FN Thomson Reuters Web of Science™ VR 1.0 PT J AU SECHLER, JMG CLOUSE, KA STREBEL, K WEIH, KA ROSENBERG, AS AF SECHLER, JMG CLOUSE, KA STREBEL, K WEIH, KA ROSENBERG, AS TI EFFECT OF RESTRICTION ENDONUCLEASES ON HIV-INFECTION SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD 20892. NIAID,MOLEC MICROBIOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD MAR 13 PY 1993 SU 17D BP 76 EP 76 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA KV880 UT WOS:A1993KV88000260 ER PT J AU GOLDING, B INMAN, J ZAITSEVA, M GOLDING, H AF GOLDING, B INMAN, J ZAITSEVA, M GOLDING, H TI BRUCELLA-ABORTUS, A POTENTIAL CARRIER FOR HIV-1 VACCINE STIMULATES HUMAN TH-1 CELLS SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 US FDA,CBER,DIV HEMATOL & VIROL,BETHESDA,MD 20014. NIAID,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD MAR 13 PY 1993 SU 17D BP 80 EP 80 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA KV880 UT WOS:A1993KV88000277 ER PT J AU HENDERSON, LE ROSSIO, JL WATERS, DJ BESS, JW SOWDER, RC JOHNSON, DG BENVENISTE, RE ARTHUR, LO AF HENDERSON, LE ROSSIO, JL WATERS, DJ BESS, JW SOWDER, RC JOHNSON, DG BENVENISTE, RE ARTHUR, LO TI CELLULAR PROTEINS PHYSICALLY ASSOCIATED WITH IMMUNODEFICIENCY VIRUSES AND THEIR ROLE IN VACCINE DEVELOPMENT SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,AIDS VACCINE PROGRAM,FREDERICK,MD 21702. RI Bess, Jr., Julian/B-5343-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD MAR 13 PY 1993 SU 17D BP 81 EP 81 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA KV880 UT WOS:A1993KV88000279 ER PT J AU WALKER, CM HIRSCH, V JOHNSON, P YILMA, T GIAVEDONI, L MARTHAS, M ERIKSON, A AF WALKER, CM HIRSCH, V JOHNSON, P YILMA, T GIAVEDONI, L MARTHAS, M ERIKSON, A TI TYPE-SPECIFIC AND COMMON CTL RESPONSES AGAINST THE SIMIAN IMMUNODEFICIENCY VIRUS ENVELOPE PROTEIN IN INFECTED RHESUS MACAQUES SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 CHIRON CORP,EMERYVILLE,CA 94608. NIH TWINBROOK,ROCKVILLE,MD. OHIO STATE UNIV,COLUMBUS,OH 43210. UNIV CALIF DAVIS,DAVIS,CA 95616. NR 0 TC 0 Z9 0 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 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD MAR 13 PY 1993 SU 17D BP 87 EP 87 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA KV880 UT WOS:A1993KV88000302 ER PT J AU BENNINK, JR BACIK, I LAPHAM, C ARNOLD, D SPIES, T COX, J DENG, YP DAY, P ANDERSON, R RESTIFO, N EISENLOHR, L ESQUIVEL, F YEWDELL, JW AF BENNINK, JR BACIK, I LAPHAM, C ARNOLD, D SPIES, T COX, J DENG, YP DAY, P ANDERSON, R RESTIFO, N EISENLOHR, L ESQUIVEL, F YEWDELL, JW TI PRESENTATION OF VIRAL-ANTIGENS TO CYTOTOXIC T-LYMPHOCYTES SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 NIAID,BETHESDA,MD 20892. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. NCI,BETHESDA,MD 20892. THOMAS JEFFERSON CANC INST,PHILADELPHIA,PA. RI Restifo, Nicholas/A-5713-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD MAR 13 PY 1993 SU 17D BP 90 EP 90 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA KV880 UT WOS:A1993KV88000310 ER PT J AU RESTIFO, NP YEWDELL, JW BENNINK, JR BACIK, I KAWAKAMI, Y ESQUIVEL, F ROSENBERG, SA AF RESTIFO, NP YEWDELL, JW BENNINK, JR BACIK, I KAWAKAMI, Y ESQUIVEL, F ROSENBERG, SA TI MANIPULATING THE ANTIGEN PROCESSING MACHINERY AND TUMOR IMMUNOLOGY SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. NIAID,BETHESDA,MD 20892. RI Restifo, Nicholas/A-5713-2008 NR 0 TC 0 Z9 0 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 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD MAR 13 PY 1993 SU 17D BP 91 EP 91 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA KV880 UT WOS:A1993KV88000314 ER PT J AU KAWAKAMI, Y ONEIL, BH NISHIMURA, MI RESTIFO, NP TOPALIAN, SL HOM, SS YANNELLI, JR SHILYANSKY, J SHAMAMIAN, P DELGADO, CH ELIYAHU, S CHARMLEY, P YEWDELL, JW BENNINK, JR HOOD, LE ROSENBERG, SA AF KAWAKAMI, Y ONEIL, BH NISHIMURA, MI RESTIFO, NP TOPALIAN, SL HOM, SS YANNELLI, JR SHILYANSKY, J SHAMAMIAN, P DELGADO, CH ELIYAHU, S CHARMLEY, P YEWDELL, JW BENNINK, JR HOOD, LE ROSENBERG, SA TI T-CELL IMMUNITY TO ONCOGENIC PROTEINS INCLUDING MUTATED P21 RAS AND CHIMERIC P210 BCR-ABL SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 NIAID,VIRAL DIS LAB,BETHESDA,MD 20892. NCI,SURG BRANCH,BETHESDA,MD 20892. VIRGINIA MASON RES CTR,SEATTLE,WA 98101. UNIV WASHINGTON,DEPT MOLEC BIOTECHNOL,SEATTLE,WA 98195. RI Restifo, Nicholas/A-5713-2008; yewdell, jyewdell@nih.gov/A-1702-2012; Kawakami, Yutaka /E-7429-2013 OI Kawakami, Yutaka /0000-0003-4836-2855 NR 1 TC 0 Z9 0 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 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD MAR 13 PY 1993 SU 17D BP 93 EP 93 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA KV880 UT WOS:A1993KV88000318 ER PT J AU BERZOFSKY, JA AF BERZOFSKY, JA TI SYNTHETIC PEPTIDE STRATEGIES IN THE INDUCTION AND ANALYSIS OF T-CELL RESPONSES TO HIV AND TUMORS SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 NCI,METAB BRANCH,MOLEC IMMUNOGENET & VACCINE RES SECT,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD MAR 13 PY 1993 SU 17D BP 97 EP 97 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA KV880 UT WOS:A1993KV88000329 ER PT J AU COHEN, PA ROSENBERG, SA MULE, JJ AF COHEN, PA ROSENBERG, SA MULE, JJ TI ANTIGEN-PULSED DENDRITIC CELLS ARE POTENT STIMULATORS OF TUMOR-SPECIFIC CD4+ T-CELLS SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 NCI,SURG BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD MAR 13 PY 1993 SU 17D BP 98 EP 98 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA KV880 UT WOS:A1993KV88000331 ER PT J AU FOMI, G CAVALLO, F PERICLE, F DIPIERRO, F GIOVARELLI, M GULINO, A VACCA, A COLOMBO, MP FERRARI, G MODESTI, A MUSIANI, P STOPPACCIARO, A LOLLINI, PL NANNI, P NICOLETTI, G DEGIOVANNI, C BOSCO, MC YOUNG, H AF FOMI, G CAVALLO, F PERICLE, F DIPIERRO, F GIOVARELLI, M GULINO, A VACCA, A COLOMBO, MP FERRARI, G MODESTI, A MUSIANI, P STOPPACCIARO, A LOLLINI, PL NANNI, P NICOLETTI, G DEGIOVANNI, C BOSCO, MC YOUNG, H TI CYTOKINE-INDUCED TUMOR IMMUNOGENICITY - FROM EXOGENOUS CYTOKINES TO GENE-THERAPY SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 CNR,CTR IMMUNOGENET & HISTOCOMPATIBIL,I-10126 TURIN,ITALY. UNIV TURIN,I-10124 TURIN,ITALY. UNIV LAQUILA,I-67100 LAQUILA,ITALY. IST NAZL TUMORI,I-20133 MILAN,ITALY. IST SCI SAN RAFFAELE,MILAN,ITALY. UNIV CHIETI,CHIETI,ITALY. UNIV ROME,I-00100 ROME,ITALY. UNIV BOLOGNA,I-40126 BOLOGNA,ITALY. NCI,FREDERICK,MD 21701. RI Lollini, Pier Luigi/A-7644-2008; De Giovanni, Carla/B-1312-2009; Bosco, Maria Carla/J-7928-2016 OI Lollini, Pier Luigi/0000-0003-1702-4108; Bosco, Maria Carla/0000-0003-1857-7193 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD MAR 13 PY 1993 SU 17D BP 98 EP 98 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA KV880 UT WOS:A1993KV88000332 ER PT J AU HENDERSON, RA COX, AL SAKAGUCHI, K APPELLA, E SHABANOWITZ, J ENGELHARD, VH HUNT, DF AF HENDERSON, RA COX, AL SAKAGUCHI, K APPELLA, E SHABANOWITZ, J ENGELHARD, VH HUNT, DF TI IDENTIFICATION OF HLA-A2.1-RESTRICTED T-CELL EPITOPES USING TANDEM MASS-SPECTROMETRY SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 UNIV VIRGINIA,DEPT MICROBIOL,CHARLOTTESVILLE,VA 22903. UNIV VIRGINIA,DEPT CHEM,CHARLOTTESVILLE,VA 22903. NIH,BETHESDA,MD 20892. RI Hunt, Donald/I-6936-2012 OI Hunt, Donald/0000-0003-2815-6368 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD MAR 13 PY 1993 SU 17D BP 104 EP 104 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA KV880 UT WOS:A1993KV88000352 ER PT J AU NISHIMURA, MI KAWAKAMI, Y CHARMLEY, P ONEIL, B SHILYANSKY, J YANNELLI, JR ROSENBERG, SA HOOD, LE AF NISHIMURA, MI KAWAKAMI, Y CHARMLEY, P ONEIL, B SHILYANSKY, J YANNELLI, JR ROSENBERG, SA HOOD, LE TI T-CELL RECEPTOR (TCR) V GENE USAGE IN MELANOMA SPECIFIC TUMOR INFILTRATING LYMPHOCYTES (TIL) SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 NCI,SURG BRANCH,BETHESDA,MD 20892. VIRGINIA MASON RES CTR,SEATTLE,WA 98101. UNIV WASHINGTON,DEPT MOLEC BIOTECHNOL,SEATTLE,WA 98195. RI Kawakami, Yutaka /E-7429-2013 OI Kawakami, Yutaka /0000-0003-4836-2855 NR 0 TC 0 Z9 0 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 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD MAR 13 PY 1993 SU 17D BP 110 EP 110 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA KV880 UT WOS:A1993KV88000374 ER PT J AU SHILYANSKY, J NISHIMURA, MI YANELLI, JR KAWAKAMI, Y ONEIL, B MULE, JJ ROSENBERG, SA AF SHILYANSKY, J NISHIMURA, MI YANELLI, JR KAWAKAMI, Y ONEIL, B MULE, JJ ROSENBERG, SA TI T-CELL RECEPTOR VARIABLE GENE USAGE IN MELANOMA SPECIFIC TIL CLONES AND LINES SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 NCI,SURG BRANCH,BETHESDA,MD 20892. RI Kawakami, Yutaka /E-7429-2013 OI Kawakami, Yutaka /0000-0003-4836-2855 NR 0 TC 0 Z9 0 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 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD MAR 13 PY 1993 SU 17D BP 111 EP 111 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA KV880 UT WOS:A1993KV88000380 ER PT J AU YANUCK, M CARBONE, D PENDLETON, CD TSUKUI, T MINNA, JD BERZOFSKY, JA AF YANUCK, M CARBONE, D PENDLETON, CD TSUKUI, T MINNA, JD BERZOFSKY, JA TI A MUTANT P53 TUMOR SUPPRESSOR PROTEIN IS A TARGET FOR PEPTIDE-INDUCED CD8+ CYTOTOXIC T-CELLS SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 NCI,METAB BRANCH,MOLEC IMMUNOGENET & VACCINE RES SECT,BETHESDA,MD 20892. UNIV TEXAS,SW MED CTR,SIMMONS CANC CTR,DALLAS,TX 75235. UNIV TEXAS,HOWARD HUGHES MED INST,DALLAS,TX 75235. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD MAR 13 PY 1993 SU 17D BP 113 EP 113 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA KV880 UT WOS:A1993KV88000386 ER PT J AU OCHOA, AC MIZOGUCHI, H OSHEA, JJ LOEFFLER, CM LONGO, DL AF OCHOA, AC MIZOGUCHI, H OSHEA, JJ LOEFFLER, CM LONGO, DL TI ALTERATIONS IN SIGNAL TRANSDUCTION MOLECULES IN T-LYMPHOCYTES FROM TUMOR-BEARING MICE SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 NCI,PRI DYNCORP,CLIN SERV PROGRAM,FREDERICK,MD 21702. NCI,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21702. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD MAR 13 PY 1993 SU 17D BP 117 EP 117 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA KV880 UT WOS:A1993KV88000402 ER PT J AU OGASAWARA, M ROSENBERG, SA AF OGASAWARA, M ROSENBERG, SA TI ENHANCED EXPRESSION OF MHC MOLECULES AND STIMULATION OF AUTOLOGOUS TUMOR INFILTRATING LYMPHOCYTES FOLLOWING TRANSDUCTION OF MELANOMA-CELLS WITH IFN-GAMMA GENES SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 NCI,SURG BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD MAR 13 PY 1993 SU 17D BP 120 EP 120 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA KV880 UT WOS:A1993KV88000413 ER PT J AU WILTROUT, RH KOMSCHLIES, KL FRANCO, JL GRUYS, E BACK, TT PARDOLL, DM POST, LC FENTON, RG AF WILTROUT, RH KOMSCHLIES, KL FRANCO, JL GRUYS, E BACK, TT PARDOLL, DM POST, LC FENTON, RG TI CYTOKINE TRANSFECTED 3T3 FIBROBLASTS INHIBIT THE PROGRESSION OF MURINE RENAL-CANCER SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,BCDP,FREDERICK,MD 21702. JOHNS HOPKINS UNIV,DEPT MED,BALTIMORE,MD 21205. NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21702. NR 1 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD MAR 13 PY 1993 SU 17D BP 121 EP 121 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA KV880 UT WOS:A1993KV88000419 ER PT J AU FRANCO, JL WILTROUT, RH MIZOGUCHI, H OCHOA, AC OSHEA, JJ LONGO, DL KOMSCHLIES, KL AF FRANCO, JL WILTROUT, RH MIZOGUCHI, H OCHOA, AC OSHEA, JJ LONGO, DL KOMSCHLIES, KL TI TREATMENT OF ESTABLISHED MURINE RENAL-CELL CARCINOMA WITH FLAVONE-8-ACETIC ACID (FAA) AND RHIL-2 CORRELATES WITH REVERSAL OF TUMOR-INDUCED T-CELL SIGNAL TRANSDUCTION DEFECTS SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 PRI DYNCORP,EXPTL IMMUNOL LAB,FREDERICK,MD 21702. PRI DYNCORP,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21702. PRI DYNCORP,CLIN SERV PROGRAM,FREDERICK,MD 21702. PRI DYN CORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD MAR 13 PY 1993 SU 17D BP 131 EP 131 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA KV880 UT WOS:A1993KV88000457 ER PT J AU KOMSCHLIES, KL MURPHY, WJ LONGO, DL GREGORIO, TA WILTROUT, RH AF KOMSCHLIES, KL MURPHY, WJ LONGO, DL GREGORIO, TA WILTROUT, RH TI THE INVIVO EFFECTS OF RHIL-7 ON T-CELL NUMBER AND FUNCTION IN NORMAL OR TUMOR-BEARING MICE SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 PRI DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. NCI,FCRDC,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21702. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD MAR 13 PY 1993 SU 17D BP 133 EP 133 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA KV880 UT WOS:A1993KV88000465 ER PT J AU FOWLER, DH GRESS, RE AF FOWLER, DH GRESS, RE TI TH-2 LIKE CELLS REGULATE ALLOREACTIVITY INVIVO SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 NCI,DCBDC,EIB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD MAR 13 PY 1993 SU 17D BP 137 EP 137 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA KV880 UT WOS:A1993KV88000479 ER PT J AU ARKING, R DUDAS, SP BUCK, S FORCE, A NICHOLSON, M BAKER, G AF ARKING, R DUDAS, SP BUCK, S FORCE, A NICHOLSON, M BAKER, G TI GENETIC AND MOLECULAR ANALYSIS OF LONGEVITY ASSURANCE GENES IN DROSOPHILA SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 WAYNE STATE UNIV,DETROIT,MI 48202. NIA,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD MAR 13 PY 1993 SU 17D BP 143 EP 143 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA KV880 UT WOS:A1993KV88000496 ER PT J AU STADTMAN, ER AF STADTMAN, ER TI MODIFICATION OF PROTEIN BY OZONE, METAL ION-CATALYZED REACTIONS, AND BY LIPID-PEROXIDATION PRODUCTS SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 NHLBI,BIOCHEM LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD MAR 13 PY 1993 SU 17D BP 143 EP 143 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA KV880 UT WOS:A1993KV88000495 ER PT J AU FINIELSMARLIER, F DIPASQUALE, B MARINI, AM PAUL, S YOULE, RJ AF FINIELSMARLIER, F DIPASQUALE, B MARINI, AM PAUL, S YOULE, RJ TI GLUTAMATE INDUCES APOPTOTIC CELL-DEATH IN PRIMARY CULTURES OF THE NERVOUS-SYSTEM SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 NINCDS,SURG NEUROL BRANCH,BETHESDA,MD 20892. NIMH,MOLEC PHARMACOL SECT,BETHESDA,MD 20892. NIMH,CLIN NEUROSCI BRANCH,BETHESDA,MD 20892. NR 1 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD MAR 13 PY 1993 SU 17D BP 149 EP 149 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA KV880 UT WOS:A1993KV88000514 ER PT J AU PRESTON, GA BARRETT, JC AF PRESTON, GA BARRETT, JC TI DEREGULATION OF APOPTOSIS IN PRENEOPLASTIC CELL-LINES IS LINKED TO IMMORTALIZATION AND LOSS OF TUMOR SUPPRESSOR GENE-FUNCTION SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 NIEHS,MOLEC CARCINOGENESIS LAB,RES TRIANGLE PK,NC 27709. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD MAR 13 PY 1993 SU 17D BP 151 EP 151 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA KV880 UT WOS:A1993KV88000520 ER PT J AU WONG, P LAKINS, J TAILLEFER, D PUTILINA, T CHADER, G TENNISWOOD, M AF WONG, P LAKINS, J TAILLEFER, D PUTILINA, T CHADER, G TENNISWOOD, M TI HUMAN TRPM-2 - ISOLATION AND MOLECULAR CHARACTERIZATION SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 UNIV OTTAWA,DEPT BIOCHEM,OTTAWA K1N 6N5,ONTARIO,CANADA. NEI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD MAR 13 PY 1993 SU 17D BP 151 EP 151 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA KV880 UT WOS:A1993KV88000523 ER PT J AU NOTARIO, V LOOME, JF DIPAOLO, JA DRITSCHILO, A VELASCO, JA AF NOTARIO, V LOOME, JF DIPAOLO, JA DRITSCHILO, A VELASCO, JA TI INDUCTION OF CELLULAR SENESCENCE IN HUMAN CERVICAL TUMOR-CELL LINES BY P53 SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 GEORGETOWN UNIV,MED CTR,DEPT RADIAT MED,WASHINGTON,DC 20007. NCI,BIOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD MAR 13 PY 1993 SU 17D BP 156 EP 156 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA KV880 UT WOS:A1993KV88000539 ER PT J AU ANDERSON, CW LEESMILLER, SP LIN, D MERCER, WE SAKAGUCHI, K FISCELLA, M ULLRICH, S APPELLA, E AF ANDERSON, CW LEESMILLER, SP LIN, D MERCER, WE SAKAGUCHI, K FISCELLA, M ULLRICH, S APPELLA, E TI PHOSPHORYLATION OF THE P53 TUMOR SUPPRESSOR PROTEIN BY THE DNA-ACTIVATED PROTEIN-KINASE SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 BROOKHAVEN NATL LAB,DEPT BIOL,UPTON,NY 11973. THOMAS JEFFERSON UNIV,JEFFERSON CANC INST,PHILADELPHIA,PA 19107. NCI,CELL BIOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD MAR 13 PY 1993 SU 17D BP 157 EP 157 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA KV880 UT WOS:A1993KV88000543 ER PT J AU CHERNAK, JM AF CHERNAK, JM TI THE 5' UPSTREAM REGULATORY REGION OF THE RAT AMYLOID PRECURSOR PROTEIN GENE SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 NIA,MOLEC NEUROBIOL UNIT,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD MAR 13 PY 1993 SU 17D BP 158 EP 158 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA KV880 UT WOS:A1993KV88000548 ER PT J AU BOHR, VA KRUK, P AF BOHR, VA KRUK, P TI DNA DAMAGE AND REPAIR IN TELOMERES SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 NIA,MOLEC GENET LAB,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD MAR 13 PY 1993 SU 17D BP 163 EP 163 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA KV880 UT WOS:A1993KV88000568 ER PT J AU BURKHART, BA SCHIESTL, RA BARRETT, JC AF BURKHART, BA SCHIESTL, RA BARRETT, JC TI HOMOLOGOUS TRANSCRIPTS ARE EXPRESSED IN HUMAN AND HAMSTER EXPONENTIAL FIBROBLASTS SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 NIEHS,MOLEC CARCINOGENESIS LAB,RES TRIANGLE PK,NC 27709. HARVARD UNIV,DEPT MOLEC CELLULAR TOXICOL,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD MAR 13 PY 1993 SU 17D BP 164 EP 164 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA KV880 UT WOS:A1993KV88000569 ER PT J AU RAMPINO, NJ BOHR, VA AF RAMPINO, NJ BOHR, VA TI LEVELS OF GENE SPECIFIC REPAIR DURING G(1)-PHASE SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 NIA,MOLEC GENET LAB,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD MAR 13 PY 1993 SU 17D BP 166 EP 166 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA KV880 UT WOS:A1993KV88000580 ER PT J AU ELLENBERG, SS FOULKES, MA AF ELLENBERG, SS FOULKES, MA TI THE POTENTIAL UTILITY OF LARGE, SIMPLE TRIALS IN AIDS DRUG DEVELOPMENT SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 NIAID,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD MAR 13 PY 1993 SU 17D BP 173 EP 173 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA KV880 UT WOS:A1993KV88000600 ER PT J AU HOUGHTON, PJ STEWART, CF MEYER, WH HOROWITZ, ME HOUGHTON, JA AF HOUGHTON, PJ STEWART, CF MEYER, WH HOROWITZ, ME HOUGHTON, JA TI DEVELOPING NEW AGENTS FOR TREATMENT OF CHILDHOOD-CANCER SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 ST JUDE CHILDRENS RES HOSP, MEMPHIS, TN 38101 USA. NCI, PEDIAT ONCOL BRANCH, BETHESDA, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD MAR 13 PY 1993 SU 17D BP 173 EP 173 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA KV880 UT WOS:A1993KV88000598 ER PT J AU FRIEDMAN, MA AF FRIEDMAN, MA TI JUDGING THE EFFICACY OF ANTICANCER AGENTS - RESPONSE RATES, QUALITY-OF-LIFE, AND SURVIVAL SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 NCI,DIV CANC TREATMENT,CANC THERAPY EVALUAT PROGRAM,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD MAR 13 PY 1993 SU 17D BP 174 EP 174 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA KV880 UT WOS:A1993KV88000601 ER PT J AU BOLUYT, MO ONEILL, L ZHENG, JS MEREDITH, A LAKATTA, EG CROW, MT AF BOLUYT, MO ONEILL, L ZHENG, JS MEREDITH, A LAKATTA, EG CROW, MT TI ADRENERGIC-RECEPTOR STIMULATION OF PREPROENKEPHALIN GENE-EXPRESSION IN CARDIAC MYOCYTES AND NON-MYOCYTES SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 NIA,GRC,CARDIOVASC SCI LAB,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 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 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD MAR 13 PY 1993 SU 17D BP 227 EP 227 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA KV880 UT WOS:A1993KV88000784 ER PT J AU ZHENG, JS BOLUYT, MO ONEILL, L MEREDITH, A CROW, MT LAKATTA, EG AF ZHENG, JS BOLUYT, MO ONEILL, L MEREDITH, A CROW, MT LAKATTA, EG TI STIMULATION OF P2-PURINERGIC RECEPTORS INCREASES C-FOS, C-JUN AND JUN-B GENE-EXPRESSION IN CULTURED NEONATAL CARDIAC VENTRICULAR MYOCYTES SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 NIA,CARDIOVASC SCI LAB,GRC,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 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 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD MAR 13 PY 1993 SU 17D BP 235 EP 235 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA KV880 UT WOS:A1993KV88000815 ER PT J AU SOPPET, D TSOULFAS, P TESSAROLLO, L REID, S BLAIR, J MAZZULLA, M PARADA, LF AF SOPPET, D TSOULFAS, P TESSAROLLO, L REID, S BLAIR, J MAZZULLA, M PARADA, LF TI TOWARD UNDERSTANDING TRK/NEUROTROPHIN RECEPTOR FUNCTION SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21701. RI Parada, luis/B-9400-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD MAR 13 PY 1993 SU 17D BP 243 EP 243 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA KV880 UT WOS:A1993KV88000834 ER PT J AU BUONANNO, A BEERS, R EFTIMIE, R BASU, S AF BUONANNO, A BEERS, R EFTIMIE, R BASU, S TI DIFFERENT ELECTRICAL-ACTIVITY PATTERNS SELECTIVELY REGULATE GENE-EXPRESSION SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 NIH,DEV NEUROBIOL LAB,BETHESDA,MD 20892. NR 1 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD MAR 13 PY 1993 SU 17D BP 250 EP 250 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA KV880 UT WOS:A1993KV88000859 ER PT J AU CHAO, TSO FOSTER, DA RAPP, U ROSNER, MR AF CHAO, TSO FOSTER, DA RAPP, U ROSNER, MR TI SELECTIVE REQUIREMENT FOR RAF-1 KINASE WITHIN THE SAME CELL IN ACTIVATION OF MAP KINASE BY DIFFERENT GROWTH-FACTORS SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 UNIV CHICAGO,BEN MAY INST,CHICAGO,IL 60637. UNIV CHICAGO,DEPT PHARMACOL & PHYSIOL,CHICAGO,IL 60637. CUNY HUNTER COLL,DEPT BIOL SCI,NEW YORK,NY 10021. CUNY HUNTER COLL,INST BIOMOLEC STRUCT & FUNCT,NEW YORK,NY 10021. NCI,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21702. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD MAR 13 PY 1993 SU 17D BP 250 EP 250 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA KV880 UT WOS:A1993KV88000860 ER PT J AU COSCIA, CJ BELCHEVA, MM ROWINSKI, J BARG, J CLARK, WG GAO, XM CHUANG, DM AF COSCIA, CJ BELCHEVA, MM ROWINSKI, J BARG, J CLARK, WG GAO, XM CHUANG, DM TI NOVEL OPIOID BINDING-SITES ASSOCIATED WITH THE NUCLEI OF NG108-15 NEUROHYBRID CELLS SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 ST LOUIS UNIV,SCH MED,DEPT BIOCHEM & MOLEC BIOL,ST LOUIS,MO 63104. NIMH,BIOL PSYCHIAT BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD MAR 13 PY 1993 SU 17D BP 252 EP 252 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA KV880 UT WOS:A1993KV88000864 ER PT J AU DRESSLER, GR PHELPS, D AF DRESSLER, GR PHELPS, D TI NEUROGENIC EXPRESSION OF PAX-2 IN NORMAL AND SD MICE SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 NICHHD,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD MAR 13 PY 1993 SU 17D BP 253 EP 253 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA KV880 UT WOS:A1993KV88000869 ER PT J AU MARX, SJ BARSONY, J AF MARX, SJ BARSONY, J TI HISTOLOGY ON MICROWAVE-FIXED CELLS SHOWS RAPID REORGANIZATION OF CELLULAR PROTEINS AND CYCLIC-NUCLEOTIDES SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 NIDDKD,MINERAL METAB SECT,BETHESDA,MD 20892. NR 1 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD MAR 13 PY 1993 SU 17D BP 262 EP 262 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA KV880 UT WOS:A1993KV88000903 ER PT J AU NIELSEN, DA RASKIN, JS AKHTAR, L SCHUEBEL, KE GOLDMAN, D AF NIELSEN, DA RASKIN, JS AKHTAR, L SCHUEBEL, KE GOLDMAN, D TI STUDIES ON TRYPTOPHAN-HYDROXYLASE GENE-EXPRESSION SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 NIAAA,NEUROGENET LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD MAR 13 PY 1993 SU 17D BP 263 EP 263 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA KV880 UT WOS:A1993KV88000908 ER PT J AU PARTIN, KM WONG, LA MAYER, ML BUONANNO, A AF PARTIN, KM WONG, LA MAYER, ML BUONANNO, A TI MOLECULAR AND ELECTROPHYSIOLOGICAL CHARACTERIZATION OF A KAINATE-PREFERRING RECEPTOR EXPRESSED IN RAT DORSAL-ROOT GANGLION (DRG) SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 NICHHD,CELL & MOLEC NEUROPHYSIOL LAB,BETHESDA,MD. NICHHD,DEV NEUROBIOL LAB,BETHESDA,MD. RI Mayer, Mark/H-5500-2013; Partin, Kathryn/A-8706-2015 OI Partin, Kathryn/0000-0003-3801-3299 NR 3 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD MAR 13 PY 1993 SU 17D BP 265 EP 265 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA KV880 UT WOS:A1993KV88000915 ER PT J AU SHENG, HZ FIELDS, RD LIN, PX NELSON, PG AF SHENG, HZ FIELDS, RD LIN, PX NELSON, PG TI IEGS ARE HETEROGENEOUSLY EXPRESSED IN INDIVIDUAL NEURONS AND ARE SPECIFICALLY REGULATED BY PATTERNED NEURONAL-ACTIVITY SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 NICHHD,DEV NEUROBIOL LAB,BETHESDA,MD 20892. NR 1 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD MAR 13 PY 1993 SU 17D BP 269 EP 269 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA KV880 UT WOS:A1993KV88000933 ER PT J AU SMITH, MR AF SMITH, MR TI BIOLOGICAL-ACTIVITIES OF INTRACELLULAR SIGNAL TRANSDUCTION PATHWAY INTERMEDIATES SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 FREDERICK CANC RES & DEV CTR,BRMP,PRI DYNCORP,BCDP,FREDERICK,MD 21702. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD MAR 13 PY 1993 SU 17D BP 270 EP 270 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA KV880 UT WOS:A1993KV88000936 ER PT J AU STAUFFER, JK ANGLISTER, L BUONANNO, A AF STAUFFER, JK ANGLISTER, L BUONANNO, A TI THE CLONING AND CHARACTERIZATION OF ETS DOMAIN CDNAS FROM MUSCLE SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 NICHHD,DEV NEUROBIOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD MAR 13 PY 1993 SU 17D BP 270 EP 270 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA KV880 UT WOS:A1993KV88000937 ER PT J AU BOURS, V FRANZOSO, G AZARENKO, V PARK, S KANNO, T BROWN, K SIEBENLIST, U AF BOURS, V FRANZOSO, G AZARENKO, V PARK, S KANNO, T BROWN, K SIEBENLIST, U TI THE ONCOPROTEIN BCL-3 DIRECTLY TRANSACTIVATES THROUGH KAPPA-B MOTIFS VIA ASSOCIATION WITH DNA-BINDING P50B HOMODIMERS SO CELL LA English DT Article ID V-REL ONCOGENE; RECEPTOR-ALPHA GENE; CELL-CYCLE CONTROL; RETICULOENDOTHELIOSIS VIRUS; TRANSCRIPTION FACTOR; PROTO-ONCOGENE; C-REL; P65 SUBUNIT; CHLORAMPHENICOL ACETYLTRANSFERASE; 65-KD SUBUNIT AB Bcl-3 is an IkappaB-related protein with ankyrin repeat motifs. Its gene is located at a site of recurrent translocations in a subset of B cell chronic lymphocytic leukemias. Bcl-3 associates tightly with p50B (NFKB2, p52) homodimers in cells, and together these proteins form a ternary complex with DNA at kappaB sites. Such an association functionally leads to a novel and potent form of transactivation through the kappaB motif: the tethering of Bcl-3 to DNA via the p50B homodimers allows Bcl-3 to transactivate directly, while p50B homodimers alone cannot. Transactivation mediated by Bcl-3 requires two cooperating domains located amino- and carboxy-terminal to the ankyrin domain. Bcl-3 is localized to the nucleus, and a Bcl-3-p50B complex is detected in certain lymphoid cells. Our data reveal a novel role for Bcl-3, distinct from that of the inhibitor IkappaB. The results have implications for tumorigenesis. C1 NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. NR 79 TC 352 Z9 364 U1 0 U2 4 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD MAR 12 PY 1993 VL 72 IS 5 BP 729 EP 739 DI 10.1016/0092-8674(93)90401-B PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA KR436 UT WOS:A1993KR43600009 PM 8453667 ER PT J AU TROFATTER, JA MACCOLLIN, MM RUTTER, JL MURRELL, JR DUYAO, MP PARRY, DM ELDRIDGE, R KLEY, N MENON, AG PULASKI, K HAASE, VH AMBROSE, CM MUNROE, D BOVE, C HAINES, JL MARTUZA, RL MACDONALD, ME SEIZINGER, BR SHORT, MP BUCKLER, AJ GUSELLA, JF AF TROFATTER, JA MACCOLLIN, MM RUTTER, JL MURRELL, JR DUYAO, MP PARRY, DM ELDRIDGE, R KLEY, N MENON, AG PULASKI, K HAASE, VH AMBROSE, CM MUNROE, D BOVE, C HAINES, JL MARTUZA, RL MACDONALD, ME SEIZINGER, BR SHORT, MP BUCKLER, AJ GUSELLA, JF TI A NOVEL MOESIN-LIKE, EZRIN-LIKE, RADIXIN-LIKE GENE IS A CANDIDATE FOR THE NEUROFIBROMATOSIS-2 TUMOR SUPPRESSOR SO CELL LA English DT Article ID BILATERAL ACOUSTIC NEUROFIBROMATOSIS; PROTEIN-TYROSINE-PHOSPHATASE; TYPE-1 GENE; SEQUENCE HOMOLOGY; CDNA SEQUENCE; DNA MARKER; CHROMOSOME-22; CELLS; ASSOCIATION; CLONING AB Neurofibromatosis 2 (NF2) is a dominantly inherited disorder characterized by the occurrence of bilateral vestibular schwannomas and other central nervous system tumors including multiple meningiomas. Genetic linkage studies and investigations of both sporadic and familial tumors suggest that NF2 is caused by inactivation of a tumor suppressor gene in chromosome 22q12. We have identified a candidate gene for the NF2 tumor suppressor that has suffered nonoverlapping deletions in DNA from two independent NF2 families and alterations in meningiomas from two unrelated NF2 patients. The candidate gene encodes a 587 amino acid protein with striking similarity to several members of a family of proteins proposed to link cytoskeletal components with proteins in the cell membrane. The NF2 gene may therefore constitute a novel class of tumor suppressor gene. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02129. NCI,CLIN EPIDEMIOL BRANCH,BETHESDA,MD 20892. US PHS,BETHESDA,MD 20892. BRISTOL MYERS SQUIBB,PHARMACEUT RES INST,ONCOL DRUG DISCOVERY,PRINCETON,NJ 08543. UNIV CINCINNATI,MED CTR,DEPT MOLEC GENET,CINCINNATI,OH 45267. MIT,CTR CANC RES,CAMBRIDGE,MA 02139. GEORGETOWN UNIV,MED CTR,DEPT NEUROSURG,WASHINGTON,DC 20007. RP TROFATTER, JA (reprint author), MASSACHUSETTS GEN HOSP,MOLEC NEUROGENET UNIT,BOSTON,MA 02129, USA. RI Haines, Jonathan/C-3374-2012; Haase, Volker Hans/A-6758-2013; OI Haase, Volker Hans/0000-0002-7051-8994; Rutter, Joni/0000-0002-6502-2361 FU NHGRI NIH HHS [HG00317, HG00672]; NINDS NIH HHS [NS24279] NR 73 TC 933 Z9 950 U1 0 U2 29 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD MAR 12 PY 1993 VL 72 IS 5 BP 791 EP 800 DI 10.1016/0092-8674(93)90406-G PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA KR436 UT WOS:A1993KR43600014 PM 8453669 ER PT J AU JIN, F DEVESA, SS ZHENG, W BLOT, WJ FRAUMENI, JF GAO, YT AF JIN, F DEVESA, SS ZHENG, W BLOT, WJ FRAUMENI, JF GAO, YT TI CANCER INCIDENCE TRENDS IN URBAN SHANGHAI, 1972-1989 SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID OVARIAN-CANCER; LUNG-CANCER; CHINA AB Incidence data pertaining to more than 250,000 cancer cases diagnosed during the years 1972-1989 among residents of urban Shanghai, China, were analyzed to determine the relative importance of the various malignancies and to discover changes over time. In the most recent 3-year period, lung cancer was the most frequent cancer among men (57.0 per 100,000 person-years, age-adjusted world standard), followed by cancers of the stomach (50.1), liver (29.6), esophagus (13.3), colon (11.2) and rectum (9.4). Among women, breast cancer leads (25.1), followed by cancers of the stomach (23.2), lung (18.8), liver (10.9), colon (10.2) and rectum (7.3). The most impressive increases in incidence rates from 1972-74 to 1987-89 were observed for cancers of the gallbladder (119% and 101% among men and women, respectively), colon (85% and 78%), and brain and other nervous system (71% and 60%). In addition, increases of 20-50% occurred for cancers of the pancreas, male lung, female breast, corpus uteri, kidney, and for non-Hodgkin's lymphoma. Rates declined notably for cancers of the esophagus (-54% and -53%), cervix uteri (-86%), and to a lesser extent (10-20%) cancers of the male stomach and liver. These observed trends can be explained only partly by improvements in cancer diagnosis and completeness of the cancer registry, and most likely reflect changes in the prevalence of risk factors in this population. C1 SHANGHAI CANC INST,DEPT EPIDEMIOL,2200 XIE TU RD,SHANGHAI 200032,PEOPLES R CHINA. NCI,DIV CANC ETIOL,EPIDEMIOL & BIOSTAT PROGRAM,BETHESDA,MD 20892. NR 39 TC 67 Z9 70 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 12 PY 1993 VL 53 IS 5 BP 764 EP 770 DI 10.1002/ijc.2910530510 PG 7 WC Oncology SC Oncology GA KT463 UT WOS:A1993KT46300009 PM 8449600 ER PT J AU BENINATI, S ABBRUZZESE, A CARDINALI, M AF BENINATI, S ABBRUZZESE, A CARDINALI, M TI DIFFERENCES IN THE POSTTRANSLATIONAL MODIFICATION OF PROTEINS BY POLYAMINES BETWEEN WEAKLY AND HIGHLY METASTATIC B16 MELANOMA-CELLS SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID LIQUID-CHROMATOGRAPHIC METHOD; GAMMA-GLUTAMYL; TRANSGLUTAMINASE ACTIVITY; GUINEA-PIG; DERIVATIVES; STIMULATION; PUTRESCINE; MEMBRANES; HYPUSINE; BINDING AB The identification of (gamma-glutamyl)polyamines in proteolytic digest of proteins from the cytosolic and particulate fractions of B16-F10 and B16-F10Lr6 cell lines, originating from a spontaneous tumor in C57BL/6 mice, indicates that polyamines are incorporated into melanoma cell proteins by transglutaminases (TGases-EC 2.3.2.13). The levels of spermidine-derived protein cross-links were found to be inversely related with the metastatic potential of the 2 melanoma lines. Characterization of TGase activity in the 2 tumor cell lines showed 3 types of enzyme. The soluble cellular TGase activity (TGase C) was higher, and increased more, during the growth of the least metastasizing clone B16-F10Lr6 than in the B16-F10 line, which is the most metastasizing. Consistently, N1,N8-bis(gamma-glutamyl) spermidine, which is responsible for protein cross-link formation, was present in greater amount in B16-F10Lr6 cells. The enhancement by theophylline of soluble-TGase activity and spermidine-dependent protein cross-links of B16-F10 cells reduced, with linear dose dependence, the ability of these cells to penetrate through human fibronectin-coated membrane in an in vitro assay of invasiveness. Our data confirm and extend earlier observations indicating that the propensity of a tumor to metastasize can be indirectly related to intracellular levels of TGase activity, and provide the basis for some speculation concerning the role of polyamines as modifiers of murine melanoma cell proteins in metastasis. C1 UNIV NAPLES,DEPT BIOCHEM & BIOPHYS,I-80138 NAPLES,ITALY. NIDR,CELLULAR DEV & ONCOL LAB,BETHESDA,MD 20892. RP BENINATI, S (reprint author), UNIV ROMA TOR VERGATA,DEPT BIOL,VIA E CARNEVALE,I-00173 ROME,ITALY. OI Beninati, Simone/0000-0002-2704-0745 NR 32 TC 48 Z9 49 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 12 PY 1993 VL 53 IS 5 BP 792 EP 797 DI 10.1002/ijc.2910530515 PG 6 WC Oncology SC Oncology GA KT463 UT WOS:A1993KT46300014 PM 8095490 ER PT J AU BURKE, TR SMYTH, MS NOMIZU, M OTAKA, A ROLLER, PP AF BURKE, TR SMYTH, MS NOMIZU, M OTAKA, A ROLLER, PP TI PREPARATION OF FLUORO-4-(PHOSPHONOMETHYL)-D,L-PHENYLALANINE AND HYDROXY-4-(PHOSPHONOMETHYL)-D,L-PHENYLALANINE SUITABLY PROTECTED FOR SOLID-PHASE SYNTHESIS OF PEPTIDES CONTAINING HYDROLYTICALLY STABLE ANALOGS OF O-PHOSPHOTYROSINE SO JOURNAL OF ORGANIC CHEMISTRY LA English DT Article ID RECEPTORS; TARGETS AB 4-[(Di-tert-butylphosphono)methyl]-N-(fluoren-9-ylmethoxycarbonyl)-D,L-phenylalanine [O-di-tert-butyl-Pmp-N-Fmoc, 3] has previously been shown to be a useful reagent for the solid-phase synthesis of peptides containing the hydrolytically stable O-phosphotyrosyl mimetic, phosphonomethylphenylalanine (Pmp, 2). One potential limitation of Pmp-containing peptides relative to the corresponding phosphotyrosyl prototypes is the higher pK(a2) value of phosphonic acids as compared to that of phosphates. In an effort to prepare Pmp analogues which more closely approximate phosphotyrosyl residues, O-di-tert-butyl-Pmp-N-Fmoc derivatives were made bearing monofluoro (4), difluoro (5), and hydroxy (6) substituents at the phosphonate methylene. The synthetic utility of analogues 4 and 6 was demonstrated by solid-phase synthesis of the hexameric peptide, H-Gly-X-Val-Pro-Met-Leu-OH, where X = monofluoro Pmp and hydroxy Pmp, respectively. These peptides are analogues of the SH2 recognition motif ''phosphoTyr-Val-Pro-Met-Leu'', which is important for mitogenic cellular signal transduction. The hydrolytic lability of difluoro Pmp analogue 5 precluded its usefulness in peptide synthesis. Along with O-di-tert-butyl-Pmp-N-Fmoc (3), monofluoro (4) and hydroxy (6) derivatives may prove to be useful synthons in the preparation of peptides containing hydrolytically stable analogues of phosphotyrosyl residues. RP BURKE, TR (reprint author), NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,MED CHEM LAB,BLDG 37,RM 5C06,BETHESDA,MD 20892, USA. RI Burke, Terrence/N-2601-2014 NR 28 TC 160 Z9 161 U1 1 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-3263 J9 J ORG CHEM JI J. Org. Chem. PD MAR 12 PY 1993 VL 58 IS 6 BP 1336 EP 1340 DI 10.1021/jo00058a009 PG 5 WC Chemistry, Organic SC Chemistry GA KT166 UT WOS:A1993KT16600009 ER PT J AU HRABIE, JA KLOSE, JR WINK, DA KEEFER, LK AF HRABIE, JA KLOSE, JR WINK, DA KEEFER, LK TI NEW NITRIC OXIDE-RELEASING ZWITTERIONS DERIVED FROM POLYAMINES SO JOURNAL OF ORGANIC CHEMISTRY LA English DT Article AB The reaction of nitric oxide (NO) with polyamines has been studied, resulting in the discovery of a new type of NO-releasing compound having the structure RN[N(O)NO]-(CH2)xNH2+R' (3). Numerous examples of these zwitterionic polyamine/NO adducts have been prepared and found to be very stable solids which release NO in solution. The new compounds contain as much as 45% NO by weight and are capable of releasing it all at rates which have been shown to vary in a predictable way with structure. The half-lives in buffered aqueous solution at pH 7.4 and 22-degrees-C were shown to vary from extremely short (1.3 min for diamine 8, MeN[N(O)NO]-(CH2)4NH2+Me) to very long (56 h for triamine 18, H2NCH2CH2N[N(O)NO]-CH2CH2NH3+). In general, the longest half-lives were achieved by triamine/NO adducts and derivatives of ethylenediamine (x = 2). For any given value of x, a small increase in the size of R resulted in a relatively large increase in half-life but changes in R' appeared to have little effect. Data are presented which should allow the selection of the proper compounds to achieve a wide range of desired NO generation rates. These NO-containing zwitterions should prove to be important resources in studies of the biology of NO and may also have important pharmaceutical and chemical applications. C1 NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,CHEM SECT,FREDERICK,MD 21702. RP HRABIE, JA (reprint author), NCI,FREDERICK CANC RES & DEV CTR,DYNCORP,PROGRAM RESOURCES INC,CHEM SYNTHESIS & ANAL LAB,FREDERICK,MD 21702, USA. RI Keefer, Larry/N-3247-2014 OI Keefer, Larry/0000-0001-7489-9555 NR 13 TC 503 Z9 505 U1 3 U2 41 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-3263 J9 J ORG CHEM JI J. Org. Chem. PD MAR 12 PY 1993 VL 58 IS 6 BP 1472 EP 1476 DI 10.1021/jo00058a030 PG 5 WC Chemistry, Organic SC Chemistry GA KT166 UT WOS:A1993KT16600030 ER PT J AU TOMER, KB MCGOWN, SR DETERDING, LJ AF TOMER, KB MCGOWN, SR DETERDING, LJ TI A COMPARISON OF HYBRID AND MAGNETIC-SECTOR TANDEM MASS-SPECTROMETRY FOR IONS ABOVE M/Z 1000 SO INTERNATIONAL JOURNAL OF MASS SPECTROMETRY AND ION PROCESSES LA English DT Article DE TANDEM MASS SPECTROMETRY; HYBRID; CID; HIGHER MASS ID MS-MS; BIOMOLECULES; INSTRUMENT; PEPTIDES; FAB AB Tandem mass spectrometry data were obtained for relatively high mass precursor ions (< 1500 Da) on a hybrid tandem mass spectrometer with a high maximum zero-to-peak r.f. amplitude in the collision quadrupole, which has been shown to be necessary to focus the high mass product ions through the collision quadrupole. Comparisons are made between these data and those obtained on a tandem magnetic sector instrument. Ion transmission through MS-II of the hybrid instrument varied from 5 to 20% for collision energies of up to 500 eV and a precursor mass of 1219 with maximum transmission occurring at collision energies between 200 and 300 eV. A broad distribution of product ions across the mass range was also observed. Differences are, however. observed between the spectra obtained on the hybrid and on the magnetic sector tandem instruments. Specifically, the low mass fragment ions are enhanced in the hybrid spectra relative to those obtained on the magnetic sector tandem instrument. RP TOMER, KB (reprint author), NIEHS,MOLEC BIOPHYS LAB,POB 12233,RES TRIANGLE PK,NC 27709, USA. RI Tomer, Kenneth/E-8018-2013 NR 21 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-1176 J9 INT J MASS SPECTROM JI Int. J. Mass Spectrom. Ion Process. PD MAR 11 PY 1993 VL 124 IS 2 BP 99 EP 113 DI 10.1016/0168-1176(93)80002-V PG 15 WC Physics, Atomic, Molecular & Chemical; Spectroscopy SC Physics; Spectroscopy GA KU322 UT WOS:A1993KU32200002 ER PT J AU GRESSENS, P HILL, JM GOZES, I FRIDKIN, M BRENNEMAN, DE AF GRESSENS, P HILL, JM GOZES, I FRIDKIN, M BRENNEMAN, DE TI GROWTH-FACTOR FUNCTION OF VASOACTIVE-INTESTINAL-PEPTIDE IN WHOLE CULTURED MOUSE EMBRYOS SO NATURE LA English DT Article ID SYMPATHETIC NEUROBLASTS; NEUROTROPHIC ACTION; REGULATES MITOSIS; RAT-BRAIN; POLYPEPTIDE; ANTAGONIST; SURVIVAL; VIP; DIFFERENTIATION; QUANTITATION AB FACTORS controlling central nervous system (CNS) growth immediately after neurulation are mostly unknown. Vasoactive intestinal peptide (VIP) receptors are widely distributed in the embryonic nervous system1,2, and VIP has trophic and mitogenic properties3,4 on embryonic neural tissues but inhibits growth5 and mitosis in certain tumours6. To address the potential effects of VIP on embryonic growth, we used whole postimplantation embryo cultures7,8. After a 4-h incubation, VIP stimulated growth, increasing somite number, embryonic volume, DNA and protein content, and number of cells in S-phase. A VIP antagonist9,10 substantially inhibited these VIP-mediated increments in growth. The VIP antagonist completely suppressed VIP-stimulated mitosis in the CNS while decreasing the same. in non-neuronal tissues by 38%. In vitro autoradiography revealed GTP-sensitive and GTP-insensitive VIP receptors which were differentially regulated in VIP antagonist-treated embryos. The present study suggests that VIP acts as a growth factor on early postimplantation embryos through multiple VIP receptors that exhibit tissue-specific responses. C1 NICHHD,DEV NEUROBIOL LAB,BETHESDA,MD 20892. TEL AVIV UNIV,DEPT CHEM PATHOL,IL-69978 TEL AVIV,ISRAEL. WEIZMANN INST SCI,DEPT ORGAN CHEM,IL-76100 REHOVOT,ISRAEL. RP GRESSENS, P (reprint author), NINCDS,EXPTL NEUROPATHOL LAB,BETHESDA,MD 20892, USA. NR 33 TC 248 Z9 254 U1 1 U2 3 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD MAR 11 PY 1993 VL 362 IS 6416 BP 155 EP 158 DI 10.1038/362155a0 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA KR028 UT WOS:A1993KR02800059 PM 8383805 ER PT J AU VINAYEK, R PATTO, RJ MENOZZI, D GREGORY, J MROZINSKI, JE JENSEN, RT GARDNER, JD AF VINAYEK, R PATTO, RJ MENOZZI, D GREGORY, J MROZINSKI, JE JENSEN, RT GARDNER, JD TI OCCUPATION OF LOW-AFFINITY CHOLECYSTOKININ (CCK) RECEPTORS BY CCK ACTIVATES SIGNAL TRANSDUCTION AND STIMULATES AMYLASE SECRETION IN PANCREATIC ACINAR-CELLS SO BIOCHIMICA ET BIOPHYSICA ACTA LA English DT Article DE CHOLECYSTOKININ RECEPTOR, LOW AFFINITY; SIGNAL TRANSDUCTION; (PANCREATIC ACINAR CELL) ID GUINEA-PIG PANCREAS; INOSITOL TRISPHOSPHATE; DISPERSED ACINI; DOWN-REGULATION; FREE CALCIUM; RELEASE; BINDING; CA-2+; DESENSITIZATION; CCK-JMV-180 AB Based on the effects of monensin on binding of I-125-CCK-8 and its lack of effect on CCK-8-stimulated amylase secretion we previously proposed that pancreatic acinar cells possess three classes of CCK receptors: high-affinity receptors, low-affinity receptors and very low-affinity receptors [1]. In the present study we treated pancreatic acini with carbachol to induce a complete loss of high-affinity CCK receptors and then examined the action of CCK-8 on inositol trisphosphate IP3(1,4,5), cytosolic calcium and amylase secretion in an effort to confirm and extend our previous hypothesis. We found that first incubating pancreatic acini with 10 mM carbachol decreased binding of I-125-CCK-8 measured during a second incubation by causing a complete loss of high-affinity CCK receptors with no change in the low-affinity CCK receptors. Carbachol treatment of acini, however, did not alter the action of CCK-8 on IP3(1,4,5), cytosolic calcium or amylase secretion or the action of CCK-JMV-180 on amylase secretion or on the supramaximal inhibition of amylase secretion caused by CCK-8. The present findings support our previous hypothesis that pancreatic acinar cells possess three classes of CCK receptors and suggest that high-affinity CCK receptors do not mediate the action of CCK-8 on enzyme secretion, that low-affinity CCK receptors may mediate the action of CCK on cytosolic calcium that does not involve IP3(1,4,5) and produce the upstroke of the dose-response curve for CCK-8-stimulated amylase secretion and that very low-affinity CCK receptors mediate the actions of CCK on IP3(1,4,5) and cytosolic calcium and produce the downstroke of the dose-response curve for CCK-8-stimulated amylase secretion. Moreover, CCK-JMV-180 is a full agonist for stimulating amylase secretion by acting at low-affinity CCK receptors and is an antagonist at very low-affinity CCK receptors. C1 NIDDKD,DIGEST DIS BRANCH,BETHESDA,MD. NR 36 TC 19 Z9 19 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-3002 J9 BIOCHIM BIOPHYS ACTA PD MAR 10 PY 1993 VL 1176 IS 1-2 BP 183 EP 191 DI 10.1016/0167-4889(93)90195-U PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA KR266 UT WOS:A1993KR26600027 PM 7680902 ER PT J AU FERRIS, FL AF FERRIS, FL TI HOW EFFECTIVE ARE TREATMENTS FOR DIABETIC-RETINOPATHY SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material RP FERRIS, FL (reprint author), NEI,CLIN TRIALS BRANCH,BLDG 31,ROOM 6A24,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 12 TC 183 Z9 184 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 10 PY 1993 VL 269 IS 10 BP 1290 EP 1291 DI 10.1001/jama.269.10.1290 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA KP885 UT WOS:A1993KP88500030 PM 8437309 ER PT J AU NASHED, NT BAX, A LONCHARICH, RJ SAYER, JM JERINA, DM AF NASHED, NT BAX, A LONCHARICH, RJ SAYER, JM JERINA, DM TI METHANOLYSIS OF K-REGION ARENE OXIDES - COMPARISON BETWEEN ACID-CATALYZED AND METHOXIDE ION ADDITION-REACTIONS SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID CARCINOGENIC AROMATIC-HYDROCARBONS; POLYCYCLIC-HYDROCARBONS; ABSOLUTE-CONFIGURATION; EPOXIDE HYDROLASE; C-13 ASSIGNMENTS; FACILE SYNTHESIS; COMPLETE H-1; PHENANTHRENE; ENANTIOMERS; SOLVOLYSIS AB Reactions of K-region arene oxides of benz[a]anthracene (BA-O) and its 1- (1-MBA-O), 4- (4-MBA-O), 7- (7-MBA-O), 11- (11-MBA-O), 12-methyl- (12-MBA-O), 7,12-dimethyl-(DMBA-O), and 7-bromo- (7-BrBA-O) substituted derivatives, benzo[a]pyrene (BaP-O), benzo[c]phenanthrene (BcP-O), benzo[e]pyrene (BeP-O), benzo[g]chrysene (BgC-O), chrysene (Chr-O), dibenz[a,h]anthracene (DBA-O), phenanthrene (Phe-O), 3-bromophenanthrene (3-BrPhe-O), and pyrene (Pyr-O) with acid and methoxide ion in methanol, are compared. For the acid-catalyzed reaction, products consist of cis- and trans-methanol adducts and phenols. There is no isotope effect on the ratio of phenols to solvent adducts produced from Phe-O or BcP-O when deuterium is substituted for the hydrogen that migrates. This observation is consistent with a mechanism in which product distribution in acid is determined by the relative rates of solvent capture and conformational inversion of a carbocation intermediate. As expected, only trans-methanol adducts, consisting of regioisomeric mixtures for unsymmetrical arene oxides, are formed from the reaction of methoxide ion with K-region arene oxides. The use of methanol permits the identification of products formed at each benzylic position of unsymmetrical arene oxides. Rate data for reactivity at each position could be fitted to the equation log k(MeO)/k(MeO)Phe-O = m(log k(H)/k(H)Phe-O) + b, where k(MeO) and k(H) are the second-order rate constants of the methoxide ion addition and acid-catalyzed reaction, respectively, and k(MeO)Phe-O and k(H)Phe-O are the corresponding rate constants for the reference compound phenanthrene oxide. A plot of log k(MeO)/k(MeO)Phe-O vs log k(H)/k(H)Phe-O for the reaction of 1-MBA-O, 12-MBA-O, DMBA-O, BcP-O, and BgC-O, which have either a methyl substituent in the bay region or a sterically crowded fjord region which affects the planarity of the molecules, defined one line (m = 0.31 +/- 0.02, b = 0.67 +/- 0.09), whereas a plot of the data for the reaction of the nearly planar arene oxides BA-O, 4-MBA-O, 7-MBA-O, 11-MBA-O, BaP-O, BeP-O, Chr-O, DBA-O, Phe-O, and Pyr-O defined a different fine (m = 0.33 +/- 0.07, b = -0.05 +/- 0.05). The nonzero intercept for the sterically crowded, nonplanar arene oxides indicates a steric acceleration of their rates of methoxide ion addition. The positive slopes of both lines are consistent with an S(N)2 mechanism with an unsymmetrical transition state in which the epoxide C-O bond breaking is more advanced than the formation of the new C-O bond to methoxide ion, such that a partial positive charge is developed on the aromatic moiety. C1 NIH,DIV COMP RES & TECHNOL,MOLEC GRAPH & SIMULAT LAB,BETHESDA,MD 20892. NIADDK,CHEM PHYS LAB,BETHESDA,MD 20892. RP NASHED, NT (reprint author), NIDDKD,BIOORGAN CHEM LAB,BLDG 8,ROOM 1A02,BETHESDA,MD 20892, USA. NR 54 TC 30 Z9 30 U1 1 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD MAR 10 PY 1993 VL 115 IS 5 BP 1711 EP 1722 DI 10.1021/ja00058a015 PG 12 WC Chemistry, Multidisciplinary SC Chemistry GA KR825 UT WOS:A1993KR82500015 ER PT J AU NASHED, NT SAYER, JM JERINA, DM AF NASHED, NT SAYER, JM JERINA, DM TI ACID-CATALYZED REARRANGEMENT OF K-REGION ARENE OXIDES - OBSERVATION OF KETONE INTERMEDIATES AND A STERICALLY INDUCED CHANGE IN RATE-DETERMINING STEP SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID AQUEOUS-SOLUTION; ENOLIZATION; BROMINATION; PHENOLS; 5,6-OXIDE; TAUTOMERS; MECHANISM AB K-region arene oxides rearrange to phenols in acetonitrile in two acid-catalyzed steps: rapid rearrangement of the arene oxide to positionally isomeric keto tautomers of K-region phenols, followed by slow enolization. Accumulation of the ketones, proposed intermediates in the acid-catalyzed solvolyses of arene oxides in aqueous solution, allowed their direct spectroscopic observation and characterization for the first time under solvolytic conditions. Rate constants and products are reported for the K-region arene oxides of benz[a]anthracene, its 1-, 4-, 7-, 11-, 12-methyl, and 7,12-dimethyl substituted derivatives, benzo[a]pyrene, benzo[c]phenanthrene, 3-bromophenanthrene, chrysene, dibenz[a,h]anthracene, phenanthrene, and pyrene. No primary kinetic isotope effect is observed for ketone formation from phenanthrene 9,10-oxide. A linear correlation with a slope of 1.07 is observed between the logarithm of the second-order rate constants for acid-catalyzed reaction of the arene oxide at each K-region position in acetonitrile (first step) and in methanol (where ketone does not accumulate). Negative deviations from this correlation are observed for the formation of ketones in which the carbonyl oxygen is peri to a methyl substituent. These results are discussed in terms of a mechanism in which pseudoaxial opening of the epoxide gives an initial carbocation that must undergo conformational isomerization in order to produce phenolic products by migration of a hydrogen. For compounds that follow the correlation, the rate-determining step in both methanol and acetonitrile is formation of the carbocation. For those compounds that deviate from the correlation and whose carbocations have their hydroxyl group in a peri position to a methyl ring substituent, the rate-determining step changes from formation of the carbocation (methanol) to its conformational inversion (acetonitrile). With few exceptions, NMR and kinetic evidence show that the regioisomeric K-region keto tautomers from a given arene oxide enolize with very similar rates (k(slow)). Rates of enolization are decreased by electron withdrawing groups and by steric factors that favor nonplanarity of the ring system. A large primary kinetic isotope effect (k(H)/k(D) = 4.4) is observed for the acid-catalyzed enolization of the K-region ketone derived from phenanthrene. Slow abstraction of a proton by the solvent acetonitrile from the alpha-methylene group of the O-protonated ketone is proposed to account for these results and for the fact that ketone does not accumulate in more basic solvents. The major driving force for enolization (k(slow)) is development of aromaticity in the phenol. For unsubstituted keto tautomers, a linear relationship, log k(slow) = 31.8-39.2 (X), is observed, where X is the Huckel pi-bond character for the K-region bond of the parent hydrocarbon. RP NASHED, NT (reprint author), NIDDKD,BIOORGAN CHEM LAB,BLDG 8,ROOM 1A02,BETHESDA,MD 20892, USA. NR 19 TC 13 Z9 13 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD MAR 10 PY 1993 VL 115 IS 5 BP 1723 EP 1730 DI 10.1021/ja00058a016 PG 8 WC Chemistry, Multidisciplinary SC Chemistry GA KR825 UT WOS:A1993KR82500016 ER PT J AU NAKAJIMA, T WANG, RS ELOVAARA, E PARK, SS GELBOIN, HV VAINIO, H AF NAKAJIMA, T WANG, RS ELOVAARA, E PARK, SS GELBOIN, HV VAINIO, H TI CYTOCHROME-P450-RELATED DIFFERENCES BETWEEN RATS AND MICE IN THE METABOLISM OF BENZENE, TOLUENE AND TRICHLOROETHYLENE IN LIVER-MICROSOMES SO BIOCHEMICAL PHARMACOLOGY LA English DT Article ID ANTIBODY-DIRECTED