understand the aetiology. In treatment of the disease there have been no major improvements in survival for patients in recent decades and the importance of examining new radiotherapy modalities and defining the role of chemotherapy is emphasized, Primary prevention of oral cancer could be achieved by stopping smoking tobacco, limiting alcohol consumption to a minimum (2-3 drinks per day) and increasing intake of fruits and vegetables. To supplement these actions, while neither population screening programmes nor screening trials could be recommended by the Advisory Group, initial chemoprevention trials have produced some promising results and this represents an interesting area which is the focus of much current research. C1 NCI, DIV CANC ETIOL, BETHESDA, MD 20892 USA. CTR OSCAR LAMBRET, F-59020 LILLE, FRANCE. PORTUGUESE ACAD ORAL MED, LISBON, PORTUGAL. FREE UNIV AMSTERDAM HOSP, AMSTERDAM, NETHERLANDS. UCL EASTMAN DENT INST ORAL HLTHCARE SCI, LONDON, ENGLAND. RP BOYLE, P (reprint author), EUROPEAN INST ONCOL, VIA RIPAMONTI 435, I-20141 MILAN, ITALY. RI Macfarlane, Gary/I-9521-2014; Boyle, Peter/A-4402-2014 OI Macfarlane, Gary/0000-0003-2322-3314; Boyle, Peter/0000-0001-6251-0610 NR 96 TC 11 Z9 12 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1368-8375 J9 ORAL ONCOL JI Oral Oncol. PD MAR PY 1995 VL 31B IS 2 BP 75 EP 85 PG 11 WC Oncology; Dentistry, Oral Surgery & Medicine SC Oncology; Dentistry, Oral Surgery & Medicine GA RA049 UT WOS:A1995RA04900001 ER PT J AU YEUDALL, WA PATERSON, IC PATEL, V PRIME, SS AF YEUDALL, WA PATERSON, IC PATEL, V PRIME, SS TI PRESENCE OF HUMAN PAPILLOMAVIRUS SEQUENCES IN TUMOR-DERIVED HUMAN ORAL KERATINOCYTES EXPRESSING MUTANT P53 SO ORAL ONCOLOGY-EUROPEAN JOURNAL OF CANCER PART B LA English DT Article DE P53; GENE MUTATION; ORAL CANCER; CHEMICAL CARCINOGENS; TUMOR SUPPRESSOR; TUMOR PROGRESSION; VIRAL ONCOGENESIS; HUMAN PAPILLOMAVIRUS ID SQUAMOUS-CELL CARCINOMA; SUPPRESSOR GENE; LUNG-CANCER; RAS MUTATIONS; NECK-CANCER; PROTEIN; LINES; TRANSFORMATION; FREQUENT; HEAD AB A series of eight oral epithelial cell Lines derived from untreated human oral squamous cell carcinomas, which had arisen in patients with different tobacco histories, were examined for the presence of human papillomavirus (HPV) DNA, expression of stable p53 protein and p53 point mutation. Polymerase chain reaction (PCR)-based screening, but not Southern blot analysis, showed HPV-16 early region sequences to be present at low copy number(<1 copy per cell) in two cell lines at early passage (3-5) in vitro (H400, T45), implying that only subpopulations of cells harboured viral DNA. HPV sequences were undetectable in cells at later passage (12-15), suggesting that viral sequences had been lost during growth in vitro, or that negative selection of HPV-containing cells had occurred. High levels of p53 were detected in the two HPV-positive cell lines and in three others (H103, H314, H357) by Western blotting, suggesting expression of mutant (stable) p53 molecules. A sixth cell line (H157) expressed a truncated p53. Sequence analysis of exons 2-11 of the p53 gene revealed missense mutations in six cell lines, one of which (H413) did not result in high levels of protein, and nonsense mutations in the remaining two cell lines (H157, H376). The results suggest that p53 mutation is a frequent genetic event in oral cancer. In addition, the expression of mutant p53 in oral cancer cells does not preclude a papillomaviral aetiology for these tumours. Analysis of p53 expression alone may result in underestimation of the frequency of p53 mutations in human cancers. In contrast to other studies, we demonstrate that positive staining of p53 in oral cancer does not necessarily reflect a tobacco aetiology. C1 UNIV BRISTOL,DEPT ORAL MED PATHOL & MICROBIOL,BRISTOL BS1 2LY,AVON,ENGLAND. RP YEUDALL, WA (reprint author), NIDR,CELLULAR DEV & ONCOL LAB,BLDG 30,ROOM 208,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Paterson, Ian/G-8688-2011 NR 51 TC 44 Z9 44 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0964-1955 J9 ORAL ONCOL JI Oral Oncol.-Eur. J. Cancer Pt. B PD MAR PY 1995 VL 31B IS 2 BP 136 EP 143 PG 8 WC Oncology; Dentistry, Oral Surgery & Medicine SC Oncology; Dentistry, Oral Surgery & Medicine GA RA049 UT WOS:A1995RA04900009 ER PT J AU BYASSMITH, MG MAX, MB MUIR, J KINGMAN, A AF BYASSMITH, MG MAX, MB MUIR, J KINGMAN, A TI TRANSDERMAL CLONIDINE COMPARED TO PLACEBO IN PAINFUL DIABETIC NEUROPATHY USING A 2-STAGE ENRICHED ENROLLMENT DESIGN SO PAIN LA English DT Article DE CLONIDINE; CONTROLLED CLINICAL TRIAL; DIABETIC NEUROPATHY; NEUROPATHIC PAIN; ANALGESIA; ANALGESIC ID SYMPATHETICALLY MAINTAINED PAIN; RELIEVES POSTHERPETIC NEURALGIA; TOOTH-PULP SENSATIONS; RATIO SCALES; DOUBLE-BLIND; AMITRIPTYLINE; TRIALS; DESCRIPTORS; DESIPRAMINE; ANALGESIA AB Because a variety of mechanisms may generate pain in neuropathic pain syndromes, conventional clinical trial methods may fail to identify some potentially useful drugs; a drug affecting just a single mechanism may work in too few patients to yield a statistically significant result for the trial. To test a previous clinical observation that approximately one-quarter of patients with painful diabetic neuropathy appear responsive to clonidine, we conducted a formal clinical trial of transdermal clonidine in painful diabetic neuropathy patients using a 2-stage enriched enrollment design. In the first stage (study I), 41 patients with painful diabetic neuropathy completed a randomized, 3-period crossover comparison of transdermal clonidine (titrated from 0.1 to 0.3 mg/day) to placebo patches. Twelve apparent responders from study I were entered into the 'enriched enrollment' second stage (study II), consisting of an additional 4 double-blind, randomized, 1-week treatment periods with transdermal clonidine and placebo. Study I showed that in the overall group of 41 patients, pain intensity differed little during clonidine and placebo treatment. In study II, however, the 12 apparent responders from study I had 20% less pain with clonidine than placebo (95% confidence interval (CI): 4-35% pain reduction; P = 0.015), confirming that their pain was responsive to clonidine. None of the 3 consistent clonidine responders who were tested with the cr-adrenergic blocker phentolamine had relief of pain, suggesting that clonidine's pain relief is not mediated by a decrease in sympathetic outflow. A post-hoc analysis of many variables suggested that patients who described their pain as sharp and shooting may have a greater likelihood of responding to clonidine. The results of this study support the hypothesis that there is a subset of patients with painful diabetic neuropathy who benefit from systemic clonidine administration and illustrate the value of an enriched enrollment technique in analgesic trials. C1 NIDR, NEUROBIOL & ANESTHESIOL BRANCH, BETHESDA, MD 20892 USA. NIDR, EPIDEMIOL & ORAL DIS PREVENT PROGRAM, BETHESDA, MD 20892 USA. NIH, CTR CLIN, DEPT NURSING, BETHESDA, MD 20892 USA. NR 41 TC 112 Z9 113 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 EI 1872-6623 J9 PAIN JI Pain PD MAR PY 1995 VL 60 IS 3 BP 267 EP 274 DI 10.1016/0304-3959(94)00121-T PG 8 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA QL440 UT WOS:A1995QL44000004 PM 7596622 ER PT J AU DHAWAN, S HEREDIA, A WAHL, LM EPSTEIN, JS MELTZER, MS HEWLETT, IK AF DHAWAN, S HEREDIA, A WAHL, LM EPSTEIN, JS MELTZER, MS HEWLETT, IK TI INTERFERON-GAMMA-INDUCED DOWN-REGULATION OF CD4 INHIBITS THE ENTRY OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 IN PRIMARY MONOCYTES SO PATHOBIOLOGY LA English DT Article DE HUMAN IMMUNODEFICIENCY VIRUS TYPE-1; PATHOGENESIS; MONOCYTES; INTERFERON-GAMMA; TUMOR NECROSIS FACTOR-ALPHA ID IFN-GAMMA; MONONUCLEAR PHAGOCYTES; INFECTED-CELLS; MACROPHAGES; AIDS; REPLICATION; ACTIVATION; MECHANISM; NITRITE; ALPHA AB We have previously shown that the treatment of monocytes with interferon-gamma (IFN-gamma) prior to exposure with human immunodeficiency virus type-1 (HIV) results in complete inhibition of HIV infection of monocytes. In the present report, we have extended this study to obtain information on the mechanism(s) underlying IFN-gamma-induced inhibition of HIV infection of monocytes. To examine the effect of IFN-gamma on HIV entry, the first event in the infectious cycle of the virus, we amplified HIV-gag sequences in the genomic DNA and RNA of IFN-gamma treated monocytes, and found no evidence for the presence of either proviral DNA or HIV RNA sequences. These results were consistent with the absence of intracellular HIV particles either in the latent or actively replicating state as determined by flow-cytometric analysis of these cells. Furthermore, no HIV-induced cytopathic effects, such as multinucleated giant cell formation or cell death, were observed in IFN-gamma-treated monocytes after their exposure to HIV. Stimulation of IFN-gamma-treated monocytes 6 days postinfection with tumor necrosis factor-alpha(TNF-alpha), which is known to augment HIV replication in the infected cells, did not result in the induction of the HIV indicating the absence of latent HIV infection in IFN-gamma-treated monocytes. Treatment of monocytes with IFN-gamma, TNF-alpha, or with a combination of the two agents which is known to induce antimicrobial free radical nitric oxide (NO2- in the murine system did not induce NO(2)(-)production human monocytes suggesting the antiviral activity of IFN-gamma to be independent of NO(2)(-)mediated killing of HIV or HIV-infected monocytes. Interestingly, CD4 expression on the surface of monocytes was substantially downregulated by IFN-gamma treatment, and was directly related to intracellular HIV-p24 levels. These results indicate that IFN-gamma-mediated inhibition of HIV infection of monocytes was not due to virus latency or killing of these cells, but was primarily due to downregulation of CD4 expression resulting in the inhibition of HIV entry into monocytes. C1 NIDR,IMMUNOL LAB,BETHESDA,MD 20892. WALTER REED ARMY INST RES,DEPT CELLULAR IMMUNOL,WASHINGTON,DC. RP DHAWAN, S (reprint author), US FDA,CTR BIOL EVALUAT & RES,DIV TRANSFUS TRANSMITTED DIS,MOLEC VIROL LAB,ROCKVILLE,MD 20852, USA. NR 23 TC 28 Z9 30 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-2008 J9 PATHOBIOLOGY JI Pathobiology PD MAR-APR PY 1995 VL 63 IS 2 BP 93 EP 99 DI 10.1159/000163939 PG 7 WC Cell Biology; Pathology SC Cell Biology; Pathology GA RY038 UT WOS:A1995RY03800006 PM 8554705 ER PT J AU MOFENSON, LM AF MOFENSON, LM TI A CRITICAL-REVIEW OF STUDIES EVALUATING THE RELATIONSHIP OF MODE OF DELIVERY TO PERINATAL TRANSMISSION OF HUMAN-IMMUNODEFICIENCY-VIRUS SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Review DE HUMAN IMMUNODEFICIENCY VIRUS; CESAREAN SECTION; PERINATAL TRANSMISSION ID HIV-1 INFECTION; EARLY DIAGNOSIS; BREAST-MILK; INFANTS; TYPE-1; WOMEN; ASSAY RP MOFENSON, LM (reprint author), NICHHD,CTR RES MOTHERS & INFANTS,ADOLESCENT & MATERNAL AIDS BRANCH,EXECUT BLDG,ROOM 4B11,BETHESDA,MD 20892, USA. OI Mofenson, Lynne/0000-0002-2818-9808 NR 36 TC 35 Z9 35 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0891-3668 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD MAR PY 1995 VL 14 IS 3 BP 169 EP 177 DI 10.1097/00006454-199503000-00001 PG 9 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA QL716 UT WOS:A1995QL71600001 PM 7761180 ER PT J AU HUNT, CE AF HUNT, CE TI SUDDEN-INFANT-DEATH-SYNDROME AND SUBSEQUENT SIBLINGS SO PEDIATRICS LA English DT Note ID APNEA; RISK C1 CASE WESTERN RESERVE UNIV,DEPT PEDIAT,CLEVELAND,OH 44106. RAINBOW BABIES & CHILDRENS HOSP,CTR SLEEP DISORDERS,CLEVELAND,OH 44106. BOSTON UNIV,SCH PUBL HLTH,BOSTON,MA. BOSTON UNIV,BOSTON CITY HOSP,MED CTR,DEPT PEDIAT,BOSTON,MA 02118. KAPIOLANI MED CTR WOMEN & CHILDREN,DEPT PSYCHIAT,HONOLULU,HI. CHILDRENS HOSP LOS ANGELES,DIV NEONATOL & PEDIAT PULMONOL,LOS ANGELES,CA 90027. LAC,DEPT PEDIAT,LOS ANGELES,CA. USC,WOMENS HOSP,MED CTR,LOS ANGELES,CA. TOLEDO HOSP,CTR PEDIAT PULM,DEPT PEDIAT,TOLEDO,OH. CHILDRENS HOSP LOS ANGELES,DIV NEONATOL & PULMONOL,LOS ANGELES,CA 90027. YALE UNIV,SCH MED,DEPT PEDIAT,NEW HAVEN,CT 06510. CASE WESTERN RESERVE UNIV,METROHLTH MED CTR,DEPT OBSTET & GYNECOL,CLEVELAND,OH. UNIV SO CALIF,WOMENS HOSP,MED CTR,LOS ANGELES,CA 90033. NICHHD,BETHESDA,MD. RUSH PRESBYTERIAN ST LUKES MED CTR,DEPT PEDIAT,CHICAGO,IL 60612. KAPIOLANI MED CTR WOMEN & CHILDREN,DEPT PEDIAT,HONOLULU,HI. RUSH PRESBYTERIAN ST LUKES MED CTR,CTR SIDS RES & DISORDERS RESP CONTROL,CHICAGO,IL 60612. NICHHD,CRMC,PREGNANCY & PERINATOL BRANCH,ROCKVILLE,MD. RP HUNT, CE (reprint author), MED COLL OHIO,DEPT PEDIAT,POB 10008,TOLEDO,OH 43699, USA. NR 18 TC 5 Z9 6 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 MAR PY 1995 VL 95 IS 3 BP 430 EP 432 PG 3 WC Pediatrics SC Pediatrics GA QK322 UT WOS:A1995QK32200022 PM 7862487 ER PT J AU BAPTISTA, T TENEUD, L CONTRERAS, Q ALASTRE, T BURGUERA, JL DEBURGUERA, M DEBAPTISTA, E WEIS, S HERNANDEZ, L AF BAPTISTA, T TENEUD, L CONTRERAS, Q ALASTRE, T BURGUERA, JL DEBURGUERA, M DEBAPTISTA, E WEIS, S HERNANDEZ, L TI LITHIUM AND BODY-WEIGHT GAIN SO PHARMACOPSYCHIATRY LA English DT Review ID FOOD-INTAKE; PSYCHIATRIC-DISORDERS; SYSTEMIC SULPIRIDE; RATS; HYPOTHALAMUS; INCREASE; OBESITY; MICRODIALYSIS; BROMOCRIPTINE; SCHIZOPHRENIA AB Weight gain is an undesirable side-effect of long-term lithium administration which notably interferes with treatment compliance. The mechanisms of this weight gain remain unclear, making its management in patents difficult. In this paper, studies describing the features of this weight gain in patients and in rats treated with chronic lithium administration are reviewed. The effects of lithium on body weight differ between patients and rats in a number of ways, including the observation that excessive weight gain is observed in both male and female patients, but only in female rats, Nevertheless, an animal model of lithium-induced weight gain may be able to provide useful insights into some of the specific mechanisms involved, particularly those related to interactions with gonadal steroid function. We discuss the effects of lithium on the endocrine system, neurotransmitters, metabolism, electrolyte regulation, and feeding behavior, which might underlie lithium's effects on body weight. Finally, suggestions for the management of weight gain in the clinical setting are presented, These include, in the long term, dietary control and physical activity and, in the short term, choosing among several drugs that have been tested either in patients or in animal models of obesity, If weight gain still cannot be controlled and treatment compliance is at risk, the mood stabilizers carbamazepine or valproic acid might be substituted for lithium treatment. C1 UNIV LOS ANDES,DEPT PSYCHIAT,MERIDA,VENEZUELA. UNIV LOS ANDES,SCH CHEM,MOLEC SPECTROSCOPY LAB,MERIDA,VENEZUELA. UNIV LOS ANDES,SCH PHARM,DEPT MICROBIOL,MERIDA,VENEZUELA. NIH,BIOL PSYCHIAT BRANCH,BETHESDA,MD 20892. RP BAPTISTA, T (reprint author), UNIV LOS ANDES,SCH MED,BEHAV PHYSIOL LAB,APARTADO 93,MERIDA 5101,VENEZUELA. NR 76 TC 76 Z9 77 U1 0 U2 3 PU GEORG THIEME VERLAG PI STUTTGART PA P O BOX 30 11 20, D-70451 STUTTGART, GERMANY SN 0176-3679 J9 PHARMACOPSYCHIATRY JI Pharmacopsychiatry PD MAR PY 1995 VL 28 IS 2 BP 35 EP 44 DI 10.1055/s-2007-979586 PG 10 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA QV552 UT WOS:A1995QV55200001 PM 7624385 ER PT J AU RESZKA, KJ CHIGNELL, CF AF RESZKA, KJ CHIGNELL, CF TI PHOTOCHEMISTRY OF 2-MERCAPTOPYRIDINES .3. EPR STUDY OF PHOTOPRODUCTION OF HYDROXYL RADICALS BY N-HYDROXYPYRIDINE-2-THIONE USING 5,5-DIMETHYL-1-PYRROLINE N-OXIDE IN AQUEOUS-SOLUTIONS SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID ELECTRON-SPIN RESONANCE; IRON CHELATORS; CELL-LINES; N-HYDROXY-2-THIOPYRIDONE; DERIVATIVES; PHOTOLYSIS AB N-Hydroxypyridine-2-thione, 2-S-PyrNOH, a potent antimicrobial, antifungal and anticancer agent, is photochemically active and upon UV irradiation generates free radicals. We have employed EPR and the spin-trap 5,5-dimethyl-1-pyrroline N-oxide (DMPO) to investigate the photochemistry in aqueous solutions of 2-S-PyrNOH (used here in the form of a sodium salt, 2-S-PyrNONa). We found that upon photoactivation 2-S-PyrNONa can follow two different pathways: it can produce hydroxyl radicals and/or it can act as a photoreducing agent. The capacity of 2-S-PyrNONa to produce (OH)-O-. radicals has been demonstrated by: (1) EPR detection of the DMPO/(OH)-O-. adduct in UV-irradiated samples; (2) inhibition of the DMPO/(OH)-O-. formation by (OH)-O-. scavengers such as methyl alcohol, formate and DMSO and (3) by detection of EPR signals of DMPO adducts with radicals derived from reaction of (OH)-O-. with these inhibitors. The photoreductive capacity of 2-S-PyrNONa was deduced from the observation that the amplitude of the EPR signal of the spin adduct DMPO/(OH)-O-. decreased on UV irradiation in air-free pH 7.0 buffers and that the signal recovered in the dark and after aeration. The ability to generate free radicals upon UV irradiation suggests that 2-S-PyrNONa can be regarded as a potential photocytotoxic agent. This feature may be relevant to the biological action of this compound. Our findings also emphasize that caution should be used when 2-S-PyrNOH is employed as a source of (OH)-O-. radicals in biological or chemical systems. RP RESZKA, KJ (reprint author), NIEHS,MOLEC BIOPHYS LAB,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 16 TC 17 Z9 17 U1 1 U2 2 PU AMER SOC PHOTOBIOLOGY PI AUGUSTA PA BIOTECH PARK, 1021 15TH ST, SUITE 9, AUGUSTA, GA 30901-3158 SN 0031-8655 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD MAR PY 1995 VL 61 IS 3 BP 269 EP 275 DI 10.1111/j.1751-1097.1995.tb03970.x PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA QK926 UT WOS:A1995QK92600005 ER PT J AU PETRAGLIA, F AGUZZOLI, L FLORIO, P BAUMANN, P GENAZZANI, AD DICARLO, C ROMERO, R AF PETRAGLIA, F AGUZZOLI, L FLORIO, P BAUMANN, P GENAZZANI, AD DICARLO, C ROMERO, R TI MATERNAL PLASMA AND PLACENTAL IMMUNOREACTIVE CORTICOTROPIN-RELEASING FACTOR CONCENTRATIONS IN INFECTION-ASSOCIATED TERM AND PRETERM DELIVERY SO PLACENTA LA English DT Article ID AMNIOTIC-FLUID INTERLEUKIN-6; PRETERM LABOR; LOCAL STIMULATION; HORMONE GENE; FACTOR CRF; PREGNANCY; PARTURITION; CYTOKINES; MEMBRANES; INVITRO AB The present study aimed to investigate whether microbial invasion of the amniotic cavity affects maternal plasma or placental immunoreactive corticotrophin releasing factor (ir-CRF) concentrations in pregnant women with pre-term or term labour. A cross-sectional study was conducted collecting blood samples in: (I) women with pre-term labour and intact membranes (25-36 weeks), with or without microbial invasion of the amniotic cavity (subdivided into three groups: IA, no microbial invasion of the amniotic cavity, delivery at term, n = 54; group IB, delivery < 48 h, no microbial invasion of the amniotic cavity, n = IO; group IC, delivery < 48 h, microbial invasion of the amniotic cavity, n = 8); (2) women at term, not in labour and without microbial invasion of the amniotic cavity (n = 15); (3) women in spontaneous active labour at term without (A) (n = 55) or with (B) (n = 16) microbial invasion of the amniotic cavity; and (4) healthy women not in labour at 25-36 weeks of gestation (n = 25). Specimens of trophoblast tissue were collected from pregnant women with pre-term labour (no microbial invasion of the amniotic cavity, n = 6; microbial invasion of the amniotic cavity, n = 4) or delivering at term (no microbial invasion of the amniotic cavity, n = 8; microbial invasion of the amniotic cavity, n = 4). A specific radioimmunoassay on acidic extracts of plasma or placental specimens was used. Patients with pre-term labour showed higher plasma ir-CRF concentration than healthy women at the same gestational age or at term not in labour, and those with microbial invasion of the amniotic cavity, had higher plasma ir-CRF concentrations than the ones without microbial invasion of the amniotic cavity (P < 0.05). Term labour was associated with elevated plasma ir-CRF concentrations, not affected by, the presence or absence of microbial invasion of the amniotic cavity. Placental ir-CRF concentrations in women with pre-term labour, in absence of microbial invasion of the amniotic cavity, mere significantly lower than in women with pre-term labour associated with microbial invasion of the amniotic cavity (P < 0.05). These findings showing a different pattern of maternal and placenta ir-CRF concentrations between pre-term labour with ol without microbial invasion of the amniotic cavity, support the hypothesis of an impact of infection on neuroendocrine activity, of human placenta. C1 WAYNE STATE UNIV,HUTZEL HOSP,DEPT OBSTET & GYNECOL,DETROIT,MI. NICHHD,PERINATOL BRANCH,BETHESDA,MD 20892. RP PETRAGLIA, F (reprint author), UNIV MODENA,SCH MED,DEPT OBSTET & GYNECOL,VIA POZZO 71,I-41100 MODENA,ITALY. RI PETRAGLIA, Felice/K-6535-2016 OI PETRAGLIA, Felice/0000-0002-8851-625X NR 29 TC 47 Z9 49 U1 0 U2 3 PU W B SAUNDERS CO LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0143-4004 J9 PLACENTA JI Placenta PD MAR PY 1995 VL 16 IS 2 BP 157 EP 164 DI 10.1016/0143-4004(95)90004-7 PG 8 WC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology SC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology GA QN164 UT WOS:A1995QN16400005 PM 7792279 ER PT J AU CHO, MH TAN, Z ERNEUX, C SHEARS, SB BOSS, WF AF CHO, MH TAN, Z ERNEUX, C SHEARS, SB BOSS, WF TI THE EFFECTS OF MASTOPARAN ON THE CARROT CELL PLASMA-MEMBRANE POLYPHOSPHOINOSITIDE PHOSPHOLIPASE-C SO PLANT PHYSIOLOGY LA English DT Article ID GTP-BINDING PROTEIN; WASP VENOM; SIGNAL TRANSDUCTION; INOSITOL PHOSPHATES; SUSPENSION-CULTURE; LILIUM-LONGIFLORUM; DUNALIELLA-SALINA; HUMAN-PLATELETS; KINASE-C; ACTIVATION AB When [H-3]inositol-labeled carrot (Daucus carota L.) cells were treated with 10 or 25 mu M wasp venom peptide mastoparan or the active analog Mas-7 there was a rapid loss of more than 70% of [H-3]phosphatidylinositol-4-monophosphate (PIP) and [H-3]phosphatidylinositol-4,5-bisphosphate (PIP2) and a 3- and 4-fold increase in [H-3]inositol-1,4-P-2 and [H-3]inositol-1,4,5-P-3, respectively. The identity of [H-3]inositol-1,4,5-P-3 was confirmed by phosphorylation with inositol-1,4,5-P-3 3-kinase and co-migration with inositol-1,3,4,5-P-4. The changes in phosphoinositides were evident within 1 min. The loss of [H-3]PIP was evident only when cells were treated with the higher concentrations (10 and 25 mu M) of mastoparan or Mas-7. At 1 mu M Mas-7, [H-3]PIP increased. The inactive mastoparan analog Mas-17 had little or no effect on [H-3]PIP or [H-3]PIP, hydrolysis in vivo. Neomycin (100 mu M) inhibited the uptake of Mas-7 and thereby inhibited the Mas-7-stimulated hydrolysis of [H-3]PIP and [H-3]PIP2. Plasma membranes isolated from mastoparan-treated cells had increased PIP-phospholipase C (PLC) activity. However, when Mas-7 was added to isolated plasma membranes from control cells, it had no effect on PIP-PLC activity at low concentrations and inhibited PIP-PLC at concentrations greater than 10 ELM. In addition, guanosine-5'-O-(3-thiotriphosphate) had no effect on the PIP-PLC activity when added to plasma membranes isolated from either the Mas-7-treated or control cells. The fact that Mas-7 did not stimulate PIP-PLC activity in vitro indicated that the Mas-7-induced increase in PIP-PLC in vivo required a factor that was lost from the membrane during isolation. C1 N CAROLINA STATE UNIV,DEPT BOT,RALEIGH,NC 27695. NIEHS,CELLULAR & MOLEC PHARMACOL LAB,RES TRIANGLE PK,NC 27709. FREE UNIV BRUSSELS,SCH MED,INST INTERDISCIPLINARY RES,B-1070 BRUSSELS,BELGIUM. NR 83 TC 53 Z9 54 U1 0 U2 2 PU AMER SOC PLANT PHYSIOLOGISTS PI ROCKVILLE PA 15501 MONONA DRIVE, ROCKVILLE, MD 20855 SN 0032-0889 J9 PLANT PHYSIOL JI Plant Physiol. PD MAR PY 1995 VL 107 IS 3 BP 845 EP 856 DI 10.1104/pp.107.3.845 PG 12 WC Plant Sciences SC Plant Sciences GA QM688 UT WOS:A1995QM68800021 PM 7716245 ER PT J AU LUNSFORD, RD AF LUNSFORD, RD TI A TN4001 DELIVERY SYSTEM FOR STREPTOCOCCUS-GORDONII (CHALLIS) SO PLASMID LA English DT Note ID STAPHYLOCOCCUS-AUREUS; RESISTANCE TRANSPOSON; GENTAMICIN; DETERMINANT; EXPRESSION; INSERTION; SEQUENCE AB The Staphylococcus aureus transposon Tn4001 was found to transpose in Streptococcus gordonii. Transposition sites appeared to be randomly distributed, and the element was stable in the absence of antibiotic selection. An increase in transposition frequency was noted when the delivery plasmid was propagated in a Dam(-) Dcm(-) Escherichia coli host strain. The utility of Tn4001 was demonstrated by the generation of lactose-negative mutants. Small size, clonal stability, random transposition, and known nucleotide sequence make Tn4001 a useful addition to the repertoire of tools available to the streptococcal geneticist. (C) 1995 Academic Press, Inc. RP LUNSFORD, RD (reprint author), NIDR,MICROBIAL ECOL LAB,BETHESDA,MD 20892, USA. NR 11 TC 21 Z9 21 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0147-619X J9 PLASMID JI Plasmid PD MAR PY 1995 VL 33 IS 2 BP 153 EP 157 DI 10.1006/plas.1995.1016 PG 5 WC Genetics & Heredity; Microbiology SC Genetics & Heredity; Microbiology GA QN022 UT WOS:A1995QN02200007 PM 7597109 ER PT J AU HEIMENDINGER, J FENG, Z EMMONS, K STODDARD, A KINNE, S BIENER, L SORENSEN, G ABRAMS, D VARNES, J BOUTWELL, B AF HEIMENDINGER, J FENG, Z EMMONS, K STODDARD, A KINNE, S BIENER, L SORENSEN, G ABRAMS, D VARNES, J BOUTWELL, B TI THE WORKING WELL TRIAL - BASE-LINE DIETARY AND SMOKING BEHAVIORS OF EMPLOYEES AND RELATED WORKSITE CHARACTERISTICS SO PREVENTIVE MEDICINE LA English DT Article ID UNITED-STATES; CANCER; POLICY; MODEL AB Background. The Working Well Trial, the largest randomized worksite health promotion trial to date, tests the effects of cancer prevention and control interventions on dietary and smoking behaviors of employees and the worksite environment. The trial is a 5-year cooperative agreement conducted in 57 matched pairs of worksites in 16 states by four study centers, a coordinating center, and the National Cancer Institute. The dual aims of this paper are to: (a) present a baseline description of the dietary and smoking habits of 20,801 employees, who are predominantly blue-collar workers; and (b) describe the social and physical environments of their worksites that may facilitate or hinder health behavior changes. Methods. The self-administered baseline survey of individuals consisted of a core set of questions common across all study centers on diet and smoking. The organizational survey consisted to eight instruments administered via interviews with key informants in each worksite. Continuous variables were analyzed by a mixed linear model and binary data were analyzed by the Generalized Estimating Equation. Results. The population represented is largely male (67.5%) and blue collar (53.5%). Mean levels of fat and fiber intakes were close to the national averages (36.6% of calories as fat and 13.1 g of fiber). Smoking prevalence (25.2%) was slightly lower than the national average. The worksites had a high level of health promotion activites (42% had nutrition programs, 53% had smoking control programs), but lacked environmental support for dietary behavior change and perceived support for smoking cessation. Conclusions. These findings replicate and extend previous research results to a large sample of diverse, largely blue-collar worksites. In addition the baseline results lay a foundation for the development of new insight into the relationship between individual and organizational level variables that may interact to influence behavioral and cultural norms. (C) 1995 Academic Press, Inc. C1 FRED HUTCHINSON CANC RES CTR,SEATTLE,WA 98104. BROWN UNIV,MIRIAM HOSP,PROVIDENCE,RI 02912. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. UNIV MASSACHUSETTS,BOSTON,MA 02125. UNIV FLORIDA,GAINESVILLE,FL 32611. UNIV TEXAS,MD ANDERSON CANC CTR,HOUSTON,TX 77025. RP HEIMENDINGER, J (reprint author), NCI,BETHESDA,MD 20892, USA. OI Biener, Lois/0000-0002-4130-8138 FU NCI NIH HHS [UO1 CA51671, UO1 CA51686, UO1 CA51687] NR 47 TC 40 Z9 40 U1 3 U2 7 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0091-7435 J9 PREV MED JI Prev. Med. PD MAR PY 1995 VL 24 IS 2 BP 180 EP 193 DI 10.1006/pmed.1995.1032 PG 14 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA QT209 UT WOS:A1995QT20900017 PM 7597021 ER PT J AU HOFFMAN, RC CASTNER, BJ GERHART, M GIBSON, MG RASMUSSEN, BD MARCH, CJ WEATHERBEE, J TSANG, M GUSTCHINA, A SCHALKHIHI, C RESHETNIKOVA, L WLODAWER, A AF HOFFMAN, RC CASTNER, BJ GERHART, M GIBSON, MG RASMUSSEN, BD MARCH, CJ WEATHERBEE, J TSANG, M GUSTCHINA, A SCHALKHIHI, C RESHETNIKOVA, L WLODAWER, A TI DIRECT EVIDENCE OF A HETEROTRIMERIC COMPLEX OF HUMAN INTERLEUKIN-4 WITH ITS RECEPTORS SO PROTEIN SCIENCE LA English DT Article DE INTERLEUKIN-4; INTERLEUKIN-4 RECEPTOR; INTERLEUKIN-2 RECEPTOR GAMMA-CHAIN; STOICHIOMETRY ID STIMULATORY FACTOR-I; GAMMA-CHAIN; SIGNAL-TRANSDUCTION; CRYSTAL-STRUCTURE; FUNCTIONAL COMPONENT; MOLECULAR-CLONING; IL-2 RECEPTOR; BINDING; CYTOKINES; IDENTIFICATION AB The mode of binding of interleukin-4 (IL-4) to its two known receptors, specific receptor IL-4R and a shared receptor gamma(c), was investigated using gel filtration and gel electrophoresis. A ternary complex between IL-4 and the soluble domains of the two receptors was shown to exist in solution. The association constant between gamma(c) and the stable complex of IL-4/sIL-4R is in the millimolar range, making the ternary complex a feasible target for crystallization studies. C1 NCI,FREDERICK CANC RES & DEV CTR,MACROMOLEC STRUCT LAB,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. IMMUNEX RES & DEV CORP,SEATTLE,WA 98101. RES & DEV SYST,DIV BIOTECHNOL,MINNEAPOLIS,MN 55413. FU NCI NIH HHS [N01-CO-46000] NR 41 TC 14 Z9 14 U1 0 U2 0 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 MAR PY 1995 VL 4 IS 3 BP 382 EP 386 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QN567 UT WOS:A1995QN56700004 PM 7795521 ER PT J AU CASTONGUAY, LA BRYANT, SH SNOW, PM FETROW, JS AF CASTONGUAY, LA BRYANT, SH SNOW, PM FETROW, JS TI A PROPOSED STRUCTURAL MODEL OF DOMAIN-1 OF FASCICLIN-III NEURAL CELL-ADHESION PROTEIN-BASED ON AN INVERSE FOLDING ALGORITHM SO PROTEIN SCIENCE LA English DT Article DE FASCICLIN III; HOMOLOGY MODELING; IMMUNOGLOBULIN SUPERFAMILY; INVERSE FOLDING ALGORITHM; NEURAL ADHESION PROTEIN; PROTEIN MODELING; PROTEIN STRUCTURE PREDICTION; SEQUENCE TO STRUCTURE ALIGNMENT ALGORITHM; THREADING ALGORITHM ID IMMUNOGLOBULIN SUPERFAMILY; HUMAN CD4; 3-DIMENSIONAL STRUCTURE; BINDING; DROSOPHILA; RECOGNITION; SEQUENCES; EVOLUTION; RESIDUES; MOLECULE AB Fasciclin III is an integral membrane protein expressed on a subset of axons in the developing Drosophila nervous system. It consists of an intracellular domain, a transmembrane region, and an extracellular region composed of three domains, each predicted to form an immunoglobulin-like fold. The most N-terminal of these domains is expected to be important in mediating cell-cell recognition events during nervous system development. To learn more about the structure/function relationships in this cellular recognition molecule, a model structure of this domain was built. A sequence-to-structure alignment algorithm was used to align the protein sequence of the fasciclin III first domain to the immunoglobulin McPC603 structure. Based on this alignment, a model of the domain was built using standard homology modeling techniques. Side-chain conformations were automatically modeled using a rotamer search algorithm and the model was minimized to relax atomic overlaps; The resulting model is compact and has chemical characteristics consistent with related globular protein structures. This model is a de novo test of the sequence-to-structure alignment algorithm and is currently being used as the basis for mutagenesis experiments to discern the parts of the fasciclin III protein that are necessary for homophilic molecular recognition in the developing Drosophila nervous system. C1 SUNY ALBANY, DEPT BIOL SCI, ALBANY, NY 12222 USA. SUNY ALBANY, CTR MOLEC GENET, ALBANY, NY 12222 USA. NATL LIB MED, NATL CTR BIOTECHNOL INFORMAT, BETHESDA, MD 20894 USA. NR 39 TC 3 Z9 3 U1 0 U2 0 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 MAR PY 1995 VL 4 IS 3 BP 472 EP 483 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QN567 UT WOS:A1995QN56700014 PM 7795530 ER PT J AU BRYNGELSON, JD ONUCHIC, JN SOCCI, ND WOLYNES, PG AF BRYNGELSON, JD ONUCHIC, JN SOCCI, ND WOLYNES, PG TI FUNNELS, PATHWAYS, AND THE ENERGY LANDSCAPE OF PROTEIN-FOLDING - A SYNTHESIS SO PROTEINS-STRUCTURE FUNCTION AND GENETICS LA English DT Review DE PROTEIN FOLDING; ENERGY LANDSCAPE; FOLDING PATHWAY; FOLDING FUNNEL; LATTICE SIMULATION; FOLDING THERMODYNAMICS; FOLDING KINETICS; PROTEIN ENGINEERING ID GLOBULAR-PROTEINS; CHYMOTRYPSIN INHIBITOR-2; STATISTICAL-MECHANICS; PRESSURE DENATURATION; TERTIARY STRUCTURE; PHAGE-T4 LYSOZYME; TRANSITION-STATE; MODEL PROTEINS; FOLDED STATES; SPIN-GLASSES AB The understanding, and even the description of protein folding is impeded by the complexity of the process. Much of this complexity can be described and understood by taking a statistical approach to the energetics of protein conformation, that is, to the energy landscape. The statistical energy landscape approach explains when and why unique behaviors, such as specific folding pathways, occur in some proteins and more generally explains the distinction between folding processes common to all sequences and those peculiar to individual sequences, This approach also gives new, quantitative insights into the interpretation of experiments and simulations of protein folding thermodynamics and kinetics. Specifically, the picture provides simple explanations for folding as a two-state first-order phase transition, for the origin of metastable collapsed unfolded states and for the curved Arrhenius plots observed in both laboratory experiments and discrete lattice simulations. The relation of these quantitative ideas to folding pathways, to uniexponential vs. multiexponential behavior in protein folding experiments and to the effect of mutations on folding is also discussed. The success of energy landscape ideas in protein structure prediction is also described. The use of the energy landscape approach for analyzing data is illustrated with a quantitative analysis of some recent simulations, and a qualitative analysis of experiments on the folding of three proteins. The work unifies several previously proposed ideas concerning the mechanism protein folding and delimits the regions of validity of these ideas under different thermodynamic conditions (C) 1995 Wiley-Liss, Inc. C1 UNIV CALIF SAN DIEGO,DEPT PHYS,0319,LA JOLLA,CA 92093. UNIV ILLINOIS,SCH CHEM SCI,URBANA,IL 61801. UNIV ILLINOIS,BECKMAN INST,URBANA,IL 61801. RP BRYNGELSON, JD (reprint author), NIH,DIV COMP RES & TECHNOL,PHYS SCI LAB,BETHESDA,MD 20892, USA. FU NIGMS NIH HHS [1 R01 GM44557] NR 132 TC 1755 Z9 1768 U1 34 U2 299 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 MAR PY 1995 VL 21 IS 3 BP 167 EP 195 DI 10.1002/prot.340210302 PG 29 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA QP249 UT WOS:A1995QP24900001 PM 7784423 ER PT J AU DEERFIELD, DW FOX, DJ HEADGORDON, M HISKEY, RG PEDERSEN, LG AF DEERFIELD, DW FOX, DJ HEADGORDON, M HISKEY, RG PEDERSEN, LG TI THE FIRST SOLVATION SHELL OF MAGNESIUM-ION IN A MODEL PROTEIN ENVIRONMENT WITH FORMATE, WATER, AND X-NH3, H2S, IMIDAZOLE, FORMALDEHYDE, AND CHLORIDE AS LIGANDS - AN AB-INITIO STUDY SO PROTEINS-STRUCTURE FUNCTION AND GENETICS LA English DT Article DE CARBOXYLATE; MAGNESIUM; HYDRATION; LIGAND ID H-RAS P21; CRYSTAL-STRUCTURE; CARBOXYLATE INTERACTIONS; 3-DIMENSIONAL STRUCTURE; MOLECULAR MECHANICS; ESCHERICHIA-COLI; CATALYTIC DOMAIN; EF-TU; CALCIUM; BINDING AB The first coordination shell of an Mg(II) ion in a model protein environment is studied. Complexes containing a model carboxylate, an Mg(II) ion, various ligands (NH3, H2S, imidazole, and formaldehyde) and water of hydration about the divalent metal ion were geometry optimized. We find that for complexes with the same coordination number, the unidentate carboxylate-Mg(II) ion is greater than 10 kcal mol(-1) more stable than the bidentate orientation. Imidazole was found to be the most stable ligand, followed in order by NH3, formaldehyde, H2O, and H2S. (C) 1995 Wiley-Liss, Inc. C1 GAUSSIAN INC,PITTSBURGH,PA 15106. UNIV CALIF BERKELEY,DEPT CHEM,BERKELEY,CA 94720. UNIV N CAROLINA,DEPT CHEM,CHAPEL HILL,NC 27599. NIEHS,RES TRIANGLE PK,NC 27709. RP DEERFIELD, DW (reprint author), PITTSBURGH SUPERCOMP CTR,4400 5TH AVE,PITTSBURGH,PA 15213, USA. RI Pedersen, Lee/E-3405-2013 OI Pedersen, Lee/0000-0003-1262-9861 FU NCRR NIH HHS [1 P41 RR06009]; NHLBI NIH HHS [HL-27995, HL-20161] NR 44 TC 16 Z9 16 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 0887-3585 J9 PROTEINS JI Proteins PD MAR PY 1995 VL 21 IS 3 BP 244 EP 255 DI 10.1002/prot.340210307 PG 12 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA QP249 UT WOS:A1995QP24900006 PM 7784428 ER PT J AU COSTA, PT MCCRAE, RR AF COSTA, PT MCCRAE, RR TI SOLID GROUND IN THE WETLANDS OF PERSONALITY - A REPLY TO BLOCK SO PSYCHOLOGICAL BULLETIN LA English DT Review ID 5-FACTOR MODEL; NATURAL-LANGUAGE; DIMENSIONS; INVENTORY; TRAITS AB The five-factor model (FFM) of personality offers a structural organization of personality traits in terms of 5 broad factors. J. Block's ( 1995) critique of the FFM failed to recognize the utility of a trait taxonomy and the intent of research designed to test the 5-factor hypothesis. In a number of instances he omitted reference to empirical evidence that addresses concerns he raised; this evidence shows strong support for the FFM beyond the lexical and questionnaire traditions he reviews. Many of his suggestions for improving the quality of personality research are valuable, but are likely to be more fruitful when used in conjunction with established knowledge about the structure of personality traits: the FFM. RP COSTA, PT (reprint author), NIA,GERONTOL RES CTR,PERSONAL & COGNIT LAB,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. OI Costa, Paul/0000-0003-4375-1712 NR 46 TC 111 Z9 111 U1 5 U2 19 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 0033-2909 J9 PSYCHOL BULL JI Psychol. Bull. PD MAR PY 1995 VL 117 IS 2 BP 216 EP 220 DI 10.1037//0033-2909.117.2.216 PG 5 WC Psychology; Psychology, Multidisciplinary SC Psychology GA QM884 UT WOS:A1995QM88400002 PM 7724688 ER PT J AU BURT, DB ZEMBAR, MJ NIEDEREHE, G AF BURT, DB ZEMBAR, MJ NIEDEREHE, G TI DEPRESSION AND MEMORY IMPAIRMENT - A METAANALYSIS OF THE ASSOCIATION, ITS PATTERN, AND SPECIFICITY SO PSYCHOLOGICAL BULLETIN LA English DT Review ID SIGNAL-DETECTION ANALYSIS; ALZHEIMER-TYPE DEMENTIA; REVISED KENDRICK BATTERY; RECOGNITION-MEMORY; PARKINSONS-DISEASE; AFFECTIVE-DISORDERS; COGNITIVE DEFICITS; VERBAL MEMORY; OLDER ADULTS; OUTPATIENT DEPRESSIVES AB The existing evidence paints an unclear picture of whether an association exists between depression and memory impairment. The purpose of this investigation was to determine whether depression is associated with memory impairment, whether moderator variables determine the extent of this association, and whether any obtained association is unique to depression. Meta-analytic techniques were used to synthesize data from 99 studies on recall and 48 studies on recognition in clinically depressed and nondepressed samples. Associations between memory impairment and other psychiatric disorders( e.g., schizophrenia, dementia) were also examined. A significant, stable association between depression and memory impairment was revealed. Further analyses indicated, however, that it is likely that depression is linked to particular aspects of memory, the linkage is found in particular subsets of depressed individuals, and memory impairment is not unique to depression. C1 UNIV HALLE WITTENBERG,O-4010 HALLE,GERMANY. NIMH,MENTAL DISORDERS AGING RES BRANCH,BETHESDA,MD. RP BURT, DB (reprint author), UNIV TEXAS,HLTH SCI CTR,INST MENTAL SCI,CTR HUMAN DEV RES,1300 MOURSUND AVE,HOUSTON,TX 77030, USA. FU NIMH NIH HHS [MH18392, MH43577] NR 203 TC 524 Z9 533 U1 10 U2 64 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 0033-2909 J9 PSYCHOL BULL JI Psychol. Bull. PD MAR PY 1995 VL 117 IS 2 BP 285 EP 305 DI 10.1037//0033-2909.117.2.285 PG 21 WC Psychology; Psychology, Multidisciplinary SC Psychology GA QM884 UT WOS:A1995QM88400008 PM 7724692 ER PT J AU MCCLOSKEY, M RAPP, B YANTIS, S RUBIN, G BACON, WF DAGNELIE, G GORDON, B ALIMINOSA, D BOATMAN, DF BADECKER, W JOHNSON, DN TUSA, RJ PALMER, E AF MCCLOSKEY, M RAPP, B YANTIS, S RUBIN, G BACON, WF DAGNELIE, G GORDON, B ALIMINOSA, D BOATMAN, DF BADECKER, W JOHNSON, DN TUSA, RJ PALMER, E TI A DEVELOPMENTAL DEFICIT IN LOCALIZING OBJECTS FROM VISION SO PSYCHOLOGICAL SCIENCE LA English DT Article ID DYSLEXIA AB We describe a college student, A.H., with a developmental deficit in determining the location of objects from vision. The deficit is selective in that (a) localization from auditory or tactile information is intact; (b) A.H. reports the identity of mislocalized objects accurately; (c) visual localization errors preserve certain parameters of the target location; and (d) visual localization is severely impaired under certain stimulus conditions, but nearly intact under other conditions. These results bear on the representation and processing of location information in the visual system, and also have implications for understanding developmental dyslexia. C1 NASA,AMES RES CTR,MOFFETT FIELD,CA 94035. NIAAA,ROCKVILLE,MD 20852. RP MCCLOSKEY, M (reprint author), JOHNS HOPKINS UNIV,DEPT COGNIT SCI,BALTIMORE,MD 21218, USA. RI Yantis, Steven/A-7488-2009 NR 19 TC 27 Z9 27 U1 3 U2 6 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0956-7976 J9 PSYCHOL SCI JI Psychol. Sci. PD MAR PY 1995 VL 6 IS 2 BP 112 EP 117 DI 10.1111/j.1467-9280.1995.tb00316.x PG 6 WC Psychology, Multidisciplinary SC Psychology GA QR665 UT WOS:A1995QR66500008 ER PT J AU GIAMBRA, LM ARENBERG, D ZONDERMAN, AB KAWAS, C AF GIAMBRA, LM ARENBERG, D ZONDERMAN, AB KAWAS, C TI ADULT LIFE-SPAN CHANGES IN IMMEDIATE VISUAL MEMORY AND VERBAL INTELLIGENCE SO PSYCHOLOGY AND AGING LA English DT Article ID RETENTION TEST; AGE; PERFORMANCE; PATTERNS AB A sample of 558 women and 1,163 men 17 to 102 years old, screened for neurodegenerative and neuropsychiatric disease, was administered tests of immediate visual memory (Benton Visual Retention Test) and crystallized intelligence (Wechsler Adult Intelligence Scale Vocabulary subtest) from 1 to 5 times over 27.7 years. Cross-sectional and longitudinal evidence led to the conclusion that the 65-74-year decade was a watershed for decremental changes in immediate visual memory and verbal intelligence. Age accounted for considerably less variance in vocabulary than in immediate memory. The proportion of individuals whose longitudinal trajectories were contrary to group trends decreased substantially with increased age; observed age changes remained when analyses were restricted to individuals who had perfect or near-perfect mental status scores. Selected neuronal loss and slower reproduction times were considered as possible causes. C1 JOHNS HOPKINS MED INST,DEPT NEUROL,BALTIMORE,MD 21205. RP GIAMBRA, LM (reprint author), NIA,GERONTOL RES CTR,NATHAN W SHOCK LABS,PERSONAL & COGNIT LAB,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. OI Costa, Paul/0000-0003-4375-1712; Zonderman, Alan B/0000-0002-6523-4778 NR 35 TC 69 Z9 69 U1 0 U2 5 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 0882-7974 J9 PSYCHOL AGING JI Psychol. Aging PD MAR PY 1995 VL 10 IS 1 BP 123 EP 139 DI 10.1037//0882-7974.10.1.123 PG 17 WC Gerontology; Psychology, Developmental SC Geriatrics & Gerontology; Psychology GA QN045 UT WOS:A1995QN04500013 PM 7779310 ER PT J AU HYDE, TM EGAN, MF WING, LL WYATT, RJ WEINBERGER, DR KLEINMAN, JE AF HYDE, TM EGAN, MF WING, LL WYATT, RJ WEINBERGER, DR KLEINMAN, JE TI PERSISTENT CATALEPSY ASSOCIATED WITH 7 DYSKINESIAS IN RATS TREATED WITH CHRONIC INJECTIONS OF HALOPERIDOL DECANOATE SO PSYCHOPHARMACOLOGY LA English DT Article DE CATALEPSY; VACUOUS CHEWING MOVEMENTS; PARKINSONISM; TARDIVE DYSKINESIA; HALOPERIDOL ID VACUOUS JAW MOVEMENTS; TARDIVE-DYSKINESIA; BASAL GANGLIA; INDUCED PARKINSONISM; RECEPTOR ANTAGONIST; DOPAMINE-RECEPTORS; ORAL DYSKINESIA; PREVALENCE; D1; ORGANIZATION AB Patients who develop persistent parkinsonism while on chronic neuroleptic therapy may be predisposed towards the development of tardive dyskinesia (TD). We investigated this issue in an animal model of TD by examining the association between catalepsy and the syndrome of neuroleptic-induced vacuous chewing movements (VCMs). VCMs were measured every 3 weeks for 33 weeks while rats received injections of haloperidol decanoate. Catalepsy was measured after the second through the seventh injections of the depot neuroleptic. There were no correlations between the severity of catalepsy scores after the second or third injections of haloperidol and the severity of the overall VCM syndrome. However, the severity of the catalepsy score following the third through seventh injections of haloperidol strongly correlated with the concurrent number of VCMs. Persistent high catalepsy scores across the six catalepsy rating sessions were strongly associated with the development of persistent severe VCMs. These findings suggest that, to the extent that persistent parkinsonian signs in humans are associated with a propensity towards the development of TD, the VCM syndrome in rats is at least a partially faithful animal model of this relationship. C1 ST ELIZABETH HOSP,NIMH,INTRAMURAL RES PROGRAM,NEUROPSYCHIAT BRANCH,WASHINGTON,DC 20032. RP HYDE, TM (reprint author), ST ELIZABETH HOSP,NIMH,INTRAMURAL RES PROGRAM,CLIN BRAIN DISORDERS BRANCH,WASHINGTON,DC 20032, USA. NR 55 TC 12 Z9 12 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD MAR PY 1995 VL 118 IS 2 BP 142 EP 149 DI 10.1007/BF02245832 PG 8 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA QR462 UT WOS:A1995QR46200009 PM 7617800 ER PT J AU RON, E LUBIN, JH SHORE, RE MABUCHI, K MODAN, B POTTERN, LM SCHNEIDER, AB TUCKER, MA BOICE, JD AF RON, E LUBIN, JH SHORE, RE MABUCHI, K MODAN, B POTTERN, LM SCHNEIDER, AB TUCKER, MA BOICE, JD TI THYROID-CANCER AFTER EXPOSURE TO EXTERNAL RADIATION - A POOLED ANALYSIS OF 7 STUDIES SO RADIATION RESEARCH LA English DT Article ID CHILDHOOD IRRADIATION; RETROSPECTIVE COHORT; NECK IRRADIATION; SKIN HEMANGIOMA; TINEA CAPITIS; THYMUS GLAND; INDUCED HEAD; FOLLOW-UP; TUMORS; RADIOTHERAPY AB The thyroid gland of children is especially vulnerable to the carcinogenic action of ionizing radiation. To provide insights into various modifying influences on risk, seven major studies with organ doses to individual subjects were evaluated. Five cohort studies (atomic bomb survivors, children treated for tinea capitis, two studies of children irradiated for enlarged tonsils, and infants irradiated for an enlarged thymus gland) and two case-control studies (patients with cervical cancer and childhood cancer) were studied. The combined studies include almost 120,000 people (approximately 58,000 exposed to a wide range of doses and 61,000 nonexposed subjects), nearly 700 thyroid cancers and 3,000,000 person years of follow-up. For persons exposed to radiation before age 15 years, linearity best described the dose response, even down to 0.10 Gy. At the highest doses (greater than or equal to 10 Gy), associated with cancer therapy, there appeared to be a decrease or leveling of risk. For childhood exposures, the pooled excess relative risk per Gy (ERR/Gy) was 7.7 (95% CI = 2.1, 28.7) and the excess absolute risk per 10(4) PY Gy (EAR/10(4) PY Gy) was 4.4 (95% CI = 1.9, 10.1). The attributable risk percent (AR%) at 1 Gy was 88%. However, these summary estimates were affected strongly by age at exposure even within this limited age range. The ERR was greater (P = 0.07) for females than males, but the findings from the individual studies were not consistent. The EAR was higher among women, reflecting their higher rate of naturally occurring thyroid cancer. The distribution of ERR over time followed neither a simple multiplicative nor an additive pattern in relation to background occurrence. Only two cases were seen within 5 years of exposure. The ERR began to decline about 30 years after exposure but was still elevated at 40 years. Risk also decreased significantly with increasing age at exposure, with little risk apparent after age 20 years. Based on limited data, there was a suggestion that spreading dose over time (from a few days to > 1 year) may lower risk, possibly due to the opportunity for cellular repair mechanisms to operate. The thyroid gland in children has one of the highest risk coefficients of any organ and is the only tissue with convincing evidence for risk at about 0.10 Gy. (C) 1995 by Radiation Research Society C1 NYU,MED CTR,DEPT ENVIRONM MED,NEW YORK,NY 10010. RADIAT EFFECTS RES FDN,DEPT EPIDEMIOL,HIROSHIMA 732,JAPAN. RADIAT EFFECTS RES FDN,DEPT EPIDEMIOL PATHOL,HIROSHIMA 732,JAPAN. CHAIM SHEBA MED CTR,DEPT CLIN EPIDEMIOL,IL-52621 TEL HASHOMER,ISRAEL. UNIV ILLINOIS,MICHAEL REESE HOSP & MED CTR,DEPT ENDOCRINOL & METAB,CHICAGO,IL 60616. RP RON, E (reprint author), NCI,EPIDEMIOL & BIOSTAT PROGRAM,BETHESDA,MD 20892, USA. RI Tucker, Margaret/B-4297-2015; Ain, Kenneth/A-5179-2012 OI Ain, Kenneth/0000-0002-2668-934X NR 56 TC 773 Z9 814 U1 3 U2 24 PU RADIATION RESEARCH SOC PI OAK BROOK PA 2021 SPRING RD, STE 600, OAK BROOK, IL 60521 SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD MAR PY 1995 VL 141 IS 3 BP 259 EP 277 DI 10.2307/3579003 PG 19 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA QH651 UT WOS:A1995QH65100004 PM 7871153 ER PT J AU CHOYKE, PL GLENN, GM WALTHER, MM PATRONAS, NJ LINEHAN, WM ZBAR, B AF CHOYKE, PL GLENN, GM WALTHER, MM PATRONAS, NJ LINEHAN, WM ZBAR, B TI VONHIPPEL-LINDAU DISEASE - GENETIC, CLINICAL, AND IMAGING FEATURES SO RADIOLOGY LA English DT Review DE ANGIOMA, CENTRAL NERVOUS SYSTEM; KIDNEY NEOPLASMS; PANCREAS, CYSTS; PHEOCHROMOCYTOMA; STATE-OF-ART REVIEWS; VONHIPPEL-LINDAU DISEASE ID RENAL-CELL CARCINOMA; CENTRAL-NERVOUS-SYSTEM; BILE-DUCT OBSTRUCTION; CEREBELLAR HEMANGIOBLASTOMA; PANCREATIC INVOLVEMENT; PAPILLARY