CHARACTERIZATION; MONOCLONAL-ANTIBODIES; CYTOCHROME-P-450; PHARMACOKINETICS; PROTEINS; ETHANOL AB In evaluating the risks to humans of exposure to chemicals, the results of studies in rodents are sometimes used as a basis for extrapolation. It is therefore important to elucidate differences in metabolism among species. Differences in cytochrome P450-catalysed oxidation of benzene, toluene and trichloroethylene (TRI) between male Wistar rats and male B6C3F1 mice were investigated by immunoblot and immunoinhibition assays using monoclonal antibodies (MAbs) to cytochrome P450 (CYP1A1/2, CYP2B1/2, CYP2E1 and CYP2C11/6). Immunoblot analysis showed that anti-CYP2B1/2 did not detect any protein in either untreated rat or mouse liver microsomes, whereas with anti-CYP2E1 and/or anti-CYP1A1/2 a clear-cut band was seen more in liver microsomes from mice than from rats. Mouse liver microsomes had a greater monooxidation activity for benzene and TRI than rat liver microsomes; mice also had a higher rate of aromatic hydroxylation of toluene at low substrate concentration, but a low rate of side-chain oxidation when a high concentration of toluene was used. The metabolism of benzene was saturated in mice at around 0.23 mM, but the metabolism of the other two solvents was not saturated in either rats or mice at the low concentrations used. Anti-CYP2E1 inhibited the metabolism of benzene, toluene and TRI in microsomes from mice to a greater extent than in rats, while anti-CYP2C11/6 inhibited their metabolism in rats to a greater extent than in mice; anti-CYP1A1/2 inhibited the metabolism of TRI only in microsomes from mice. These results indicate that (i) male B6C3F1 mice have more CYP2E1 and 1A1/2 than male Wistar rats, whereas rats have more CYP2C11/6 than mice; (ii) rats and mice express CYP2B1/2 but they are not immunochemically detectable; (iii) CYP2E1 and 2C11/6 in both species are responsible for the metabolism of benzene, toluene and TRI, whereas CYP1A1/2 in mice catalyses the oxidation of TRI. The differences in the metabolism of benzene, toluene and TRI in rats and in mice may therefore depend, at least in part, on differences in the distribution of P450 isozymes between the two species. C1 INST OCCUPAT HLTH,DEPT IND HYG & TOXICOL,SF-00250 HELSINKI,FINLAND. NCI,MOLEC CARCINOGENESIS LAB,BETHESDA,MD 20892. INT AGCY RES CANC,F-69372 LYON,FRANCE. RP NAKAJIMA, T (reprint author), SHINSHU UNIV,SCH MED,DEPT HYG,MATSUMOTO,NAGANO 390,JAPAN. NR 27 TC 69 Z9 70 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD MAR 9 PY 1993 VL 45 IS 5 BP 1079 EP 1085 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA KT666 UT WOS:A1993KT66600013 PM 8461037 ER PT J AU SUTKOWSKI, EM MAHER, F LAURENZA, A SIMPSON, IA SEAMON, KB AF SUTKOWSKI, EM MAHER, F LAURENZA, A SIMPSON, IA SEAMON, KB TI INTERACTION OF 7-BROMOACETYL-7-DESACETYLFORSKOLIN, AN ALKYLATING DERIVATIVE OF FORSKOLIN, WITH BOVINE BRAIN ADENYLYL CYCLASE AND HUMAN ERYTHROCYTE GLUCOSE TRANSPORTER SO BIOCHEMISTRY LA English DT Article ID H-3 FORSKOLIN; RAT-BRAIN; CATALYTIC UNIT; BINDING-SITES; F-ACTIN; PURIFICATION; MEMBRANES; PROTEIN; ALPHA; SEQUENCE AB 7-Bromoacetyl-7-desacetylforskolin (BrAcFsk), an alkylating derivative of forskolin, activated adenylyl cyclase and irreversibly blocked high affinity forskolin binding sites in human platelet membranes and rat brain membranes (Laurenza et al., 1990). Photoincorporation of an iodinated arylazido derivative of forskolin, I-125-6-AIPP-Fsk, into adenylyl cyclase in bovine brain membranes was irreversibly inhibited by BrAcFsk but not by 1,9-dideoxy-BrAcFsk, suggesting that BrAcFsk was reacting specifically with a nucleophilic group(s) at the forskolin binding site of adenylyl cyclase. Immunoblotting with antiforskolin antiserum demonstrated that partially purified bovine brain adenylyl cyclase had incorporated BrAcFsk. The interaction of BrAcFsk with the glucose transporter in human erythrocyte membranes was examined in a similar manner. Photoincorporation of I-125-7-AIPP-Fsk, an iodinated arylazido derivative of forskolin which is specific for the glucose transporter, into the glucose transporter was not irreversibly inhibited by BrAcFsk, suggesting that, in contrast to adenylyl cyclase, there is no reactive nucleophilic group at the forskolin binding site on the human erythrocyte glucose transporter. The immunoblotting procedure with antiforskolin antiserum confirmed that BrAcFsk was not covalently attached to human erythrocyte glucose transporter. C1 US FDA,DIV BIOCHEM & BIOPHYS,MOLEC PHARMACOL LAB,8800 ROCKVILLE PIKE,BETHESDA,MD 20892. NIDDKD,MCNEB,EXPTL DIABET METAB & NUTR SECT,BETHESDA,MD 20892. NR 44 TC 4 Z9 4 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAR 9 PY 1993 VL 32 IS 9 BP 2415 EP 2422 DI 10.1021/bi00060a037 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA KQ860 UT WOS:A1993KQ86000037 PM 8443181 ER PT J AU ROSENTHAL, NE AF ROSENTHAL, NE TI A DECADE OF SAD AND LIGHT THERAPY - A CITATION-CLASSIC COMMENTARY ON SEASONAL AFFECTIVE-DISORDER - A DESCRIPTION OF THE SYNDROME AND PRELIMINARY FINDINGS WITH LIGHT THERAPY - BY ROSENTHAL,N.E., SACK,D.A., GILLIN,J.C., LEWY,A.J., GOODWIN,F.K., DAVENPORT,Y., MUELLER,P.S., NEWSOME,D.A., WEHR,T.A. SO CURRENT CONTENTS/CLINICAL MEDICINE LA English DT Article RP ROSENTHAL, NE (reprint author), NIH,BLDG 10,ROOM 4S-239,BETHESDA,MD 20892, USA. NR 7 TC 0 Z9 0 U1 2 U2 6 PU INST SCI INFORM INC PI PHILADELPHIA PA 3501 MARKET ST, PHILADELPHIA, PA 19104 SN 0891-3358 J9 CC/CLIN MED PD MAR 8 PY 1993 IS 10 BP 8 EP 8 PG 1 WC Multidisciplinary Sciences; Social Sciences, Interdisciplinary SC Science & Technology - Other Topics; Social Sciences - Other Topics GA KM598 UT WOS:A1993KM59800001 ER PT J AU SURRATT, CK PERSICO, AM YANG, XD EDGAR, SR BIRD, GS HAWKINS, AL GRIFFIN, CA LI, X JABS, EW UHL, GR AF SURRATT, CK PERSICO, AM YANG, XD EDGAR, SR BIRD, GS HAWKINS, AL GRIFFIN, CA LI, X JABS, EW UHL, GR TI A HUMAN SYNAPTIC VESICLE MONOAMINE TRANSPORTER CDNA PREDICTS POSTTRANSLATIONAL MODIFICATIONS, REVEALS CHROMOSOME-10 GENE LOCALIZATION AND IDENTIFIES TAQI RFLPS SO FEBS LETTERS LA English DT Article DE MONOAMINE TRANSPORTER; CHROMOSOMAL MAPPING; POLYMORPHISM; N-LINKED GLYCOSYLATION ID PROTEIN-KINASE-C; DOPAMINE TRANSPORTER; INSITU HYBRIDIZATION; CHROMAFFIN GRANULES; PARKINSONS-DISEASE; CLONING; EXPRESSION; SITES; NEUROTRANSMITTER; REQUIREMENTS AB A human vesicular monoamine transporter cDNA has been identified by screening a human brainstem library using sequences from the rat brain synaptic vesicle monoamine transporter (SVMT) [(1992) Cell 70, 539-55 1; (1992) Proc. Natl. Acad. Sci. USA 89,10993-109971. The hSVMT shares 92% amino acid identity with the rat sequence, but displays one less consensus site for asparagine N-linked glycosylation and one more consensus site for phosphorylation by protein kinase C. The human SVMT gene maps to chromosome 10q25 using Southern blotting analysis of human/rodent hybrid cell lines and fluorescent in situ hybridization approaches. The cDNA, and a subclone, recognize TaqI polymorphisms that may prove useful to assess this gene's involvement in neuropsychiatric disorders involving monoaminergic brain systems. C1 NIDA,ADDICT RES CTR,BOX 5180,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROL,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,CTR ONCOL,DEPT NEUROSCI,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT PEDIAT,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT MED,BALTIMORE,MD 21205. OI Jabs, Ethylin/0000-0001-8983-5466 FU NCI NIH HHS [2P30 CA 06973-29]; NIGMS NIH HHS [5P01 GM1015-02] NR 32 TC 70 Z9 71 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD MAR 8 PY 1993 VL 318 IS 3 BP 325 EP 330 DI 10.1016/0014-5793(93)80539-7 PG 6 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA KQ172 UT WOS:A1993KQ17200026 PM 8095030 ER PT J AU PARK, DG JHON, DY LEE, CW LEE, KH RHEE, SG AF PARK, DG JHON, DY LEE, CW LEE, KH RHEE, SG TI ACTIVATION OF PHOSPHOLIPASE-C ISOZYMES BY G-PROTEIN BETA-GAMMA SUBUNITS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Note ID SIGNAL TRANSDUCTION; ALPHA-SUBUNIT; BOVINE BRAIN; PURIFICATION; IDENTIFICATION; MEMBRANES; CYCLASE AB The betagamma subunits of guanine nucleotide-binding proteins (G proteins) have been shown to activate unidentified phospholipase C (PLC) isozymes (Camps, M., Hou, C., Sidiropoulos, D., Stock, J. B., Jakobs, K. H., and Gierschik, P. (1992) Eur. J. Biochem. 206, 821-831; Blank, J. L., Brattain, K. A., and Exton, J. H. (1992) J. Biol. Chem. 267, 23069-23075). To identify these target PLC isozymes, we measured the effect of bovine brain G protein betagamma subunits on PLC-beta1, PLC-beta2, PLC-beta3, PLC-gamma1, and PLC-delta1 activity by reconstituting purified protein components with lipid vesicles containing [H-3]phosphatidylinositol 4,5-bisphosphate (PtdIns 4,5-P2). A nearly saturating concentration of betagamma produced 2.5-, 4-, 8.5-, and 2-fold increases in PLC-beta1, PLC-beta2, PLC-beta3, and PLC-delta1 activity, respectively, and no activation of PLC-gamma1, in the presence of 0.2 muM free Ca2+. The betagamma-dependent activation of the PLC-beta isozymes does not appear to be the result of increased affinity of the enzymes for Ca2+. The betagamma-dependent PLC activation could be reversed by addition of the GDP-bound form of the alpha subunit of G(o). The alpha subunits of G(q) class G proteins have been shown to activate PLC-beta isozymes in the order of PLC-beta1 greater-than-or-equal-to PLC-beta3 >> PLC-beta2, which differs from the order of PLC-beta3 > PLC-beta2 > PLC-beta1 for betagamma-dependent activation. Furthermore, the half-maximal concentration of betagamma (25 nM) required to activate PLC-beta3 is much higher than that of G(q) alpha subunits (0.6 nM) required to activate PLC-beta1. These results suggest that the extracellular signals that induce the dissociation of G(o) or G(i), the heterotrimeric G proteins abundant in brain, should enhance the hydrolysis of PtdIns 4,5-P2 in brain primarily through activation of PLC-beta3 (PLC-beta2 is not detectable in brain). However, signals that activate the less abundant G(q) class heterotrimers should result in the activation primarily of PLC-beta1 and PLC-beta3 by the corresponding alpha subunits. C1 NHLBI,BIOCHEM LAB,BLDG 3,RM 122,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. NR 34 TC 250 Z9 254 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 MAR 5 PY 1993 VL 268 IS 7 BP 4573 EP 4576 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA KP884 UT WOS:A1993KP88400002 PM 8383116 ER PT J AU RAU, DC GANGULY, C KORN, ED AF RAU, DC GANGULY, C KORN, ED TI A STRUCTURAL DIFFERENCE BETWEEN FILAMENTS OF PHOSPHORYLATED AND DEPHOSPHORYLATED ACANTHAMOEBA MYOSIN-II REVEALED BY ELECTRIC BIREFRINGENCE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ACTIVATED ATPASE ACTIVITY; AMINO-ACID-SEQUENCE; HEAVY-CHAIN; MG2+-ATPASE ACTIVITY; PROTEOLYTIC REMOVAL; INTEGRAL-EQUATIONS; ACTIN; PURIFICATION; CASTELLANII; SITES AB The actin-activated Mg2+-ATPase activity of filamentous Acanthamoeba myosin II is regulated by the state of phosphorylation of three sites at the C terminus of each heavy chain. This phosphorylation at the tip of the tails of monomers in a bipolar filament abolishes the activity of sites some 90 nm distant in the globular heads. Previous studies with copolymeric filaments of phosphorylated and dephosphorylated monomers strongly indicated that the activity of each monomer in a filament is dependent on the level of phosphorylation of neighboring monomers in the filament. We report here electric birefringence measurements showing that, although the overall structures of phosphorylated and dephosphorylated filaments are very similar, large, Mg2+ concentration-dependent differences in internal motion and flexibility are observed. Filaments of dephosphorylated myosin II appear to be about 50-fold stiffer than filaments of phosphorylated myosin II at 4 mM Mg2+. These results are consistent with a model in which the stiffness of the putative hinge region within the rod-like tail of each monomer is determined by the phosphorylation state of the C-terminal tails of overlapping, neighboring monomers. The flexibility of the filaments appears to be directly related to their actin-activated Mg2+-ATPase activity. C1 NHLBI,CELL BIOL LAB,BETHESDA,MD 20892. RP RAU, DC (reprint author), NIDDKD,BIOCHEM & METAB LAB,BLDG 10,RM 9B-07,BETHESDA,MD 20892, USA. RI Korn, Edward/F-9929-2012 NR 33 TC 14 Z9 14 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 5 PY 1993 VL 268 IS 7 BP 4612 EP 4621 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA KP884 UT WOS:A1993KP88400012 PM 8444836 ER PT J AU RAU, DC AF RAU, DC TI CALCULATION OF BIREFRINGENCE SIGNAL KINETICS FOR COUPLED MOTIONS WITHIN MYOSIN-II FILAMENTS - APPENDIX SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article RP RAU, DC (reprint author), NIDDKD,BIOCHEM & METAB LAB,BETHESDA,MD 20892, USA. NR 4 TC 4 Z9 4 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 5 PY 1993 VL 268 IS 7 BP 4622 EP 4624 PG 3 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA KP884 UT WOS:A1993KP88400013 ER PT J AU LANKFORD, SP COSSON, P BONIFACINO, JS KLAUSNER, RD AF LANKFORD, SP COSSON, P BONIFACINO, JS KLAUSNER, RD TI TRANSMEMBRANE DOMAIN LENGTH AFFECTS CHARGE-MEDIATED RETENTION AND DEGRADATION OF PROTEINS WITHIN THE ENDOPLASMIC-RETICULUM SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CELL ANTIGEN RECEPTOR; MEMBRANE-SPANNING DOMAIN; PRE-GOLGI DEGRADATION; AMINO-ACID; COMPLEX; CHAINS; GLYCOPROTEIN; EXPRESSION; TRANSPORT; ER AB Previous studies have shown that the presence of potentially charged amino acid residues within the transmembrane domains of type I integral membrane proteins can result in protein retention and, in some eases, degradation within the endoplasmic reticulum (ER). An apparent exception to this observation is the CD3-epsilon chain of the T-cell antigen receptor complex, which is relatively stable in spite of having a transmembrane aspartic acid residue. A chimeric protein (TepsilonT) made by replacing the transmembrane domain of the Tac antigen with that of CD3-epsilon was normally transported to the cell surface, indicating that the transmembrane domain of CD3-epsilon was essentially unable to confer the phenotype of ER retention and degradation to another protein. Progressive shortening of the TepsilonT transmembrane domain, however, resulted in increasing retention and degradation of the mutant proteins in the ER. Conversely, a mutant Tac protein containing a single aspartic acid residue in its transmembrane domain was found to be retained and degraded in the ER, but when the transmembrane domain was lengthened, ER retention and degradation of the protein were abrogated. The aspartic acid residue in the transmembrane domain of all of these mutant proteins could mediate assembly with another protein having an arginine residue in its transmembrane domain, independent of the length of the transmembrane sequence. These findings demonstrate that the length of the hydrophobic transmembrane sequence has a critical influence on the ability of potentially charged transmembrane residues to cause protein retention and degradation in the ER. C1 NICHHD,CELL BIOL & METAB BRANCH,BETHESDA,MD 20892. OI Bonifacino, Juan S./0000-0002-5673-6370 NR 26 TC 35 Z9 35 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 5 PY 1993 VL 268 IS 7 BP 4814 EP 4820 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA KP884 UT WOS:A1993KP88400041 PM 8444858 ER PT J AU EVANS, MK ROBBINS, JH GANGES, MB TARONE, RE NAIRN, RS BOHR, VA AF EVANS, MK ROBBINS, JH GANGES, MB TARONE, RE NAIRN, RS BOHR, VA TI GENE-SPECIFIC DNA-REPAIR IN XERODERMA-PIGMENTOSUM COMPLEMENTATION GROUP-A, GROUP-C, GROUP-D, AND GROUP-F - RELATION TO CELLULAR-SURVIVAL AND CLINICAL-FEATURES SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TRANSCRIPTIONALLY ACTIVE DNA; DIHYDROFOLATE-REDUCTASE GENE; IRRADIATED MAMMALIAN-CELLS; PYRIMIDINE DIMERS; TRANSCRIBED STRAND; COCKAYNE SYNDROME; DHFR GENE; FIBROBLASTS; SENSITIVITY; EFFICIENT AB We have examined the gene- and strand-specific DNA repair of UV-induced cyclobutane pyrimidine dimers in fibroblasts from normal individuals and from patients with the DNA repair-deficient disorder xeroderma pigmentosum (XP). Cells were studied from XP complementation groups A, C, D, and F. DNA repair was assessed in the essential, active gene, dihydrofolate reductase (DHFR), in the active c-myc protooncogene, and in the transcriptionally inactive delta-globin gene. In addition, repair was studied in the individual strands of the DHFR gene in normal and group C cells. In the two strains of group C cells, we find preferential DNA repair of the DHFR gene and a strand bias of the repair with more repair in the transcribed strand. This is in general accordance with previously published reports (Venema, J., van Hoffen, A., Natarajan, A. T., van Zeeland, A. A., and Mullenders, L. H. F. (1990) Nucleic Acids Res. 18, 443-448; Venema, J., van Hoffen, A., Karcagi, V., Natarajan, A. T., van Zeeland, A. A., and Mullenders, L. H. F. (1991) Mol. Cell. Biol. 11, 4128-4134), but we now find that there is more repair in the nontranscribed strand and less in the transcribed strand than what has been observed previously. In XP group A and D strains, we find little or no gene-specific DNA repair. In cells from an individual in XP complementation group F, we find less repair of dimers in the active gene than what has been observed for the overall genome. We have also measured the colony-forming ability of the strains after treatment with UV and find that this measure of survival does not correlate with the level of gene-specific repair of dimers. Thus, XP group F represents a novel repair phenotype with little or no gene-specific repair of dimers, but with relatively high UV resistance. We also evaluate the XP patients' clinical features in relation to gene-specific repair of dimers. C1 NCI,DIV CANC TREATMENT,MOLEC PHARMACOL LAB,BETHESDA,MD 20892. NCI,DIV CANC BIOL DIAG & CTR,DERMATOL BRANCH,BETHESDA,MD 20892. NCI,DIV CANC ETIOL,BIOSTAT BRANCH,BETHESDA,MD 20892. UNIV TEXAS,MD ANDERSON CANC CTR,DEPT CARCINOGENESIS,SMITHVILLE,TX 78957. NR 33 TC 74 Z9 74 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 MAR 5 PY 1993 VL 268 IS 7 BP 4839 EP 4847 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA KP884 UT WOS:A1993KP88400045 PM 8444862 ER PT J AU MESRI, EA KREITMAN, RJ FU, YM EPSTEIN, SE PASTAN, I AF MESRI, EA KREITMAN, RJ FU, YM EPSTEIN, SE PASTAN, I TI HEPARIN-BINDING TRANSFORMING GROWTH-FACTOR ALPHA-PSEUDOMONAS EXOTOXIN-A - A HEPARAN SULFATE-MODULATED RECOMBINANT TOXIN CYTOTOXIC TO CANCER-CELLS AND PROLIFERATING SMOOTH-MUSCLE CELLS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FUSION PROTEIN; FIBROBLAST GROWTH; ANIMAL TOXICITY; CHIMERIC TOXINS; ATHEROSCLEROSIS; IMMUNOTOXIN; AERUGINOSA; DOMAINS; MICE AB TGFalpha-PE40, a recombinant toxin in which transforming growth factor alpha (TGFalpha) is fused to a mutant form of Pseudomonas exotoxin, is selectively cytotoxic to cells bearing epidermal growth factor (EGF) receptors. Heparin binding EGF-like growth factor is a potent mitogen for smooth muscle cells capable of binding to both the EGF receptor and to immobilized heparin (Higashiyama, S., Abraham, J., Miller, J., Fiddes, J., and Klagsbrun, M. (1991) Science 251, 936-938). To study the effect of the heparin-binding domain in a chimeric toxin targeted to the EGF receptor, we fused the DNA sequence corresponding to the putative NH2-terminal heparin-binding (HB) domain of HB-EGF to chimeric toxins composed of TGFalpha and two different recombinant forms of Pseudomonas exotoxin (PE). One of these is a truncated form of PE devoid of the binding domain (TGFalpha-PE38); another is a mutant form of full-length toxin containing inactivating mutations in the binding domain and an altered carboxyl terminus (TGFalpha-PE(4E)KDEL). The resulting chimeric toxins HB-TGFalpha-PE38 and HB-TGFalpha-PE(4E)KDEL were expressed in Escherichia coli as inclusion bodies, refolded, and purified by heparin affinity chromatography. Both of the toxins were eluted from heparin at 0.8 M NaCl, in contrast to their respective TGFalpha toxins which were eluted at 0.15 M. Binding studies on A431 cells showed that the HB-TGFalpha toxins bound to the EGF receptor with an affinity similar to that of the TGFalpha toxins. However, cell killing studies on a panel of malignant cell lines showed that cytotoxicity was strongly affected by the presence of the HB domain. Cell lines expressing high numbers of EGF receptors such as A431 and KB were less sensitive to toxins containing the HB domain. Cells with low number of EGF receptors had similar responses to both types of toxins (MCF-7 and LNCaP) or were more sensitive to the toxin with the added HB domain (HEP-G2). HB-TGFalpha-PE(4E)KDEL was over 10-fold more cytotoxic against proliferating vascular smooth muscle cells (VSMC) than to quiescent VSMC. Moreover, HB-TGFalpha-PE(4E)KDEL was 6-fold more potent than TGFalpha-PE(4E)KDEL to proliferating VSMC. Competition studies with EGF and/or heparin showed that heparin blocks the cytotoxicity of HB-TGF toxins and the inhibitory action of heparin is stronger in cells expressing lower number of EGF receptors. In addition, experiments with heparitinase-treated cells showed that in cells with low numbers of EGF receptors the binding of the HB domain to cell surface heparan sulfate proteoglycans appears to facilitate the internalization of the toxin. We conclude that addition of a HB domain to TGFalpha-PE38 or TGFalpha-PE(4E)KDEL confers the ability to bind to and to be modulated by heparin-like molecules and increases their cytotoxicity to cells expressing low numbers of EGF receptor and proliferating smooth muscle cells. C1 NCI, DIV CANC DIAG BIOL & CTR, MOLEC BIOL LAB, 9000 ROCKVILLE PIKE, BETHESDA, MD 20892 USA. NHLBI, CARDIOL BRANCH, BETHESDA, MD 20892 USA. NR 52 TC 22 Z9 22 U1 0 U2 2 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 5 PY 1993 VL 268 IS 7 BP 4853 EP 4862 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA KP884 UT WOS:A1993KP88400047 PM 8444864 ER PT J AU SERVENTI, IM CAVANAUGH, E MOSS, J VAUGHAN, M AF SERVENTI, IM CAVANAUGH, E MOSS, J VAUGHAN, M TI CHARACTERIZATION OF THE GENE FOR ADP-RIBOSYLATION FACTOR (ARF)-2, A DEVELOPMENTALLY REGULATED, SELECTIVELY EXPRESSED MEMBER OF THE ARF FAMILY OF SIMILAR-TO-20-KDA GUANINE NUCLEOTIDE-BINDING PROTEINS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID KI-RAS GENE; CHOLERA-TOXIN; MESSENGER-RNA; MAMMALIAN-CELLS; PROMOTER REGION; PLASMID DNA; FUNCTIONAL-CHARACTERIZATION; ADENYLATE-CYCLASE; ALPHA-SUBUNIT; GTP AB ADP-ribosylation factors (ARFs) are a family of approximately 20-kDa guanine nucleotide-binding proteins that stimulate the ADP-ribosyltransferase activities of cholera toxin in vitro and function in protein trafficking in vivo. The six cloned mammalian ARFs can be grouped into three classes based on size and sequence identity. ARF 2 is a class I ARF, whose approximately 2.6-kilobase mRNA exhibits species and tissue selective expression and is developmentally regulated in rat brain. Here we report the sequence, structure, and functional promoter region of the bovine ARF 2 gene, which was facilitated by constructing a composite cDNA. The ARF 2 cDNA, constructed from a partial cDNA clone and polymerase chain reaction-amplified fragments from reverse-transcribed poly(A)+ RNA, was approximately 2270 base pairs (bp) (minus the poly(A) tail). In the 3'-untranslated region, there are two potential polyadenylation signals, ATTAAA and AATAAA, at positions 1064 and 2232, respectively, and two ATTTA motifs, believed to signal mRNA degradation, at positions 2115 and 2165. The ARF 2 gene, represented in three overlapping genomic clones, spans approximately 20 kilobase pairs with five exons and four introns. Consensus sequences for guanine nucleotide-binding and GTP hydrolysis are in separate exons, except for the NKXD sequence, which is divided by intron 4. There are multiple transcriptional initiation sites. Transient transfection of embryonic trachea cells with deletion constructs defined the functional promoter region to be within 400 bp upstream of the most 5' site of transcription initiation. This 400-bp region lacks a TATA-like sequence but contains six inverted CCAAT boxes, four potential Sp1-binding sites, and a potential AP-2-binding site. Although the pattern of expression of ARF 2 is unique among the ARFs, the structures of the class I ARF genes are conserved among its members and across species. RP SERVENTI, IM (reprint author), NHLBI,CELLULAR METAB LAB,RM 5N307,BLDG 10,BETHESDA,MD 20892, USA. NR 55 TC 30 Z9 31 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 5 PY 1993 VL 268 IS 7 BP 4863 EP 4872 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA KP884 UT WOS:A1993KP88400048 PM 8444865 ER PT J AU RABEN, N SHERMAN, J MILLER, F MENA, H PLOTZ, P AF RABEN, N SHERMAN, J MILLER, F MENA, H PLOTZ, P TI A 5' SPLICE JUNCTION MUTATION LEADING TO EXON DELETION IN AN ASHKENAZIC JEWISH FAMILY WITH PHOSPHOFRUCTOKINASE DEFICIENCY (TARUI DISEASE) SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GRADIENT GEL-ELECTROPHORESIS; TAY-SACHS DISEASE; SOMATIC-CELL HYBRIDS; PRE-MESSENGER RNA; NONSENSE MUTATIONS; TERMINATION CODON; GENE; SITE; IDENTIFICATION; ISOZYMES AB A deficiency of the muscle isoform of the enzyme, phosphofructokinase (PFK, EC 2.7.1.11), leads to an illness (glycogenosis, Type VII) characterized by myopathy and hemolysis. A patient with this disease and an affected sister were found to have a G to A substitution at the 5' donor site of intron 5 of the PFK-M gene. This mutation led to a splicing defect: a complete deletion of the preceding exon in the patient's mRNA. The patient, an affected sister, and related and unrelated family members, who were of Ashkenazic Jewish background, were screened for the mutation by denaturing gradient gel electrophoresis and by allele specific hybridization of genomic DNA. The affected sisters are homozygous for the mutation, and their children, who are unaffected, are heterozygous. The only previously characterized genetic defect in this disease, found in a Japanese patient, was a G to T mutation at the beginning of intron 15 with splicing to a cryptic site within exon 15 (1). Both mutations lead to in-frame deletions, but of different parts of the protein. The differences between the two aberrant proteins may account for clinical differences between our patients and the Japanese patient. C1 US FDA,CTR BIOL EVALUAT & RES,MOLEC IMMUNOL LAB,BETHESDA,MD 20892. ARMED FORCES INST PATHOL,DEPT NEUROPATHOL,WASHINGTON,DC 20306. RP RABEN, N (reprint author), NIAMSD,ARTHRITIS & RHEUMAT BRANCH,BETHESDA,MD 20892, USA. OI Miller, Frederick/0000-0003-2831-9593 NR 48 TC 43 Z9 43 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 MAR 5 PY 1993 VL 268 IS 7 BP 4963 EP 4967 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA KP884 UT WOS:A1993KP88400061 PM 8444874 ER PT J AU KHAN, WA BLOBE, G HALPERN, A TAYLOR, W WETSEL, WC BURNS, D LOOMIS, C HANNUN, YA AF KHAN, WA BLOBE, G HALPERN, A TAYLOR, W WETSEL, WC BURNS, D LOOMIS, C HANNUN, YA TI SELECTIVE REGULATION OF PROTEIN-KINASE-C ISOENZYMES BY OLEIC-ACID IN HUMAN PLATELETS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID UNSATURATED FATTY-ACIDS; PHORBOL ESTER; CELLULAR-REGULATION; MIXED MICELLES; ACTIVATION; INHIBITION; MEMBRANE; BINDING; PHOSPHATIDYLSERINE; DIACYLGLYCEROL AB Cis-unsaturated fatty acids activate soluble protein kinase C (PKC) in vitro and in intact platelets. The following studies were conducted to determine the effects of oleate on individual isoenzymes of PKC in human platelets. Human platelets were found to contain predominantly PKC alpha, beta(I), beta(II), and delta with minor immunoreactivity for PKC epsilon, zeta, and eta. In intact platelets, sodium oleate caused a time-dependent redistribution of PKC alpha, beta(II), and delta from cytosol to membrane fractions with little effects on PKC beta(I). On the other hand, PMA and thrombin induced translocation of all four isoenzymes of PKC. In vitro, oleate partially activated (50% of V(max)) purified calcium-dependent PKC (alpha, beta(I), and beta(II) with an EC50 of 50 muM whereas it fully activated (100% of V(max)) purified calcium-independent PKC (predominantly delta) with an EC50 of 5 muM. The selective effects of oleate on PKC isoenzymes were investigated in platelet cytosol which contains endogenous PKC and its physiologic substrates. Under these conditions, oleate potently activated calcium-independent PKC causing the phosphorylation of the 40-kDa substrate. Activation of calcium-dependent isoforms occurred only at higher concentrations of oleate. Thus, oleate activates multiple isoenzymes of PKC with predominant effects on calcium-independent PKC. C1 DUKE UNIV,MED CTR,DEPT MED,BOX 3355,DURHAM,NC 27710. DUKE UNIV,MED CTR,DEPT CELL BIOL,DURHAM,NC 27710. NIEHS,MOLEC & INTEGRATED NEUROSCI LAB,RES TRIANGLE PK,NC 27709. SPHINX PHARMACEUT,DURHAM,NC 27717. FU NCI NIH HHS [CA-47741]; NHLBI NIH HHS [HL-43707] NR 32 TC 99 Z9 99 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 5 PY 1993 VL 268 IS 7 BP 5063 EP 5068 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA KP884 UT WOS:A1993KP88400074 PM 8444883 ER PT J AU HAMAWY, MM MERGENHAGEN, SE SIRAGANIAN, RP AF HAMAWY, MM MERGENHAGEN, SE SIRAGANIAN, RP TI CELL ADHERENCE TO FIBRONECTIN AND THE AGGREGATION OF THE HIGH-AFFINITY IMMUNOGLOBULIN-E RECEPTOR SYNERGISTICALLY REGULATE TYROSINE PHOSPHORYLATION OF 105-115-KDA PROTEINS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BASOPHILIC LEUKEMIA-CELLS; VIRUS-TRANSFORMED CELLS; TUMOR-NECROSIS-FACTOR; SIGNAL TRANSDUCTION; 2H3 CELLS; HISTAMINE-RELEASE; HUMAN NEUTROPHILS; PHORBOL ESTER; T-CELLS; EXTRACELLULAR-MATRIX AB Adherence of cells to extracellular matrix components modulates cellular responses. Here we compared the array of tyrosine phosphorylated proteins induced by the aggregation of the high affinity receptor for IgE (FcepsilonRI) in fibronectin-adherent and in nonadherent rat basophilic leukemia (RBL-2H3) cells. Adherence to fibronectin in the absence of FcepsilonRI aggregation induced tyrosine phosphorylation of 105-115-kDa proteins. This phosphorylation was reversed by EDTA and by a synthetic peptide containing the sequence Arg-Gly-Asp, demonstrating a requirement for fibronectin-integrin interaction. Aggregation of FcepsilonRI in fibronectin-adherent cells markedly enhanced the tyrosine phosphorylation of the same 105-115-kDa proteins. There were minimal differences in tyrosine phosphorylation of other proteins induced by the aggregation of FcepsilonRI in nonadherent and in fibronectin-adherent cells. Direct activation of protein kinase C and/or increase in calcium influx induced the phosphorylation of the 105-115-kDa proteins only in fibronectin-adherent cells. The magnitude of the phosphorylation of the 105-115-kDa proteins induced by the aggregation of FcepsilonRI in fibronectin-adherent cells was substantially greater than the sum of that due to adherence to fibronectin and the aggregation of FcepsilonRI in nonadherent cells. Therefore, cell adherence and the aggregation of FcepsilonRI synergistically regulate tyrosine phosphorylation of the 105-115 kDa proteins. RP HAMAWY, MM (reprint author), NIDR,IMMUNOL LAB,BLDG 10,RM 1N106,BETHESDA,MD 20892, USA. NR 62 TC 64 Z9 64 U1 1 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 5 PY 1993 VL 268 IS 7 BP 5227 EP 5233 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA KP884 UT WOS:A1993KP88400095 PM 8444898 ER PT J AU WEEKS, BS DESAI, K LOEWENSTEIN, PM KLOTMAN, ME KLOTMAN, PE GREEN, M KLEINMAN, HK AF WEEKS, BS DESAI, K LOEWENSTEIN, PM KLOTMAN, ME KLOTMAN, PE GREEN, M KLEINMAN, HK TI IDENTIFICATION OF A NOVEL CELL ATTACHMENT DOMAIN IN THE HIV-1 TAT PROTEIN AND ITS 90-KDA CELL-SURFACE BINDING-PROTEIN SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; ARG-GLY-ASP; GROWTH-FACTOR; RECEPTORS; INTEGRINS; ADHESION; TERMINI; RGD AB The HIV-1 transactivator protein Tat is essential for viral gene expression and replication. Tat is taken up by cells and transactivates the HIV-LTR promoter in the cell nucleus. The present studies show that cells adhere to both synthetic and recombinant Tat, and, using synthetic peptides, we localize the binding site to a region spanning amino acid residues 49-57 (peptide Tat49-57). Tat49-57 also inhibited cell attachment to solid phase full-length Tat peptide and to recombinant Tat protein. Using Tat peptide affinity chromatography, we identified a 90-kDa cell surface protein that binds to Tat. The 90-kDa protein could be eluted from the Tat column using the Tat49-57 peptide. A 90-kDa cell surface Tat binding protein was also identified by co-precipitation with Tat after incubation with radiolabeled cell membrane preparations. Co-precipitation of the 90-kDa protein was inhibited by competition with a Tat49-65 peptide, but not with Tat55-86. Our findings suggest that cellular attachment to Tat is mediated through a 90-kDa cell surface protein that binds to a Tat domain between amino acids 49 and 57. C1 ST LOUIS UNIV,MED CTR,INST MOLEC VIROL,ST LOUIS,MO 63110. NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. RP WEEKS, BS (reprint author), NIDR,DEV BIOL LAB,BETHESDA,MD 20892, USA. RI klotman, mary/A-1921-2016 FU NIAID NIH HHS [AI28201, 5 K06 AI04739] NR 17 TC 71 Z9 76 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 5 PY 1993 VL 268 IS 7 BP 5279 EP 5284 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA KP884 UT WOS:A1993KP88400102 PM 8444901 ER PT J AU SAIKAWA, Y KNIGHT, CB SAIKAWA, T PAGE, ST CHABNER, BA ELWOOD, PC AF SAIKAWA, Y KNIGHT, CB SAIKAWA, T PAGE, ST CHABNER, BA ELWOOD, PC TI DECREASED EXPRESSION OF THE HUMAN FOLATE RECEPTOR MEDIATES TRANSPORT-DEFECTIVE METHOTREXATE RESISTANCE IN KB CELLS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HAMSTER OVARY CELLS; BINDING-PROTEIN; L1210 CELLS; DIHYDROFOLATE-REDUCTASE; MEMBRANE-TRANSPORT; LEUKEMIA-CELLS; FLUORESCEINATED METHOTREXATE; SYNTHETASE-ACTIVITY; HEPATOMA-CELLS; AFFINITY AB The human membrane-associated folate binding protein, or folate receptor (hFR), is a necessary component of folate and methotrexate (MTX) transport in some cell lines. To investigate the role of hFR in acquired MTX resistance in human cells, we characterized nine MTX-resistant clones selected from human nasopharyngeal epidermoid carcinoma (KB) cells (cells which transport folates/anti-folates via the hFR) cultured in media containing low folate concentrations. Compared with wild type KB cells, the level of resistance of the clones ranges from 2- to 80-fold higher and the resistant phenotypes of the clones are characterized as follows. 1) DHFR levels are increased (3-13-fold) in four of nine clones; 2) MTX polyglutamation is not detectably different; 3) the extents of MTX efflux are similar; 4) initial rates of MTX efflux are similar except for two clones which exhibit slightly faster efflux rates (approximately 2-fold); and 5) the V(max) for specific MTX and 5-methyltetrahydrofolate transport are decreased (2-18-fold) in all mutants. The K(t) values for MTX transport of each mutant are similar to the K(t) of KB cells. These results indicate that all nine MTX-resistant clones exhibit defective MTX transport and that four clones also have increased DHFR levels. Based on folic acid binding assays, the hFR is reduced by 1.8-24-fold in these clones relative to KB cell hFR expression. Western, Northern, and Southern analyses are consistent with decreased hFR expression in these clones rather than mutations, resulting in alterations in the size or ligand binding affinities of the hFR. The decrement in hFR expression correlates closely with the degree of reduction in MTX transport V(max) for each clone. Since folate and MTX influx proceed via hFR in KB cells and in these mutants, the correlation (R2 = 0.90) between hFR expression and the MTX transport V(max) of each clone indicates that hFR expression is an important determinant of acquired MTX resistance in this human tumor cell line. These studies demonstrate that defective transport (manifested by decreased V(max)) resulting from decreased expression of the hFR is frequent in KB cells cultured under these conditions and suggest that modulation of hFR may be relevant to MTX cytotoxicity or resistance in tissues or cells expressing functionally significant levels of hFR. C1 NCI,MED BRANCH,BLDG 10,RM 12N226,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. NR 65 TC 37 Z9 37 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 5 PY 1993 VL 268 IS 7 BP 5293 EP 5301 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA KP884 UT WOS:A1993KP88400104 PM 7680349 ER PT J AU NICHOLLS, PJ JOHNSON, VG ANDREW, SM HOOGENBOOM, HR RAUS, JCM YOULE, RJ AF NICHOLLS, PJ JOHNSON, VG ANDREW, SM HOOGENBOOM, HR RAUS, JCM YOULE, RJ TI CHARACTERIZATION OF SINGLE-CHAIN ANTIBODY (SFV)-TOXIN FUSION PROTEINS PRODUCED INVITRO IN RABBIT RETICULOCYTE LYSATE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN TRANSFERRIN RECEPTOR; DIPHTHERIA-TOXIN RECEPTOR; FRAGMENT D-DIMER; PSEUDOMONAS EXOTOXIN; ESCHERICHIA-COLI; RECOMBINANT IMMUNOTOXIN; GENETIC CONSTRUCTION; OVERLAP EXTENSION; VARIABLE DOMAINS; PLASMA-MEMBRANE AB Chimeric proteins consisting of a fusion between binding-deficient mutants of diphtheria toxin (DT) or Pseudomonas exotoxin A (PE) and a single-chain antibody (E6 sFv) against the human transferrin receptor (TfnR) were expressed in a rabbit reticulocyte lysate system. Molecules utilizing PE40 (the carboxyl terminus 40 kDa of PE, lacking the binding domain) exhibited significant E6 sFv-mediated, cell type-specific cytotoxicity (IC50 1 x 10(-10) M) against a human erythroleukemia-derived cell line, K562. In contrast, a fusion protein between the same sFv and a DT mutant, DTM1 (containing two amino acid substitutions in the binding domain [S(508)F, S(525)F]) was not significantly cytotoxic, despite being enzymatically active. A tripartite protein in the form NH2-DTM1-E6 sFv-PE40-COOH exhibited cytotoxicity comparable to that of the PE40-sFv fusion (IC50 1 x 10(-10) M), suggesting that the deficit in activity of DTM1-sFv is not a function of misfolding of the sFv moiety or of a reduced ability to bind TfnR. In contrast to DTM1-E6 sFv, a fusion protein between a second DT mutant, CRM 107 [S(525)F], and the E6 sFv was specifically cytotoxic (IC50 1 X 10(-9) M), and toxicity could be blocked by addition of excess E6 antibody. The cell-free in vitro expression system we describe is rapid and may be used to express functional toxin-sFv fusion proteins. No protein refolding procedures are required, and the technique may be used to express proteins which, due to restrictions imposed on manipulation of toxin-encoding genes in Escherichia coli, could not be produced by more conventional methods. C1 US FDA,CBER,DIV BACTERIAL PROD,BACTERIAL TOXINS LAB,BETHESDA,MD 20892. NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892. LIMBURGS UNIV CENTRUM,DR L WILLEMS INST,B-3610 DIEPENBEEK,BELGIUM. LIMBURGS UNIV CENTRUM,DEPT WNIF,B-3610 DIEPENBEEK,BELGIUM. RP NICHOLLS, PJ (reprint author), NINCDS,SURG NEUROL BRANCH,BIOCHEM SECT,BETHESDA,MD 20892, USA. NR 55 TC 32 Z9 32 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 MAR 5 PY 1993 VL 268 IS 7 BP 5302 EP 5308 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA KP884 UT WOS:A1993KP88400105 PM 8444903 ER PT J AU TORRENCE, PF KINJO, J KHAMNEI, S GREIG, NH AF TORRENCE, PF KINJO, J KHAMNEI, S GREIG, NH TI SYNTHESIS AND PHARMACOKINETICS OF A DIHYDROPYRIDINE CHEMICAL DELIVERY SYSTEM FOR THE ANTIIMMUNODEFICIENCY VIRUS AGENT DIDEOXYCYTIDINE SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID HUMAN IMMUNODEFICIENCY VIRUS; CENTRAL NERVOUS-SYSTEM; AIDS DEMENTIA COMPLEX; BIOLOGICAL-MEMBRANES; CEREBROSPINAL-FLUID; BRAIN; 2',3'-DIDEOXYCYTIDINE; ZIDOVUDINE; INVITRO; 3'-AZIDO-3'-DEOXYTHYMIDINE AB In order to explore the possibility that a dihydropyridine/pyridinium redox chemical delivery system might enhance significantly the brain uptake of the anti-HIV agent dideoxycytidine (DDC), we prepared a DDC derivative which bore the 1,4-dihydro-1-methyl-3-pyridylcarbonyl moiety at both the cytidine exocyclic amino moiety and the sugar 5'-hydroxyl function; namely, [(1,4N-bis-[(1,4-dihydro-1-methyl-3-pyridinyl)carbonyl]-2',3'-dideoxycytidine(2). In cell-free extracts of rat brain tissue, compound 2 was readily converted to free DDC by stepwise oxidation and hydrolysis of the dihydropyridyl groups. Time-dependent plasma and brain concentrations of DDC and 2 were determined following iv administration of 2 (49.3 mg/kg) to rats. Compound 2 could be detected in brain, reaching peak concentrations of 7.7 +/- 2.9 nmol/g at 15 min. Low levels of DDC also were detected with a peak concentration of 1.4 +/- 0.5 nmol/g at 240 min after injection. The brain/plasma concentration integral of compound 2 was 0.95 whereas that for DDC in brain as a ratio of combined DDC and compound 2 levels in plasma was 0.24. Despite this, brain concentrations remained low and not significantly different from those achieved following administration of DDC alone. C1 NIA,NEUROSCI LAB,BETHESDA,MD 20892. RP TORRENCE, PF (reprint author), NIDDKD,MED CHEM LAB,BIOMED CHEM SECT,BLDG 8,RM B2A02,BETHESDA,MD 20892, USA. NR 28 TC 21 Z9 21 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD MAR 5 PY 1993 VL 36 IS 5 BP 529 EP 537 DI 10.1021/jm00057a002 PG 9 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA KR250 UT WOS:A1993KR25000002 PM 8388473 ER PT J AU SUN, L MCPHAIL, AT HAMEL, E LIN, CM HASTIE, SB CHANG, JJ LEE, KH AF SUN, L MCPHAIL, AT HAMEL, E LIN, CM HASTIE, SB CHANG, JJ LEE, KH TI ANTITUMOR AGENTS .139. SYNTHESIS AND BIOLOGICAL EVALUATION OF THIOCOLCHICINE ANALOGS 5,6-DIHYDRO-6(S)-(ACYLOXY) AND 5,6-DIHYDRO-6(S)-[(AROYLOXY)METHYL]-1,2,3-TRIMETHOXY-9-(METHYLTHIO)-8H-C YCLOHEPTA[A]NAPHTHALEN-8-ONES AS NOVEL CYTOTOXIC AND ANTIMITOTIC AGENTS SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID B-RING; METHYL-ETHER; TUBULIN; COLCHICINE; BINDING; COMBRETASTATIN-A-4; CONFIGURATION; INHIBITOR AB A series of novel thiocolchicine analogs, 5,6-dihydro-6(S)-(acyloxy)- and 5,6-dihydro-6(S)-[(aroyloxy)-methyl]-1,2,3-trimethoxy-9-(methylthio)-8H-cyclohepta[a]naphthalen-8-ones, possessing a six-membered ring B, have been synthesized and evaluated for their cytotoxicity against various tumor cell lines, including solid tumor cell lines, and for their interaction with tubulin. The configuration of the parent alcohol (compound 5) was established unequivocally as (aR,6S) by X-ray crystallographic analysis. The side chain at the C(6) position is in a pseudoaxial orientation. The optical properties and H-1 NMR data indicated that these compounds have the same conformations in solution as in the solid state. Biological results showed that compounds (5, 6, 14,15,17, and 18) bearing a small side chain at C(6) demonstrate high potency in inhibiting tubulin polymerization and binding of radiolabeled colchicine to tubulin. The most cytotoxic compounds were 14, 15, 17, and 18, with good activity against several solid tumor cell lines. To explain the strong antitubulin activity of compound 5 (with an aR configured biaryl system in contrast to the aS configuration previously described for colchicinoids, allocolchicinoids, and steganacin) we speculate that a rapid atropisomerism equilibrium must exist for 5 and its active derivatives. This equilibrium would yield adequate amounts of aS-configured conformers that interact strongly with tubulin. Since the optically inactive 18 is also a potent inhibitor of tubulin, the configuration of the side chain of these six-membered ring B analogs cannot be essential for their binding to tubulin. Instead we propose that the size of ring B and of its side chain play important roles in tubulin binding activity by affecting the rotation of the rings A and C along their linking C-C bond axis. C1 UNIV N CAROLINA,SCH PHARM,DIV MED CHEM & NAT PROD,NAT PROD LAB,CHAPEL HILL,NC 27599. DUKE UNIV,PAUL M GROSS CHEM LAB,DEPT CHEM,DURHAM,NC 27706. NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,MOLEC PHARMACOL LAB,BETHESDA,MD 20892. SUNY BINGHAMTON,DEPT CHEM,BINGHAMTON,NY 13902. UNIV N CAROLINA,SCH MED,DEPT LAB ANIM MED,CHAPEL HILL,NC 27599. RI Bane, Susan/C-1414-2013 OI Bane, Susan/0000-0002-4270-6314 FU NCI NIH HHS [CA 17625] NR 41 TC 28 Z9 30 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD MAR 5 PY 1993 VL 36 IS 5 BP 544 EP 551 DI 10.1021/jm00057a004 PG 8 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA KR250 UT WOS:A1993KR25000004 PM 8496935 ER PT J AU HE, XS BOWEN, WD LEE, KS WILLIAMS, W WEINBERGER, DR DECOSTA, BR AF HE, XS BOWEN, WD LEE, KS WILLIAMS, W WEINBERGER, DR DECOSTA, BR TI SYNTHESIS AND BINDING CHARACTERISTICS OF POTENTIAL SPECT IMAGING AGENTS FOR SIGMA-1 AND SIGMA-2 BINDING-SITES SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID RECEPTOR LIGANDS; HIGHLY POTENT; TOMOGRAPHY; AFFINITY; INVITRO; BRAIN AB 2-,3-, and 4-iodophenyl derivatives of the high-affinity sigma ligand N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-(1-pyrrolidinyl)ethylamine (1) were synthesized in two to four steps starting from N-methyl-2-(1-pyrrolidinyl)ethylamine. These compounds were evaluated for their capacity to label both sigma1 and sigma2 subtypes in vitro. Sigma-1 binding affinity was determined by measuring competition with [H-3]-(+)-pentazocine binding to guinea pig brain membranes while sigma2 binding was evaluated through competition with [3H]DTG binding to rat liver membranes in the presence of excess dextrallorphan. The binding data revealed that N-[2-(3-iodophenyl)ethyl]-N-methyl-2-(1-pyrrolidinyl)ethylamine (2) and N-[2-(4-iodophenyl)ethyl]-N-methyl-2-(l-pyrrolidinyl)ethylamine (3) displayed almost identical binding affinity at sigma1 sites to the parent compound 1. This suggests that the 3- or 4-iodo group can effectively substitute for the 3,4-dichloro substituents of 1. In this series of compounds, K(i)'s at the al site varied from 2.0 nM for N-(4-iodobenzyl)-N-methyl-2-(1-pyrrolidinyl)ethylamine (6) to 26.6 nM for N-(2-iodobenzyl)-N-methyl-2-(l-pyrrolidinyl)ethylamine (4). K(i)'s for a2 site ranged from 8.1 nM for 1 to 220 nM for N-(3-bromobenzyl)-N-methyl-2-(1-pyrrolidinyl)ethylamine (11) while the sigma2/a, ratio varied from 1.8 for 4 to 25 for 11. Comparing halogen substitution, the trend Cl = I > Br > F was observed for binding affinity at sigma1 sites; no such trend was observed at sigma2 sites. On the basis of the binding data, compounds 2 and 3 were selected for labeling with I-123. Thus, treatment of the corresponding 3- and 4-(tributylstannyl) intermediates (7 and 8) with (NaI)-I-123 in the presence of excess CH3CO3H furnished [I-123]-2 and [I-123]-3 in up to 70% radiochemical yield. Preliminary in vitro binding with [I-123]-3 indicated up to 97% specific binding with guinea pig brain membranes. C1 NIDDKD,MED CHEM LAB,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. NIMH,CLIN BRAIN DISORDERS BRANCH,WASHINGTON,DC 20032. NR 28 TC 25 Z9 25 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD MAR 5 PY 1993 VL 36 IS 5 BP 566 EP 571 DI 10.1021/jm00057a006 PG 6 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA KR250 UT WOS:A1993KR25000006 PM 8496936 ER PT J AU BUSHMAN, FD AF BUSHMAN, FD TI THE BACTERIOPHAGE-434 RIGHT OPERATOR ROLES OF O(R)1, O(R)2 AND O(R)3 SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE PHAGE-434; 434-RIGHT OPERATOR; 434-REPRESSOR; 434-CRO; PHAGE INDUCTION ID DNA-BINDING; PHAGE 434; ESCHERICHIA-COLI; POSITIVE CONTROL; GENE-REGULATION; LAMBDA-CRO; REPRESSOR; TRANSCRIPTION; PROMOTERS; COMPLEX RP BUSHMAN, FD (reprint author), NIDDKD,MOLEC BIOL LAB,BETHESDA,MD 20892, USA. NR 46 TC 28 Z9 28 U1 0 U2 1 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD MAR 5 PY 1993 VL 230 IS 1 BP 28 EP 40 DI 10.1006/jmbi.1993.1123 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA KR933 UT WOS:A1993KR93300006 PM 8450541 ER PT J AU KALIA, YN BROCKLEHURST, SM HIPPS, DS APPELLA, E SAKAGUCHI, K PERHAM, RN AF KALIA, YN BROCKLEHURST, SM HIPPS, DS APPELLA, E SAKAGUCHI, K PERHAM, RN TI THE HIGH-RESOLUTION STRUCTURE OF THE PERIPHERAL SUBUNIT-BINDING DOMAIN OF DIHYDROLIPOAMIDE ACETYLTRANSFERASE FROM THE PYRUVATE-DEHYDROGENASE MULTIENZYME COMPLEX OF BACILLUS-STEAROTHERMOPHILUS SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE NUCLEAR MAGNETIC RESONANCE; PROTEIN STRUCTURE; PROTEIN DOMAIN; DIHYDROLIPOAMIDE ACETYLTRANSFERASE; DYNAMIC SIMULATED ANNEALING ID NUCLEAR MAGNETIC-RESONANCE; PROTON COUPLING-CONSTANTS; MULTI-ENZYME COMPLEX; NMR-SPECTROSCOPY; STEREOSPECIFIC ASSIGNMENTS; SECONDARY STRUCTURE; COHERENCE-TRANSFER; PROTEIN STRUCTURES; SEQUENCE-ANALYSIS; H-1-NMR SPECTRA C1 UNIV CAMBRIDGE,DEPT BIOCHEM,CAMBRIDGE CTR MOLEC RECOGNIT,TENNIS COURT RD,CAMBRIDGE CB2 1QW,ENGLAND. NCI,CELL BIOL LAB,BETHESDA,MD 20892. OI Kalia, Yogeshvar/0000-0001-9049-5489 NR 63 TC 89 Z9 91 U1 0 U2 5 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD MAR 5 PY 1993 VL 230 IS 1 BP 323 EP 341 DI 10.1006/jmbi.1993.1145 PG 19 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA KR933 UT WOS:A1993KR93300028 PM 8450544 ER PT J AU SUNAGA, K CHUANG, DM ISHITANI, R AF SUNAGA, K CHUANG, DM ISHITANI, R TI AUTORADIOGRAPHIC DEMONSTRATION OF AN INCREASE IN MUSCARINIC CHOLINERGIC RECEPTORS IN CEREBELLAR GRANULE CELLS TREATED WITH TETRAHYDROAMINOACRIDINE SO NEUROSCIENCE LETTERS LA English DT Article DE TETRAHYDROAMINOACRIDINE; ALZHEIMERS DISEASE; DEMENTIA; CEREBELLAR GRANULE CELLS; NEUROTROPHIC FACTORS; MUSCARINIC CHOLINERGIC RECEPTORS; RECEPTOR AUTORADIOGRAPHY ID AMINO-ACIDS; CULTURE; DEPOLARIZATION; RELEASE AB The neurotrophic and neurosurviving effects of 9-amino-1,2,3,4-tetrahydroacridine (THA), a putative antidementia agent, were studied in cultured granule cells using biochemical and morphological methods. The addition of 30 muM THA to cultures grown in 15 mM K+-containing media markedly increased cell survival and enhanced [H-3]N-methylscopolamine binding to muscarinic cholinergic receptors (mAChRs). Furthermore, receptor autoradiographic studies revealed that neuronal cells were labelled over both cell bodies and fibers by the [H-3]receptor ligand. These observations provide direct evidence that THA promotes the expression of mAChR binding sites in differentiating cerebellar granule cells. C1 JOSAI UNIV,NEUROPHARMACOL GRP,SAKADO,SAITAMA 35002,JAPAN. NATL INST MENTAL HLTH,BIOL PSYCHIAT BRANCH,MOLEC NEUROBIOL SECT,BETHESDA,MD 20892. NR 12 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD MAR 5 PY 1993 VL 151 IS 1 BP 45 EP 47 DI 10.1016/0304-3940(93)90041-I PG 3 WC Neurosciences SC Neurosciences & Neurology GA KQ914 UT WOS:A1993KQ91400012 PM 8469436 ER PT J AU TAL, M BENNETT, GJ AF TAL, M BENNETT, GJ TI DEXTRORPHAN RELIEVES NEUROPATHIC HEAT-EVOKED HYPERALGESIA IN THE RAT SO NEUROSCIENCE LETTERS LA English DT Article DE ANALGESIA; DEXTROMETHORPHAN; DEXTRORPHAN; HYPERALGESIA; NMDA ANTAGONIST; PERIPHERAL NEUROPATHY ID METHYL-D-ASPARTATE; PERIPHERAL MONONEUROPATHY; CEREBROCORTICAL NEURONS; NMDA ANTAGONIST; DEXTROMETHORPHAN; PHENCYCLIDINE; NEUROTOXICITY; LEVORPHANOL; MODEL; BRAIN AB Dextrorphan (DEX), a non-competitive NMDA receptor antagonist, was given intraperitoneally and intrathecally (i.t.) to rats with an experimental painful peripheral mononeuropathy. The neuropathy was created by placing loosely constrictive ligatures around the sciatic nerve, and the pain threshold was studied with the paw-flick method. The effects of DEX on the neuropathic heat-evoked hyperalgesia that follows this nerve injury were determined during the period of peak symptom severity. DEX given i.p. relieved heat-evoked hyperalgesia in a dose-dependent manner without producing motor impairment. The highest doses tested (12.5 and 25 mg/kg) produced a large but incomplete block (about 50%). DEX had no effect on the responsiveness of the paw on the control side. i.t. injection of 20 mug DEX completely blocked heat-hyperalgesia when tested 1 h later, again, the effect was achieved without motor impairment and without any change on the control side. These results suggest that DEX may be useful in the treatment of human neuropathic pain. C1 NIDR, NAB, BLDG 30, ROOM B-20, 9000 ROCKVILLE PIKE, BETHESDA, MD 20892 USA. NR 25 TC 121 Z9 122 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD MAR 5 PY 1993 VL 151 IS 1 BP 107 EP 110 DI 10.1016/0304-3940(93)90058-S PG 4 WC Neurosciences SC Neurosciences & Neurology GA KQ914 UT WOS:A1993KQ91400029 PM 8385757 ER PT J AU DRESSLER, GR WILKINSON, JE ROTHENPIELER, UW PATTERSON, LT WILLIAMSSIMONS, L WESTPHAL, H AF DRESSLER, GR WILKINSON, JE ROTHENPIELER, UW PATTERSON, LT WILLIAMSSIMONS, L WESTPHAL, H TI DEREGULATION OF PAX-2 EXPRESSION IN TRANSGENIC MICE GENERATES SEVERE KIDNEY ABNORMALITIES SO NATURE LA English DT Article ID PROMOTER; GENE AB THE Pax genes comprise a family of transcription factors active in specific tissues during embryonic development and are associated with at least three developmental mutations in mouse and man1,2. In the developing kidney, Pax-2 is expressed in the induced mesenchyme, in the ureter epithelium, and in early epithelial structures derived from the mesenchyme3. Pax-2 expression is repressed upon terminal differentiation of the renal tubule epithelium, but persists in the undifferentiated epithelium of human Wilms' tumours4,5. We have produced a dominant gain-of-function mutation in transgenic mice by deregulating the expression of the mouse Pax-2 gene. The data obtained with four independently derived transgenic embryos and with one transgenic line demonstrate that deregulated