CYSTADENOMA; NATURAL-HISTORY; FOLLOW-UP; DIAGNOSIS; TUMORS AB von Hippel-Lindau (VHL) disease is an autosomal dominant disorder that causes retinal hemangioblastomas, hemangioblastomas of the central nervous system, endolymphatic sac tumors, renal cell carcinomas, pancreatic cysts and tumors, pheochromocytomas, and epididymal cystadenomas, among other less common manifestations. Although this entity has been recognized for almost 70 years, recent developments in the genetics and imaging of VHL disease have greatly improved understanding of the disease and its natural history. This review describes the major events that led to the discovery of the gene for VHL and will familiarize the reader with recent developments in the magnetic resonance Imaging, computed tomographic, and ultrasound findings of this entity. Despite advances in the genetic understanding of this disease, imaging techniques will continue to play a major role in the diagnosis, management, and treatment of VHL. C1 NCI,CTR & DIAG,DIV CANC BIOL,CANC DIAG BRANCH,FREDERICK,MD 21701. NCI,DIV UROL ONCOL,SURG BRANCH,FREDERICK,MD 21701. NCI,FREDERICK CANC RES FACIL,IMMUNOBIOL LAB,FREDERICK,MD. NIH,BETHESDA,MD 20892. RP CHOYKE, PL (reprint author), HENRY M JACKSON FDN,WARREN GRANT MAGNUSON CLIN CTR,DEPT DIAGNOST RADIOL,FREDERICK,MD, USA. NR 109 TC 275 Z9 291 U1 1 U2 4 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0033-8419 J9 RADIOLOGY JI Radiology PD MAR PY 1995 VL 194 IS 3 BP 629 EP 642 PG 14 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA QG918 UT WOS:A1995QG91800002 PM 7862955 ER PT J AU MATTAY, VS WEINBERGER, DR BARRIOS, FA SOBERING, GS KOTRLA, KJ VANGELDEREN, P DUYN, JH SEXTON, RH MOONEN, CTW FRANK, JA AF MATTAY, VS WEINBERGER, DR BARRIOS, FA SOBERING, GS KOTRLA, KJ VANGELDEREN, P DUYN, JH SEXTON, RH MOONEN, CTW FRANK, JA TI BRAIN MAPPING WITH FUNCTIONAL MR-IMAGING - COMPARISON OF GRADIENT-ECHO-BASED EXOGENOUS AND ENDOGENOUS CONTRAST TECHNIQUES SO RADIOLOGY LA English DT Article DE BLOOD, FLOW DYNAMICS; BRAIN, FUNCTION; BRAIN, MR; MAGNETIC RESONANCE (MR), RAPID IMAGING ID SENSORY STIMULATION; CORTEX; TIME; ACTIVATION; EPI AB PURPOSE: To compare directly the two most widely used methods of functional magnetic resonance (MR) imaging-dynamic contrast material-enhanced MR imaging and blood oxygenation level-dependent (BOLD) MR imaging. MATERIALS AND METHODS: Five healthy volunteers underwent dynamic contrast-enhanced and BOLD MR imaging with a conventional 1.5-T MR unit during visual stimulation and a dark control state. BOLD studies were performed with a gradient-echo sequence, and dynamic MR imaging was performed with an echo-shifted gradient-echo sequence after intravenous administration of a bolus of gadopentetate dimeglumine. RESULTS: A significantly greater percentage signal change was found with dynamic MR imaging than with the BOLD technique. The extent of area activated was also significantly greater. CONCLUSION: With standard clinical imagers and these gradient-echo-based techniques, greater percentage activation and area of activation can be achieved with dynamic MR imaging than with BOLD MR imaging. C1 NIH,DIAGNOST RADIOL RES LAB,BETHESDA,MD 20892. NIH,IN VIVO NMR RES CTR,BIOMED ENGN INSTRUMENTAT PROGRAM,BETHESDA,MD 20892. NIMH,CLIN BRAIN DISORDERS BRANCH,WASHINGTON,DC. COMPUTAT PHYS,FAIRFAX,VA. RI Duyn, Jozef/F-2483-2010; Barrios, Fernando/B-4295-2012; Barrios, Fernando/D-1591-2016; Moonen, Chrit/K-4434-2016 OI Barrios, Fernando/0000-0002-5699-4222; Moonen, Chrit/0000-0001-5593-3121 NR 22 TC 11 Z9 11 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0033-8419 J9 RADIOLOGY JI Radiology PD MAR PY 1995 VL 194 IS 3 BP 687 EP 691 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA QG918 UT WOS:A1995QG91800011 PM 7862963 ER PT J AU CHIODETTI, L SCHWARTZ, RH AF CHIODETTI, L SCHWARTZ, RH TI THE ROLE OF CD28 IN THE ACTIVATION OF T-LYMPHOCYTES TO PROLIFERATE IN RESPONSE TO IL4 SO RESEARCH IN IMMUNOLOGY LA English DT Article ID CTLA-4 COUNTER-RECEPTOR; CELL ACTIVATION; CLONAL ANERGY; ANTIGEN; INDUCTION; IL-2; EXPRESSION; PATHWAY; SIGNAL; B7 RP CHIODETTI, L (reprint author), NIAID,CELLULAR & MOLEC IMMUNOL LAB,BETHESDA,MD 20892, USA. NR 23 TC 2 Z9 2 U1 0 U2 0 PU EDITIONS SCIENTIFIQUES ELSEVIER PI PARIS CEDEX 15 PA 141 RUE JAVEL, 75747 PARIS CEDEX 15, FRANCE SN 0923-2494 J9 RES IMMUNOL JI Res. Immunol. PD MAR-APR PY 1995 VL 146 IS 3 BP 169 EP 171 DI 10.1016/0923-2494(96)80252-5 PG 3 WC Immunology SC Immunology GA RP877 UT WOS:A1995RP87700008 PM 8525048 ER PT J AU FIGUEROA, JP WARD, E LUTHI, TE VERMUND, SH BRATHWAITE, AR BURK, RD AF FIGUEROA, JP WARD, E LUTHI, TE VERMUND, SH BRATHWAITE, AR BURK, RD TI PREVALENCE OF HUMAN PAPILLOMAVIRUS AMONG STD CLINIC ATTENDERS IN JAMAICA - ASSOCIATION OF YOUNGER AGE AND INCREASED SEXUAL-ACTIVITY SO SEXUALLY TRANSMITTED DISEASES LA English DT Article ID CERVICAL NEOPLASIA; INFECTION; WOMEN; ADOLESCENTS; CANCER; POPULATION; KINGSTON; ANDREW AB Background and Objectives: Human papillomavirus is the major etiologic agent of cervical cancer. Although the incidence of cancer of the cervix is high in Jamaica, the prevalence of human papillomavirus among Jamaican women has not been defined. Goal of the Study: To estimate the prevalence of human papillomavirus infection and associated risk factors in women attending an STD clinic in Kingston, Jamaica. Study Design: A cross-sectional survey was done of 202 women attending an STD clinic in Kingston in 1990. Cervical and vaginal cells were collected by lavage, and human papillomavirus genomes were detected in extracted DNA using low-stringency Southern blot hybridization. Results: Fifty-eight (28.7%) women were identified as HPV positive. Prevalence of HPV by age group was 39% in women 15-19 years old, 33% of women 20-24 years old, 31% in women 25-29 years old, and 17% in those 30 years or older. Increasing age was significantly associated with a lower prevalence of human papillomavirus infection (test for trend, P = 0.025). The effect of age was independent of years of sexual activity. Women reporting more than one sexual partner per month on average were found to have a significantly higher HPV prevalence (odds ratio 2.87, 95% confidence Interval 1.29-6.38), as were women who reported more frequent sex (test for trend, P = 0.006). Conclusions: Sexual behavior is associated with risk of human papillomavirus infection. The decrease of human papillomavirus prevalence in older women agrees with other studies that argue in favor of a biological effect, such as increased immunity to human papillomavirus with age. A better understanding of why immunity to human papillomavirus may develop in older women may provide the basis for developing an effective vaccine to prevent cancer of the cervix. C1 ALBERT EINSTEIN COLL MED,DEPT PEDIAT,BRONX,NY 10467. ALBERT EINSTEIN COLL MED,DEPT MICROBIOL & IMMUNOL,BRONX,NY 10467. ALBERT EINSTEIN COLL MED,DEPT OBSTET & GYNECOL,BRONX,NY 10467. NIAID,DIV AIDS,BETHESDA,MD 20892. RP FIGUEROA, JP (reprint author), MINIST HLTH,EPIDEMIOL UNIT,30-34 HALF WAY TREE RD,KINGSTON 5,JAMAICA. OI Vermund, Sten/0000-0001-7289-8698 NR 26 TC 36 Z9 37 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0148-5717 J9 SEX TRANSM DIS JI Sex. Transm. Dis. PD MAR-APR PY 1995 VL 22 IS 2 BP 114 EP 118 DI 10.1097/00007435-199503000-00007 PG 5 WC Infectious Diseases SC Infectious Diseases GA QN753 UT WOS:A1995QN75300007 PM 7624812 ER PT J AU SCHOLMERICH, A FRACASSO, MP LAMB, ME BROBERG, AG AF SCHOLMERICH, A FRACASSO, MP LAMB, ME BROBERG, AG TI INTERACTIONAL HARMONY AT 7 AND 10 MONTHS OF AGE PREDICTS SECURITY OF ATTACHMENT AS MEASURED BY Q-SORT RATINGS SO SOCIAL DEVELOPMENT LA English DT Article DE ATTACHMENT; MOTHER-INFANT INTERACTION; PARENTAL BEHAVIOR; Q-SORT RATINGS ID INFANT-MOTHER ATTACHMENT; MATERNAL SENSITIVITY; Q-SET; BEHAVIOR; SYNCHRONY; TEMPERAMENT; STABILITY; VALIDITY; ORIGINS AB Fifty-eight infants and their mothers were observed at home for 45 minutes at seven and ten months of age using a detailed behavioral checklist. During these observations, the degree of mutual interactional engagement was also rated on a 4-point scale every 20 seconds. The attachment security of 38 infants was assessed at 13 months using mothers' reports on the Attachment Q-set (AQS, Waters, 1987). Composite measures of mother-infant interaction derived from the behavioral observations were moderately, stable over time. Measures of maternal interactive behaviors and ratings of mutual engagement were highly correlated. Mothers' and infants' behaviors were combined into an index of behavioral harmony that was sensitive to differences in the infants' attachment security three and six months later. Using a stepwise multiple regression, 43% of the valiance in the AQS-scores tvas explained by behavioral harmony at seven months, mutual engagement at 10 months, and infant fuss/cry at seven months. RP SCHOLMERICH, A (reprint author), NICHHD,SOCIAL & EMOT DEV SECT,9190 ROCKVILLE PIKE,BETHESDA,MD 20814, USA. RI Schoelmerich, Axel/C-9039-2009 OI Schoelmerich, Axel/0000-0002-9844-3920 NR 34 TC 11 Z9 11 U1 1 U2 6 PU BLACKWELL PUBL LTD PI OXFORD PA 108 COWLEY RD, OXFORD, OXON, ENGLAND OX4 1JF SN 0961-205X J9 SOC DEV JI Soc. Dev. PD MAR PY 1995 VL 4 IS 1 BP 62 EP 74 DI 10.1111/j.1467-9507.1995.tb00051.x PG 13 WC Psychology, Developmental SC Psychology GA QV099 UT WOS:A1995QV09900005 ER PT J AU BERGER, R MEZEY, E CLANCY, KP HARTA, G WRIGHT, RM REPINE, JE BROWN, RH BROWNSTEIN, M PATTERSON, D AF BERGER, R MEZEY, E CLANCY, KP HARTA, G WRIGHT, RM REPINE, JE BROWN, RH BROWNSTEIN, M PATTERSON, D TI ANALYSIS OF ALDEHYDE OXIDASE AND XANTHINE DEHYDROGENASE OXIDASE AS POSSIBLE CANDIDATE GENES FOR AUTOSOMAL RECESSIVE FAMILIAL AMYOTROPHIC-LATERAL-SCLEROSIS SO SOMATIC CELL AND MOLECULAR GENETICS LA English DT Article ID SUPEROXIDE-DISMUTASE; CLONING; CONVERSION; PROTEIN; YEAST AB Recently, point mutations in superoxide dismutase 1 (SOD1) have been shown to lead to a subset of autosomal dominantly inherited familial amyotrophic lateral sclerosis (ALS). These findings have led to the hypothesis that defects in oxygen radical metabolism may be involved in the pathogenesis of ALS. Therefore, we decided to analyze other enzymes involved in oxygen radical metabolism for possible involvement in other forms of ALS. We report here analysis of two genes encoding the molybdenum hydroxylases aldehyde oxidase (AO) and xanthine dehydrogenase/oxidase (XDH) for involvement in ALS. Of particular interest, one gene identified as encoding aldehyde oxidase is shown to map to 2q33, a region recently shown to contain a gene responsible for a familial form of ALS with autosomal recessive inheritance (FALS-AR). The AO gene appeals to be located within 280, 000 bp of simple sequence repeat marker D2S116, which shows no recombination with the FALS-AR locus. The AO gene is highly expressed in glial cells of human spinal cord. In addition, we mapped a gene for XDH to 2p22, a region previously shown to contain a highly homologous but different form of XDH. Neither of these XDH genes appears to be highly expressed in human spinal cord. This evidence suggests that AO may be a candidate gene for FALS-AR. C1 NIH,BETHESDA,MD 20892. MASSACHUSETTS GEN HOSP,BOSTON,MA 02129. UNIV COLORADO,HLTH SCI CTR,DENVER,CO 80262. WEBB WARING INST BIOMED RES,DENVER,CO 80262. RP BERGER, R (reprint author), ELEANOR ROOSEVELT INST,DENVER,CO 80206, USA. RI Brownstein, Michael/B-8609-2009 FU NIA NIH HHS [AG00029, F32AGO5666]; NINDS NIH HHS [1PO1NS31248-01] NR 39 TC 49 Z9 52 U1 0 U2 1 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0740-7750 J9 SOMAT CELL MOLEC GEN JI Somat.Cell Mol.Genet. PD MAR PY 1995 VL 21 IS 2 BP 121 EP 131 DI 10.1007/BF02255787 PG 11 WC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity GA RV992 UT WOS:A1995RV99200004 PM 7570184 ER PT J AU TEMECK, BK PASS, HI AF TEMECK, BK PASS, HI TI ESOPHAGOPLEURAL FISTULA - A COMPLICATION OF PHOTODYNAMIC THERAPY SO SOUTHERN MEDICAL JOURNAL LA English DT Article ID ESOPHAGEAL AB Mesothelioma of the pleura remains an incurable disease for which novel treatments are being investigated. One of these is intraoperative photodynamic therapy (PDT), using the principle of cell cytotoxicity produced by light-activated sensitization. We report a complication of this therapy that defined the maximal tolerated dose of PDT, ie, esophagopleural fistula, in two consecutive patients who had received the same dose of PDT at the time of extrapleural pneumonectomy. C1 NCI,SURG BRANCH,THORAC ONCOL SECT,BETHESDA,MD 20892. NR 15 TC 11 Z9 11 U1 0 U2 0 PU SOUTHERN MEDICAL ASSN PI BIRMINGHAM PA 35 LAKESHORE DR PO BOX 190088, BIRMINGHAM, AL 35219 SN 0038-4348 J9 SOUTHERN MED J JI South.Med.J. PD MAR PY 1995 VL 88 IS 3 BP 271 EP 274 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA QK962 UT WOS:A1995QK96200005 PM 7886521 ER PT J AU YERGEY, AL TEFFERA, Y ESTEBAN, NV ABRAMSON, FP AF YERGEY, AL TEFFERA, Y ESTEBAN, NV ABRAMSON, FP TI DIRECT DETERMINATION OF HUMAN URINARY CORTISOL METABOLITES BY HPLC/CRIMS SO STEROIDS LA English DT Article DE CORTISOL; HPLC; MASS SPECTROMETRY; METABOLITES; CRIMS ID CHROMATOGRAPHY MASS-SPECTROMETRY; CHEMICAL-REACTION INTERFACE; <1,2,3,4-C-13>CORTISOL; PIGLETS; C-13 AB Feasibility of using high performance liquid chromatographic input to the chemical reaction interface mass spectrometry system was assessed by measuring the profile of hydrolyzed urinary metabolites of [9,12,12-H-2(3)]cortisol in six human subjects with no preparation other than hydrolysis and solid phase extraction. Relative amounts of tetrahydrocortisol, tetrahydrocortisone, and cortolones (as the sum of alpha- and beta-) were 0.417 +/- 0.047, 0.523 +/- 0.036 and 0.059 +/- 0.019, respectively. The constant reproducibility of the measurements coupled with a profile consistent with that observed by other workers shows that the technique represents an important tool in the determination of metabolites of endogenous molecules. C1 GEORGE WASHINGTON UNIV,MED CTR,DEPT PHARMACOL,WASHINGTON,DC 20037. RP YERGEY, AL (reprint author), NICHHD,METAB ANAL & MASS SPECT SECT,BLDG 10,ROOM 6C101,BETHESDA,MD 20892, USA. FU NIGMS NIH HHS [1-R43-GM43669] NR 15 TC 10 Z9 10 U1 0 U2 1 PU BUTTERWORTH-HEINEMANN PI WOBURN PA 225 WILDWOOD AVE #UNITB PO BOX 4500, WOBURN, MA 01801-2084 SN 0039-128X J9 STEROIDS JI Steroids PD MAR PY 1995 VL 60 IS 3 BP 295 EP 298 DI 10.1016/0039-128X(94)00071-J PG 4 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA QP782 UT WOS:A1995QP78200010 PM 7792835 ER PT J AU BURKE, GL EVANS, GW RILEY, WA SHARRETT, AR HOWARD, G BARNES, RW ROSAMOND, W CROW, RS RAUTAHARJU, PM HEISS, G AF BURKE, GL EVANS, GW RILEY, WA SHARRETT, AR HOWARD, G BARNES, RW ROSAMOND, W CROW, RS RAUTAHARJU, PM HEISS, G TI ARTERIAL-WALL THICKNESS IS ASSOCIATED WITH PREVALENT CARDIOVASCULAR-DISEASE IN MIDDLE-AGED ADULTS - THE ATHEROSCLEROSIS RISK IN COMMUNITIES (ARIC) STUDY SO STROKE LA English DT Article DE ATHEROSCLEROSIS; CARDIOVASCULAR DISEASES; EPIDEMIOLOGY; ULTRASONICS ID CAROTID ATHEROSCLEROSIS; ULTRASOUND AB Background and Purpose This study was done to assess the relationship between prevalent cardiovascular disease and arterial wall thickness in middle-aged US adults. Methods The association of preexisting coronary heart disease, cerebrovascular disease, and peripheral vascular disease with carotid and popliteal intimal-medial thickness (IMT) (measured by B-mode ultrasound) was assessed in 13 870 black and white men and women, aged 45 to 64, during the Atherosclerosis Risk in Communities (ARIC) Study baseline examination (1987 through 1989). Prevalent disease was determined according to both participant self-report and measurements at the baseline examination (including electrocardiogram, fasting blood glucose, and medication use). Results Across four race and gender strata, mean carotid far wall IMT was consistently greater in participants with prevalent clinical cardiovascular disease than in disease-free subjects. Similarly, the prevalence of cardiovascular disease was consistently greater in participants with progressively thicker IMT. The greatest differences in carotid IMT associated with prevalent disease were observed for reported symptomatic peripheral vascular disease (0.09 to 0.22 mm greater IMT in the four race-gender groups). Conclusions These data document the substantially greater arterial wall thickness observed in middle-aged adults with prevalent cardiovascular disease. Both carotid and popliteal arterial IMT were related to clinically manifest cardiovascular disease affecting distant vascular beds, such as the cerebral, peripheral, and coronary artery vascular beds. C1 UNIV N CAROLINA,BOWMAN GRAY SCH MED,DEPT PUBL HLTH SCI,CHAPEL HILL,NC. UNIV N CAROLINA,BOWMAN GRAY SCH MED,DEPT NEUROL,CHAPEL HILL,NC. UNIV N CAROLINA,SCH PUBL HLTH,DEPT EPIDEMIOL,CHAPEL HILL,NC. ARIC,CTR ULTRASOUND READING,WINSTON SALEM,NC. NHLBI,BETHESDA,MD. UNIV MINNESOTA,SCH PUBL HLTH,DIV EPIDEMIOL,MINNEAPOLIS,MN. UNIV ALBERTA,CTR ECG READING,EDMONTON,AB,CANADA. FU NHLBI NIH HHS [N01-HC-55016, N01-HC-55015, N01-HC-55018] NR 26 TC 628 Z9 643 U1 1 U2 14 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0039-2499 J9 STROKE JI Stroke PD MAR PY 1995 VL 26 IS 3 BP 386 EP 391 PG 6 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA QK056 UT WOS:A1995QK05600006 PM 7886711 ER PT J AU MOSCICKI, EK AF MOSCICKI, EK TI EPIDEMIOLOGY OF SUICIDAL-BEHAVIOR SO SUICIDE AND LIFE-THREATENING BEHAVIOR LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Association-of-Suicidology CY APR, 1994 CL NEW YORK, NY SP AMER ASSOC SUICIDOL ID SAN-DIEGO SUICIDE; ADRENERGIC-RECEPTOR BINDING; RISK-FACTORS; ADOLESCENT SUICIDE; TEENAGE SUICIDE; PSYCHOLOGICAL AUTOPSY; GENERAL POPULATION; SUBSTANCE ABUSE; UNITED-STATES; HIGH-SCHOOL AB This paper presents the epidemiology of suicide and discusses the known risk factors for suicide within a framework designed to encourage a systematic approach to theory testing and prevention. Mental and addictive disorders are the most powerful of the multiple risk factors for suicide in all age groups. Since risk factors for suicide rarely occur in isolation, prevention efforts are more likely to succeed if multiple risk factors are targeted. C1 NIMH,SUICIDE RES CONSORTIUM,ROCKVILLE,MD 20857. RP MOSCICKI, EK (reprint author), NIMH,PREVENT RES BRANCH,ROOM 10-85,5600 FISHERS LANE,ROCKVILLE,MD 20857, USA. FU NIMH NIH HHS [U01 MH33870, U01 MH33883, U01 MH34224] NR 94 TC 142 Z9 147 U1 2 U2 6 PU GUILFORD PRESS PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 SN 0363-0234 J9 SUICIDE LIFE-THREAT JI Suicide Life-Threat. Behav. PD SPR PY 1995 VL 25 IS 1 BP 22 EP 35 PG 14 WC Psychiatry; Psychology, Multidisciplinary SC Psychiatry; Psychology GA QV248 UT WOS:A1995QV24800004 PM 7631373 ER PT J AU HOLMES, PV DEBARTOLOMEIS, A KOPRIVICA, V CRAWLEY, JN AF HOLMES, PV DEBARTOLOMEIS, A KOPRIVICA, V CRAWLEY, JN TI LACK OF EFFECT OF CHRONIC MORPHINE TREATMENT AND NALOXONE-PRECIPITATED WITHDRAWAL ON TYROSINE-HYDROXYLASE, GALANIN, AND NEUROPEPTIDE-Y MESSENGER-RNA LEVELS IN THE RAT LOCUS-COERULEUS SO SYNAPSE LA English DT Article DE OPIATE DEPENDENCE; NOREPINEPHRINE; COEXISTENCE; NEUROPEPTIDE; C-FOS; CORTICOTROPIN-RELEASING FACTOR; BARRINGTONS NUCLEUS ID MESSENGER-RNA LEVELS; OPIATE-WITHDRAWAL; CERULEUS NEURONS; PARAVENTRICULAR NUCLEUS; INSITU HYBRIDIZATION; SEQUENCE-ANALYSIS; CORTICOTROPIN; BRAIN; EXPRESSION; CLONIDINE AB Morphine dependence was experimentally induced in rats by daily injection of increasing doses of morphine for seven days, Withdrawal was precipitated in half of the morphine-dependent rats by a single injection of naloxone on day 8. Behavioral signs of withdrawal were evident in the morphine/naloxone group. Gene expression in locus coeruleus (LC) neurons was investigated using quantitative in situ hybridization analysis. Messenger RNA (mRNA) levels for tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine synthesis, and for precursors to galanin (GAL) and neuropeptide Y (NPY), peptides that coexist with norepinephrine in LC neurons, were not altered by chronic morphine treatment or naloxone-precipitated withdrawal. In contrast, mRNA levels for c-fos were dramatically elevated in the LC following naloxone-precipitated withdrawal. Chronic morphine treatment caused a small decrease in levels of mRNA encoding the precursor to corticotropin-releasing factor (CRF) in Barrington's nucleus. Although long-term adaptations of LC neurons have previously been implicated in the development of morphine tolerance, dependence, and withdrawal, alterations in the levels of TH, GAL, or NPY mRNA in the LC apparently do not underlie this process. (C) 1995 Wiley-Liss, Inc.* RP HOLMES, PV (reprint author), NIMH,EXPTL THERAPEUT BRANCH,BEHAV NEUROPHARMACOL SECT,BLDG 10,ROOM 4N214,BETHESDA,MD 20892, USA. NR 47 TC 17 Z9 17 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0887-4476 J9 SYNAPSE JI Synapse PD MAR PY 1995 VL 19 IS 3 BP 197 EP 205 DI 10.1002/syn.890190307 PG 9 WC Neurosciences SC Neurosciences & Neurology GA QM232 UT WOS:A1995QM23200006 PM 7540319 ER PT J AU VOLKOW, ND GATLEY, SJ FOWLER, JS CHEN, R LOGAN, J DEWEY, SL DING, YS PAPPAS, N KING, P MACGREGOR, RR KUHAR, MJ CARROLL, FI WOLF, AP AF VOLKOW, ND GATLEY, SJ FOWLER, JS CHEN, R LOGAN, J DEWEY, SL DING, YS PAPPAS, N KING, P MACGREGOR, RR KUHAR, MJ CARROLL, FI WOLF, AP TI LONG-LASTING INHIBITION OF IN-VIVO COCAINE BINDING TO DOPAMINE TRANSPORTERS BY 3-BETA-(4-IODOPHENYL)TROPANE-2-CARBOXYLIC ACID METHYL-ESTER - RTI-55 OR BETA-CIT SO SYNAPSE LA English DT Article DE C-11; BABOON; PET ID AGONIST-INDUCED DESENSITIZATION; UPTAKE SITES; SEROTONIN TRANSPORTERS; NONHUMAN-PRIMATES; RECEPTORS; INVIVO; BRAIN; BABOON; SPECT; PAROXETINE AB Cocaine analogs such as 3 beta-(4-iodophenyl)tropane-2 beta-carboxylic acid methyl ester (RTI-55 or beta CIT) with a higher affinity for the dopamine transporter (DAT) may be potentially useful in interfering with cocaine's actions in brain. This study evaluates the time course of the effects of RTI-55 on cocaine binding in baboon brain using PET and [C-11]cocaine. [C-11]Cocaine binding was measured prior to, and 90 minutes, 24 hours, 4-5 days and 11-13 days after RTI-55 (0.3 mg/kg i.v.). Parallel studies with [H-3]cocaine and RTI-55 (0.5 mg/kg i.v. or 2 mg/kg i.p.) were performed in the mouse. RTI-55 significantly inhibited [C-11]cocaine binding at 90 minutes and 24 hours after administration. The half-life for the clearance of RTI-55 from the DAT was estimated to be 2 to 3 days in the baboon brain. In the mouse brain, RTI-55 significantly inhibited [H-3]cocaine binding at 60 and 180 minutes after administration and recovery was observed at 12 hours. These results document long-lasting inhibition of cocaine binding by RTI-55 and corroborate that binding kinetics of RTI-55 in striatum observed in imaging studies with [I-123]RTI-55 represents binding to DATs. (C) 1995 Wiley-Liss, Inc. C1 BROOKHAVEN NATL LAB,DEPT CHEM,UPTON,NY 11973. SUNY STONY BROOK,DEPT PSYCHIAT,STONY BROOK,NY 11794. NIDA,ADDICT RES CTR,NEUROSCI BRANCH,BALTIMORE,MD 21224. RES TRIANGLE INST,RES TRIANGLE PK,NC 27709. RP VOLKOW, ND (reprint author), BROOKHAVEN NATL LAB,DEPT MED,BLDG 490,UPTON,NY 11973, USA. RI Chen, Robert/B-3899-2009 OI Chen, Robert/0000-0002-8371-8629 FU NIDA NIH HHS [5RO1-DA06278] NR 32 TC 13 Z9 13 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 0887-4476 J9 SYNAPSE JI Synapse PD MAR PY 1995 VL 19 IS 3 BP 206 EP 211 DI 10.1002/syn.890190308 PG 6 WC Neurosciences SC Neurosciences & Neurology GA QM232 UT WOS:A1995QM23200007 PM 7784960 ER PT J AU PERSICO, AM SCHINDLER, CW ZACZEK, R BRANNOCK, MT UHL, GR AF PERSICO, AM SCHINDLER, CW ZACZEK, R BRANNOCK, MT UHL, GR TI BRAIN TRANSCRIPTION FACTOR GENE-EXPRESSION, NEUROTRANSMITTER LEVELS, AND NOVELTY RESPONSE BEHAVIORS - ALTERATIONS DURING RAT AMPHETAMINE WITHDRAWAL AND FOLLOWING CHRONIC INJECTION STRESS SO SYNAPSE LA English DT Review DE IMMEDIATE-EARLY GENES; C-FOS; PSYCHOSTIMULANT; PREFRONTAL CORTEX; STRIATUM; DEPRESSION ID 3,4-DIHYDROXYPHENYLACETIC ACID DOPAC; MESSENGER-RNA EXPRESSION; SERUM GROWTH-FACTORS; IMMEDIATE-EARLY GENE; C-FOS GENE; DOPAMINE RELEASE; CEREBRAL-CORTEX; REWARD REGIONS; JUN-B; HIPPOCAMPAL NOREPINEPHRINE AB Transcription factors are known to act as gene expression regulators, possibly linking extracellular stimuli to long-term modifications at the neuronal level. Such modifications may potentially underlie chronic psychostimulant- and stress-induced behavioral alterations. This study illustrates how a 2 week, twice daily 7.5 mg/kg d-amphetamine or saline regimen alters rat brain regional expression of transcription factor genes, including c-fos, fos-B, jun-B, c-jun, and zif 268, and seeks potential correlations between those changes and alterations in neurotransmitter levels and behavioral novelty responses. Amphetamine withdrawal-induced decreases in transcription factor mRNA levels, assessed using Northern blot analysis, appear most prominent in prefrontal cortex, begin approximately 12 h after the last injection, and largely recover to control levels by 54 h. Prefrontal cortical and striatal dopamine content, assessed using HPLC, decrease and recover over a similar time course. Behavioral ''stereotypy time'' manifest by animals exposed to a novel environment, a measure sensitive to psychostimulant withdrawal, also decreases beginning 12 h after the last injection, is still significantly reduced at 54 h, and recovers at 72 h. Chronic saline injections are followed by a consistent decrease in transcription factor gene expression, observed 6 h after the last injection, followed by a ''rebound'' increase at 12 h. These changes are accompanied by dramatic, mostly biphasic alterations in prefrontal cortical biogenic amines and by a short-lived increase in striatal dopamine turnover. At the same time, rats display much longer-lasting decreases in locomotor responses when exposed to a novel environment, with recovery occurring only 54 h after the last injection. The delayed recovery of behavioral responses to novelty is consistent with potential involvement of changes in transcription factor-mediated gene expression in neurochemical mechanisms underlying psychostimulant withdrawal and chronic injection stress-induced behavioral alterations. (C) 1995 Wiley-Liss, Inc.* C1 NIDA,ADDICT RES CTR,MOLEC NEUROBIOL BRANCH,BALTIMORE,MD 21224. NIDA,ADDICT RES CTR,BEHAV PHARMACOL & GENET SECT,BALTIMORE,MD 21224. DUPONT MERCK PHARMACEUT CO,WILMINGTON,DE 19880. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROL,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROSCI,BALTIMORE,MD 21224. NR 130 TC 53 Z9 53 U1 2 U2 5 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0887-4476 J9 SYNAPSE JI Synapse PD MAR PY 1995 VL 19 IS 3 BP 212 EP 227 DI 10.1002/syn.890190309 PG 16 WC Neurosciences SC Neurosciences & Neurology GA QM232 UT WOS:A1995QM23200008 PM 7784961 ER PT J AU THADANI, PV AF THADANI, PV TI BIOLOGICAL MECHANISMS AND PERINATAL EXPOSURE TO ABUSED DRUGS SO SYNAPSE LA English DT Editorial Material DE DRUGS OF ABUSE; SOMATIC GROWTH; NEUROBEHAVIORAL FUNCTION; PERINATAL ID INFANT-DEATH-SYNDROME; PRENATAL COCAINE; FETAL SHEEP; RAT; RESPONSES; PREGNANCY; ALTERS; GROWTH AB Use of illicit and licit drugs during pregnancy is a major public health concern, as it can have adverse effects on the developing fetus, Infants born of women addicted to narcotics, cocaine, alcohol, or polydrugs often undergo a characteristic withdrawal syndrome and may have physical, behavioral, and/or neurological abnormalities. As it is not feasible to ascertain whether these functional changes in human infants are produced by abused substance(s) per se or by a combination of complex socioeconomic factors and polydrug use, researchers in recent years have developed and utilized various innovative animal models to assess drug-induced alterations and their biological mechanisms during the developmental period under a controlled environment. To promote interdisciplinary communications as well as to assess the progress and the future needs in this area, the National Institute on Drug Abuse (NIDA) held a technical review at which biomedical researchers discussed their current findings in various physiological systems. This report summarizes the major findings and the methodological and experimental issues discussed at the conference. The meeting was held in Washington, DC, on May 25 and 26, 1994. (C) 1995 Wiley-Liss, Inc.* RP THADANI, PV (reprint author), NIDA,DIV BASIC RES,PARKLAWN BLDG,ROOM 10A-19,5600 FISHERS LANE,ROCKVILLE,MD 20857, USA. NR 36 TC 8 Z9 8 U1 1 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0887-4476 J9 SYNAPSE JI Synapse PD MAR PY 1995 VL 19 IS 3 BP 228 EP 232 DI 10.1002/syn.890190310 PG 5 WC Neurosciences SC Neurosciences & Neurology GA QM232 UT WOS:A1995QM23200009 PM 7784962 ER PT J AU WARD, JM HARDISTY, JF HAILEY, JR STREETT, CS AF WARD, JM HARDISTY, JF HAILEY, JR STREETT, CS TI PEER-REVIEW IN TOXICOLOGIC PATHOLOGY SO TOXICOLOGIC PATHOLOGY LA English DT Article; Proceedings Paper CT 13th International Symposium of the Society-of-Toxicologic-Pathologists, Role of Drug Metabolism and Pharmacokinetics in Toxicologic Pathology CY JUN 05-09, 1994 CL CHARLESTON, SC SP SOC TOXICOL PATHOLOGISTS DE PATHOLOGY WORKING GROUP (PWG); TOXICOLOGY; EXPERT PANEL; CARCINOGENESIS; BIOASSAY AB Peer review of histopathology findings in safety assessment studies involving rodents and other animals is a relatively recent procedure in toxicologic pathology. It serves to ensure the integrity of the pathology evaluation in safety studies, encourages consistency of diagnostic criteria and use of common terminology, and provides a method of continuing education for participants. The use of a standardized system of pathology nomenclature and diagnostic criteria, such as the Society of Toxicologic Pathologist's Guides for Toxicologic Pathology, is of great value in the procedure. Pathology reviews may involve government-sponsored bioassay programs, in-house industrial corporations, or individual peer reviews suggested or required by government regulatory agencies. Pathology Working Groups can be an integral part of the review process. The extent of the peer review is primarily dependent on the study results; however, other variables such as confidence of the data, study size and duration, complexity, and purpose are also important considerations. Essential components of any peer review, however, include selection of tissues/lesions for review, by a reviewing pathologist, discrepancy resolution, data modification, and documentation of all aspects of the review process. Specific procedures for pathology peer review are discussed. Disagreements among pathologists discovered in peer reviews can be resolved by several methods and examples will be presented. The entire pathology peer review process should be a learning experience for all involved and can help ensure the integrity of animal toxicology studies used for important regulatory decisions involving the use of chemicals in our society. RP WARD, JM (reprint author), NCI,FREDERICK CANC RES & DEV CTR,FAIRVIEW 201,FREDERICK,MD 21702, USA. NR 0 TC 31 Z9 32 U1 0 U2 0 PU SOC TOXICOLOGIC PATHOLOGISTS PI LAWRENCE PA 1041 NEW HAMPSHIRE ST PO BOX 368, LAWRENCE, KS 66044 SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD MAR-APR PY 1995 VL 23 IS 2 BP 226 EP 234 PG 9 WC Pathology; Toxicology SC Pathology; Toxicology GA QU178 UT WOS:A1995QU17800018 PM 7569679 ER PT J AU CIRVELLO, JD RADOVSKY, A HEATH, JE FARNELL, DR LINDAMOOD, C AF CIRVELLO, JD RADOVSKY, A HEATH, JE FARNELL, DR LINDAMOOD, C TI TOXICITY AND CARCINOGENICITY OF T-BUTYL ALCOHOL IN RATS AND MICE FOLLOWING CHRONIC EXPOSURE IN DRINKING-WATER SO TOXICOLOGY AND INDUSTRIAL HEALTH LA English DT Article DE CARCINOGENICITY; KIDNEY; MICE; RATS; T-BUTYL ALCOHOL; THYROID; TOXICITY; URINARY BLADDER ID LIVER AB t-Butyl alcohol (TBA) was administered in drinking water to F344/N rats and B6C3F(1) mice for two years using 60 animals/dose/sex/species. Male rats received doses of 0, 1.25, 2.5, or 5 mg/ml and females received 0, 2.5, 5, or 10 mg/ml, resulting in average daily doses of approximately 85, 195, or 420 mg TBA/kg body weight for males and 175, 330, or 650 mg/kg for females. Ten rats per group were evaluated after 15 months. Male and female mice received doses of 0, 5, 10, or 20 mg/ml, resulting in average daily doses of approximately 535, 1,035, or 2,065 mg TBA/kg body weight for males and 510, 1,015, or 2,105 mg/kg for females. Survival was significantly reduced in male rats receiving 5 mg/ml, female rats receiving 10 mg/ml, and male mice receiving 20 mg/ml. Long-term exposure to TBA produced increased incidences of renal tubule adenoma and carcinoma in male rats; transitional epithelial hyperplasia of the kidney in male and female rats; follicular cell adenoma of the thyroid in female mice; and follicular cell hyperplasia of the thyroid and inflammation and hyperplasia of the urinary bladder in male and female mice. In addition, a slight increase in follicular cell adenoma or carcinoma of the thyroid (combined) in male mice may have been related to the administration of TBA. C1 SO RES INST,BIRMINGHAM,AL 35255. SOLVAY PHARMACEUT SA,MARIETTA,GA. RP CIRVELLO, JD (reprint author), NIEHS,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 30 TC 67 Z9 70 U1 0 U2 4 PU PRINCETON SCIENTIFIC PUBL INC PI PRINCETON PA PO BOX 2155, PRINCETON, NJ 08543 SN 0748-2337 J9 TOXICOL IND HEALTH JI Toxicol. Ind. Health PD MAR-APR PY 1995 VL 11 IS 2 BP 151 EP 165 PG 15 WC Public, Environmental & Occupational Health; Toxicology SC Public, Environmental & Occupational Health; Toxicology GA RH360 UT WOS:A1995RH36000003 PM 7491631 ER PT J AU HENGEN, PN AF HENGEN, PN TI METHODS AND REAGENTS - REAMPLIFICATION OF PCR FRAGMENTS SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Article ID GENE AMPLIFICATION AB Methods and reagents is a unique monthly column that highlights current discussions in the newsgroup bionet.molbio.methds-reagnts, available on the Internet. This month's column discusses difficulties encountered by some netters while trying to reamplify DNA made by the polymerase chain reaction. For details on how to partake in the newsgroup, see the accompanying box. RP HENGEN, PN (reprint author), NCI,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702, USA. NR 8 TC 6 Z9 7 U1 0 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 MAR PY 1995 VL 20 IS 3 BP 124 EP 125 DI 10.1016/S0968-0004(00)88980-X PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QL581 UT WOS:A1995QL58100010 PM 7709432 ER PT J AU HOYER, D BELL, GI BERELOWITZ, M EPELBAUM, J FENIUK, W HUMPHREY, PPA OCARROLL, AM PATEL, YC SCHONBRUNN, A TAYLOR, JE REISINE, T AF HOYER, D BELL, GI BERELOWITZ, M EPELBAUM, J FENIUK, W HUMPHREY, PPA OCARROLL, AM PATEL, YC SCHONBRUNN, A TAYLOR, JE REISINE, T TI CLASSIFICATION AND NOMENCLATURE OF SOMATOSTATIN RECEPTORS SO TRENDS IN PHARMACOLOGICAL SCIENCES LA English DT Note ID RAT-BRAIN; MOLECULAR-CLONING; FUNCTIONAL-CHARACTERIZATION; EXPRESSION; SUBTYPES; ANALOGS; SUBPOPULATION; PITUITARY; FAMILY; SSTR3 AB There is considerable controversy about the classification acid nomenclature of somatostatin receptors. To date, five distinct receptor genes have been cloned and named chronologically according to their respective publication dates, but two were unfortunately given the same appellation (SSTR(4)). Consensually, a nomenclature for the recombinant receptors has been agreed according to IUPHAR guidelines (sst(1), sst(2), sst(3), sst(4) and sst(5)). However, a more informative classification is to be preferred for the future, employing all classification criteria in an integrated scheme. It is already apparent that the five recombinant receptors fall into two classes or groups, on the basis of not only structure but also pharmacological characteristics. One class (already referred to by some as SRIF(1)) appears to comprise sst(2), sst(3) and sst(5) receptor subtypes. The other class (SRIF(2)) appears to comprise the other two recombinant receptor subtypes (sst(1) and sst(4)). This promising approach is discussed but it is acknowledged that much more data from endogenous receptors in whole tissues are needed before further recommendations on somatostatin receptor nomenclature can be made. C1 UNIV CHICAGO,HOWARD HUGHES MED INST,CHICAGO,IL 60637. SUNY STONY BROOK,STONY BROOK,NY 11794. INSERM,U159,F-75014 PARIS,FRANCE. UNIV CAMBRIDGE,GLAXO INST APPL PHARMACOL,DEPT PHARMACOL,CAMBRIDGE CB2 1QJ,ENGLAND. NIMH,CELL BIOL LAB,BETHESDA,MD 20892. MCGILL UNIV,ROYAL VICTORIA HOSP,DEPT MED NEUROL & NEUROSURG,MONTREAL,PQ H3A 1A1,CANADA. UNIV TEXAS,DEPT PHARMACOL,HOUSTON,TX 77225. BIOMEASURE INC,MILFORD,MA 01757. UNIV PENN,SCH MED,DEPT PHARMACOL,PHILADELPHIA,PA 19104. RP HOYER, D (reprint author), SANDOZ PHARMA LTD,PRECLIN RES,360-604,CH-4002 BASEL,SWITZERLAND. RI Epelbaum, Jacques/B-2263-2013; Ain, Kenneth/A-5179-2012; OI Ain, Kenneth/0000-0002-2668-934X; Hoyer, Daniel/0000-0002-1405-7089 NR 38 TC 464 Z9 466 U1 4 U2 12 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0165-6147 J9 TRENDS PHARMACOL SCI JI Trends Pharmacol. Sci. PD MAR PY 1995 VL 16 IS 3 BP 86 EP 88 DI 10.1016/S0165-6147(00)88988-9 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA QV655 UT WOS:A1995QV65500004 PM 7792934 ER PT J AU CROWE, JE AF CROWE, JE TI CURRENT APPROACHES TO THE DEVELOPMENT OF VACCINES AGAINST DISEASE CAUSED BY RESPIRATORY SYNCYTIAL VIRUS (RSV) AND PARAINFLUENZA VIRUS (PIV) - A MEETING REPORT OF THE WHO PROGRAM FOR VACCINE DEVELOPMENT SO VACCINE LA English DT Editorial Material C1 NIAID,INFECT DIS LAB,BETHESDA,MD 20892. RI Crowe, James/B-5549-2009 OI Crowe, James/0000-0002-0049-1079 NR 0 TC 52 Z9 57 U1 0 U2 0 PU BUTTERWORTH-HEINEMANN LTD PI OXFORD PA LINACRE HOUSE JORDAN HILL, OXFORD, OXON, ENGLAND OX2 8DP SN 0264-410X J9 VACCINE JI Vaccine PD MAR PY 1995 VL 13 IS 4 BP 415 EP 421 DI 10.1016/0264-410X(95)98266-D PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA QR842 UT WOS:A1995QR84200015 PM 7793140 ER PT J AU SANDERS, JM GRIFFIN, RJ BURKA, LT MATTHEWS, HB AF SANDERS, JM GRIFFIN, RJ BURKA, LT MATTHEWS, HB TI TOXICOKINETICS OF THE CHOLINOMIMETIC COMPOUND BENZYLTRIMETHYLAMMONIUM CHLORIDE IN THE MALE-RAT AND MOUSE SO XENOBIOTICA LA English DT Article ID EXCRETION AB 1. Benzyltrimethylammonium chloride (BTMAC)-derived radioactivity was rapidly eliminated from the F344 rat and the B6C3F(1) mouse following p.o. administration of 0.63-63 mg/kg of [ring-U-C-14] BTMAC. Greater than 90% of the radioactivity was excreted in urine and faeces within 24-h post-dosing. 2. BTMAC was poorly to moderately absorbed from the GI tract following p.o. administration. The percent of total dose absorbed did not exceed either 40% in the rat or 15% in the mouse. 3. Absorption was linear, but limited, over time following dermal administration of 63 mg/kg to the rat. Less than 10% of the total dose was absorbed from the skin within 24 h of BTMAC application. 4. Metabolism of BTMAC was minimal in both the rat and mouse. Toxicity (excessive cholinergic stimulation and mortality) appears to be attributable to the parent compound. 5. The limited absorption and rapid elimination of BTMAC should result in little or no bioaccumulation in tissues following repeated exposure to low levels of this compound. The results suggest that greater human health risks map be associated with acute high level exposure rather than chronic low level exposure. C1 NIEHS,ENVIRONM TOXICOL PROGRAM,CHEM BRANCH,RES TRIANGLE PK,NC 27709. NR 15 TC 2 Z9 2 U1 2 U2 2 PU TAYLOR & FRANCIS LTD LONDON PI LONDON PA ONE GUNDPOWDER SQUARE, LONDON, ENGLAND EC4A 3DE SN 0049-8254 J9 XENOBIOTICA JI Xenobiotica PD MAR PY 1995 VL 25 IS 3 BP 303 EP 313 PG 11 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA QT786 UT WOS:A1995QT78600009 PM 7618356 ER PT J AU FARRES, J WANG, TTY CUNNINGHAM, SJ WEINER, H AF FARRES, J WANG, TTY CUNNINGHAM, SJ WEINER, H TI INVESTIGATION OF THE ACTIVE-SITE CYSTEINE RESIDUE OF RAT-LIVER MITOCHONDRIAL ALDEHYDE DEHYDROGENASE BY SITE-DIRECTED MUTAGENESIS SO BIOCHEMISTRY LA English DT Article ID METHYLMALONATE-SEMIALDEHYDE DEHYDROGENASE; ESCHERICHIA-COLI; SHEEP LIVER; CHEMICAL MODIFICATION; MOLECULAR-CLONING; ALCOHOL-DEHYDROGENASE; MUTANT ENZYMES; GENE; IDENTIFICATION; CDNA AB To determine the active site cysteine residue in aldehyde dehydrogenase, we mutated amino acid residues 49, 162, and 302 of recombinantly expressed rat liver mitochondrial (class 2) aldehyde dehydrogenase. The C49A and C162A mutants were fully active tetrameric enzymes, although the C162A mutant was found to be highly unstable. The C302A mutant was also a tetramer and bound coenzyme, but lacked both dehydrogenase and esterase activities. To test for the role of cysteine 302 as a nucleophile, the residue was mutated to a serine, a poor nucleophile. This C302S mutant was active but was a much poorer catalyst, with a k(cat)/K-m value 7 x 10(5) times lower than that of the recombinant native enzyme. Unlike with native enzyme where deacylation is rate limiting, formation of the serine hemiacetal intermediate appeared to be the rate-limiting step. Cysteine 302 is the only strictly conserved cysteine residue among all the available sequences of the aldehyde dehydrogenase superfamily, supporting the role of this residue as the active site nucleophile of aldehyde dehydrogenase. C1 PURDUE UNIV,DEPT BIOCHEM,W LAFAYETTE,IN 47907. UNIV AUTONOMA BARCELONA,UNITAT CIENCIES,DEPT BIOQUIM & BIOL MOLEC,E-08193 BARCELONA,SPAIN. NCI,NUTR & MOLEC REGULAT LAB,FREDERICK,MD 21702. RI Farres, Jaume/F-8648-2016 OI Farres, Jaume/0000-0001-9069-3987 FU NIAAA NIH HHS [AA05812] NR 67 TC 133 Z9 134 U1 1 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD FEB 28 PY 1995 VL 34 IS 8 BP 2592 EP 2598 DI 10.1021/bi00008a025 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QJ955 UT WOS:A1995QJ95500025 PM 7873540 ER PT J AU RESING, KA MANSOUR, SJ HERMANN, AS JOHNSON, RS CANDIA, JM FUKASAWA, K VANDEWOUDE, GF AHN, NG AF RESING, KA MANSOUR, SJ HERMANN, AS JOHNSON, RS CANDIA, JM FUKASAWA, K VANDEWOUDE, GF AHN, NG TI DETERMINATION OF V-MOS-CATALYZED PHOSPHORYLATION SITES AND AUTOPHOSPHORYLATION SITES ON MAP KINASE KINASE BY ESI/MS SO BIOCHEMISTRY LA English DT Article ID XENOPUS-OOCYTES; ELECTROSPRAY IONIZATION; MASS-SPECTROMETRY; PROTEIN-KINASES; GROWTH-FACTOR; IDENTIFICATION; ACTIVATION; CELLS; INVITRO; ACID AB MAP kinase kinase (MAPKK), a key component of the MAP kinase cascade, is activated through phosphorylation by several protein kinases, including the oncogene v-Mos and its cellular counterpart, c-Mos. The v-Mos-catalyzed phosphorylation sites on recombinant MAPKK1 were identified by electrospray ionization mass spectrometry as S-218 and S-222, located within a sequence that aligns with the T loop structure of cAMP-dependent protein kinase; these are the same as the Raf-1 phosphorylation sites identified previously [Alessi, D. R., et al. (1994) EMBO J. 13, 1610-1619]. Phosphorylation of these sites was kinetically ordered, with S-222 preferred over S-218. Intramolecular autophosphorylation of MAPKK occurred at several residues and was increased upon the stimulation of MAPKK activity by v-Mos. Major autophosphorylation sites were residues S-298 and Y-300. Minor autophosphorylation sites included T-23, S-299, S-218, and either S-24 or S-25. Sequence similarities were noted between MAPKK autophosphorylation sites and exogenous phosphorylation sites on MAP kinase. Phosphorylation of either S-218 or S-222 was sufficient for partial MAPKK activation by Mos, and phosphorylation of S-222 alone was sufficient for autophosphorylation at S-298 and Y-300. Mass spectral analysis was also performed on MAPKK1 purified from rabbit skeletal muscle. The peptide containing S-218 and S-222 was observed in only a singly phosphorylated form, and the peptide containing S-298, S-299, and Y-300 was observed in multiply phosphorylated forms, suggesting that MAPKK is only partially phosphorylated within the T loop but significantly modified in the autophosphorylation loop under physiological conditions. C1 UNIV COLORADO, DEPT CHEM & BIOCHEM, BOULDER, CO 80309 USA. UNIV COLORADO, DEPT MOLEC CELLULAR & DEV BIOL, BOULDER, CO 80309 USA. UNIV COLORADO, HOWARD HUGHES MED INST, BOULDER, CO 80309 USA. UNIV WASHINGTON, DEPT BIOCHEM, SEATTLE, WA 98195 USA. NCI, FREDERICK CANC RES & DEV CTR, ABL BASIC RES PROGRAM, FREDERICK, MD 21702 USA. FU NCRR NIH HHS [RR05543]; NIAMS NIH HHS [AR39730]; NIGMS NIH HHS [GM48521] NR 47 TC 65 Z9 65 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 FEB 28 PY 1995 VL 34 IS 8 BP 2610 EP 2620 DI 10.1021/bi00008a027 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QJ955 UT WOS:A1995QJ95500027 PM 7873542 ER PT J AU YOKOMORI, N MOORE, R NEGISHI, M AF YOKOMORI, N MOORE, R NEGISHI, M TI SEXUALLY DIMORPHIC DNA DEMETHYLATION IN THE PROMOTER OF THE SLP (SEX-LIMITED PROTEIN) GENE IN MOUSE-LIVER SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID TESTOSTERONE 16-ALPHA-HYDROXYLASE C-P-45016-ALPHA; METHYLATION; EXPRESSION; ANDROGEN; COMPLEMENT; REGION; FAMILY; CELLS AB Mouse Slp, a duplicate of the fourth complement component (C4) gene, exhibits EDTA-independent complement activity with a hepatic expression that is male specific. To provide an underlying mechanism for the male-specific expression, we have analyzed the promoter activity of the various 5'-flanking sequences and CpG demethylation of the Slp gene. Transient transfections using HepG2 cells indicate that the element TTCCGGGC (nt -124 to -117) regulates the promoter activity. Moreover, CpG at position -121 of this regulatory element is demethylated to a much higher degree in males than in females. This sexually dimorphic DNA demethylation is consistent with the male-specific expression of the Slp gene in DBA/2 males. The regulatory element binds to the different TTCCGGGC-specific nuclear proteins depending on the methylation of the CpG site. In contrast, the corresponding CpG at position -119 of the C4 gene, which is expressed in both males and females, is demethylated at equal and high levels in both sexes. We therefore propose that the DNA demethylation and methylation-sensitive transcription factors may be a part of the regulatory mechanism for the male-specific expression of the Slp gene. RP YOKOMORI, N (reprint author), NIEHS,REPROD & DEV TOXICOL LAB,PHARMACOGENET SECT,RES TRIANGLE PK,NC 27709, USA. NR 27 TC 52 Z9 52 U1 1 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 28 PY 1995 VL 92 IS 5 BP 1302 EP 1306 DI 10.1073/pnas.92.5.1302 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA QK077 UT WOS:A1995QK07700013 PM 7877972 ER PT J AU KOHN, EC ALESSANDRO, R SPOONSTER, J WERSTO, RP LIOTTA, LA AF KOHN, EC ALESSANDRO, R SPOONSTER, J WERSTO, RP LIOTTA, LA TI ANGIOGENESIS - ROLE OF CALCIUM-MEDIATED SIGNAL-TRANSDUCTION SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID FIBROBLAST GROWTH-FACTOR; RECEPTOR TYROSINE KINASES; ENDOTHELIAL-CELLS; INOSITOL PHOSPHATES; INHIBITOR; MOTILITY; INFLUX; LOCALIZATION; ACTIVATION; INDUCTION AB During angiogenesis, endothelial cells react to stimulation with finely tuned signaling responses, The role of calcium-regulated signaling in angiogenesis has not been defined, This study investigated the calcium dependency of endothelial cell proliferation and invasion by using an inhibitor of ligand-stimulated calcium influx, CAI (carboxy-amidotriazole). Incubation with CAI significantly inhibited proliferation of human umbilical vein endothelial cells (HUVECs) in response to serum (IC50 = 1 mu M) or basic fibroblast growth factor (FGF2; P-2 < 0.005 at 10 mu M). Statistically significant inhibition of HUVEC adhesion and motility to basement membrane proteins laminin, fibronectin, and type IV collagen was demonstrated (adhesion, P-2 < 0.004-0.01; motility, P-2 < 0.009-0.018). Marked inhibition of native and FGF2-induced gelatinase activity was shown by zymogram analysis and was confirmed by Northern blot analysis. CAI inhibited HUVEC tube formation on Matrigel and inhibited in vivo angiogenesis in the chicken chorioallantoic membrane assay, 67% at 20 mu M and 56% at 10 mu M compared with 16% for an inactive CAI analog or 9% for 0.1% dimethyl sulfoxide control. Incubation of HUVECs with CAI and/or FGF2 followed by immunoprecipitation with anti-phosphotyrosine antibody showed inhibition of FGF2-induced tyrosine phosphorylation of proteins in the range 110-150 kDa. These results suggest that calcium-regulated events are important in native and FGF2-stimulated HUVEC proliferation and invasion, perhaps through regulation of FGF2-induced phosphorylation events, and indicate a role for calcium in the regulation of angiogenesis in vivo. RP KOHN, EC (reprint author), NCI,PATHOL LAB,SIGNAL TRANSDUCT & PREVENT UNIT,BLDG 10,BETHESDA,MD 20892, USA. NR 37 TC 196 Z9 199 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 FEB 28 PY 1995 VL 92 IS 5 BP 1307 EP 1311 DI 10.1073/pnas.92.5.1307 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA QK077 UT WOS:A1995QK07700014 PM 7533291 ER PT J AU CUNHA, AD RAUSCH, DM EIDEN, LE AF CUNHA, AD RAUSCH, DM EIDEN, LE TI AN EARLY INCREASE IN SOMATOSTATIN MESSENGER-RNA EXPRESSION IN THE FRONTAL-CORTEX OF RHESUS-MONKEYS INFECTED WITH SIMIAN IMMUNODEFICIENCY VIRUS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE AIDS; DEMENTIA; LENTIVIRUS; SOMATOSTATIN ID CEREBRAL-CORTEX; NEURONS; BRAIN; LOCALIZATION; ENCEPHALITIS; DEMENTIA; GENE AB Motor and cognitive impairment is common in human immunodeficiency virus disease in humans and simian immunodeficiency virus (SIV) disease in rhesus monkeys. We have examined peptide neurotransmitter expression in the frontal cortex of SIV-infected rhesus monkeys to identify alterations in cortical neurons that might explain this impairment. A 2-fold higher number of preprosomatostatin (SRIF) mRNA-positive interneurons was observed in layer IV of frontal cortex in two separate cohorts of SIV-infected animals compared to uninfected controls. Increased SRIF mRNA expression in layer IV was independent of clinical signs of immunodeficiency disease and was associated with both motor and cognitive impairment. Altered SRIF mRNA expression in deeper cortical layers was associated specifically with motor impairment. Increased SRIF mRNA expression occurred without detectable changes in cortical cell density. These data suggest