Pax-2 expression results in histologically abnormal and dysfunctional renal epithelium with properties similar to congenital nephrotic syndrome. Thus, repression of Pax-2 is required for normal kidney development and persistent expression of Pax-2 may restrict the differentiation potential of renal epithelial cells. C1 UNIV TENNESSEE,COLL VET MED,DEPT PATHOBIOL,KNOXVILLE,TN 37901. RP DRESSLER, GR (reprint author), NICHHD,MAMMALIAN GENES & DEV LAB,BETHESDA,MD 20892, USA. NR 16 TC 239 Z9 241 U1 0 U2 0 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD MAR 4 PY 1993 VL 362 IS 6415 BP 65 EP 67 DI 10.1038/362065a0 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA KP976 UT WOS:A1993KP97600061 PM 8383297 ER PT J AU HARRISON, BC MARCHESERAGONA, SP GILBERT, SP CHENG, NQ STEVEN, AC JOHNSON, KA AF HARRISON, BC MARCHESERAGONA, SP GILBERT, SP CHENG, NQ STEVEN, AC JOHNSON, KA TI DECORATION OF THE MICROTUBULE SURFACE BY ONE KINESIN HEAD PER TUBULIN HETERODIMER SO NATURE LA English DT Article ID MOTILITY; ATPASE; IDENTIFICATION AB KINESIN, a microtubule-dependent ATPase, is believed to be involved in anterograde axonal transport. The kinesin head, which contains both microtubule and ATP binding sites, has the necessary components for the generation of force and motility1. We have used saturation binding and electron microscopy to examine the interaction of the kinesin motor domain with the microtubule surface and found that binding saturated at one kinesin head per tubulin heterodimer. Both negative staining and cryo-electron microscopy revealed a regular pattern of kinesin bound to the microtubule surface, with an axial repeat of 8 nm. Optical diffraction analysis of decorated microtubules showed a strong layer-line at this spacing, confirming that one kinesin head binds per tubulin heterodimer. The addition of Mg-ATP to the microtubule-kinesin complex resulted in the complete dissociation of kinesin from the microtubule surface. C1 PENN STATE UNIV,DEPT MOLEC & CELL BIOL,UNIV PK,PA 16802. NIAMSD,STRUCT BIOL LAB,BETHESDA,MD 20892. NR 13 TC 75 Z9 75 U1 1 U2 2 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD MAR 4 PY 1993 VL 362 IS 6415 BP 73 EP 75 DI 10.1038/362073a0 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA KP976 UT WOS:A1993KP97600064 PM 8095324 ER PT J AU FRIEDMAN, MA CHABNER, BA TRIMBLE, EL ADAMS, J ARBUCK, SG AF FRIEDMAN, MA CHABNER, BA TRIMBLE, EL ADAMS, J ARBUCK, SG TI UNREALISTIC EXPECTATIONS IN THE DIAGNOSIS AND TREATMENT OF OVARIAN-CANCER SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter RP FRIEDMAN, MA (reprint author), NIH,BETHESDA,MD 20892, USA. NR 4 TC 0 Z9 0 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 4 PY 1993 VL 328 IS 9 BP 664 EP 664 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA KP680 UT WOS:A1993KP68000022 PM 8094229 ER PT J AU SIDRANSKY, E GINNS, EI AF SIDRANSKY, E GINNS, EI TI CLINICAL HETEROGENEITY AMONG PATIENTS WITH GAUCHERS-DISEASE SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID HUMAN GLUCOCEREBROSIDASE GENE; ASHKENAZI JEWS; MUTATION; FREQUENCY; SEQUENCE RP SIDRANSKY, E (reprint author), NIMH,CLIN NEUROSCI BRANCH,MOLEC NEUROGENET SECT,CLIN GENET UNIT,BETHESDA,MD 20892, USA. NR 34 TC 30 Z9 30 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 3 PY 1993 VL 269 IS 9 BP 1154 EP 1157 DI 10.1001/jama.269.9.1154 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA KN611 UT WOS:A1993KN61100033 PM 8433471 ER PT J AU BASHKIN, J HAYES, JJ TULLIUS, TD WOLFFE, AP AF BASHKIN, J HAYES, JJ TULLIUS, TD WOLFFE, AP TI STRUCTURE OF DNA IN A NUCLEOSOME CORE AT HIGH SALT CONCENTRATION AND AT HIGH-TEMPERATURE SO BIOCHEMISTRY LA English DT Note ID TUMOR VIRUS PROMOTER; THERMAL-DENATURATION; HISTONE OCTAMER; 5S RNA; CHROMATIN; TRANSCRIPTION; PARTICLES; SEQUENCES; INVITRO; PROTEIN AB We have used hydroxyl radical cleavage of DNA to probe the organization of the nucleosome core at high salt concentration and high temperature. The rotational and translational positioning of a DNA fragment, containing part of the Xenopus borealis 5S RNA gene, on the histone octamer is maintained between salt concentrations of 0.0 and 0.8 M NaCl and between temperatures of 0 and 75-degrees-C. These results provide evidence that the energy of bending DNA around the nucleosome is independent of salt concentration and temperature in this range. They illustrate the severe energetic requirements necessary to displace DNA from previously organized contacts with histones in the nucleosome core. C1 NIH,MOLEC EMBRYOL LAB,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,DEPT CHEM,BALTIMORE,MD 21218. RI Tullius, Thomas/A-9685-2008 OI Tullius, Thomas/0000-0003-4425-796X FU NCI NIH HHS [CA 01208]; NIGMS NIH HHS [GM 41930] NR 40 TC 28 Z9 28 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAR 2 PY 1993 VL 32 IS 8 BP 1895 EP 1898 DI 10.1021/bi00059a002 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA KP582 UT WOS:A1993KP58200002 PM 8383529 ER PT J AU FLEISCHER, B MCINTYRE, JO KEMPNER, ES AF FLEISCHER, B MCINTYRE, JO KEMPNER, ES TI TARGET SIZES OF GALACTOSYLTRANSFERASE, SIALYLTRANSFERASE, AND URIDINE DIPHOSPHATASE IN GOLGI-APPARATUS OF RAT-LIVER SO BIOCHEMISTRY LA English DT Article ID RADIATION-INACTIVATION; NUCLEOSIDE-DIPHOSPHATASE; GLYCOPROTEIN; LOCALIZATION; VESICLES; BETA-1,4-GALACTOSYLTRANSFERASE; ALPHA-2,6-SIALYLTRANSFERASE; SIALYLTRANSFERASE; PURIFICATION; ORIENTATION AB Target inactivation analysis was used to measure the functional size of uridine diphosphogalactose: N-acetylglucosamine beta(1,4)galactosyltransferase (galactosyltransferase), cytidine monophospho-N-acetylneuraminic acid:beta-galactoside alpha(2,6)sialyltransferase (sialyltransferase), and uridine diphosphatase (UDPase) in Golgi membranes isolated from rat liver. The size of nucleoside diphosphatase (NDPase), an enzyme similar to UDPase but localized in rat liver endoplasmic reticulum, was also estimated by target inactivation analysis. The related enzymes, UDPase and NDPase, have target sizes of 96 +/- 4 and 77 +/- 3 kDa, while galactosyltransferase and sialyltransferase have target sizes of 97 +/- 10 and 130 +/- 20 kDa, respectively. The target inactivation sizes of galactosyltransferase and of sialyltransferase are about twice the monomer molecular weights of these enzymes obtained from sedimentation studies of the solubilized membranes as well as those predicted from previously reported cDNA sequences. We conclude from our studies that galactosyltransferase and sialyltransferase probably function as dimers in the Golgi membrane. C1 NIAMSD, PHYS BIOL LAB, BETHESDA, MD 20892 USA. RP FLEISCHER, B (reprint author), VANDERBILT UNIV, DEPT MOLEC BIOL, NASHVILLE, TN 37235 USA. NR 36 TC 19 Z9 20 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 MAR 2 PY 1993 VL 32 IS 8 BP 2076 EP 2081 DI 10.1021/bi00059a027 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA KP582 UT WOS:A1993KP58200027 PM 8383532 ER PT J AU SHMUELI, U STEIN, Z WEISS, GH AF SHMUELI, U STEIN, Z WEISS, GH TI SPACE-GROUP SYMMETRY AND ATOMIC HETEROGENEITY ON INTENSITY STATISTICS SO ACTA CHIMICA HUNGARICA-MODELS IN CHEMISTRY LA English DT Article ID RANDOM-WALK MODELS; TRIGONOMETRIC STRUCTURE FACTOR; CRYSTALLOGRAPHIC STATISTICS; PDFS; PROBABILITY; MOMENTS AB Intensity statistics based on the structure-factor model, which account explicitly for atomic composition and space group symmetry are reviewed and discussed. This article deals with the correction-factor approach, which approximates the actual probability density function (p.d.f.) of the structure factor by a product of its central limit theorem approximation and an expansion in terms of orthogonal polynomials, and an ab initio Fourier representation of the required p.d.f. Both approaches account for atomic composition and together allow for all space-group symmetries. The correction-factor method is formally applicable to all space groups but performs poorly for space groups of low symmetries, and generally better as the symmetry increases, while Fourier p.d.f.'s are available for the space groups up to No. 206 (Fd3BAR), and perform very well for all of them. The highest cubic space groups can be efficiently dealt with by the correction-factor method, even in the case of extremely heterogeneous asymmetric units. C1 NIH,DIV COMP RES & TECHNOL,PHYS SCI LAB,BETHESDA,MD 20892. TEL AVIV UNIV,SCH CHEM,IL-69978 TEL AVIV,ISRAEL. RP SHMUELI, U (reprint author), UNIV AMSTERDAM,CRISTALLOG LAB,NIEUWE ACHTERGRACHT 166,1018 WV AMSTERDAM,NETHERLANDS. NR 41 TC 0 Z9 0 U1 0 U2 0 PU AKADEMIAI KIADO PI BUDAPEST PA PO BOX 245, H-1519 BUDAPEST, HUNGARY SN 0231-3146 J9 ACTA CHIM HUNG PD MAR-APR PY 1993 VL 130 IS 2 BP 261 EP 278 PG 18 WC Chemistry, Multidisciplinary SC Chemistry GA LP650 UT WOS:A1993LP65000011 ER PT J AU POSNER, Y SHMUELI, U WEISS, GH AF POSNER, Y SHMUELI, U WEISS, GH TI EXACT CONDITIONAL DISTRIBUTION OF A 3-PHASE INVARIANT IN THE SPACE GROUP-P1 .3. CONSTRUCTION OF AN IMPROVED COCHRAN-LIKE APPROXIMATION SO ACTA CRYSTALLOGRAPHICA SECTION A LA English DT Article ID RANDOM-WALK MODELS; JOINT PROBABILITY-DISTRIBUTION; CRYSTALLOGRAPHIC STATISTICS; DERIVATION; PDFS AB An exact representation of the accurately computable conditional probability density function (c.p.d.f.) of the three-phase invariant for the space group P1 was developed in paper I of this series [Shmueli, Rabinovich & Weiss (1989). Acta Cryst. A45, 361-367]. The computation of this function is too time-consuming for it to be of practical value. It is therefore desirable to find simple approximations based on the exact result that may be more accurate than the familiar Cochran approximation or its extensions. One such approximation, presented here, has the same functional form as the Cochran approximation but with a modified parameter in place of that appearing in Cochran's distribution. Some of the numerical procedures used in the estimation of this modified parameter are also discussed. C1 NIH,DIV COMP RES & TECHNOL,PHYS SCI LAB,BETHESDA,MD 20892. RP POSNER, Y (reprint author), TEL AVIV UNIV,SCH CHEM,IL-69978 TEL AVIV,ISRAEL. RI DISKIN POSNER, YAEL/K-1757-2012 OI DISKIN POSNER, YAEL/0000-0002-9008-8477 NR 21 TC 1 Z9 1 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0108-7673 J9 ACTA CRYSTALLOGR A JI Acta Crystallogr. Sect. A PD MAR 1 PY 1993 VL 49 BP 260 EP 265 DI 10.1107/S0108767392005506 PN 2 PG 6 WC Chemistry, Multidisciplinary; Crystallography SC Chemistry; Crystallography GA KR354 UT WOS:A1993KR35400002 PM 8447985 ER PT J AU OERTER, KE MANASCO, PK BARNES, KM JONES, J HILL, S CUTLER, GB AF OERTER, KE MANASCO, PK BARNES, KM JONES, J HILL, S CUTLER, GB TI EFFECTS OF LUTEINIZING-HORMONE-RELEASING HORMONE AGONISTS ON FINAL HEIGHT IN LUTEINIZING-HORMONE-RELEASING HORMONE-DEPENDENT PRECOCIOUS PUBERTY SO ACTA PAEDIATRICA LA English DT Article; Proceedings Paper CT 14TH INTERNATIONAL SYMP ON GROWTH AND GROWTH DISORDERS CY OCT, 1992 CL BUDAPEST, HUNGARY ID LONG-ACTING ANALOG; TERM TREATMENT; LHRH AGONIST; SEXUAL PRECOCITY; BONE MATURATION; SOMATIC GROWTH; GNRH ANALOG; GIRLS; CHILDREN; THERAPY RP OERTER, KE (reprint author), NICHHD,DEV ENDOCRINOL BRANCH,BETHESDA,MD 20892, USA. NR 37 TC 3 Z9 4 U1 0 U2 0 PU SCANDINAVIAN UNIVERSITY PRESS PI OSLO PA PO BOX 2959 TOYEN, JOURNAL DIVISION CUSTOMER SERVICE, N-0608 OSLO, NORWAY SN 0803-5253 J9 ACTA PAEDIATR JI Acta Paediatr. PD MAR PY 1993 VL 82 SU 388 BP 62 EP 69 PG 8 WC Pediatrics SC Pediatrics GA LD888 UT WOS:A1993LD88800014 ER PT J AU ROUNSAVILLE, BJ BRYANT, K BABOR, T KRANZLER, H KADDEN, R AF ROUNSAVILLE, BJ BRYANT, K BABOR, T KRANZLER, H KADDEN, R TI CROSS SYSTEM AGREEMENT FOR SUBSTANCE USE DISORDERS - DSM-III-R, DSM-IV AND ICD-10 SO ADDICTION LA English DT Article ID DEPENDENCE; CIDI AB This report presents results of a field trial of Substance Use Disorders as defined by DSM-III-R, DSM-IV (proposed) and ICD-10. Diagnoses based on the three systems were derived from interviews using the Composite International Diagnostic Interview (CIDI) in a heterogeneous sample of 521 adults drawn from clinical and community settings. Two issues are addressed: (1) cross system agreement; and (2) syndrome coherence of proposed criterion sets for Substance Dependence in each of the three systems. Findings were as follows: (1) Cross system agreement for Dependence was generally high, especially between DSM-III-R and DSM-IV. (2) Cross system agreement was lower for DSM-III-R and DSM-IV Abuse and very low for DSM-IV Abuse and ICD-10 Harmful Use. (3) Agreement varied across drug categories with lowest DSM-III-R/DSM-IV agreement for alcohol abuse and DSM-IV/ICD-10 agreement for marijuana use disorders. (4) Overall prevalence differed for the three systems with DSM-IV yielding highest rates followed by DSM-III-R and ICD-10 in that order. (5) Factor analysis of Dependence criteria showed high loadings of all items on a single factor across the three diagnostic systems and for all categories of drugs. Implications for validity of the dependence syndrome construct and for revisions in DSM-IV are discussed. C1 NIAAA,ROCKVILLE,MD 20852. UNIV CONNECTICUT,CTR HLTH,DEPT PSYCHIAT,FARMINGTON,CT 06032. RP ROUNSAVILLE, BJ (reprint author), YALE UNIV,SCH MED,SUBST ABUSE TREATMENT UNIT,27 SYLVAN AVE,NEW HAVEN,CT 06519, USA. NR 19 TC 61 Z9 62 U1 3 U2 3 PU CARFAX PUBL CO PI ABINGDON PA PO BOX 25, ABINGDON, OXFORDSHIRE, ENGLAND OX14 3UE SN 0965-2140 J9 ADDICTION JI Addiction PD MAR PY 1993 VL 88 IS 3 BP 337 EP 348 DI 10.1111/j.1360-0443.1993.tb00821.x PG 12 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA KR152 UT WOS:A1993KR15200003 PM 8461851 ER PT J AU GRANT, BF AF GRANT, BF TI ICD-10 HARMFUL USE OF ALCOHOL AND THE ALCOHOL DEPENDENCE SYNDROME - PREVALENCE AND IMPLICATIONS SO ADDICTION LA English DT Article AB Data from a 1988 survey on United States drinking practices and related problems was used to derive the prevalence and population estimates of harmful use of alcohol and the alcohol dependence syndrome as defined in the ICD-10 Clinical Descriptions and Diagnostic Guidelines Version (ICD-10-CDDG). Corresponding estimates were also presented for ICD-10-CDDG diagnoses that incorporated the duration criterion of the ICD-10-Diagnostic Criteria for Research Version (ICD-10-DCR). The prevalence of ICD-10 harmful use and dependence combined, with and without the duration criterion, were 5.2% and 7.1%, respectively. Corresponding harmful use rates were negligible (0.27%). Implications of the extremely low prevalence of harmful use in the US population and the impact of the duration criterion on the rates are discussed in terms of the fundamental nature of alcohol use disorders as syndromes and the viability of the harmful use of alcohol category as originally conceptualized. RP GRANT, BF (reprint author), NIAAA,DIV BIOMETRY & EPIDEMIOL,5600 FISHERS LANE,ROOM 14C-26,ROCKVILLE,MD 20857, USA. NR 6 TC 15 Z9 16 U1 0 U2 0 PU CARFAX PUBL CO PI ABINGDON PA PO BOX 25, ABINGDON, OXFORDSHIRE, ENGLAND OX14 3UE SN 0965-2140 J9 ADDICTION JI Addiction PD MAR PY 1993 VL 88 IS 3 BP 413 EP 420 DI 10.1111/j.1360-0443.1993.tb00829.x PG 8 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA KR152 UT WOS:A1993KR15200011 PM 8461858 ER PT J AU STRICKLER, HD BLANCHARD, JF VLAHOV, D TAYLOR, E MUNOZ, A NELSON, KE MARGOLICK, JB AF STRICKLER, HD BLANCHARD, JF VLAHOV, D TAYLOR, E MUNOZ, A NELSON, KE MARGOLICK, JB TI ELEVATED SERUM LEVELS OF NEOPTERIN BUT NOT BETA-2-MICROGLOBULIN IN HIV-1-SERONEGATIVE INJECTING DRUG-USERS SO AIDS LA English DT Article DE NEOPTERIN; BETA-2-MICROGLOBULIN; INJECTING DRUG USE; HEROIN; COCAINE; HIV ID HUMAN IMMUNODEFICIENCY VIRUS; HIV INFECTION; DISEASE PROGRESSION; MARKER; ACTIVATION; LYMPHADENOPATHY; CLASSIFICATION; LYMPHOCYTES; TYPE-1; BLOOD AB Objective: To determine whether injecting drug use is associated with cellular immune activation in the absence of HIV-1 infection. Design: Serum levels of neopterin and beta2-Microglobulin (beta2M) were measured cross-sectionally in injecting drug users (IDU) enrolled in a prospective study. Subjects and methods: Two hundred and nineteen HIV-1-seronegative, healthy heterosexual black male IDU aged 21-49 years were selected from the Baltimore-based AIDS Linked to Intravenous Experiences (ALIVE) study. The possibility of including subjects in the process of seroconverting to HIV-1 was minimized by restricting the study to individuals who remained seronegative 6 months after the specimens used for analysis were collected. Results: Mean serum beta2M levels were not statistically different among groups of IDU whose usual pattern of injection was at least once a day for up to 3 consecutive days (daily users; n = 65), less than once per day (less-than-daily users; n = 75), or not at all for at least 2 weeks (non-recent users; n = 79). In contrast, the mean neopterin level was significantly (P = 0.039) greater in daily users (6.17 nmol/1) than in the other two groups (5.07 and 5.19 nmol/l, respectively, which were not statistically different). These Results were not affected, by the frequency of using borrowed non-sterile works or by other demographic and risk factor variables. Conclusions: Frequent injecting drug use may be independently associated with a small elevation of serum neopterin levels, but not beta2M levels. Although the occurrence of a type 1 error in this sample cannot be completely excluded, serum neopterin may be more sensitive than serum beta2M in detecting activation of immunocompetent cells associated with frequent injecting drug use in this population. C1 JOHNS HOPKINS UNIV, SCH HYG & PUBL HLTH, DEPT EPIDEMIOL, BALTIMORE, MD 21218 USA. JOHNS HOPKINS UNIV, SCH HYG & PUBL HLTH, DEPT ENVIRONM HLTH SCI, BALTIMORE, MD 21218 USA. DEPT HLTH, WINNIPEG, MB, CANADA. RP NCI, DIV CANC ETIOL, VIRAL EPIDEMIOL BRANCH, BLDG EPN, RM 434, BETHESDA, MD 20892 USA. FU NIDA NIH HHS [DA 05911, DA 04334] NR 34 TC 15 Z9 15 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0269-9370 EI 1473-5571 J9 AIDS JI Aids PD MAR PY 1993 VL 7 IS 3 BP 361 EP 367 DI 10.1097/00002030-199303000-00009 PG 7 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA KT079 UT WOS:A1993KT07900009 PM 8471199 ER PT J AU FREIMAN, JP HELFERT, KE HAMRELL, MR STEIN, DS AF FREIMAN, JP HELFERT, KE HAMRELL, MR STEIN, DS TI HEPATOMEGALY WITH SEVERE STEATOSIS IN HIV-SEROPOSITIVE PATIENTS SO AIDS LA English DT Article DE HEPATOMEGALY; STEATOSIS; HIV; ZIDOVUDINE ID IMMUNE-DEFICIENCY SYNDROME; HUMAN-IMMUNODEFICIENCY-VIRUS; SYNDROME AIDS; REYES-SYNDROME; DRUG-ABUSE; LIVER; INFECTION; DISEASE AB Objective. To describe death attributed to severe hepatomegaly and macrovesicular steatosis without inflammation or necrosis in HIV-seropositive patients without AIDS. Patients: Patients from the AIDS Clinical Trials Group (ACTG) Adverse Reactions and the Food and Drug Administration's (FDA) Spontaneous Report databases. Results: Six fatal and two non-fatal cases in which no known cause of hepatic steatosis could be found were identified. With one possible exception, none of the six fatal cases had a diagnosis of AIDS and all were in reasonable nutritional status (as indicated by weight and/or serum albumin); the majority were mildly to moderately overweight. All had received at least 6 months of antiretroviral therapy, and all had gastrointestinal complaints without other non-hepatic abdominal pathology. At least three out of the six had no history of progressively abnormal liver function tests until a few weeks prior to the onset of symptoms and subsequent death. Further investigation of the FDA and ACTG databases identified two similar but non-fatal cases in which abnormalities resolved after cessation of antiretroviral therapy. Conclusions: The cases described represent a degree of hepatic abnormalities that has not been reported previously in HIV-seropositive patients, and are probably an underestimate of actual incidence, since patients with possible etiologies of liver disease were excluded from the clinical history, laboratory, microbiologic, or histologic examination. The etiology of hepatic disease may be associated with antiretroviral therapy, HIV, or an unidentifiable infection, and requires further investigation. C1 NIAID,DIV AIDS,MED BRANCH,6003 EXECUT BLVD,RM 2C25,ROCKVILLE,MD 20852. US FDA,CTR DRUG EVALUAT & RES,OFF EPIDEMIOL & BIOSTAT,ROCKVILLE,MD 20857. NIAID,PHARMACEUT & REGULATORY AFFAIRS BRANCH,ROCKVILLE,MD. NR 31 TC 123 Z9 124 U1 0 U2 0 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 1993 VL 7 IS 3 BP 379 EP 385 DI 10.1097/00002030-199303000-00012 PG 7 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA KT079 UT WOS:A1993KT07900012 PM 8471200 ER PT J AU KOPP, JB ROONEY, JF WOHLENBERG, C DORFMAN, N MARINOS, NJ BRYANT, JL KATZ, SI NOTKINS, AL KLOTMAN, PE AF KOPP, JB ROONEY, JF WOHLENBERG, C DORFMAN, N MARINOS, NJ BRYANT, JL KATZ, SI NOTKINS, AL KLOTMAN, PE TI CUTANEOUS DISORDERS AND VIRAL GENE-EXPRESSION IN HIV-1 TRANSGENIC MICE SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; EPIDERMAL LANGERHANS CELLS; POLYMERASE CHAIN-REACTION; LONG TERMINAL REPEAT; AIDS-RELATED COMPLEX; KAPOSIS-SARCOMA; SKIN; INFECTION; ACTIVATION; DISEASE AB Patients infected with HIV-1 experience several hyperproliferative skin disorders, including seborrheic dermatitis, ichthyosis, and psoriasis. Transgenic mice carrying a subgenomic HIV-1 proviral construct lacking the gag and pol genes were found to develop proliferative epidermal lesions, manifested as diffuse epidermal hyperplasia in homozygous transgenic mice and benign papillomas in heterozygous transgenic mice. Nonpapillomatous skin from both homozygotes and heterozygotes expressed viral RNA, and the viral envelope protein gp120 was localized to the suprabasal keratinocyte. Papillomas contained increased amounts of both viral mRNA and envelope glycoprotein. Exposure of transgenic mice to doses of ultraviolet B (UV-B) irradiation that induced cutaneous injury increased viral gene expression and resulted in the development of papillomas within 14-21 days. Cutaneous injury induced by phenol and liquid nitrogen had similar effects. These data support a role for HIV-1 gene products in the pathogenesis of proliferative epidermal disorders associated with HIV-1 infection. Further, they suggest that the process of wound repair increases HIV-1 gene expression in this transgenic mouse model. C1 NIDR,ORAL MED LAB,BETHESDA,MD 20892. NIDR,ANIM CARE UNIT,BETHESDA,MD 20892. NCI,DERMATOL BRANCH,BETHESDA,MD 20892. RP KOPP, JB (reprint author), NIDR,DEV BIOL LAB,BLDG 30,ROOM 430,BETHESDA,MD 20892, USA. OI Kopp, Jeffrey/0000-0001-9052-186X NR 32 TC 44 Z9 44 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 1993 VL 9 IS 3 BP 267 EP 275 DI 10.1089/aid.1993.9.267 PG 9 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA KU198 UT WOS:A1993KU19800011 PM 8471318 ER PT J AU COHEN, SG AF COHEN, SG TI SPAIN, PORTUGAL, COLUMBUS,CHRISTOPHER AND THE JEWISH PHYSICIAN .2. SO ALLERGY PROCEEDINGS LA English DT Article RP COHEN, SG (reprint author), NIAID,BETHESDA,MD 20892, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU OCEAN SIDE PUBLICATIONS INC PI PROVIDENCE PA 95 PITMAN ST, PROVIDENCE, RI 02906 SN 1046-9354 J9 ALLERGY PROC JI Allergy Proc. PD MAR-APR PY 1993 VL 14 IS 2 BP 145 EP 153 DI 10.2500/108854193778812080 PG 9 WC Allergy SC Allergy GA LC081 UT WOS:A1993LC08100023 PM 8514179 ER PT J AU ROBERTS, WC AF ROBERTS, WC TI 93 HEARTS GREATER-THAN-OR-EQUAL-TO-90 YEARS OF AGE SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Note ID NECROPSY PATIENTS C1 NHLBI,PATHOL BRANCH,BETHESDA,MD 20892. NR 4 TC 12 Z9 12 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD MAR 1 PY 1993 VL 71 IS 7 BP 599 EP 602 DI 10.1016/0002-9149(93)90519-I PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA KN630 UT WOS:A1993KN63000017 PM 8438749 ER PT J AU MAUTNER, SL MAUTNER, GC CURRY, CL ROBERTS, WC AF MAUTNER, SL MAUTNER, GC CURRY, CL ROBERTS, WC TI MASSIVE PERIGRAFT AORTIC-ANEURYSM LATE AFTER COMPOSITE GRAFT REPLACEMENT OF THE ASCENDING AORTA AND AORTIC-VALVE IN THE MARFAN-SYNDROME SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID SURGICAL-TREATMENT; ROOT REPLACEMENT; EXPERIENCE; ANGIOGRAPHY; REPAIR C1 HOWARD UNIV,MED CTR,DEPT MED,WASHINGTON,DC 20059. RP MAUTNER, SL (reprint author), NHLBI,PATHOL BRANCH,BLDG 10,ROOM 2N-258,BETHESDA,MD 20892, USA. NR 17 TC 2 Z9 2 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD MAR 1 PY 1993 VL 71 IS 7 BP 624 EP 627 DI 10.1016/0002-9149(93)90529-L PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA KN630 UT WOS:A1993KN63000027 PM 8438759 ER PT J AU ANASTASSIADES, O IAKOVOU, E STAVRIDOU, N GOGAS, J KARAMERIS, A AF ANASTASSIADES, O IAKOVOU, E STAVRIDOU, N GOGAS, J KARAMERIS, A TI MULTICENTRICITY IN BREAST-CANCER - A STUDY OF 366 CASES SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE BREAST CANCER; MULTICENTRICITY ID INTRADUCTAL CARCINOMA; RECEPTORS; SURVIVAL; ESTROGEN; INSITU; BIOPSY AB A total of 366 consecutive modified radical mastectomy specimens were studied for determination of multicentricity. The authors found that 187 samples (49.1%) were multicentric. Ten specimens contained in situ carcinoma without an infiltrating component; eight of them were multicentric. Multicentricity was correlated with various laboratory and clinical features, including patient age, tumor size, histologic type of breast cancer, tumor grade, presence and values of estrogen and progesterone receptors, the amount of solid tissue in the breast, and the family history. The data were organized in eight independent dimensions, four ordinal and four cardinal. Correlation analysis was applied to a cross tabulation supplemented with other statistical tests. The authors found that the factors related to multicentricity were the age of the patient, the size and the histologic type of the tumor, levels of the progesterone receptors more than 50 fmol/mg of protein, and the amount of solid tissue in the breasts. Tumor grade, estrogen receptors levels, and family history were not related to multicentricity. It was concluded that multicentricity is a frequent property of breast cancer. It is more common in young and perimenopausal women. Multicentricity occurs in small tumors but is more common in larger ones. C1 GEN HOSP ATHENS,DEPT PATHOL,ATHENS,GREECE. UNIV ATHENS,PROPEDEUT SURG UNIT 2,ATHENS,GREECE. NCI,PATHOL LAB,BETHESDA,MD 20892. NR 31 TC 52 Z9 52 U1 1 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD MAR PY 1993 VL 99 IS 3 BP 238 EP 243 PG 6 WC Pathology SC Pathology GA KR561 UT WOS:A1993KR56100005 PM 8447284 ER PT J AU GOLDSTEIN, AM DRACOPOLI, NC HO, EC FRASER, MC KEARNS, KS BALE, SJ MCBRIDE, OW CLARK, WH TUCKER, MA AF GOLDSTEIN, AM DRACOPOLI, NC HO, EC FRASER, MC KEARNS, KS BALE, SJ MCBRIDE, OW CLARK, WH TUCKER, MA TI FURTHER EVIDENCE FOR A LOCUS FOR CUTANEOUS MALIGNANT-MELANOMA DYSPLASTIC NEVUS (CMM/DN) ON CHROMOSOME IP, AND EVIDENCE FOR GENETIC-HETEROGENEITY SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID PRECURSOR LESIONS; PRONE FAMILIES; LINKAGE; RISK AB Assignment of a susceptibility locus for cutaneous malignant melanoma-dysplastic nevus (CMM/DN) to chromosome 1p remains controversial. We examined the relationship between CMM/DN and markers D1S47, PND, and D1S160 on seven new families (set B) plus updated versions of six previously reported families (set A). Three linkage analyses were performed: (1) CMM alone-all individuals without confirmed melanoma or borderline lesions were considered unaffected (model I); (2) CMM/DN with variable age at onset and sporadics (model II); and (3) CMM/DN using the model of Bale et al. (model III). For CMM alone and D1S47, Z(max) = 3.12 at theta = .10. For D1S160 and CMM alone, Z(max) = 1.76 at theta = .10. PND showed no evidence for linkage to CMM alone. Models II and III showed strong evidence for linkage to D1S47, D1S160, and PND in the set A pedigrees but not in the set B families. We tested for homogeneity of CMM/DN (model II) by splitting families into two groups on the basis of (1) the proportion of CMM/DN cases and (2) the occurrence of immune-related tumors. In group 1 there was significant evidence of heterogeneity with both D1S47 and D1S160, and in group 2 there was significant evidence of heterogeneity with D1S160. Thus, diagnostic, clinical, and genetic heterogeneity are the likely reasons that previous studies have failed to confirm linkage of CMM/DN to chromosome 1p. The results showed significant evidence for a CMM locus linked to D1S47, as well as significant evidence for heterogeneity with only a subset of the families appearing linked to chromosome 1p. C1 NCI,BIOCHEM LAB,BETHESDA,MD 20892. NIAMSD,SKIN BIOL LAB,GENET STUDIES SECT,BETHESDA,MD. MIT,DEPT BIOL,CAMBRIDGE,MA 02139. UNIV PENN,SCH MED,DEPT DERMATOL,PHILADELPHIA,PA 19104. UNIV PENN,SCH MED,PIGMENTED LES STUDY GRP,PHILADELPHIA,PA 19104. RP GOLDSTEIN, AM (reprint author), NCI,GENET EPIDEMIOL BRANCH,FAMILY STUDIES SECT,EXECUT PLAZA N,ROOM 439,BETHESDA,MD 20892, USA. RI Tucker, Margaret/B-4297-2015 NR 38 TC 122 Z9 122 U1 0 U2 1 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 1993 VL 52 IS 3 BP 537 EP 550 PG 14 WC Genetics & Heredity SC Genetics & Heredity GA KR720 UT WOS:A1993KR72000011 PM 8447320 ER PT J AU SCHAPIRO, MB AF SCHAPIRO, MB TI MR QUANTIFICATION OF BRAIN STRUCTURES SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Letter ID QUANTITATIVE CT ANALYSIS; ADULT DOWNS-SYNDROME; DIFFERENT AGES RP SCHAPIRO, MB (reprint author), NIA,NEUROSCI LAB,BLDG 10,RM 6C414,BETHESDA,MD 20892, USA. NR 11 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD MAR-APR PY 1993 VL 14 IS 2 BP 507 EP 508 PG 2 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA KR570 UT WOS:A1993KR57000044 PM 8456741 ER PT J AU QUINTERO, RA ROMERO, R MAHONEY, MJ ABUHAMAD, A VECCHIO, M HOLDEN, J HOBBINS, JC AF QUINTERO, RA ROMERO, R MAHONEY, MJ ABUHAMAD, A VECCHIO, M HOLDEN, J HOBBINS, JC TI EMBRYOSCOPIC DEMONSTRATION OF HEMORRHAGIC LESIONS ON THE HUMAN EMBRYO AFTER PLACENTAL TRAUMA SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE EMBRYOSCOPY; CHORIONIC VILLUS SAMPLING; CONGENITAL ANOMALIES ID LIMB ABNORMALITIES AB OBJECTIVE: The purpose of this study was to evaluate embryoscopically the effect of placental trauma on the human embryo. STUDY DESIGN: Patients undergoing elective first-trimester termination of pregnancy underwent transcervical embryoscopy both before and after chorionic villus sampling. If hemorrhagic lesions were not observed on the fetus after chorionic villus sampling, partial placental detachment was performed with a blunt instrument, and the fetus was again observed. RESULTS: Hemorrhagic lesions were observed in 20 of 43 fetuses. In 13 of them, the lesions occurred after placental trauma with the chorionic villus sampling catheter alone (30%), whereas lesions were observed in the remaining seven patients after additional blunt placental disruption. The lesions were located most frequently on the cephalic region, and they grew in size during the observation period. Gestational age or amount of chorionic villus sampling tissue was not different between fetuses with or without lesions. CONCLUSION: Placental trauma results in embryoscopically demonstrable hemorrhagic lesions on the human embryo. Whereas some of these lesions may be of no consequence, others may lead to permanent changes. If similar lesions occur in deeper tissues, they could cause disruptions in development and conceivably could be related to anomalies reported in infants born to women who have had chorionic villus sampling procedures. Embryoscopy affords the opportunity to study possible mechanisms involved in the occurrence of anomalies. C1 YALE UNIV,SCH MED,DEPT OBSTET & GYNECOL,NEW HAVEN,CT 06510. YALE UNIV,SCH MED,DEPT GENET,NEW HAVEN,CT 06510. NICHHD,PERINATOL BRANCH,BETHESDA,MD 20892. RP QUINTERO, RA (reprint author), WAYNE STATE UNIV,HUTZEL HOSP,DEPT OBSTET & GYNECOL,4707 ST ANTOINE BLVD,DETROIT,MI 48201, USA. NR 10 TC 23 Z9 23 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 1993 VL 168 IS 3 BP 756 EP 759 PN 1 PG 4 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA KT624 UT WOS:A1993KT62400003 PM 8456875 ER PT J AU BUEKENS, P WILCOX, A AF BUEKENS, P WILCOX, A TI WHY DO SMALL TWINS HAVE A LOWER MORTALITY-RATE THAN SMALL SINGLETONS SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE EPIDEMIOLOGIC METHODS; LOW BIRTH WEIGHT; PERINATAL MORTALITY; TWINS ID PERINATAL-MORTALITY; BIRTH-WEIGHT; INFANT-MORTALITY; MULTIPLE BIRTHS; UNITED-STATES; EPIDEMIOLOGY AB OBJECTIVE: We propose an interpretation of the paradoxically better survival rate among low-birth-weight twins compared with low-birth-weight singletons. STUDY DESIGN: We used data from Belgian birth and death certificates for 1983 and 1984. The data include 229,964 singletons, 2175 first twins, and 2153 second twins. Weight-specific perinatal mortality rates of twins and singletons were compared; the birth-weight distributions were adjusted to a single mean and SD. RESULTS: After adjustment, mortality rates at every weight were higher for twins than for singletons. CONCLUSIONS: The appearance of better survival among small twins compared with small singletons disappears after adjustment to relative birth-weight. There is a large risk resulting from twinning that falls on all twins, regardless of their weight. C1 NIEHS,EPIDEMIOL BRANCH,RES TRIANGLE PK,NC 27709. RP BUEKENS, P (reprint author), FREE UNIV BRUSSELS,SCH PUBL HLTH,DEPT EPIDEMIOL & SOCIAL MED,808 ROUTE LENNIK,CP 590,B-1070 BRUSSELS,BELGIUM. OI Wilcox, Allen/0000-0002-3376-1311 NR 27 TC 62 Z9 63 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 1993 VL 168 IS 3 BP 937 EP 941 PN 1 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA KT624 UT WOS:A1993KT62400038 PM 8456906 ER PT J AU CHEEVER, AW AF CHEEVER, AW TI SCHISTOSOMIASIS - INFECTION VERSUS DISEASE AND HYPERSENSITIVITY VERSUS IMMUNITY SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Editorial Material ID TRANSFORMING GROWTH FACTOR-BETA-1; MURINE SCHISTOSOMIASIS; HEPATIC-FIBROSIS; GRANULOMA-FORMATION; MANSONI INFECTION; ANTIGEN; IMMUNOREGULATION; ASSOCIATION; ANTIBODIES; MORBIDITY RP CHEEVER, AW (reprint author), NIAID,PARASIT DIS LAB,BLDG 4,ROOM 126,BETHESDA,MD 20892, USA. NR 36 TC 30 Z9 31 U1 0 U2 0 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 1993 VL 142 IS 3 BP 699 EP 702 PG 4 WC Pathology SC Pathology GA KR805 UT WOS:A1993KR80500006 PM 8456933 ER PT J AU LATZKOVITS, L CSERR, HF PARK, JT PATLAK, CS PETTIGREW, KD RIMANOCZY, A AF LATZKOVITS, L CSERR, HF PARK, JT PATLAK, CS PETTIGREW, KD RIMANOCZY, A TI EFFECTS OF ARGININE VASOPRESSIN AND ATRIOPEPTIN ON GLIAL-CELL VOLUME MEASURED AS 3-MG SPACE SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE 3-O-METHYLGLUCOSE; CELL VOLUME REGULATION; NEUROPEPTIDES; V(1) RECEPTORS ID ATRIAL-NATRIURETIC-FACTOR; RAT ASTROGLIAL CELLS; ISCHEMIC BRAIN EDEMA; SUBARACHNOID HEMORRHAGE; ACUTE HYPERNATREMIA; WATER; BLOOD; PERMEABILITY; BARRIER; PEPTIDE AB This study evaluates the hypothesis that arginine vasopressin (AVP) and atriopeptin, peptide hormones synthesized and released within the brain, are regulators of brain cell volume using cultured astroglial cells derived from newborn rats. Cell water content, regarded as volume, was measured in defined, serum-free medium as the 3-O-methylglucose (3-MG) space. Initial experiments established conditions such that glucose, which competes with 3-MG for the glucose carrier, would not interfere with the measurement of the 3-MG space. AVP increased the 3-MG space of glial cells by an average of 25% between 30 and 120 min of exposure, whereas atriopeptin decreased it by 32%. The 3-MG space remained close to normal after coadministration of both peptides. The AVP-dependent increase in 3-MG space was blocked both by the V1 antagonist d(CH2)5Tyr(Me)AVP (Manning compound) and by the cotransport inhibitor, bumetanide. Results are consistent with a role for AVP and atriopeptin in the homeostasis of atroglial cell volume. C1 BROWN UNIV,PHYSIOL SECT,BOX G-B3,PROVIDENCE,RI 02912. SUNY STONY BROOK,DEPT NEUROSURG,STONY BROOK,NY 11794. NATL INST MENTAL HLTH,DIV EPIDEMIOL,BETHESDA,MD 20892. NATL INST MENTAL HLTH,SERV RES,BETHESDA,MD 20892. FU NINDS NIH HHS [NS-11050] NR 48 TC 46 Z9 46 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0002-9513 J9 AM J PHYSIOL JI Am. J. Physiol. PD MAR PY 1993 VL 264 IS 3 BP C603 EP C608 PN 1 PG 6 WC Physiology SC Physiology GA KV270 UT WOS:A1993KV27000012 PM 8460666 ER PT J AU FLESSNER, MF MEJIA, R KNEPPER, MA AF FLESSNER, MF MEJIA, R KNEPPER, MA TI AMMONIUM AND BICARBONATE TRANSPORT IN ISOLATED PERFUSED RODENT LONG-LOOP THIN DESCENDING LIMBS SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE AMMONIA; CHINCHILLA; RAT; HENLES LOOP; CARBONIC ANHYDRASE ID COLLECTING DUCT; ASCENDING LIMB; RAT; KIDNEY; TUBULES; NH4+; NEPHRONS; NH3 AB Ammonium accumulates in the renal medullas of antidiuretic mammals. The accumulation process is thought to involve countercurrent multiplication, energy-dependent recycling between the ascending and descending limbs of Henle's loop. To investigate the role of the long-loop thin descending limb (LDL) in countercurrent multiplication of ammonium, we have perfused outer medullary and inner medullary subsegments of the chinchilla LDL (and inner medullary subsegments of rat LDL) in vitro and measured the fluxes of total ammonia and total CO2. No spontaneous fluxes of total ammonia or total CO2 occurred in the absence of imposed concentration gradients. When transepithelial concentration gradients were imposed, passive total ammonia and total CO2 transport were observed in all subsegments, although the permeabilities varied with distance along the descending limb. Passive total ammonia transport occurred through a combination of NH3 and direct NH4+ permeation. The outer medullary segment was the most permeable to NH4+. The deep inner medullary segment was the most permeable to bicarbonate. Addition of carbonic anhydrase to the lumen accelerated passive NH3 entry in the outer medullary LDL, indicating that little or no luminal carbonic anhydrase is endogenously present. The passive secretion of NH4+ and NH3 into the LDL may contribute to the countercurrent multiplication of ammonium in the rodent renal medulla. C1 NHLBI,KIDNEY & ELECTROLYTE METAB LAB,BLDG 10,RM 6N307,BETHESDA,MD 20892. NR 30 TC 13 Z9 13 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0002-9513 J9 AM J PHYSIOL JI Am. J. Physiol. PD MAR PY 1993 VL 264 IS 3 BP F388 EP F396 PN 2 PG 9 WC Physiology SC Physiology GA KV271 UT WOS:A1993KV27100071 PM 8456952 ER PT J AU MEJIA, R FLESSNER, MF KNEPPER, MA AF MEJIA, R FLESSNER, MF KNEPPER, MA TI MODEL OF AMMONIUM AND BICARBONATE TRANSPORT ALONG LDL - IMPLICATIONS FOR ALKALINIZATION OF LUMINAL FLUID SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article ID PROXIMAL STRAIGHT TUBULES; PHOSPHATE TRANSPORT; CONVOLUTED TUBULE; DESCENDING LIMBS; SODIUM-CHLORIDE; WATER TRANSPORT; HENLES LOOP; RAT; PERMEABILITY; SEGMENTS AB Luminal fluid exiting the proximal convoluted tubule of a juxtamedullary nephron is alkalinized as it passes through the long-loop thin descending limb of Henle (LDL). Three potential mechanisms of alkalinization are 1) concentration of bicarbonate by water abstraction, 2) direct bicarbonate entry, and 3) NH3 entry. We have used a mathematical model of the LDL to investigate these mechanisms. With permeabilities of HCO3-, NH3, and NH4+ measured for subsegments of the chinchilla LDL [M. F. Flessner, R. Mejia, and M. A. Knepper. Am. J. Physiol. 264 (Renal Fluid Electrolyte Physiol. 33): F388-F396, 1993], the osmotic water permeability of each segment [C.-L. Chou and M. A. Knepper. Am. J. Physiol. 263 (Renal Fluid Electrolyte Physiol. 32): F417-F426, 1992], and appropriate parameters from the literature, we have used the model to calculate hypothetical pH, HCO3- concentration, and NH3 concentration of the luminal fluid as it descends the LDL within an assumed interstitium. After eliminating each mechanism in tum by setting the appropriate permeability to zero, we recalculated the axial profiles. Our results suggest that, although all three mechanisms individually contribute to LDL alkalinization, NH3 entry likely plays the dominant role. RP MEJIA, R (reprint author), NHLBI,KIDNEY & ELECTROLYTE METAB LAB,BLDG 10,RM 6N-307,BETHESDA,MD 20892, USA. NR 32 TC 0 Z9 0 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0002-9513 J9 AM J PHYSIOL JI Am. J. Physiol. PD MAR PY 1993 VL 264 IS 3 BP F396 EP F403 PN 2 PG 8 WC Physiology SC Physiology GA KV271 UT WOS:A1993KV27100072 ER PT J AU TAKEDA, M HOMMA, T BREYER, MD HORIBA, N HOOVER, RL KAWAMOTO, S ICHIKAWA, I KON, V AF TAKEDA, M HOMMA, T BREYER, MD HORIBA, N HOOVER, RL KAWAMOTO, S ICHIKAWA, I KON, V TI VOLUME AND AGONIST-INDUCED REGULATION OF MYOSIN LIGHT-CHAIN PHOSPHORYLATION IN GLOMERULAR MESANGIAL CELLS SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE 2-DIMENSIONAL PHOSPHOPEPTIDE MAPPING; HYPEROSMOTIC STRESS ID SMOOTH-MUSCLE MYOSIN; PROTEIN KINASE-C; CONTRACTILE ELEMENTS; HEAVY-MEROMYOSIN; PLATELET MYOSIN; VASOPRESSIN; ACTIVATION; PHOSPHATASE; COTRANSPORT; DEPLETION AB We investigated whether cell volume decrease per se can activate intracellular mechanisms leading to mesangial cell contraction. For this purpose, we applied hyperosmotic stress to cultured glomerular mesangial cells and examined the effects on phosphorylation of myosin light chain (MLCP). Compared with control cells, hyperosmotic stress (390 mosmol/kg) attained by either NaCl or raffinose significantly increased MLCP to 140.7 +/- 7.0% (n = 5) and 134.8 +/- 7.7% (n = 4), respectively, in parallel with a decrease in the cell volume. This increase was comparable to that achieved by the following agonists: arginine vasopressin (AVP, 100 nM; n = 5) and endothelin-1 (ET, 10 nM; n = 5). By using two-dimensional tryptic phosphopeptide mapping, contribution of myosin light-chain kinase (MLCK) and protein kinase C (PKC) to the observed phosphorylation was examined by identifying phosphorylation at serine-19 (by MLCK) and at serine-1 or serine-2 (by PKC). Under resting conditions, relative distribution of phosphorylation between MLCK and PKC sites was 60.1 +/- 8.4 and 39.9 +/- 8.4%. The relative contribution by these enzymes remained similar during hyperosmotic stress or agonist stimulation. Since cytosolic Ca2+ concentration ([Ca2+]i) is an important determinant of MLCP, we also examined [Ca2+]i in these settings. While AVP and ET-induced a characteristic transient spike in [Ca2+]i, hyperosmotic stress caused a gradual and modest increase in [Ca2+]i. These studies show that, in mesangial cells, reduction in cell volume induces MLCP through mechanisms distinct from those involved in agonist-induced events. C1 VANDERBILT UNIV,MED CTR,SCH MED,DEPT PEDIAT,DIV PEDIAT NEPHROL,NASHVILLE,TN 37232. NHLBI,MOLEC CARDIOL LAB,BETHESDA,MD 20892. VANDERBILT UNIV,MED CTR,SCH MED,DEPT MED,NASHVILLE,TN 37232. VANDERBILT UNIV,MED CTR,SCH MED,DEPT PATHOL,NASHVILLE,TN 37232. FU NHLBI NIH HHS [HL-36526]; NIDDK NIH HHS [DK-37869, DK-42158] NR 29 TC 47 Z9 47 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0002-9513 J9 AM J PHYSIOL JI Am. J. Physiol. PD MAR PY 1993 VL 264 IS 3 BP F421 EP F426 PN 2 PG 6 WC Physiology SC Physiology GA KV271 UT WOS:A1993KV27100076 PM 8456955 ER PT J AU HIRAMATSU, Y KAWAI, R REBA, RC SIMON, TR BAUM, BJ BLASBERG, RG AF HIRAMATSU, Y KAWAI, R REBA, RC SIMON, TR BAUM, BJ BLASBERG, RG TI KINETIC-ANALYSIS OF RAT PAROTID-GLAND MUSCARINIC RECEPTORS INVIVO - COMPARISON WITH BRAIN AND HEART SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE QUINUCLIDINYL IODOBENZILATE; MUSCARINIC CHOLINERGIC RECEPTOR; PHARMACOKINETICS; SALIVARY GLANDS ID POSITRON EMISSION TOMOGRAPHY; OPIATE ANTAGONIST CYCLOFOXY; BINDING-SITES; CEREBROVASCULAR TRANSPORT; ACETYLCHOLINE-RECEPTORS; QUINUCLIDINYL BENZILATE; INACTIVE ENANTIOMERS; CHOLINERGIC RECEPTOR; ADENYLYL CYCLASE; HIGH-AFFINITY AB (RR)- and (SS)-quinuclidinyl iodobenzilate enantiomers [(RR)- and (SS)-IQNB, active and inert, respectively] have been synthesized for quantitative evaluation of muscarinic acetylcholine receptor (mAChR) binding. Pharmacokinetic approaches have not been used previously to assess in vivo IQNB binding in nonexcitable tissues. We have applied this method to examine mAChRs in rat parotid gland in comparison to those in brain and heart. Short-term infusion studies in vivo showed that the 'instantaneous' reversible binding of (RR)- and (SS)-IQNB was high in the parotid (greater nonspecific binding potential), intermediate in the heart, and lowest in cortex and cerebellum. Long-term bolus injection experiments showed that the parotid gland mAChRs possessed a binding potential for receptor specific sites (380), which was intermediate between that of parietal cortex (930) and cerebellum (10) and greater than that of heart (165). In vitro binding to plasma membranes was generally consistent with the in vivo findings. In aggregate, these studies show that mAChRs can be evaluated in vivo in a nonexcitable tissue with the use of stereospecific ligands and a pharmacokinetic approach. The data suggest that IQNB, a mAChR antagonist, can identify characteristics of specific binding sites, which may reflect tissue differences. C1 NIDR,CLIN INVEST & PATIENT CARE BRANCE,BLDG 10,RM IN-113,BETHESDA,MD 20892. NIH,CTR CLIN,DEPT NUCL MED,BETHESDA,MD 20892. GEORGE WASHINGTON UNIV,MED CTR,DEPT RADIOL,WASHINGTON,DC 20037. FU NINDS NIH HHS [NS-22215] NR 43 TC 9 Z9 9 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0002-9513 J9 AM J PHYSIOL JI Am. J. Physiol. PD MAR PY 1993 VL 264 IS 3 BP G541 EP G552 PN 1 PG 12 WC Physiology SC Physiology GA KV270 UT WOS:A1993KV27000075 PM 8460706 ER PT J AU GAMBASSI, G CAPOGROSSI, MC KLOCKOW, M LAKATTA, EG AF GAMBASSI, G CAPOGROSSI, MC KLOCKOW, M LAKATTA, EG TI ENANTIOMERIC DISSECTION OF THE EFFECTS OF THE INOTROPIC AGENT, EMD-53998, IN SINGLE CARDIAC MYOCYTES SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE CALCIUM; CONTRACTION; THIADIAZINONE DERIVATIVES; MYOFILAMENT CALCIUM ION SENSITIVITY; INOTROPIC AGENTS ID CHRONIC HEART-FAILURE; CARDIOTONIC AGENT; CALCIUM SENSITIVITY; CONGESTIVE CARDIOMYOPATHY; VENTRICULAR MYOCYTES; CYCLIC-AMP; MUSCLE; CA++; RESPONSIVENESS; SENSITIZATION AB The effects of the thiadiazinone derivative, 5-[1-(3,4-dimethoxybenzoyl)-1,2,3,4-tetrahydrochinolin-6-yl]-6-methyl-3,6-dihydro-2H-1,3,4-thiadiazin-2-on (EMD 53998), and of its (+)EMD 57033 and (-)EMD 57439 enantiomers, were tested on the contractile properties and cytosolic [Ca2+] ([Ca2+]i) transients of single intact guinea pig cardiac myocytes. Cells were loaded with the ester form of the fluorescent probe, indo-1, and bathed in a N-2-hydroxyethyl-piperazine-N'-2-ethanesulfonic acid-buffered solution at 25-degrees-C (1 mM of CaCl2, 1 Hz stimulation rate). All three substances exerted a pronounced increase in twitch amplitude: the maximal effect of the racemate (380% of control value) was approximately the sum of the effects of its two enantiomers (186 and 236% of control value for the (+)- and (-)-enantiomer, respectively). The [Ca2+]i transient, measured as the 410-to-490 nm indo-1 fluorescence ratio transient after excitation, was increased by the racemate and its (-)-enantiomer (172 and 152% of control value, respectively), but was not increased by the (+)-enantiomer. The racemate and the (-)-enantiomer, but not the (+)-enantiomer, markedly reduced the contraction duration and [Ca2+]i transient duration. In unstimulated cells resting length was significantly reduced by the (+)-enantiomer, and this was accompanied by a decrease in indo-1 fluorescence; the (-)-enantiomer had no effect on either parameter. In the presence of 2,3 butanedione monoxime (BDM), which markedly reduces twitch amplitude by inhibiting cross-bridge mechanics, addition of the (+)-enantiomer restored the twitch contraction to above the pre-BDM level without augmenting the [Ca2+]i transient. In contrast, the (-)-enantiomer failed to reverse the BDM-induced contractile depression, even though it caused a significant increase of the [Ca2+]i transient. Thus, in intact cells the positive inotropic effect of EMD 53998 is due to specific properties of its enantiomers: the (-)-enantiomer has adenosine 3',5'-cyclic monophosphate-like effects (increase in amplitude and reduction of [Ca2+]i transient and contraction durations), whereas the (+)-enantiomer enhances the myofilament-Ca2+ interaction. C1 NIA,GERONTOL RES CTR,CARDIOVASC SCI LAB,4940 EASTERN AVE,BALTIMORE,MD 21224. E MERCK AG,DEPT PHARMACEUT RES,W-6100 DARMSTADT,GERMANY. NR 42 TC 52 Z9 52 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0002-9513 J9 AM J PHYSIOL JI Am. J. Physiol. PD MAR PY 1993 VL 264 IS 3 BP H728 EP H738 PN 2 PG 11 WC Physiology SC Physiology GA KV271 UT WOS:A1993KV27100010 PM 8384421 ER PT J AU KARSON, CN CASANOVA, MF KLEINMAN, JE GRIFFIN, WST AF KARSON, CN CASANOVA, MF KLEINMAN, JE GRIFFIN, WST TI CHOLINE-ACETYLTRANSFERASE IN SCHIZOPHRENIA SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID ALZHEIMERS-DISEASE; BRAIN; NEURONS; GLIOSIS; METHYLPHENIDATE; SYMPTOMS; NUCLEUS AB Objective: To test the hypothesis that schizophrenia involves altered cholinergic tone in the pons, the authors studied post-mortem brain tissue from subjects with schizophrenia. Method: The authors used Western immunoblot to measure the concentration of choline acetyltransferase, an acetylcholine synthesizing enzyme, in the post-mortem brain tissue of 25 schizophrenic subjects and 28 nonschizophrenic comparison subjects. They also measured the concentration of glial fibrillary acidic protein, a protein from astrocytes, to examine the question of neurodegeneration. Results: The pontine choline acetyltransferase concentrations of the schizophrenic subjects were 46% lower than those of comparison subjects, a significant difference. Glial fibrillary acidic protein concentrations did not differ between the two groups. Conclusions: The lower concentration of choline acetyltransferase in the pontine tegmentum of schizophrenic subjects compared with comparison subjects suggests involvement of pontine cholinergic neurons in schizophrenia. C1 UNIV ARKANSAS MED SCI HOSP,LITTLE ROCK,AR 72205. VET ADM MED CTR,LITTLE ROCK,AR. NIMH,WASHINGTON,DC 20032. FU NIMH NIH HHS [MH-45729] NR 28 TC 85 Z9 86 U1 0 U2 0 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD MAR PY 1993 VL 150 IS 3 BP 454 EP 459 PG 6 WC Psychiatry SC Psychiatry GA KN845 UT WOS:A1993KN84500012 PM 8434662 ER PT J AU ALTEMUS, M PIGOTT, T LHEUREUX, F DAVIS, CL RUBINOW, DR MURPHY, DL GOLD, PW AF ALTEMUS, M PIGOTT, T LHEUREUX, F DAVIS, CL RUBINOW, DR MURPHY, DL GOLD, PW TI CSF SOMATOSTATIN IN OBSESSIVE-COMPULSIVE DISORDER SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID CORTICOTROPIN-RELEASING FACTOR; CEREBROSPINAL-FLUID SOMATOSTATIN; GROWTH-HORMONE SECRETION; CENTRAL NERVOUS-SYSTEM; HYPOTHALAMIC SOMATOSTATIN; DEPRESSED-PATIENTS; CEREBRAL-CORTEX; DISEASE; BEHAVIOR; RATS AB Objective: Because the central administration of somatostatin to experimental animals produces behaviors with some similarities to the compulsions of patients with obsessive-compulsive disorder and because serotonin reuptake inhibitors have been reported to reduce brain content of somatostatin, the authors examined central somatostatin activity in patients with obsessive-compulsive disorder. Method: CSF for measurement of somatostatin was obtained from 15 drug-free outpatients with obsessive-compulsive disorder and 27 normal volunteers. Results: The mean CSF somatostatin level was significantly higher in the patients with obsessive-compulsive disorder than in the normal subjects. Conclusions: Although the functional significance of this finding is unknown, these data are consistent with a role for somatostatin in the clinical symptomatology of obsessive-compulsive disorder and its response to neuropharmacological agents. The high levels of CSF somatostatin reported here in a patient subgroup whose predominant symptoms consisted of overly focused, perseverative thought processes are in contrast to the consistently low levels of CSF somatostatin seen in patients with a spectrum of disorders characterized by substantial cognitive deficits. C1 NIMH,CLIN SCI LAB,BETHESDA,MD 20892. NIMH,INTRAMURAL RES PROGRAM,CLIN NEUROENDOCRINOL BRANCH,BETHESDA,MD 20892. NIMH,BIOL PSYCHIAT BRANCH,BETHESDA,MD 20892. NR 49 TC 21 Z9 22 U1 0 U2 1 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 1993 VL 150 IS 3 BP 460 EP 464 PG 5 WC Psychiatry SC Psychiatry GA KN845 UT WOS:A1993KN84500013 PM 8094599 ER PT J AU KLEINMAN, HK SCHNAPER, HW AF KLEINMAN, HK SCHNAPER, HW TI BASEMENT-MEMBRANE MATRICES IN TISSUE-DEVELOPMENT SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article ID A-CHAIN; LAMININ; PROTEINS RP KLEINMAN, HK (reprint author), NIDR,DEV BIOL LAB,BLDG 30,ROOM 407,BETHESDA,MD 20892, USA. NR 15 TC 10 Z9 10 U1 0 U2 0 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 1993 VL 8 IS 3 BP 238 EP 239 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA KY235 UT WOS:A1993KY23500002 PM 8448014 ER PT J AU WU, T RIEVES, D LARIVEE, P LOGUN, C LAWRENCE, MG SHELHAMER, JH AF WU, T RIEVES, D LARIVEE, P LOGUN, C LAWRENCE, MG SHELHAMER, JH TI PRODUCTION OF EICOSANOIDS IN RESPONSE TO ENDOTHELIN-1 AND IDENTIFICATION OF SPECIFIC ENDOTHELIN-1 BINDING-SITES IN AIRWAY EPITHELIAL-CELLS SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article ID VASCULAR SMOOTH-MUSCLE; GUINEA-PIG AIRWAYS; VASOCONSTRICTOR PEPTIDE; NEUTRAL ENDOPEPTIDASE; TRACHEAL EPITHELIUM; CHLORIDE SECRETION; BRONCHOCONSTRICTOR; RELEASE; PHOSPHORAMIDON; ACCUMULATION AB The effect of endothelin-1 (ET-1) on arachidonate metabolism in the respiratory epithelium was investigated in primary cultures of feline tracheal epithelial cells. Subconfluent epithelial cell cultures were stimulated by ET-1, and eicosanoid generation was determined by high performance liquid chromatography (HLPC) of H-3-labeled arachidonic acid (AA) metabolites and by radioimmunoassay (RIA) of corresponding nonradiolabeled HPLC elution. The HPLC chromatograms of [H-3]AA-prelabeled samples revealed that ET-1 (10(-5) M) augmented the release of prostaglandin (PG) E2, 12-hydroxyeicosatetraenoic acid (HETE), PGF2alpha, and AA. RIA of corresponding nonradiolabeled HPLC elution demonstrated a significantly increased release of PGE2, PGF2alpha, and 12-HETE as well as 5-HETE in response to ET-1 stimulation. 5-HETE release from ET-1-stimulated cells was further identified by gas chromatography/mass spectrometry (GC/MS). The stimulating effect of ET-1 on AA metabolism was dose dependent (10(-5) to 10(-7) M) and peaked within 1 h with a progressive decline over the subsequent hours. Using I-125-labeled ET-1 as radioligand, the presence of specific binding sites for ET-1 was demonstrated in cultured feline tracheal epithelial cells. ET-1 binding reached equilibrium within 1 h at 37-degrees-C. Scatchard analysis suggested the existence of two saturable binding sites, with the estimated equilibrium dissociation constant (K(d)) of 35.3 pM and maximal binding capacity (Bmax) of 15.0 fmol/10(7) cells for the higher affinity binding site and K(d) of 205.9 pM and Bmax of 35.0 fmol/10(7) cells for the lower affinity binding site. Thus ET-1 binds to receptors on airway epithelial cells and initiates the production of a variety of AA metabolites that may modulate airway inflammatory responses. C1 NIH,DEPT CRIT CARE MED,BLDG 10,ROOM 7D43,BETHESDA,MD 20892. NR 44 TC 30 Z9 31 U1 0 U2 0 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 1993 VL 8 IS 3 BP 282 EP 290 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA KY235 UT WOS:A1993KY23500009 PM 8448018 ER PT J AU RODGERS, GP WALKER, EC PODGOR, MJ AF RODGERS, GP WALKER, EC PODGOR, MJ TI IS RELATIVE HYPERTENSION A RISK FACTOR FOR VASOOCCLUSIVE COMPLICATIONS IN SICKLE-CELL DISEASE SO AMERICAN JOURNAL OF THE MEDICAL SCIENCES LA English DT Article DE HYPERTENSION; MICROVASCULAR DISEASE; EPIGENETIC EFFECTS; RENAL DISEASE; VASOMOTOR TONE ID ANEMIA; PREVALENCE; RHEOLOGY; PRESSURE; FLOW AB Supine arterial blood pressure measurements of 89 patients with homozygous sickle cell disease and normal renal function were compared with those of an age-, race-, and sex-matched normal population and with those of individuals who had similar levels of anemia due to beta thalassemia. Consistent with previous reports, sickle cell patients had significantly lower blood pressure than the normal population. However, within most age groups, sickle cell patients tended to have higher than expected blood pressure than individuals with similar or less severe degrees of anemia. Furthermore, the authors have found an association between cerebrovascular accident and elevated blood pressure in men, even in a range of systolic and diastolic pressures that would be considered normal by conventional standards. These results reiterate the intricate relationship that exists between factors governing red cell rheology and microvascular tone. They also raise the possibility that ''relative'' hypertension may be associated with other vaso-occlusive manifestations of the sickle cell syndromes. RP RODGERS, GP (reprint author), NIDDK,CHEM BIOL LAB,BETHESDA,MD 20892, USA. NR 34 TC 37 Z9 37 U1 0 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0002-9629 J9 AM J MED SCI JI Am. J. Med. Sci. PD MAR PY 1993 VL 305 IS 3 BP 150 EP 156 DI 10.1097/00000441-199303000-00004 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA KR740 UT WOS:A1993KR74000004 PM 8447334 ER PT J AU JAN, LR YANG, CS HENCHAL, LS SUMIYOSHI, H SUMMERS, PL DUBOIS, DR LAI, CJ AF JAN, LR YANG, CS HENCHAL, LS SUMIYOSHI, H SUMMERS, PL DUBOIS, DR LAI, CJ TI INCREASED IMMUNOGENICITY AND PROTECTIVE EFFICACY IN OUTBRED AND INBRED MICE BY STRATEGIC CARBOXYL-TERMINAL TRUNCATION OF JAPANESE ENCEPHALITIS-VIRUS ENVELOPE GLYCOPROTEIN SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID MONOCLONAL-ANTIBODIES; STRUCTURAL PROTEINS; NUCLEOTIDE-SEQUENCE; MEMBRANE-PROTEINS; ANTIGENIC DETERMINANTS; FLAVIVIRUS; RESISTANCE; INFECTION; GENOME; GENE AB We constructed recombinant vaccinia viruses expressing the full-length envelope (E) glycoprotein of Japanese encephalitis virus (JEV) or a strategically truncated E glycoprotein, approximately 80% of the N-terminal sequence, and compared their antigenic structure and protective immunity in mice. The truncation site in the JEV E glycoprotein sequence corresponds to the position that had been shown to increase the immunogenicity of dengue type 4 or type 2 virus E glycoprotein. Analysis of the JEV E glycoprotein in recombinant virus-infected cells showed that C-terminally truncated E retains an antigenic structure similar to that of the full-length E glycoprotein. The full-length JEV E glycoprotein was detected predominantly intracellularly, while a small fraction (< 2%) was present on the cell surface. On the other hand, the truncated 80% E glycoprotein exhibited an alteration in the intracellular transport pathway resulting in increased accumulation (10-25%) on the cell surface and secretion (6-10%) into the medium. The C-terminally truncated E glycoprotein induced a greater antibody response and a higher level of protective immunity than did the full-length E glycoprotein in outbred CD-1 mice as well as in two strains of inbred mice that differ in their resistance to intraperitoneal (ip) JEV infection. In the case of outbred CD-1 and inbred C57/B1 mice, which possess a dominant autosomal genetic locus that controls resistance to a high dose of ip infection of JEV or the capacity to acquire resistance to intracerebral JEV infection, truncated E glycoprotein induced a higher titer of JEV neutralizing antibodies. C1 NATL TAIWAN UNIV,COLL MED,GRAD INST MICROBIOL,TAIPEI,TAIWAN. NATL INST PREVENT MED,TAIPEI,TAIWAN. WALTER REED ARMY INST RES,DEPT BIOL,WASHINGTON,DC 20307. RP JAN, LR (reprint author), NIAID,INFECT DIS LAB,MOLEC VIRAL BIOL SECT,BETHESDA,MD 20892, USA. NR 31 TC 30 Z9 31 U1 0 U2 1 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DRIVE SUITE 130, MCLEAN, VA 22101 SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD MAR PY 1993 VL 48 IS 3 BP 412 EP 423 PG 12 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA KX849 UT WOS:A1993KX84900016 PM 8385887 ER PT J AU BRINDLEY, PJ GAZZINELLI, RT DENKERS, EY DAVIS, SW DUBEY, JP BELFORT, R MARTINS, MC SILVEIRA, C JAMRA, L WATERS, AP SHER, A AF BRINDLEY, PJ GAZZINELLI, RT DENKERS, EY DAVIS, SW DUBEY, JP BELFORT, R MARTINS, MC SILVEIRA, C JAMRA, L WATERS, AP SHER, A TI DIFFERENTIATION OF TOXOPLASMA-GONDII FROM CLOSELY RELATED COCCIDIA BY RIBOPRINT ANALYSIS AND A SURFACE-ANTIGEN GENE POLYMERASE CHAIN-REACTION SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID NEOSPORA-CANINUM; CONGENITAL TOXOPLASMOSIS; DNA-POLYMERASE; SARCOCYSTIS; DIAGNOSIS; INVITRO; CYSTS; DOGS AB The tachyzoite of the human pathogen Toxoplasma gondii is morphologically indistinguishable from the proliferative stages of some other zoonotic coccidia, including Sarcocystis. To determine the identity of such coccidia obtained from human tissues and other sources, we compared riboprints (through restriction enzyme analysis of the polymerase chain reaction [PCR]-amplified small subunit rRNA gene) of the following protozoa: the RH and ts-4 strains of T. gondii, lines OH3 and S11, which are two recently isolated T. gondii-like parasites from Brazil, Neospora caninum, Sarcocystis species, and the malarial parasite Plasmodium berghei. In addition, the protozoan genomes were examined by PCR for homologs of surface antigen genes of T. gondii, and by Southern hybridization to the heterologous rRNA gene probe pSM 389. Strains OH3, S11, ts-4, and RH shared identical riboprints, and OH3, S11, and ts-4 have p22 and p30 surface antigen gene structures similar to RH. In contrast, riboprints for N. caninum and T. gondii differ with respect to Dde 1 sites, and moreover, their genomes vary significantly from one another at both the p22 and p30 gene loci. The riboprints of Sarcocystis and P. berghei differ markedly from T. gondii and N. caninum and from each other. Bam HI pSM 389 restriction fragment length polymorphisms differentiate ts-4 from RH, OH 3, and S11. Our results confirm that OH3 and S11 are indeed T. gondii, but that N. caninum and T. gondii are likely to be separate species, thereby resolving previous uncertainties concerning the identity of these parasites. Together, the variation in riboprints and surface antigen gene structure reflects the phylogenetic diversity among these coccidia, and in addition, confirms the value of riboprinting in the identification of apicomplexan parasites such as T gondii. C1 USDA, INST LIVESTOCK & POULTRY SCI, ZOONOT DIS LAB, BELTSVILLE, MD 20705 USA. ESCOLA PAULISTA MED SCH, BR-04023 SAO PAULO, BRAZIL. RP BRINDLEY, PJ (reprint author), NIAID, PARASIT DIS LAB, BETHESDA, MD 20892 USA. RI Waters, Andy/C-9377-2009; Belfort Jr, Rubens/E-2252-2012 OI Waters, Andy/0000-0001-8900-2982; Belfort Jr, Rubens/0000-0002-8422-3898 NR 28 TC 56 Z9 57 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 EI 1476-1645 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD MAR PY 1993 VL 48 IS 3 BP 447 EP 456 PG 10 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA KX849 UT WOS:A1993KX84900020 PM 8470780 ER PT J AU LEE, CH IGARASHI, Y HOHMAN, RJ KAULBACH, H WHITE, MV KALINER, MA AF LEE, CH IGARASHI, Y HOHMAN, RJ KAULBACH, H WHITE, MV KALINER, MA TI DISTRIBUTION OF SECRETORY LEUKOPROTEASE INHIBITOR IN THE HUMAN NASAL AIRWAY SO AMERICAN REVIEW OF RESPIRATORY DISEASE LA English DT Article ID BRONCHIAL PROTEASE INHIBITOR; MAST-CELL CHYMASE; ELASTASE; ANTILEUKOPROTEASE; THERAPY; FLUIDS; ASTHMA AB Secretory leukoprotease inhibitor (SLPI) is a secreted glandular protein thought to regulate elastase activity and, more recently, to inhibit both mast cell chymase activity and histamine release from mast cells. To begin to examine the possible role of SLPI in humans, we determined the distribution of SLPI in the human nasal mucosa and quantitated the functional activity of SLPI in nasal lavage fluid. Immunochemical staining of the nasal mucosa revealed intense, selective immunoreactivity in the serous cells of the submucosal glands. The level of SLPI in nasal secretions was measured by enzyme immunoassay. In control subjects (n = 8), the level of SLPI in nasal lavage fluid (NLF) after saline challenge (baseline level) was 2.5 +/- 0.5 mug/ml, accounting for 3.3 +/- 0.6% of total protein in nasal secretions. After methacholine (MCh) and histamine (HIST) challenge, the level of SLPI increased to 7.0 +/- 1.4 and 6.1 +/- 1.6 mug/ml, respectively (both p < 0.05). In atopic patients (n = 8), the level of SLPI after MCh and HIST challenge increased from a baseline level of 7.6 +/- 2.0 mug/ml to 22.1 +/- 6.4 and 25.2 +/- 10.5 mug/ml, respectively. After allergen challenge, the concentration of SLPI increased significantly in atopic patients, whereas there was no increase in the level of SLPI in control subjects. Western blot analysis of MCh-induced nasal secretions revealed a single band with a molecular weight of 12 kD, the same as recombinant SLPI. Functionally active SLPI (inhibition of neutrophil elastase activity) in nasal lavage fluid (NLF) was 220.9 +/- 31.4 nM, and approximately 97% of anti-HNE (human neutrophil elastase) capacity found in NLF was due to SLPI. These results indicate that SLPI is selectively present in large quantities in serous cells in the nasal mucosa and that it constitutes a significant portion of the total protein in nasal secretions. SLPI is secreted on challenge not only with MCh or HIST but also, in atopic patients, with allergen, and it likely helps regulate inflammatory protease activity on the mucosal surface. C1 NIAID,CLIN INVEST LAB,ALLERG DIS SECT,BLDG 10,RM 11C205,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. NR 26 TC 54 Z9 56 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 0003-0805 J9 AM REV RESPIR DIS JI Am. Rev. Respir. Dis. PD MAR PY 1993 VL 147 IS 3 BP 710 EP 716 PG 7 WC Respiratory System SC Respiratory System GA KR251 UT WOS:A1993KR25100034 PM 8095126 ER PT J AU DORWARD, DW AF DORWARD, DW TI DETECTION AND QUANTITATION OF HEME-CONTAINING PROTEINS BY CHEMILUMINESCENCE SO ANALYTICAL BIOCHEMISTRY LA English DT Article RP DORWARD, DW (reprint author), NIAID,ROCKY MT LABS,VECTORS & PATHOGENS LAB,HAMILTON,MT 59840, USA. NR 11 TC 27 Z9 28 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD MAR PY 1993 VL 209 IS 2 BP 219 EP 223 DI 10.1006/abio.1993.1110 PG 5 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA KR444 UT WOS:A1993KR44400002 PM 8470793 ER PT J AU BROWN, PS ROBERTS, CS MCINTOSH, CL SWAIN, JA CLARK, RE AF BROWN, PS ROBERTS, CS MCINTOSH, CL SWAIN, JA CLARK, RE TI RELATION BETWEEN CHOICE OF PROSTHESES AND LATE OUTCOME IN DOUBLE-VALVE REPLACEMENT SO ANNALS OF THORACIC SURGERY LA English DT Article ID MITRAL-VALVE; RISK-FACTORS; EXPERIENCE; BIOPROSTHESIS; MORBIDITY; MORTALITY; PROGNOSIS AB The purpose of this study was to determine if the combination of a mechanical and bioprosthetic valve in the aortic and mitral positions influences late morbidity and mortality when compared with patients who had dual mechanical or dual bioprosthetic valves inserted. We reviewed the course of 89 hospital survivors of combined aortic and mitral valve replacement. The mean postoperative follow-up interval was 6.6 years, with a total follow-up of 583 years (98% complete). At 12 months after operation, mean functional class decreased from 3.1 to 1.7 (p < 0.05) and mean cardiac index increased from 2.1 to 2.5 L . min-1 . m-2 (p < 0.05). Actuarial survival for the 89 patients (exclusive of < 30-day or in-hospital mortality, 14%) was 70%, 51%, and 33% at 5, 10, and 15 years. Freedom from reoperation was 93%, 78%, and 68%, and freedom from combined thromboembolism and anticoagulant-related hemorrhage was 82%, 60%, and 50%. These results show that there was no difference in overall survival in patients with dual mechanical valves, dual bioprosthetic valves, or a combination of both types at 15 years. There was, however, a lower reoperation rate in the group with dual mechanical valves as compared with the group with dual bioprosthetic valves (p < 0.05 at 10 years) or with a combination of valves (p < 0.05 at 15 years). The higher the number of mechanical valves the higher the combined risk of thromboembolism and anticoagulant-related hemorrhage. Patients who received one or two Starr-Edwards prostheses had significantly higher rates of thromboembolism and anticoagulant-related hemorrhage and a lower survival than those who received other valve combinations. Patients who received two Hancock bioprostheses had significantly higher rates of reoperation and a decreased incidence of combined thromboembolic and anticoagulant-related hemorrhagic events (p < 0.05 at 10 years). We conclude that combining a mechanical prosthesis and a bioprosthesis in the same patient is disadvantageous. C1 NHLBI,SURG BRANCH,BETHESDA,MD 20892. NR 28 TC 14 Z9 14 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD MAR PY 1993 VL 55 IS 3 BP 631 EP 640 PG 10 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA KT989 UT WOS:A1993KT98900015 PM 8452425 ER PT J AU STEVENS, RC LAIZURE, SC SANDERS, PL STEIN, DS AF STEVENS, RC LAIZURE, SC SANDERS, PL STEIN, DS TI MULTIPLE-DOSE PHARMACOKINETICS OF 12 MILLIGRAMS OF TRIMETHOPRIM AND 60 MILLIGRAMS OF SULFAMETHOXAZOLE PER KILOGRAM OF BODY-WEIGHT PER DAY IN HEALTHY-VOLUNTEERS SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID PNEUMOCYSTIS-CARINII PNEUMONIA; ACQUIRED-IMMUNODEFICIENCY-SYNDROME; PENTAMIDINE; DAPSONE; TRIAL; AIDS AB The disposition of 12 mg of trimethoprim and 60 mg of sulfamethoxazole per kg of body weight in six healthy male volunteers is described. The daily dose was evenly divided and administered orally every 6 h for 13 consecutive doses. Individual drug components were assayed by high-performance liquid chromatography. Steady-state concentrations in serum for trimethoprim and sulfamethoxazole were within the purported therapeutic ranges for treating Pneumocystis carinii pneumonia. Co-trimoxazole was well tolerated, and no subject withdrew from the study because of toxicity. Comparison of the pharmacokinetic parameters in this study with those of our previous findings indicates that the elimination of trimethoprim-sulfamethoxazole follows a first-order process within the dose ranges assessed. Administration of 15- to 20-mg/kg trimethoprim and 75- to 100-mg/kg sulfamethoxazole in four evenly divided doses for the first 24 h followed by 12 and 60 mg/kg/day, respectively, for the remainder of therapy rapidly attains concentrations in serum within the proposed P. carinii pneumonia therapeutic range. Clinical trials are indicated to evaluate this dosing scheme, which may decrease exposure to potentially excessive concentrations of trimethoprim and sulfamethoxazole. C1 NIAID,DIV AIDS,ROCKVILLE,MD 20852. RP STEVENS, RC (reprint author), UNIV TENNESSEE CTR HLTH SCI,DEPT CLIN PHARM,26 S DUNLAP ST,MEMPHIS,TN 38163, USA. NR 21 TC 19 Z9 19 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD MAR PY 1993 VL 37 IS 3 BP 448 EP 452 PG 5 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA KP921 UT WOS:A1993KP92100012 PM 8460913 ER PT J AU ROILIDES, E PASCHALIDES, P FREIFELD, A PIZZO, PA AF ROILIDES, E PASCHALIDES, P FREIFELD, A PIZZO, PA TI SUPPRESSION OF POLYMORPHONUCLEAR LEUKOCYTE BACTERICIDAL ACTIVITY BY SURAMIN SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID COLONY-STIMULATING FACTOR; HUMAN-NEUTROPHILS; CHEMOTHERAPEUTIC-AGENTS; PHAGOCYTOSIS; LYSOSOMES; INVITRO; FUSION AB Suramin is a polyanionic compound with potent antineoplastic properties. Because polymorphonuclear leukocytes (PMNs) are a crucial component of host defenses against bacteria and fungi, the effects of suramin on PMN function were studied in vitro. PMNs from healthy donors were incubated with concentrations of suramin of 1 to 1,000 mug/ml (within and exceeding the therapeutic range) for 30 min, and PMN functional parameters were subsequently assessed. Suramin had no effect on viability, chemotaxis to N-formylmethionyl leucyl phenylalanine, phagocytosis of Candida albicans, or superoxide anion production in response to phorbol myristate acetate and formylmethionyl leucyl phenylalanine. Fungicidal activity against C. albicans blastoconidia was unaffected at a suramin concentration of <500 mug/ml, whereas at higher concentrations a slight suppression was observed (P = 0.04). Bactericidal activity against Staphylococcus aureus was significantly suppressed by concentrations of greater-than-or-equal-to 100 mug/ml (P < 0.01). Phagocytosis of S. aureus was also significantly impaired at greater-than-or-equal-to 10 mug/ml (P < 0.05). The presence of 10% human serum during pretreatment did not abrogate the suramin-induced suppression of bactericidal activity. Treatment of PMNs with granulocyte colony-stimulating factor (4,000 U/ml) for 30 min prior to the addition of suramin (250 mug/ml) improved the bactericidal defect (P = 0.02). The PMN functional impairment may be related to increased susceptibility to bacterial infections, and granulocyte colony-stimulating factor may improve the defect. C1 NCI,PEDIAT BRANCH,INFECT DIS SECT,BETHESDA,MD 20892. NR 23 TC 12 Z9 12 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD MAR PY 1993 VL 37 IS 3 BP 495 EP 500 PG 6 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA KP921 UT WOS:A1993KP92100019 PM 7681657 ER PT J AU BHAMRE, S ANANDATHEERATHAVARADA, HK SHANKAR, SK BOYD, MR RAVINDRANATH, V AF BHAMRE, S ANANDATHEERATHAVARADA, HK SHANKAR, SK BOYD, MR RAVINDRANATH, V TI PURIFICATION OF MULTIPLE FORMS OF CYTOCHROME-P450 FROM A HUMAN BRAIN AND RECONSTITUTION OF CATALYTIC ACTIVITIES SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article ID HUMAN-LIVER CYTOCHROME-P-450; OXIDATIVE DRUG-METABOLISM; IMMUNOCHEMICAL PROPERTIES; GENETIC-POLYMORPHISM; POLYACRYLAMIDE GELS; RAT-BRAIN; MICROSOMES; REDUCTASE; PROTEINS; CYTOCHROMES-P-450 C1 NATL INST MENTAL HLTH & NEUROSCI,DEPT NEUROCHEM,HUSUR RD,BANGALORE 560029,KARNATAKA,INDIA. NCI,DRUG DISCOVERY RES & DEV LAB,FREDERICK,MD 21702. NATL INST MENTAL HLTH & NEUROSCI,DEPT NEUROPATHOL,BANGALORE 560029,KARNATAKA,INDIA. NR 38 TC 31 Z9 31 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD MAR PY 1993 VL 301 IS 2 BP 251 EP 255 DI 10.1006/abbi.1993.1141 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA KR034 UT WOS:A1993KR03400008 PM 8460938 ER PT J AU SZWEDA, LI STADTMAN, ER AF SZWEDA, LI STADTMAN, ER TI OXIDATIVE MODIFICATION OF GLUCOSE-6-PHOSPHATE-DEHYDROGENASE FROM LEUCONOSTOC-MESENTEROIDES BY AN IRON(II)-CITRATE COMPLEX SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article ID HUMAN-ERYTHROCYTE GLUCOSE-6-PHOSPHATE-DEHYDROGENASE; METAL-CATALYZED OXIDATION; MIXED-FUNCTION OXIDATION; GLUTAMINE-SYNTHETASE; PROTEINS; SEQUENCE; RESIDUE; CONSEQUENCES; MECHANISM; PEPTIDE RP SZWEDA, LI (reprint author), NHLBI,BIOCHEM LAB,BLDG 3,ROOM 221,BETHESDA,MD 20892, USA. NR 33 TC 24 Z9 25 U1 0 U2 3 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD MAR PY 1993 VL 301 IS 2 BP 391 EP 395 DI 10.1006/abbi.1993.1161 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA KR034 UT WOS:A1993KR03400028 PM 8460948 ER PT J AU BERGER, BB EGWUAGU, CE FREEMAN, WR WILEY, CA AF BERGER, BB EGWUAGU, CE FREEMAN, WR WILEY, CA TI MILIARY TOXOPLASMIC RETINITIS IN ACQUIRED-IMMUNODEFICIENCY-SYNDROME SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID OCULAR TOXOPLASMOSIS; RETINOCHOROIDITIS; BIOPSY; GONDII AB A unique pattern of bilateral miliary retinitis due to ocular toxoplasmosis developed in a patient in the late stages of acquired immunodeficiency syndrome. Results of serologic tests for toxoplasmosis remained negative throughout the clinical course of his ocular disease. The retinitis was unresponsive to a brief course of antitoxoplasmosis therapy. At autopsy, the histopathologic material was consistent with toxoplasmic retinitis and the DNA polymerase chain reaction was positive for toxoplasmosis. Recognition of this pattern of retinitis is important in the appropriate treatment of immunosuppressed patients with retinitis. C1 UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX 78284. NEI,BETHESDA,MD 20892. UNIV CALIF SAN DIEGO,SHILEY EYE CTR,LA JOLLA,CA 92093. UNIV CALIF SAN DIEGO,DEPT PATHOL,LA JOLLA,CA 92093. RP BERGER, BB (reprint author), RETINA CLIN AUSTIN,3705 MED PKWY,SUITE 410,AUSTIN,TX 78705, USA. FU PHS HHS [EDYO 7366] NR 20 TC 22 Z9 23 U1 0 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 1993 VL 111 IS 3 BP 373 EP 376 PG 4 WC Ophthalmology SC Ophthalmology GA KR446 UT WOS:A1993KR44600031 PM 8447750 ER PT J AU MEDEIROS, LJ BHAGAT, SKM NAYLOR, P FOWLER, D JAFFE, ES STETLERSTEVENSON, M AF MEDEIROS, LJ BHAGAT, SKM NAYLOR, P FOWLER, D JAFFE, ES STETLERSTEVENSON, M TI MALIGNANT THYMOMA ASSOCIATED WITH T-CELL LYMPHOCYTOSIS - A CASE-REPORT WITH IMMUNOPHENOTYPIC AND GENE REARRANGEMENT ANALYSIS SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID THYMOSIN-ALPHA-1; THYMOSIN-BETA-4; LYMPHOMAS; SERUM AB Patients with malignant thymoma rarely may also have a peripheral T-cell lymphocytosis. ''Lymphocyte spillover'' from the thymus into the peripheral blood as well as a second, associated neoplasm (ie, T-cell chronic lymphocytic leukemia) are two hypotheses that have been proposed to explain this clinical phenomenon. We describe another patient with a lymphocyte-rich malignant thymoma associated with peripheral T-cell lymphocytosis. At the time of initial diagnosis, the patient's complete blood cell count was unremarkable. However, subsequent to the development of pulmonary metastases, the patient developed persistent lymphocytosis. The total leukocyte count ranged from 20 to 30 x 10(9)/L, 80% of these cells being lymphocytes. Immunophenotypic analysis of peripheral blood specimens from this patient proved that the circulating cells were mature, polyclonal T cells. The cells expressed the alpha/beta T-cell receptor and the pan-T-cell antigens CD2, CD3, CD5, and CD7, and were negative for both terminal deoxynucleotidyl transferase (TdT) and the CD1 antigen. A mixture of T-helper (CD4+) and T-suppressor (CD8+) cells were present in a ratio of 1:1.6. Gene rearrangement studies revealed that the T-cell receptor beta chain and the immunoglobulin heavy-chain genes were in the germline configuration. Serum samples from this patient were also analyzed for thymic hormones; the level of thymosin alpha1 was markedly elevated, while that of thymosin beta4 was decreased. These results effectively exclude the hypothesis that the lymphocytosis represents a second, associated neoplasm. The lymphocyte spillover hypothesis also seems unlikely (although not excluded), since the lymphocytes in lymphocyte-rich thymomas usually have an immature thymic cortical immunophenotype. Furthermore, one might expect nonspecific elevation of all thymic hormone levels with lymphocyte spillover. Thus, we suggest that the lymphocytosis results from a poorly defined immunoregulatory disorder, related to the presence of thymoma, and perhaps secondary thymic hormone imbalance. C1 NCI,MED BRANCH,BETHESDA,MD 20892. GEORGE WASHINGTON UNIV,DEPT BIOCHEM,WASHINGTON,DC 20052. RP MEDEIROS, LJ (reprint author), NCI,PATHOL LAB,BLDG 10,ROOM 2A-33,BETHESDA,MD 20892, USA. NR 18 TC 24 Z9 24 U1 0 U2 1 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD MAR PY 1993 VL 117 IS 3 BP 279 EP 283 PG 5 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA KQ558 UT WOS:A1993KQ55800011 PM 8382915 ER PT J AU KERR, GS FLEISHER, TA HALLAHAN, CW LEAVITT, RY FAUCI, AS HOFFMAN, GS AF KERR, GS FLEISHER, TA HALLAHAN, CW LEAVITT, RY FAUCI, AS HOFFMAN, GS TI LIMITED PROGNOSTIC VALUE OF CHANGES IN ANTINEUTROPHIL CYTOPLASMIC ANTIBODY TITER IN PATIENTS WITH WEGENER GRANULOMATOSIS SO ARTHRITIS AND RHEUMATISM LA English DT Article ID AUTOANTIBODY-ASSOCIATED GLOMERULONEPHRITIS; VASCULITIS; NEUTROPHILS; DIAGNOSIS; BIOPSIES AB Objective. To assess the correlation and prognostic value of antineutrophil cytoplasmic antibody (cANCA) titers with disease activity in patients with Wegener's granulomatosis (WG). Methods. One hundred six patients with WG had serum ANCA determinations; 72 had serial titers obtained routinely at 1-3-month intervals. One hundred twelve subjects (19 of whom were healthy donors) served as controls. All serum samples were tested for cANCA by an indirect immunofluorescence technique. A prospective analysis of disease activity and cANCA values was performed. Disease activity was assessed according to clinical, laboratory, radiographic, and histopathologic findings. Results. Positivity for cANCA was a sensitive (88%) marker of active WG. However, changes in serial titers, temporally correlated with a change in disease status in only 64% of patients. Furthermore, an increase in the cANCA titer preceded clinical exacerbation of disease in only 24% of patients who had been in remission or had low-grade, smoldering disease. Conclusion. A rise in cANCA titer alone should not be considered adequate evidence of an impending clinical exacerbation, and therefore does not justify initiating or increasing immunosuppressive therapy. C1 NIAID,IMMUNOREGULAT LAB,VASCULITIS & RELATED DIS SECT,BLDG 10,BETHESDA,MD 20892. NIH,CTR CLIN,DEPT CLIN PATHOL,BETHESDA,MD 20892. NR 21 TC 227 Z9 230 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD MAR PY 1993 VL 36 IS 3 BP 365 EP 371 DI 10.1002/art.1780360312 PG 7 WC Rheumatology SC Rheumatology GA KR798 UT WOS:A1993KR79800011 PM 8452581 ER PT J AU SKARLATOS, SI ROUIS, M CHAPMAN, MJ KRUTH, HS AF SKARLATOS, SI ROUIS, M CHAPMAN, MJ KRUTH, HS TI HETEROGENEITY OF CELLULAR CHOLESTERYL ESTER ACCUMULATION BY HUMAN MONOCYTE-DERIVED MACROPHAGES SO ATHEROSCLEROSIS LA English DT Article DE MONOCYTE-MACROPHAGES; NON-LIPOPROTEIN CHOLESTEROL; ACETYLATED LDL; FILIPIN; ATHEROSCLEROSIS; HLA-DR ANTIGEN ID LOW-DENSITY LIPOPROTEIN; HOMOZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA; MOUSE PERITONEAL-MACROPHAGES; NIEMANN-PICK DISEASE; ACYL COENZYME-A; ACYLTRANSFERASE ACTIVITY; FLUORESCENCE MICROSCOPY; HUMAN-FIBROBLASTS; HLA-DR; CELLS AB We have studied cholesteryl ester accumulation in human monocyte-derived macrophages, which together with smooth muscle cells, represent the major cell types that accumulate cholesterol in atherosclerotic lesions. Monocyte-derived macrophages were incubated with either acetylated low density lipoprotein (AcLDL) or non-lipoprotein cholesterol and the question as to whether all of the cells, or specific cell subpopulations could accumulate cholesteryl ester was examined. We stained cholesteryl ester in monocyte-macrophages with the fluorescent probe filipin. Cholesteryl ester accumulated as lipid droplets that were widely dispersed in the cell cytoplasm. Interestingly, no more than 65% of monocytemacrophages accumulated cholesteryl ester during the 1st day of incubation with non-lipoprotein cholesterol. By 2 days of incubation, greater than 90% of cells displayed cholesteryl ester deposition. The cholesteryl ester which accumulated during the 2nd day of incubation was derived from unesterified cholesterol that had accumulated during the 1st day of incubation. This finding was substantiated by the following: (1) chemical measurements showed that the total cholesterol content of monocyte-macrophages did not increase further after the 1st day of incubation, and (2) all monocyte-macrophages had accumulated fluorescent tagged cholesterol during the 1st day of incubation. In contrast to the results obtained with non-lipoprotein cholesterol, more than 90% of monocyte-macrophages incubated with AcLDL for 1 day accumulated cholesteryl ester in two experiments. However, less than 62% of monocyte-macrophages accumulated cholesteryl ester in two other experiments, thereby resembling results obtained with non-lipoprotein cholesterol. Again, the lack of cholesteryl ester accumulation with AcLDL was not due to a lack of uptake of AcLDL, as greater than 90% of monocyte-macrophages accumulated fluorescent tagged AcLDL. The observed heterogeneity in cholesterol esterification among human monocyte-macrophages suggests,that functional subpopulations of these cells may exist with respect to cholesterol processing. However, heterogeneity in cholesteryl ester accumulation did not seem to correlate with expression of HLA-DR antigen, a marker of immunological activation of macrophages. Other sources of heterogeneity most likely result from inter-cellular variation at one or more levels of regulation of the cholesterol trafficking and esterification process. C1 NHLBI,MOLEC DIS BRANCH,EXPTL ATHEROSCLEROSIS SECT,BLDG 10,ROOM 5N-113,BETHESDA,MD 20892. HOP PITIE,INSERM,U321,UNITE RECH LIPOPROT & ATHEROGENESE,F-75651 PARIS 13,FRANCE. RI Rouis, Mustapha/E-4993-2016 NR 48 TC 8 Z9 8 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0021-9150 J9 ATHEROSCLEROSIS JI Atherosclerosis PD MAR PY 1993 VL 99 IS 2 BP 229 EP 240 DI 10.1016/0021-9150(93)90025-P PG 12 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA LA809 UT WOS:A1993LA80900009 PM 7684908 ER PT J AU NOGUCHI, CT SCHECHTER, AN RODGERS, GP AF NOGUCHI, CT SCHECHTER, AN RODGERS, GP TI SICKLE-CELL DISEASE PATHOPHYSIOLOGY SO BAILLIERES CLINICAL HAEMATOLOGY LA English DT Review ID FETAL-HEMOGLOBIN PRODUCTION; GENE-CLUSTER HAPLOTYPES; TRANSGENIC MOUSE MODEL; GAMMA-GLOBIN SYNTHESIS; INDUCED CATION FLUXES; DENSE RED-CELLS; OXYGEN-AFFINITY; DEOXYHEMOGLOBIN-S; INTRACELLULAR POLYMERIZATION; VASCULAR ENDOTHELIUM C1 NIH, DEPT HLTH & HUMAN SERV, BETHESDA, MD 20892 USA. NIDDKD, CHEM BIOL LAB, MOLEC HAEMATOL UNIT, BETHESDA, MD 20892 USA. OI Schechter, Alan N/0000-0002-5235-9408 NR 194 TC 35 Z9 35 U1 0 U2 3 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 1993 VL 6 IS 1 BP 57 EP 91 DI 10.1016/S0950-3536(05)80066-6 PG 35 WC Hematology SC Hematology GA KZ920 UT WOS:A1993KZ92000004 PM 8353318 ER PT J AU DURCAN, MJ GOLDMAN, D AF DURCAN, MJ GOLDMAN, D TI GENOMIC IMPRINTING - IMPLICATIONS FOR BEHAVIORAL-GENETICS SO BEHAVIOR GENETICS LA English DT Article; Proceedings Paper CT SYMP ON GENETICS AND ALCOHOLISM / MEETING OF THE BEHAVIOR GENETICS ASSOC CY JUL 01-05, 1992 CL BOULDER, CO SP NIAAA, UNIV COLORADO, VICE CHANCELLOR ACAD AFFAIRS, UNIV COLORADO COUNCIL RES & CREAT WORK, INST BEHAV GENET DE GENOMIC IMPRINTING; BEHAVIOR; NEUROBEHAVIORAL DISORDERS; ALCOHOLISM; PATERNAL ALCOHOL SYNDROME ID PATERNAL ALCOHOL-CONSUMPTION; PRADER-WILLI SYNDROME; DNA METHYLATION; GLOBIN GENE; EXPRESSION; TRANSGENE; EXPOSURE; ANGELMAN; MICE; RATS AB In recent years it has become apparent that the parental origin of genetic material has an impact on gene expression and this effect has become known as genomic imprinting. The evidence for the influence of genomic imprinting on behavior and in the etiology of certain neurobehavioral disorders is discussed. The possibilities for a role for genomic imprinting in the inheritance of behaviors related to alcohol abuse and alcoholism and in the paternal alcohol syndrome are also explored. C1 NIA,NEUROGENET LAB,BLDG 10,ROOM 3C102,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. RI Goldman, David/F-9772-2010 OI Goldman, David/0000-0002-1724-5405 NR 64 TC 11 Z9 11 U1 0 U2 1 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0001-8244 J9 BEHAV GENET JI Behav. Genet. PD MAR PY 1993 VL 23 IS 2 BP 137 EP 143 DI 10.1007/BF01067418 PG 7 WC Behavioral Sciences; Genetics & Heredity; Psychology, Multidisciplinary SC Behavioral Sciences; Genetics & Heredity; Psychology GA LC383 UT WOS:A1993LC38300006 PM 8512528 ER PT J AU TAYAMA, M SOEDA, S KISHIMOTO, Y MARTIN, BM CALLAHAN, JW HIRAIWA, M OBRIEN, JS AF TAYAMA, M SOEDA, S KISHIMOTO, Y MARTIN, BM CALLAHAN, JW HIRAIWA, M OBRIEN, JS TI EFFECT OF SAPOSINS ON ACID SPHINGOMYELINASE SO BIOCHEMICAL JOURNAL LA English DT Article ID SPHINGOLIPID ACTIVATOR PROTEINS; NIEMANN-PICK DISEASE; ENZYMATIC-HYDROLYSIS; PURIFICATION; LIPOSOMES AB The effect of saposins (A, B, C and D) on acid sphingomyelinase activity was determined using a crude human kidney sphingomyelinase preparation and a purified sphingomyelinase preparation from human placenta. Saposin D stimulated the activity of the crude enzyme by increasing its apparent K(m) and V(max). values for sphingomyelin hydrolysis. Unlike the crude enzyme, the activity of the purified enzyme was strongly inhibited by saposin D as well as other saposins. Saposin D decreased the apparent K(m) and V(max) values of purified sphingomyelinase activity. The effects of saposin D on the activity of different sphingomyelinase preparations appear to depend on Triton X-100, which is present in the crude enzyme but not in the purified enzyme. When the detergent was removed from the crude preparation, the effect of saposin D changed from being stimulatory to inhibitory. Conversely, when the detergent is added to the purified enzyme, the effect of saposin D on sphingomyelinase activity changed from being inhibitory to stimulatory. While other saposins were inhibitory or had no effect on sphingomyelinase activity in the above assay system, not only saposin D but also saposins A and C exhibited a stimulatory effect upon purified sphingomyelinase activity when the substrate, sphingomyelin, was added in the form of liposomes without detergent. Saposin B was not only inhibitory in the liposome system, but also reduced the stimulatory effect of saposins A, C and D. These observations indicate that the stimulatory effect of saposins A, C and D on acid sphingomyelinase activity is greatly influenced by the physical environment of the enzyme and suggest that similar effects by saposins may be exerted in lysosomal membranes. C1 UNIV CALIF SAN DIEGO,SCH MED,DEPT NEUROSCI,LA JOLLA,CA 92093. UNIV CALIF SAN DIEGO,SCH MED,CTR MOLEC GENET,LA JOLLA,CA 92093. NIMH,MOLEC NEUROGENET UNIT,BETHESDA,MD 20892. HOSP SICK CHILDREN,RES INST,TORONTO M5G 1X8,ONTARIO,CANADA. FU NICHD NIH HHS [HD-18983]; NINDS NIH HHS [NS-08682, NS-13559] NR 12 TC 26 Z9 26 U1 0 U2 2 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON, ENGLAND W1N 3AJ SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD MAR 1 PY 1993 VL 290 BP 401 EP 404 PN 2 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA KT729 UT WOS:A1993KT72900016 PM 8452527 ER PT J AU ALBRO, PW CORBETT, JT SCHROEDER, JL AF ALBRO, PW CORBETT, JT SCHROEDER, JL TI ENDOGENOUS LIPIDS OF THE EARTHWORM LUMBRICUS-TERRESTRIS SO BIOCHEMISTRY AND CELL BIOLOGY-BIOCHIMIE ET BIOLOGIE CELLULAIRE LA English DT Note DE EARTHWORM; LUMBRICUS; LIPIDS; GANGLIOSIDES; METABOLISM AB Earthworms (Lumbricus terrestris) were given [1-C-14]-labeled palmitic acid by gavage on days 0 and 3, and sacrificed on day 7. The distribution of label among lipid classes indicated that glycerides, sterol esters, cerebrosides, sulfatides, phosphatidylethanolamine, phosphatidylserine and (or) phosphatidylinositol, phosphatidylcholine, and sphingomyelin turn over in, or are synthesized by, the earthworm. Free fatty acids still had the highest specific radioactivity of any lipid class at the end of the experiment. Incorporation of label into sterol and hydrocarbon fractions was insignificant and there was no detectable label incorporated into gangliosides. Phosphatidylethanolamine apparently turned over quite slowly compared with other lipid classes, while the cerebroside fraction became highly labeled. Elongation of palmitic acid to stearate and oxidation to CO2 occurred extensively, but there was no evidence for desaturation. RP ALBRO, PW (reprint author), NIEHS,MOLEC BIOPHYS LAB,POB 12 233,RES TRIANGLE PK,NC 27709, USA. NR 8 TC 9 Z9 10 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 1993 VL 71 IS 3-4 BP 220 EP 221 PG 2 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA LQ050 UT WOS:A1993LQ05000016 PM 8398080 ER PT J AU KREITMAN, RJ BATRA, JK SEETHARAM, S CHAUDHARY, VK FITZGERALD, DJ PASTAN, I AF KREITMAN, RJ BATRA, JK SEETHARAM, S CHAUDHARY, VK FITZGERALD, DJ PASTAN, I TI SINGLE-CHAIN IMMUNOTOXIN FUSIONS BETWEEN ANTI-TAC AND PSEUDOMONAS EXOTOXIN - RELATIVE IMPORTANCE OF THE 2 TOXIN DISULFIDE BONDS SO BIOCONJUGATE CHEMISTRY LA English DT Article ID RECOMBINANT IMMUNOTOXIN; CYTOTOXIC ACTIVITY; DIPHTHERIA-TOXIN; ESCHERICHIA-COLI; DOMAIN-II; PROTEIN; RECEPTOR; BINDING; AERUGINOSA; CELLS AB Anti-Tac(Fv)-PE40 is a recombinant single-chain immunotoxin in which the variable heavy and light domains of the anti-IL2 receptor antibody, anti-Tac, are connected to each other by a peptide linker and then fused to PE40, a truncated form of Pseudomonas exotoxin (PE). This fusion protein has four disulfide bonds: one in each of the two variables domains, one in domain II (Cys 265-287), and one in domain Ib (Cys 372-379) of PE. To study the importance of the disulfide bonds of the toxin to the activity of single-chain immunotoxins, we constructed mutants in which either the cysteines in the toxin were changed to alanines or the amino acids 365-380 of PE were deleted. We began this study with anti-Tac(Fv)-PE40 and a more active variant, anti-Tac(Fv)-PE40KDEL, in which the carbonyl terminus is changed from REDLK to KDEL. From these proteins we made anti-Tac(Fv)-PE404A and anti-Tac(Fv)-PE40KDEL4A, respectively, by converting cysteins at amino acids 265, 287, 372, and 379 of PE to alanines. This change resulted in a 20-100-fold loss of activity toward human target cells, but no significant change in binding affinity to p55. To determine the importance of the second toxin disulfide bond, we removed amino acids 365-380 from anti-Tac(Fv)-PE40, anti-Tac(Fv)-PE40KDEL, and anti-Tac(Fv)-PE40KDEL4A, resulting in anti-Tac(Fv)-PE38, anti-Tac(Fv)-PE38KDEL, and anti-Tac(Fv)-PE38KDEL2A, respectively. This deletion resulted in a slight increase in cytotoxicity toward some target cells. Anti-Tac(Fv)-PE38KDEL and anti-Tac(Fv)-PE40KDEL were up to 300-fold more cytotoxic than their respective mutants which contained alanines only at positions 265 and 287. Thus the first disulfide bond of the toxin (Cys 265-287) is much more important for cytotoxicity than the second one (Cys 372-379). We found that anti-Tac(Fv)-PE40KDEL and anti-Tac(Fv)-PE38KDEL were the most active agents in vitro and had the same half-life in mice and the maximum tolerated dose was also the same for each. C1 NCI,DIV CANC BIOL DIAG & CTR,MOLEC BIOL LAB,BETHESDA,MD 20892. NR 27 TC 65 Z9 66 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 1043-1802 J9 BIOCONJUGATE CHEM JI Bioconjugate Chem. PD MAR-APR PY 1993 VL 4 IS 2 BP 112 EP 120 DI 10.1021/bc00020a002 PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA KV635 UT WOS:A1993KV63500002 PM 7873642 ER PT J AU GRUBER, BL HERSH, SP HALL, NRS WALETZKY, LR KUNZ, JF CARPENTER, JK KVERNO, KS WEISS, SM AF GRUBER, BL HERSH, SP HALL, NRS WALETZKY, LR KUNZ, JF CARPENTER, JK KVERNO, KS WEISS, SM TI IMMUNOLOGICAL RESPONSES OF BREAST-CANCER PATIENTS TO BEHAVIORAL INTERVENTIONS SO BIOFEEDBACK AND SELF-REGULATION LA English DT Article DE BIOFEEDBACK (PSYCHOLOGY); BREAST NEOPLASMS; PSYCHONEUROIMMUNOLOGY; BEHAVIOR THERAPY; RELAXATION TECHNIQUES ID BIOFEEDBACK-ASSISTED RELAXATION; IMMUNE FUNCTION; BLOOD-PRESSURE; IMMUNOCOMPETENCE; SURVIVAL; IMAGERY; STRESS; SYSTEM AB This article reports the results of an 18-month study of immune system and psychological changes in stage 1 breast cancer patients provided with relaxation, guided imagery, and biofeedback training. Thirteen lymph node negative patients who had recovered from a modified radical mastectomy were randomly assigned to either an immediate treatment or a delayed treatment control group. Multiple pre-post psychological measures were performed. Significant effects were found in natural killer cell (NK) activity (p < .017), mixed lymphocyte responsiveness (MLR) (p < .001), concanavalin A (Con-A) responsiveness (p < .001), and the number of peripheral blood lymphocytes (PBL) (p < .01). No significant psychological changes were detected; however, reductions were seen in psychological inventory scales measuring anxiety. The results show that behavioral interventions can be correlated with immune system measures, thereby replicating the results of an earlier pilot study from our Center. Discussion is provided on differential T-cell and B-cell responsiveness to behavioral interventions. C1 GEORGETOWN UNIV,MED CTR,DEPT PSYCHIAT & OBSTET & GYNECOL,WASHINGTON,DC 20007. GEORGE WASHINGTON UNIV,SCH MED,DEPT PSYCHIAT & PEDIAT,WASHINGTON,DC 20052. NCI,PEDIAT ONCOL BRANCH,BETHESDA,MD 20892. UNIV S FLORIDA,SCH MED,DEPT PSYCHIAT,TAMPA,FL 33620. RP GRUBER, BL (reprint author), MED ILLNESS COUNSELING CTR,2 WISCONSIN CIRCLE,SUITE 530,CHEVY CHASE,MD 20815, USA. NR 37 TC 89 Z9 92 U1 0 U2 5 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0363-3586 J9 BIOFEEDBACK SELF-REG JI Biofeedback Self-Regul. PD MAR PY 1993 VL 18 IS 1 BP 1 EP 22 DI 10.1007/BF00999510 PG 22 WC Psychology, Clinical SC Psychology GA KR743 UT WOS:A1993KR74300001 PM 8448236 ER PT J AU MARTIN, A PIGOTT, TA LALONDE, FM DALTON, I DUBBERT, B MURPHY, DL AF MARTIN, A PIGOTT, TA LALONDE, FM DALTON, I DUBBERT, B MURPHY, DL TI LACK OF EVIDENCE FOR HUNTINGTONS DISEASE-LIKE COGNITIVE DYSFUNCTION IN OBSESSIVE-COMPULSIVE DISORDER SO BIOLOGICAL PSYCHIATRY LA English DT Article DE OBSESSIVE-COMPULSIVE DISORDER (OCD); COGNITION; ATTENTION; MEMORY; PROCEDURAL LEARNING; BASAL GANGLIA ID GLUCOSE METABOLIC RATES; CEREBRAL BLOOD-FLOW; MAGNETIC-RESONANCE; TOMOGRAPHY; TRICHOTILLOMANIA; CLOMIPRAMINE; RECOGNITION; IMPAIRMENT; SLOWNESS; DEMENTIA AB Cognitive deficits in patients with structural lesions of the basal ganglia (e.g., Huntington's disease) commonly include slowed processing, reduced verbal fluency, difficulty switching set, impaired egocentric spatial ability, poor recall, and impaired acquisition of motor skills. The goal of this study was to determine if patients with obsessive-compulsive disorder (OCD) would have a similar pattern of cognitive dysfunction. A battery of neuropsychological tests, including reaction time-based measures of cognitive processing speed and a test of procedural, motor-skill learning, was administered to 17 unmedicated OCD patients and 16 age-and education-matched normal controls. Eleven individuals with trichotillomania, matched with the OCD patients on age, education, age at symptom onset, depression, and anxiety were also tested. Contrary to expectation, neither the OCD nor trichotillomania patients were impaired on any of the measures in the battery. The essentially normal performance by these patients suggests that the brain regions responsible for cognitive dysfunction in patients with Huntington's disease may differ from those associated with OCD. RP MARTIN, A (reprint author), NIMH,CLIN SCI LAB,BLDG 10,ROOM 3D-41,BETHESDA,MD 20892, USA. RI martin, alex/B-6176-2009 NR 56 TC 43 Z9 43 U1 9 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAR 1 PY 1993 VL 33 IS 5 BP 345 EP 353 DI 10.1016/0006-3223(93)90323-6 PG 9 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA KV420 UT WOS:A1993KV42000005 PM 8471692 ER PT J AU GERRARD, TL THORPE, R JEFFCOATE, S REYNOLDS, C AF GERRARD, TL THORPE, R JEFFCOATE, S REYNOLDS, C TI BIOLOGICAL POTENCY STANDARDS FOR CYTOKINES AND GROWTH-FACTORS SO BIOLOGICALS LA English DT Note C1 NATL INST BIOL STAND & CONTROLS,WHO,INT LAB BIOL STANDARDISAT,LONDON,ENGLAND. NCI,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21701. RP GERRARD, TL (reprint author), US FDA,CTR BIOL EVALUAT & RES,DIV CYTOKINE BIOL,1401 ROCKVILLE PIKE,ROCKVILLE,MD 20852, USA. RI Thorpe, Robin/E-6853-2013 NR 0 TC 2 Z9 2 U1 0 U2 0 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 1045-1056 J9 BIOLOGICALS JI Biologicals PD MAR PY 1993 VL 21 IS 1 BP 77 EP 79 DI 10.1006/biol.1993.1049 PG 3 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA LV059 UT WOS:A1993LV05900007 PM 8217121 ER PT J AU GRASSO, P HEINDEL, JJ POWELL, CJ REICHERT, LE AF GRASSO, P HEINDEL, JJ POWELL, CJ REICHERT, LE TI EFFECTS OF MONO(2-ETHYLHEXYL) PHTHALATE, A TESTICULAR TOXICANT, ON FOLLICLE-STIMULATING-HORMONE BINDING TO MEMBRANES FROM CULTURED RAT SERTOLI CELLS SO BIOLOGY OF REPRODUCTION LA English DT Article ID N-PENTYL PHTHALATE; DI-(2-ETHYLHEXYL) PHTHALATE; DI(2-ETHYLHEXYL) PHTHALATE; ACID ESTERS; ATROPHY; TESTIS; ZINC; METABOLITES; TOXICITY; PROTEIN AB The widely used plasticizer di(2-ethylhexyl) phthalate (DEHP) is a male reproductive toxicant. Its toxicity has been shown to be due primarily to the action of its metabolite mono(2-ethylhexyl) phthalate (MEHP) on Sertoli cells. We have previously shown that at least one of the sites of action of MEHP on the Sertoli cell is the cAMP second messenger system. MEHP inhibits the ability of FSH but not isoproterenol, forskolin, or cholera toxin to stimulate cAMP accumulation in cultured Sertoli cells in a dose- and time-dependent manner. To further characterize this effect of MEHP, we prepared a light membrane fraction from control and MEHP-treated Sertoli cells cultured from 18-day-old Fischer 344 rats and measured FSH binding in a radioligand receptor assay using I-125-labeled human FSH (I-125-hFSH). MEHP inhibited FSH binding when preincubated with Sertoli cells in culture but not when added simultaneously with I-125-hFSH to the purified membrane preparation. Attenuation of FSH binding was evident after a 3-h preincubation with 100 muM MEHP (18%) and was maximal after 15-24 h of preincubation (70-90%). Preincubation of Sertoli cells for 24 h with 100 muM DEHP had no effect on FSH binding. Half-maximal inhibition occurred at approximately 0.1 muM MEHP. Scatchard analysis indicated a four-fold decrease in FSH affinity with no change in receptor concentration. Exposure of Sertoli cells to MEHP amplified the attenuating effect of guanosine triphosphate (GTP) on FSH binding, suggesting that the action of MEHP may be at the level of the GTP-binding protein that couples the FSH receptor to the adenylate cyclase catalytic subunit. This effect of MEHP is age-independent over the range of 18-45 days. The active metabolites of the other phthalates toxic in vivo, i.e., monobutyl phthalate and monopentyl phthalate, also reduced FSH binding to Sertoli cell membranes but only from the older animals. Monomethyl phthalate, which is not a testicular toxicant in vivo, had no effect on FSH binding from animals at any age tested. We conclude that the ability of certain phthalate esters to reduce FSH binding to Sertoli cell membranes is likely to be at least a part of the mechanism responsible for their testicular toxicity. C1 NIEHS,NATL TOXICOL PROGRAM,DEV S REPROD TOXICOL GRP,POB 12233,MD E1-02,RES TRIANGLE PK,NC 27709. ALBANY MED COLL,DEPT BIOCHEM & MOLEC BIOL,ALBANY,NY 12208. FU NICHD NIH HHS [HD-13938] NR 30 TC 60 Z9 61 U1 1 U2 8 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PD MAR PY 1993 VL 48 IS 3 BP 454 EP 459 DI 10.1095/biolreprod48.3.454 PG 6 WC Reproductive Biology SC Reproductive Biology GA LD899 UT WOS:A1993LD89900003 PM 8384005 ER PT J AU ZHOU, JA BONDY, C AF ZHOU, JA BONDY, C TI ANATOMY OF THE HUMAN OVARIAN INSULIN-LIKE GROWTH-FACTOR SYSTEM SO BIOLOGY OF REPRODUCTION LA English DT Article ID FACTOR-BINDING-PROTEIN; I IGF-I; LOW-MOLECULAR-WEIGHT; GRANULOSA-CELLS; GENE-EXPRESSION; MESSENGER-RNA; FOLLICULAR-FLUID; RECEPTOR GENE; RAT OVARY; FOLLICLES AB In situ hybridization was used to map insulin-like growth factor (IGF) system gene expression in ovaries from an anencephalic infant and several young women. Growing oocytes in infant and mature ovaries expressed transcripts for IGF-I and IGF-II, respectively, and all oocytes expressed abundant IGF-I receptor transcripts, raising the possibility of autocrine IGF function in oocyte maturation. IGF-I mRNA was not detected in the mature ovary, but IGF-II mRNA was localized in follicular blood vessels and in granulosa cells (GC) and was especially abundant in the GC of atretic as opposed to young follicles. IGF-I receptor mRNA was abundant in GC of antral and atretic follicles, and was expressed at low levels in the thecal interstitial compartments. IGF-binding protein (IGFBP) 1 mRNA was not detected, but IGFBPs 2-5 mRNAs each demonstrated a unique ovarian distribution. IGFBP2 mRNA was abundant in GC and thecal cells at all stages of development. IGFBP3 mRNA was detected only in the endothelium of ovarian blood vessels. IGFBP4 mRNA was also localized in endothelium, but in addition was present in stromal connective tissue and in GC of the one Graafian follicle detected in this study, but not consistently in atretic follicles. IGFBP5 mRNA was expressed by luminal or cumulus GC in virtually all follicles and was highly abundant in stromal interstitial cells of the mature ovary. Insofar as our limited sample allows developmental analysis, gene expression for the IGF-I receptor and IGF-II in GC and for IGFBP5 in interstitial cells appeared to be developmentally or hormonally regulated, as their mRNAs were significantly more abundant in mature ovaries than in ovaries from an anencephalic infant. GC gene expression for IGFBP2 and IGFBP5, in contrast, appears to be constitutive. In summary, the intensity, compartmentalization, and developmental regulation of IGF system gene expression in the human ovary support the view that IGFs play an important and complex role in ovarian physiology. The striking evidence of IGF ligand and receptor gene expression in human oocytes suggests that IGFs have a role in growth from the earliest moments in development. RP ZHOU, JA (reprint author), NICHHD,DEV ENDOCRINOL BRANCH,BG 10,RM 10N262,BETHESDA,MD 20892, USA. NR 39 TC 158 Z9 162 U1 0 U2 2 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PD MAR PY 1993 VL 48 IS 3 BP 467 EP 482 DI 10.1095/biolreprod48.3.467 PG 16 WC Reproductive Biology SC Reproductive Biology GA LD899 UT WOS:A1993LD89900005 PM 7680905 ER PT J AU FULCHER, KD WELCH, JE DAVIS, CM OBRIEN, DA EDDY, EM AF FULCHER, KD WELCH, JE DAVIS, CM OBRIEN, DA EDDY, EM TI CHARACTERIZATION OF LAMININ RECEPTOR MESSENGER-RIBONUCLEIC-ACID AND PROTEIN EXPRESSION IN MOUSE SPERMATOGENIC CELLS SO BIOLOGY OF REPRODUCTION LA English DT Article ID RAT SERTOLI CELLS; MALE GERM LINE; TRANSLATIONAL REGULATION; GENE FAMILY; DIFFERENTIAL EXPRESSION; EXTRACELLULAR-MATRIX; MOLECULAR-CLONING; EMBRYONIC RETINA; ANTIBODY PROBES; RNA AB A cDNA proposed to encode the mouse laminin receptor (MLR) was isolated from a mouse round spermatid expression library. The cDNA contained complete coding and 3' untranslated regions but was missing the first 42 bases from the 5' untranslated region. Northern blot analysis using a 3' EcoRI fragment of the cDNA identified a 1.2-kb transcript in mouse testes and all somatic tissues tested. Additional transcripts of 1.3 and 0.9 kb were present in round spermatids isolated from mouse testes. Northern blots using ribonuclease (RNase) H-treated poly(A)+ RNA indicated that the difference in the size of 1.3-kb round spermatid transcripts and 1.2-kb transcripts was due to differing poly(A)+ tail lengths. The 0.9-kb round spermatid transcript hybridized to all but the 5' end of the 1.2-kb MLR cDNA, suggesting that an alternate start site is used or that transcript processing occurs in these cells. Immunoblot analysis identified proteins in spermatogenic cells corresponding to the 67-70-kDa MLR and its 43-kDa precursor. In addition, ligand binding studies and affinity chromatography procedures indicated that spermatogenic cell proteins of these sizes bind laminin. However, spermatocytes and spermatids are spatially isolated from laminin in the testes, and MLR may have other functions in these cells. C1 GLAXO RES INST,DEPT CELL