two mechanisms for cortical dysfunction associated with lentivirus infection. Increased SRIF mRNA expression in layer IV may be due to altered patterns of activity in cortical afferents that project to layer IV, while increased SRIF mRNA expression in deeper cortical layers could reflect susceptibility to locally generated mediators in response to primate lentivirus infection of the brain. Altered function of somatostatinergic interneurons may contribute to primate lentivirus-induced encephalopathy. RP CUNHA, AD (reprint author), NIMH,CELL BIOL LAB,MOLEC NEUROSCI SECT,BLDG 36,ROOM 3A 17,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 32 TC 0 Z9 0 U1 1 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 28 PY 1995 VL 92 IS 5 BP 1371 EP 1375 DI 10.1073/pnas.92.5.1371 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA QK077 UT WOS:A1995QK07700027 ER PT J AU LEHEL, C OLAH, Z JAKAB, G ANDERSON, WB AF LEHEL, C OLAH, Z JAKAB, G ANDERSON, WB TI PROTEIN-KINASE C-EPSILON IS LOCALIZED TO THE GOLGI VIA ITS ZINC-FINGER DOMAIN AND MODULATES GOLGI FUNCTION SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID PHORBOL ESTERS; CELLS; RECONSTITUTION; ASSOCIATION; ACTIVATION; MEMBRANE; ISOFORM; ALPHA; TUMORIGENICITY; FIBROBLASTS AB Protein kinase C (PKC) is a multigene family of serine/threonine kinases that are central to many signal transduction pathways. Among the PKC isozymes, only PKC epsilon has been reported to exhibit full oncogenic potential. PKC epsilon also displays unique substrate specificity and intracellular localization. To examine the interrelationship between the biological effects and domain structure of PKC epsilon, NIH 3T3 cells were stably transfected to overexpress different epitope-tagged fragments of PKC epsilon. The overexpressed proteins each contain the epsilon-tag peptide at the C terminus to allow ready detection with an antibody specific for the tag. The holo-PKC epsilon was found to localize with the Golgi network and other compartments, whereas the zinc-finger domain localized exclusively at the Golgi. Golgi-specific glycosaminoglycan sulfation was strongly inhibited in cells overexpressing either holo-PKC epsilon or its zinc-finger domain, while the secretion of sulfated glycosaminoglycans into the medium was impaired in cells expressing the PKC epsilon zinc-finger domain. Thus, these results suggest that PKC epsilon may be involved in specifically regulating Golgi-related processes. Further, the results indicate that PKC epsilon domains other than the kinase domain may also have biological activity and that the zinc-finger domain may function as a subcellular localization signal. C1 NCI,CELLULAR ONCOL LAB,BETHESDA,MD 20892. NINCDS,CLIN NEUROSCI BRANCH,BETHESDA,MD 20892. NINCDS,EXPTL NEUROPATHOL LAB,BETHESDA,MD 20892. NR 33 TC 115 Z9 116 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 28 PY 1995 VL 92 IS 5 BP 1406 EP 1410 DI 10.1073/pnas.92.5.1406 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA QK077 UT WOS:A1995QK07700034 PM 7877991 ER PT J AU BLANCO, JCG WANG, IM TSAI, SY TSAI, MJ OMALLEY, BW JURUTKA, PW HAUSSLER, MR OZATO, K AF BLANCO, JCG WANG, IM TSAI, SY TSAI, MJ OMALLEY, BW JURUTKA, PW HAUSSLER, MR OZATO, K TI TRANSCRIPTION FACTOR TFIIB AND THE VITAMIN-D RECEPTOR COOPERATIVELY ACTIVATE LIGAND-DEPENDENT TRANSCRIPTION SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE BASAL TRANSCRIPTION FACTOR; NUCLEAR HORMONE RECEPTOR; ACTIVATOR; TRANSFECTION; VITAMIN-D-RESPONSIVE ELEMENT ID RNA POLYMERASE-II; RETINOIC ACID RECEPTOR; FUNCTIONAL DOMAINS; GENE; HORMONE; BINDING; CELLS; DNA; S300-II; MEDIATE AB The active metabolite of vitamin D, 1,25-dihydroxyvitamin D-3 [1,25(OH)(2)D-3], regulates gene transcription through binding to the vitamin D receptor (VDR), a member of the nuclear hormone receptor superfamily. Sequence-specific transcription factors, including nuclear hormone receptors, are thought to interact with the basal transcription complex to regulate transcription. In glutathione S-transferase fusion-based protein-protein binding assays we found that VDR specifically binds to TFIIB, a component of the basal complex, and that the interaction requires select domains of each protein. To assess the functional significance of this interaction, transfection assays were performed with a 1,25(OH)(2)D-3-responsive reporter construct. In P19 embryonal carcinoma cells cotransfection of VDR and TFIIB cooperatively activated reporter transcription, while each factor alone gave very low to no activation. This activation was dependent on 1,25(OH)(2)D-3 and the dose of TFIIB and VDR transfected, demonstrating that a nuclear hormone receptor functionally interacts with TFIIB in vivo. In contrast, transfection of NIH 3T3 cells generated strong reporter activation by 1,25(OH)(2)D-3 in the presence of VDR alone, and cotransfection of TFIIB led to specific dose-dependent repression of reporter activity. Taken together, these results indicate that TFIIB-nuclear hormone receptor interaction plays a critical role in ligand-dependent transcription, which is apparently modulated by a cell-type-specific accessory factor. C1 NICHHD,MOLEC GROWTH REGULAT LAB,BETHESDA,MD 20892. BAYLOR COLL MED,DEPT CELL BIOL,HOUSTON,TX 77030. UNIV ARIZONA,COLL MED,DEPT BIOCHEM,TUCSON,AZ 85724. OI Jurutka, Peter/0000-0002-4950-9161 FU NIAMS NIH HHS [AR15781]; NIDDK NIH HHS [DK33351] NR 42 TC 171 Z9 172 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 28 PY 1995 VL 92 IS 5 BP 1535 EP 1539 DI 10.1073/pnas.92.5.1535 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA QK077 UT WOS:A1995QK07700060 PM 7878015 ER PT J AU BUSCAIL, L ESTEVE, JP SAINTLAURENT, N BERTRAND, V REISINE, T OCARROLL, AM BELL, GI SCHALLY, AV VAYSSE, N SUSINI, C AF BUSCAIL, L ESTEVE, JP SAINTLAURENT, N BERTRAND, V REISINE, T OCARROLL, AM BELL, GI SCHALLY, AV VAYSSE, N SUSINI, C TI INHIBITION OF CELL-PROLIFERATION BY THE SOMATOSTATIN ANALOG RC-160 IS MEDIATED BY SOMATOSTATIN RECEPTOR SUBTYPES SSTR2 AND SSTR5 THROUGH DIFFERENT MECHANISMS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID MOLECULAR-CLONING; GROWTH; DEPHOSPHORYLATION; EXPRESSION; HYDROLYSIS; SECRETION; BOMBESIN; CALCIUM; TUMORS; TRACT AB Effects of the stable somatostatin analogue RC-160 on cell proliferation, tyrosine phosphatase activity, and intracellular calcium concentration were investigated in CHO cells expressing the five somatostatin receptor subtypes SSTR1 to -5. Binding experiments were performed on crude membranes by using [I-125-labeled Tyr(11)] somatostatin-14; RC-160 exhibited moderate-to-high affinities for SSTR2, -3, and -5 (IC50, 0.17, 0.1, and 21 nM, respectively) and low affinity for SSTR1 and -4 (IC50, 200 and 620 nM, respectively). Cell proliferation was induced in CHO cells by 10% (vol/vol) fetal calf serum, 1 mu M insulin, or 0.1 mu M cholecystokinin (CCK)-8; RC-160 inhibited serum-induced proliferation of CHO cells expressing SSTR2 and SSTR5 (EC(50), 53 and 150 pM, respectively) but had no effect on growth of cells expressing SSTR1, -3, or -4. In SSTR2-expressing cells, orthovanadate suppressed the growth inhibitory effect of RC-160. This analogue inhibited insulin-induced proliferation and rapidly stimulated the activity of a tyrosine phosphatase in only this cellular clone. This latter effect was observed at doses of RC-160 (EC(50), 4.6 pM) similar to those required to inhibit growth (EC(50), 53 pM) and binding to the receptor (IC50, 170 pM), implicating tyrosine phosphatase as a transducer of the growth inhibition signal in SSTR2-expressing cells. In SSTR5-expressing cells, the phosphatase pathway was not involved in the inhibitory effect of RC-160 on cell growth, since this action was not influenced by tyrosine and serine/threonine phosphatase inhibitors. In addition, in SSTR5-expressing cells, RC-160 inhibited CCK-stimulated intracellular calcium mobilization at doses (EC(50), 0.35 nM) similar to those necessary to inhibit somatostatin-14 binding (IC50, 21 nM) and CCK-induced cell proliferation (EC(50), 1.1 nhl). This suggests that the inositol phospholipid/calcium pathway could be involved in the antiproliferative effect of RC-160 mediated by SSTR5 in these cells. RC-160 had no effect on the basal or carbachol-stimulated calcium concentration in cells expressing SSTR1 to -4. Thus, we conclude that SSTR2 and SSTR5 bind RC-160 with high affinity and mediate the RC-160-induced inhibition of cell growth by distinct mechanisms. C1 UNIV PENN,SCH MED,DEPT PHARMACOL,PHILADELPHIA,PA 19114. NIMH,CELL BIOL LAB,BETHESDA,MD 20892. UNIV CHICAGO,HOWARD HUGHES MED INST,CHICAGO,IL 60637. VET AFFAIRS MED CTR,NEW ORLEANS,LA 70112. TULANE UNIV,SCH MED,NEW ORLEANS,LA 70112. RP BUSCAIL, L (reprint author), CHU RANGUEIL,INST LOUIS BUGNARD,INSERM,U151,F-31054 TOULOUSE,FRANCE. RI Ain, Kenneth/A-5179-2012 OI Ain, Kenneth/0000-0002-2668-934X NR 36 TC 263 Z9 267 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 FEB 28 PY 1995 VL 92 IS 5 BP 1580 EP 1584 DI 10.1073/pnas.92.5.1580 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA QK077 UT WOS:A1995QK07700069 PM 7878022 ER PT J AU ABDELMALEK, Z SWOPE, VB SUZUKI, I AKCALI, C HARRIGER, MD BOYCE, ST URABE, K HEARING, VJ AF ABDELMALEK, Z SWOPE, VB SUZUKI, I AKCALI, C HARRIGER, MD BOYCE, ST URABE, K HEARING, VJ TI MITOGENIC AND MELANOGENIC STIMULATION OF NORMAL HUMAN MELANOCYTES BY MELANOTROPIC PEPTIDES SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CULTURED HUMAN MELANOCYTES; MELANOMA-CELLS; MSH RECEPTORS; HORMONE; EXPRESSION; INVITRO; PIGMENTATION; TYROSINASE; OUTGROWTH; CLONING AB The significance of melanotropic hormones as physiologic regulators of cutaneous pigmentation in humans is still controversial. Until recently, no direct effect for melanotropins could be demonstrated on human melanocytes, Here we present conclusive evidence that alpha-melanotropin (alpha-melanocyte-stimulating hormone, alpha-MSH) and the related hormone corticotropin (adrenocorticotropic hormone, ACTH) stimulate the proliferation and melanogenesis of human melanocytes maintained in culture in a growth medium lacking any AMP inducer. The minimal. effective dose of either hormone is 0.1 nM. In time-course experiments, the increase in cell number and tyrosinase activity became evident after one treatment of the melanocytes with 100 nM alpha-MSH for 48 hr. The mitogenic effect gradually increased to 50-270% above control, depending on the individual melanocyte strain, with continuous treatment with 100 nM alpha-MSH for 8 days, whereas the melanogenic effect became maximal (70-450% increase above control) after 4 days of treatment. Western blot analysis of tyrosinase and the tyrosinase-related proteins TRP-1 and TRP-2 revealed that alpha-MSH increased the expression of those three melanogenic proteins, This was not accompanied by any change in their mRNA levels after brief (1.5-24 hr) or prolonged (6 days) treatment with 100 nM alpha-MSH, suggesting that the increased expression of these melanogenic proteins was due to posttranscriptional events. These results demonstrate both mitogenic and melanogenic effects of alpha-MSH and ACTH on human melanocytes. That both hormones are effective at subnanomolar concentrations, combined with the presence of melanotropin receptors on human melanocytes, strongly suggests that these melanotropins play a physiologic role in regulating human cutaneous pigmentation. C1 POLA LABS,YOKOHAMA,KANAGAWA,JAPAN. SHRINERS BURNS INST,CINCINNATI,OH 45220. UNIV CINCINNATI,COLL MED,DEPT SURG,CINCINNATI,OH 45267. NIH,CELL BIOL LAB,BETHESDA,MD 20892. RP ABDELMALEK, Z (reprint author), UNIV CINCINNATI,COLL MED,DEPT DERMATOL,POB 670592,CINCINNATI,OH 45267, USA. FU NIEHS NIH HHS [5P30 ES06096-02] NR 37 TC 275 Z9 288 U1 3 U2 8 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 28 PY 1995 VL 92 IS 5 BP 1789 EP 1793 DI 10.1073/pnas.92.5.1789 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA QK077 UT WOS:A1995QK07700111 PM 7878059 ER PT J AU THALL, PF SIMON, RM ESTEY, EH AF THALL, PF SIMON, RM ESTEY, EH TI BAYESIAN SEQUENTIAL MONITORING DESIGNS FOR SINGLE-ARM CLINICAL-TRIALS WITH MULTIPLE OUTCOMES SO STATISTICS IN MEDICINE LA English DT Article ID END-POINTS; ENDPOINTS AB We present a Bayesian approach for monitoring multiple outcomes in single-arm clinical trials. Each patient's response may include both adverse events and efficacy outcomes, possibly occurring at different study times. We use a Dirichlet-multinomial model to accommodate general discrete multivariate responses. We present Bayesian decision criteria and monitoring boundaries for early termination of studies with unacceptably high rates of adverse outcomes or with low rates of desirable outcomes. Each stopping rule is constructed either to maintain equivalence or to achieve a specified level of improvement of a particular event rate for the experimental treatment, compared with that of standard therapy. We avoid explicit specification of costs and a loss function. We evaluate the joint behaviour of the multiple decision rules using frequentist criteria. One chooses a design by considering several parameterizations under relevant fixed values of the multiple outcome probability vector. Applications include trials where response is the cross-product of multiple simultaneous binary outcomes, and hierarchical structures that reflect successive stages of treatment response, disease progression and survival. We illustrate the approach with a variety of single-arm cancer trials, including bio-chemotherapy acute leukaemia trials, bone marrow transplantation trials, and an anti-infection trial. The number of elementary patient outcomes in each of these trials varies from three to seven, with as many as four monitoring boundaries running simultaneously. We provide general guidelines for eliciting and parameterizing Dirichlet priors and for specifying design parameters. C1 NCI,DIV CANC TREATMENT,BIOMETR RES BRANCH,BETHESDA,MD 20892. UNIV TEXAS,MD ANDERSON CANC CTR,DEPT HEMATOL,HOUSTON,TX 77030. RP THALL, PF (reprint author), UNIV TEXAS,MD ANDERSON CANC CTR,DEPT BIOMATH,BOX 237,1515 HOLOCOMBE BLVD,HOUSTON,TX 77030, USA. NR 26 TC 104 Z9 105 U1 0 U2 6 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0277-6715 J9 STAT MED JI Stat. Med. PD FEB 28 PY 1995 VL 14 IS 4 BP 357 EP 379 DI 10.1002/sim.4780140404 PG 23 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 QH434 UT WOS:A1995QH43400003 PM 7746977 ER PT J AU OBRIEN, MC UENO, T JAHAN, N ZAJAC-KAYE, M MITSUYA, H AF OBRIEN, MC UENO, T JAHAN, N ZAJAC-KAYE, M MITSUYA, H TI HIV-1 EXPRESSION INDUCED BY ANTICANCER AGENTS IN LATENTLY HIV-1-INFECTED ACH2 CELLS SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; NECROSIS FACTOR-ALPHA; NF-KAPPA-B; TRANSCRIPTION FACTOR; T-CELLS; GENE; DNA; METHYLATION; INDUCTION; CYTOTOXICITY AB The expression of human immunodeficiency virus type 1 (HIV-1) in infected cells is induced (or enhanced) by a number of agents including phorbol myristate acetate (PMA), phytohemagglutinin (PHA), certain infectious agents, certain cytokines, and ultraviolet light. ACH2 cells represent latently HIV-1-infected T-cells, which produce only a low level of HIV-1 in vitro. We found that various anti-cancer agents including 5-azacytidine (5-AZC), 5-fluorouracil (5-FU), methotrexate, cytosine arabinoside, and vinblastine potentiated the expression of HIV-1 in ACH2 cells. There was no evidence of altered DNA methylation patterns in ACH2 cells cultured with 5-FU unlike with 5-AZC. The NF-KB binding activity was found to be enhanced in ACH2 cells exposed to 5-FU (but not in those exposed to 5-AZC) as assessed by the mobility shift assay using an oligonucleotide containing two NF-kappa B binding sites. These data suggest that the use of certain anti-cancer agents may induce (or enhance) the expression of HIV-1. (C) 1995 Academic Press, Inc. C1 NCI, DIV CANC TREATMENT, BIOL CHEM LAB, DEV THERAPEUT PROGRAM, BETHESDA, MD 20892 USA. RP OBRIEN, MC (reprint author), NCI, CLIN ONCOL PROGRAM, MED BRANCH, EXPTL RETROVIROL SECT, BETHESDA, MD 20892 USA. RI Ueno, Takamasa/F-5788-2013 OI Ueno, Takamasa/0000-0003-4852-4236 NR 31 TC 17 Z9 18 U1 0 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD FEB 27 PY 1995 VL 207 IS 3 BP 903 EP 909 DI 10.1006/bbrc.1995.1271 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA QJ139 UT WOS:A1995QJ13900004 PM 7532407 ER PT J AU VONLUBITZ, DKJE CARTER, MF DEUTSCH, SI LIN, RCS MASTROPAOLO, J MESHULAM, Y JACOBSON, KA AF VONLUBITZ, DKJE CARTER, MF DEUTSCH, SI LIN, RCS MASTROPAOLO, J MESHULAM, Y JACOBSON, KA TI THE EFFECTS OF ADENOSINE A(3) RECEPTOR STIMULATION ON SEIZURES IN MICE SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE SEIZURE; ADENOSINE A(3) RECEPTOR; PROTECTION; (MOUSE) ID MOLECULAR-CLONING; MAST-CELLS; RELEASE; DAMAGE; BRAIN; ACID; RAT AB We have previously shown that acute preischemic adenosine A(3) receptor stimulation results in an increased postischemic damage, while chronic stimulation of this receptor diminishes it. Since several pathophysiological phenomena are common for both ischemia and seizures, we have explored the effect of acute and chronic administration of the adenosine A(3) receptor selective agonist IB-MECA (N-6-(3-iodobenzyl) adenosine-5'-N-methylcarboxamide) prior to seizures induced by N-methyl-D-aspartate (NMDA), pentamethylenetetrazole, or electric shock. At 100 mu g/kg, acutely injected IB-MECA was protective in chemically but not electrically induced seizures. In chronic administration of IB-MECA, significant protection against chemically induced seizures was obtained in all studied measures, i.e., seizure latency, neurological impairment, and survival. Although threshold voltage was unchanged in electrically induced seizures, a chronic regimen of IB-MECA significantly reduced postepileptic mortality. Since the combination of an arteriole-constricting compound 48/80 and hypotension-inducing clonidine injected prior to NMDA results in a significant protection against seizures, and since acute stimulation of adenosine A(3) receptor causes both arteriolar constriction and severe hypotension, there is a possibility that the protection obtained by the acutely administered drug may result from inadequate delivery of chemoconvulsants to the brain. It is, however, unknown whether the protective effect of chronically administered IB-MECA is related to the effect of the drug on blood flow, neuronal mechanisms, or both. C1 VET AFFAIRS MED CTR, PSYCHIAT SERV, WASHINGTON, DC 20422 USA. HAHNEMANN UNIV, DEPT PHYSIOL & BIOPHYS, PHILADELPHIA, PA 19102 USA. RP NIDDK, 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 [Z99 DK999999, Z01 DK031117-20] NR 29 TC 66 Z9 67 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 FEB 24 PY 1995 VL 275 IS 1 BP 23 EP 29 DI 10.1016/0014-2999(94)00734-O PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA QJ702 UT WOS:A1995QJ70200004 PM 7774659 ER PT J AU BUBB, MR SPECTOR, I BERSHADSKY, AD KORN, ED AF BUBB, MR SPECTOR, I BERSHADSKY, AD KORN, ED TI SWINHOLIDE-A IS A MICROFILAMENT DISRUPTING MARINE TOXIN THAT STABILIZES ACTIN DIMERS AND SEVERS ACTIN-FILAMENTS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Note ID SPONGE THEONELLA-SWINHOEI; F-ACTIN; CYTOCHALASIN-D; POLYMERIZATION; GELSOLIN; BINDING; MACROLIDE; DEPOLYMERIZATION; PENTOXIFYLLINE; ORGANIZATION AB Swinholide A, isolated from the marine sponge Theonella swinhoei, is a 44-carbon ring dimeric dilactone macrolide with a 2-fold axis of symmetry. Recent studies have elucidated its unusual structure and shown that it has potent cytotoxic activity, We now report that swinholide A disrupts the actin cytoskeleton of cells grown in culture, sequesters actin dimers in vitro in both polymerizing and non-polymerizing buffers with a binding stoichiometry of one swinholide A molecule per actin dimer, and rapidly severs F-actin in vitro with high cooperativity, These unique properties are sufficient to explain the cytotoxicity of swinholide A. They also suggest that swinholide A might be a model for studies of the mechanism of action of F-actin severing proteins and be therapeutically useful in conditions where filamentous actin contributes to pathologically high viscosities. C1 NHLBI,CELL BIOL LAB,BETHESDA,MD 20892. SUNY STONY BROOK,HLTH SCI CTR,DEPT PHYSIOL & BIOPHYS,STONY BROOK,NY 11794. WEIZMANN INST SCI,DEPT CHEM IMMUNOL,IL-76100 REHOVOT,ISRAEL. RI Korn, Edward/F-9929-2012 NR 37 TC 121 Z9 125 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD FEB 24 PY 1995 VL 270 IS 8 BP 3463 EP 3466 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QH688 UT WOS:A1995QH68800001 PM 7876075 ER PT J AU COPELAND, WC TAN, XH AF COPELAND, WC TAN, XH TI ACTIVE-SITE MAPPING OF THE CATALYTIC MOUSE PRIMASE SUBUNIT BY ALANINE SCANNING MUTAGENESIS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DNA-POLYMERASE-ALPHA; MOLECULAR-CLONING; CRYSTAL-STRUCTURE; ESCHERICHIA-COLI; INITIATION; YEAST; RNA; REPLICATION; CELLS; PURIFICATION AB In the eukaryotic cell, DNA synthesis is initiated by DNA primase associated with DNA polymerase alpha. The eukaryotic primase is composed of two subunits, p49 and p58, where the p49 subunit contains the catalytic active site, Mutagenesis of the cDNA for the p49 subunit was initiated to demonstrate a functional correlation of conserved residues among the eukaryotic primases and DNA polymerases, Fourteen invariant charged residues in the smaller catalytic mouse primase subunit, p49, were changed to alanine, These mutant proteins were expressed, purified, and enzymatically characterized for primer synthesis, Analyses of the mutant proteins indicate that residues 104-111 are most critical for primer synthesis and form part of the active site, Alanine substitution in residues Glu(105), Asp(109) and Asp(111) produced protein with no detectable activity in direct primase assays, indicating that these residues may form part of a conserved carboxylic triad also observed in the active sites of DNA polymerases and reverse transcriptases, Ah other mutant proteins showed a dramatic decrease in catalysis, while mutation of two residues, Arg(162) and Arg(163), caused an increase in K-m(NTP). Analysis of these mutant proteins in specific assays designed to separately investigate dinucleotide formation (initiation) and elongation of primer indicates that these two activities utilize the same active site within the p49 subunit, Finally, mutations in three active site codons produced protein with reduced affinity with the p58 subunit, suggesting that p58 may interact directly with active site residues. RP COPELAND, WC (reprint author), NIEHS,MOLEC GENET LAB,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 39 TC 28 Z9 28 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD FEB 24 PY 1995 VL 270 IS 8 BP 3905 EP 3913 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QH688 UT WOS:A1995QH68800067 PM 7876136 ER PT J AU ISHIKAWA, Y MUKAIDA, N KUNO, K RICE, N OKAMOTO, S MATSUSHIMA, K AF ISHIKAWA, Y MUKAIDA, N KUNO, K RICE, N OKAMOTO, S MATSUSHIMA, K TI ESTABLISHMENT OF LIPOPOLYSACCHARIDE-DEPENDENT NUCLEAR FACTOR KAPPA-B ACTIVATION IN A CELL-FREE SYSTEM SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TUMOR-NECROSIS-FACTOR; PROTEIN-TYROSINE PHOSPHORYLATION; MESSENGER-RNA EXPRESSION; FACTOR-ALPHA; BACTERIAL LIPOPOLYSACCHARIDE; TRANSCRIPTION FACTOR; INTERLEUKIN-8 GENE; BINDING PROTEIN; INFLAMMATORY CYTOKINES; MURINE MACROPHAGES AB Nuclear factor kappa B (NF-kappa B), consisting of p50 and p65, is bound to a cytoplasmic retention protein, I kappa B, in a resting state, and the stimulation of cells with a variety of inflammatory stimuli induces the dissociation of NF-kappa B from I kappa B and the nuclear translocation of NF-kappa B, thereby activating several genes involved in inflammatory responses, such as interleukin (IL)-6, IL-8, and tumor necrosis factor alpha. In order to elucidate the precise mechanism of NE-kappa B activation, we have established Lipopolysaccharide (LPS)-dependent NF-kappa B activation in a cell-free system using plasma membrane-enriched, cytosol, and nuclear fractions extracted from a human monocytic cell Line, THP-1, by disruption with sonication followed by a differential centrifugation. The combination of plasma membrane enriched fraction and cytosol was sufficient to activate NF-kappa B in a LPS/CD14-dependent manner only in the presence of ATP as judged by the binding of NF-kappa B to the IL-8 gene kappa B site on an electrophoretic mobility shift assay. LPS-dependent NP-kappa B activation was inhibited by protein kinase inhibitors, such as staurosporine, herbimycin A, tyrphostin, and genistein, but not mitogen-activated protein kinase substrate, cGMP-dependent protein kinase, cAMP-dependent protein kinase, protein kinase C, and calmodulin-dependent protein kinase II inhibitory peptides, suggesting that staurosporine-sensitive kinase(s) as well as tyrosine kinase(s) are involved in LPS-mediated NF-kappa B activation. In addition, LPS induced the phosphorylation of I kappa B-alpha, starting at 5 min after the stimulation in a cell-free system. Moreover, the phosphorylation was inhibited by herbimycin A and tyrphostin, but not staurosporine, suggesting that these protein kinase inhibitors act at distinct steps of signal transmission. Establishment of ligand-dependent activation of NF-kappa B in a cell-free system will facilitate identification of protein kinase(s) and its substrate(s) involved in LPS-mediated NF-kappa B activation. C1 KANAZAWA UNIV,CANC RES INST,DEPT PHARMACOL,KANAZAWA,ISHIKAWA 920,JAPAN. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. RI Mukaida, Naofumi/D-7623-2011 OI Mukaida, Naofumi/0000-0002-4193-1851 NR 42 TC 77 Z9 77 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD FEB 24 PY 1995 VL 270 IS 8 BP 4158 EP 4164 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QH688 UT WOS:A1995QH68800102 PM 7876168 ER PT J AU SCHOKET, B POIRIER, MC VINCZE, I AF SCHOKET, B POIRIER, MC VINCZE, I TI BIOMONITORING OF GENOTOXIC EXPOSURE IN ALUMINUM PLANT WORKERS BY DETERMINATION OF DNA-ADDUCTS IN HUMAN PERIPHERAL-BLOOD LYMPHOCYTES SO SCIENCE OF THE TOTAL ENVIRONMENT LA English DT Article; Proceedings Paper CT International Conference on the Environmental and Health Aspects Related to the Production of Aluminium CY JUN 28-30, 1994 CL BERGEN, NORWAY SP NATL INST OCCUPAT HLTH OSLO, NORDIC ALUMINIUM IND SECRETARIAT HLTH ENVIRONM & SAFETY DE DNA ADDUCT; P-32 POSTLABELING; ELISA; HUMAN; BIOMONITORING; ALUMINUM; BLOOD; LYMPHOCYTE; POLYCYCLIC AROMATIC HYDROCARBON ID POLYCYCLIC AROMATIC-HYDROCARBONS; COKE-OVEN WORKERS; P-32 POSTLABELING ASSAY; FOUNDRY WORKERS; MOLECULAR EPIDEMIOLOGY; DEOXYRIBONUCLEIC-ACID; CIGARETTE-SMOKING; LUNG-CANCER; CELLS; CARCINOGENS AB A longitudinal human biomonitoring study has been performed in two Hungarian primary aluminium production plants that operated Soderberg cells. Carcinogen-DNA adducts have been determined by P-32-postlabelling and competitive enzyme-linked immunosorbent assay in peripheral blood lymphocytes from potroom workers and occupationally unexposed control individuals. Blood samples were collected on three occasions; the first two occasions were 1 year apart during normal operation, and the last samples were taken 6 months after close-down of aluminium production. Assays of the first set of samples demonstrated no significant difference between the control group and workers in Plant I. Workers in Plant II had significantly higher DNA adduct levels than individuals in the control group and workers in Plant I. One year later a significant elevation of DNA adducts was detected in Plant I so that values approached those seen in Plant II, which remained unchanged. In the last sample set there was no difference between former potroom workers and occupationally unexposed individuals. The results suggest that carcinogen-DNA adducts are a useful biomarker for monitoring occupational genotoxic exposure to polycyclic aromatic hydrocarbons, and that the findings can contribute to improved health risk assessment. C1 NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BETHESDA,MD 20892. RP SCHOKET, B (reprint author), JOHAN BELA NATL INST PUBL HLTH,DEPT BIOCHEM,GYALI UT 2-6,H-1097 BUDAPEST,HUNGARY. NR 43 TC 19 Z9 20 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0048-9697 J9 SCI TOTAL ENVIRON JI Sci. Total Environ. PD FEB 24 PY 1995 VL 163 BP 153 EP 163 DI 10.1016/0048-9697(95)04492-J PG 11 WC Environmental Sciences SC Environmental Sciences & Ecology GA QL128 UT WOS:A1995QL12800015 PM 7716493 ER PT J AU BREWER, HB AF BREWER, HB TI LIPIDS - INTRODUCTION SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Editorial Material RP BREWER, HB (reprint author), NHLBI,BLDG 10,ROOM 7N115,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CAHNERS PUBL CO PI NEW YORK PA 249 WEST 17 STREET, NEW YORK, NY 10011 SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD FEB 23 PY 1995 VL 75 IS 6 BP B43 EP B44 DI 10.1016/0002-9149(95)80010-P PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA QH854 UT WOS:A1995QH85400010 PM 7863973 ER PT J AU ROBERTS, WC STEINBERG, D FALK, E ALEXANDER, RW FOGELMAN, AM BREWER, HB GANZ, P GIMBRONE, MA MILLER, GJ HARRISON, DG KRAUSS, RM GRUNDY, SM WEITZ, JI HARKER, LA AF ROBERTS, WC STEINBERG, D FALK, E ALEXANDER, RW FOGELMAN, AM BREWER, HB GANZ, P GIMBRONE, MA MILLER, GJ HARRISON, DG KRAUSS, RM GRUNDY, SM WEITZ, JI HARKER, LA TI ROUND-TABLE DISCUSSION SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Discussion C1 EMORY UNIV,SCH MED,DIV CARDIOL,ATLANTA,GA 30322. ODENSE UNIV,INST FORENS MED,DK-5000 ODENSE C,DENMARK. UNIV CALIF LOS ANGELES,SCH MED,DEPT MED,DIV CARDIOL,LOS ANGELES,CA 90024. NHLBI,MOLEC DIS BRANCH,BETHESDA,MD 20892. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DIV VASC RES,BOSTON,MA 02215. ST BARTHOLOMEWS HOSP,WOLFSON INST PREVENTAT MED,MRC,EPIDEMIOL & MED CARE UNIT,LONDON EC1M 6BQ,ENGLAND. UNIV CALIF BERKELEY,LAWRENCE BERKELEY LAB,DONNER LAB,BERKELEY,CA 94720. HAMILTON CIV HOSP,RES CTR,EXPTL THROMBOSIS & ATHEROSCLEROSIS RES GRP,HAMILTON,ON L8V 1C3,CANADA. UNIV TEXAS,SW MED CTR,DEPT CLIN NUTR,DALLAS,TX 75235. EMORY UNIV,DIV HEMATOL & ONCOL,ATLANTA,GA 30322. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DIV CARDIOVASC,BOSTON,MA 02115. RP ROBERTS, WC (reprint author), BAYLOR UNIV,MED CTR,BAYLOR CARDIOVASC INST,DALLAS,TX, USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU CAHNERS PUBL CO PI NEW YORK PA 249 WEST 17 STREET, NEW YORK, NY 10011 SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD FEB 23 PY 1995 VL 75 IS 6 BP B93 EP B97 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA QH854 UT WOS:A1995QH85400021 ER PT J AU PERLMAN, JA JOHNSON, K NAYFIELD, S FORD, LG AF PERLMAN, JA JOHNSON, K NAYFIELD, S FORD, LG TI ESTROGEN REPLACEMENT THERAPY IN BREAST-CANCER SURVIVORS SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter RP PERLMAN, JA (reprint author), NCI,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 FEB 22 PY 1995 VL 273 IS 8 BP 619 EP 620 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA QG748 UT WOS:A1995QG74800018 PM 7844867 ER PT J AU MAHADEVAN, D THANKI, N AROCA, P MCPHIE, P YU, JC BEELER, J SANTOS, E WLODAWER, A HEIDARAN, MA AF MAHADEVAN, D THANKI, N AROCA, P MCPHIE, P YU, JC BEELER, J SANTOS, E WLODAWER, A HEIDARAN, MA TI A DIVALENT METAL-ION BINDING-SITE IN THE KINASE INSERT DOMAIN OF THE ALPHA-PLATELET-DERIVED GROWTH-FACTOR RECEPTOR REGULATES ITS ASSOCIATION WITH SH2 DOMAINS SO BIOCHEMISTRY LA English DT Article ID DEPENDENT PROTEIN-KINASE; FACTOR-BETA-RECEPTOR; PHOSPHATIDYLINOSITOL 3-KINASE; SIGNAL TRANSDUCTION; SECONDARY STRUCTURE; CATALYTIC SUBUNIT; PDGF RECEPTOR; NITROCELLULOSE MEMBRANE; GLOBULAR PROTEINS; HIGH-AFFINITY AB TO investigate the effects of metal ion binding to the alpha-PDGFR kinase insert domain, a PCR product representing amino acid residues 691-795 (104 amino acids) was bacterially expressed and purified. Secondary structure prediction and circular dichroism spectroscopy indicated this domain to be a mixed alpha+beta protein with a large coil/turn contribution. This 16 kDa, soluble, nonphosphorylated domain bound to Ca-45(2+) and Zn-65(2+) through a common shared site. Of the unlabeled divalent and trivalent metal ions tested, Ho3+ = Zn2+ > Ni2+ > Ca2+ = Mn2+ > Mg2+, Ba2+ in competing for Ca-45(2+) binding to this domain. In the presence of Ca2+ ions, the conformation of the KI domain changed significantly, and this changed conformation was resistant to subtilisin proteolysis. However, in the presence of Zn2+ ions, the conformation of the KI domain changed only slightly. Nevertheless, Zn2+ ions were more effective in rendering the KI domain resistant to proteolysis as compared to that shown by Ca2+ ions. In vitro binding studies using purified baculovirus-expressed alpha-PDGFR showed a marked increase in binding the p85 N-SH2 domain in the presence of Ca2+ or Zn2+ ions (K-D = 0.5 mu M), suggesting that metal ion binding enhances association of the p85 N-SH2 domain with the receptor. To confirm this, association of the alpha-PDGFR with the p85 N-SH2 domain was tested in the presence of the KI domain. The nonphosphorylated KI domain was effective in competing with the alpha-PDGFR for the binding of the p85 N-SH2 domain. This effect was more pronounced in the presence of Ca2+ ions. Microinjection of this domain into Xenopus oocytes delayed maturation in the presence of insulin but not progesterone. This suggests that the KI domain has a correctly folded three-dimensional structure compatible with biological activity. Together these findings indicate that the recombinant alpha-PDGFR KI domain binds the p85 N-SH2 domain and this binding is modulated by the presence of a novel divalent metal ion binding site within its structure. C1 NCI, CELLULAR & MOLEC BIOL LAB, BETHESDA, MD 20892 USA. NCI, FREDERICK CANC RES & DEV CTR, ABL BASIC RES PROGRAM, MACROMOLEC STRUCT LAB, FREDERICK, MD 21702 USA. NIDDK, BIOCHEM & METAB LAB, BETHESDA, MD 20982 USA. FU NCI NIH HHS [N01-CO-74101] NR 66 TC 10 Z9 10 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD FEB 21 PY 1995 VL 34 IS 7 BP 2095 EP 2106 DI 10.1021/bi00007a002 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QH590 UT WOS:A1995QH59000002 PM 7857921 ER PT J AU XU, Y YANKIE, L SHEN, L JUNG, YS MARIANO, PS DUNAWAYMARIANO, D MARTIN, BM AF XU, Y YANKIE, L SHEN, L JUNG, YS MARIANO, PS DUNAWAYMARIANO, D MARTIN, BM TI LOCATION OF THE CATALYTIC SITE FOR PHOSPHOENOLPYRUVATE FORMATION WITHIN THE PRIMARY STRUCTURE OF CLOSTRIDIUM-SYMBIOSUM PYRUVATE PHOSPHATE DIKINASE .1. IDENTIFICATION OF AN ESSENTIAL CYSTEINE BY CHEMICAL MODIFICATION WITH [1-C-14]BROMOPYRUVATE AND SITE-DIRECTED MUTAGENESIS SO BIOCHEMISTRY LA English DT Article ID SUGAR PHOSPHOTRANSFERASE SYSTEM; BACTERIAL PHOSPHOENOLPYRUVATE; ORTHOPHOSPHATE DIKINASE; ENZYME-I; SEQUENCE; MAIZE; PLANT; GENE AB Pyruvate phosphate dikinase (PPDK) catalyzes the interconversion of adenosine 5'-triphosphate (ATP), orthophosphate (P-i), and pyruvate with adenosine 5'-monophosphate (AMP), pyrophosphate (PPi), and phosphoenolpyruvate (PEP). The reaction takes place according to the following steps: (1) E + ATP + P-i reversible arrow E-PP.AMP.P-i, (2) E-PP.AMP.P-i reversible arrow E-P + AMP + PPi, and (3) E-P + pyruvate reversible arrow E + PEP, where E represents free enzyme; E-PP, pyrophosphorylenzyme; and E-P, phosphorylenzyme. Steps 1 and 2 comprise the nucleotide partial reaction, and step 3 comprises the pyruvate partial reaction. The present studies were carried out to locate amino acid residues within the primary structure of Clostridium symbiosum PPDK participating in the catalysis of the pyruvate partial reaction. The enzyme was treated with the affinity label [1-C-14]bromopyruvate, reduced with NaBH4, proteolyzed with trypsin, and chromatographed on an HPLC column. The radiolabeled tryptic peptide isolate was sequenced to reveal Cys 831 as the site of alkylation. Using PCR techniques Cys 831 was replaced by Ala, and the C831A PPDK mutant formed was then subjected to kinetic analysis. Rapid quench studies of single turnover reactions on the enzyme showed that the mutant is as efficient as wild-type PPDK in catalyzing the nucleotide partial reaction while it is unable to catalyze the pyruvate partial reaction. These results were interpreted as evidence for a role of Cys 831 in pyruvate/PEP binding and/or catalysis. C1 UNIV MARYLAND,DEPT CHEM & BIOCHEM,COLLEGE PK,MD 20742. NIMH,CLIN NEUROSCI BRANCH,MOLEC NEUROGENET UNIT,BETHESDA,MD 20892. FU NIGMS NIH HHS [GM-36260, GM-27257] NR 25 TC 22 Z9 23 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD FEB 21 PY 1995 VL 34 IS 7 BP 2181 EP 2187 DI 10.1021/bi00007a011 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QH590 UT WOS:A1995QH59000011 PM 7857929 ER PT J AU XU, Y MCGUIRE, M DUNAWAYMARIANO, D MARTIN, BM AF XU, Y MCGUIRE, M DUNAWAYMARIANO, D MARTIN, BM TI SEPARATE SITE CATALYSIS BY PYRUVATE PHOSPHATE DIKINASE AS REVEALED BY DELETION MUTANTS SO BIOCHEMISTRY LA English DT Article ID SUGAR PHOSPHOTRANSFERASE SYSTEM; BACTERIAL PHOSPHOENOLPYRUVATE; KINASE; IDENTIFICATION; EXPRESSION; DOMAINS; ATP AB Previous studies had indicated that pyruvate phosphate dikinase (PPDK), an enzyme which catalyzes the interconversion of adenosine 5'-triphosphate (ATP), orthophosphate (P-i), and pyruvate with adenosine 5'-monophosphate (AMP), pyrophosphate (PPi), and phosphoenolpyruvate (PEP), is made up of 25, 13, 18, and 35 kDa domains [Carroll, L. J., Xu, Y., Thrall, S. H., Martin, B. M., and Dunaway-Mariano, D. (1994) Biochemistry 33, 1134]. The catalytic histidine (which mediates the phosphoryl group transfers from ATP to P-i and pyruvate) is located on the 18 kDa domain while the 25 and 13 kDa domains appear to contain the ATP binding site and the 35 kDa domain appears to contain the pyruvate binding site, respectively. The goal of this investigation was to examine functional interdependency of the putative ATP and pyruvate binding domains. Two truncated forms of PPDK were created by using recombinant DNA techniques. The 35 kDa (C-terminal) deletion mutant was found to catalyze the E + ATP + P-i reversible arrow E-P + AMP + PPi partial reaction but not the E-P + pyruvate reversible arrow E + PEP partial reaction. The 25 kDa (N-terminal) deletion mutant was found to catalyze the E-P + pyruvate reversible arrow E + PEP partial reaction but not the E + ATP + P-i reversible arrow E-P + AMP + PPi partial reaction. Neither mutant catalyzes the full ATP + P-i + pyruvate reversible arrow AMP + PPi + PEP reaction. These results are interpreted to mean that the ATP and pyruvate binding domains in PPDK are functionally independent, thus providing evidence for separate active sites for catalysis of the two partial reactions. C1 UNIV MARYLAND,DEPT CHEM & BIOCHEM,COLLEGE PK,MD 20742. NIMH,CLIN NEUROSCI BRANCH,MOLEC NEUROGENET UNIT,BETHESDA,MD 20892. FU NIGMS NIH HHS [GM-36260] NR 23 TC 14 Z9 15 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD FEB 21 PY 1995 VL 34 IS 7 BP 2195 EP 2202 DI 10.1021/bi00007a013 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QH590 UT WOS:A1995QH59000013 PM 7857931 ER PT J AU LEIBENLUFT, E CLARK, CH MYERS, FS AF LEIBENLUFT, E CLARK, CH MYERS, FS TI THE REPRODUCIBILITY OF DEPRESSIVE AND HYPOMANIC SYMPTOMS ACROSS REPEATED EPISODES IN PATIENTS WITH RAPID-CYCLING BIPOLAR DISORDER SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE BIPOLAR DISORDER; RAPID CYCLING; HYPERSOMNIA; HYPOMANIA ID STABILITY; MANIA AB The purpose of this study is to determine the stability of symptoms of hypomania and depression across repeated affective episodes in patients with rapid-cycling bipolar disorder. Nine patients had a total of 30 depressive episodes and 31 hypomanic episodes during the period of observation. Standardized observer ratings indicated that the three symptoms most consistently reported during depressive episodes were fatiguability, decreased work activities and hypersomnia. These results as well as those from the standarized observer ratings of hypomania indicate that depression in this population consists of a lethargic, hypoactive state while hypomania may be a heightened state of activation. The clinical and theoretical implications of these findings are discussed. C1 NIMH,CLIN PSYCHOBIOL BRANCH,BETHESDA,MD 20892. NR 16 TC 12 Z9 12 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect Disord. PD FEB 21 PY 1995 VL 33 IS 2 BP 83 EP 88 DI 10.1016/0165-0327(94)00077-M PG 6 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA QJ346 UT WOS:A1995QJ34600003 PM 7759665 ER PT J AU BENNING, C HUANG, ZH GAGE, DA AF BENNING, C HUANG, ZH GAGE, DA TI ACCUMULATION OF A NOVEL GLYCOLIPID AND A BETAINE LIPID IN CELLS OF RHODOBACTER-SPHAEROIDES GROWN UNDER PHOSPHATE LIMITATION SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE BETAINE LIPIDS; GLYCOLIPIDS; PHOSPHOLIPIDS; PHOTOSYNTHETIC BACTERIA; RHODOBACTER SPHAEROIDES; PHOSPHATE STRESS ID OCHROMONAS-DANICA; REPLACEMENT AB Cells of the photosynthetic bacterium Rhodobacter sphaeroides grown under phosphate-limiting conditions accumulated nonphosphorous glycolipids and lipids carrying head groups derived from amino acids. Concomitantly, the relative amount of phosphoglycerolipids decreased from 90 to 22 mol% of total polar lipids in the membranes. Two lipids, not detectable in cells grown under standard conditions, were synthesized during phosphate-limited growth. Fast atom bombardment mass spectroscopy, exact mass measurements, H-1 NMR spectroscopy, sugar composition analysis, and methylation analysis of the predominant glycolipid led to the identification of the novel compound 1,2-di-O-acyl-3-O-[alpha-D-glucopyranosyl-(1 -> 4)-O-beta-D-galactopyranosyl]glycerol. The second lipid was identified as the betaine lipid 1,2-di-O-acyl-[4'-(N,N,N-trimethyl)homoserine]glycerol by cochromatography employing an authentic standard from Chlamydomonas reinhardtii, fast atom bombardment mass spectroscopy, exact mass measurements, and 1H NMR spectroscopy. Prior to this observation, the occurrence of this lipid was thought to be restricted to lower plants and algae. Apparently, these newly synthesized nonphosphorous lipids, in addition to the sulfo- and the ornithine lipid also found in R. sphaeroides grown under optimal conditions, take over the role of phosphoglycerolipids in phosphate-deprived cells. (C) 1995 Academic Press, Inc. C1 MICHIGAN STATE UNIV,NIH,MASS SPECTROMETRY FACIL,DEPT BIOCHEM,E LANSING,MI 48824. RP BENNING, C (reprint author), INST GENBIOL FORSCH BERLIN GMBH,IHNESTR 63,D-14195 BERLIN,GERMANY. FU NCRR NIH HHS [RR00480] NR 32 TC 150 Z9 157 U1 6 U2 22 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD FEB 20 PY 1995 VL 317 IS 1 BP 103 EP 111 DI 10.1006/abbi.1995.1141 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA QK397 UT WOS:A1995QK39700014 PM 7872771 ER PT J AU BERGSTEN, P YU, R KEHRL, J LEVINE, M AF BERGSTEN, P YU, R KEHRL, J LEVINE, M TI ASCORBIC-ACID TRANSPORT AND DISTRIBUTION IN HUMAN B-LYMPHOCYTES SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE ASCORBIC ACID; B LYMPHOCYTES; TRANSPORT ID COULOMETRIC ELECTROCHEMICAL DETECTION; PERFORMANCE LIQUID-CHROMATOGRAPHY; DEHYDROASCORBIC ACID; HUMAN-NEUTROPHILS; HUMAN-LEUKOCYTES; VITAMIN-C; BLOOD; PLASMA; CELLS; ACCUMULATION AB Ascorbic acid (vitamin C) transport was investigated inhuman B lymphocytes. The vitamin was transported by two components. The first was a high-affinity activity with an apparent K-m of 7-10 mu M and V-max of 0.14 mM/h (3.11 X 10(-4) mu mol X h(-1) X mg protein(-1)). The activity was concentration and temperature dependent, saturable, and inhibited by carbonylcyanide-p-trifluoromethoxyphenylhydrazone and ouabain and generated ascorbic acid accumulation against a concentration gradient. Kinetics for the second component were indeterminate because ascorbate was not accumulated against a concentration gradient. Subcellular fractionation revealed that intracellular ascorbic acid in human B lymphocytes was >90% localized to the cytosol and not protein bound. Kinetic parameters of high-affinity ascorbic acid transport could operate effectively with plasma concentrations normally found in humans. (C) 1995 Academic Press, Inc. C1 UNIV UPPSALA,BIOMEDICUM,DEPT MED CELL BIOL,S-75123 UPPSALA,SWEDEN. UNIV ULSAN,DEPT FOOD & NUTR,ULSAN 680749,SOUTH KOREA. NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. RP BERGSTEN, P (reprint author), NIDDKD,CELL BIOL & GENET LAB,BETHESDA,MD 20892, USA. OI Kehrl, John/0000-0002-6526-159X NR 43 TC 36 Z9 36 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD FEB 20 PY 1995 VL 317 IS 1 BP 208 EP 214 DI 10.1006/abbi.1995.1155 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA QK397 UT WOS:A1995QK39700028 PM 7872786 ER PT J AU OVERBY, LH BUCKPITT, AR LAWTON, MP ATTAASAFOADJEI, E SCHULZE, J PHILPOT, RM AF OVERBY, LH BUCKPITT, AR LAWTON, MP ATTAASAFOADJEI, E SCHULZE, J PHILPOT, RM TI CHARACTERIZATION OF FLAVIN-CONTAINING MONOOXYGENASE-5 (FMO5) CLONED FROM HUMAN AND GUINEA-PIG - EVIDENCE THAT THE UNIQUE CATALYTIC PROPERTIES OF FMO5 ARE NOT CONFINED TO THE RABBIT ORTHOLOG SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article ID FUNCTION AMINE OXIDASE; LIVER-MICROSOMES; ESCHERICHIA-COLI; PRIMARY ALKYLAMINES; COVALENT STRUCTURE; RIBONUCLEIC-ACID; PRIMARY SEQUENCE; MULTIPLE FORMS; LUNG; PURIFICATION AB Several full-length clones encoding the human and guinea pig orthologs of flavin-containing monooxygenase 5 (FMO5) have been isolated from libraries constructed with hepatic mRNA. The clones were detected by hybridization with the cDNA encoding FMO5 expressed in rabbit. The human and guinea pig cDNAs encode for proteins of 533 amino acids that contain putative pyrophosphate binding domains characteristic of mammalian FMOs. The sequences derived for the human and guinea pig FMO5 proteins are 87% identical and are 85 and 82% identical, respectively, to the sequence of rabbit FMO5. As is the case with other FMOs, FMO5 in human and guinea pig is encoded by multiple transcripts. Rabbit FMO5 expressed in Escherichia coli was purified and used to elicit antibodies in goat. These antibodies detected FMO5 in samples from livers of adult humans, rabbits, and guinea pigs and fetal livers of humans. The human and guinea pig forms of FMO5 were expressed in E. coli and characterized. Neither enzyme effectively catalyzed the metabolism of methimazole, a general FMO substrate; however, both were active with n-octylamine. The responses of the human FMO5 and guinea pig FMO5 to detergent, ions and elevated temperature are all similar to the responses described for rabbit FMO5. These results indicate that the unique properties of FMO5 from rabbit are species-independent and that this form of the flavin-containing monooxygenase is not readily classified as a drug-metabolizing enzyme. (C) 1995 Academic Press, Inc. C1 NIEHS,CELLULAR & MOLEC PHARMACOL LAB,MOLEC PHARMACOL SECT,RES TRIANGLE PK,NC 27709. LAWRENCE LIVERMORE NATL LAB,DEPT PHARMACOL & TOXICOL,DAVIS,CA 95616. UNIV MUNICH,WALTHER STRAUB INST PHARMAKOL & TOXIKOL,D-80336 MUNICH,GERMANY. RI atta, ayman/E-9273-2017 NR 47 TC 66 Z9 68 U1 0 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD FEB 20 PY 1995 VL 317 IS 1 BP 275 EP 284 DI 10.1006/abbi.1995.1163 PG 10 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA QK397 UT WOS:A1995QK39700036 PM 7872795 ER PT J AU BHAMRE, S BHAGWAT, SV SHANKAR, SK BOYD, MR RAVINDRANATH, V AF BHAMRE, S BHAGWAT, SV SHANKAR, SK BOYD, MR RAVINDRANATH, V TI FLAVIN-CONTAINING MONOOXYGENASE MEDIATED METABOLISM OF PSYCHOACTIVE-DRUGS BY HUMAN BRAIN MICROSOMES SO BRAIN RESEARCH LA English DT Note DE BRAIN; FLAVIN-CONTAINING MONOOXYGENASE; METABOLISM; NEUROLEPTIC; ANTIDEPRESSANT; MONOOXYGENASE; HUMAN BRAIN ID HUMAN LIVER; LOCALIZATION; PROTEINS; CLONING; OXIDASE; TISSUE AB Flavin-containing monooxygenases (FMO) catalyze the oxidation of certain xenobiotics and drugs which contain a nucleophilic heteroatom. Here we report the first assessment of human brain flavin-containing monooxygenase from tissues obtained at autopsy from seven traffic accident victims. Human brain microsomes catalyzed the S-oxidation or N-oxidation of model substrates methimazole and N,N-dimethylaniline, respectively. The psychoactive drugs chlorpromazine, imipramine and fluoxetine, were also metabolized by human brain FMO. 