BIOL,RES TRIANGLE PK,NC 27709. UNIV N CAROLINA,DEPT PEDIAT,REPROD BIOL LAB,CHAPEL HILL,NC 27595. UNIV N CAROLINA,DEPT CELL BIOL,REPROD BIOL LAB,CHAPEL HILL,NC 27595. UNIV N CAROLINA,DEPT ANAT,REPROD BIOL LAB,CHAPEL HILL,NC 27595. RP FULCHER, KD (reprint author), NIEHS,REPROD & DEV TOXICOL LAB,GAMETE BIOL SECT,BLDG 101,C4-04,POB 12233,RES TRIANGLE PK,NC 27709, USA. FU NICHD NIH HHS [P30-HD-18968, HD-26485, R01 HD026485] NR 52 TC 17 Z9 18 U1 0 U2 1 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PD MAR PY 1993 VL 48 IS 3 BP 674 EP 682 DI 10.1095/biolreprod48.3.674 PG 9 WC Reproductive Biology SC Reproductive Biology GA LD899 UT WOS:A1993LD89900031 PM 8452943 ER PT J AU TANG, DI GELLER, NL POCOCK, SJ AF TANG, DI GELLER, NL POCOCK, SJ TI ON THE DESIGN AND ANALYSIS OF RANDOMIZED CLINICAL-TRIALS WITH MULTIPLE END-POINTS SO BIOMETRICS LA English DT Article DE CLINICAL TRIAL DESIGN AND ANALYSIS; GROUP SEQUENTIAL TRIALS; MULTIPLE HYPOTHESIS TESTING; OBRIENS STATISTIC; REPEATED SIGNIFICANCE TESTS AB This paper considers some methods for reducing the number of significance tests undertaken when analyzing and reporting results of clinical trials. Emphasis is placed on designing and analyzing clinical trials to examine a composite hypothesis concerning multiple endpoints and combining this multiple endpoint methodology with group sequential methodology. Four methods for composite hypotheses are considered: an ordinary least squares and a generalized least squares approach both due to O'Brien (1984, Biometrics 40, 1079-1087), a new modification of these, and an approximate likelihood ratio test, due to Tang, Gnecco, and Geller (1989, Biometrika 76, 577-583). These are extended for group sequential use. In particular, simulation is used to generate critical values and sequences of nominal significance levels for the approximate likelihood ratio test, which is not normally distributed. An example is given and the relative merits of the suggested approaches are discussed. C1 NHLBI,BIOSTAT RES BRANCH,FED BLDG,ROOM 2A11,7550 WISCONSIN AVE,BETHESDA,MD 20892. NATHAN S KLINE INST PSYCHIAT RES,DIV STAT SCI & EPIDEMIOL,ORANGEBURG,NY 10962. UNIV LONDON LONDON SCH HYG & TROP MED,MED STAT UNIT,LONDON WC1E 7HT,ENGLAND. FU NCI NIH HHS [CA43074]; NIMH NIH HHS [MH42959] NR 15 TC 63 Z9 63 U1 0 U2 5 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 1993 VL 49 IS 1 BP 23 EP 30 DI 10.2307/2532599 PG 8 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA LB230 UT WOS:A1993LB23000003 PM 8513104 ER PT J AU FREEDMAN, LS MIDTHUNE, DN BROWN, CC STEELE, V KELLOFF, GJ AF FREEDMAN, LS MIDTHUNE, DN BROWN, CC STEELE, V KELLOFF, GJ TI STATISTICAL-ANALYSIS OF ANIMAL CANCER CHEMOPREVENTION EXPERIMENTS SO BIOMETRICS LA English DT Article DE CARCINOGEN; GOODNESS OF FIT; NEGATIVE BINOMIAL; POISSON; SURVIVAL ANALYSIS; TUMOR INITIATION; TUMOR PROMOTION ID CLINICAL-TRIALS AB We explore the use of a statistical model proposed by Kokoska (1987, Biometrics 43, 525-534) for the analysis of animal cancer chemoprevention experiments. We show, using an example, that the results derived from the method can be sensitive to the parametric forms of the distributions that are assumed, particularly to the distribution of the number of tumors per animal. We propose goodness-of-fit tests to aid in the choice of the distributions. C1 INFORMAT MANAGEMENT SERV INC,SILVER SPRING,MD 20902. NCI,DIV CANC PREVENT & CONTROL,CHEMOPREVENT BRANCH,BETHESDA,MD 20892. RP FREEDMAN, LS (reprint author), NCI,DIV CANC PREVENT & CONTROL,BIOMETRY BRANCH,EXECUT PLAZA N,BETHESDA,MD 20892, USA. NR 6 TC 14 Z9 14 U1 0 U2 0 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 1993 VL 49 IS 1 BP 259 EP 268 PG 10 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA LB230 UT WOS:A1993LB23000025 PM 8513108 ER PT J AU GOLDBERG, ER COHEN, LA AF GOLDBERG, ER COHEN, LA TI MODELS FOR INVIVO DEIODINATION OF 2-IODOHISTIDINE SO BIOORGANIC CHEMISTRY LA English DT Article ID I IODOTHYRONINE DEIODINASE; HETEROAROMATIC SYSTEMS; PLASMODIUM-FALCIPARUM; HISTIDINE ANALOGS; ISOTOPE EXCHANGE; RING HYDROGENS; SELENOCYSTEINE; IMIDAZOLE-2-THIONES; SUBSTITUTION; DERIVATIVES RP GOLDBERG, ER (reprint author), NIDDKD,BIOORGAN CHEM LAB,BETHESDA,MD 20892, USA. NR 49 TC 4 Z9 4 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0045-2068 J9 BIOORG CHEM JI Bioorganic Chem. PD MAR PY 1993 VL 21 IS 1 BP 41 EP 48 DI 10.1006/bioo.1993.1006 PG 8 WC Biochemistry & Molecular Biology; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA LA644 UT WOS:A1993LA64400006 ER PT J AU ANSARI, A SZABO, A AF ANSARI, A SZABO, A TI THEORY OF PHOTOSELECTION BY INTENSE LIGHT-PULSES - INFLUENCE OF REORIENTATIONAL DYNAMICS AND CHEMICAL-KINETICS ON ABSORBENCY MEASUREMENTS SO BIOPHYSICAL JOURNAL LA English DT Article ID RESOLVED INFRARED-SPECTROSCOPY; FLUORESCENCE DEPOLARIZATION; MACROMOLECULES; MEMBRANES AB The theory of absorbance measurements on a system (e.g., chromophore(s) in a protein) that undergoes a sequence of reactions initiated by a linearly polarized light pulse is developed for excitation pulses of arbitrary intensity. This formalism is based on a set of master equations describing the time evolution of the orientational distribution function of the various species resulting from excitation, reorientational dynamics, and chemical kinetics. For intense but short excitation pulses, the changes in absorbance (for arbitrary polarization directions of the excitation and probe pulses) and the absorption anisotropy are expressed in terms of reorientational correlation functions. The influence of the internal motions of the chromophore as well as the overall motions of the molecules is considered. When the duration of the excitation pulse is long compared to the time-scale of internal motions but comparable to the overall correlation time of the molecule that is reorienting isotropically, the problem of calculating the changes in absorbance is reduced to the solution of a set ot first-order coupled differential equations. Emphasis is placed on obtaining explicit results for quantities that are measured in photolysis and fluorescence experiments so as to facilitate the analysis of experimental data. RP ANSARI, A (reprint author), NIDDKD,CHEM PHYS LAB,BETHESDA,MD 20892, USA. RI Szabo, Attila/H-3867-2012 NR 15 TC 35 Z9 35 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD MAR PY 1993 VL 64 IS 3 BP 838 EP 851 PG 14 WC Biophysics SC Biophysics GA KR826 UT WOS:A1993KR82600031 PM 8471729 ER PT J AU ANSARI, A JONES, CM HENRY, ER HOFRICHTER, J EATON, WA AF ANSARI, A JONES, CM HENRY, ER HOFRICHTER, J EATON, WA TI PHOTOSELECTION IN POLARIZED PHOTOLYSIS EXPERIMENTS ON HEME-PROTEINS SO BIOPHYSICAL JOURNAL LA English DT Article ID RESOLVED INFRARED-SPECTROSCOPY; CONFORMATIONAL-CHANGES; CARBON-MONOXIDE; GEMINATE RECOMBINATION; HUMAN-HEMOGLOBIN; OPTICAL-SPECTRA; LIGAND-BINDING; DYNAMICS; MYOGLOBIN; RESOLUTION AB Polarized photolysis experiments have been performed on the carbon monoxide complex of myoglobin to assess the effects of photoselection on the kinetics of ligand rebinding and to investigate the reorientational dynamics of the heme plane. The results are analyzed in terms of the optical theory developed in the preceding paper by Ansari and Szabo. Changes in optical density arising from rotational diffusion of the photoselected population produce large deviations from the true geminate ligand rebinding curves if measurements are made with only a single polarization. The apparent ligand rebinding curves are significantly distorted even at photolysis levels greater than 90%. These deviations are eliminated by obtaining isotropically-averaged optical densities from measurements using both parallel and perpendicular polarizations of the probe pulse. These experiments also yield the optical anisotropy, which gives a novel method for accurately determining the degree of photolysis, as well as important information on the reorientational dynamics of the heme plane. The correlation time for the overall rotational diffusion of the molecule is obtained f rom the decay of the anisotropy. The anisotropy prior to rotational diffusion is lower than that predicted for a rigidly attached, perfectly circular absorber, corresponding to an apparent order parameter of S = 0.95 +/- 0.02. Polarized absorption data on single crystals suggest that the decreased anisotropy results more from internal motions of the heme plane which take place on time scales shorter than the duration of the laser pulse (10 ns) than from out-of-plane polarized transitions. RP ANSARI, A (reprint author), NIDDKD,CHEM PHYS LAB,BLDG 2,BETHESDA,MD 20892, USA. RI Henry, Eric/J-3414-2013 OI Henry, Eric/0000-0002-5648-8696 NR 52 TC 34 Z9 34 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD MAR PY 1993 VL 64 IS 3 BP 852 EP 868 PG 17 WC Biophysics SC Biophysics GA KR826 UT WOS:A1993KR82600032 PM 8471730 ER PT J AU HENRY, ER AF HENRY, ER TI MOLECULAR-DYNAMICS SIMULATIONS OF HEME REORIENTATIONAL MOTIONS IN MYOGLOBIN SO BIOPHYSICAL JOURNAL LA English DT Article ID FLUORESCENCE DEPOLARIZATION; CARBON-MONOXIDE; PROTEINS; SPECTROSCOPY; HEMOGLOBIN; REFINEMENT; GEOMETRY; ENERGY AB Molecular dynamics simulations of 2-ns duration were performed on carbonmonoxymyoglobin and deoxymyoglobin in vacuo to study the reorientational dynamics of the heme group. The heme in both simulations undergoes reorientations of approximately 5-degrees amplitude on a subpicosecond time scale, which produce a rapid initial decay in the reorientational correlation function to about 0.99. The heme also experiences infrequent changes in average orientation of approximately 10-degrees amplitude, which lead to a larger slow decay of the reorientational correlation function over a period of hundreds of picoseconds. The simulations have not converged with respect to these infrequent transitions. However, an estimate of the order parameter for rapid internal motions of the heme from those orientations which are sampled by the simulations suggests that the subnanosecond orientational dynamics of the heme accounts for at least 30% of the unresolved initial anisotropy decay observed in the nanosecond time-resolved optical absorption experiments on myoglobin reported by Ansari et al. in a companion paper (Ansari, A., C. M. Jones, E. R. Henry, J. Hofrichter, and W. A. Eaton, 1992. Biophys. J. 64:852-868.). A more complete sampling of the accessible heme orientations would most likely increase this fraction further, The simulation of the liganded molecule also suggests that the conformational dynamics of the CO ligand may contribute significantly to discrepancies between the ligand conformation as probed by x-ray diffraction and by infrared-optical photoselection experiments. The protein backbone explores multiple conformations during the simulations, with the largest structural changes appearing in the E and F helices, which are in contact with the heme. The variations in the heme orientation correlate with the conformational dynamics of the protein on a time scale of hundreds of picoseconds, suggesting that the heme orientation may provide a useful probe of dynamical processes in the protein. RP HENRY, ER (reprint author), NIDDKD,CHEM PHYS LAB,BLDG 2,ROOM B1-04,9000 ROCKVILLE PIKE 2-122,BETHESDA,MD 20892, USA. RI Henry, Eric/J-3414-2013 OI Henry, Eric/0000-0002-5648-8696 NR 26 TC 19 Z9 19 U1 1 U2 5 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD MAR PY 1993 VL 64 IS 3 BP 869 EP 885 PG 17 WC Biophysics SC Biophysics GA KR826 UT WOS:A1993KR82600033 PM 8471731 ER PT J AU VANDENHEUVEL, JP TYSON, FL BELL, DA AF VANDENHEUVEL, JP TYSON, FL BELL, DA TI CONSTRUCTION OF RECOMBINANT RNA TEMPLATES FOR USE AS INTERNAL STANDARDS IN QUANTITATIVE RT-PCR SO BIOTECHNIQUES LA English DT Note ID POLYMERASE CHAIN-REACTION; MESSENGER-RNA; EXPRESSION; DNA; GENE AB The PCR has proven to be useful in the analysis of gene expression of specific mRNAs. Although PCR is able to detect rare mRNA transcripts following reverse transcription PCR, determining relative or absolute copy number can be difficult due to sample-to-sample variation. The use of a recombinant mRNA internal standard that contains target mRNA primer sequences greatly improves reproducibility of quantitation. Reverse transcription PCR products generated from the internal standard can be distinguished from the product generated from the target gene mRNA because of their size difference. In this report we present a facile and general PCR-based method for synthesis of internal standards that may be used as competitive or co-amplified templates for quantitative reverse transcription PCR. C1 NIEHS,BIOCHEM RISK ANAL LAB,POB 12233,MD C3-03,RES TRIANGLE PK,NC 27709. NIEHS,MOLEC TOXICOL LAB,RES TRIANGLE PK,NC 27709. PURDUE UNIV,PHARMACOL & TOXICOL LAB,W LAFAYETTE,IN 47907. NR 14 TC 164 Z9 164 U1 0 U2 2 PU EATON PUBLISHING CO PI NATICK PA 154 E. CENTRAL ST, NATICK, MA 01760 SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD MAR PY 1993 VL 14 IS 3 BP 395 EP 398 PG 4 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA KQ889 UT WOS:A1993KQ88900023 PM 7681298 ER PT J AU KANTARJIAN, HM BERAN, M ELLIS, A ZWELLING, L OBRIEN, S CAZENAVE, L KOLLER, C RIOS, MB PLUNKETT, W KEATING, MJ ESTEY, EH AF KANTARJIAN, HM BERAN, M ELLIS, A ZWELLING, L OBRIEN, S CAZENAVE, L KOLLER, C RIOS, MB PLUNKETT, W KEATING, MJ ESTEY, EH TI PHASE-I STUDY OF TOPOTECAN, A NEW TOPOISOMERASE-I INHIBITOR, IN PATIENTS WITH REFRACTORY OR RELAPSED ACUTE-LEUKEMIA SO BLOOD LA English DT Article ID DNA; CAMPTOTHECIN; POISONS; BINDING; CELLS C1 UNIV TEXAS,MD ANDERSON CANC CTR,DEPT MED ONCOL,HOUSTON,TX 77030. NCI,BETHESDA,MD 20892. RP KANTARJIAN, HM (reprint author), UNIV TEXAS,MD ANDERSON CANC CTR,DEPT HEMATOL,BOX 61,1515 HOLCOMBE BLVD,HOUSTON,TX 77030, USA. FU NCI NIH HHS [CA32839] NR 29 TC 141 Z9 143 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 1993 VL 81 IS 5 BP 1146 EP 1151 PG 6 WC Hematology SC Hematology GA KP977 UT WOS:A1993KP97700005 PM 8382970 ER PT J AU SOLARY, E BERTRAND, R KOHN, KW POMMIER, Y AF SOLARY, E BERTRAND, R KOHN, KW POMMIER, Y TI DIFFERENTIAL INDUCTION OF APOPTOSIS IN UNDIFFERENTIATED AND DIFFERENTIATED HL-60 CELLS BY DNA TOPOISOMERASE-I AND TOPOISOMERASE-II INHIBITORS SO BLOOD LA English DT Article ID HUMAN-LEUKEMIA-CELLS; PROTEIN-KINASE-C; GENE-EXPRESSION; GROWTH-FACTOR; PROGRAMMED DEATH; TUMOR PROMOTERS; LYMPHOCYTES-T; RETINOIC ACID; CYTO-TOXICITY; B-CELLS C1 NCI,DIV CANC TREATMENT,MOLEC PHARMACOL LAB,DEV THERAPEUT PROGRAM,BLDG 37,ROOM 5C27,BETHESDA,MD 20892. NR 79 TC 187 Z9 192 U1 1 U2 4 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD MAR 1 PY 1993 VL 81 IS 5 BP 1359 EP 1368 PG 10 WC Hematology SC Hematology GA KP977 UT WOS:A1993KP97700033 PM 8382972 ER PT J AU BIANCHI, S PAGLIERANI, M ZAMPI, G CARDONA, G CATALIOTTI, L BONARDI, R CIATTO, S AF BIANCHI, S PAGLIERANI, M ZAMPI, G CARDONA, G CATALIOTTI, L BONARDI, R CIATTO, S TI PROGNOSTIC-SIGNIFICANCE OF C-ERBB-2 EXPRESSION IN NODE NEGATIVE BREAST-CANCER SO BRITISH JOURNAL OF CANCER LA English DT Article ID HER-2 NEU ONCOGENE; PROTEIN OVEREXPRESSION; CARCINOMA; AMPLIFICATION AB The prognostic value of c-erbB-2 oncogene expression was studied retrospectively in a consecutive series of 230 node negative breast cancers, followed-up for at least 7 years after primary treatment. The expression of c-erbB-2 oncoprotein was determined on formalin-fixed paraffin-embedded tissue, using a monoclonal anti-c-erbB-2 antibody by the avidin-biotin immunoperoxidase method. Positive immunostaining was observed in 20.9% of cases, whereas strong diffuse positivity was recorded only in 8.7% of cases. C-erbB-2 gene product showed no association to T category or nuclear grade. A significant association of c-erbB-2 expression to prognosis was observed only for cases showing a strong diffuse immunostaining, but such an association was no longer statistically significant at multivariate analysis adjusting for other prognostic factors such as T category and nuclear grading. C-erbB-2 expression is of no value to predict the clinical course of node negative patients in the current practice. C1 CTR STUDIO PREVENZ ONCOL,VIALE A VOLTA 171,I-50131 FLORENCE,ITALY. UNIV FLORENCE,INST ANAT & ISTOL PATOL,I-50121 FLORENCE,ITALY. UNIV FLORENCE,INST PATOL CHIRURG 2,I-50121 FLORENCE,ITALY. UNIV FLORENCE,INST CLIN CHIRURG 1,I-50121 FLORENCE,ITALY. NATL CANC INST,GENOA,ITALY. NR 27 TC 74 Z9 75 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD MAR PY 1993 VL 67 IS 3 BP 625 EP 629 DI 10.1038/bjc.1993.114 PG 5 WC Oncology SC Oncology GA KP200 UT WOS:A1993KP20000034 PM 8094977 ER PT J AU GOODWIN, FK AF GOODWIN, FK TI PREDICTORS OF ANTIDEPRESSANT RESPONSE SO BULLETIN OF THE MENNINGER CLINIC LA English DT Article ID MONOAMINE-OXIDASE INHIBITORS; MAJOR DEPRESSIVE DISORDER; TOTAL SLEEP-DEPRIVATION; REFRACTORY DEPRESSION; ATYPICAL DEPRESSION; ENDOGENOUS-DEPRESSION; DRUG RESPONSE; II ERROR; IMIPRAMINE; TRANYLCYPROMINE AB The development of new pharmacological agents has dramatically improved the treatment of major depressive disorders. But the question of whether there are reliable predictors of response to a particular agent or class of agent remains to be answered completely. The author provides an overview of current understanding of antidepressant response prediction in terms of three sources of variance: clinical variables, biological variables, and pharmacological response. He also notes evidence of the effectiveness of two nonpharmacological treatments, sleep deprivation therapy and light therapy. RP GOODWIN, FK (reprint author), NIMH, 5600 FISHERS LANE, ROOM 17 99, ROCKVILLE, MD 20857 USA. NR 72 TC 26 Z9 26 U1 2 U2 2 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 USA SN 0025-9284 EI 1943-2828 J9 B MENNINGER CLIN JI Bull. Menninger Clin. PD SPR PY 1993 VL 57 IS 2 BP 146 EP 160 PG 15 WC Psychiatry; Psychology, Psychoanalysis SC Psychiatry; Psychology GA LC530 UT WOS:A1993LC53000002 PM 8508153 ER PT J AU PESTALOZZI, BC SOTOS, GA CHOYKE, PL FISHERMAN, JS COWAN, KH OSHAUGHNESSY, JA AF PESTALOZZI, BC SOTOS, GA CHOYKE, PL FISHERMAN, JS COWAN, KH OSHAUGHNESSY, JA TI TYPHLITIS RESULTING FROM TREATMENT WITH TAXOL AND DOXORUBICIN IN PATIENTS WITH METASTATIC BREAST-CANCER SO CANCER LA English DT Article DE TYPHLITIS; TAXOL; DOXORUBICIN; METASTATIC BREAST CANCER ID PHASE-I; INFUSION; TOXICITY AB Background. Typhlitis is being recognized with increasing frequency as a serious complication of aggressive chemotherapy for hematologic and solid malignancies. Methods. In this report the authors describe two cases of typhlitis in patients with metastatic breast cancer treated with taxol and doxorubicin. Results. Both cases occurred during the first cycle of treatment with taxol (180 mg/m2) and doxorubicin (75 mg/m2), being given simultaneously as 72-hour continuous intravenous infusions. Conclusion. Two cases of typhlitis have occurred after combined treatment with taxol and doxorubicin, while typhlitis has not been described after treatment with either drug alone. C1 NCI,DEPT DIAGNOST RADIOL,BETHESDA,MD 20892. RP PESTALOZZI, BC (reprint author), NCI,MED BRANCH,9000 ROCKVILLE PIKE,BLDG 10,ROOM 12N226,BETHESDA,MD 20892, USA. NR 13 TC 61 Z9 62 U1 0 U2 4 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD MAR 1 PY 1993 VL 71 IS 5 BP 1797 EP 1800 DI 10.1002/1097-0142(19930301)71:5<1797::AID-CNCR2820710514>3.0.CO;2-B PG 4 WC Oncology SC Oncology GA KP990 UT WOS:A1993KP99000013 PM 8095437 ER PT J AU VALDEZ, IH WOLFF, A ATKINSON, JC MACYNSKI, AA FOX, PC AF VALDEZ, IH WOLFF, A ATKINSON, JC MACYNSKI, AA FOX, PC TI USE OF PILOCARPINE DURING HEAD AND NECK RADIATION-THERAPY TO REDUCE XEROSTOMIA AND SALIVARY DYSFUNCTION SO CANCER LA English DT Article DE XEROSTOMIA; RADIATION THERAPY; SALIVARY GLAND; PAROTID GLAND; PILOCARPINE; SIALOGOGUE ID GASTROINTESTINAL SYSTEMS; GLAND DYSFUNCTION; RADIOTHERAPY AB Background. Salivary gland hypofunction commonly develops during radiation therapy to the head and neck region. This study evaluated whether the sialogogue pilocarpine given during radiation therapy may reduce the severity of xerostomia and salivary dysfunction. Methods. Nine patients requiring head, neck, or mantle radiation therapy participated in this double-blind, placebo-controlled trial. The patients took either 5 mg of pilocarpine or placebo four times daily for 3 months, beginning the day before radiation therapy. Subjective complaints and salivary functions were assessed. Results. The pilocarpine-treated group had a lower frequency of oral symptoms during treatment than the placebo-treated group. Although salivary flow decreased in atl patients, the pilocarpine-treated group had smaller reductions in flow. No drug effect was observed in glands that were irradiated completely. Thus, pilocarpine appeared to stimulate salivary tissues outside the radiation field. Conclusions. These results suggest that stimulation with pilocarpine may reduce the severity of salivary dysfunction and associated oral symptoms during radiation therapy. RP VALDEZ, IH (reprint author), NIDR,CLIN INVEST & PATIENT CARE BRANCH,BLDG 10,RM 1N-113,BETHESDA,MD 20892, USA. NR 15 TC 70 Z9 74 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 0008-543X J9 CANCER JI Cancer PD MAR 1 PY 1993 VL 71 IS 5 BP 1848 EP 1851 DI 10.1002/1097-0142(19930301)71:5<1848::AID-CNCR2820710522>3.0.CO;2-F PG 4 WC Oncology SC Oncology GA KP990 UT WOS:A1993KP99000021 PM 8448748 ER PT J AU CALVO, B KASHIMIRI, SVS HUTZELL, P HAND, PH SLAVINCHIORINI, DC SCHLOM, J ZAREMBA, S AF CALVO, B KASHIMIRI, SVS HUTZELL, P HAND, PH SLAVINCHIORINI, DC SCHLOM, J ZAREMBA, S TI CONSTRUCTION AND PURIFICATION OF DOMAIN-DELETED IMMUNOGLOBULIN VARIANTS OF THE RECOMBINANT CHIMERIC B72.3 (Y1) MONOCLONAL-ANTIBODY SO CANCER BIOTHERAPY LA English DT Article DE DOMAIN-DELETED ANTIBODIES; TUMOR-ASSOCIATED ANTIGEN; TAG-72; PROTEIN-G ID ESCHERICHIA-COLI; CANCER-PATIENTS; TUMOR-CELLS; EXPRESSION; CARCINOMA; RADIOLOCALIZATION; LOCALIZATION; PROTEINS AB Chimeric antibodies have been produced against a pancarcinomic tumor associated antigen, TAG-72, by fusing the genes for the variable region of mouse MAb B72.3 to the genes for the constant region of human IgG. In our efforts to optimize the pharmacokinetics of plasma clearance and the efficiency of tumor localization and penetrance of cB72.3, we have now developed truncated versions of immunoglobulin heavy chains. The domain-deleted antibodies are produced by transfecting cells that produce chimeric kappa chains with expression vectors that encode chimeric heavy chains lacking the sequences that encode the C(H)2 domain, C(H)3 domain, or both. Despite the absence of these domains, the transfectomas secrete H2L2 tetramers with appropriate antigenic specificity. All the domain-deleted immunoglobulins can be purified by chromatography on Protein G Sepharose which binds to a site on the Fab region that is retained in the domain-deleted antibodies. The C(H)2C(H)3 domain-deleted immunoglobulin produced in cell culture is analogous in size to enzymatically produced F(ab')2. C1 NCI,TUMOR IMMUNOL & BIOL LAB,9000 ROCKVILLE PIKE,BLDG 10,ROOM 8B07,BETHESDA,MD 20892. NR 29 TC 7 Z9 7 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1062-8401 J9 CANCER BIOTHERAPY JI Cancer Biother. PD SPR PY 1993 VL 8 IS 1 BP 95 EP 109 DI 10.1089/cbr.1993.8.95 PG 15 WC Oncology SC Oncology GA LL850 UT WOS:A1993LL85000012 PM 7529083 ER PT J AU BROWN, LM BURMEISTER, LF EVERETT, GD BLAIR, A AF BROWN, LM BURMEISTER, LF EVERETT, GD BLAIR, A TI PESTICIDE EXPOSURES AND MULTIPLE-MYELOMA IN IOWA MEN SO CANCER CAUSES & CONTROL LA English DT Article DE CASE-CONTROL STUDY; EPIDEMIOLOGY; ETIOLOGY; FARMING; MULTIPLE MYELOMA; PESTICIDES; UNITED-STATES AB A population-based case-control study of 173 White men with multiple myeloma (MM) and 650 controls was conducted in Iowa (United States), an area with a large farming population, to evaluate the association between MM, agricultural risk factors, and exposure to individual pesticides. A slight nonsignificantly elevated risk for MM was seen among farmers (odds ratio [OR] = 1.2, 95 percent confidence interval [CI] = 0.8-1.7). Although slight excesses were observed, there were no significant associations between MM and handling either classes of pesticides or specific pesticides. Thus, this study found little evidence to suggest an association between risk of MM and farming or pesticides. RP BROWN, LM (reprint author), NCI,EPIDEMIOL & BIOSTAT PROGRAM,EXECUT PLAZA N,ROOM 415,BETHESDA,MD 20892, USA. FU NIEHS NIH HHS [ES 03099] NR 0 TC 47 Z9 47 U1 0 U2 5 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 1993 VL 4 IS 2 BP 153 EP 156 DI 10.1007/BF00053156 PG 4 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA KR651 UT WOS:A1993KR65100010 PM 8481493 ER PT J AU HAYES, RB FRIEDELL, GH ZAHM, SH COLE, P AF HAYES, RB FRIEDELL, GH ZAHM, SH COLE, P TI ARE THE KNOWN BLADDER-CANCER RISK-FACTORS ASSOCIATED WITH MORE ADVANCED BLADDER-CANCER SO CANCER CAUSES & CONTROL LA English DT Article DE AROMATIC AMINES; BLADDER CANCER; OCCUPATION; RISK FACTORS; TOBACCO; UNITED-STATES AB Risk factors for superficial and invasive bladder cancer were examined in a case-control study of 470 cases identified in 1967-68 in the Brockton and Boston Standard Metropolitan Areas (MA, United States) and of 500 population-based controls. Histologic specimens were reviewed and classified as superficial or invasive, following a standardized protocol. The tobacco-associated risk for superficial bladder cancer was odds ratio (OR) = 2.6 (95 percent confidence interval [CI] = 1.7-4.1) and the risk for invasive bladder cancer was OR = 1.7 (CI = 1.1-2.5). For subjects less than 60 years of age, the risks were greater for invasive tumors (OR = 4.3, CI = 1.2-15) than for superficial tumors (OR = 2.0, CI = 0.9-4.2), but this pattern for tobacco use was not found in older subjects. A strong trend of increased risk with increased amount of cigarettes smoked was shown only for invasive bladder tumors. No clear pattern of excess risk for invasive bladder tumors was seen for age at first use and years since last use of tobacco. The risk associated with occupational exposure to aromatic amine bladder carcinogens was OR = 1.7 (CI = 0.8-3.3) for superficial and OR = 1.5 (CI = 0.8-3.0) for invasive bladder cancer. For subjects less than 60 years of age, the risks were greater for invasive (OR = 12.0, CI = 2.1-65) than for superficial tumors (OR = 4.3, CI = 0.8-24), but this pattern for occupational exposure was not found in older subjects. Risk by age at first exposure to occupational aromatic-amine, bladder carcinogens was similar for superficial and invasive tumors. Overall, there was no association between known bladder-cancer risk-factors and more advanced bladder cancer. The relative risk associated with cigarette smoking and occupational exposure to aromatic amines was higher for invasive than superficial cancer only for men less than 60 years of age. RP HAYES, RB (reprint author), NCI,ENVIRONM EPIDEMIOL BRANCH,EPN 418,BETHESDA,MD 20892, USA. RI Zahm, Shelia/B-5025-2015 NR 0 TC 28 Z9 28 U1 1 U2 1 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 1993 VL 4 IS 2 BP 157 EP 162 DI 10.1007/BF00053157 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA KR651 UT WOS:A1993KR65100011 PM 8481494 ER PT J AU CHOW, WH LINET, MS MCLAUGHLIN, JK HSING, AW CHIEN, HTC BLOT, WJ AF CHOW, WH LINET, MS MCLAUGHLIN, JK HSING, AW CHIEN, HTC BLOT, WJ TI RISK-FACTORS FOR SMALL-INTESTINE CANCER SO CANCER CAUSES & CONTROL LA English DT Article DE ALCOHOL; DIET; SMALL INTESTINE CANCER; TOBACCO; UNITED-STATES AB Small intestine cancer is relatively rare. Clinical reports have suggested that several medical conditions may predispose to increased occurrence of this cancer, but otherwise its etiology is unknown. In one of the first case-control studies of this cancer, we compared questionnaire responses provided by next-of-kin of 430 persons who died of small intestine cancer cf 921 controls who died of other causes. Subjects were identified from decedents included in the 1986 United States National Mortality Followback Survey. The questionnaires sought information on demographic and lifestyle characteristics, including diet and use of tobacco and alcohol. Tobacco and alcohol consumption were unrelated to risk of small intestine cancer, but weekly or more frequent consumption of red meat and monthly or more frequent intake of salt-cured/smoked foods were associated with two- to three fold increases in risk. The findings suggest that dietary factors probably are involved in risk of small intestine cancer, but additional research in other settings is required to clarify the determinants of these rare cancers. RP CHOW, WH (reprint author), NCI,DIV CANC ETIOL,EPIDEMIOL & BIOSTAT PROGRAM,6130 EXECUT BLVD,EPN ROOM 403,ROCKVILLE,MD 20852, USA. NR 0 TC 61 Z9 65 U1 0 U2 0 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 1993 VL 4 IS 2 BP 163 EP 169 DI 10.1007/BF00053158 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA KR651 UT WOS:A1993KR65100012 PM 8481495 ER PT J AU HUTSON, PR TUTSCH, K SPRIGGS, D CHRISTIAN, M RAGO, R MUTCH, R WILDING, G AF HUTSON, PR TUTSCH, K SPRIGGS, D CHRISTIAN, M RAGO, R MUTCH, R WILDING, G TI EVIDENCE OF AN ABSORPTION PHASE AFTER SHORT INTRAVENOUS SURAMIN INFUSIONS SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE SURAMIN; ABSORPTION; PHARMACOKINETICS ID HEPARIN; PHARMACOKINETICS; THERAPY AB Suramin was given as an intravenous infusion to 16 cancer patients in a phase I trial. Individual pharmacokinetic parameters were calculated from a test dose given 1 week prior to the administration of a full-dose (350-700 mg/m2) regimen of 1-h loading and maintenance infusions. A distribution phase of 3.8 h was found. Plasma suramin concentrations were noted to increase following cessation of the intravenous test infusion in eight subjects. A model is proposed in which high-capacity, low-affinity binding of suramin to a shallow compartment adjacent to the intravascular space occurs rapidly during infusion, followed by absorption back into the measured blood pool with binding to plasma albumin. Despite the observable presence of this postinfusion peak shortly after the cessation of the brief suramin infusion, the pharmacokinetics of suramin were best characterized by a traditional two-compartment model. The dose-adjusted area under the concentration-time curve (AUC) increased with dose, supporting a hypothesis of sustained absorption of suramin to vascular endothelium but also raising the possibility of dose-dependent clearance. C1 UNIV WISCONSIN,DEPT HUMAN ONCOL,MADISON,WI 53706. WILLIAM S MIDDLETON MEM VET ADM MED CTR,NCI,CTEP,DCT,MADISON,WI 53705. RP HUTSON, PR (reprint author), UNIV WISCONSIN,SCH PHARM,425 N CHARTER ST,MADISON,WI 53706, USA. FU NCI NIH HHS [N01-CM-07306, T32-CA09614]; NCRR NIH HHS [M01-RR03186] NR 20 TC 6 Z9 6 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD MAR PY 1993 VL 31 IS 6 BP 495 EP 499 DI 10.1007/BF00685042 PG 5 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA KT115 UT WOS:A1993KT11500013 PM 8453691 ER PT J AU YOU, WC BLOT, WJ ZHANG, L KNELLER, RW LI, JY JIN, ML CHANG, YS ZENG, XR ZHAO, L FRAUMENI, JF XU, GW SAMLOFF, MI AF YOU, WC BLOT, WJ ZHANG, L KNELLER, RW LI, JY JIN, ML CHANG, YS ZENG, XR ZHAO, L FRAUMENI, JF XU, GW SAMLOFF, MI TI SERUM PEPSINOGENS IN RELATION TO PRECANCEROUS GASTRIC-LESIONS IN A POPULATION AT HIGH-RISK FOR GASTRIC-CANCER SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID ATROPHIC GASTRITIS; MUCOSAL HISTOLOGY; PERNICIOUS-ANEMIA AB Concentrations of serum pepsinogens (PG) I and II were determined for 3252 randomly selected adults who participated in a population-based gastroscopic screening in an area of China with one of the world's highest rates of gastric cancer. PG I and II concentrations in both sexes tended to be higher than reported in other countries, with levels generally higher among males than females. PG I tended to decrease and PG II to increase with age, but the most pronounced associations were between PG I:II ratios and gastric histology. Median PG I:II ratios monotonically declined from 9.1 to 7.2 to 5.7 to 5.4 to 3.8 among those with superficial gastritis, chronic atrophic gastritis, intestinal metaplasia, dysplasia, and stomach cancer, respectively. The prevalence of dysplasia was nearly 3 times greater among those with PG I:II ratios less than 3 compared with those whose PG I:II ratios were greater than 10. While average levels differed significantly among the histologic groups, the PG I:II ratios were neither sensitive nor specific markers of an individual's likelihood of advanced gastric lesions in this population. C1 LINQU PUBL HLTH BUR,SHANDONG 252600,PEOPLES R CHINA. NCI,BETHESDA,MD 20892. VET ADM MED CTR,SEPULVEDA,CA 91343. WEIFANG MED INST,WEIFANG 261041,SHANDONG,PEOPLES R CHINA. RP YOU, WC (reprint author), BEIJING INST CANC RES,BEIJING 100034,PEOPLES R CHINA. FU NCI NIH HHS [N01-CP-05631, N01-CP-15620, N01-CP-95660] NR 12 TC 32 Z9 34 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAR-APR PY 1993 VL 2 IS 2 BP 113 EP 117 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA KR070 UT WOS:A1993KR07000005 PM 8467245 ER PT J AU REDDEL, RR SALGHETTI, SE WILLEY, JC OHNUKI, Y KE, Y GERWIN, BI LECHNER, JF HARRIS, CC AF REDDEL, RR SALGHETTI, SE WILLEY, JC OHNUKI, Y KE, Y GERWIN, BI LECHNER, JF HARRIS, CC TI DEVELOPMENT OF TUMORIGENICITY IN SIMIAN VIRUS-40-IMMORTALIZED HUMAN BRONCHIAL EPITHELIAL-CELL LINES SO CANCER RESEARCH LA English DT Article ID ATHYMIC NUDE MICE; NEOPLASTIC TRANSFORMATION; SQUAMOUS DIFFERENTIATION; SV40-TRANSFORMED HUMAN; CHAIN-REACTION; HUMAN-LUNG; SHORT ARM; HUMAN DNA; CARCINOMA; CHROMOSOME-3 AB Of five SV40-transformed clonal human bronchial epithelial cell lines previously shown to be nontumorigenic at early passages (R. R. Reddel et al., Cancer Res., 48:1904-1909,1988), two lines (BES-1A1 and BEAS-2B) from different donors have become weakly tumorigenic with further passaging. BES-1A1 passage 26 cells formed tumors in 3 of 9 athymic nude mice given s.c. injections, whereas BEAS-2B cells of greater-than-or-equal-to 32 passages formed highly cystic tumors at 8 of 58 injection sites after long latency periods [17 +/- 7 (SD) weeks]. These tumors took a total of 36 +/- 8 weeks to reach a diameter of 1.0 cm. Tumor cell lines were established from four BEAS-2B tumors, and these are resistant to the growth-inhibitory effects of serum, an inducer of squamous differentiation in BEAS-2B and normal bronchial epithelial cells. This finding supports the hypothesis that development of resistance to inducers of terminal squamous differentiation may be a step in the process of bronchial carcinogenesis. One of these tumor cell lines, B39-TL, is significantly more tumorigenic than the others and has a deletion from the short arm of chromosome 3 as has been described previously for some naturally occurring human bronchial carcinomas. Thus, from the clonally derived BEAS-2B cell line, cell populations with various degrees of tumorigenicity have developed. Analysis of the changes in these cells may yield insights into the multiple events involved in acquisition of the tumorigenic phenotype. C1 CHILDRENS MED RES INST,WESTMEAD,NSW 2145,AUSTRALIA. NCI,HUMAN CARCINOGENESIS LAB,BETHESDA,MD 20892. HUNTINGTON MED RES INST,PASADENA,CA 91101. RI Reddel, Roger/A-6635-2014 OI Reddel, Roger/0000-0002-6302-6107 NR 45 TC 48 Z9 51 U1 1 U2 4 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 1993 VL 53 IS 5 BP 985 EP 991 PG 7 WC Oncology SC Oncology GA KN706 UT WOS:A1993KN70600009 PM 8094998 ER PT J AU YATSUNAMI, J KOMORI, A OHTA, T SUGANUMA, M YUSPA, SH FUJIKI, H AF YATSUNAMI, J KOMORI, A OHTA, T SUGANUMA, M YUSPA, SH FUJIKI, H TI HYPERPHOSPHORYLATION OF CYTOKERATINS BY OKADAIC ACID CLASS TUMOR PROMOTERS IN PRIMARY HUMAN KERATINOCYTES SO CANCER RESEARCH LA English DT Article ID GENE-EXPRESSION; PROTEIN PHOSPHATASES; CALYCULIN-A; PHOSPHORYLATION; INHIBITOR; VIMENTIN; CELLS AB Okadaic acid, dinophysistoxin-1 (35-methylokadaic acid), and calyculin A are potent tumor promoters on mouse skin (H. Fujiki, M. Suganuma, S. Nishiwaki, S. Yoshizawa, J. Yatsunami, R. Matsushima, H. Furuya, S. Okabe, S. Matsunaga, and T. Sugimura. In: R. D'Amato, T. J. Slaga, W. Farland, and C. Henry (eds.), Relevance of Animal Studies to the Evaluation of Human Cancer Risk, pp. 337-350. New York: John Wiley and Sons, Inc., 1992). These tumor promoters, which are also inhibitors of protein phosphatases 1 and 2A, induced hyperphosphorylation of M(r) 60,000, M(r) 58,000, M(r) 56,000, M(r) 52,000, M(r) 42,000, and M(r) 27,000 proteins in PHK 16-I cells, human keratinocytes immortalized by human papillomavirus type 16. Except for the M(r) 27,000 protein, these hyperphosphorylated proteins were identified to be cytokeratin peptides (CK) CK 5, CK 6, CK 7, CK 16, and CK 19,by anti-cytokeratin antibodies. CK 5 and CK 6 were more strongly phosphorylated than CK 16 and CK 19. The in vitro hyperphosphorylation of these cytokeratins was also found by incubation with an enzyme fraction containing a mixture of protein phosphatase 2A and protein kinases isolated from mouse brain and various concentrations of dinophysistoxin-1. Indirect immunofluorescence microscopy with anti-cytokeratin antibodies revealed that the hyperphosphorylated cytokeratins had retracted to the perinuclear area. The hyperphosphorylated M(r) 27,000 protein was identified as a heat shock protein, HSP27. Hyperphosphorylation of HSP27 and intermediate filaments, such as cytokeratins, is one of the early biochemical changes, or pleiotropic effects, in cells induced by the okadaic acid class of tumor promoters. C1 NATL CANC CTR,RES INST,DIV CANC PREVENT,TOKYO 104,JAPAN. NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BETHESDA,MD 20892. NR 28 TC 31 Z9 31 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 1993 VL 53 IS 5 BP 992 EP 996 PG 5 WC Oncology SC Oncology GA KN706 UT WOS:A1993KN70600010 PM 7679949 ER PT J AU BLANEY, SM BALIS, FM COLE, DE CRAIG, C REID, JM AMES, MM KRAILO, M REAMAN, G HAMMOND, D POPLACK, DG AF BLANEY, SM BALIS, FM COLE, DE CRAIG, C REID, JM AMES, MM KRAILO, M REAMAN, G HAMMOND, D POPLACK, DG TI PEDIATRIC PHASE-I TRIAL AND PHARMACOKINETIC STUDY OF TOPOTECAN ADMINISTERED AS A 24-HOUR CONTINUOUS INFUSION SO CANCER RESEARCH LA English DT Article ID LINKED DNA BREAKS; CAMPTOTHECIN NSC-100880; TOPOISOMERASE-I AB Topotecan, a water-soluble semisynthetic analogue of camptothecin, is the first topoisomerase I inhibitor to undergo evaluation in pediatric patients with refractory malignancies. A phase I and pharmacokinetic study was performed to determine the maximum tolerated dose (MTD) and dose-limiting toxicities, the incidence and severity of other toxicities, and the pharmacokinetics of topotecan in children. Twenty-nine patients received 42-courses of i.v. topotecan administered as a 24-h continuous infusion every 21 days at doses ranging from 2.0 to 7.5 mg/m2. Dose-related hematological toxicity was the dose-limiting toxicity. Leukopenia, neutropenia, and thrombocytopenia occurred sporadically at the 3.0- to 5.5-mg/m2 dose levels, but at 7.5 mg/m2 4 of 5 patients experienced dose-limiting thrombocytopenia (grade 4) and 2 of 5 had dose-limiting neutropenia (grade 4). No other dose-limiting toxicities were observed. Nausea and vomiting were mild and occurred in <20 and 10% of patients, respectively. Grade 2 hematuria occurred in one patient. No objective responses were observed. Pharmacokinetic studies revealed a linear relationship between the steady-state topotecan concentration and dose. The mean steady-state concentration at the MTD was 18.2 +/- 3.7 nmol/liter and the total body clearance was 28.3 +/- 6.5 liters/h/m2. Elimination was biexponential with a t1/2alpha of 14.4 +/- 1.8 min and a t1/2beta of 2.9 +/- 1.1 h. The recommended starting dose for phase 11 pediatric trials is 5.5 mg/m2. Although this dose exceeds the MTD identified in heavily pretreated adult patients receiving topotecan on the same schedule, it is less than the MTD for minimally pretreated adult patients. Therefore, dose escalation to 7.5 mg/m2 in phase II pediatric trials should be considered for patients who tolerate treatment well at the 5.5-mg/m2 dose. C1 WALTER REED ARMY MED CTR,WASHINGTON,DC 20307. CHILDRENS STUDY CANC GRP,ARCADIA,CA 91006. RP BLANEY, SM (reprint author), NCI,PEDIAT BRANCH,BLDG 10,ROOM 13N240,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. FU NCI NIH HHS [CA13539] NR 24 TC 97 Z9 97 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 1993 VL 53 IS 5 BP 1032 EP 1036 PG 5 WC Oncology SC Oncology GA KN706 UT WOS:A1993KN70600017 PM 8439950 ER PT J AU TSAI, CM HSIAO, SH FREY, CM CHANG, KT PERNG, RP GAZDAR, AF KRAMER, BS AF TSAI, CM HSIAO, SH FREY, CM CHANG, KT PERNG, RP GAZDAR, AF KRAMER, BS TI COMBINATION CYTOTOXIC EFFECTS OF CIS-DIAMMINEDICHLOROPLATINUM(II) AND 5-FLUOROURACIL WITH AND WITHOUT LEUCOVORIN AGAINST HUMAN NON-SMALL-CELL LUNG-CANCER CELL-LINES SO CANCER RESEARCH LA English DT Article ID METASTATIC COLORECTAL-CARCINOMA; HIGH-DOSE LEUCOVORIN; AMINO-ACID-TRANSPORT; PHASE-III TRIAL; CONTINUOUS INFUSION; NECK-CANCER; ADVANCED HEAD; CISPLATIN; CHEMOTHERAPY; FLUOROURACIL AB Both cisplatin (CDDP) and leucovorin (LV) have been shown to enhance cytotoxicity of 5-fluorouracil (FUra) against murine and human neoplasms by increasing intracellular reduced folate concentrations. We were interest ed in their use in a combination to inhibit non-small cell lung cancer (NSCLC) cell growth and therefore conducted an in vitro study to investigate the cytotoxic activities of combinations of CDDP plus FUra, with and without LV (20 muM), against seven NSCLC cell lines. A tetrazolium assay with application of the classical isobole method was used to test drug combinations. We found that LV enhanced FUra but not CDDP cytotoxicity and that the degree of enhancement was negatively correlated with the effect of FUra. There was an overall additive combination effect of CDDP plus FUra, although there may be synergy at higher effect levels. There was synergy to a combination of CDDP, FUra, and LV, presumably primarily related to the synergistic effects of adding LV to FUra. In summary, LV and CDDP enhanced FUra cytotoxicity in a complementary fashion and there was clear synergy of a combination of CDDP, FUra, and LV against a panel of NSCLC cell lines. Our in vitro results provide a rationale for controlled clinical studies of this three-drug regimen in patients with NSCLC. C1 NCI,SURVEILLANCE PROGRAM,BETHESDA,MD 20892. NCI,EARLY DETECT & COMMUNITY ONCOL PROGRAM,BETHESDA,MD 20892. UNIV TEXAS,SW MED CTR,SIMMONS CANC CTR,DALLAS,TX 75235. RP TSAI, CM (reprint author), VET GEN HOSP,DEPT CHEST,TAIPEI,TAIWAN. NR 36 TC 29 Z9 36 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAR 1 PY 1993 VL 53 IS 5 BP 1079 EP 1084 PG 6 WC Oncology SC Oncology GA KN706 UT WOS:A1993KN70600024 PM 8382553 ER PT J AU NOBORI, T SZINAI, I AMOX, D PARKER, B OLOPADE, OI BUCHHAGEN, DL CARSON, DA AF NOBORI, T SZINAI, I AMOX, D PARKER, B OLOPADE, OI BUCHHAGEN, DL CARSON, DA TI METHYLTHIOADENOSINE PHOSPHORYLASE-DEFICIENCY IN HUMAN NONSMALL CELL LUNG CANCERS SO CANCER RESEARCH LA English DT Article ID L-METHIONINE; 5,10-DIDEAZATETRAHYDROFOLIC ACID; MAMMALIAN-CELLS; CULTURE; METABOLISM; 5'-METHYLTHIOADENOSINE; DEPRIVATION; GROWTH; LINES; TUMOR AB Methylthioadenosine (MeSAdo) phosphorylase, a purine metabolic enzyme, is present in all normal mammalian tissues. A deficiency of this enzyme has been reported in some human leukemias and lymphomas and in a few solid tumors. In the present study, a specific immunoassay was used to assess the enzyme levels in human non-small cell lung cancer cell lines and primary tumors. We also tested the effects of MeSAdo phosphorylase-selective chemotherapy on the in vitro growth of enzyme-positive and enzyme-negative lung cancer cell lines. Of 29 non-small cell lung cancers, 9 (6 cell lines and 3 primary tumors, 31%) lacked detectable immunoreactive enzyme protein. Both 5,10-dideazatetrahydrofolate, an inhibitor of de novo purine synthesis, and methionine depletion, combined with MeSAdo, prevented the growth of the enzyme-negative non-small cell lung cancer cells under conditions in which enzyme-positive cells utilized MeSAdo to endogenously synthesize purine nucleotides and methionine. Our data suggest that MeSAdo phosphorylase deficiency is frequently found in non-small cell lung cancers and can be exploited in designing enzyme-selective chemotherapy. C1 UNIV CALIF SAN DIEGO,SAM & ROSE STEIN INST RES AGING,LA JOLLA,CA 92093. UNIV CALIF SAN DIEGO,CTR CANC,LA JOLLA,CA 92093. UNIV CHICAGO,DEPT MED,HEMATOL ONCOL SECT,CHICAGO,IL 60637. USN,NCI,ONCOL BRANCH,BETHESDA,MD 20814. RP NOBORI, T (reprint author), UNIV CALIF SAN DIEGO,DEPT MED,LA JOLLA,CA 92093, USA. FU NCI NIH HHS [P30 CA23100]; NIAID NIH HHS [AI24466]; NIGMS NIH HHS [GM23200] NR 31 TC 45 Z9 46 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 1993 VL 53 IS 5 BP 1098 EP 1101 PG 4 WC Oncology SC Oncology GA KN706 UT WOS:A1993KN70600027 PM 8382555 ER PT J AU DATTA, AK SHI, XL KASPRZAK, KS AF DATTA, AK SHI, XL KASPRZAK, KS TI EFFECT OF CARNOSINE HOMOCARNOSINE AND ANSERINE ON HYDROXYLATION OF THE GUANINE MOIETY IN 2'-DEOXYGUANOSINE, DNA AND NUCLEOHISTONE WITH HYDROGEN-PEROXIDE IN THE PRESENCE OF NICKEL(II) SO CARCINOGENESIS LA English DT Article ID ASCITES TUMOR-CELLS; LIPID-PEROXIDATION; DAMAGE; MUTAGENESIS; MUSCLE; BASES; SITE AB The oxidation of 2'-deoxyguanosine (dG) to 8-hydroxy-2'-deoxyguanosine (8-OH-dG) in free dG and the dG residues of DNA and nucleohistone with H2O2 in the presence of Ni(II) and histidyl oligopeptides, carnosine, homocarnosine and anserine was studied at physiological pH. The oxidation of free dG with H2O2 was enhanced by the oligopeptides, but not by Ni(II) alone. Much greater enhancement was produced by equimolar mixtures of Ni(II) with any of the oligopeptides or with L-histidine. In contrast, the oxidation of dG residues in DNA and nucleohistone with H2O2 was not affected by the oligopeptides, but was enhanced by Ni(II). The latter enhancement remained practically unchanged when Ni(II) was accompanied by equimolar amounts of homocarnosine or anserine, whereas carnosine tended to attenuate that enhancement. The extent of formation of 8-OH-dG in free dG depended on time and concentration of H2O2 and was highest at pH 7.4. An electron spin resonance study of the reaction mixture containing H2O2, Ni(II), carnosine, homocarnosine and/or anserine provided evidence for the generation of .OH radical in the reaction media. Although it has previously been concluded that carnosine, anserine and homocarnosine might serve as anti-oxidants, the present study does not support that conclusion and shows that these compounds may even act as pro-oxidants, especially when they are complexed with Ni(II). The results suggest that carnosine, homocarnosine and anserine, by enhancing oxidation of the free dG pool, may potentiate the carcinogenic effects of Ni(II) since the resulting 8-OH-dG can be misincorporated into DNA and thus produce a mutagenic lesion. C1 NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21702. RI Shi, Xianglin/B-8588-2012 NR 32 TC 24 Z9 24 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD MAR PY 1993 VL 14 IS 3 BP 417 EP 422 DI 10.1093/carcin/14.3.417 PG 6 WC Oncology SC Oncology GA KT301 UT WOS:A1993KT30100013 PM 8384089 ER PT J AU DE LUCA, LM SLY, L JONES, CS CHEN, LC AF DE LUCA, LM SLY, L JONES, CS CHEN, LC TI EFFECTS OF DIETARY RETINOIC ACID ON SKIN PAPILLOMA AND CARCINOMA FORMATION IN FEMALE SENCAR MICE SO CARCINOGENESIS LA English DT Note ID SQUAMOUS-CELL CARCINOMA; MOUSE SKIN; TUMOR PROMOTION; 13-CIS-RETINOIC ACID; INHIBITION; ISOTRETINOIN; CONVERSION; PREVENTION; INITIATION; INDUCTION AB Previously we have shown that dietary retinoids are essential for papilloma formation induced by either an initiation-promotion or a complete skin carcinogenesis protocol. The present study was conducted to further determine the effect of dietary retinoic acid (RA) on papilloma formation and the conversion of papillomas to carcinomas. Skin tumors were induced in 3 week old female SENCAR mice by an initiation-promotion protocol with one application of 20 mug of 7,12-dimethylbenz[a]anthracene (DMBA), followed by 20 weekly applications of 2 mug of 12-O-tetradecanoylphorbol-13-acetate (TPA). Mice were fed RA at one of the three doses: 0.3 (nutritionally marginal dose), 3 (near physiological) and 30 (pharmacological) mug/g of diet. Mice fed 30 mug of RA/g of diet had the same survival rate as the other two groups despite a lower body weight and all three groups had similar papilloma incidence, which reached 100% at age 18 weeks. Mice fed 3 mug of RA/g of diet had the highest papilloma yield (approximately 14 papillomas/mouse) of all groups and ft peaked between weeks 18 and 38 of age. These papillomas later regressed such that mice from all three groups had about the same papilloma yield at week 44 of age. Mice fed 30 mug of RA/g of diet failed to develop any visible carcinoma, while mice fed 0.3 or 3 mug/g showed 1.9% conversion of papillomas to carcinomas. Therefore, dietary RA at 30 mug/g of diet inhibited the conversion of papillomas to carcinomas without affecting papilloma incidence. In addition, dietary RA at 30 and 0.3 mug/g of diet lowered papilloma yield. C1 BIOCON, ROCKVILLE, MD USA. RP DE LUCA, LM (reprint author), NCI, CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB, BETHESDA, MD 20892 USA. NR 42 TC 27 Z9 27 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD MAR PY 1993 VL 14 IS 3 BP 539 EP 542 DI 10.1093/carcin/14.3.539 PG 4 WC Oncology SC Oncology GA KT301 UT WOS:A1993KT30100032 PM 8453733 ER PT J AU GRAHAM, GJ ZHOU, L WEATHERBEE, JA TSANG, MLS NAPOLITANO, M LEONARD, WJ PRAGNELL, IB AF GRAHAM, GJ ZHOU, L WEATHERBEE, JA TSANG, MLS NAPOLITANO, M LEONARD, WJ PRAGNELL, IB TI CHARACTERIZATION OF A RECEPTOR FOR MACROPHAGE INFLAMMATORY PROTEIN-1-ALPHA AND RELATED PROTEINS ON HUMAN AND MURINE CELLS SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID HUMAN INTERLEUKIN-8 RECEPTOR; 3-DIMENSIONAL STRUCTURE; SURFACE RECEPTORS; PLATELET FACTOR-4; STEM-CELLS; IDENTIFICATION; MONOCYTES; CYTOKINE; INVITRO; BINDING AB Macrophage inflammatory protein 1alpha (MIP-1alpha) is a potent stem cell inhibitor and a member of a large and expanding family of related cytokines. In an effort to understand the molecular basis of the activities of MIP-1alpha, we have sought to characterize the cellular receptors for this molecule. Our results demonstrate the presence of abundant MIP-1alpha receptors on both human and murine cells. The receptor on K562 cells can bind a range of members of the MIP-1alpha family and may thus be a general MIP-1alpha family receptor. Murine FDCPmix cells also bind a range of members of this peptide family, although the receptor(s) that they express appear somewhat more selective for peptides capable of displaying stem cell inhibitory properties. The human and murine receptors do not bind members of the related interleukin 8 family of peptides and are thus distinct from the recently cloned interleukin 8 receptor. We suggest that the receptor on the murine cell is a candidate for the receptor responsible for articulating stem cell inhibitory signals following MIP-1alpha binding. C1 IST SAN RAFFAELE, I-20132 MILAN, ITALY. NHLBI, PULM & MOLEC IMMUNOL SECT, BETHESDA, MD 20892 USA. R&D SYST INC, MINNEAPOLIS, MN 55413 USA. RP GRAHAM, GJ (reprint author), BEATSON INST CANC RES, CANC RES CAMPAIGN, BEATSON LABS, GARSCUBE ESTATE, SWITCHBACK RD, GLASGOW G61 1BD, SCOTLAND. RI Graham, Gerard/D-1240-2009 NR 35 TC 38 Z9 38 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1044-9523 J9 CELL GROWTH DIFFER JI Cell Growth Differ. PD MAR PY 1993 VL 4 IS 3 BP 137 EP 146 PG 10 WC Cell Biology SC Cell Biology GA KT858 UT WOS:A1993KT85800001 PM 8385474 ER PT J AU ETO, K SUZUKI, S SINGH, VK SHINOHARA, T AF ETO, K SUZUKI, S SINGH, VK SHINOHARA, T TI IMMUNIZATION WITH RECOMBINANT ESCHERICHIA-COLI EXPRESSING RETINAL S-ANTIGEN-INDUCED EXPERIMENTAL AUTOIMMUNE UVEITIS (EAU) IN LEWIS RATS SO CELLULAR IMMUNOLOGY LA English DT Article ID MYELIN BASIC-PROTEIN; LYMPHOCYTE CROSS-REACTION; T-CELL RECEPTOR; MOLECULAR MIMICRY; UVEITOPATHOGENIC SITE; ADOPTIVE TRANSFER; BOVINE RETINA; ENCEPHALOMYELITIS; UVEORETINITIS; DISEASE C1 NEI,RETINAL CELL & MOLEC BIOL LAB,MOLEC BIOL SECT,BLDG 6,ROOM 327,BETHESDA,MD 20892. OI Shinohara, Toshimichi/0000-0002-7197-9039 NR 53 TC 6 Z9 6 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD MAR PY 1993 VL 147 IS 1 BP 203 EP 214 DI 10.1006/cimm.1993.1060 PG 12 WC Cell Biology; Immunology SC Cell Biology; Immunology GA KT854 UT WOS:A1993KT85400018 PM 8462112 ER PT J AU HERMOUET, S DEMAZANCOURT, P SPIEGEL, AM AF HERMOUET, S DEMAZANCOURT, P SPIEGEL, AM TI MITOGENIC EFFECTS OF PERTUSSIS TOXIN-SENSITIVE G-PROTEIN ALPHA-SUBUNITS - THE MITOGENIC ACTION OF ALPHA-I2 IN NIH 3T3 CELLS IS MIMICKED BY ALPHA-I1, BUT NOT ALPHA-I3 SO CELLULAR SIGNALLING LA English DT Article DE FIBROBLASTS; PROLIFERATION; PTX-SENSITIVE G-PROTEINS ID GTP-BINDING-PROTEIN; ADENYLYL CYCLASE; SIGNAL TRANSDUCTION; MESSENGER-RNA; EXPRESSION; GI2; INHIBITION; GROWTH; IDENTIFICATION; PROLIFERATION AB In fibroblasts and other cell types, pertussis toxin (PTX) inhibits DNA synthesis in response to serum and certain growth factors. GTPase deficient forms of the PTX-sensitive G-protein alpha(i2) subunit have been shown to induce partial transformation in fibroblasts. In order to determine whether other PTX-sensitive G-proteins can stimulate mitogenic pathways, we stably expressed constitutively activated G-protein alpha(i1), and alpha(i3) subunits in NIH 3T3 cells. Expression of activated alpha(i1), alpha(i2) or alpha(i3) results in inhibition of forskolin-stimulated cAMP accumulation in intact cells. Constitutively activated alpha(i1), but not alpha(i3), induces a loss of contact inhibition, a loss of anchorage-dependence, a reduced serum requirement and a decreased doubling time in NIH 3T3 cells. We conclude that alpha(i1) and alpha(i2) are both capable of transducing mitogenic signals, but that alpha(i3) is not involved in the regulation of fibroblast growth. Furthermore, adenylyl cyclase inhibition is clearly not sufficient to explain the effect of alpha(i2) on fibroblast growth. RP HERMOUET, S (reprint author), NIDDKD,MOLEC PATHOPHYSIOL BRANCH,BLDG 10,ROOM 8C101,BETHESDA,MD 20892, USA. NR 56 TC 22 Z9 22 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0898-6568 J9 CELL SIGNAL JI Cell. Signal. PD MAR PY 1993 VL 5 IS 2 BP 215 EP 225 DI 10.1016/0898-6568(93)90072-T PG 11 WC Cell Biology SC Cell Biology GA KV156 UT WOS:A1993KV15600011 PM 8388703 ER PT J AU PUMFORD, NR MYERS, TG DAVILA, JC HIGHET, RJ POHL, LR AF PUMFORD, NR MYERS, TG DAVILA, JC HIGHET, RJ POHL, LR TI IMMUNOCHEMICAL DETECTION OF LIVER PROTEIN ADDUCTS OF THE NONSTEROIDAL ANTIINFLAMMATORY DRUG DICLOFENAC SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Note ID SODIUM VOLTAREN; HEPATITIS; HEPATOTOXICITY; METABOLITES; ANTIBODIES; BIOTRANSFORMATION; CONJUGATION; ACYLATION; HALOTHANE; ANIMALS AB Serious idiosyncratic hepatic injury has been associated with the use of many nonsteroidal antiinflammatory drugs, including the widely prescribed agent diclofenac. In order to investigate the possibility that covalent protein adducts of reactive metabolites of diclofenac might be responsible for the hepatotoxicity produced by this drug, we have developed a polyclonal antibody that can recognize such adducts in tissues. Immunoblotting revealed that protein adducts of reactive metabolites of diclofenac of 50, 70, 110, and 140 kDa were formed in the livers of mice treated with diclofenac. In the future, it will be determined whether these adducts can cause hepatotoxicity by either a hypersensitivity or metabolic mechanism. Similar approaches may be used to study the protein adducts and mechanisms of hepatotoxicity of other nonsteroidal antiinflammatory drugs. C1 NHLBI,CHEM PHARMACOL LAB,BLDG 10,ROOM 8N 115,BETHESDA,MD 20892. NHLBI,BIOPHYS CHEM LAB,BETHESDA,MD 20892. NR 29 TC 87 Z9 88 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD MAR-APR PY 1993 VL 6 IS 2 BP 147 EP 150 DI 10.1021/tx00032a002 PG 4 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA KT721 UT WOS:A1993KT72100002 PM 8477004 ER PT J AU NIMS, RW SYI, JL WINK, DA NELSON, VC THOMAS, PE JONES, CR DIWAN, BA KEEFER, LK RICE, JM LUBET, RA AF NIMS, RW SYI, JL WINK, DA NELSON, VC THOMAS, PE JONES, CR DIWAN, BA KEEFER, LK RICE, JM LUBET, RA TI HEPATIC CYTOCHROME-P450 2B-TYPE INDUCTION BY ETHYL PHENYL-SUBSTITUTED CONGENERS OF PHENOBARBITAL IN THE RAT SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID LIVER MICROSOMAL CYTOCHROME-P-450; EPOXIDE HYDROLASE; TESTOSTERONE HYDROXYLATION; POLYCHLORINATED-BIPHENYLS; N-NITROSODIETHYLAMINE; FLUOROMETRIC ASSAY; ENZYME-INDUCTION; INDUCERS; SERIES; DEALKYLATION AB As part of an investigation of the structural requirements for the induction, by phenobarbital-type inducers, of a coordinate pleiotropic response consisting of increases in hepatic cytochrome P450 2B (P450 2B) activity, increases in other phase I and II enzyme activities, and liver hypertrophy, we have examined a series of analogues of phenobarbital in which the ethyl/phenyl substitution at the sp3 carbon of the parent molecule was kept constant while the heterocyclic portion of the molecule was modified. The induction of hepatic P450 2B protein and ethoxy-, pentoxy-, and (benzyloxy)resorufin O-dealkylation activities, and epoxide hydration activity and liver/body weight ratio increase were examined in male F344/NCr rats fed the various congeners for 14 days at doses equimolar to 500 ppm phenobarbital. Increases in the measured parameters were maximal in rats fed phenobarbital or 5-ethyl-5-phenylhydantoin. The responses to primidone or 2-ethyl-2-phenylsuccinimide were approximately 65% of maximal, while glutethimide yielded a response approximately 50% of maximal. Induction of this response in rats fed the ring-opened and decarboxylated analogues, (ethylphenylacetyl)urea and 2-ethyl-2-phenylmalonamide, were <25% of maximal. 