'Western' immunoblot analyses revealed immunological cross-reactivity of the human brain FMO with rabbit pulmonary FMO. Immunocytochemistry further revealed the localization of the FMO predominantly in the neuronal cell bodies in the magnocellular reticular nuclei, colliculi and substantia nigra. Human brain clearly contains an active FMO system, and it is conceivable that such enzyme(s) are significantly involved in the local metabolism and modulation of pharmacological effects of psychoactive drugs. C1 NATL INST MENTAL HLTH & NEUROSCI,DEPT NEUROCHEM,BANGALORE 560029,KARNATAKA,INDIA. NATL INST MENTAL HLTH & NEUROSCI,DEPT NEUROPATHOL,BANGALORE 560029,KARNATAKA,INDIA. NCI,DEV THERAPEUT PROGRAM,DRUG DISCOVERY RES & DEV LAB,FREDERICK,MD 21702. NR 19 TC 28 Z9 29 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD FEB 20 PY 1995 VL 672 IS 1-2 BP 276 EP 280 DI 10.1016/0006-8993(94)01135-5 PG 5 WC Neurosciences SC Neurosciences & Neurology GA QJ465 UT WOS:A1995QJ46500030 PM 7749747 ER PT J AU HELZLSOUER, KJ HARRIS, EL PARSHAD, R FOGEL, S BIGBEE, WL SANFORD, KK AF HELZLSOUER, KJ HARRIS, EL PARSHAD, R FOGEL, S BIGBEE, WL SANFORD, KK TI FAMILIAL CLUSTERING OF BREAST-CANCER - POSSIBLE INTERACTION BETWEEN DNA-REPAIR PROFICIENCY AND RADIATION EXPOSURE IN THE DEVELOPMENT OF BREAST-CANCER SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID FLUOROSCOPIC EXAMINATIONS; ATAXIA-TELANGIECTASIA; CHROMATID DAMAGE; TUBERCULOSIS; SENSITIVITY; IRRADIATION; LINKAGE; WOMEN; CHEST; LOCUS AB The capacity of peripheral blood lymphocytes to repair X-ray-induced DNA damage, manifest as chromatid damage 30-90 min after G(2)-phase X-irradiation, was measured among available members of a family exhibiting a cluster of breast-cancer cases occurring in one generation. The cancer patients had been exposed to repeated chest fluoroscopic examinations during early childhood and adolescence. The development of breast cancer was correlated with DNA repair proficiency and history of radiation exposure. The results of the family study provide preliminary support for the hypothesis that a deficiency in repair of X-irradiation DNA damage may be a susceptibility factor for the development of breast cancer. This hypothesis, however, requires confirmation in a larger study. Studying the combined effect of susceptibility factors and environmental exposures may enhance our knowledge of the etiology of breast cancer and provide leads for effective prevention strategies aimed at reducing exposures or altering susceptibility to unavoidable exposures. (C) 1995 Wiley-Liss, Inc. C1 KAISER PERMANENTE,CTR HLTH RES,PORTLAND,OR. HOWARD UNIV,COLL MED,DEPT PATHOL,WASHINGTON,DC 20059. JOHNS HOPKINS UNIV HOSP,DEPT SURG,BALTIMORE,MD. LAWRENCE LIVERMORE NATL LAB,LIVERMORE,CA. NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. RP HELZLSOUER, KJ (reprint author), JOHNS HOPKINS MED INST,SCH HYG & PUBL HLTH,DEPT EPIDEMIOL,ROOM 6033,615 N WOLFE ST,BALTIMORE,MD 21205, USA. NR 20 TC 53 Z9 55 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD FEB 20 PY 1995 VL 64 IS 1 BP 14 EP 17 DI 10.1002/ijc.2910640105 PG 4 WC Oncology SC Oncology GA QW977 UT WOS:A1995QW97700004 PM 7665242 ER PT J AU CAHOUR, A PLETNEV, A VAZEILLEFALCOZ, M ROSEN, L LAI, CJ AF CAHOUR, A PLETNEV, A VAZEILLEFALCOZ, M ROSEN, L LAI, CJ TI GROWTH-RESTRICTED DENGUE VIRUS MUTANTS CONTAINING DELETIONS IN THE 5' NONCODING REGION OF THE RNA GENOME SO VIROLOGY LA English DT Article ID YELLOW-FEVER VIRUS; TYPE-4 VIRUS; NONSTRUCTURAL PROTEINS; OCTAPEPTIDE SEQUENCE; STRUCTURAL PROTEINS; SECONDARY STRUCTURE; DEFINED MUTATIONS; POLIOVIRUS RNA; TICK-BORNE; VIRAL-RNA AB The dengue type 4 virus (DEN4) RNA genome contains a 101-nt 5' noncoding (NC) sequence which is predicted to form a stable secondary structure. DEN4 cDNA from which infectious RNA can be transcribed was used to engineer deletions in the 5' NC region for functional analysis of RNA structure and for isolation of DEN4 mutants that could be evaluated as candidates for use in a live attenuated vaccine. Eleven distinct deletions in the region of the DEN4 genome between nts 18 and 98 were constructed; each mutation was predicted to alter or disrupt the local base-parings in the 5' NC RNA structure. An infectious virus was not recovered from the RNA transcripts of five of these deletion mutants. Significantly, four of the five apparently lethal deletions were located in a 5- to 6-nt base-paired region of a predicted long stem or adjacent to it. In contrast, with one exception, mutants which yielded infectious virus had deletions which were located in a loop or short stem region. The effect of the deletions on the efficiency of translation of viral RNA transcripts was examined in vitro. The RNA transcripts of deletion constructs which did not yield viable virus were translated at an efficiency ranging from 40 to 160% that of wild-type virus transcripts. The translation efficiency of infectious RNA transcripts also varied. Deletion mutants recovered from RNA transcripts that exhibited low to moderate efficiency of translation had a small plaque morphology and exhibited reduced growth in simian LLC-MK(2) and mosquito C6/36 cells compared to the wild-type virus. Among the 11 mutant constructs, deletion of nts 82-87 caused the greatest reduction in translation efficiency. Nevertheless, an infectious virus was recovered from LLC-MK(2) cells transfected with the RNA transcripts of mutant d(82-87). The progeny of this mutant produced small plaques on LLC-MK(2) cells and grew to low titer in these cells. Unlike wild-type DEN4 or other DEN4 deletion mutants tested, mutant d(82-87) failed to produce plaques on C6/36 cells and was also replication-defective in Aedes aegypti and Aedes albopictus following intrathoracic inoculation. (C) 1995 Academic Press, Inc. C1 NIAID,INFECT DIS LAB,MOLEC VIRAL BIOL SECT,BETHESDA,MD 20892. INST PASTEUR,UNITE ECOL SYST VECTORIELS,F-75724 PARIS 15,FRANCE. NR 41 TC 105 Z9 112 U1 3 U2 3 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD FEB 20 PY 1995 VL 207 IS 1 BP 68 EP 76 DI 10.1006/viro.1995.1052 PG 9 WC Virology SC Virology GA QJ657 UT WOS:A1995QJ65700007 PM 7871753 ER PT J AU GRANT, RF WINDSOR, SK MALINAK, CJ BARTZ, CR SABO, A BENVENISTE, RE TSAI, CC AF GRANT, RF WINDSOR, SK MALINAK, CJ BARTZ, CR SABO, A BENVENISTE, RE TSAI, CC TI CHARACTERIZATION OF INFECTIOUS TYPE-D RETROVIRUS FROM BABOONS SO VIROLOGY LA English DT Note ID ACQUIRED IMMUNODEFICIENCY SYNDROME; COMPLETE NUCLEOTIDE-SEQUENCE; IMMUNE-DEFICIENCY SYNDROME; RETROPERITONEAL FIBROMATOSIS; SIMIAN AIDS; RHESUS MACAQUES; VIRUS; TRANSMISSION; GENOME; SRV-1 AB Infectious virus resembling type D simian retrovirus (SRV) was isolated from Ethiopian baboons (Papio cynocephalus) (SRV-Pc) housed at the University of Washington Regional Primate Research Center. When baboon peripheral blood mononuclear cells (PBMC) or tissues were cocultured with the H-9 human T-cell line or the Raji human B-cell line, large multinucleated syncytia positive for sRV-2 antigens were observed microscopically. Immunoblot analysis of purified SRV-Pc from cell culture supernatants demonstrated that the viral core and envelope proteins reacted with rabbit anti-SRV-2 serum. Fresh PBMC and cocultured cells were positive by polymerase chain reaction using two different sets of SRV-2 primers. Preliminary sequence analysis of two separate isolates from portions of the SRV-Pc p27 and gp20 regions revealed homology with SRV-1, SRV-2, and Mason-Pfizer monkey virus. The homologies in the p27 segment were 91-94% and the homologies in the gp20 segment were 72-75%. (C) 1995 Academic Press, Inc. C1 UNIV WASHINGTON,REG PRIMATE RES CTR,SEATTLE,WA 98195. NCI,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21702. FU NCI NIH HHS [5RO1-CA54747]; NCRR NIH HHS [RR00166] NR 17 TC 24 Z9 25 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD FEB 20 PY 1995 VL 207 IS 1 BP 292 EP 296 DI 10.1006/viro.1995.1080 PG 5 WC Virology SC Virology GA QJ657 UT WOS:A1995QJ65700035 PM 7871741 ER PT J AU BRIDGES, SH SARVER, N AF BRIDGES, SH SARVER, N TI GENE-THERAPY AND IMMUNE RESTORATION FOR HIV DISEASE SO LANCET LA English DT Review ID IMMUNODEFICIENCY-VIRUS TYPE-1; RETROVIRAL VECTORS; T-LYMPHOCYTES; CD4+ CELLS; EXPRESSION; INFECTION; RIBOZYMES; PROTEIN; INVIVO; MOUSE C1 NIAID,DIV AIDS,TARGETED INTERVENT BRANCH,BETHESDA,MD 20892. NR 47 TC 55 Z9 55 U1 0 U2 0 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0099-5355 J9 LANCET JI Lancet PD FEB 18 PY 1995 VL 345 IS 8947 BP 427 EP 432 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA QG904 UT WOS:A1995QG90400015 PM 7853956 ER PT J AU CUPLER, EJ DALAKAS, MC AF CUPLER, EJ DALAKAS, MC TI EXACERBATION OF PERIPHERAL NEUROPATHY BY LAMIVUDINE SO LANCET LA English DT Letter ID 2',3'-DIDEOXYCYTIDINE RP CUPLER, EJ (reprint author), NINCDS,MED NEUROL BRANCH,BETHESDA,MD 20892, USA. NR 5 TC 23 Z9 23 U1 0 U2 0 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0099-5355 J9 LANCET JI Lancet PD FEB 18 PY 1995 VL 345 IS 8947 BP 460 EP 461 DI 10.1016/S0140-6736(95)90447-6 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA QG904 UT WOS:A1995QG90400057 PM 7853984 ER PT J AU GREENE, LE ZINNER, R NAFICY, S EISENBERG, E AF GREENE, LE ZINNER, R NAFICY, S EISENBERG, E TI EFFECT OF NUCLEOTIDE ON THE BINDING OF PEPTIDES TO 70-KDA HEAT-SHOCK PROTEIN SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MOLECULAR CHAPERONE BIP; UNCOATING ATPASE; MUSCLE-CONTRACTION; UNFOLDED PROTEINS; COATED VESICLES; HSP70; CLATHRIN; DISSOCIATION; COMPLEX; HSC70 AB In previous work we found that bovine brain hsp70 has a single binding site for nucleotide, and that, with ATP at this site, the rates of association and dissociation of clathrin from hsp70 are fast, whereas with ADP at this site, these rates are unmeasurably slow. In the present study we show, first, that peptide C, cytochrome c peptide, and RNase S peptide bind competitively with clathrin, suggesting that they bind to the same site on hsp70, although RNase S peptide binds an order of magnitude more weakly than peptide C and cytochrome c peptide. Second, we show that, with ADP bound to hsp70, as occurs with clathrin, the rate constant for dissociation of peptide markedly decreases compared to the rate constant observed in ATP. In contrast, ADP only slightly decreases the rate of association of peptide. Based on these data we propose a model in which substrates of hsp70 bind to and dissociate from the ATP form of the enzyme, while, following ATP hydrolysis, they are locked onto the ADP form of the enzyme, unable to dissociate until ADP is released and ATP rebinds. C1 GEORGETOWN UNIV,SCH MED,WASHINGTON,DC 20007. RP GREENE, LE (reprint author), NHLBI,CELL BIOL LAB,BLDG 3,RM B1-17,3 CTR DR MSC 0301,BETHESDA,MD 20892, USA. NR 40 TC 94 Z9 95 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 J9 J BIOL CHEM JI J. Biol. Chem. PD FEB 17 PY 1995 VL 270 IS 7 BP 2967 EP 2973 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QG471 UT WOS:A1995QG47100015 PM 7852376 ER PT J AU FERRARI, G ANDERSON, BL STEPHENS, RM KAPLAN, DR GREENE, LA AF FERRARI, G ANDERSON, BL STEPHENS, RM KAPLAN, DR GREENE, LA TI PREVENTION OF APOPTOTIC NEURONAL DEATH BY G(M1) GANGLIOSIDE - INVOLVEMENT OF TRK NEUROTROPHIN RECEPTORS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NERVE GROWTH-FACTOR; DEPENDENT PROTEIN-KINASE; CYTOPLASMIC FREE CA2+; AMINO-ACID RECEPTORS; FACTOR DEPRIVATION; GM1 GANGLIOSIDE; PC12 CELLS; PHEOCHROMOCYTOMA CELLS; SYMPATHETIC NEURONS; NEURITE OUTGROWTH AB We have used serum-deprived cultures of wild type and genetically modified PC12 cells to investigate the molecular mechanisms by which monosialoganglioside (G(M1)) rescues neuronal cells from apoptotic death elicited by withdrawal of trophic support, Our findings indicate that G(M1)-promoted survival can be mediated in part by the Trk NGF receptor as well as by TrkB, and potentially by tyrosine kinase receptors for additional neurotrophic growth factors. Experiments employing K-252a, an inhibitor of Trk kinases, and PC12 cells overexpressing a dominant inhibitory form of Trk both indicate that a portion of the survival-promoting activity of G(M1) is evoked by receptor dimerization and autophosphorylation, In consonance with this we find that G(M1) stimulates Trk tyrosine autophosphorylation and Trk-associated protein kinase activity, These observations may provide a mechanism to account for the reported in vitro and in vivo trophic actions of G(M1). C1 COLUMBIA UNIV,COLL PHYS & SURG,DEPT PATHOL,NEW YORK,NY 10032. COLUMBIA UNIV,COLL PHYS & SURG,CTR NEUROBIOL & BEHAV,NEW YORK,NY 10032. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. FU NCI NIH HHS [N0I-CO-7410I] NR 73 TC 166 Z9 177 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD FEB 17 PY 1995 VL 270 IS 7 BP 3074 EP 3080 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QG471 UT WOS:A1995QG47100030 PM 7852388 ER PT J AU CIOTTI, M YEATMAN, MT SOKOL, RJ OWENS, IS AF CIOTTI, M YEATMAN, MT SOKOL, RJ OWENS, IS TI ALTERED CODING FOR A STRICTLY CONSERVED DI-GLYCINE IN THE MAJOR BILIRUBIN UDP-GLUCURONOSYLTRANSFERASE OF A CRIGLER-NAJJAR TYPE-I PATIENT SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID UGT1 GENE-COMPLEX; CDNA SEQUENCE; COS-1 CELLS; CLONING; EXPRESSION; RAT; PHENOL; IDENTIFICATION; LOCUS; DEFICIENCIES AB The characterization (Ritter, J.K., Chen, F., Sheen, Y. Y., Tran, H. M., Kimura, S., Yeatman, M. T., and Owens, I. S. (1992) J. Biol. Chem. 267, 3257-3261) of the single copy UGT1 gene complex locus encoding both bilirubin and phenol UDP-glucuronosyltransferases (transferase) has been critical to the determination of genetic defects in Crigler-Najjar patients. The complex (UGT1A-UGT1M) codes for at least two bilirubin, three bilirubin-like, and eight phenol transferase isozymes. In the 5' region, a minimum of 13 different exons 1, each with an upstream promoter, are arrayed in series with 4 common exons in the 3' region of the locus. Each exon 1 encodes the amino terminus of a transferase, and the common exons encode the common carboxyl terminus of each isoform. Although a deleterious mutation in a common exon inactivates the entire locus, a deleterious mutation in an exon 1, as we report here for the UGT1A gene in a Crigler-Najjar Type I patient, affects the amino terminus of that s ingle isoform. Recessively inherited mutant alleles for the predominant bilirubin isozyme, the HUG-Br1 protein, substituted Arg for Gly at codon 276 (G276R) in exon 1 of UGT1A abolishing a conserved di-glycine. The mutant HUG-Br1-G276R protein expressed in COS-1 cells had no detectable bilirubin glucuronidating activity at either pH 7.6 or 6.4. Although each of the bilirubin-type isozymes contains a conserved peptide between residues 270 and 288, all UDP-glucuronosyltransferases contain a di-glycine at approximately position 276-277, making it strictly conserved. Structure-func tion relationship was studied by site-directed mutations of the HUG-Br1 cDNA; G276A, G276Q, G276E, G276I, and P270G mutants were inactive, and V275I- and P285G-altered transferases expressed normal activity. Conservation of residues between the related baculoviral ecdysone UDP-glucosyltransferase and the UDP-glucuronosyltransferases confirms the critical role of the Gly-276 as well as other residues. C1 NICHHD,GENET DISORDERS DRUG METAB SECT,HUMAN GENET BRANCH,BETHESDA,MD 20892. CHILDRENS HOSP,CTR PEDIAT LIVER,DENVER,CO 80218. FU NCRR NIH HHS [RR00069] NR 35 TC 42 Z9 44 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 J9 J BIOL CHEM JI J. Biol. Chem. PD FEB 17 PY 1995 VL 270 IS 7 BP 3284 EP 3291 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QG471 UT WOS:A1995QG47100060 PM 7852413 ER PT J AU UTANI, A NOMIZU, M SUGIYAMA, S MIYAMOTO, S ROLLER, PP YAMADA, Y AF UTANI, A NOMIZU, M SUGIYAMA, S MIYAMOTO, S ROLLER, PP YAMADA, Y TI A SPECIFIC SEQUENCE OF THE LAMININ ALPHA-2 CHAIN CRITICAL FOR THE INITIATION OF HETEROTRIMER ASSEMBLY SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BASEMENT-MEMBRANE PROTEINS; NEUROMUSCULAR-JUNCTION; MULTIDOMAIN PROTEIN; MECHANISM; REPEATS; FOS AB Triple-stranded laminin molecules assemble via an alpha-helical coiled-coil structure spanning approximately 600 amino acid residues of each chain. We reported that the C termini of the beta 1 and gamma 1 chains direct the specific dimer and trimer assembly (Utani, A., Nomizu, M., Timpl, R., Roller, P. P., and Yamada, Y. (1994) J. Biol. Chem. 269, 19167-19175). In this study, we focused on the mechanism of trimer formation of the alpha 2 chain utilizing three different approaches. First, competition assays using mutated recombinant alpha 2 chain defined a 25-amino acid sequence at the C terminus of the long arm as an essential site for assembly with beta 1 and gamma 1 chain. Site-specific mutations and synthetic peptides of this site revealed that both positively charged amino acid residues and the alpha-helical structure within this site were critical. Second, overexpression studies of recombinant alpha 2 chain long arm confirmed that the C-terminal end was critical for the trimer assembly within NIH 3T3 cells. Third, circular dichroism spectroscopic examination of the complexes reconstituted in vitro revealed dynamic conformational changes of the alpha 2 and gamma 1 chains in the process of assembly. These studies also revealed that the proper folding of the extreme C terminus of alpha 2 chain was critical for the stability of trimer. From these data, it is concluded that the C terminus of alpha 2 chain long arm is required for the effective initiation of laminin heterotrimer assembly. C1 NCI,MED CHEM LAB,BETHESDA,MD 20892. RP UTANI, A (reprint author), NIDR,DEV BIOL LAB,BETHESDA,MD 20892, USA. NR 29 TC 27 Z9 27 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 J9 J BIOL CHEM JI J. Biol. Chem. PD FEB 17 PY 1995 VL 270 IS 7 BP 3292 EP 3298 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QG471 UT WOS:A1995QG47100061 PM 7852414 ER PT J AU PRIOLA, SA CAUGHEY, B WEHRLY, K CHESEBRO, B AF PRIOLA, SA CAUGHEY, B WEHRLY, K CHESEBRO, B TI A 60-KDA PRION PROTEIN (PRP) WITH PROPERTIES OF BOTH THE NORMAL AND SCRAPIE-ASSOCIATED FORMS OF PRP SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NEURO-BLASTOMA CELLS; PHYSICAL-PROPERTIES; AGENT; PURIFICATION; RESISTANT; PHOSPHOLIPASE; BIOSYNTHESIS; INFECTIVITY; CONVERSION; FIBRILS AB Scrapie is a transmissible spongiform encephalopathy of sheep and other mammals in which disease appears to be caused by the accumulation of an abnormal form of a host protein, prion protein (PrP), in the brain and other tissues. The process by which the normal protease-sensitive form of PrP is converted into the abnormal protease-resistant form is unknown. Several hypotheses predict that oligomeric forms of either the normal or abnormal PrP may act as intermediates in the conversion process. We have now identified a 60-kDa PrP derived from hamster PrP expressed in murine neuroblastoma cells, Peptide mapping studies provided evidence that the 60-kDa PrP was composed solely of PrP and, based on its molecular mass, appeared to be a PrP dimer. The 60-kDa PrP was not dissociated under sev eral harsh denaturing conditions, which indicated that it was covalently linked. It was similar to the disease-associated form of PrP in that it formed large aggre gates. However, it resembled the normal form of PrP in that it was sensitive to proteinase K and had a short metabolic half-life. The 60-kDa PrP, therefore, had characteristics of both the normal and disease-associated forms of PrP. Formation and aggregation of the 60-kDa hamster PrP occurs in uninfected mouse neuroblastoma cells, which suggests that hamster PrP has a predispo sition to aggregate even in the absence of scrapie infec tivity. Similar 60-kDa PrP bands were identified in scrapie-infected hamster brain but not in uninfected brain. Therefore, a 60-kDa molecule might participate in the scrapie-associated conversion of protease-sensitive PrP to protease-resistant PrP. RP PRIOLA, SA (reprint author), NIAID, ROCKY MT LABS, PERSISTENT VIRAL DIS LAB, HAMILTON, MT 59840 USA. NR 50 TC 65 Z9 67 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD FEB 17 PY 1995 VL 270 IS 7 BP 3299 EP 3305 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QG471 UT WOS:A1995QG47100062 PM 7852415 ER PT J AU BENYA, RV KUSUI, T BATTEY, JF JENSEN, RT AF BENYA, RV KUSUI, T BATTEY, JF JENSEN, RT TI CHRONIC DESENSITIZATION AND DOWN-REGULATION OF THE GASTRIN-RELEASING PEPTIDE RECEPTOR ARE MEDIATED BY A PROTEIN-KINASE C-DEPENDENT MECHANISM SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID AGONIST-PROMOTED DESENSITIZATION; BOMBESIN-LIKE PEPTIDES; GROWTH-FACTOR RECEPTOR; GUINEA-PIG PANCREAS; SWISS 3T3 CELLS; MUSCARINIC RECEPTORS; BETA-2-ADRENERGIC RECEPTOR; HOMOLOGOUS DESENSITIZATION; MOLECULAR MECHANISMS; SIGNAL TRANSDUCTION AB The cellular basis of down-regulation and desensitization in phospholipase C-linked receptors is unclear. Recent studies with some receptors suggest that elements in the carboxyl terminus of the receptor are important in mediating these processes. Three mutant gastrin-releasing peptide receptors (GRP-R) were studied: one whose last 37 carboxyl-terminal amino acids were eliminated (construct MGT346); one that replaced all of the carboxyl-terminal Ser and Thr eliminated in MGT346 with Ala, Asn, or Gly (construct JF1); and one that selectively replaced the Ser and Thr of the protein kinase C consensus sequence (PKC-CS) located within the same region with alanine (construct TS360AA). Desensitization was assessed by measuring the ability to activate phospholipase C and increase cellular [H-3]inositol phosphates, or increase [Ca2+](i), after pre-exposure to 3 nM bombesin for 24 h. Wild-type GRP-R was maximally desensitized and down-regulated after a 24-h exposure to 3 nM bombesin, and removal of the PKC-CS alone markedly attenuated each process. Elimination of additional serines and threonines by truncation (MGT346) or replacement (JF1) did not decrease down-regulation or desensitization further. To coli firm the necessity of sec ond messenger activation in mediating down-regulation, we further investigated two additional mutant GRP-R that bound agonist with high affinity but fail to activate phospholipase C (constructs R139G and A263E). Neither construct underwent significant down-regulation. Removal of all GRP-R carboxyl-terminal Ser or Thr, either by MGT346 or JF1, reduced internalization by > 80%, whereas elimination of the PKC-CS in TS360AA only attenuated internalization by 21 +/- 2%. These data suggest that activation of the distal carboxyl-terminal PKC-CS is essential for chronic desensitization and down-regulation of the GRP-R, and provide no evidence for involvement of second messenger-independent processes. In contrast, internalization is equally regulated by both second messenger-dependent and independent processes. C1 NIDDK,DIGEST DIS BRANCH,BETHESDA,MD 20892. NCI,BIOL CHEM LAB,DEV THERAPEUT PROGRAM,BETHESDA,MD 20892. NR 57 TC 24 Z9 24 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 J9 J BIOL CHEM JI J. Biol. Chem. PD FEB 17 PY 1995 VL 270 IS 7 BP 3346 EP 3352 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QG471 UT WOS:A1995QG47100068 PM 7852420 ER PT J AU HADARI, YR PAZ, K DEKEL, R MESTROVIC, T ACCILI, D ZICK, Y AF HADARI, YR PAZ, K DEKEL, R MESTROVIC, T ACCILI, D ZICK, Y TI GALECTIN-8 - A NEW RAT LECTIN, RELATED TO GALECTIN-4 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GALACTOSIDE-BINDING-PROTEIN; CARBOHYDRATE-RECOGNITION; MUSCLE LECTIN; GROWTH-FACTOR; RECEPTOR; LAMININ; IDENTIFICATION; SPECIFICITY; EXPRESSION; SECRETION AB A protein of 35 kDa which has the characteristic properties of galectins (S-type lectins) was cloned from rat liver cDNA expression library. Since names for galectins 1-7 were already assigned, this new protein was named galectin-8. Three lines of evidence demonstrate that galectin-8 is indeed a novel galectin: (i) its deduced amino acid sequence contains two domains with conserved motifs that are implicated in the carbohydrate binding of galectins, (ii) in vitro translation products of galectin-8 cDNA or bacterially expressed recombinant galectin-8 are biologically active and possess sugar binding and hemagglutination activity, and (iii) a protein of the expected size (34 kDa) that binds to lactosyl-Sepharose and reacts with galectin-8-specific antibodies is present in rat liver and comprises similar to 0.025% of the total Triton X-100-soluble hepatic proteins. Overall, galectin-8 is structurally related (34% identity) to galectin-4, a soluble rat galectin with two carbohydrate-binding domains in the same polypeptide chain, joined by a link peptide. Nonetheless, several important features distinguish these two galectins: (i) Northern blot analysis revealed that, unlike galectin-4 that is confined to the intestine and stomach, galectin-8 is expressed in liver, kidney, cardiac muscle, lung, and brain; (ii) unlike galectin-4, but similar to galectins-1 and -2, galectin-8 contains 4 Cys residues; (iii) the link peptide of galectin-8 is unique and bears no similarity to any known protein; (iv) the N-terminal carbohydrate-binding region of galectin-8 contains a unique WG-E-I motif instead of the consensus WG-E-R/K motif implicated as playing an essential role in sugar-binding of all galectins. Together with galectin-4, galectin-8 therefore represents a subfamily of galectins consisting of a tandem repeat of structurally different carbohydrate recognition domains within a single polypeptide chain. C1 WEIZMANN INST SCI, DEPT CHEM IMMUNOL, IL-76100 REHOVOT, ISRAEL. TECHNION ISRAEL INST TECHNOL, SCH MED, IL-31096 HAIFA, ISRAEL. UNIV ZAGREB, SCH MED, ZAGREB 41000, CROATIA. NIH, DIABET BRANCH, BETHESDA, MD 20892 USA. NR 45 TC 140 Z9 142 U1 0 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD FEB 17 PY 1995 VL 270 IS 7 BP 3447 EP 3453 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QG471 UT WOS:A1995QG47100083 PM 7852431 ER PT J AU SHIBUSAWA, Y MUGIYAMA, M MATSUMOTO, U ITO, Y AF SHIBUSAWA, Y MUGIYAMA, M MATSUMOTO, U ITO, Y TI COMPLEMENTARY USE OF COUNTERCURRENT CHROMATOGRAPHY AND HYDROXYAPATITE CHROMATOGRAPHY FOR THE SEPARATION OF 3 MAIN CLASSES OF LIPOPROTEINS FROM HUMAN SERUM SO JOURNAL OF CHROMATOGRAPHY B-BIOMEDICAL APPLICATIONS LA English DT Article ID COIL PLANET CENTRIFUGE; PERFORMANCE LIQUID-CHROMATOGRAPHY; GEL-PERMEATION CHROMATOGRAPHY; HIGH-DENSITY LIPOPROTEIN; CHOLESTEROL; PHASE; PROTEINS; SYSTEMS AB High-density, low-density and very-low-density lipoproteins (HDLs, LDLs and VLDLs) were purified from human serum by the combined use of counter-current chromatography (CCC) and hydroxyapatite chromatography. Polymer-phase CCC of human serum using the cross-axis coil planet centrifuge yielded two lipoprotein fractions, one containing HDLs and LDLs and the other VLDLs and serum proteins. Each fraction was concentrated and subjected to hydroxyapatite chromatography to obtain three lipoprotein fractions, all free from serum proteins. Each lipoprotein was confirmed by agarose gel electrophoresis. C1 NHLBI,BIOPHYS CHEM LAB,BETHESDA,MD 20892. RP SHIBUSAWA, Y (reprint author), TOKYO COLL PHARM,DEPT ANALYT CHEM,1432-1 HORINOUCHI,HACHIOJI,TOKYO 19203,JAPAN. NR 21 TC 13 Z9 15 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-4347 