5-Ethyl-5-phenyloxazolidinedione caused minimal increases in the measured end points when administered at a dose equimolar to 500 ppm phenobarbital. The profound differences among the congeners in ability to induce P450 2B protein and associated catalytic activities were not due to differences in food consumption by the various groups of rats. Rather, structural differences (presence or absence of hydrogen bond donors or acceptors) and those physicochemical properties (lipophilicity and acid-base dissociation constant) of the compounds which govern the rates and extents of systemic absorption and ionization in biological fluids would appear to play major roles in the ability of the various compounds to induce this activity. C1 NCI,PRI DYNCORP,FREDERICK CANC RES & DEV CTR,ADV SCI COMP LAB,CHEM SYNTH & ANAL LAB,FREDERICK,MD 21702. NCI,PRI DYNCORP,FREDERICK CANC RES & DEV CTR,BIOL CARCINOGEN & DEV PROGRAM,FREDERICK,MD 21702. RUTGERS STATE UNIV,COLL PHARM,DEPT CHEM BIOL,PISCATAWAY,NJ 08855. RP NIMS, RW (reprint author), NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,BLDG 538,ROOM 205E,FREDERICK,MD 21702, USA. RI Keefer, Larry/N-3247-2014 OI Keefer, Larry/0000-0001-7489-9555 FU NCI NIH HHS [N01-CO-74102] NR 69 TC 15 Z9 15 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD MAR-APR PY 1993 VL 6 IS 2 BP 180 EP 187 DI 10.1021/tx00032a007 PG 8 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA KT721 UT WOS:A1993KT72100007 PM 8477009 ER PT J AU NIMS, RW SINCLAIR, PR SINCLAIR, JF THOMAS, PE JONES, CR MELLINI, DW SYI, JL LUBET, RA AF NIMS, RW SINCLAIR, PR SINCLAIR, JF THOMAS, PE JONES, CR MELLINI, DW SYI, JL LUBET, RA TI PHARMACODYNAMICS OF CYTOCHROME-P450-2B INDUCTION BY PHENOBARBITAL, 5-ETHYL-5-PHENYLHYDANTOIN, AND 5-ETHYL-5-PHENYLOXAZOLIDINEDIONE IN THE MALE-RAT LIVER OR IN CULTURED RAT HEPATOCYTES SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID HEPATIC MICROSOMAL-ENZYMES; MONO-OXYGENASE ACTIVITY; TESTOSTERONE HYDROXYLATION; GENE-EXPRESSION; INDUCTION; ISOZYMES; SERIES; CYTOCHROMES-P-450; RESPONSIVENESS; DEALKYLATION AB The pharmacodynamics of rat hepatic cytochrome P450 2B (P450 2B) induction by phenobarbital (PB) and two structural congeners, dl-5-ethyl-5-phenylhydantoin (EPH) and dl-5-ethyl-5-phenyloxazolidinedione (EPO), were investigated. The in vivo induction of P450 2B was probed in F344/NCr rats by measuring immunoreactive hepatic P450 2B1 protein and by assaying the hepatic 16beta-hydroxylation of testosterone and O-dealkylation of (benzyloxy)-and pentoxyresorufin. The induction of (benzyloxy)resorufin O-dealkylation activity was also measured in adult rat hepatocyte cultures exposed to the three xenobiotics. The concentration of xenobiotic at the putative active site in the in vivo studies was approximated by measuring serum total xenobiotic levels, while in the hepatocyte culture studies, the nominal xenobiotic concentration in the culture medium was used. Concentration-dependent induction of P450 2B activities was observed in the in vivo and hepatocyte culture studies. The in vivo ED50 values for P450 2B induction were approximately 110, approximately 100, and approximately 3000 dietary ppm (14 days administration) for PB, EPH, and EPO, respectively. The in vivo EC50 values for P450 2B induction were approximately 9, approximately 6, and approximately 130 muM (total serum) for PB, EPH, and EPO, respectively. In cultured rat hepatocytes, the ED50 values for induction of (benzyloxy)resorufin O-dealkylation activity were 14.5, 14.2, and 108 muM for PB, EPH, and EPO, respectively. These data indicate that pharmacodynamic results obtained with cultured hepatocytes represent a good qualitative and quantitative approximation of the in vivo hepatic responses in male rats caused by PB-type inducers. In both systems, EPH and PB were approximately equivalent in potency for P450 2B induction, while EPO was roughly an order of magnitude less potent. C1 VET ADM MED CTR,WHITE RIVER JCT,VT 05009. RUTGERS STATE UNIV,COLL PHARM,DEPT CHEM BIOL,PISCATAWAY,NJ 08855. NCI,PROGRAM RESOURCES INC DYNCORP,FREDERICK CANC RES & DEV CTR,BIOL CARCINOGENSIS & DEV PROGRAM,FREDERICK,MD 21702. NCI,PROGRAM RESOURCES INC DYNCORP,FREDERICK CANC RES & DEV CTR,ADV SCI COMP LAB,FREDERICK,MD 21702. RP NIMS, RW (reprint author), NCI,FREDERICK CANC RES & DEV CTR,CHEM SECT,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21702, USA. FU NCI NIH HHS [N01-CO-74102] NR 40 TC 14 Z9 14 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD MAR-APR PY 1993 VL 6 IS 2 BP 188 EP 196 DI 10.1021/tx00032a008 PG 9 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA KT721 UT WOS:A1993KT72100008 PM 8477010 ER PT J AU FISHER, MB HAYDEN, PJ BRUSCHI, SA DULIK, DM YANG, Y WARD, AJI STEVENS, JL AF FISHER, MB HAYDEN, PJ BRUSCHI, SA DULIK, DM YANG, Y WARD, AJI STEVENS, JL TI FORMATION, CHARACTERIZATION, AND IMMUNOREACTIVITY OF LYSINE THIOAMIDE ADDUCTS FROM FLUORINATED NEPHROTOXIC CYSTEINE CONJUGATES INVITRO AND INVIVO SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID BETA-LYASE; MERCAPTURIC ACID; S-CONJUGATE; TOXICITY; RAT; GLUTATHIONE; MECHANISM; METABOLISM; HALOTHANE; S-(1,2-DICHLOROVINYL)-L-CYSTEINE AB Fluorinated nephrotoxic cysteine conjugates undergo bioactivation via the beta-lyase pathway to thionoacetyl fluorides (TAF), the putative reactive intermediates. The TAF derived from S-(1,1,2,2-tetrafluoroethyl)-L-cysteine (TFEC) difluorothionoacetylates amine nucleophiles found in proteins and lipids. A specific antisera, raised against (trifluoroacetamido)lysine adducts formed in vivo after halothane treatment, has previously been used to localize TFEC-derived protein adducts immunohistochemically, and a good correlation between adduction and toxicity was demonstrated. Interestingly, thioamide formation is facilitated by acyl-transfer catalysts such as imidazoles and phenols. However, although putative lysine adducts have been reported to be formed from the related TAF derived from S-(2-chloro-1,1,2-trifluoroethyl)-L-cysteine (CTFC), protein adducts derived from CTFC metabolism have not been completely characterized. In the present investigation we characterize (chlorofluorothionoacetamido)lysine (CFTAL) adduct formation during S-(2-chloro-1,1,2-trifluoroethyl)-L-cysteine (CTFC) metabolism, both in vitro and in vivo. Our data indicate that formation of CTFC-derived lysine thioamides was not as dependent on nucleophilic catalysis as observed for TFEC, and this appears to be due to an apparent greater reactivity of the TAF resulting in a higher trapping efficiency in the absence of catalyst. Also, qualitative and quantitative differences in the structures and time course of CTFC versus TFEC adduct breakdown were observed. Antibodies raised against the halothane metabolite protein adduct (trifluoroacetamido)lysine cross-react with specific mitochondrial proteins from the kidneys of TFEC-treated rats. Using this antibody, we have found that the pattern of adducted proteins from TFEC- and CTFC-treated Fischer rats was similar, but the intensity was considerably lower after treatment with equimolar concentrations of CTFC in vivo. C1 W ALTON JONES CELL SCI CTR,OLD BARN RD,LAKE PLACID,NY 12946. CLARKSON UNIV,DEPT CHEM,POTSDAM,NY 13699. SMITHKLINE BEECHAM PHARMACEUT,DRUG METAB & PHARMACOKINET,KING OF PRUSSIA,PA 19406. NIEHS,MOLEC BIOPHYS LAB,RES TRIANGLE PK,NC 27709. FU NIDDK NIH HHS [DK38925] NR 37 TC 12 Z9 13 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD MAR-APR PY 1993 VL 6 IS 2 BP 223 EP 230 DI 10.1021/tx00032a012 PG 8 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA KT721 UT WOS:A1993KT72100012 PM 8477013 ER PT J AU HAYDEN, PJ CHIGNELL, CF AF HAYDEN, PJ CHIGNELL, CF TI DETECTION AND CHARACTERIZATION OF 9-ANTHRON-10-YL RADICALS FORMED BY ANTIPSORIATIC AND TUMOR-PROMOTING 9-ANTHRONES IN AQUEOUS BUFFERS SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID ORNITHINE DECARBOXYLASE INDUCTION; ANTHRALIN-DERIVED TRANSIENTS; DITHRANOL ANTHRALIN; 10-ACYL ANALOGS; MODEL SYSTEMS; SENCAR MICE; SKIN; OXYGEN; 1,8-DIHYDROXY-9-ANTHRONE; KERATINOCYTES AB Certain 1,8-dihydroxy-9-anthrones have been used for the topical treatment of psoriasis for over seventy-five years. The therapeutic usefulness of these compounds is limited, however, by side effects including severe skin inflammation and staining. Antipsoriatic 9-anthrones are also tumor promoters in mouse skin. The chemical mechanisms underlying the biological properties of 9-anthrones are believed to involve the generation of free radical products such as 9-anthron-10-yl radicals or secondary oxygen radicals such as O2.- or OH.. However, the specific role that 9-anthron-10-yl radicals may play in mediating the biological effects of 9-anthrones is uncertain because these species have not been detected in biological systems. In the present study we have used the EPR spin trapping technique to demonstrate for the first time the formation of the 1,8-dihydroxy-9-anthron-10-yl radical in aqueous buffers. Additionally, in order to gain information concerning the role of 9-anthron-10-yl radicals in tumor promotion and antipsoriatic activities, we have used this technique to investigate the formation of these radical species by a series of 9-anthrones of known tumor-promoting and antipsoriatic activities. All of the 9-anthrones studied formed spin adducts with 3,5-dibromo-4-nitrosobenzenesulfonic acid in aqueous buffers. The formation of these adducts was pH-dependent, being favored at alkaline pH. The results demonstrate that the ability to form 9-anthron-10-yl radicals in aqueous buffers is a common, but not exclusive, property of tumor-promoting and antipsoriatic anthrones and suggest that other factors may also be important for producing the biological effects of these compounds. C1 NIEHS,MOLEC BIOPHYS LAB,POB 12233,RES TRIANGLE PK,NC 27709. NR 50 TC 14 Z9 14 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD MAR-APR PY 1993 VL 6 IS 2 BP 231 EP 237 DI 10.1021/tx00032a013 PG 7 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA KT721 UT WOS:A1993KT72100013 PM 8386561 ER PT J AU SHARRETT, AR AF SHARRETT, AR TI INVASIVE VERSUS NONINVASIVE STUDIES OF RISK-FACTORS AND ATHEROSCLEROSIS SO CIRCULATION LA English DT Article DE ARTERIOSCLEROSIS; CORONARY ARTERY DISEASE; ARTERIES, CAROTID ID CORONARY-ARTERY DISEASE; ACUTE MYOCARDIAL-INFARCTION; APOLIPOPROTEIN-A-I; HEART-DISEASE; SERUM-LIPIDS; PLASMA-LIPIDS; LIPOPROTEINS; SEVERITY; ARTERIOGRAPHY; ANGIOGRAPHY AB Associations of risk factors with atherosclerosis may be assessed by either invasive methods for measuring the arterial disease, such as angiography, or noninvasive methods; these methods differ in their potential for bias. Biases associated with coronary angiography may be difficult to control in statistical analysis, either because they are unrecognized or because they are amenable to neither stratification nor multivariate analysis. Problems in control selection include the likelihood that angiography controls overrepresent related ischemic or noncoronary cardiac conditions with their own risk factor associations. Differential misclassification is more likely in the clinical setting when invasive studies are used than in a research setting involving ultrasound imaging of carotid arteries. Nondifferential misclassification, however, affects both types of studies and clouds interpretation of the comparative strength of risk factor associations with atherosclerosis assessed by the two methods. Recent angiographic studies have generally provided insufficient information to evaluate these biases. However, with proper attention to such biases, one may be able to learn much about early and late stages of atherosclerosis by comparing risk factor associations with disease measured by both coronary angiography and carotid ultrasound. RP SHARRETT, AR (reprint author), NHLBI,FED BLDG,ROOM 2C08,BETHESDA,MD 20892, USA. NR 58 TC 15 Z9 15 U1 1 U2 2 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD MAR PY 1993 VL 87 IS 3 SU S BP 48 EP 53 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA KR796 UT WOS:A1993KR79600007 ER PT J AU PROBSTFIELD, JL BYINGTON, RP EGAN, DA ESPELAND, MA MARGITIC, SE RILEY, WA FURBERG, CD AF PROBSTFIELD, JL BYINGTON, RP EGAN, DA ESPELAND, MA MARGITIC, SE RILEY, WA FURBERG, CD TI METHODOLOGICAL ISSUES FACING STUDIES OF ATHEROSCLEROTIC CHANGE SO CIRCULATION LA English DT Article DE ARTERIOGRAPHY; ATHEROSCLEROSIS; ULTRASONOGRAPHY, B-MODE; CLINICAL TRIALS ID CAROTID ATHEROSCLEROSIS; CLINICAL-TRIALS; SURROGATE ENDPOINTS; ARTERIAL-WALL; B-MODE; PROGRESSION; CHOLESTEROL; THICKNESS; STENOSIS AB Background. The association between coronary heart disease and lesions of the coronary arteries has led to investigations of different interventions on atherosclerotic change. Currently, B-mode ultrasound of the peripheral arterial vessels, rather than arteriography of the coronary arteries, provides the most accurate evaluation of atherosclerotic disease extent in the patient. Methods and Results. When measuring the effect of risk factor modification on atherosclerotic change, it is important to select appropriate methods and end points for quantifying disease and evaluating subsequent change. Measurements must be valid, precise, and reliable and require appropriate a priori definitions of end points and their change. Consistent methodology within studies is crucial. Multiple measurements and data reduction methods can increase the efficiency of comparisons and merit careful consideration. Missing data arising from nonvisualization of sites complicate analyses. Identifying both covariates of atherosclerotic change and possible confounding interventions require monitoring biochemical, physiological, and/or clinical variables and making inferences from these. Conclusions. To strengthen the rationale for use of B-mode ultrasonography in assessing the natural history of atherosclerosis, four methodological issues must be addressed: evaluation of primary end points using composite and/or individual measurements of atherosclerotic assessment from the carotid arteries, evaluation of new methodology that may allow assessment of the anatomy of specific lesions and/or their potential for rupture, development of methods making complementary use of both angiographic measurements of lumen diameter and ultrasound assessment of the arterial wall, and concrete demonstration of a direct link between increasing intimal-medial thickness and subsequent clinical events. The use of a continuous variable (intimal-medial thickness) in ultrasound studies offers cost/benefit advantages; this methodology continues to evolve. C1 WAKE FOREST UNIV, BOWMAN GRAY SCH MED, DEPT PUBL HLTH SCI, WINSTON SALEM, NC 27103 USA. WAKE FOREST UNIV, BOWMAN GRAY SCH MED, DEPT NEUROL, WINSTON SALEM, NC 27103 USA. RP PROBSTFIELD, JL (reprint author), NHLBI, DECA, CLIN TRIALS BRANCH, FED BLDG 5C 10, 7550 WISCONSIN AVE, BETHESDA, MD 20892 USA. NR 39 TC 30 Z9 30 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD MAR PY 1993 VL 87 IS 3 SU S BP 74 EP 81 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA KR796 UT WOS:A1993KR79600011 ER PT J AU MANOLIO, TA ETTINGER, WH TRACY, RP KULLER, LH BORHANI, NO LYNCH, JC FRIED, LP BURKE, GL CODY, ME CRUISE, RG ETTINGER, WH FURBERG, CD HEISS, G KLOPFENSTEIN, HS LEFKOWITZ, DS LYLES, MF MITTELMARK, MB TELL, GS TOOLE, JF BOMMER, W LEE, M ROBBINS, J SCHENKER, M BRYAN, RN BUSH, TL CHABOT, J COMSTOCK, GW FRIED, LP GERMAN, PS HILL, J KITTNER, SJ KUMANYIKA, S POWE, NR PRICE, TR ROCK, R SZKLO, M BONK, J KULLER, LH MCLAUGHLIN, B MEYER, P NEWMAN, A ORCHARD, TJ RUTAN, GH SCHULZ, R SMITH, VE WOLFSON, SK ANTONCULVER, H GARDIN, JM KNOLL, M KUROSAKI, T WONG, N OLEARY, DH POLAK, JF POTTER, J BOVILL, E CORNELL, E HOWARD, P TRACY, RP ENRIGHT, P TOOGOOD, S CALHOUN, K CALHOUN, H MONTAGUE, P RAUTAHARJU, F RAUTAHARJU, P BORHANI, NO FITZPATRICK, AL HERMANSON, BK KRONMAL, RA PSATY, BM SISCOVICK, DS SHEMANSKI, L WAHL, PW BILD, DE MANOLIO, TA SAVAGE, PJ SMITH, P AF MANOLIO, TA ETTINGER, WH TRACY, RP KULLER, LH BORHANI, NO LYNCH, JC FRIED, LP BURKE, GL CODY, ME CRUISE, RG ETTINGER, WH FURBERG, CD HEISS, G KLOPFENSTEIN, HS LEFKOWITZ, DS LYLES, MF MITTELMARK, MB TELL, GS TOOLE, JF BOMMER, W LEE, M ROBBINS, J SCHENKER, M BRYAN, RN BUSH, TL CHABOT, J COMSTOCK, GW FRIED, LP GERMAN, PS HILL, J KITTNER, SJ KUMANYIKA, S POWE, NR PRICE, TR ROCK, R SZKLO, M BONK, J KULLER, LH MCLAUGHLIN, B MEYER, P NEWMAN, A ORCHARD, TJ RUTAN, GH SCHULZ, R SMITH, VE WOLFSON, SK ANTONCULVER, H GARDIN, JM KNOLL, M KUROSAKI, T WONG, N OLEARY, DH POLAK, JF POTTER, J BOVILL, E CORNELL, E HOWARD, P TRACY, RP ENRIGHT, P TOOGOOD, S CALHOUN, K CALHOUN, H MONTAGUE, P RAUTAHARJU, F RAUTAHARJU, P BORHANI, NO FITZPATRICK, AL HERMANSON, BK KRONMAL, RA PSATY, BM SISCOVICK, DS SHEMANSKI, L WAHL, PW BILD, DE MANOLIO, TA SAVAGE, PJ SMITH, P TI EPIDEMIOLOGY OF LOW CHOLESTEROL LEVELS IN OLDER ADULTS - THE CARDIOVASCULAR HEALTH STUDY SO CIRCULATION LA English DT Article DE POPULATION-BASED STUDY; AGING; EPIDEMIOLOGY; RISK FACTORS ID CORONARY HEART-DISEASE; INDEPENDENT RISK FACTOR; TUMOR-NECROSIS-FACTOR; HUMAN-COLON CANCER; SERUM-CHOLESTEROL; FAMILY HISTORY; HYPOCHOLESTEROLEMIA; LIPOPROTEIN; MORTALITY; PLASMA AB Background. Low cholesterol levels have been associated with increased mortality from stroke, cancer, and other noncardiovascular diseases, but the reasons for this association remain unclear. One explanation is that persons with low cholesterol levels have early or occult disease that eventually leads to their deaths. Methods and Results. This possibility was explored in 2,091 men and 2,714 women 65-100 years old in the Cardiovascular Health Study, a multicenter observational study of risk factors for heart disease and stroke in older adults. Cholesterol levels less-than-or-equal-to 160 mg/dL were present in 11.6% of men and 3.7% of women and increased in prevalence with age. After adjustment for age, total cholesterol levels in this range were associated with a twofold increased prevalence of treated diabetes in men and women and with a twofold increased prevalence of cancer diagnosed in the preceding 5 years in women only. Low cholesterol was also associated with lower levels of hemoglobin, albumin, and factor VII, suggesting a link with hepatic synthetic function. On multivariate analysis, factors most strongly associated with low cholesterol levels in men and women were decreased factor VII levels, decreased albumin, and diabetes. Conclusions. Cross-sectional associations with low cholesterol levels differ by sex and suggest poorer health by some measures. The observed relations with treated diabetes and impaired hepatic synthetic function should be examined for risk of mortality in longitudinal data from this and other observational studies. C1 JOHNS HOPKINS UNIV,DEPT EPIDEMIOL,BALTIMORE,MD 21218. WAKE FOREST UNIV,BOWMAN GRAY SCH MED,DEPT INTERNAL MED,WINSTON SALEM,NC 27103. WAKE FOREST UNIV,BOWMAN GRAY SCH MED,DEPT PUBL HLTH SCI,WINSTON SALEM,NC 27103. UNIV VERMONT,DEPT PATHOL,BURLINGTON,VT 05405. UNIV PITTSBURGH,GRAD SCH PUBL HLTH,PITTSBURGH,PA 15260. UNIV WASHINGTON,DEPT BIOSTAT,SEATTLE,WA 98195. JOHNS HOPKINS UNIV,DEPT MED,BALTIMORE,MD 21218. UNIV ALBERTA,CTR ELECTROCARDIOG READING,EDMONTON T6G 2E1,ALBERTA,CANADA. UNIV WASHINGTON,CTR COORDINATING,SEATTLE,WA 98195. WAKE FOREST UNIV,BOWMAN GRAY SCH MED,WINSTON SALEM,NC 27103. UNIV CALIF DAVIS,DAVIS,CA 95616. UNIV CALIF IRVINE,CTR ECHOCARDIOG READING,IRVINE,CA 92717. NEW ENGLAND DEACONESS HOSP,CTR ULTRASOUND READING,BOSTON,MA 02215. UNIV VERMONT,CENT BLOOD ANAL LAB,BURLINGTON,VT 05405. MAYO CLIN & MAYO FDN,CTR PULM FUNCT READING,ROCHESTER,MN 55905. RP MANOLIO, TA (reprint author), NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,FED BLDG,ROOM 301,7550 WISCONSIN AVE,BETHESDA,MD 20892, USA. RI Tell, Grethe/G-5639-2015; Newman, Anne/C-6408-2013 OI Tell, Grethe/0000-0003-1386-1638; Newman, Anne/0000-0002-0106-1150 FU NHLBI NIH HHS [N01-HC-85080, N01-HC-85079, N01-HC-85081] NR 48 TC 67 Z9 67 U1 7 U2 8 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD MAR PY 1993 VL 87 IS 3 BP 728 EP 737 PG 10 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA KQ923 UT WOS:A1993KQ92300003 PM 8443893 ER PT J AU ZHANG, J YU, ZX FUJITA, S YAMAGUCHI, ML FERRANS, VJ AF ZHANG, J YU, ZX FUJITA, S YAMAGUCHI, ML FERRANS, VJ TI INTERSTITIAL DENDRITIC CELLS OF THE RAT-HEART - QUANTITATIVE AND ULTRASTRUCTURAL-CHANGES IN EXPERIMENTAL MYOCARDIAL-INFARCTION SO CIRCULATION LA English DT Article DE IMMUNOHISTOCHEMISTRY; MHC ANTIGENS; MONOCLONAL ANTIBODIES; T-HELPER LYMPHOCYTES ID HISTOCOMPATIBILITY COMPLEX ANTIGENS; CLASS-II; MONOCLONAL ANTIBODY; ALLOGRAFT-REJECTION; IMMUNE-RESPONSE; LYMPHOCYTES-T; EXPRESSION; INVIVO; HETEROGENEITY; INTERLEUKIN-2 AB Background. This study was undertaken to investigate the qualitative and quantitative changes that interstitial dendritic cells (IDC) of the heart undergo during the time course of experimental myocardial infarction. Methods and Results. Left coronary arterial ligations were performed in 43 rats that were killed 2, 4, 7, 14, and 21 days after surgery. Thirteen unoperated and 39 sham-operated rats were used as controls. Frozen sections were stained with monoclonal antibodies (OX 6 and W3/25) to identify and count IDC by light microscopy. Immunoelectron microscopy was also used to identify IDC. The number of IDC per mm2 of tissue section was calculated for all hearts. In hearts with myocardial infarction, IDC were counted in three areas: the center of the myocardial infarction, the border zone, and the noninfarcted left ventricle. In OX 6 antibody-stained preparations, the number of IDC per mm2 was 82+/-10 in the left ventricle of unoperated rats. Hearts with myocardial infarction showed marked increases in the numbers of IDC per mm2 in the border zone (796+/-79 at 7 days and 528+/-98 at 14 days). In the border zone, IDC often were associated with small clusters of T-helper lymphocytes, which reacted with W3/25 antibody (the rat homologue of human CD4). The center of the myocardial infarction showed an increase in IDC only on day 7 (120+/-18). By 21 days, IDC in the border zone were only slightly increase (159+/-15). Conclusions. These findings suggest that IDC migrate to the myocardial infarction border zone. They participate in the activation of lymphocytes and in the initiation of immune responses and decrease in number as inflammation subsides and scarring develops. C1 NHLBI,PATHOL BRANCH,ULTRASTRUCT SECT,BLDG 10,ROOM 2N240,BETHESDA,MD 20892. US FDA,DIV RES & TESTING,LAUREL,MD. NR 41 TC 39 Z9 44 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD MAR PY 1993 VL 87 IS 3 BP 909 EP 920 PG 12 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA KQ923 UT WOS:A1993KQ92300023 PM 8443911 ER PT J AU KARHUMAKI, E VILJANEN, ME COTTLERFOX, M RANKI, A FOX, CH KROHN, KJE AF KARHUMAKI, E VILJANEN, ME COTTLERFOX, M RANKI, A FOX, CH KROHN, KJE TI AN IMPROVED ENRICHMENT METHOD FOR FUNCTIONALLY COMPETENT, HIGHLY PURIFIED PERIPHERAL-BLOOD DENDRITIC CELLS AND ITS APPLICATION TO HIV-INFECTED BLOOD-SAMPLES SO CLINICAL AND EXPERIMENTAL IMMUNOLOGY LA English DT Article DE DENDRITIC CELLS; ANTIGEN PRESENTATION; HIV ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACCESSORY CELLS; HUMAN-MONOCYTES; VEILED CELLS; ANTIGENS; MACROPHAGES; RESPONSES; REQUIREMENT; RECOGNITION; LYMPHOCYTES AB Dendritic cells (DC) were purified from human peripheral blood using a rapid and simple method based on magnetic depletion of phagocytes with carbonyl iron, followed by centrifugation of non-phagocytic cells on a Percoll density gradient and depletion of lymphocytes and macrophages/monocytes with a panel of MoAbs and immunomagnetic beads. Enriched DC were obtained with >99% purity as judged by non-specific esterase (NSE) staining. After isolation, these cells, representing 0.4% of the starting mononuclear cell population, still function as potent antigen-presenting cells for purified T lymphocytes. The present results confirm the ability of human peripheral blood DC to present soluble antigens to T cells including microbial antigens and show, further, that DC are more potent soluble antigen-presenting cells than monocytes. The method was successfully applied to the purification of DC from the blood of HIV-infected individuals. We could not detect decreased numbers of DC in four individuals with early HIV infection and no replicating HIV was detected by in situ hybridization in the DC. C1 UNIV TAMPERE,INST BIOMED SCI,DEPT PATHOL,POB 607,SF-33101 TAMPERE,FINLAND. NIAID,BETHESDA,MD 20892. NIH,CTR CLIN,DEPT TRANSFUS MED,BETHESDA,MD 20892. UNIV HELSINKI,CENT HOSP,DEPT DERMATOL & VENEREOL,SF-00290 HELSINKI 29,FINLAND. NR 39 TC 20 Z9 20 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0009-9104 J9 CLIN EXP IMMUNOL JI Clin. Exp. Immunol. PD MAR PY 1993 VL 91 IS 3 BP 482 EP 488 PG 7 WC Immunology SC Immunology GA KP267 UT WOS:A1993KP26700023 PM 8383023 ER PT J AU FOX, PC DATILES, M ATKINSON, JC MACYNSKI, AA SCOTT, J FLETCHER, D VALDEZ, IH KURRASCH, RHM DELAPENHA, R JACKSON, W AF FOX, PC DATILES, M ATKINSON, JC MACYNSKI, AA SCOTT, J FLETCHER, D VALDEZ, IH KURRASCH, RHM DELAPENHA, R JACKSON, W TI PREDNISONE AND PIROXICAM FOR TREATMENT OF PRIMARY SJOGRENS-SYNDROME SO CLINICAL AND EXPERIMENTAL RHEUMATOLOGY LA English DT Article DE SJOGRENS SYNDROME; SALIVARY GLANDS; LACRIMAL GLANDS; STEROIDS; NONSTEROIDAL ANTIINFLAMMATORY DRUGS ID SALIVARY-GLANDS; DOUBLE-BLIND; BROMHEXINE; XEROSTOMIA; BIOPSY AB Primary Sjogren's syndrome is a systemic autoimmune exocrinopathy characterized by a lymphoplasmacytic infiltrate and destruction of salivary and lacrimal glandular tissues. There is no widely accepted or effective systemic therapy for this disorder. The purpose of this 6-month randomized, double-blinded, placebo-controlled study was to examine the effects of prednisone (30 mg, alternate days), piroxicam (20 mg, daily), or placebo on the salivary, lacrimal and immunologic alterations of primary Sjogren's syndrome. Eight patients were enrolled in each group. Salivary and lacrimal function were assessed at entry and at the completion of treatment. Labial minor salivary gland tissue was obtained at these times and examined for intensity of infiltration (focus scores) and for the relative proportion of glandular elements. Serologic and subjective evaluations were done as well, and patients were monitored for therapy-related side effects. Neither active treatment led to significant improvement in salivary or lacrimal function, although prednisone improved salivary flow in selected patients and was associated with positive subjective responses. Prednisone also significantly decreased the serum total protein, IgG, IgA, and sedimentation rate and increased the white cell count. There were no significant alterations in either focus scores or the percentage of glandular component tissues of minor glands with either active treatment. This study demonstrated that 6 months of prednisone or piroxicam at the doses utilized failed to improve the histological or functional parameters of salivary and lacrimal glands in primary Sjogren's syndrome. C1 UNIV LIVERPOOL,SCH DENT SURG,LIVERPOOL L69 3BX,ENGLAND. NEI,CLIN BRANCH,BETHESDA,MD 20892. RP FOX, PC (reprint author), NIDR,CLIN INVEST & PATIENT CARE BRANCH,BLDG 10,ROOM 1N-113,BETHESDA,MD 20892, USA. OI Datiles, Manuel III B./0000-0003-4660-1664 NR 20 TC 54 Z9 56 U1 0 U2 0 PU CLINICAL & EXPER RHEUMATOLOGY PI PISA PA VIA SANTA MARIA 31, 56126 PISA, ITALY SN 0392-856X J9 CLIN EXP RHEUMATOL JI Clin. Exp. Rheumatol. PD MAR-APR PY 1993 VL 11 IS 2 BP 149 EP 156 PG 8 WC Rheumatology SC Rheumatology GA LA405 UT WOS:A1993LA40500007 PM 8508556 ER PT J AU LOCASCIOBROWN, L PLANT, AL CHESLER, R KROLL, M RUDDEL, M DURST, RA AF LOCASCIOBROWN, L PLANT, AL CHESLER, R KROLL, M RUDDEL, M DURST, RA TI LIPOSOME-BASED FLOW-INJECTION IMMUNOASSAY FOR DETERMINING THEOPHYLLINE IN SERUM SO CLINICAL CHEMISTRY LA English DT Article DE IMMUNOREACTOR; MONOCLONAL ANTIBODIES; FLUORESCENCE POLARIZATION IMMUNOASSAY COMPARED ID ENZYME-IMMUNOASSAY; PLASMA AB We developed a method for quantitatively determining theophylline in serum, using a heterogeneous immunoassay called flow-injection immunoanalysis. The reaction involves competition between serum theophylline and theophylline-labeled liposomes. Separation occurs on a solid-phase reactor column containing immobilized antibody to theophylline incorporated in a flow-injection system. Subsequent lysis of the bound liposomes provides sensitive detection of the analyte. Effective regeneration of the immobilized antibody activity allows the reactor to be reused for hundreds of sequential samples. Comparison of the results of the flow-injection immunoassay method with results obtained with a commercially available fluorescence polarization method showed an excellent correlation. C1 NIH,CTR CLIN,DEPT CLIN PATHOL,BETHESDA,MD 20892. CORNELL UNIV,NEW YORK STATE AGR EXPT STN,ANALYT LABS,GENEVA,NY 14456. RP LOCASCIOBROWN, L (reprint author), NATL INST STAND & TECHNOL,GAITHERSBURG,MD 20899, USA. NR 14 TC 47 Z9 48 U1 1 U2 1 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD MAR PY 1993 VL 39 IS 3 BP 386 EP 391 PG 6 WC Medical Laboratory Technology SC Medical Laboratory Technology GA KR845 UT WOS:A1993KR84500004 PM 8448847 ER PT J AU KROLL, MH EMANCIPATOR, K AF KROLL, MH EMANCIPATOR, K TI A THEORETICAL EVALUATION OF LINEARITY SO CLINICAL CHEMISTRY LA English DT Article DE METHOD EVALUATION; METHOD ASSESSMENT; REPORTABLE RANGE; STATISTICS ID ASSAY LINEARITY AB The measure of linearity is an important part of the evaluation of a method. According to the NCCLS guidelines (Document EP6-P), results of a linearity experiment are fit to a straight line and judged linear either by visual evaluation, which is subjective, or by the lack-of-fit test. This approach depends on the precision of the method, is not necessarily conclusive, and fails to be quantitative. We define linearity as a measure of how well a first-order (linear) polynomial fits the data compared with a higher-order (nonlinear) polynomial. The major property of a linear polynomial is that the first derivative is a constant. The nonlinearity of a method can be measured by the difference between these two polynomials (first-order and higher-order) at specific values or, as an average, the root-mean difference. This approach is independent of the precision of the assay and is conclusive, quantitative, and objective. C1 CORNELL UNIV,MED CTR,COLL MED,DEPT PATHOL,NEW YORK,NY 10021. RP KROLL, MH (reprint author), NIH,CTR CLIN,DEPT CLIN PATHOL,BLDG 10,ROOM 2C-407,BETHESDA,MD 20892, USA. NR 12 TC 54 Z9 58 U1 0 U2 3 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD MAR PY 1993 VL 39 IS 3 BP 405 EP 413 PG 9 WC Medical Laboratory Technology SC Medical Laboratory Technology GA KR845 UT WOS:A1993KR84500007 PM 8448849 ER PT J AU MIXSON, AJ RENAULT, JC RANSOM, S BODENNER, DL WEINTRAUB, BD AF MIXSON, AJ RENAULT, JC RANSOM, S BODENNER, DL WEINTRAUB, BD TI IDENTIFICATION OF A NOVEL MUTATION IN THE GENE ENCODING THE BETA-TRIIODOTHYRONINE RECEPTOR IN A PATIENT WITH APPARENT SELECTIVE PITUITARY RESISTANCE TO THYROID-HORMONE SO CLINICAL ENDOCRINOLOGY LA English DT Note ID C-ERBA-BETA; LIGAND-BINDING DOMAIN; INAPPROPRIATE SECRETION; GENERALIZED RESISTANCE; TSH HYPERSECRETION; BASE MUTATION; MESSENGER-RNA; HYPERTHYROIDISM; TRIAC; BROMOCRIPTINE AB OBJECTIVE We investigated whether the first patient (L-F3) reported as having selective pituitary resistance had a mutation in the hTRbeta gene. We compared the clinical parameters of this case with those of patients with generalized resistance to thyroid hormone. DESIGN The patient, L-F3, was part of a study at the NIH to identity mutations by sequencing the hTRbeta gene in kindreds with thyroid hormone resistance. The clinical data of L-F3 as well as patients with generalized resistance to thyroid hormone were compared and analysed retrospectively. MEASUREMENT We amplified by the polymerase chain reaction and then sequenced exons 5 to 10 of the hTRbeta gene in L-F3 and a normal control. Upon finding the mutation in L-F3, we measured the affinity constant of this mutated hTRbeta receptor. Criteria developed previously were used to assess tissue responsiveness to thyroid hormone of L-F3. RESULTS We identilled a C to T transition at base 1297 in codon 333 of the hTRbeta gene in the first patient (L-F3) reported as having apparent selective pituitary resistance. This base substitution resulted in more than a fourfold decrease in T3-binding affinity for the hTRbeta1 receptor. The mutation of L-F3 occurred in the dimerization domain of exon 9, a region where the majority of mutations of kindreds with generalized thyroid hormone resistance have been found. Furthermore, the nucleotide substitution at base 1297 found in the apparent selective pituitary resistant case, L-F3, was the same as in an unrelated patient (K-T3) with generalized resistance to thyroid hormone. As a result, we compared the clinical parameters of both patients and found that they had similar patterns of resistance in several tissues. Besides the bone resistance present in both kindreds, the apparent selective pituitary resistance case also had liver and neuromuscular resistance. CONCLUSIONS These findings suggest that apparent selective pituitary resistance and generalized resistance to thyroid hormone are not qualitatively different syndromes. Nevertheless, identification of selective pituitary resistance is a useful clinical distinction since such patients with clinical and biochemical features of hyperthyroidism appear to benefit from reduction in serum thyroid hormone concentrations. In contrast, patients with more conventional forms of thyroid hormone resistance require no treatment or may benefit from increased concentrations of thyroid hormone. RP MIXSON, AJ (reprint author), NIDDKD,MOLEC & CELLULAR ENDOCRINOL BRANCH,BETHESDA,MD 20892, USA. NR 34 TC 36 Z9 37 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0300-0664 J9 CLIN ENDOCRINOL JI Clin. Endocrinol. PD MAR PY 1993 VL 38 IS 3 BP 227 EP 234 DI 10.1111/j.1365-2265.1993.tb00999.x PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA KN705 UT WOS:A1993KN70500001 PM 8384535 ER PT J AU GENKA, S DEUTSCH, J SHETTY, UH STAHLE, PL JOHN, V LIEBERBURG, IM ALIOSMAN, F RAPOPORT, SI GREIG, NH AF GENKA, S DEUTSCH, J SHETTY, UH STAHLE, PL JOHN, V LIEBERBURG, IM ALIOSMAN, F RAPOPORT, SI GREIG, NH TI DEVELOPMENT OF LIPOPHILIC ANTICANCER AGENTS FOR THE TREATMENT OF BRAIN-TUMORS BY THE ESTERIFICATION OF WATER-SOLUBLE CHLORAMBUCIL SO CLINICAL & EXPERIMENTAL METASTASIS LA English DT Article DE ALKYLATING AGENTS; BLOOD BRAIN BARRIER; BRAIN; CANCER PHARMACOKINETICS; CHLORAMBUCIL; CHLORAMBUCIL ESTERS; LIPOPHILICITY; PLASMA; RAT ID CHOLINERGIC AGONIST ARECOLINE; RAT; DELIVERY; PLASMA; PHARMACOKINETICS; CHEMOTHERAPY; MELPHALAN; PRODRUGS; BARRIER; BINDING AB The lipophilic derivatives of the anticancer alkylating agent chlorambucil, chlorambucil-methyl, -isopropyl and -tertiary butyl esters, were synthesized and administered i.v. to anesthetized rats. Plasma and brain concentrations of these agents and of their active metabolites, chlorambucil and phenylacetic mustard, then were determined by high-performance liquid chromatography between 5 and 60 min. Whereas large amounts of chlorambucil-tertiary butyl ester entered and were maintained in brain, lower amounts of chlorambucil-isopropyl ester and no chlorambucil-methyl ester were found in brain. The comparative brain/plasma concentration-time integral ratios of the total active agents generated from chlorambucil-tertiary butyl, -isopropyl and -methyl esters were 0.85, 0.12 and 0.06, respectively, compared to a ratio of 0.02 for chlorambucil. In vitro alkylating activity of each ester was compared to that of equimolar chlorambucil, by reaction with 4-(p-nitrobenzyl)pyridine. Each ester possessed high intrinsic alkylating activity, equal to 38.4, 57.0 and 69.9% of chlorambucil activity, for the -tertiary butyl, -isopropyl and -methyl esters, respectively. Therefore each is an active antineoplastic agent irrespective of whether or not chlorambucil is regenerated. The rates of ester hydrolysis of these derivatives to chlorambucil were measured in fresh rat blood and in liver and brain homogenates at 37-degrees-C. Chlorambucil-methyl and -isopropyl esters were hydrolysed quickly within 30 s in blood and liver, whereas chlorambucil-tertiary butyl ester was more stable with half-lives of approximately 7 h and 2 h, respectively. All proved to be relatively stable in brain homogenate. Steric hindrance around the ester linkage of chlorambucil-tertiary butyl ester reduces its affinity to and rate of hydrolysis by plasma and liver esterases, and allows it to accumulate within the brain. Chlorambucil-tertiary butyl ester maintains high levels in brain despite rapidly declining plasma concentrations and, due to these favorable pharmacokinetics and to its intrinsic anticancer activity, it possesses promising characteristics for the treatment of malignant brain tumors. C1 NIA,NEUROSCI LAB,BLDG 10,RM 6C 103,BETHESDA,MD 20892. ATHENA NEUROSCI INC,SAN FRANCISCO,CA. UNIV TEXAS,MD ANDERSON CANC CTR,DEPT EXPTL PEDIAT,HOUSTON,TX 77025. NR 49 TC 23 Z9 23 U1 0 U2 3 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0262-0898 J9 CLIN EXP METASTAS JI Clin. Exp. Metastasis PD MAR PY 1993 VL 11 IS 2 BP 131 EP 140 DI 10.1007/BF00114971 PG 10 WC Oncology SC Oncology GA KQ572 UT WOS:A1993KQ57200001 PM 8444006 ER PT J AU NARIAI, T GREIG, NH DEGEORGE, JJ GENKA, S RAPOPORT, SI AF NARIAI, T GREIG, NH DEGEORGE, JJ GENKA, S RAPOPORT, SI TI INTRAVENOUSLY INJECTED RADIOLABELED FATTY-ACIDS IMAGE BRAIN-TUMOR PHOSPHOLIPIDS INVIVO - DIFFERENTIAL UPTAKES OF PALMITATE, ARACHIDONATE AND DOCOSAHEXAENOATE SO CLINICAL & EXPERIMENTAL METASTASIS LA English DT Article DE ARACHIDONIC ACID; BRAIN METABOLISM; DOCOSAHEXAENOIC ACID; FATTY ACIDS; IMAGING, LIPIDS; PALMITIC ACID; QUANTITATIVE AUTORADIOGRAPHY; BRAIN TUMOR ID UNANESTHETIZED RATS; CELLS; METABOLISM; LIPIDS; AUTORADIOGRAPHY; CHEMOTHERAPY; METASTASES; TURNOVER; GLIOMAS; MODEL AB This paper investigates the incorporation of intravenously (i.v.) administered radiolabelled fatty acids-[9, 10-H-3]palmitate (H-3-PA), [1-C-14]arachidonate (C-14-AA) and [1-C-14]docosahexaenoate (C-14-DHA) - into intracerebrally implanted tumours in awake Fischer-344 rats. A suspension of Walker 256 carcinosarcoma tumour cells (1 X 10(6) cells) was implanted into the right cerebral hemisphere of 8- to 9-week-old rats. Seven days after implantation, the awake rat was infused i.v. for 5 min with H-3-PA (6.4 mCi/kg), C-14-AA (170 muCi/kg) or C-14-DHA (100 muCi/kg). Twenty minutes after the start of infusion, the rat was killed and coronal brain sections were obtained for quantitative autoradiography and histology. Each fatty acid showed well-demarcated incorporation into tumour tissue. Areas of necrosis or haemorrhage showed no or small levels of incorporation. The ratios of incorporation into the tumour to incorporation into contralateral brain regions were 2.8-5.5 for H-3-PA, 2.1-3.3 for C-14-AA and 1.5-2.2 for C-14-DHA. The mean ratios differed significantly between the fatty acids (p < 0.01). H-3-PA was not incorporated into necrotic tumours despite the presence of an open blood-tumour barrier, indicated by extravasated horseradish peroxidase. The incorporation rate constant of H-3-PA was similar for small intracerebral and large extracerebral tumours. The results show that H-3-PA, C-14-AA and C-14-DHA are incorporated more readily into tumour tissue than into brain, and that the increase is primarily due to increased utilization of fatty acids by tumour cells and not due to a high blood-tumour permeability. The relative increases in rates of incorporation for the different fatty acids may be related to lipid composition of the tumour and to the requirement of and specific role of these fatty acids in tumour cell growth and division. C1 NIA,NEUROSCI LAB,BLDG 10,ROOM 6C 103,BETHESDA,MD 20892. NR 46 TC 16 Z9 16 U1 0 U2 1 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0262-0898 J9 CLIN EXP METASTAS JI Clin. Exp. Metastasis PD MAR PY 1993 VL 11 IS 2 BP 141 EP 149 DI 10.1007/BF00114972 PG 9 WC Oncology SC Oncology GA KQ572 UT WOS:A1993KQ57200002 PM 8444007 ER PT J AU JOHNSON, BE AF JOHNSON, BE TI MANAGEMENT OF SMALL-CELL LUNG-CANCER SO CLINICS IN CHEST MEDICINE LA English DT Article ID HIGH-DOSE CYCLOPHOSPHAMIDE; SOUTHWEST-ONCOLOGY-GROUP; INTENSIVE WEEKLY CHEMOTHERAPY; CROSS-RESISTANT CHEMOTHERAPY; MEDICAL-RESEARCH-COUNCIL; LONG-TERM SURVIVAL; PHASE-II TRIAL; COMBINATION CHEMOTHERAPY; RANDOMIZED TRIAL; BRONCHOGENIC-CARCINOMA RP JOHNSON, BE (reprint author), NATL NAVAL MED CTR, NCI,USN,MED ONCOL BRANCH,LUNG CANC BIOL SECT, BLDG 8, ROOM 5101, BETHESDA, MD 20889 USA. NR 120 TC 17 Z9 17 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0272-5231 J9 CLIN CHEST MED JI Clin. Chest Med. PD MAR PY 1993 VL 14 IS 1 BP 173 EP 187 PG 15 WC Respiratory System SC Respiratory System GA KT126 UT WOS:A1993KT12600015 PM 8384962 ER PT J AU SHIONO, PH KLEBANOFF, MA AF SHIONO, PH KLEBANOFF, MA TI A REVIEW OF RISK SCORING FOR PRETERM BIRTH SO CLINICS IN PERINATOLOGY LA English DT Article ID PREVENTION; SYSTEM; PREMATURITY; PREDICTION; PREGNANCY; DELIVERY; LABOR C1 NICHHD,DIV EPIDEMIOL STAT & PREVENT RES,BETHESDA,MD 20892. RP SHIONO, PH (reprint author), DAVID & LUCILE PACKARD FDN,CTR FUTURE CHILDREN,300 2ND ST,102,LOS ALTOS,CA 94022, USA. NR 42 TC 29 Z9 30 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0095-5108 J9 CLIN PERINATOL JI Clin. Perinatol. PD MAR PY 1993 VL 20 IS 1 BP 107 EP 125 PG 19 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA LA273 UT WOS:A1993LA27300008 PM 8458160 ER PT J AU LEIBENLUFT, E MADDEN, PA DICK, SE ROSENTHAL, NE AF LEIBENLUFT, E MADDEN, PA DICK, SE ROSENTHAL, NE TI PRIMARY DEPRESSIVES WITH SECONDARY ALCOHOLISM COMPARED WITH ALCOHOLICS AND DEPRESSIVES SO COMPREHENSIVE PSYCHIATRY LA English DT Article ID AFFECTIVE-DISORDER; MAJOR DEPRESSION; DRUG-ABUSE; PERSONALITY RP LEIBENLUFT, E (reprint author), NIMH,CLIN PSYCHOL BRANCH,BLDG 10,ROOM 4S-239,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 23 TC 17 Z9 17 U1 2 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0010-440X J9 COMPR PSYCHIAT JI Compr. Psychiat. PD MAR-APR PY 1993 VL 34 IS 2 BP 83 EP 86 DI 10.1016/0010-440X(93)90051-5 PG 4 WC Psychiatry SC Psychiatry GA KQ920 UT WOS:A1993KQ92000002 PM 8485985 ER PT J AU PINEDA, R CHAN, CC NI, M HAYDEN, BJ JOHNSON, MA NICKERSON, J CHADER, GJ AF PINEDA, R CHAN, CC NI, M HAYDEN, BJ JOHNSON, MA NICKERSON, J CHADER, GJ TI HUMAN RETINOBLASTOMA CELLS EXPRESS ALPHA-B-CRYSTALLIN INVIVO AND INVITRO SO CURRENT EYE RESEARCH LA English DT Article ID NON-LENTICULAR TISSUES; LENS; IMMUNOHISTOCHEMISTRY; PROTEIN; GENE AB AlphaB-crystallin is a major lens protein that is a member of the heat-shock family of proteins. Using immunohistochemical and northern blot techniques, we now demonstrate its Presence in freshly-fixed retinoblastoma tissue. The Protein is also abundantly expressed in cultured human retinoblastoma cells (Y-79 NEI, WERI Rb-1) as well as two subcultured Y-79 lines (ATCC and GM01232C). High expression of alphaB-crystallin may be involved in tumor growth and/or be a marker for general oncogenic ''stress'' in the tumor tissue. C1 NIH,RETINAL CELL & MOLEC BIOL LAB,BLDG 10,ROOM 10N216,BETHESDA,MD 20892. NIH,IMMUNOL LAB,BETHESDA,MD 20892. HOWARD HUGHES MED INST,BETHESDA,MD 20892. NR 27 TC 15 Z9 15 U1 0 U2 1 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 1993 VL 12 IS 3 BP 239 EP 245 DI 10.3109/02713689308999469 PG 7 WC Ophthalmology SC Ophthalmology GA KV173 UT WOS:A1993KV17300005 PM 8482112 ER PT J AU GAUDET, SJ TSILOU, E CHADER, GJ AF GAUDET, SJ TSILOU, E CHADER, GJ TI IDENTIFICATION AND CHARACTERIZATION OF ARYLAMINE N-ACETYLTRANSFERASE ACTIVITY FROM THE BOVINE RETINAL-PIGMENT EPITHELIUM SO CURRENT EYE RESEARCH LA English DT Article ID PINEAL-GLAND; HUMAN-LIVER; ACETYLATION; MELATONIN; EYE AB Arylamine N-acetyltransferase (NAT) activity was identified and characterized in bovine retinal Pigment epithelium (RPE) cells. Upon examining the RPE supernatant for multiple ionic species, one major NAT activity peak was detected. Based upon its substrate specificity, it is best described as an arylamine NAT. However, there . detectable arylalkylamine NAT activity within this peak. Further purification via size-exclusion HPLC revealed multiple peaks of NAT activity, although the major peak (around 30 kDa) again Predominantly exhibits arylamine NAT activity. However, substrate specificity studies indicate that this arylamine NAT activity is able to acetylate specific arylalkylamine substrates. This arylamine NAT demonstrates a monomorphic pattern of acetylation since it acetylates rho-aminobenzoic acid rather than sulfamethazine. It also demonstrates a low sensitivity to methotrexate inhibition indicated by the high IC50 value (570 muM). The mode of inhibition by methotrexate is uncompetitive as demonstrated by kinetic analysis. RP GAUDET, SJ (reprint author), NEI,RETINAL CELL & MOLEC BIOL LAB,BLDG 6,RM 309,BETHESDA,MD 20892, USA. NR 18 TC 2 Z9 2 U1 0 U2 1 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 1993 VL 12 IS 3 BP 271 EP 278 DI 10.3109/02713689308999473 PG 8 WC Ophthalmology SC Ophthalmology GA KV173 UT WOS:A1993KV17300009 PM 8482116 ER PT J AU PIETRINI, P AZARI, NP GRADY, CL SALERNO, JA GONZALESAVILES, A HESTON, LL PETTIGREW, KD HORWITZ, B HAXBY, JV SCHAPIRO, MB AF PIETRINI, P AZARI, NP GRADY, CL SALERNO, JA GONZALESAVILES, A HESTON, LL PETTIGREW, KD HORWITZ, B HAXBY, JV SCHAPIRO, MB TI PATTERN OF CEREBRAL METABOLIC INTERACTIONS IN A SUBJECT WITH ISOLATED AMNESIA AT RISK FOR ALZHEIMERS-DISEASE - A LONGITUDINAL EVALUATION SO DEMENTIA LA English DT Article DE POSITRON EMISSION TOMOGRAPHY; FLUORODEOXYGLUCOSE; HUMAN; ALZHEIMERS DISEASE; CEREBRAL GLUCOSE METABOLISM; EARLY DIAGNOSIS; AT RISK; DISCRIMINANT ANALYSIS ID POSITRON EMISSION TOMOGRAPHY; GLUCOSE-UTILIZATION; DEMENTIA; ASYMMETRIES AB A pattern of reduced cerebral metabolic rate for glucose (rCMRglc) has been shown by positron emission tomography (PET) in patients with dementia of the Alzheimer type. To verify if a similar rCMRglc pattern is present in subjects 'at risk' for Alzheimer's disease (AD), we used high-resolution PET to longitudinally study a subject with isolated memory impairment and a family history for autosomal dominant AD. Initial rCMRglc data did not reveal any consistent abnormality as compared to a group of sex- and age-matched healthy controls. However, 1 year later, a follow-up evaluation did reveal reduced parietal rCMRglc values coinciding with a worsening of cognitive impairment, which suggested that standard analyses of resting rCMRglc data may not be useful in the early diagnosis of AD. In contrast, when a previously determined discriminant function for distinguishing controls from AD patients was applied, the subject was correctly identified as an AD patient on both PET scans. C1 UNIV WASHINGTON,DEPT PSYCHIAT,SEATTLE,WA 98195. NIMH,DIV APPL & SERV RES,BETHESDA,MD 20892. RP PIETRINI, P (reprint author), NIA,NEUROSCI LAB,BLDG 10,ROOM 6C414,ROCKVILL PIKE,BETHESDA,MD 20892, USA. NR 20 TC 38 Z9 38 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1013-7424 J9 DEMENTIA JI Dementia PD MAR-APR PY 1993 VL 4 IS 2 BP 94 EP 101 DI 10.1159/000107349 PG 8 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA LA198 UT WOS:A1993LA19800006 PM 8358518 ER PT J AU ROYCE, LS KIBBEY, MC MERTZ, P KLEINMAN, HK BAUM, BJ AF ROYCE, LS KIBBEY, MC MERTZ, P KLEINMAN, HK BAUM, BJ TI HUMAN NEOPLASTIC SUBMANDIBULAR INTERCALATED DUCT CELLS EXPRESS AN ACINAR PHENOTYPE WHEN CULTURED ON A BASEMENT-MEMBRANE MATRIX SO DIFFERENTIATION LA English DT Article ID MOUSE SALIVARY EPITHELIUM; CAPILLARY-LIKE STRUCTURES; HUMAN-ENDOTHELIAL CELLS; BRANCHING MORPHOGENESIS; EXTRACELLULAR-MATRIX; BASAL LAMINA; NEURITE OUTGROWTH; DIFFERENTIATION; GLAND; ACID AB Culture of the human neoplastic submandibular gland intercalated duct cell line, HSG, on the basement membrane extract Matrigel induces dramatic morphologic changes and cytodifferentiation. Transmission electron microscopy demonstrated an acinar cell phenotype with polarized cells containing a well-developed Golgi apparatus, multiple microvilli-like projections from the apical surfaces into a lumenal-like area, and numerous granule-like organelles. Amylase, an acinar cell marker, was detected by both immunocytochemical and Northern blot analyses. A 50% reduction in [H-3]thymidine incorporation by cells cultured on Matrigel, as compared to cells cultured on tissue culture plates, confirmed the differentiated phenotype of the cells. Multiple components of Matrigel appear to contribute to the morphologic differentiation of the HSG cells since antibodies to both laminin and collagen IV, as well as the laminin-derived bioactive peptide containing SIKVAV, have potent inhibitory effects on HSG cell organization on Matrigel. Collectively, these data indicate that culture of HSG cells on Matrigel is a useful model to study salivary gland acinar development. C1 NIDR,DEV BIOL LAB,BETHESDA,MD 20892. RP ROYCE, LS (reprint author), NIDR,CLIN INVEST & PATIENT CARE BRANCH,BLDG 10 RM 1N-112,BETHESDA,MD 20892, USA. NR 43 TC 74 Z9 74 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0301-4681 J9 DIFFERENTIATION JI Differentiation PD MAR PY 1993 VL 52 IS 3 BP 247 EP 255 DI 10.1111/j.1432-0436.1993.tb00637.x PG 9 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA KT689 UT WOS:A1993KT68900007 PM 7683292 ER PT J AU DUDLEY, MW PEET, NP DEMETER, DA WEINTRAUB, HJR IJZERMAN, AP NORDVALL, G VANGALEN, PJM JACOBSON, KA AF DUDLEY, MW PEET, NP DEMETER, DA WEINTRAUB, HJR IJZERMAN, AP NORDVALL, G VANGALEN, PJM JACOBSON, KA TI ADENOSINE-A1-RECEPTOR AND LIGAND MOLECULAR MODELING SO DRUG DEVELOPMENT RESEARCH LA English DT Article; Proceedings Paper CT PURINES 92 : PHARMACOLOGY AND CLINICAL APPLICATIONS CY JUN, 1992 CL UNIV MILAN, MILAN, ITALY SP PURINE CLUB ITALY, ALFA WASSERMAN, AMITY, ASTRO MED, BOEHRINGER INGELHEIM, CAMILLO CORI, CHIESI, CIBA GEIGY, CRINOS, DUPONT NEN HO UNIV MILAN DE ADENOSINE; THEOPHYLLINE; MDL 100; 991; N6-C8 MODEL; R-PIA ID COMPUTER-GRAPHICS; BINDING-SITE; RAT-BRAIN; ANTAGONISTS; BACTERIORHODOPSIN; RESOLUTION; CLONING AB This symposium provided a forum for presentations by the relevant groups on ligand design and ligand binding on the adenosine A1 receptor. Agreement appears to exist that the ''N6-C-8'' model of ligand binding to the receptor is the preferred mode. A consensus has not yet been reached on the actual placement of the ligand in the receptor and the exact amino acids which interact in its binding. Two viable models exist at present. Both can be tested with selective site-directed mutagenic studies on the A1 receptor as well as with additional designed ligands. C1 CTR BIOPHARMACEUT SCI,LEIDEN,NETHERLANDS. KAROLINSKA INST,S-10401 STOCKHOLM 60,SWEDEN. NIH,BETHESDA,MD 20892. RP DUDLEY, MW (reprint author), MARION MERRELL DOW RES INST,2110 E GALBRAITH RD,CINCINNATI,OH 45215, USA. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 NR 25 TC 28 Z9 28 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0272-4391 J9 DRUG DEVELOP RES JI Drug Dev. Res. PD MAR PY 1993 VL 28 IS 3 BP 237 EP 243 DI 10.1002/ddr.430280309 PG 7 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA KV613 UT WOS:A1993KV61300008 ER PT J AU AHLUWALIA, G COONEY, DA HARTMAN, NR MITSUYA, H YARCHOAN, R FRIDLAND, A BRODER, S JOHNS, DG AF AHLUWALIA, G COONEY, DA HARTMAN, NR MITSUYA, H YARCHOAN, R FRIDLAND, A BRODER, S JOHNS, DG TI ANOMALOUS ACCUMULATION AND DECAY OF 2',3'-DIDEOXYADENOSINE-5'-TRIPHOSPHATE IN HUMAN T-CELL CULTURES EXPOSED TO THE ANTI-HIV DRUG 2',3'-DIDEOXYINOSINE SO DRUG METABOLISM AND DISPOSITION LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; HUMAN LYMPHOID-CELLS; AIDS-RELATED COMPLEX; IMP DEHYDROGENASE STIMULATE; PHASE-I TRIAL; 3'-AZIDO-3'-DEOXYTHYMIDINE; PHOSPHORYLATION; PHARMACOKINETICS; INFECTIVITY; INHIBITION AB The rates of accumulation and decay of 2',3'-dideoxyadenosine-5'-triphosphate (ddATP) have been examined after incubation with the anti-human immunodeficiency virus (HIV) agents 2',3'-dideoxyinosine (ddIno) and 2',3'-dideoxyadenosine (ddAdo) in human T-cell systems frequently used for assay of anti-HIV agents (MOLT-4 and CEM). Formation of ddATP from ddIno or ddAdo was rapid and concentration-dependent, with no saturation of phosphorylation being observed up to extremely high levels (1 mM) of drug. Rates of removal of ddATP from MOLT-4 cells were slow (t1/2 = 25-40 hr) and appeared to be monophasic. These unusually long half-times for ddATP utilization are not a general property of purine dideoxypurine nucleosides: when the corresponding guanine analog (2',3'-dideoxyguanosine) was examined under the same conditions, the t1/2 of ddGTP removal was only 3-5 hr. Similar results were observed with the human T-cell line CCRF-CEM. Coadministration with ddIno of inosine monophosphate dehydrogenase inhibitors, such as ribavirin and tiazofurin, yielded higher levels of ddATP in MOLT-4 and CEM cells, but did not influence the slow removal of ddATP from T-cells. The long half-time for disappearance of ddATP from cells may permit the maintenance of pharmacologically effective levels of ddATP within cells with relatively infrequent administration of the parent drug (ddIno or ddAdo). C1 NCI, MED CHEM LAB, BLDG 37, ROOM SB22, BETHESDA, MD 20892 USA. NCI, CLIN ONCOL PROGRAM, BETHESDA, MD 20892 USA. ST JUDE CHILDRENS RES HOSP, MEMPHIS, TN 38101 USA. NR 26 TC 41 Z9 41 U1 0 U2 0 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0090-9556 J9 DRUG METAB DISPOS JI Drug Metab. Dispos. PD MAR-APR PY 1993 VL 21 IS 2 BP 369 EP 376 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA KV611 UT WOS:A1993KV61100026 PM 8097711 ER PT J AU JABBARI, B COATS, M SALAZAR, A MARTIN, A SCHEROKMAN, B LAWS, WA AF JABBARI, B COATS, M SALAZAR, A MARTIN, A SCHEROKMAN, B LAWS, WA TI LONGITUDINAL-STUDY OF EEG AND EVOKED-POTENTIALS IN NEUROLOGICALLY ASYMPTOMATIC HIV-INFECTED SUBJECTS SO ELECTROENCEPHALOGRAPHY AND CLINICAL NEUROPHYSIOLOGY LA English DT Article DE HIV INFECTION; AIDS; ELECTROCEPHALOGRAM; EVOKED POTENTIALS; ASYMPTOMATIC SUBJECTS ID HUMAN-IMMUNODEFICIENCY-VIRUS; NERVOUS-SYSTEM; AIDS; MANIFESTATIONS; ABNORMALITIES; DEMENTIA; SPECTRUM; COMPLEX; BRAIN AB Serial electroencephalograms (EEGs) and multimodality evoked potentials (EPs) were performed along with neurological and neuropsychological evaluation, cerebrospinal fluid assessment and magnetic resonance imaging at 6 month intervals in 73 neurologically asymptomatic HIV infected subjects. The results were compared with 50 age- and sex-matched controls. EEG was abnormal in 2 subjects (3%) initially and was abnormal in 7 (9%) subjects by the last examination. EEG abnormality (diffuse slowing) correlated significantly with slowed reaction time in neuropsychological testing (P < 0.05). VEP and BAEP provided low yields of 1.3% and 4% respectively. SEP was abnormal in 7 (9%) of the subjects initially and in 10 (13%) subjects by the last testing, with 80% of the abnormalities seen on the posterior tibial study. In 3 subjects, initial SEP abnormalities predicted later development of myelopathy and peripheral neuropathy. Event-related auditory evoked potentials were performed in 39 subjects. They were abnormal in 5 subjects initially (12%) and in 6 subjects (15%) by the last examination and more commonly in advanced stages of the illness with lower T4 counts. This data shows the evolution and association of electrophysiological abnormalities in early HIV infection and suggests a predictive value for SEP in HIV infected asymptomatic individuals. C1 HM JACKSON FDN,BETHESDA,MD. UNIFORMED SERV UNIV HLTH SCI,DEPT NEUROL,BETHESDA,MD 20814. NIMH,CLIN SCI LAB,BETHESDA,MD 20892. RP JABBARI, B (reprint author), WALTER REED ARMY MED CTR,NEUROL SERV,DIV CLIN NEUROPHYSIOL,WASHINGTON,DC 20307, USA. RI martin, alex/B-6176-2009 NR 28 TC 43 Z9 43 U1 0 U2 3 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0013-4694 J9 ELECTROEN CLIN NEURO JI Electroencephalogr. Clin. Neurophysiol. PD MAR PY 1993 VL 86 IS 3 BP 145 EP 151 DI 10.1016/0013-4694(93)90001-C PG 7 WC Engineering, Biomedical; Clinical Neurology SC Engineering; Neurosciences & Neurology GA KU494 UT WOS:A1993KU49400001 PM 7680989 ER PT J AU TORO, C MATSUMOTO, J DEUSCHL, G ROTH, BJ HALLETT, M AF TORO, C MATSUMOTO, J DEUSCHL, G ROTH, BJ HALLETT, M TI SOURCE ANALYSIS OF SCALP-RECORDED MOVEMENT-RELATED ELECTRICAL POTENTIALS SO ELECTROENCEPHALOGRAPHY AND CLINICAL NEUROPHYSIOLOGY LA English DT Article DE PREMOTOR POTENTIALS; BRAIN ELECTRIC SOURCE ANALYSIS; MOTOR CORTEX ID CONTRASTING NEURONAL-ACTIVITY; SUPPLEMENTARY MOTOR AREA; CEREBRAL BLOOD-FLOW; CORTICAL POTENTIALS; FINGER MOVEMENTS; TOPOGRAPHY; CORTEX; MONKEYS; FIELDS; HUMANS AB We used brain electric source analysis to study the sources generating the movement-related cortical potentials during the interval from 200 msec before to 200 msec after the movement onset. Dipole solutions were obtained for the peak of the negative slope (pNS') and the frontal peak of the motor potential (fpMP) on scalp-recorded movement-related electrical potentials elicited by self-paced, repetitive unilateral finger movements in 10 normal volunteers. Two sources in homologous areas on each side of a spherical head model provided a satisfactory solution for the activity occurring at the instant of the pNS' in all subjects. The fpMP was modeled by a contralateral source and a midline source in 6 subjects and by a single contralateral source in the remaining 4 subjects. The percentage of the residual variance, or goodness-of-fit, over the interval from -200 to 200 msec, using the solutions derived at pNS' and fpMP, was low. The results support the hypothesis that the NS' originates from the activity of bilateral generators in the sensorimotor cortex, and the motor potential arises from the combined activity of sources in the contralateral postcentral regions and the supplementary motor area. C1 NINCDS,MED NEUROL BRANCH,HUMAN MOTOR CONTROL SECT,BLDG 10,ROOM 5N226,BETHESDA,MD 20892. NATL CTR RES RESOURCES,BIOMED ENGN & INSTRUMENT PROGRAM,BETHESDA,MD 20892. RI Roth, Bradley/A-4920-2008; Deuschl, Gunther/A-7986-2010 NR 31 TC 88 Z9 88 U1 2 U2 2 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0013-4694 J9 ELECTROEN CLIN NEURO JI Electroencephalogr. Clin. Neurophysiol. PD MAR PY 1993 VL 86 IS 3 BP 167 EP 175 DI 10.1016/0013-4694(93)90004-F PG 9 WC Engineering, Biomedical; Clinical Neurology SC Engineering; Neurosciences & Neurology GA KU494 UT WOS:A1993KU49400004 PM 7680992 ER PT J AU ZSOLNAI, A ORBAN, L CHRAMBACH, A AF ZSOLNAI, A ORBAN, L CHRAMBACH, A TI AGAROSE ELECTROPHORESIS OF DNA IN DISCONTINUOUS BUFFERS, USING A HORIZONTAL SLAB APPARATUS AND A BUFFER SYSTEM WITH IMPROVED PROPERTIES SO ELECTROPHORESIS LA English DT Article ID GEL-ELECTROPHORESIS; SIZE STANDARDS; POLYACRYLAMIDE; PARTICLES AB Using a horizontal slab apparatus with a buffer in the reservoirs at the level of the gel (''sea-level electrophoresis''), the retrograde discontinuous buffer system reported by Wiltfang et al. for sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) of proteins was applied to DNA electrophoresis. This application yielded the advantages of an increased displacement rate of the moving boundary front and a decrease in the concentration of the counterion base in the resolving phase, which yielded reduced relative mobility values at equivalent gel concentrations and practicable low buffer concentrations. The change of relative mobilities (R(f)) with a variation of field strength is decreased compared to that of the migration rate in the continuous Tris-boric-acid-EDTA (TBE) buffer and thus the robustness of the system is improved, as well as the efficiency of separation. The system of Wiltfang et al. has in common with previously described discontinuous DNA systems, that it is able to stack DNA from dilute samples and is insensitive to sample components with lower net mobilities than DNA, such as acetate. However, the variance of R(f) at constant current density in the discontinuous buffer system is not improved over that of the migration rate at constant field strength in the continuous TBE buffer. C1 NICHHD,THEORET & PHYS BIOL LAB,BLDG 10,RM 6C101,BETHESDA,MD 20892. AGR BIOTECHNOL CTR,INST MOLEC GENET,GODOLLO,HUNGARY. UNIV VESZPREM,DEPT ORGAN CHEM,VESZPREM,HUNGARY. RI Zsolnai, Attila/F-6441-2011; OI Zsolnai, Attila/0000-0002-8382-1503; Orban, Laszlo/0000-0001-5435-5948 NR 12 TC 8 Z9 8 U1 1 U2 4 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 1993 VL 14 IS 3 BP 179 EP 184 DI 10.1002/elps.1150140130 PG 6 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA KV630 UT WOS:A1993KV63000003 PM 8486128 ER PT J AU TIETZ, D CHRAMBACH, A AF TIETZ, D CHRAMBACH, A TI DNA SHAPE AND SEPARATION EFFICIENCY IN POLYMER MEDIA - A COMPUTERIZED METHOD BASED ON ELECTROPHORETIC MOBILITY DATA SO ELECTROPHORESIS LA English DT Article ID POLYACRYLAMIDE-GEL ELECTROPHORESIS; ELECTRON-MICROSCOPIC OBSERVATIONS; CAPILLARY ELECTROPHORESIS; RESTRICTION FRAGMENTS; ZONE ELECTROPHORESIS; INFORMATION; PROTEINS AB The computer program ELPHOFIT for evaluation of the nonlinear plots of log-(mobility) vs. polymer concentration (Ferguson plots) in terms of molecular and polymer properties has been extended to yield a measure of the molecular sieving capacity of the polymer medium. The usefulness of the extended program, version 2.2, was exemplified by the evaluation of DNA shape and separation efficiency in solutions and gels of agarose and polyacrylamide, using previous reports in the literature as a data base. That application of the extended program yields the following results:(i) The size of migrating DNA can be compared with an equivalent sphere having the same free mobility for a particular set of experimental conditions. The decrease in size of the equivalent sphere with polymer concentration previously demonstrated for agarose solutions applies to all of these polymer media; it reveals a steep, hyperbolic decline of that radius in uncrosslinked polyacrylamide solutions in contrast to the shallow decline in the other three media. (ii) The separation efficiency of polyacrylamide gels exceeds that of uncrosslinked polyacrylamide solutions; the separation efficiency of agarose solutions for DNA smaller than 1 kb in length is higher than that of polyacrylamide solutions. Program ELPHOFIT 2.2 is available on request from the first author. C1 NICHHD,MACROMOLEC ANAL SECT,THEORET & PHYS BIOL LAB,BLDG 10,RM 6C-101,BETHESDA,MD 20892. NR 45 TC 28 Z9 28 U1 1 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 1993 VL 14 IS 3 BP 185 EP 190 DI 10.1002/elps.1150140131 PG 6 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA KV630 UT WOS:A1993KV63000004 PM 8486129 ER PT J AU WHITE, BH KLEIN, DC AF WHITE, BH KLEIN, DC TI DEVELOPMENTAL APPEARANCE OF PINEAL ADRENERGIC -] GUANOSINE 3',5'-MONOPHOSPHATE RESPONSE IS DETERMINED BY A PROCESS DOWN-STREAM FROM ELEVATION OF INTRACELLULAR CA-2+ - POSSIBLE INVOLVEMENT OF A DIFFUSIBLE FACTOR SO ENDOCRINOLOGY LA English DT Article ID PROTEIN KINASE-C; SEROTONIN N-ACETYLTRANSFERASE; RAT PINEALOCYTES; CYCLIC-AMP; GUANYLATE-CYCLASE; PHOTONEURAL REGULATION; CGMP ACCUMULATION; ADENYLATE-CYCLASE; ORGAN-CULTURE; STIMULATION AB Adrenergic stimulation of the adult pineal gland increases cAMP and cGMP production by over 100-fold. Beta-Adrenergic stimulation results in G8alpha-mediated cyclase activation; alpha1-adrenergic activation potentiates the beta-adrenergic effects through mechanisms mediated by the intracellular Ca2+ concentration ([Ca2+]i) and Ca2+-phospholipid-dependent protein kinase. Developmental analysis of these responses has indicated that the adrenergic stimulation of cAMP is present several days after birth, but the cGMP response develops only after the second week of life. In the study presented here, the adrenergic --> cGMP response was analyzed in pineal glands from 10- and 25-day-old rats, with the intention of determining the basis of the developmental appearance of this response. Organ culture and tissue homogenate studies indicated that guanylate cyclase activity, cGMP phosphodiesterase activity, and adrenergic elevation of phospholipase-A2 were similar in pineal glands from 10- and 25-day-old rats. Norepinephrine stimulated an increase in [Ca2+]i in dispersed pinealocytes from 10-day-old rats, as has been previously demonstrated in adult pinealocytes. In contrast, several treatments that elevate [Ca2+]i had no effect on cGMP accumulation in forskolin-treated or beta-adrenergically activated glands from 10-day-old rats, but were fully effective in similarly treated glands from 25-day-old rats. However, glands from 10-day-old animals showed a 33-fold accumulation of cGMP when they were cultured together with glands from 25-day-old rats. These studies indicate that whereas many elements in the system that mediate adrenergic regulation of pineal cGMP are fully developed at 10 days of age, the developmental appearance of the cGMP response is triggered by the development of a process down-stream of the alpha1-adrenergic stimulation of [Ca2+]i, and this process may involve a diffusible factor. C1 NICHHD,DEV NEUROBIOL LAB,NEUROENDOCRINOL SECT,BLDG 36,ROOM 4A07,BETHESDA,MD 20892. NR 49 TC 15 Z9 15 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 1993 VL 132 IS 3 BP 1026 EP 1034 DI 10.1210/en.132.3.1026 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA KP290 UT WOS:A1993KP29000014 PM 8095011 ER PT J AU LEWTAS, J MUMFORD, J EVERSON, RB HULKA, B WILCOSKY, T KOZUMBO, W THOMPSON, C GEORGE, M DOBIAS, L SRAM, R LI, XM GALLAGHER, J AF LEWTAS, J MUMFORD, J EVERSON, RB HULKA, B WILCOSKY, T KOZUMBO, W THOMPSON, C GEORGE, M DOBIAS, L SRAM, R LI, XM GALLAGHER, J TI COMPARISON OF DNA ADDUCTS FROM EXPOSURE TO COMPLEX-MIXTURES IN VARIOUS HUMAN TISSUES AND EXPERIMENTAL SYSTEMS SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article; Proceedings Paper CT CONF ON BIOMONITORING AND SUSCEPTIBILITY MARKERS IN HUMAN CANCER : APPLICATIONS IN MOLECULAR EPIDEMIOLOGY AND RISK ASSESSMENT CY OCT 26-NOV 01, 1991 CL KAILUA KONA, HI SP INT AGCY RES CANC, NATL CTR TOXICOL RES, US EPA, COMMISS EUROPEAN COMMUNITIES, NATL CANC INST ID WHITE BLOOD-CELLS; P-32 POSTLABELING ANALYSIS; P-32-POSTLABELING ANALYSIS; FOUNDRY WORKERS; AIR-POLLUTION; LYMPHOCYTES; DAMAGE; ASSAY; MICE; SKIN AB DNA adducts derived from complex mixtures of polycyclic aromatic compounds emitted from tobacco smoke are compared to industrial pollution sources (e.g., coke ovens and aluminum smelters), smoky coal burning, and urban air pollution. Exposures to coke oven emissions and smoky coal, both potent rodent skin tumor initiators and lung carcinogens in humans, result in high levels of DNA adducts compared to tobacco smoke in the in vitro calf thymus DNA model system, in cultured lymphocytes, and in the mouse skin assay. Using tobacco smoke as a model in human studies, we have compared relative DNA adduct levels detected in blood lymphocytes, placental tissue, bronchoalveolar lung lavage cells, sperm, and autopsy tissues of smokers and nonsmokers Adduct levels in DNA isolated from smokers were highest in human heart and lung tissue with smaller but detectable differences in placental tissue and lung lavage cells. Comparison of the DNA adduct levels resulting from human exposure to different complex mixtures shows that emissions from coke ovens, aluminum smelters, and smoky coal result in higher DNA adduct levels than tobacco smoke exposure. These studies suggest that humans exposed to complex combustion mixtures will have higher DNA adduct levels in target cells (e.g., lung) as compared to nontarget cells (e.g., lymphocytes) and that the adduct levels will be dependent on the genotoxic and DNA adduct-forming potency of the mixture. C1 UNIV N CAROLINA,CHAPEL HILL,NC 27599. ENVIRONM HLTH RES & TESTING INC,RES TRIANGLE PK,NC 27709. NIEHS,RES TRIANGLE PK,NC 27709. REG INST HYG,CS-72892 OSTRAVA,CZECHOSLOVAKIA. INST EXPTL MED,CS-12000 PRAGUE,CZECHOSLOVAKIA. INST ENVIRONM HLTH & ENGN,BEIJING,PEOPLES R CHINA. RP LEWTAS, J (reprint author), US EPA,HLTH EFFECTS RES LAB,GENET BIOASSAY BRANCH,RES TRIANGLE PK,NC 27711, USA. RI Sram, Radim/H-2455-2014 OI Sram, Radim/0000-0003-4256-3816 NR 37 TC 58 Z9 58 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 1993 VL 99 BP 89 EP 97 DI 10.2307/3431463 PG 9 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA LC430 UT WOS:A1993LC43000015 PM 8319665 ER PT J AU POIRIER, MC REED, E SHAMKHANI, H TARONE, RE GUPTABURT, S AF POIRIER, MC REED, E SHAMKHANI, H TARONE, RE GUPTABURT, S TI PLATINUM DRUG DNA INTERACTIONS IN HUMAN TISSUES MEASURED BY CISPLATIN DNA ENZYME-LINKED-IMMUNOSORBENT-ASSAY AND ATOMIC ABSORBENCY SPECTROSCOPY SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article; Proceedings Paper CT CONF ON BIOMONITORING AND SUSCEPTIBILITY MARKERS IN HUMAN CANCER : APPLICATIONS IN MOLECULAR EPIDEMIOLOGY AND RISK ASSESSMENT CY OCT 26-NOV 01, 1991 CL KAILUA KONA, HI SP INT AGCY RES CANC, NATL CTR TOXICOL RES, US EPA, COMMISS EUROPEAN COMMUNITIES, NATL CANC INST ID OVARIAN-CANCER PATIENTS; ADDUCT LEVELS; LEUKOCYTE DNA; CHEMOTHERAPY; QUANTITATION; EXPOSURE; INVITRO; REMOVAL; REPAIR AB Studies of platinum drug-DNA adduct formation in tissues of cancer patients have involved both atomic absorbance spectroscopy (AAS), which measures total DNA-bound platinum, and anti-cisplatin-DNA enzyme-linked immunosorbent assay (ELISA), which detects a fraction of the AAS-measurable adduct. These studies were designed to explore mechanisms of drug-DNA interactions, to make correlations with clinical outcome, and possibly to validate DNA adduct measurements for use in occupational and environmental biomonitoring. The results, determined by both ELISA and AAS, demonstrate that cisplatin and its analog carboplatin bind to DNA in many human organs, including kidney, brain, peripheral nerve, and bone marrow, which are sites for drug toxicity. Platinum was also observed bound to ovarian tumor DNA. The adducts were highly persistent, being measurable in tissues obtained at autopsy up to 15 months after the last administration of platinum chemotherapy. A comparison of blood cell DNA adduct levels, determined by ELISA, and the clinical response of 139 patients with ovarian, testicular, colon, or breast cancer demonstrated a strong correlation between failure to form DNA adducts and failure of therapy. Conversely, patients who formed high levels of DNA adduct were most likely to respond favorably. A similar correlation was not observed for adducts determined by AAS; that is, the average total DNA-bound platinum levels were the same for patients who did not respond to therapy and for patients who had any kind of response. Thus, in this study, human blood cell DNA adducts measured by ELISA correlate with tumor remission, while those measured by AAS do not. C1 NCI,TUMOR PROMOT DIV CANC ETIOL,BETHESDA,MD 20892. NCI,DIV CANC TREATMENT,MED BRANCH,BETHESDA,MD 20892. NCI,DIV CANC ETIOL,BIOSTAT BRANCH,BETHESDA,MD 20892. RP POIRIER, MC (reprint author), NCI,CELLULAR CARCINOGENESIS LAB,BLDG 37,ROOM 3B25,BETHESDA,MD 20892, USA. NR 25 TC 23 Z9 23 U1 0 U2 1 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 1993 VL 99 BP 149 EP 154 DI 10.2307/3431471 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA LC430 UT WOS:A1993LC43000023 PM 8319613 ER PT J AU GALLAGHER, J GEORGE, M KOHAN, M THOMPSON, C SHANK, T LEWTAS, J AF GALLAGHER, J GEORGE, M KOHAN, M THOMPSON, C SHANK, T LEWTAS, J TI DETECTION AND COMPARISON OF DNA ADDUCTS AFTER INVITRO AND INVIVO DIESEL EMISSION EXPOSURES SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article; Proceedings Paper CT CONF ON BIOMONITORING AND SUSCEPTIBILITY MARKERS IN HUMAN CANCER : APPLICATIONS IN MOLECULAR EPIDEMIOLOGY AND RISK ASSESSMENT CY OCT 26-NOV 01, 1991 CL KAILUA KONA, HI SP INT AGCY RES CANC, NATL CTR TOXICOL RES, US EPA, COMMISS EUROPEAN COMMUNITIES, NATL CANC INST ID ENHANCEMENT; SENSITIVITY; LYMPHOCYTES; BINDING; ASSAY AB Development of methods to evaluate certain classes of polycyclic aromatic compounds (PAC) detected in complex mixtures to which humans are exposed would greatly improVe the diagnostic potential of P-32-postlabeling analysis. Identification of DNA adduct patterns or specific exposure-related marker adducts would strengthen associations between observed DNA adducts and exposures to different environmental pollutants (e.g., kerosene, cigarette smoke, coke oven, and diesel). We have compared diesel-modified DNA adduct patterns in various in vitro and in vivo rodent model systems and compared them to DNA reactive oxidative and reductive metabolites of 1-nitropyrene. The formation of nitrated polycyclic aromatic hydrocarbon (nitrated PAH) DNA adducts, derived from the metabolism of diesel extract constituents, was enhanced relative to other PAH-derived DNA adducts via xanthine oxidase-catalyzed nitroreduction. These adducts were detectable only by the butanol extraction version of the postlabeling analysis. Five major DNA adducts were detected in human lymphocytes treated in vitro with diesel extract. A major adduct detected in human lymphocytes treated in vitro with diesel extract comigrated with a major adduct detected in lymphocyte DNA treated with benzo[a]pyrene (BaP) alone. Other adducts that co-migrated with the major BaP-derived adducts were detected in skin and lung DNA isolated from rodents topically treated with (50 mg) diesel extract and the major adduct detected in calf thymus DNA treated with rat liver S9 and diesel particle extract. Postlabeling of lung DNA isolated from rodents exposed via lung inhalation for 24 months to diesel combustion emissions resulted in the formation of a major nuclease-P1-sensitive DNA adduct that did not co-migrate with the major BaP-diol epoxide adduct. Based on its sensitivity to nuclease-P1, this adduct may be an N-substituted aryl adduct. Marker adducts detected in the various test systems presented here will assist in characterizing nuclease-P1-sensitive nitrated PAH adducts in humans. C1 ENVIRONM HLTH RES & TESTING INC,RES TRIANGLE PK,NC 27709. NIEHS,NATL TOXICOL PROGRAM,RES TRIANGLE PK,NC 27709. RP GALLAGHER, J (reprint author), US EPA,HLTH EFFECTS RES LAB,MD 68A,RES TRIANGLE PK,NC 27711, USA. NR 18 TC 24 Z9 24 U1 1 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 1993 VL 99 BP 225 EP 228 DI 10.2307/3431487 PG 4 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA LC430 UT WOS:A1993LC43000039 PM 8319629 ER PT J AU ASSENNATO, G FERRI, GM TOCKMAN, MS POIRIER, MC SCHOKET, B PORRO, A CORRADO, V STRICKLAND, PT AF ASSENNATO, G FERRI, GM TOCKMAN, MS POIRIER, MC SCHOKET, B PORRO, A CORRADO, V STRICKLAND, PT TI BIOMARKERS OF CARCINOGEN EXPOSURE AND CANCER RISK IN A COKE PLANT SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article; Proceedings Paper CT CONF ON BIOMONITORING AND SUSCEPTIBILITY MARKERS IN HUMAN CANCER : APPLICATIONS IN MOLECULAR EPIDEMIOLOGY AND RISK ASSESSMENT CY OCT 26-NOV 01, 1991 CL KAILUA KONA, HI SP INT AGCY RES CANC, NATL CTR TOXICOL RES, US EPA, COMMISS EUROPEAN COMMUNITIES, NATL CANC INST ID LUNG-CANCER; DNA; EPIDEMIOLOGY; CELLS AB To evaluate the association between an indicator of carcinogen exposure (peripheral blood leukocyte DNA adducts of polycyclic aromatic hydrocarbons) and an early indicator of neoplastic transformation (sputum epithelial cell membrane antigens binding by monoclonal antibodies against small cell lung cancer and against nonsmall cell lung cancer), a survey of 350 coke-oven workers and 100 unexposed workers was planned. This paper reports a pilot investigation on a subgroup of 23 coke-oven workers and 8 unexposed controls. A ''gas regulator'' worker with positive tumor antigen binding was identified. Results show that smokers, subjects with decreased pulmonary function (forced expiratory volume in 1 sec/forced vital capacity% < 80), and those with morphological dysplasia of sputum cells have higher levels of DNA adducts. The gas regulators showed the highest values for adducts; however, no significant difference of adduct levels was found between the coke-oven group and unexposed controls. C1 UNIV BARI,IST MED LAVORO,POLICLIN,PIAZZA G CESARE,I-70124 BARI,ITALY. JOHNS HOPKINS SCH HYG & PUBL HLTH,DIV OCCUPAT MED,BALTIMORE,MD 21205. NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT,BETHESDA,MD 20892. NR 16 TC 10 Z9 10 U1 0 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 1993 VL 99 BP 237 EP 239 DI 10.2307/3431490 PG 3 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA LC430 UT WOS:A1993LC43000042 PM 8319632 ER PT J AU WESTON, A BOWMAN, ED SHIELDS, PG TRIVERS, GE POIRIER, MC SANTELLA, RM MANCHESTER, DK AF WESTON, A BOWMAN, ED SHIELDS, PG TRIVERS, GE POIRIER, MC SANTELLA, RM MANCHESTER, DK TI DETECTION OF POLYCYCLIC AROMATIC HYDROCARBON DNA ADDUCTS IN HUMAN LUNG SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article ID BENZOPYRENE DIOL EPOXIDE; HUMAN-PLACENTA AB Synchronous fluorescence spectroscopy has been combined with immunoaffinity chromatography (IAC) and HPLC to detect polycyclic aromatic hydrocarbon (PAH)-DNA adducts and measure r-7,t-8-dihydroxy-t-9, 10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE)-DNA adducts in human tissues and cells. A monoclonal antibody (8E11) that recognizes a range of PAH-DNA adducts, but not chemically unrelated adducts, was used to prepare IAC columns. Samples of DNA (25 from human lung and 8 positive and negative controls) were hydrolyzed enzymically and subjected to IAC. Adducts captured by the antibodies and eluted in NaOH (50 mM) were analyzed for fluorescent properties. The spectral fluorescence excitation-emission matrices suggested the presence of mixtures of PAH-DNA adducts in some of the eluates. The eluates were subsequently hydrolyzed with acid (HCI, 0.1 N, 3 hr) and re-analyzed by synchronous fluorescence spectroscopy using a wavelength differential of 34 nm. In 6 of the 25 human lung DNA samples, materials with HPLC retention times identical to benzo[a]pyrene-7,10/8,9-tetrahydrotetrol were found to have fluorescence characteristics indistinguishable from pyrene. Comparisons with appropriate standards indicated that BPDE-DNA adduct levels were between 1 and 40 adducts in 10(8) unmodified nucleotides. No correlation was observed between lung DNA-adduct levels and measures of recent smoking (serum cotinine), but tissue samples taken from different portions of the same lungs showed variation in the DNA adduct levels detected. This finding complicates interpretation of the data and has important implications for the design of future experiments. RP WESTON, A (reprint author), NCI, HUMAN CARCINOGENESIS LAB, BLDG 37, ROOM 2C1B, BETHESDA, MD 20892 USA. NR 9 TC 14 Z9 14 U1 0 U2 0 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD MAR PY 1993 VL 99 BP 257 EP 259 DI 10.2307/3431495 PG 3 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA LC430 UT WOS:A1993LC43000047 PM 8319638 ER PT J AU WILSON, VL TAFFE, BG SHIELDS, PG POVEY, AC HARRIS, CC AF WILSON, VL TAFFE, BG SHIELDS, PG POVEY, AC HARRIS, CC TI DETECTION AND QUANTIFICATION OF 8-HYDROXYDEOXYGUANOSINE ADDUCTS IN PERIPHERAL-BLOOD OF PEOPLE EXPOSED TO IONIZING-RADIATION SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article; Proceedings Paper CT CONF ON BIOMONITORING AND SUSCEPTIBILITY MARKERS IN HUMAN CANCER : APPLICATIONS IN MOLECULAR EPIDEMIOLOGY AND RISK ASSESSMENT CY OCT 26-NOV 01, 1991 CL KAILUA KONA, HI SP INT AGCY RES CANC, NATL CTR TOXICOL RES, US EPA, COMMISS EUROPEAN COMMUNITIES, NATL CANC INST ID DNA; RADICALS; DAMAGE AB Ionizing radiation produces a variety of damaging insults to nucleic acids, including the promutagenic lesion 8-hydroxydeoxyguanosine. In the present study, the 8-hydroxydeoxyguanosine content of peripheral blood leukocyte DNA isolated from individuals exposed to therapeutic doses of ionizing radiation was determined by a HPLC-coupled P-32-postlabeling assay. Peripheral blood leukocyte DNA from individuals irradiated with 18-200 cGy were observed to contain 24.5 times as much 8-hydroxydeoxyguanosine as that from unexposed individuals. These results were confirmed by the use of a HPLC-coupled electrochemical detection system. Thus, human exposure to ionizing radiation significantly increased the circulating leukocyte DNA content of 8-hydroxydeoxyguanosine. C1 CHILDRENS HOSP,KEMPE RES CTR,DENVER,CO 80218. UNIV COLORADO,HLTH SCI CTR,DEPT PATHOL,DENVER,CO 80218. NCI,DIV CANC ETIOL,HUMAN CARCINOGENESIS LAB,BETHESDA,MD 20892. RP WILSON, VL (reprint author), CHILDRENS HOSP,DEPT PATHOL,MOLEC GENET ONCOL LAB,B120,1056E 19TH AVE,DENVER,CO 80218, USA. RI Shields, Peter/I-1644-2012 NR 11 TC 56 Z9 56 U1 0 U2 3 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 1993 VL 99 BP 261 EP 263 DI 10.2307/3431496 PG 3 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA LC430 UT WOS:A1993LC43000048 PM 8319639 ER PT J AU ROTHMAN, N POIRIER, MC HAAS, RA CORREAVILLASENOR, A FORD, P HANSEN, JA OTOOLE, T STRICKLAND, PT AF ROTHMAN, N POIRIER, MC HAAS, RA CORREAVILLASENOR, A FORD, P HANSEN, JA OTOOLE, T STRICKLAND, PT TI ASSOCIATION OF PAH DNA ADDUCTS IN PERIPHERAL WHITE BLOOD-CELLS WITH DIETARY EXPOSURE TO POLYAROMATIC HYDROCARBONS SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article; Proceedings Paper CT CONF ON BIOMONITORING AND SUSCEPTIBILITY MARKERS IN HUMAN CANCER : APPLICATIONS IN MOLECULAR EPIDEMIOLOGY AND RISK ASSESSMENT CY OCT 26-NOV 01, 1991 CL KAILUA KONA, HI SP INT AGCY RES CANC, NATL CTR TOXICOL RES, US EPA, COMMISS EUROPEAN COMMUNITIES, NATL CANC INST ID AROMATIC-HYDROCARBONS; WORKERS AB Previous investigations suggest that dietary sources of polycyclic aromatic hydrocarbons (PAHs) contribute to the PAH-DNA adduct load in peripheral white blood cells (WBCs). In the current study, we measured PAH-DNA adducts by enzyme-linked immunosorbent assay in WBCs obtained from 47 California wildland (forest) firefighters at two time points (early and late) during an active forest fire season. PAH-DNA adduct levels were not associated with recent firefighting activity, but were positively associated with frequency of charbroiled food consumption in the previous 2 weeks. In addition, adduct levels declined with time since last ingestion of charbroiled rood. These studies indicate that recent consumption of charbroiled food contributes to the PAH-DNA adduct load in peripheral WBCs. C1 NCI,EPIDEMIOL & BIOSTAT PROGRAM,BETHESDA,MD 20892. NCI,CHEM & PHYS CARCINOGENESIS PROGRAM,BETHESDA,MD 20892. CALIF DEPT HLTH SERV,BERKELEY,CA 94704. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT EPIDEMIOL,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT ENVIRONM HLTH SCI,BALTIMORE,MD 21205. FU NIEHS NIH HHS [ES03819] NR 13 TC 40 Z9 41 U1 0 U2 4 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 1993 VL 99 BP 265 EP 267 DI 10.2307/3431497 PG 3 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA LC430 UT WOS:A1993LC43000049 PM 8319640 ER PT J AU CULP, SJ POIRIER, MC BELAND, FA AF CULP, SJ POIRIER, MC BELAND, FA TI BIPHASIC REMOVAL OF DNA ADDUCTS IN A REPETITIVE DNA-SEQUENCE AFTER DIETARY ADMINISTRATION OF 2-ACETYLAMINOFLUORENE SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article; Proceedings Paper CT CONF ON BIOMONITORING AND SUSCEPTIBILITY MARKERS IN HUMAN CANCER : APPLICATIONS IN MOLECULAR EPIDEMIOLOGY AND RISK ASSESSMENT CY OCT 26-NOV 01, 1991 CL KAILUA KONA, HI SP INT AGCY RES CANC, NATL CTR TOXICOL RES, US EPA, COMMISS EUROPEAN COMMUNITIES, NATL CANC INST ID RAT-LIVER; INVIVO AB Dietary administration of the hepatocarcinogen 2-acetylaminofluorene (2-AAF) to rats results in the formation of a major hepatic DNA adduct, N-(deoxyguanosin-8-yl)-2-aminofluorene (dG-C8-AF). In liver DNA, dG-C8-AF reaches steady-state conditions after approximately 2 weeks of feeding and is removed in a biphasic manner. In these experiments, we have quantified adduct concentrations in a 370 base-pair repetitive DNA fragment to determine if the adduct levels and kinetics of adduct removal were similar to those found in total genomic DNA. Male F344 rats were fed 0.02% 2-AAF for 28 days and were sacrificed at intermittent times up to 56 days after being returned to the control diet. Hepatic DNA adduct levels were measured by P-32-postlabeling or radioimmunoassay (RIA) in total genomic DNA and in a 370 base-pair fragment obtained by digesting genomic DNA with Hind III. Biphasic removal of dG-C8-AF, which composed about 90% of the total adducts measured, was observed in total genomic DNA, with comparable rate constants being detected by both P-32-postlabeling and RIA. P-32-Postlabeling also showed analogous biphasic removal of dG-C8-AF in the 370 base-pair fragment. A second adduct, 3-(deoxyguanosin-N2-yl)-2-AAF (dG-N2-AAF), which accounted for about 10% of the total adducts measured, showed similar biphasic removal kinetics in the total genomic DNA and the 370 base-pair fragment; however, as compared to dG-C8-AF, little removal of dG-N2-AAF was observed during the slow phase. C1 NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BETHESDA,MD 20892. RP CULP, SJ (reprint author), NATL CTR TOXICOL RES,DIV BIOCHEM TOXICOL,HFT-110,JEFFERSON,AR 72079, USA. NR 9 TC 34 Z9 34 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 1993 VL 99 BP 273 EP 275 DI 10.2307/3431499 PG 3 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA LC430 UT WOS:A1993LC43000051 PM 8319642 ER PT J AU TALASKA, G SCHAMER, M SKIPPER, P TANNENBAUM, S CAPORASO, N KADLUBAR, F BARTSCH, H VINEIS, P AF TALASKA, G SCHAMER, M SKIPPER, P TANNENBAUM, S CAPORASO, N KADLUBAR, F BARTSCH, H VINEIS, P TI CARCINOGEN-DNA ADDUCTS IN EXFOLIATED UROTHELIAL CELLS - TECHNIQUES FOR NONINVASIVE HUMAN MONITORING SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article; Proceedings Paper CT CONF ON BIOMONITORING AND SUSCEPTIBILITY MARKERS IN HUMAN CANCER : APPLICATIONS IN MOLECULAR EPIDEMIOLOGY AND RISK ASSESSMENT CY OCT 26-NOV 01, 1991 CL KAILUA KONA, HI SP INT AGCY RES CANC, NATL CTR TOXICOL RES, US EPA, COMMISS EUROPEAN COMMUNITIES, NATL CANC INST ID HEMOGLOBIN ADDUCTS; CIGARETTE-SMOKING; PHENOTYPE AB Detection of carcinogen-DNA adducts m DNA from exfoliated urothelial cells from animals and humans exposed to potential environmental carcinogens is described. In an animal model, 4-aminobiphenyl-DNA adducts were detected, and the shape of the dose-response curve was related to the levels of 4-aminobiphenyl-hemoglobin adducts. In a human study, five distinct adducts were two to nine times higher in smokers than in nonsmokers. The association of four adduct measures with smoking was corroborated by significant correlations with levels of 4-aminobiphenyl-hemoglobin adducts, type and number of cigarettes smoked, and/or urinary mutagenicity. One adduct seemed chromatographically similar to N-(deoxyguanosin-8-yl)-4-aminobiphenyl. This adduct showed the strongest correlation with 4-aminobiphenyl-hemoglobin adduct levels. These data suggest that noninvasive techniques can be applied to the study of carcinogen-DNA adducts in the target organ of humans at risk for urinary bladder cancer. C1 MIT,DEPT CHEM,CAMBRIDGE,MA 02139. MIT,DIV TOXICOL,CAMBRIDGE,MA 02139. NCI,FAMILY STUDIES SECT,BETHESDA,MD 20892. NATL CTR TOXICOL RES,JEFFERSON,AR 72079. INT AGCY RES CANC,F-69372 LYON,FRANCE. RP TALASKA, G (reprint author), UNIV CINCINNATI,INST ENVIRONM HLTH ML056,CINCINNATI,OH 45267, USA. NR 12 TC 30 Z9 30 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 1993 VL 99 BP 289 EP 291 DI 10.2307/3431503 PG 3 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA LC430 UT WOS:A1993LC43000055 PM 8319646 ER PT J AU SCHOKET, B PHILLIPS, DH POIRIER, MC VINCZE, I AF SCHOKET, B PHILLIPS, DH POIRIER, MC VINCZE, I TI DNA ADDUCTS IN PERIPHERAL-BLOOD LYMPHOCYTES FROM ALUMINUM PRODUCTION PLANT WORKERS DETERMINED BY P-32 POSTLABELING AND ENZYME-LINKED-IMMUNOSORBENT-ASSAY SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article; Proceedings Paper CT CONF ON BIOMONITORING AND SUSCEPTIBILITY MARKERS IN HUMAN CANCER : APPLICATIONS IN MOLECULAR EPIDEMIOLOGY AND RISK ASSESSMENT CY OCT 26-NOV 01, 1991 CL KAILUA KONA, HI SP INT AGCY RES CANC, NATL CTR TOXICOL RES, US EPA, COMMISS EUROPEAN COMMUNITIES, NATL CANC INST AB P-32-Postlabeling analysis and enzyme-linked immunosorbent assay (ELISA) have been used to detect DNA adducts in peripheral blood lymphocytes from primary aluminum production plant workers who were exposed occupationally to a mixture of polycyclic aromatic hydrocarbons (PAHs). Preliminary results reported hem are from a comparative study being performed in two aluminum plants. The levels of aromatic DNA adducts have been determined by the P-32-postlabeling assay in samples collected on two occasions, 1 year apart. PAH-DNA adduct levels have also been determined by competitive ELISA in the second set of DNA samples. The results show the necessity of follow-up biomonitoring studies to detect possible alterations in biological effect induced by changing exposures. The comparison of the results obtained by P-32-postlabeling and ELISA may lead to a better understanding of the power and weaknesses of the two methods applied in these studies. C1 NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BETHESDA,MD 20892. INST CANC RES,HADDOW LABS,SUTTON SM2 5PX,SURREY,ENGLAND. RP SCHOKET, B (reprint author), JOHAN BELA NATL INST PUBL HLTH,DEPT BIOCHEM,GYALI UT 2-6,H-1097 BUDAPEST,HUNGARY. NR 10 TC 24 Z9 25 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 1993 VL 99 BP 307 EP 309 DI 10.2307/3431507 PG 3 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA LC430 UT WOS:A1993LC43000059 PM 8319650 ER PT J AU JOHNSON, ES AF JOHNSON, ES TI IMPORTANT ASPECTS OF THE EVIDENCE FOR TCDD CARCINOGENICITY IN MAN SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article; Proceedings Paper CT CONF ON BIOMONITORING AND SUSCEPTIBILITY MARKERS IN HUMAN CANCER : APPLICATIONS IN MOLECULAR EPIDEMIOLOGY AND RISK ASSESSMENT CY OCT 26-NOV 01, 1991 CL KAILUA KONA, HI SP INT AGCY RES CANC, NATL CTR TOXICOL RES, US EPA, COMMISS EUROPEAN COMMUNITIES, NATL CANC INST ID SOFT-TISSUE SARCOMAS; NON-HODGKINS LYMPHOMA; PHENOXY HERBICIDES; CANCER MORTALITY; CASE-REFERENT; OCCUPATIONAL EXPOSURES; MALIGNANT-LYMPHOMAS; HEALTH-STATUS; WORKERS; CHLOROPHENOLS AB Most of the evidence for the carcinogenicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in humans has centered on whether TCDD causes soft-tissue sarcomas (STS) and malignant lymphomas (ML). Recently, reports from two of the largest occupational cohort studies have become available. A critical reappraisal of these and other recent reports indicates that it is unlikely that TCDD causes malignant lymphomas in humans. For STS, the evidence for an etiologic role for TCDD is not convincing. However, more data and further clarification are needed before a clear and objective evaluation can be made. Factors such as level of exposure, sex, and host susceptibility may be critical determinants of whether cancer occurs; there is evidence from both humans and animals that these factors play a role, and therefore these factors should be considered in future evaluations. There is a serious need to rule out the possibility that observed effects are due to other concomitant exposures. Consideration of the carcinogenic effects of TCDD in animals reveals consistency with the human data and points to other cancers such as those of the thyroid gland and lung, for example, which are more likely candidates for investigating the role of TCDD in their occurrence, while at the same time providing a basis for a better understanding and interpretation of the human data. Them are now sufficient epidemiologic studies in place that will provide a better climate for a definitive evaluation in the near future. RP JOHNSON, ES (reprint author), NIEHS,EPIDEMIOL BRANCH,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 56 TC 29 Z9 29 U1 1 U2 1 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 1993 VL 99 BP 383 EP 390 DI 10.2307/3431512 PG 8 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA LC430 UT WOS:A1993LC43000064 PM 8319655 ER PT J AU DEBLER, EA LIPOVAC, MN LAJTHA, A ZLOKOVIC, BV DUNLOP, DS JACOBSON, AE RICE, KC DECOSTA, B REITH, MEA AF DEBLER, EA LIPOVAC, MN LAJTHA, A ZLOKOVIC, BV DUNLOP, DS JACOBSON, AE RICE, KC DECOSTA, B REITH, MEA TI METAPHIT-INDUCED AUDIOGENIC-SEIZURES IN MICE .1. PHARMACOLOGICAL CHARACTERIZATION SO EPILEPSIA LA English DT Article DE METAPHIT; CONVULSIONS; N-METHYL-D-ASPARTATE; GABA; ANTICONVULSANTS; NEUROLOGIC MODELS; AUDIOGENIC SEIZURES ID GAMMA-AMINOBUTYRIC-ACID; PHENCYCLIDINE-LIKE DRUGS; ANTICONVULSANT DRUGS; INDUCED CONVULSIONS; LABORATORY EVALUATION; ANTIEPILEPTIC DRUGS; NMDA-ANTAGONISTS; RECEPTORS; EPILEPSY; GLYCINE AB Metaphit [an analogue of phencyclidine (PCP) with an acylating isothiocyanate group] induced audiogenic clonic to clonic-tonic seizures in mice exposed to audio stimulation 24 h after metaphit administration. The incidence of seizures was reduced by treatment 30 min before audio stimulation with specific PCP-like compounds [5-methyl-10,11-dihydro-5H-dibenzo(a,d)cyclo-hepten-5,10-imine maleate (MK-801), and PCP itself], competitive N-methyl-D-aspartate antagonists 2-amino-5-phosphonopentanoic acid (AP-5 and NPC-12626), antiepileptic drugs [phenobarbital (PB), phenytoin (PHT)], and gamma-aminobutyric acid (GABA) agonists (muscimol and diazepam). In contrast, when given in conjunction with metaphit, most of these drugs were ineffective in protecting animals from audiogenic seizures 24 h later. Only compounds with long half-lives (t1/2) such as MK-801, PB, and PHT had a protective effect. High-performance liquid chromatography (HPLC) determination of [H-3]MK-801 showed its long-term presence in the brain after intraperitoneal (i.p.) administration of [H-3]MK-801. Audiogenic seizures observed 24 h after metaphit administration were potentiated by administration of the GABA antagonist picrotoxin 15 min before audio stimulation, and picrotoxin-induced spontaneous seizures were enhanced by pretreatment (24 h earlier) with a dose of metaphit that in itself did not produce spontaneous seizures at the time of the picrotoxin test. Similar observations were made with N-methyl D-aspartic acid (NMDA) instead of picrotoxin. Thus, an interplay exists between excitatory glutaminergic and inhibitory GABAergic circuitries in the metaphit seizure model. C1 NATHAN S KLINE INST,DIV NEUROCHEM,ORANGEBURG,NY. NIDDKD,MED CHEM LAB,BETHESDA,MD. UNIV SO CALIF,SCH MED,LOS ANGELES,CA 90033. FU NIDA NIH HHS [DA 03025] NR 49 TC 17 Z9 17 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD MAR-APR PY 1993 VL 34 IS 2 BP 201 EP 210 DI 10.1111/j.1528-1157.1993.tb02400.x PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA KV517 UT WOS:A1993KV51700001 PM 8384106 ER PT J AU LIPOVAC, MN DEBLER, EA ZLOKOVIC, BV JACOBSON, AE RICE, KC DECOSTA, B SELMECI, G CHI, L REITH, MEA AF LIPOVAC, MN DEBLER, EA ZLOKOVIC, BV JACOBSON, AE RICE, KC DECOSTA, B SELMECI, G CHI, L REITH, MEA TI METAPHIT-INDUCED AUDIOGENIC-SEIZURES IN MICE .2. STUDIES ON N-METHYL-D-ASPARTIC ACID, GABA, AND SODIUM-CHANNEL RECEPTORS AND ON THE DISPOSITION OF METAPHIT IN THE BRAIN SO EPILEPSIA LA English DT Article DE METAPHIT-INDUCED AUDIOGENIC SEIZURES, RECEPTOR SYSTEMS; CONVULSIONS; NEUROLOGIC MODELS; NEUROTRANSMITTERS; N-METHYL-D-ASPARTIC ACID; GABA ID BATRACHOTOXININ-A 20-ALPHA-BENZOATE; MOUSE CEREBRAL-CORTEX; BINDING-SITES; PHENCYCLIDINE RECEPTOR; DOPAMINE UPTAKE; RAT; COMPLEX; ANTICONVULSANT; LIGAND; INHIBITION AB We previously demonstrated that metaphit (a phencyclidine analogue with an acylating isothiocyanate group) induces occurrence of audiogenic seizures in mice exposed to audio stimulation 24 h after metaphit administration. We have studied various receptor systems associated with excitatory and inhibitory networks: sites for competitive and noncompetitive antagonists of the N-methyl D-aspartic acid (NMDA) receptor complex, for [H-3]muscimol on the gamma-aminobutyric acid (GABA) receptor complex, and for [H-3]batrachotoxinin A20-alpha-benzoate on the voltage-dependent sodium channel. Mice were examined for neurochemical changes at 24 h after pretreatment with metaphit, when susceptibility to audiogenic seizures is greatest. Ex vivo receptor binding studies detected no changes; in vivo labeling of the phencyclidine site in the NMDA receptor complex was reduced by 20% in cortical and midbrain regions, A separate group of experiments was aimed at measuring brain levels of metaphit. One minute after retroorbital administration of [H-3]metaphit at a dose sufficient to produce susceptibility to audiogenic seizures 24 h later, the brain level of [H-3]metaphit (determined by high-performance liquid chromatography. HPLC) was 49 pmol/mg tissue; at 1, 4, and 24 h, the level was 12, 6, and 1.4 pmol/mg tissue or muM if metaphit was evenly distributed throughout the brain. Although the observed metaphit concentrations during the first 4 h are high enough to acylate receptors, no firm evidence for acylation was found for most of the examined receptors. Finally, the time course of the brain level of metaphit showing a continuous decrease is entirely different from that of development of the seizure susceptibility, which peaks at 18-24 h. C1 NATHAN S KLINE INST,DIV NEUROCHEM,ORANGEBURG,NY. NIDDKD,MED CHEM LAB,BETHESDA,MD. UNIV SO CALIF,SCH MED,LOS ANGELES,CA 90033. RI Reith, Maarten/A-4601-2008 FU NIDA NIH HHS [DA 03025] NR 41 TC 17 Z9 17 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD MAR-APR PY 1993 VL 34 IS 2 BP 211 EP 219 DI 10.1111/j.1528-1157.1993.tb02401.x PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA KV517 UT WOS:A1993KV51700002 PM 8384107 ER PT J AU WONG, ML SMITH, MA LICINIO, J DOI, SQ WEISS, SRB POST, RM GOLD, PW AF WONG, ML SMITH, MA LICINIO, J DOI, SQ WEISS, SRB POST, RM GOLD, PW TI DIFFERENTIAL-EFFECTS OF KINDLED AND ELECTRICALLY INDUCED SEIZURES ON A GLUTAMATE RECEPTOR (GLUR1) GENE-EXPRESSION SO EPILEPSY RESEARCH LA English DT Article DE MODE OF SEIZURE INDUCTION; GLUTAMATE RECEPTOR GENE EXPRESSION ID HIPPOCAMPAL SYNAPTIC-MEMBRANES; FUNCTIONAL EXPRESSION; MESSENGER-RNA; KAINIC ACID; RAT-BRAIN; MECHANISMS; ASPARTATE; INCREASE; CLONING; KAINATE AB To address the question of whether the mode of seizure induction contributes to the effects of seizures on glutamate receptor gene expression, we examined rat dorsal hippocampal slides by in situ hybridization after kindling by electrical stimulation of the amygdala. or after electrically induced tonic-clonic seizures. Levels of a glutamate receptor subtype (GluR1) mRNA were analyzed at three periods post kindled seizures and found to be decreased only in brains that were obtained 24 h after the last kindled seizure. This downregulation of GluR1 mRNA was transient and was observed only in animals that had behavioral manifestations after being electrically stimulated. It is probable that maintenance of the kindled state cannot be explained by a long-lasting change in GluR1 gene expression. Repeated electroshock-induced seizures increased GluR1 mRNA levels in the hippocampus. Our results show that mode of induction is an important determinant of the effects of seizures on the levels of expression of a glutamate receptor gene. C1 NIMH,CLIN NEUROENDOCRINOL BRANCH,BETHESDA,MD 20892. NIMH,BIOL PSYCHIAT BRANCH,BETHESDA,MD 20892. NIDDKD,METAB DIS BRANCH,BETHESDA,MD 20892. RI Wong, Ma-Li/D-7903-2011; Licinio, Julio/L-4244-2013 OI Licinio, Julio/0000-0001-6905-5884 NR 33 TC 29 Z9 29 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-1211 J9 EPILEPSY RES JI Epilepsy Res. PD MAR PY 1993 VL 14 IS 3 BP 221 EP 227 DI 10.1016/0920-1211(93)90046-A PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA KY765 UT WOS:A1993KY76500004 PM 8504792 ER PT J AU ALMOUZNI, G WOLFFE, AP AF ALMOUZNI, G WOLFFE, AP TI NUCLEAR ASSEMBLY, STRUCTURE, AND FUNCTION - THE USE OF XENOPUS INVITRO SYSTEMS SO EXPERIMENTAL CELL RESEARCH LA English DT Review ID CELL-FREE SYSTEM; RNA-POLYMERASE-III; GENE-TRANSCRIPTION COMPLEX; DNA-REPLICATION INVITRO; INTERNAL CONTROL REGION; MYC PROTO-ONCOGENE; LAEVIS OOCYTES; EGG EXTRACTS; DEVELOPMENTAL REGULATION; ESTROGEN-RECEPTOR C1 NICHHD,MOLEC EMBRYOL LAB,BLDG 6,ROOM B1A-13,BETHESDA,MD 20892. NR 184 TC 95 Z9 97 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD MAR PY 1993 VL 205 IS 1 BP 1 EP 15 DI 10.1006/excr.1993.1051 PG 15 WC Oncology; Cell Biology SC Oncology; Cell Biology GA KT147 UT WOS:A1993KT14700001 PM 8453983 ER PT J AU WARBURG, A SCHNEIDER, I AF WARBURG, A SCHNEIDER, I TI INVITRO CULTURE OF THE MOSQUITO STAGES OF PLASMODIUM-FALCIPARUM SO EXPERIMENTAL PARASITOLOGY LA English DT Article DE BASEMENT MEMBRANE; MATRIGEL; OOCYSTS; OOKINETES; PLASMODIUM-FALCIPARUM; PLASMODIUM-GALLINACEUM; SPOROGONY; SPOROZOITES ID MALARIA PARASITES; DROSOPHILA C1 WALTER REED ARMY INST RES,DEPT ENTOMOL,WASHINGTON,DC 20307. RP WARBURG, A (reprint author), NIAID,MALARIA RES LAB,BLDG 4,ROOM 126,BETHESDA,MD 20892, USA. NR 21 TC 33 Z9 34 U1 0 U2 3 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0014-4894 J9 EXP PARASITOL JI Exp. Parasitol. PD MAR PY 1993 VL 76 IS 2 BP 121 EP 126 DI 10.1006/expr.1993.1014 PG 6 WC Parasitology SC Parasitology GA KU483 UT WOS:A1993KU48300003 PM 8454020 ER PT J AU RABIN, R GORDON, SL LYMN, RW TODD, PW FREY, MAB SULZMAN, FM AF RABIN, R GORDON, SL LYMN, RW TODD, PW FREY, MAB SULZMAN, FM TI EFFECTS OF SPACEFLIGHT ON THE MUSCULOSKELETAL SYSTEM - NIH AND NASA FUTURE-DIRECTIONS SO FASEB JOURNAL LA English DT Article ID MYOSIN HEAVY-CHAIN; MYOTENDINOUS JUNCTION; MUSCLE; EXPRESSION; DYSTROPHIN; ATROPHY; BONE AB ''The Effects of Space Travel on the Musculoskeletal System,'' a workshop held at the National Institutes of Health on October 3 and 4, 1990, was sponsored jointly by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) and the National Aeronautics and Space Administration (NASA) Attended by 80 invitees, it was chaired by Michael F. Holick, Boston University School of Medicine, and Kenneth M. Baldwin, University of California at Irvine. Participants reviewed the normal function and structure of bone and muscle, as well as independent and interactive responses of these tissues to activity and disuse on Earth and in the microgravity environment of space. They then focused on those future directions of research, summarized in this report, that are relevant to the missions and interests of both agencies. A comprehensive review of the presentations is available from NIAMS.2 C1 NIAMSD,BETHESDA,MD 20892. LOCKHEED ENGN & SCI CO,DEPT LIFE SUPPORT,WASHINGTON,DC 20024. NASA,DIV LIFE SCI,WASHINGTON,DC 20546. UNIV COLORADO,DEPT CHEM ENGN,BOULDER,CO 80309. RP RABIN, R (reprint author), CTR SPACE & ADV TECHNOL,9302 LEE HWY,STE 400,FAIRFAX,VA 22031, USA. NR 26 TC 15 Z9 15 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR PY 1993 VL 7 IS 5 BP 396 EP 398 PG 3 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA KV351 UT WOS:A1993KV35100002 PM 8462780 ER PT