J9 J CHROMATOGR B JI J. Chromatogr. B-Biomed. Appl. PD FEB 17 PY 1995 VL 664 IS 2 BP 295 EP 301 DI 10.1016/0378-4347(94)00485-N PG 7 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA QK387 UT WOS:A1995QK38700002 PM 7780580 ER PT J AU PU, YM ZIFFER, H AF PU, YM ZIFFER, H TI SYNTHESIS AND ANTIMALARIAL ACTIVITIES OF 12-BETA-ALLYLDEOXOARTEMISININ AND ITS DERIVATIVES SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID QINGHAOSU ARTEMISININ; CHEMISTRY; DRUG; ACID; CONCISE AB Synthesis of 12 beta-allyldeoxoartemisinin from dihydroartemisinin and subsequent transformations to other 12 beta-alkyldeoxoartemisinins are described. All compounds were tested in vitro versus two drug-resistant strains (Plasmodium falciparum) of malaria. The in vivo activity and toxicity of the most active compound, 12 beta-propyldeoxoartemisinin, were comparable to that of arteether. C1 NIDDK,PHYS CHEM LAB,BETHESDA,MD 20892. NR 26 TC 52 Z9 53 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD FEB 17 PY 1995 VL 38 IS 4 BP 613 EP 616 DI 10.1021/jm00004a007 PG 4 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA QG979 UT WOS:A1995QG97900007 PM 7861409 ER PT J AU MASTORAKOS, G CIZZA, G KVETNANSKY, R BERGAMINI, E BLACKMAN, MR GOLD, PW CHROUSOS, GP AF MASTORAKOS, G CIZZA, G KVETNANSKY, R BERGAMINI, E BLACKMAN, MR GOLD, PW CHROUSOS, GP TI AGING AND ACUTE STRESS DECREASE CORTICOTROPIN-RELEASING HORMONE IN THE OVARY OF THE FISCHER 344/N RAT SO LIFE SCIENCES LA English DT Article DE FOLLICLE; CORPUS LUTEUM; IMMOBILIZATION; FEMALE RAT; CORTICOSTERONE ID FACTOR RECEPTORS; IMMOBILIZATION STRESS; NERVOUS-SYSTEM; LEYDIG-CELLS; SPINAL-CORD; SECRETION; LOCALIZATION; TESTIS; MACROPHAGES; INVITRO AB Corticotropin-releasing hormone (CRH), originally isolated from the hypothalamus, is widely distributed in many extrahypothalamic central nervous system sites, and in the periphery. Immunoreactive (ir)-CRH has been identified in rat and human inflammatory sites, in rat testicular Leydig cells, and in rat thecal and stromal ovarian cells. In the current study, we investigated whether aging and stress are associated with changes in ovarian ir-CRH in the rat. Healthy young (3-4 mo) and old (24 mo) female Fischer 344/N rats (6 per group) were studied in the morning, before and after being stressed by 120 min of immobilization, and were sacrificed by decapitation. Young females were all in proestrous, and old females were in constant anestrous. Pre-immobilization corticosterone (CORT) levels were similar in both age groups; immobilization produced a dramatic increase in CORT in both groups; however, the increase was smaller in the old rats, although this did not reach statistical significance (P < 0.06). Immunoreactive CRH was detected in the ovaries of all rats, and its distribution and intensity were quantified masked to the age and treatment group, in the theca, granulosa, stroma, and corpus luteum. At baseline, ir-CRH was 50% lower in old than in young rats in the theca and stroma by both distribution and intensity. Stress was associated with a decrease of ir-CRH levels in the theca in both age groups, albeit to a significantly lesser extent in old rats (old 35% versus young 70%). These data suggest a functional and, perhaps, developmental role for ovarian CRH. C1 NICHHD,DEV ENDOCRINOL BRANCH,BETHESDA,MD 20892. NIMH,CLIN NEUROENDOCRINOL BRANCH,BETHESDA,MD 20892. NINCDS,CLIN NEUROENDOCRINOL BRANCH,BETHESDA,MD 20892. UNIV PISA,IST PATOL GEN,I-56100 PISA,ITALY. JOHNS HOPKINS UNIV,SCH MED,DEPT MED,BALTIMORE,MD 21224. NR 36 TC 7 Z9 7 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0024-3205 J9 LIFE SCI JI Life Sci. PD FEB 17 PY 1995 VL 56 IS 13 BP 1065 EP 1071 DI 10.1016/0024-3205(95)00042-5 PG 7 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA QJ790 UT WOS:A1995QJ79000002 PM 9001439 ER PT J AU MALNATI, MS PERUZZI, M PARKER, KC BIDDISON, WE CICCONE, E MORETTA, A LONG, EO AF MALNATI, MS PERUZZI, M PARKER, KC BIDDISON, WE CICCONE, E MORETTA, A LONG, EO TI PEPTIDE SPECIFICITY IN THE RECOGNITION OF MHC CLASS-I BY NATURAL-KILLER-CELL CLONES SO SCIENCE LA English DT Article ID VIRUS-INFECTED CELLS; COMPLEX CLASS-I; NK CLONES; HLA-C; MOLECULES; BINDING; HLA-B27; LYSIS; SELF; BETA-2-MICROGLOBULIN AB Recognition by natural killer (NK) cells of major histocompatibility complex (MHC) class I molecules on target cells inhibits NK-mediated lysis. Here, inhibition of NK clones by HLA-B*2705 molecules mutated at single amino acids in the peptide binding site varied among HLA-B*2705-specific NK clones. In addition, a subset of such NK clones was inhibited by only one of several self peptides loaded onto HLA-B*2705 molecules expressed in peptide transporter-deficient cells, showing that recognition was peptide-specific. These data demonstrate that specific self peptides, complexed with MHC class I, provide protection from NK-mediated lysis. C1 NIAID,IMMUNOGENET LAB,ROCKVILLE,MD 20852. NIAID,MOLEC STRUCT LAB,ROCKVILLE,MD 20852. NINCDS,NEUROIMMUNOL BRANCH,BETHESDA,MD 20892. IST NAZL RIC CANC,I-16132 GENOA,ITALY. UNIV GENOA,IST ISTOL & EMBRIOL GEN,I-16132 GENOA,ITALY. RI Long, Eric/G-5475-2011; OI Long, Eric/0000-0002-7793-3728; Parker, Kenneth/0000-0002-6282-2478 NR 31 TC 251 Z9 253 U1 0 U2 3 PU AMER ASSOC ADVAN SCIENCE PI WASHINGTON PA 1333 H ST NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD FEB 17 PY 1995 VL 267 IS 5200 BP 1016 EP 1018 DI 10.1126/science.7863326 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA QG990 UT WOS:A1995QG99000036 PM 7863326 ER PT J AU CASTAGNINO, P BIESOVA, Z WONG, WT FAZIOLI, F GILL, GN DIFIORE, PP AF CASTAGNINO, P BIESOVA, Z WONG, WT FAZIOLI, F GILL, GN DIFIORE, PP TI DIRECT BINDING OF EPS8 TO THE JUXTAMEMBRANE DOMAIN OF EGFR IS PHOSPHOTYROSINE-INDEPENDENT AND SH2-INDEPENDENT SO ONCOGENE LA English DT Article DE EPS8; EGFR; JUXTAMEMBRANE; BINDING ID GROWTH-FACTOR RECEPTOR; SIGNALING PROTEINS; TYROSINE KINASES; SH3 DOMAINS; PHOSPHORYLATION; SPECIFICITY; THREONINE; ERBB-2 AB Several signal transducers bind through their SH2 domains to phosphotyrosine-containing motifs present in receptor tyrosine kinases (RTKs). However, the juxtamembrane regions of the epidermal growth factor receptor (EGFR) and of the related erbB-2 protein, while important in mitogenic signaling, lack demonstrable tyrosine phosphorylation sites, suggesting that other modalities of receptor-transducer interactions exist. A candidate for investigating this type of association is p97(eps8), a recently described substrate for RTKs. p97(eps8) is phosphorylated by several RTKs, associates with EGFR in vivo and, upon overexpression, enhances the transduction of EGFR-mediated mitogenic signals. Here we report that eps8 binds directly to the juxtamembrane region of EGFR through a domain that does not bear resemblance to SH2 domains and by a mechanism that does not require the presence of phosphotyrosine residues. Thus, the physical association between EGFR and eps8 represents a novel interaction between RTKs and their substrates. C1 NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. UNIV CALIF SAN DIEGO,DEPT MED,LA JOLLA,CA 92093. FAC MED & CHIRURG BARI,IST MICROBIOL,BARI,ITALY. RI Di Fiore, Pier Paolo/K-2130-2012 OI Di Fiore, Pier Paolo/0000-0002-2252-0950 FU NIDDK NIH HHS [DK 13149] NR 33 TC 39 Z9 39 U1 0 U2 2 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HANTS, ENGLAND RG21 2XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD FEB 16 PY 1995 VL 10 IS 4 BP 723 EP 729 PG 7 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA QH612 UT WOS:A1995QH61200012 PM 7532293 ER PT J AU SUN, Y HILDESHEIM, A LANIER, AEP CAO, Y YAO, KT RAABTRAUB, N YANG, CS AF SUN, Y HILDESHEIM, A LANIER, AEP CAO, Y YAO, KT RAABTRAUB, N YANG, CS TI NO POINT MUTATION BUT DECREASED EXPRESSION OF THE P16/MTS1 TUMOR-SUPPRESSOR GENE IN NASOPHARYNGEAL CARCINOMAS SO ONCOGENE LA English DT Note DE NASOPHARYNGEAL CARCINOMA; TUMOR SUPPRESSOR GENE; GENE MUTATION AND EXPRESSION ID P53; PROGRESSION; LINKAGE; REGION; PCR; DNA AB Nasopharyngeal carcinoma (NPC) is a malignancy which occurs at high incidence in southern China and southeast Asia. The molecular mechanism of this disease, however, is not well understood. Recently, a homozygous deletion and/or loss of heterozygosity on chromosome 9p21-22 was found in several primary NPCs (Huang et al., Cancer Res, 54: 4003-4006, 1994), suggesting that a potential tumor suppressor gene(s) residing in this region may play a role in nasopharyngeal carcinogenesis. Since p16/MTS1, a potential tumor suppressor gene, whose mutations/deletions are frequently found in variety of tumor cells, was mapped to chromosome 9p21, we investigated the possible involvement of this gene in the development of NPC by mutational and Northern blot analysis. SSCP-direct sequencing revealed no point mutations of the p16/MTS-1 gene in any of 42 primary NPC biopsies from three geographical regions nor in two NPC cell lines. We did, however, observe a codon 140(ala-->thr) polymorphism in the gene, which has been previously reported as a point mutation. Furthermore, Northern analysis revealed a decreased expression of the p16/MTS1 gene in two out of two NPC cell lines as compared with immortalized/nontransformed cell lines. These results suggest that down regulation rather than a point mutation of the p16/MTS1 gene may play a role in the genesis of NPC. C1 NCI,FREDERICK CANC RES & DEV CTR,CELL BIOL SECT,VIRAL CARCINOGENESIS LAB,FREDERICK,MD. NCI,ENVIRONM EPIDEMIOL BRANCH,BETHESDA,MD 20892. US PHS,INDIAN HLTH SERV,ALASKA AREA NAT HLTH SERV,ANCHORAGE,AK. HUNAN MED UNIV,INST HUMAN CANC,CHANGSHA,PEOPLES R CHINA. UNIV N CAROLINA,DEPT MICROBIOL,CHAPEL HILL,NC. NATL TAIWAN UNIV,COLL MED,INST MICROBIOL,TAIPEI 10764,TAIWAN. NR 23 TC 71 Z9 85 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HANTS, ENGLAND RG21 2XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD FEB 16 PY 1995 VL 10 IS 4 BP 785 EP 788 PG 4 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA QH612 UT WOS:A1995QH61200021 PM 7862458 ER PT J AU DEVESA, SS DONALDSON, J FEARS, T AF DEVESA, SS DONALDSON, J FEARS, T TI GRAPHICAL PRESENTATION OF TRENDS IN RATES SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE DATA DISPLAY; GRAPHS; INCIDENCE; MORTALITY; TRENDS ID PERCEPTION AB A variety of graphical approaches have been used to visually portray and analyze temporal trends, especially annual rates of change, in disease rates. In reviewing their own work, the authors have found that they could improve on their graphical presentations by choosing an arithmetic or logarithmic scale according to the research question being addressed, by selecting scaling ratios of the axes that allow one to detect specific rates of change, and by using uniform scaling ratios to facilitate comparisons across graphs. Different presentations of the same data can result in different impressions. The authors used rates over a 40-year period to illustrate the concepts involved and to investigate the portrayal of various rates of change. These principles extend to the plotting of odds ratios or relative risks, where the choice of an arithmetic rather than a logarithmic axis also can result in a misleading plot. The authors conclude that a graph should be designed and studied with care, clearly reflect the truth, convey information, and make a point without overemphasizing. For the particular problem addressed here, displaying temporal trends in disease rates, they see advantages in justifiable uniformity. Attention to plotting techniques in the epidemiologic and medical literature should be encouraged. RP DEVESA, SS (reprint author), NCI,DIV CANC ETIOL,EPIDEMIOL & BIOSTAT PROGRAM,BIOSTAT BRANCH,EXECUT PLAZA N,ROOM 415,BETHESDA,MD 20892, USA. NR 7 TC 109 Z9 110 U1 0 U2 4 PU AMER J EPIDEMIOLOGY PI BALTIMORE PA 624 N BROADWAY RM 225, BALTIMORE, MD 21205 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD FEB 15 PY 1995 VL 141 IS 4 BP 300 EP 304 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA QF832 UT WOS:A1995QF83200005 PM 7840107 ER PT J AU LOSONCZY, KG HARRIS, TB CORNONIHUNTLEY, J SIMONSICK, EM WALLACE, RB COOK, NR OSTFELD, AM BLAZER, DG AF LOSONCZY, KG HARRIS, TB CORNONIHUNTLEY, J SIMONSICK, EM WALLACE, RB COOK, NR OSTFELD, AM BLAZER, DG TI DOES WEIGHT-LOSS FROM MIDDLE-AGE TO OLD-AGE EXPLAIN THE INVERSE WEIGHT MORTALITY RELATION IN OLD-AGE SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE AGING; BODY MASS INDEX; MORTALITY; WEIGHT LOSS ID CORONARY HEART-DISEASE; ALL-CAUSE MORTALITY; BODY-MASS INDEX; RISK-FACTORS; ANGINA-PECTORIS; COHORT; DEATH; WOMEN; QUESTIONNAIRE; ACCURACY AB The authors examined body mass index at middle age, body mass index in old age, and weight change between age 50 years and old age in relation to mortality in old age. The study population from the Established populations for Epidemiologic Studies of the Elderly consisted of 6,387 whites age 70 years or older who experienced 2,650 deaths during the period 1982-1987. Mortality risk was highest for persons in the heaviest quintile of body mass index at age 50 (men, relative risk (RR) = 1.33, 95% confidence interval (CI) 1.13-1.57; women, RR = 1.31, 95% CI 1.12-1.53) compared with persons in the middle quintile. This pattern was reversed for body mass index in old age, with persons in the lowest quintile having the highest mortality risk (men, RR = 1.40, 95% CI 1.19-1.65; women, RR = 1.38, 95% CI 1.17-1.63) relative to persons in the middle quintile. This reversal was explained, in part, by weight change. Compared with persons with stable weight, those who lost 10 percent or more of body weight between age 50 and old age had the highest risk of mortality (men, RR = 1.69, 95% CI 1.45-1.97; women, RR = 1.62, 95% CI 1.38-1.90). Exclusion of participants who lost 10 percent or more of their weight and adjustment for health status eliminated the higher risk of death associated with low weight. The inverse association of weight and mortality in old age appears to reflect illness-related weight loss from heavier weight in middle-age. Weight history may be critical to understanding weight and mortality relations in old age. C1 DUKE UNIV,SCH MED,DEPT PSYCHIAT,DURHAM,NC. UNIV IOWA,COLL MED,DEPT PREVENT MED & ENVIRONM HLTH,IOWA CITY,IA. BRIGHAM & WOMENS HOSP,DEPT MED,BOSTON,MA 02115. YALE UNIV,SCH MED,DEPT EPIDEMIOL & PUBL HLTH,NEW HAVEN,CT. RP LOSONCZY, KG (reprint author), NIA,EPIDEMIOL DEMOG & BIOMETRY PROGRAM,GATEWAY BLDG,ROOM 3C-309,7201 WISCONSIN AVE,BETHESDA,MD 20892, USA. NR 34 TC 160 Z9 161 U1 1 U2 4 PU AMER J EPIDEMIOLOGY PI BALTIMORE PA 624 N BROADWAY RM 225, BALTIMORE, MD 21205 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD FEB 15 PY 1995 VL 141 IS 4 BP 312 EP 321 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA QF832 UT WOS:A1995QF83200007 PM 7840109 ER PT J AU BURCHFIEL, CM SHARP, DS CURB, JD RODRIGUEZ, BL HWANG, LJ MARCUS, EB YANO, K AF BURCHFIEL, CM SHARP, DS CURB, JD RODRIGUEZ, BL HWANG, LJ MARCUS, EB YANO, K TI PHYSICAL-ACTIVITY AND INCIDENCE OF DIABETES - THE HONOLULU HEART PROGRAM SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE ASIAN AMERICANS; DIABETES MELLITUS; EXERCISE; INCIDENCE; OBESITY ID IMPAIRED GLUCOSE-TOLERANCE; CARDIOVASCULAR RISK-FACTORS; JAPANESE MEN; INSULIN SENSITIVITY; DISEASE; MELLITUS; EXERCISE; HAWAII; STROKE; PREVALENCE AB Few prospective studies have assessed the relation between physical activity and diabetes. The authors examined this relation prospectively among 6,815 Japanese-American men in the Honolulu Heart Program who were aged 45-68 years and initially free of diagnosed diabetes in 1965-1968. A physical activity index was calculated based on time spent per day in different activity levels and a weighting factor correlated with estimated oxygen consumption. Incidence of clinically recognized diabetes was based on self-reported use of diabetic medication at one of two subsequent examinations. The age-adjusted 6-year cumulative incidence of diabetes decreased progressively with increasing quintile of physical activity from 73.8 to 34.3 per 1,000 (p < 0.0001, trend) in all men and from 53.9 to 21.7 per 1,000 (p < 0.0001, trend) among men with a non-fasting glucose level <225 mg/dl one hour after a 50-gm load, the latter group being less likely to have unrecognized diabetes at baseline. When stratified by tertile of baseline glucose, trends in incidence across physical activity quintiles were statistically significant in the low and middle tertiles but not in the high tertile. Similar inverse trends were observed for men in the lower four quintiles of body mass index, however, these trends were weaker and not significant for men in the upper quintile of body mass index. Age-adjusted odds ratios for diabetes comparing the upper with the lower four quintiles of physical activity were 0.55 (95% confidence interval (CI) 0.41-0.75) for all men and 0.50 (95% CI 0.33-0.74) for men with glucose <225 mg/dl. After adjustment for age, body mass index, subscapular/triceps skinfold ratio, systolic blood pressure, triglycerides, glucose, hematocrit, and parental history of diabetes, odds ratios were still statistically significant and similar in magnitude. Restriction of analyses to men who remained free of cardiovascular disease during the study period produced similar results, which suggests that inactivity due to subclinical cardiovascular disease is unlikely to be responsible for these findings. Risk factor-adjusted odds ratios for older men (55-68 years) demonstrated that physical activity confers at least the same degree of protection as in younger men (45-54 years). These results indicate that physical activity is associated inversely with incident diabetes and that the beneficial effect does not appear to be mediated through improvements in other risk factors assessed in this study. C1 NHLBI,EPIDEMIOL & BIOMETRY PROGRAM,HONOLULU EPIDEMIOL RES SECT,HONOLULU,HI. UNIV HAWAII,JOHN A BURNS SCH MED,HONOLULU,HI 96822. UNIV VIRGINIA,SCH MED,DEPT MED,DIV BIOSTAT,CHARLOTTESVILLE,VA 22908. RP BURCHFIEL, CM (reprint author), KUAKINI MED CTR,HONOLULU HEART PROGRAM,347 N KUAKINI ST,HONOLULU,HI 96817, USA. FU NHLBI NIH HHS [N01-HC-95099] NR 46 TC 127 Z9 129 U1 2 U2 9 PU AMER J EPIDEMIOLOGY PI BALTIMORE PA 624 N BROADWAY RM 225, BALTIMORE, MD 21205 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD FEB 15 PY 1995 VL 141 IS 4 BP 360 EP 368 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA QF832 UT WOS:A1995QF83200012 PM 7840114 ER PT J AU GREEN, L MINOR, JR AF GREEN, L MINOR, JR TI GENE-THERAPY FOR TREATING HIV-INFECTION MAY BE AN OPTION SO AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY LA English DT Letter RP GREEN, L (reprint author), NIH,WARREN GRANT MAGNUSON CLIN CTR,DEPT PHARM,BLDG 10,ROOM 1N257,BETHESDA,MD 20892, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEALTH-SYSTEM PHARMACISTS PI BETHESDA PA 7272 WISCONSIN AVE, BETHESDA, MD 20814 SN 1079-2082 J9 AM J HEALTH-SYST PH JI Am. J. Health-Syst. Pharm. PD FEB 15 PY 1995 VL 52 IS 4 BP 423 EP 423 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA QP025 UT WOS:A1995QP02500020 PM 7757875 ER PT J AU LEBIHAN, D JEZZARD, P HAXBY, J SADATO, N RUECKERT, L MATTAY, V AF LEBIHAN, D JEZZARD, P HAXBY, J SADATO, N RUECKERT, L MATTAY, V TI FUNCTIONAL MAGNETIC-RESONANCE-IMAGING OF THE BRAIN SO ANNALS OF INTERNAL MEDICINE LA English DT Editorial Material ID POSITRON-EMISSION TOMOGRAPHY; CEREBRAL BLOOD-FLOW; HUMAN VISUAL-CORTEX; SUPPLEMENTARY MOTOR AREA; SENSORY STIMULATION; CORTICAL AREAS; ACTIVATION; MOVEMENTS; ORGANIZATION; OXYGENATION AB This conference reviewed the potential scope of application for recently developed techniques for functional magnetic resonance imaging (fMRI) of the brain. The most successful technique is based on the sensitivity of magnetic resonance imaging (MRI) to magnetic effects caused by the modulation of the oxygenation state of hemoglobin, which is induced by local variations in blood flow during task activation. Typically, the MRI signal increases by a few percentage points during brain activation because blood flow and oxygen supply sharply increase. Brain activation images with excellent combined spatial and temporal resolution have been obtained noninvasively using visual, sensorimotor, or auditory stimuli, or during higher-order cognitive processes such as language or mental imagery. Although sensitive to misregistration artifacts and macroscopic vessels, MRI permits both the direct correlation of function with underlying anatomy and repeated studies on the same person. It may become the method of choice for studies of mental and cognitive processes, presurgical mapping, monitoring recovery from stroke or head injuries, exploration of seizure disorders, or monitoring the effects of neuropharmaceuticals. C1 NIH,WARREN GRANT MAGNUSON CLIN CTR,DEPT DIAGNOST RADIOL,BETHESDA,MD. NHLBI,CARDIAC ENERGET LAB,BETHESDA,MD 20892. NIMH,PSYCHOL & PSYCHOPATHOL & PATHOL LAB,FUNCT BRAIN IMAGING SECT,BETHESDA,MD. NINCDS,HUMAN MOTOR CONTROL SECT,MED NEUROL BRANCH,BETHESDA,MD. NINCDS,COGNIT NEUROSCI SECT,MED NEUROL BRANCH,BETHESDA,MD. NIMH,DIAGNOST RADIOL RES LAB,OFF INTRAURAL RES,BETHESDA,MD. NIMH,CLIN BRAIN DISORDERS BRANCH,BETHESDA,MD. RP LEBIHAN, D (reprint author), CEA,SERV HOSP FREDERIC JOLIOT,DRIPP,4 PL GEN LECLERC,F-91401 ORSAY,FRANCE. OI Jezzard, Peter/0000-0001-7912-2251 NR 75 TC 46 Z9 46 U1 0 U2 4 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD FEB 15 PY 1995 VL 122 IS 4 BP 296 EP 303 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA QF769 UT WOS:A1995QF76900010 PM 7825767 ER PT J AU DALAKAS, MC AF DALAKAS, MC TI ASEPTIC-MENINGITIS AND INTRAVENOUS IMMUNOGLOBULIN THERAPY - RESPONSE SO ANNALS OF INTERNAL MEDICINE LA English DT Letter RP DALAKAS, MC (reprint author), NIH,BETHESDA,MD 20892, USA. NR 5 TC 9 Z9 9 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD FEB 15 PY 1995 VL 122 IS 4 BP 316 EP 317 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA QF769 UT WOS:A1995QF76900021 ER PT J AU IKEDA, M TAGA, M SAKAKIBARA, H MINAGUCHI, H VONDERHAAR, BK AF IKEDA, M TAGA, M SAKAKIBARA, H MINAGUCHI, H VONDERHAAR, BK TI DETECTION OF MESSENGER-RNA FOR GONADOTROPIN-RELEASING-HORMONE (GNRH) BUT NOT FOR GNRH RECEPTORS IN MOUSE MAMMARY-GLANDS SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID HUMAN-BREAST CANCER; MOLECULAR-CLONING; EXPRESSION; CARCINOMA; AGONIST; GENE AB While gonadotropin-releasing hormone (GnRH), GnRH-like, or GnRH receptor (GnRH-R) have been reported to exist in several tissues other than brain or anterior pituitary, there is no report concerning GnRH or GnRH-R gene expression in the normal mammary gland. In order to define the production of GnRH as well as GnRH-R in the mammary gland at the molecular level we examined their gene expression in various functional stages of the mouse mammary gland using the reverse transcriptase-polymerase chain reaction (RT-PCR). GnRH mRNA transcripts were found in mouse mammary glands of mid-pregnant, lactating, and 3, 6, 9 days post-lactational mice, whereas GnRH-R mRNA transcripts were not detected in mammary glands of any functional stage. These results suggest a possible biological role of GnRH in mammary gland. (C) 1995 Academic Press, Inc. C1 NCI,TUMOR IMMUNOL & BIOL LAB,BETHESDA,MD 20892. NCI,TUMOR IMMUNOL & BIOL LAB,BETHESDA,MD 20892. YOKOHAMA CITY UNIV,SCH MED,DEPT OBSTET & GYNECOL,YOKOHAMA,KANAGAWA 232,JAPAN. NR 20 TC 12 Z9 14 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD FEB 15 PY 1995 VL 207 IS 2 BP 800 EP 806 DI 10.1006/bbrc.1995.1257 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA QG836 UT WOS:A1995QG83600045 PM 7864875 ER PT J AU ATWOOD, CS IKEDA, M VONDERHAAR, BK AF ATWOOD, CS IKEDA, M VONDERHAAR, BK TI INVOLUTION OF MOUSE MAMMARY-GLANDS IN WHOLE-ORGAN CULTURE - A MODEL FOR STUDYING PROGRAMMED CELL-DEATH SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID TRANSFORMING GROWTH FACTOR-BETA-1; EXPRESSION; APOPTOSIS; BREAST; PROLIFERATION; PREGNANCY; TISSUE; CASEIN; GENE AB The DNA fragmentation and gene expression patterns of involuting mouse mammary glands were compared to mammary glands in whole organ culture induced to involute by the withdrawal of lactogenic hormones. Non-random DNA degradation was observed both in vivo and in vitro, indicating that the withdrawal of lactogenic hormones triggers a program of epithelial cell death. Similar patterns of gene expression for the milk protein beta-casein and the apoptosis associated factors TGF-beta 1, TGF-beta 2 and TGF-beta 3 were observed in vivo and in vitro. These results indicate that the withdrawal of lactogenic hormones is responsible for decreased milk synthesis, epithelial cell death and tissue restructuring and that whole organ culture of mouse mammary glands is a useful model for studying the molecular events involved in these processes during involution. (C) 1995 Academic Press, Inc. RP ATWOOD, CS (reprint author), NCI,TUMOR IMMUNOL & BIOL LAB,BLDG 10,RM 5B56,10 CTR DR,BETHESDA,MD 20892, USA. NR 29 TC 45 Z9 45 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD FEB 15 PY 1995 VL 207 IS 2 BP 860 EP 867 DI 10.1006/bbrc.1995.1265 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA QG836 UT WOS:A1995QG83600053 PM 7864882 ER EF