J AU KOLENBRANDER, PE GANESHKUMAR, N CASSELS, FJ HUGHES, CV AF KOLENBRANDER, PE GANESHKUMAR, N CASSELS, FJ HUGHES, CV TI COAGGREGATION - SPECIFIC ADHERENCE AMONG HUMAN ORAL PLAQUE BACTERIA SO FASEB JOURNAL LA English DT Review DE COAGGREGATION; DENTAL PLAQUE; ADHESINS RECEPTORS; ADHERENCE ID PORPHYROMONAS BACTEROIDES GINGIVALIS; FIMBRIA-ASSOCIATED ADHESINS; STREPTOCOCCUS-SANGUIS; FUSOBACTERIUM-NUCLEATUM; ACTINOMYCES-VISCOSUS; CELL-SURFACE; FILAMENTOUS MICROORGANISMS; MONOCLONAL-ANTIBODIES; NUCLEOTIDE-SEQUENCE; APATITIC SURFACES AB Nearly all human oral bacteria exhibit coaggregation, cell-to-cell recognition of genetically distinct cell types. Clumps or coaggregates composed of the two kinds of cells are formed immediately upon mixing two partner cell types. Members of all 18 genera tested exhibit lactose-reversible coaggregation. Many of these interactions appear to be mediated by a lectin on one cell type that interacts with a complementary carbohydrate receptor on the other cell type. A lactose-sensitive adhesin has, been isolated from Prevotella loescheii PK1295, and it exhibits the adherence properties observed with whole cells. Other adhesins have been identified and the genes for some of them have been cloned and sequenced. One Streptococcus sanguis adhesin is a lipoprotein that appears to have a dual function of recognizing both a bacterial carbohydrate receptor and a receptor in human saliva. Carbohydrate receptors for some adhesins have been purified from five oral streptococci, and they specifically block the coaggregations with the streptococcal partners that express the complementary adhesins. Coaggregation offers an explanation for the temporally related accretion of dental plaque and bacterial recognition of mucosal surfaces. Early colonizers of the tooth surface coaggregate with each other and late colonizers of the tooth surface coaggregate with each other, but with few exceptions, early colonizers do not recognize late colonizers. Furthermore, bacteria that colonize mucosal surfaces coaggregate with each other, indicating the high degree of specificity of coaggregation in the oral bacterial population. RP KOLENBRANDER, PE (reprint author), NIDR, MICROBIAL ECOL LAB, BLDG 30, ROOM 310, 9000 ROCKVILLE PIKE, BETHESDA, MD 20892 USA. RI Hughes, Christopher/E-1438-2014 NR 57 TC 96 Z9 98 U1 1 U2 12 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD MAR PY 1993 VL 7 IS 5 BP 406 EP 413 PG 8 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA KV351 UT WOS:A1993KV35100004 PM 8462782 ER PT J AU KIM, RY WISTOW, GJ AF KIM, RY WISTOW, GJ TI EXPRESSION OF THE DUCK ALPHA-ENOLASE/TAU-CRYSTALLIN GENE IN TRANSGENIC MICE SO FASEB JOURNAL LA English DT Article DE LENS; CRYSTALLIN; ENOLASE; EVOLUTION ID LENS CRYSTALLINS; TAU-CRYSTALLIN; PROTEIN SUPERFAMILY; STRUCTURAL PROTEIN; GAMMA-CRYSTALLIN; TURTLE LENS; RECRUITMENT; EVOLUTION; ENZYME; PURIFICATION AB In many vertebrates, metabolic enzymes have been directly recruited to an additional structural role as crystallins in the eye lens. In some species the glycolytic enzyme alpha-enolase. (AlphaENO) attains high concentrations in the lens, as tau-crystallin (tauCRY). A line of transgenic mice was constructed containing the entire duck alphaENO/tauCRY gene with 5'- and 3-flanking regions and all introns. Full-sized duck alphaENO mRNA was expressed in the transgenic mice with the same pattern as the endogenous mouse alphaENO isozyme. Although there was no evidence for tissue preference, the concentration of enolase increased markedly in transgenic lens as well as in other tissues. In spite of this, transgenic lenses were transparent and the animals were normal in appearance. The increase in enolase levels in the transgenic lens mimics the stepped increase that might occur in the early stages of enzyme crystallin recruitment. These results demonstrate that lens transparency is sufficiently robust to be refractory to some increase in metabolic enzyme concentration without the need for compensatory adaptation. C1 NEI,MOLEC & DEV BIOL LAB,MOLEC STRUCT & FUNCT SECT,BLDG 6,RM 222,BETHESDA,MD 20892. NR 35 TC 8 Z9 8 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 PY 1993 VL 7 IS 5 BP 464 EP 469 PG 6 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA KV351 UT WOS:A1993KV35100011 PM 8462788 ER PT J AU SEGARS, JH WENTZ, AC AF SEGARS, JH WENTZ, AC TI A NEW HORMONE, NEW CONCEPTS, AND A NEW LEVEL OF COMPLEXITY SO FERTILITY AND STERILITY LA English DT Editorial Material DE HORMONE RECEPTORS; HETERODIMER; 9-CIS-RETINOIC ACID ID RECEPTOR SUPERFAMILY C1 NORTHWESTERN UNIV,SCH MED,DEPT OBSTET & GYNECOL,CHICAGO,IL 60611. RP SEGARS, JH (reprint author), NICHHD,DEV ENDOCRINOL BRANCH,BLDG 6,ROOM 2A11,BETHESDA,MD 20892, USA. NR 12 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC REPRODUCTIVE MEDICINE PI BIRMINGHAM PA 1209 MONTGOMERY HIGHWAY, BIRMINGHAM, AL 35216-2809 SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD MAR PY 1993 VL 59 IS 3 BP 499 EP 501 PG 3 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA KQ171 UT WOS:A1993KQ17100002 PM 8384574 ER PT J AU CAO, GH ALESSIO, HM CUTLER, RG AF CAO, GH ALESSIO, HM CUTLER, RG TI OXYGEN-RADICAL ABSORBENCY CAPACITY ASSAY FOR ANTIOXIDANTS SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE OXYGEN RADICALS; ANTIOXIDANT; ALPHA-TOCOPHEROL; BETA-CAROTENE; VITAMIN-C; URIC ACID; BILIRUBIN; FREE RADICAL ID HUMAN-BLOOD PLASMA; FLUORESCENCE-BASED ASSAY; VITAMIN-E; PEROXIDATION; MORTALITY; PROTEINS AB A relatively simple but sensitive and reliable method of quantitating the oxygen-radical absorbing capacity (ORAC) of antioxidants in serum using a few mul is described. In this assay system, beta-phycoerythrin (beta-PE) is used as an indicator protein, 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH) as a peroxyl radical generator, and 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (Trolox, a water-soluble vitamin E analogue) as a control standard. Results are expressed as ORAC units, where 1 OPAC unit equals the net protection produced by 1 muM Trolox. The uniqueness of this assay is that total antioxidant capacity of a sample is estimated by taking the oxidation reaction to completion. At this point all of the nonprotein antioxidants (which include alpha-tocopherol, vitamin C, beta-carotene, uric acid, and bilirubin) and most of the albumin in the sample are oxidized by the peroxyl radical. Results are quantified by measuring the protection produced by antioxidants. This solves many problems associated with kinetics or lag-time measurements. A linear correlation of ORAC value with concentration of serum, Trolox, vitamin C, uric acid, and bovine albumin is demonstrated. The coefficient of variation within a run is found to be about 2% and from run to run about 5%. Trolox, alpha-tocopherol, vitamin C, beta-carotene, uric acid, and bilirubin completely protect beta-PE from oxidation, while bovine albumin protects beta-PE only partially. On a molar basis, the relative peroxyl radical absorbance capacity of Trolox, alpha-tocopherol acid succinate, uric acid, bilirubin, and vitamin C is 1:1:0.92:0.84:0.52. Bovine albumin per unit weight has a lower peroxyl absorbing capacity than these antioxidants. However, the serum protein fraction, containing some lipid-soluble antioxidants, represents the major contributor to the ORAC value found in whole serum. The minimum amount of vitamin C and uric acid which could still be detectable when added to a serum supernatant fraction is 1.5 mug and 0.59 mug, respectively, which account for about 1% of the total ORAC value of the serum supernatant fraction. C1 NIA,CTR GERONTOL,4940 EASTERN AVE,BALTIMORE,MD 21224. MIAMI UNIV,DEPT PHYS EDUC,HLTH & SPORT STUDIES,OXFORD,OH 45056. NR 14 TC 914 Z9 971 U1 6 U2 142 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD MAR PY 1993 VL 14 IS 3 BP 303 EP 311 DI 10.1016/0891-5849(93)90027-R PG 9 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA KN417 UT WOS:A1993KN41700008 PM 8458588 ER PT J AU MISHRA, L MISHRA, BB HARRIS, M BAYLESS, TM MUCHMORE, AV AF MISHRA, L MISHRA, BB HARRIS, M BAYLESS, TM MUCHMORE, AV TI INVITRO-CELL AGGREGATION AND CELL-ADHESION MOLECULES IN CROHNS-DISEASE SO GASTROENTEROLOGY LA English DT Article ID HYPERSENSITIVITY GRANULOMA-FORMATION; INFLAMMATORY BOWEL-DISEASE; SUPPRESSOR EFFECTOR FACTOR; MANSONI EGGS INVITRO; SCHISTOSOMA-MANSONI; IMMUNE-RESPONSE; T-CELLS; MODULATION; ICAM-1; LFA-1 C1 NCI,METAB BRANCH,BLDG 10,ROOM 6B05,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,SCH MED,DEPT GASTROENTEROL,BALTIMORE,MD 21205. NR 37 TC 16 Z9 16 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 1993 VL 104 IS 3 BP 772 EP 779 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA KP448 UT WOS:A1993KP44800012 PM 7680015 ER PT J AU TSUI, FWL TSUI, HW MOK, S MLINARIC, I COPELAND, NG GILBERT, DJ JENKINS, NA SIMINOVITCH, KA AF TSUI, FWL TSUI, HW MOK, S MLINARIC, I COPELAND, NG GILBERT, DJ JENKINS, NA SIMINOVITCH, KA TI MOLECULAR CHARACTERIZATION AND MAPPING OF MURINE GENES ENCODING 3 MEMBERS OF THE STEFIN FAMILY OF CYSTEINE PROTEINASE-INHIBITORS SO GENOMICS LA English DT Article ID AMINO-ACID-SEQUENCE; RAY CRYSTAL-STRUCTURE; HUMAN WHOLE SALIVA; CHICKEN EGG-WHITE; HUMAN CYSTATIN-C; VIABLE MOTHEATEN; DNA-SEQUENCES; HUMAN-LIVER; EXPRESSION; MOUSE C1 UNIV TORONTO,TORONTO HOSP,DEPT MED & IMMUNOL,WESTERN DIV,TORONTO M5S 1A1,ONTARIO,CANADA. UNIV TORONTO,TORONTO HOSP,DEPT MOLEC & MED GENET,WESTERN DIV,TORONTO M5S 1A1,ONTARIO,CANADA. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. RI Siminovitch, Katherine/K-1475-2013 FU PHS HHS [R01-C0-74101] NR 46 TC 26 Z9 29 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD MAR PY 1993 VL 15 IS 3 BP 507 EP 514 DI 10.1006/geno.1993.1101 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA KU531 UT WOS:A1993KU53100006 PM 8468045 ER PT J AU HUNTER, KE SPORN, MB DAVIES, AM AF HUNTER, KE SPORN, MB DAVIES, AM TI TRANSFORMING GROWTH FACTOR-BETA-S INHIBIT MITOGEN-STIMULATED PROLIFERATION OF ASTROCYTES SO GLIA LA English DT Article DE GLIAL CELLS; CELL DIVISION; EXTRACELLULAR MATRIX ID CENTRAL NERVOUS-SYSTEM; CELL-PROLIFERATION; EXTRACELLULAR-MATRIX; EXPRESSION PATTERNS; BRAIN INJURY; MOUSE EMBRYO; GLIAL-CELLS; TGF BETA-1; FACTOR-BETA-1; EMBRYOGENESIS AB We have studied the influence of three members of the transforming growth factor-beta (TGF-beta) family of multifunctional growth factors on the proliferation of cultured astrocytes isolated from newborn mouse cerebral cortex. Although TGF-betas 1, 2, and 3 cause only a small reduction in the low level of astrocyte proliferation occurring in chemically defined medium, they each inhibit the effects of five astrocyte mitogens (bFGF, EGF, PDGF, IL-1alpha, and IL-2). Inhibition is observed when astrocytes are exposed to mitogen and TGF-beta at the same time and when they are exposed to TGF-beta prior to, and separately from, mitogen. This latter effect appears to be due to the binding of TGF-betas to astrocyte-secreted extracellular matrix. These findings raise the possibility that TGF-beta may co-operate with other growth factors to control astrocyte proliferation in vivo. C1 ST GEORGE HOSP,SCH MED,DEPT ANAT,LONDON SW17 0RE,ENGLAND. NCI,CHEMOPREVENT LAB,BETHESDA,MD 20892. RI Davies, Alun/A-4334-2010 OI Davies, Alun/0000-0001-5841-8176 NR 52 TC 94 Z9 95 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0894-1491 J9 GLIA JI Glia PD MAR PY 1993 VL 7 IS 3 BP 203 EP 211 DI 10.1002/glia.440070303 PG 9 WC Neurosciences SC Neurosciences & Neurology GA KN911 UT WOS:A1993KN91100002 PM 8454307 ER PT J AU OOI, GT TSENG, LYH RECHLER, MM AF OOI, GT TSENG, LYH RECHLER, MM TI TRANSCRIPTIONAL REGULATION OF THE RAT IGFBP-1 AND IGFBP-2 GENES SO GROWTH REGULATION LA English DT Article; Proceedings Paper CT 2ND INTERNATIONAL WORKSHOP ON IGF ( INSULIN-LIKE GROWTH FACTOR ) BINDING PROTEINS CY AUG 27-30, 1992 CL OPIO, FRANCE SP NOVO NORDISK, GENETECH, FDN GROWTH SCI JAPAN, KABI PHARM, SERONO FRANCE, LILLY FRANCE, CELTRIX PHARM, SONOFI WINTHROP, FUJISAWA PHARM, CIBA GEIGY ID FACTOR-BINDING-PROTEIN; SERUM LEVELS; AMNIOTIC-FLUID; RADIOIMMUNOASSAY RP OOI, GT (reprint author), NIDDKD,MOLEC & CELLULAR ENDOCRINOL BRANCH,GROWTH & DEV SECT,BLDG 10,ROOM 8D14,BETHESDA,MD 20892, USA. NR 20 TC 7 Z9 7 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH, MIDLOTHIAN, SCOTLAND EH1 3AF SN 0956-523X J9 GROWTH REGULAT JI Growth Regul. PD MAR PY 1993 VL 3 IS 1 BP 14 EP 17 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA KZ481 UT WOS:A1993KZ48100006 PM 7683516 ER PT J AU BACH, LA THOTAKURA, NR RECHLER, MM AF BACH, LA THOTAKURA, NR RECHLER, MM TI HUMAN INSULIN-LIKE GROWTH-FACTOR BINDING PROTEIN-6 IS O-GLYCOSYLATED SO GROWTH REGULATION LA English DT Article; Proceedings Paper CT 2ND INTERNATIONAL WORKSHOP ON IGF ( INSULIN-LIKE GROWTH FACTOR ) BINDING PROTEINS CY AUG 27-30, 1992 CL OPIO, FRANCE SP NOVO NORDISK, GENETECH, FDN GROWTH SCI JAPAN, KABI PHARM, SERONO FRANCE, LILLY FRANCE, CELTRIX PHARM, SONOFI WINTHROP, FUJISAWA PHARM, CIBA GEIGY AB Insulin-like growth factor binding protein-6 (IGFBP-6) is found in serum, cerebrospinal fluid and conditioned media from human fibroblasts. It has a marked preferential binding affinity for IGF-II over IGF-I. The present study demonstrates that IGFBP-6 purified from human cerebrospinal fluid is O-glycosylated but not N-glycosylated. Enzymatic deglycosylation does not alter the high affinity of IGFBP-6 for IGF-II (Ka 4.4+/-2.2 x 10(11) M-1) or its preference for IGF-II over IGF-I. The effect of glycosylation of IGFBP-6 on its secretion, in vivo stability or localization remains to be determined. C1 NIDDKD,MOLEC & CELLULAR ENDOCRINOL BRANCH,MOLEC REGULAT & NEUROENDOCRINOL SECT,BETHESDA,MD 20892. RP BACH, LA (reprint author), NIDDKD,GROWTH & DEV SECT,BLDG 10,RM 8D14,BETHESDA,MD 20892, USA. OI Bach, Leon/0000-0002-9062-1518 NR 18 TC 11 Z9 11 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH, MIDLOTHIAN, SCOTLAND EH1 3AF SN 0956-523X J9 GROWTH REGULAT JI Growth Regul. PD MAR PY 1993 VL 3 IS 1 BP 59 EP 62 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA KZ481 UT WOS:A1993KZ48100021 PM 7683533 ER PT J AU LEROITH, D ADAMO, ML SHEMER, J LANAU, F SHENORR, Z YARON, A ROBERTS, CT CLEMMONS, DR SHEIKH, MS SHAO, ZM CHEN, JC FONTANA, J AF LEROITH, D ADAMO, ML SHEMER, J LANAU, F SHENORR, Z YARON, A ROBERTS, CT CLEMMONS, DR SHEIKH, MS SHAO, ZM CHEN, JC FONTANA, J TI RETINOIC ACID INHIBITS GROWTH OF BREAST-CANCER CELL-LINES - THE ROLE OF INSULIN-LIKE GROWTH-FACTOR BINDING-PROTEINS SO GROWTH REGULATION LA English DT Article; Proceedings Paper CT 2ND INTERNATIONAL WORKSHOP ON IGF ( INSULIN-LIKE GROWTH FACTOR ) BINDING PROTEINS CY AUG 27-30, 1992 CL OPIO, FRANCE SP NOVO NORDISK, GENETECH, FDN GROWTH SCI JAPAN, KABI PHARM, SERONO FRANCE, LILLY FRANCE, CELTRIX PHARM, SONOFI WINTHROP, FUJISAWA PHARM, CIBA GEIGY ID MESSENGER-RNA EXPRESSION; RECEPTOR; IDENTIFICATION; PROLIFERATION C1 UNIV N CAROLINA,SCH MED,DEPT MED,CHAPEL HILL,NC 27514. UNIV MARYLAND,DEPT MED,BALTIMORE,MD 21201. UNIV MARYLAND,CTR CANC,BALTIMORE,MD 21201. VET ADM MED CTR,BALTIMORE,MD 21218. RP LEROITH, D (reprint author), NIDDK,DIABET BRANCH,BETHESDA,MD 20892, USA. OI Fontana, Joseph/0000-0003-3829-3358; Roberts, Charles/0000-0003-1756-5772 NR 21 TC 8 Z9 8 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH, MIDLOTHIAN, SCOTLAND EH1 3AF SN 0956-523X J9 GROWTH REGULAT JI Growth Regul. PD MAR PY 1993 VL 3 IS 1 BP 78 EP 80 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA KZ481 UT WOS:A1993KZ48100027 PM 7683539 ER PT J AU FLORA, JA LEFEBVRE, RC MURRAY, DM STONE, EJ ASSAF, A MITTELMARK, MB FINNEGAN, JR AF FLORA, JA LEFEBVRE, RC MURRAY, DM STONE, EJ ASSAF, A MITTELMARK, MB FINNEGAN, JR TI A COMMUNITY EDUCATION MONITORING-SYSTEM - METHODS FROM THE STANFORD-5-CITY-PROJECT, THE MINNESOTA-HEART-HEALTH-PROGRAM AND THE PAWTUCKET-HEART-HEALTH PROGRAM AND THE PAWTUCKET-HEART-HEALTH PROGRAM SO HEALTH EDUCATION RESEARCH LA English DT Article ID STANFORD 5-CITY PROJECT; CARDIOVASCULAR-DISEASE; WIDE PREVENTION; STRATEGIES; PROMOTION; DESIGN AB Understanding the process of behavior change interventions is critical to achieving campaign effectiveness and successful program replication. The present article presents a community education monitoring system (CEMS) using data from the Stanford Five-City Project (FCP), the Minnesota Heart Health Program (MHHP) and the Pawtucket Heart Health Program (PHHP). CEMS records the number and type of intervention activities, outcome objectives, targets of change (individual, organizational or environmental), channel(s) of dissemination and proportion of programs funded by the community. These data illustrate (1) the application of theory for each project, (2) data-based program administration, (3) feedback for revising programs and (4) type of reach or 'dose' information obtained from intervention monitoring. Process evaluations such as CEMS provide critical links between field realities and evaluation outcomes. This type of evaluation develops standards for measuring program reach and allows comparisons with other programs. CEMS also illustrates how programs enact theory. Validation studies are critical to the continued successful use of CEMS. The first step, however, is to develop a uniform way of describing complex multichannel behavior change programs. CEMS in a refined form should prove invaluable to health promotion program planners whether in research or service settings. C1 PROSPECT ASSOCIATES,ROCKVILLE,MD 20852. WAKE FOREST UNIV,WINSTON SALEM,NC 27103. BROWN UNIV,PROVIDENCE,RI 02912. NHLBI,BETHESDA,MD 20892. UNIV MINNESOTA,MINNEAPOLIS,MN 55455. RP FLORA, JA (reprint author), STANFORD UNIV,STANFORD,CA 94305, USA. FU NHLBI NIH HHS [HL 21906, HL 23629, HL 25523] NR 35 TC 21 Z9 21 U1 2 U2 6 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0268-1153 J9 HEALTH EDUC RES JI Health Educ. Res. PD MAR PY 1993 VL 8 IS 1 BP 81 EP 95 DI 10.1093/her/8.1.81 PG 15 WC Education & Educational Research; Public, Environmental & Occupational Health SC Education & Educational Research; Public, Environmental & Occupational Health GA KT329 UT WOS:A1993KT32900008 PM 11067188 ER PT J AU STRECHER, VJ BAUMAN, KE BOAT, B FOWLER, MG GREENBERG, R STEDMAN, H AF STRECHER, VJ BAUMAN, KE BOAT, B FOWLER, MG GREENBERG, R STEDMAN, H TI THE ROLE OF OUTCOME AND EFFICACY EXPECTATIONS IN AN INTERVENTION DESIGNED TO REDUCE INFANTS EXPOSURE TO ENVIRONMENTAL TOBACCO-SMOKE SO HEALTH EDUCATION RESEARCH LA English DT Note ID SELF-EFFICACY; BEHAVIOR AB The purpose of this paper is to examine the role of a theoretical framework in an intervention program designed to reduce infants' exposure to environmental tobacco smoke (ETS). The content of a nurse-based intervention focused on two psychosocial constructs: expectations of outcomes which may result from behaviors associated with ETS exposure and expectations of self-efficacy associated with the mother's ability to engage in these behaviors. This study found both constructs predictive of change in, and maintenance of, ETS exposure control. In particular, mothers reporting both low outcome and low efficacy expectations tended to have infants with the highest levels of ETS exposure. We also found that our intervention was effective in changing outcome and efficacy expectations in the desired direction. These findings suggest that outcome and efficacy expectations are changeable, and, therefore, represent important targets in future programs aimed at controlling ETS exposure. C1 TULANE UNIV,NEW ORLEANS,LA 70112. NIH,BETHESDA,MD 20892. RP STRECHER, VJ (reprint author), UNIV N CAROLINA,SCH PUBL HLTH,DEPT HLTH BEHAV & HLTH EDUC,CHAPEL HILL,NC 27599, USA. NR 12 TC 24 Z9 24 U1 0 U2 2 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0268-1153 J9 HEALTH EDUC RES JI Health Educ. Res. PD MAR PY 1993 VL 8 IS 1 BP 137 EP 143 DI 10.1093/her/8.1.137 PG 7 WC Education & Educational Research; Public, Environmental & Occupational Health SC Education & Educational Research; Public, Environmental & Occupational Health GA KT329 UT WOS:A1993KT32900012 PM 11067181 ER PT J AU LONGO, DL AF LONGO, DL TI IS ANYTHING BETTER THAN MOPP SO HEMATOLOGICAL ONCOLOGY LA English DT Editorial Material ID ADVANCED HODGKINS-DISEASE; COMBINATION CHEMOTHERAPY; SURVIVAL; THERAPY; ABVD; EXPERIENCE; SUPERIOR; RELAPSE; TRIAL; RISK RP LONGO, DL (reprint author), NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,FREDERICK,MD 21701, USA. NR 24 TC 1 Z9 1 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0278-0232 J9 HEMATOL ONCOL JI Hematol. Oncol. PD MAR-APR PY 1993 VL 11 IS 2 BP 65 EP 71 DI 10.1002/hon.2900110203 PG 7 WC Oncology; Hematology SC Oncology; Hematology GA MB903 UT WOS:A1993MB90300001 PM 8406376 ER PT J AU IVASCHENKO, TE BARANOV, VS DEAN, M AF IVASCHENKO, TE BARANOV, VS DEAN, M TI 2 NEW MUTATIONS DETECTED BY SINGLE-STRAND CONFORMATION POLYMORPHISM ANALYSIS IN CYSTIC-FIBROSIS FROM RUSSIA SO HUMAN GENETICS LA English DT Article ID CFTR GENE; DELETION; IDENTIFICATION; FREQUENCY AB Single-strand conformation polymorphism (SSCP) analysis followed by direct sequencing of exons containing ATP-binding domains of the cystic fibrosis transmembrane conductance regulator (CFFR) gene was performed on 80 Russian DNA samples. Two new alterations - S1196X (exon 19) and W1282R (exon 20) - and two novel polymorphisms - 1525-61 (intron 9) and 1716+12 T-C (intron 10) - were identified. Mutation S1196X changes a TCA codon to TGA and destroys an EcoRI site. Alteration W1282R results from a T-to-C change at position 3976. It was found in one Russian patient and creates an AciI site; however, it is unclear whether this is a disease-causing mutation or a polymorphism. Polymorphism 1525-61 results from an A-to-G change. Alteration 1716+12 T-C was found in a Moldovian patient and creates a new MaeII site. It is not known whether this alteration affects the splicing of the mRNA. The previously described A4002G polymorphism was encountered in approximately 9% of Russian CF chromosomes. In addition, we have found the previously described 3732delA mutation in 7 CF chromosomes, making it the second (after DELTAF508) most frequent mutation in the Russian population. C1 NCI,VIRAL CARCINOGENESIS LAB,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. ACAD MED SCI,INST OBSTET & GYNECOL,ST PETERSBURG,RUSSIA. RI Dean, Michael/G-8172-2012 OI Dean, Michael/0000-0003-2234-0631 NR 15 TC 11 Z9 11 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD MAR PY 1993 VL 91 IS 1 BP 63 EP 65 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA KR947 UT WOS:A1993KR94700013 PM 7681034 ER PT J AU TRAUPE, H VETTER, U HAPPLE, R FISHER, LW CREMERS, FPM LANDY, SJ PANKAU, R ROPERS, HH AF TRAUPE, H VETTER, U HAPPLE, R FISHER, LW CREMERS, FPM LANDY, SJ PANKAU, R ROPERS, HH TI EXCLUSION OF THE BIGLYCAN (BGN) GENE AS A CANDIDATE GENE FOR THE HAPPLE SYNDROME, EMPLOYING AN INTRAGENIC SINGLE-STRAND CONFORMATIONAL POLYMORPHISM SO HUMAN GENETICS LA English DT Letter ID DOMINANT CHONDRODYSPLASIA PUNCTATA; LOCALIZATION; DECORIN; REGION; MOUSE C1 UNIV HOSP NIJMEGEN,DEPT HUMAN GENET,6500 HB NIJMEGEN,NETHERLANDS. UNIV FRANKFURT,INST PEDIAT,W-6000 FRANKFURT,GERMANY. UNIV MARBURG,INST DERMATOL,W-3550 MARBURG,GERMANY. NIDR,BONE RES BRANCH,BETHESDA,MD 20892. ST MARYS HOSP,DEPT MED GENET,MANCHESTER M13 0JH,LANCS,ENGLAND. UNIV KIEL,INST PADIATRIE,W-2300 KIEL 1,GERMANY. RI Cremers, Frans/A-5625-2014 NR 12 TC 4 Z9 4 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD MAR PY 1993 VL 91 IS 1 BP 89 EP 90 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA KR947 UT WOS:A1993KR94700022 PM 8454295 ER PT J AU MAEKAWA, M SUDO, K KITAJIMA, M MATSUURA, Y LI, SSL KANNO, T AF MAEKAWA, M SUDO, K KITAJIMA, M MATSUURA, Y LI, SSL KANNO, T TI DETECTION AND CHARACTERIZATION OF NEW GENETIC MUTATIONS IN INDIVIDUALS HETEROZYGOUS FOR LACTATE DEHYDROGENASE-B(H) DEFICIENCY USING DNA CONFORMATION POLYMORPHISM ANALYSIS AND SILVER STAINING SO HUMAN GENETICS LA English DT Article ID AMINO-ACID-SEQUENCE; A MUSCLE; B HEART; POINT MUTATIONS; C TESTIS; MOUSE; SUBUNIT; AMPLIFICATION; ORGANIZATION; POLYMERASE AB Human lactate dehydrogenase (LDH) - B(H) mutant genes were analyzed by polymerase chain reaction (PCR) and DNA conformation polymorphism. We used polyacrylamide gradient gel and silver staining procedures for DCP analysis, and observed abnormal migration patterns in individuals heterozygous for the LDH-B deficiency. Subsequent sequence determination of the mutant alleles consistently resulted in detection of three single base substitutions (transversions), viz., a C to A at residue ''35'' (GCG, Ala-->GAG, Glu), a T to G at residue ''172'' (TTT, Phe-->GTT, Val), and an A to T at residue ''176'' (ATG, Met-->TTG, Leu). Furthermore, mismatched PCR or amplification refractory mutation system was developed for the rapid screening and confirmation of these mutations. These amino acid replacements may cause conformational changes in neighboring residues; this probably affects the active site arrangement and results in the loss of enzyme activity. C1 JIKEI UNIV, DAISAN HOSP, SCH MED, DEPT LAB MED, KOMAE 201, JAPAN. FUJITSU LTD, MINATO KU, TOKYO 105, JAPAN. NIEHS, GENET LAB, RES TRIANGLE PK, NC 27709 USA. RP MAEKAWA, M (reprint author), HAMAMATSU UNIV SCH MED, DEPT LAB MED, HANDA CHO 3600, HAMAMATSU, SHIZUOKA 43131, JAPAN. NR 29 TC 17 Z9 18 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD MAR PY 1993 VL 91 IS 2 BP 163 EP 168 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA KV912 UT WOS:A1993KV91200010 PM 8462975 ER PT J AU WILL, K STUHRMANN, M DEAN, M SCHMIDTKE, J AF WILL, K STUHRMANN, M DEAN, M SCHMIDTKE, J TI ALTERNATIVE SPLICING IN THE 1ST NUCLEOTIDE BINDING FOLD OF CFTR SO HUMAN MOLECULAR GENETICS LA English DT Article ID CYSTIC-FIBROSIS GENE; POLYMERASE CHAIN-REACTION; NONSENSE MUTATION; GEL-ELECTROPHORESIS; DNA; CONDUCTANCE; IDENTIFICATION; EXPRESSION; POLYMORPHISMS; DEFICIENCY AB CFTR mRNA transcripts were analyzed from freshly isolated nasal epithelial cells and lymphocytes (six individuals) and from lymphocytes alone from 14 further individuals. In four of these 20 individuals alternative splicing was observed within the region coding for the first nucleotide binding fold. The RNA sequence between exons 10 and 13 was converted to cDNA and amplified by the polymerase chain reaction (PCR). We detected two PCR products of 583 bp and 464 bp in length. Direct sequencing of both fragments showed that the 583 bp PCR fragment contained an additional 119 bp sequence between exon 10 and exon 11, directly at the normal junction. This insertion contains an in frame stop codon and would, if translated, cause a shift in the reading frame. This stop codon does not result in an undetectable mRNA level as seen with other nonsense mutations within the same region of the CFTR gene (1, 2, own unpublished results). The alternatively spliced mRNA was found to be transcribed from both CF and normal alleles. The 119 bp fragment was amplified from genomic DNA and from the genomic phage TE24V, which includes exon 9, intron 9, exon 10 and a part of intron 10 (3) by PCR using primers created from within the inserted sequence. In addition, the insertion was mapped to a 1Kb EcoRI fragment of phage TE24V by Southern-blot analysis. By sequencing the insert surroundings within the phage TE24V we identified consensus splice sites (donor and acceptor sites, branch point). Furthermore no alterations were detected in the splice site sequences between individuals who express the aberrantly spliced product and those who do not. C1 HANNOVER MED SCH,INST HUMAN GENET,KONSTANTY GUTSCHOW STR 8,W-3000 HANNOVER 61,GERMANY. NCI,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21702. RI Dean, Michael/G-8172-2012 OI Dean, Michael/0000-0003-2234-0631 NR 36 TC 12 Z9 12 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD MAR PY 1993 VL 2 IS 3 BP 231 EP 235 DI 10.1093/hmg/2.3.231 PG 5 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA KU137 UT WOS:A1993KU13700005 PM 7684642 ER PT J AU CROSSEY, PA MAHER, ER JONES, MH RICHARDS, FM LATIF, F PHIPPS, ME LUSH, M FOSTER, K TORY, K GREEN, JS OOSTRA, B YATES, JRW LINEHAN, WM AFFARA, NA LERMAN, M ZBAR, B NAKAMURA, Y FERGUSONSMITH, MA AF CROSSEY, PA MAHER, ER JONES, MH RICHARDS, FM LATIF, F PHIPPS, ME LUSH, M FOSTER, K TORY, K GREEN, JS OOSTRA, B YATES, JRW LINEHAN, WM AFFARA, NA LERMAN, M ZBAR, B NAKAMURA, Y FERGUSONSMITH, MA TI GENETIC-LINKAGE BETWEEN VONHIPPEL-LINDAU DISEASE AND 3 MICROSATELLITE POLYMORPHISMS REFINES THE LOCALIZATION OF THE VHL LOCUS SO HUMAN MOLECULAR GENETICS LA English DT Article ID RENAL-CELL CARCINOMA; SMALL REGION; CHROMOSOME-3; MAPS AB Von Hippel-Lindau (VHL) disease is a dominantly inherited familial cancer syndrome characterised by the development of retinal and central nervous system haemangioblastomas, renal cell carcinoma and phaeochromocytoma. The gene for VHL disease has been mapped to chromosome 3p25 - p26 and presymtomatic diagnosis using linked DNA markers is available. We have previously mapped the VHL disease gene to a 4 cM interval between D3S1250 and D3S18. To increase access to presymptomatic diagnosis and to accelerate progress towards isolating the VHL disease gene we attempted to identify microsatellite DNA markers linked to the disease gene by genetic linkage analysis in 29 families. We found significant linkage between the VHL disease gene and dinucleotide (CA) repeat polymorphisms at D3S1038 (Zmax = 22.24 at theta = 0.01, CI 0.0001 - 0.06), D3S1110 (Zmax = 11.32 at theta = 0. 07, CI 0.03-0.14) and D3S651 (Zmax = 7.73 at theta = 0.04, CI 0.008-0.13). We localised D3S1038 between D3S1250 and D3S601, and mapped D3S1110 and D3S651 centromeric to D3S1250. Multipoint linkage analysis mapped the VHL disease locus between D3S1038 and D3S18 with the maximum likelihood at D3S601. There was no evidence of locus heterogeneity. This study has (i) identified three microsatellite DNA markers in chromosome 3p25 linked to the VHL gene and (ii) narrowed the target region for the isolation of the VHL disease gene by positional cloning techniques. These findings will improve the management of families with VHL disease by improving the accuracy and availability of presymptomatic diagnosis using linked DNA markers, and will accelerate progress towards isolating the VHL disease gene. C1 UNIV CAMBRIDGE,DEPT PATHOL,CAMBRIDGE,ENGLAND. JAPANESE FDN CANC RES,INST CANC,TOKYO 170,JAPAN. NCI,FREDERICK CANC RES FACIL,IMMUNOBIOL LAB,FREDERICK,MD 21701. MEM UNIV NEWFOUNDLAND,DIV COMMUNITY MED,ST JOHNS A1C 5S7,NEWFOUNDLAND,CANADA. ERASMUS UNIV,3000 DR ROTTERDAM,NETHERLANDS. RI MAHER, EAMONN/A-9507-2008 OI MAHER, EAMONN/0000-0002-6226-6918 NR 27 TC 43 Z9 43 U1 0 U2 3 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD MAR PY 1993 VL 2 IS 3 BP 279 EP 282 DI 10.1093/hmg/2.3.279 PG 4 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA KU137 UT WOS:A1993KU13700013 PM 8499917 ER PT J AU GLAVAC, D RAVNIKGLAVAC, M DEAN, M AF GLAVAC, D RAVNIKGLAVAC, M DEAN, M TI IDENTIFICATION OF A RARE CYSTIC-FIBROSIS MUTATION (S4X) IN A SLOVENIAN POPULATION SO HUMAN MOLECULAR GENETICS LA English DT Article ID GENE; DNA C1 NCI, FREDERICK CANC RES & DEV CTR, FREDERICK, MD 21702 USA. DYNCORP, PROGRAM RESOURCES INC, BIOL CARCINOGENESIS & DEV PROGRAM, FREDERICK, MD 21702 USA. RI Dean, Michael/G-8172-2012 OI Dean, Michael/0000-0003-2234-0631 NR 13 TC 5 Z9 5 U1 0 U2 1 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 1993 VL 2 IS 3 BP 315 EP 316 DI 10.1093/hmg/2.3.315 PG 2 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA KU137 UT WOS:A1993KU13700020 PM 7684643 ER PT J AU SCHMIDT, L LI, H DUH, FMC WEI, MH LERMAN, MI ZBAR, B TORY, K AF SCHMIDT, L LI, H DUH, FMC WEI, MH LERMAN, MI ZBAR, B TORY, K TI A CENTROMERIC MICROSATELLITE PROBE ON CHROMOSOME-3 - LIB 9-95CA (D3S1338) SO HUMAN MOLECULAR GENETICS LA English DT Article C1 NCI,FREDERICK CANC RES & DEV CTR,IMMUNOBIOL LAB,FREDERICK,MD 21702. RP SCHMIDT, L (reprint author), INC DYNCORP,PROGRAM RESOURCES,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702, USA. FU NCI NIH HHS [N01-CO-74102] NR 5 TC 1 Z9 1 U1 0 U2 3 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD MAR PY 1993 VL 2 IS 3 BP 335 EP 335 DI 10.1093/hmg/2.3.335-a PG 1 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA KU137 UT WOS:A1993KU13700031 PM 8499930 ER PT J AU BLACK, HR CURB, JD PRESSEL, S PROBSTFIELD, JL STAMLER, J AF BLACK, HR CURB, JD PRESSEL, S PROBSTFIELD, JL STAMLER, J TI IMPLICATIONS OF THE SYSTOLIC HYPERTENSION IN THE ELDERLY PROGRAM SO HYPERTENSION LA English DT Article DE HYPERTENSION; SYSTOLIC; AGE FACTORS; CLINICAL TRIALS; ANTIHYPERTENSIVE THERAPY ID FACTOR INTERVENTION TRIAL; CORONARY HEART-DISEASE; EUROPEAN-WORKING-PARTY; HIGH BLOOD-PRESSURE; DRUG-TREATMENT; MORTALITY; MORBIDITY; SHEP; RISK; HYDROCHLOROTHIAZIDE AB Several imperatives drive the need to establish the merit of treating isolated systolic hypertension in the elderly. These include its higher prevalence with age, the associated excess cardiovascular risks, and the rapid aging of the population. The Systolic Hypertension in the Elderly Program demonstrated a significant reduction in stroke incidence (fatal and nonfatal) (36%. equivalent to preventing 30 strokes per 1,000 participants per 5 years). A 27% reduction in coronary heart disease incidence and a 32% reduction in all major cardiovascular events were also achieved (equivalent to the prevention of 16 and 55 events per 1,000 participants per 5 years, respectively). These results were associated with a treatment regimen in which the primary agent was low-dose chlorthalidone. The benefits accrued to all subgroups identified based on baseline age, race and sex, blood pressure, serum cholesterol levels, and electrocardiographic abnormalities. The reduction in coronary disease is consistent with predictions based on prospective epidemiological studies and is concordant with other recent intervention trials. It is a reasonable inference from the Systolic Hypertension in the Elderly Program findings that middle-aged as well as older people with isolated systolic hypertension, and people with less severe degrees of this condition, particularly when other risk factors are present, would benefit from such therapy. Another reasonable implication of the trial relates to the matter of preferred drug treatment regimens for diastolic hypertension, in middle-aged as well as older people. A low-dose diuretic regimen is clearly the initial treatment of choice for most hypertensive patients, based on demonstrated reduction in risk for major cardiovascular events, including coronary heart disease, and its safety, patient acceptance, and low cost. RP BLACK, HR (reprint author), NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,CLIN TRIALS BRANCH,FED BLDG,BETHESDA,MD 20892, USA. NR 36 TC 44 Z9 46 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0194-911X J9 HYPERTENSION JI Hypertension PD MAR PY 1993 VL 21 IS 3 BP 335 EP 343 PG 9 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA KQ789 UT WOS:A1993KQ78900012 ER PT J AU CHOUCHANE, L BROWN, TJ KINDT, TJ AF CHOUCHANE, L BROWN, TJ KINDT, TJ TI STRUCTURE AND EXPRESSION OF A NONPOLYMORPHIC RABBIT CLASS-II GENE WITH HOMOLOGY TO HLA-DOB SO IMMUNOGENETICS LA English DT Note ID MAJOR HISTOCOMPATIBILITY COMPLEX; ALPHA-GENES; CHAIN GENE; MHC GENE; BETA; DP RP CHOUCHANE, L (reprint author), NIAID,IMMUNOGENET LAB,TWINBROOK 2 FACIL,12441 PARKLAWN DR,ROCKVILLE,MD 20852, USA. NR 16 TC 7 Z9 7 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0093-7711 J9 IMMUNOGENETICS JI Immunogenetics PD MAR PY 1993 VL 38 IS 1 BP 64 EP 66 DI 10.1007/BF00216394 PG 3 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA KT179 UT WOS:A1993KT17900011 PM 8096497 ER PT J AU CLERICI, M SHEARER, GM AF CLERICI, M SHEARER, GM TI A T(H)1-]T(H)2 SWITCH IS A CRITICAL STEP IN THE ETIOLOGY OF HIV-INFECTION SO IMMUNOLOGY TODAY LA English DT Editorial Material ID HUMAN-IMMUNODEFICIENCY-VIRUS; T-HELPER-CELL; CYTOKINE PRODUCTION; TYPE-1; INDIVIDUALS; RESPONSES; ANTIGEN; INVITRO; ABNORMALITIES; INTERLEUKIN-2 AB This viewpoint proposes that an imbalance in the T(H)1-type and T(H)2-type responses contributes to the immune dysregulation associated with HIV infection, and that resistance to HIV infection and/or progression to AIDS is dependent on a T(H)1 > T(H)2 dominance. This hypothesis is based on the authors' findings that: (1) progression to AIDS is characterized by loss of IL-2- and IFN-gamma production concomitant with increases in IL-4 and IL-10; and (2) many seronegative, HIV-exposed individuals generate strong T(H)1-type responses to HIV antigens. RP CLERICI, M (reprint author), NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892, USA. NR 39 TC 1261 Z9 1275 U1 2 U2 17 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0167-5699 J9 IMMUNOL TODAY JI Immunol. Today PD MAR PY 1993 VL 14 IS 3 BP 107 EP 110 DI 10.1016/0167-5699(93)90208-3 PG 4 WC Immunology SC Immunology GA KQ271 UT WOS:A1993KQ27100004 PM 8096699 ER PT J AU TANAKA, Y ADAMS, DH SHAW, S AF TANAKA, Y ADAMS, DH SHAW, S TI PROTEOGLYCANS ON ENDOTHELIAL-CELLS PRESENT ADHESION-INDUCING CYTOKINES TO LEUKOCYTES SO IMMUNOLOGY TODAY LA English DT Editorial Material ID FIBROBLAST GROWTH-FACTOR; HEPARAN-SULFATE; T-CELL; LYMPHOCYTE RECOGNITION; CHEMOTACTIC FACTORS; PLATELET FACTOR-4; HUMAN NEUTROPHILS; CD11B CD18; ACTIVATION; RECEPTOR AB Leukocyte recruitment from the blood circulation into tissue is essential for effective immune responses, and is, consequently, carefully regulated. In this article Yoshiya Tanaka and co-workers describe a model in which proteoglycans on the luminal surface of endothelium capture pro-adhesive cytokines. These cytokines provide the adhesion-inducing signal to particular leukocyte subsets which initiates their transmigration. RP TANAKA, Y (reprint author), NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892, USA. RI Adams, David/C-9092-2009 NR 53 TC 376 Z9 378 U1 0 U2 5 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0167-5699 J9 IMMUNOL TODAY JI Immunol. Today PD MAR PY 1993 VL 14 IS 3 BP 111 EP 115 DI 10.1016/0167-5699(93)90209-4 PG 5 WC Immunology SC Immunology GA KQ271 UT WOS:A1993KQ27100005 PM 8466625 ER PT J AU IGARASHI, Y LUNDGREN, JD SHELHAMER, JH KALINER, MA WHITE, MV AF IGARASHI, Y LUNDGREN, JD SHELHAMER, JH KALINER, MA WHITE, MV TI EFFECTS OF INHIBITORS OF ARACHIDONIC-ACID METABOLISM ON SEROTONIN RELEASE FROM RAT BASOPHILIC LEUKEMIA-CELLS SO IMMUNOPHARMACOLOGY LA English DT Article DE MAST CELL; MEDIATOR RELEASE; CYCLOOXYGENASE; LIPOXYGENASE ID MOUSE BONE-MARROW; LUNG MAST-CELLS; HISTAMINE-RELEASE; PROSTAGLANDIN BIOSYNTHESIS; DIFFERENTIAL RELEASE; MEDIATED ACTIVATION; ANTIGEN CHALLENGE; GENERATION; LEUKOTRIENE; LIPOXYGENASES AB Mast cells can release arachidonic acid (AA) metabolites as well as preformed mediators with IgE mediated stimulation, and these mediators are considered to play an important role in allergic reactions. The coincident release of preformed mediators and AA metabolites suggests that AA metabolism is related to mast cell degranulation. To clarify the relationship between mast cell degranulation and AA metabolism, the effects of various AA cascade inhibitors on rat basophilic leukemia cell (RBL) mediator release induced by either anti-IgE or A23187 were examined. 5,8,11,14-eicosatetraynoic acid (ETYA) inhibited both PGD2 and LTC4/D4 generation, and partially inhibited serotonin release. Nordihydroguaiaretic acid (NDGA) caused complete inhibition of LTC4/D4 generation, and partial inhibition of PGD2 generation and serotonin release. The cyclooxygenase inhibitor, indomethacin, and the specific 5-lipoxygenase inhibitor, L-651,392 completely inhibited PGD2 and LTC4/D4 generation, respectively, without affecting release of other mediators. Both PGD2 and LTC4/D4 generation were abolished by the combination of indomethacin and L-651,392, however, serotonin release remained intact. HPLC analysis showed that no shift to other AA metabolites occurred after the treatment with these inhibitors. Mepacrine, a phospholipase A2 inhibitor, completely inhibited PGD2 and LTC4/D4 generation, as well as AArelease itself, without affecting serotonin release. Therefore, neither AA metabolism nor AA release is necessary for RBL degranulation. C1 NIAID,ALLERG DIS SECT,CLIN INVEST LAB,BLDG 10,ROOM 11C207,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. NIH,CTR CLIN,DEPT CRIT CARE MED,BETHESDA,MD 20892. OI Lundgren, Jens/0000-0001-8901-7850 NR 36 TC 11 Z9 11 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0162-3109 J9 IMMUNOPHARMACOLOGY JI Immunopharmacology PD MAR-APR PY 1993 VL 25 IS 2 BP 131 EP 144 DI 10.1016/0162-3109(93)90016-J PG 14 WC Immunology; Pharmacology & Pharmacy SC Immunology; Pharmacology & Pharmacy GA KZ506 UT WOS:A1993KZ50600005 PM 8500985 ER PT J AU ANDERSEN, RN GANESHKUMAR, N KOLENBRANDER, PE AF ANDERSEN, RN GANESHKUMAR, N KOLENBRANDER, PE TI CLONING OF THE STREPTOCOCCUS-GORDONII PK488 GENE, ENCODING AN ADHESIN WHICH MEDIATES COAGGREGATION WITH ACTINOMYCES-NAESLUNDII PK606 SO INFECTION AND IMMUNITY LA English DT Article ID VIRIDANS STREPTOCOCCUS; NUCLEOTIDE-SEQUENCE; ESCHERICHIA-COLI; ORAL BACTERIA; SANGUIS G9B; SP-NOV; VISCOSUS; EXPRESSION; SURFACES; HYDROXYAPATITE AB Coaggregation between Streptococcus gordonii PK488 and Actinomyces naeslundii PK606 is mediated by a 38-kDa streptococcal protein, designated ScaA. The gene, scaA, which encodes this protein has been cloned into Escherichia coli. A genomic S. gordonii PK488 library (in Lambda ZAP II) was screened with anti-S. gordonii immunoglobulin G absorbed with S. gordonii PK1804, an isogenic coaggregation-defective mutant of strain PK488. A positive recombinant phage was isolated, and a phagemid designated pRA1 was obtained which contained a 6.6-kb insert. Expression of scaA from pRA1 and from a subcloned internal 2.1-kb fragment was observed. The absorbed antiserum cross-reacted with a 34.7-kDa protein, SsaB, from S. sanguis 12, also a coaggregation partner of A. naeslundii PK606. Absorbed antiserum to S. gordonii PK488 and antiserum to SsaB both reacted with 38-kDa proteins in supernatants from mildly sonicated preparations from 11 other coaggregation partners of A. naeslundii PK606. Putative adhesin genes were identified in each of these coaggregation partners by Southern analysis of their genomic DNA with the cloned 2. 1 -kb fragment as a probe. A 30-base oligonucleotide probe based on the sequence of ssaB of S. sanguis 12 hybridized in an identical manner. These data extend the notion that most of the viridans streptococci that coaggregate with actinomyces are capable of expressing ScaA-related proteins. C1 NIDR,MICROBIAL ECOL LAB,BETHESDA,MD 20892. NR 35 TC 51 Z9 51 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 1993 VL 61 IS 3 BP 981 EP 987 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA KN097 UT WOS:A1993KN09700027 PM 8432618 ER PT J AU FATTOM, A SCHNEERSON, R WATSON, DC KARAKAWA, WW FITZGERALD, D PASTAN, I LI, XR SHILOACH, J BRYLA, DA ROBBINS, JB AF FATTOM, A SCHNEERSON, R WATSON, DC KARAKAWA, WW FITZGERALD, D PASTAN, I LI, XR SHILOACH, J BRYLA, DA ROBBINS, JB TI LABORATORY AND CLINICAL-EVALUATION OF CONJUGATE VACCINES COMPOSED OF STAPHYLOCOCCUS-AUREUS TYPE-5 AND TYPE-8 CAPSULAR POLYSACCHARIDES BOUND TO PSEUDOMONAS-AERUGINOSA RECOMBINANT EXOPROTEIN-A SO INFECTION AND IMMUNITY LA English DT Article ID INFLUENZAE TYPE-B; EXOTOXIN-A; BACTERIAL POLYSACCHARIDES; ANTIBODY-RESPONSE; ESCHERICHIA-COLI; CLUMPING FACTOR; PROTEIN-A; TOXIN; MILK; ENCAPSULATION AB The synthesis, standardization, and immunogenicity in young outbred mice and clinical evaluation in adult volunteers of investigational vaccines designed to induce serum antibodies to the type 5 and type 8 capsular polysaccharides (CPs) of Staphylococcus aureus are described. Conjugates composed of the type 5 CP and a sonicated preparation of a high-molecular-weight type 8 CP bound to a nontoxic recombinant protein derived from Pseudomonas aeruginosa exotoxin A (rEPA) were synthesized. The conjugates were nontoxic and elicited serum CP antibodies after two subcutaneous injections into young outbred mice; a third injection elicited a booster response. The lower-molecular-weight type 8 CP was not immunogenic in the mice, and the high-molecular-weight type 8 CP elicited low levels of antibodies without a booster effect. In the volunteers, neither the conjugates nor the type 8 CP alone caused significant local reactions or fever. The conjugates elicited type-specific antibodies of both the immunoglobulin M (IgM) and IgG classes after the first injection; a second injection 6 weeks later did not stimulate a booster effect. The high-molecular-weight type 8 CP alone, injected once only, elicited levels of IgG and IgM type-specific antibodies similar to those of the conjugate. The vaccine-induced CP antibodies were mostly of the IgG1 and IgG2 subclasses and had opsonophagocytic activity. The conjugates elicited IgG antibodies to the native exotoxin A with neutralizing activity. In summary, the type 5 and type 8 conjugates were safe and elicited biologically active antibodies to both the CP and rEPA components. C1 NCI,NATL INST CHILD HLTH & HUMAN DEV,DEV & MOLEC IMMUN,BETHESDA,MD 20892. PENN STATE UNIV,DEPT BIOCHEM,UNIV PK,PA 16802. NIDDKD,BIOTECHNOL UNIT,BETHESDA,MD 20892. NCI,NATL INST CHILD HLTH & HUMAN DEV,MOLEC BIOL LAB,BETHESDA,MD 20892. NR 58 TC 103 Z9 106 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 1993 VL 61 IS 3 BP 1023 EP 1032 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA KN097 UT WOS:A1993KN09700032 PM 8432585 ER PT J AU WHITLEY, RJ STRAUS, SE AF WHITLEY, RJ STRAUS, SE TI THERAPY FOR VARICELLA-ZOSTER VIRUS-INFECTIONS - WHERE DO WE STAND SO INFECTIOUS DISEASES IN CLINICAL PRACTICE LA English DT Review ID ACUTE HERPES-ZOSTER; ACQUIRED-IMMUNODEFICIENCY-SYNDROME; HUMAN-LEUKOCYTE INTERFERON; ORAL ACYCLOVIR; IMMUNOSUPPRESSED PATIENTS; IMMUNOCOMPROMISED PATIENTS; POSTHERPETIC NEURALGIA; VIDARABINE THERAPY; COMPARATIVE TRIAL; CHILDREN C1 UNIV ALABAMA,DEPT PEDIAT MICROBIOL & MED,BIRMINGHAM,AL 35294. NIAID,CLIN INVEST LAB,BETHESDA,MD 20892. NR 64 TC 9 Z9 9 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1056-9103 J9 INFECT DIS CLIN PRAC JI Infect. Dis. Clin. Pract. PD MAR-APR PY 1993 VL 2 IS 2 BP 100 EP 108 DI 10.1097/00019048-199303000-00003 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA MF194 UT WOS:A1993MF19400003 ER PT J AU TSUNO, K TERASAKI, H OTSU, T OKAMOTO, T SAKANASHI, Y MORIOKA, T AF TSUNO, K TERASAKI, H OTSU, T OKAMOTO, T SAKANASHI, Y MORIOKA, T TI NEWBORN EXTRACORPOREAL LUNG ASSIST USING A NOVEL DOUBLE LUMEN CATHETER AND A HEPARIN-BONDED MEMBRANE LUNG SO INTENSIVE CARE MEDICINE LA English DT Note DE EXTRACORPOREAL LUNG ASSIST (ECLA); EXTRACORPOREAL MEMBRANE OXYGENATION (ECMO); MECONIUM ASPIRATION SYNDROME ID BRAIN-LESIONS; OXYGENATION; INFANTS AB We report the clinical application of a novel double lumen catheter for veno-venous extracorporeal lung assist (ECLA) and the use of a heparin-bonded hollow fiber membrane lung, in the treatment of newborn respiratory failure. The outer lumen of the double lumen catheter was 14 Fr and was used for blood drainage; while the inner 8 Fr catheter was used for blood return. The double lumen catheter was made of spiral wire reinforced polyurethane, with a wall thickness of 0.25 mm. The hollow fiber membrane was made of non-microporous polyolefin, and was not permeable to water or plasma. We used this system to treat a newborn patient with meconium aspiration syndrome. Heparin was infused continuously at a rate of 18-25 units/kg/h, equal to 1/3 of the usual amount when a non-heparin bonded ECLA system was used and maintaining the activated clotting time near 120 s. Bleeding from cutdown sites was negligible. Only the right internal jugular vein was sacrificed. The patient was successfully weaned from ECLA and appears normal one year following discharge. C1 KUMAMOTO UNIV,SCH MED,DEPT ANESTHESIOL,KUMAMOTO 860,JAPAN. RP TSUNO, K (reprint author), NHLBI,LCB,BLDG 10,ROOM 5D 17,BETHESDA,MD 20892, USA. NR 10 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0342-4642 J9 INTENS CARE MED JI Intensive Care Med. PD MAR PY 1993 VL 19 IS 2 BP 70 EP 72 DI 10.1007/BF01708363 PG 3 WC Critical Care Medicine SC General & Internal Medicine GA KT029 UT WOS:A1993KT02900004 PM 8486871 ER PT J AU SPITZER, RL YANOVSKI, S WADDEN, T WING, R MARCUS, MD STUNKARD, A DEVLIN, M MITCHELL, J HASIN, D HORNE, RL AF SPITZER, RL YANOVSKI, S WADDEN, T WING, R MARCUS, MD STUNKARD, A DEVLIN, M MITCHELL, J HASIN, D HORNE, RL TI BINGE EATING DISORDER - ITS FURTHER VALIDATION IN A MULTISITE STUDY SO INTERNATIONAL JOURNAL OF EATING DISORDERS LA English DT Article ID DIETARY RESTRAINT; OBESITY; EATERS AB Binge eating disorder (BED) is a new eating disorder that describes the eating disturbance of a large number of individuals who suffer from recurrent binge eating but who do not regularly engage in the compensatory behaviors to avoid weight gain seen in bulimia nervosa. This multisite study of BED involved 1,785 subjects drawn from 18 weight control programs, 942 subjects from five nonpatient community samples, and 75 patients with bulimia nervosa. Approximately 29% of subjects in weight control programs met the criteria for BED. In the nonpatient community samples BED was more common than purging bulimia nervosa. The validity of BED was supported by its strong association with (1) impairment in work and social functioning, (2) overconcern with body/shape and weight, (3) general psychopathology, (4) significant amount of time in adult life on diets, (5) a history of depression, alcohol/drug abuse, and treatment for emotional problems. C1 COLUMBIA UNIV,DEPT PSYCHIAT,NEW YORK,NY 10027. NIMH,CLIN NEUROENDOCRINOL BRANCH,BETHESDA,MD 20892. SYRACUSE UNIV,SYRACUSE,NY 13244. UNIV PITTSBURGH,SCH MED,PITTSBURGH,PA 15261. UNIV PENN,PHILADELPHIA,PA 19104. UNIV MINNESOTA,DEPT PSYCHIAT,MINNEAPOLIS,MN 55455. UNIV NEVADA,SCH MED,RENO,NV 89557. NR 29 TC 518 Z9 530 U1 8 U2 39 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0276-3478 J9 INT J EAT DISORDER JI Int. J. Eating Disord. PD MAR PY 1993 VL 13 IS 2 BP 137 EP 153 PG 17 WC Psychology, Clinical; Nutrition & Dietetics; Psychiatry; Psychology SC Psychology; Nutrition & Dietetics; Psychiatry GA KN082 UT WOS:A1993KN08200001 PM 8477283 ER PT J AU SPITZER, RL STUNKARD, A YANOVSKI, S MARCUS, MD WADDEN, T WING, R MITCHELL, J HASIN, D AF SPITZER, RL STUNKARD, A YANOVSKI, S MARCUS, MD WADDEN, T WING, R MITCHELL, J HASIN, D TI BINGE EATING DISORDER SHOULD BE INCLUDED IN DSM-IV - A REPLY TO FAIRBURN ET ALS THE CLASSIFICATION OF RECURRENT OVEREATING - THE BINGE EATING DISORDER PROPOSAL SO INTERNATIONAL JOURNAL OF EATING DISORDERS LA English DT Article ID BEHAVIORAL TREATMENT; OBESITY AB Extensive recent research supports a proposal that a new eating disorder, binge eating disorder (BED), be included in DSM-IV. BED criteria define a relatively pure group of individuals who are distressed by recurrent binge eating who do not exhibit the compensatory features of bulimia nervosa. This large number of patients currently can only be diagnosed as eating disorder not otherwise specified (EDNOS). Recognizing this new disorder will help stimulate research and clinical programs for these patients. Fairburn et al.'s critique of BED fails to acknowledge the large body of knowledge that indicates that BED represents a distinct and definable subgroup of eating disordered patients and that the diagnosis provides useful information about psychopathology, prognosis, and outcome (Fairburn, Welch, & Hay [in press]. The classification of recurrent overeating: The ''binge eating disorder'' proposal. International Journal of Eating Disorders.) Against any reasonable standard for adding a new diagnosis to DSM-IV, BED meets the test. C1 COLUMBIA UNIV,NEW YORK,NY 10027. UNIV PENN,PHILADELPHIA,PA 19104. NIMH,CLIN NEUROENDOCRINOL BRANCH,BETHESDA,MD 20892. UNIV PITTSBURGH,SCH MED,PITTSBURGH,PA 15261. SYRACUSE UNIV,SYRACUSE,NY 13244. UNIV MINNESOTA,DEPT PSYCHIAT,MINNEAPOLIS,MN 55455. NR 30 TC 43 Z9 43 U1 1 U2 4 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0276-3478 J9 INT J EAT DISORDER JI Int. J. Eating Disord. PD MAR PY 1993 VL 13 IS 2 BP 161 EP 169 DI 10.1002/1098-108X(199303)13:2<161::AID-EAT2260130204>3.0.CO;2-R PG 9 WC Psychology, Clinical; Nutrition & Dietetics; Psychiatry; Psychology SC Psychology; Nutrition & Dietetics; Psychiatry GA KN082 UT WOS:A1993KN08200003 PM 8477285 ER PT J AU GWIRTSMAN, HE PRAGER, J HENKIN, R AF GWIRTSMAN, HE PRAGER, J HENKIN, R TI CASE-REPORT OF ANOREXIA-NERVOSA ASSOCIATED WITH WILSONS-DISEASE SO INTERNATIONAL JOURNAL OF EATING DISORDERS LA English DT Article ID DISORDER AB Wilson's disease is a recessively inherited disorder of copper metabolism with prominent hepatic, hematopoetic, central nervous system (CNS), and ocular involvement. Psychiatric manifestations are notoriously variable. The following case history of a patient with both anorexia nervosa and Wilson's disease is presented and discussed in the context of organic CNS lesions associated with anorexia nervosa-like syndromes. C1 UNIV CHICAGO,DEPT RADIOL,CHICAGO,IL 60637. TASTE & SMELL CLIN,WASHINGTON,DC. RP GWIRTSMAN, HE (reprint author), NIMH,MOOD ANXIETY & PERSONAL DISORDERS RES BRANCH,DIV CLIN RES,ROCKVILLE,MD 20857, USA. NR 22 TC 6 Z9 6 U1 0 U2 0 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0276-3478 J9 INT J EAT DISORDER JI Int. J. Eating Disord. PD MAR PY 1993 VL 13 IS 2 BP 241 EP 244 DI 10.1002/1098-108X(199303)13:2<241::AID-EAT2260130213>3.0.CO;2-Y PG 4 WC Psychology, Clinical; Nutrition & Dietetics; Psychiatry; Psychology SC Psychology; Nutrition & Dietetics; Psychiatry GA KN082 UT WOS:A1993KN08200012 PM 8477294 ER PT J AU GAROFALO, A CHIRIVI, RGS SCANZIANI, E MAYO, JG VECCHI, A GIAVAZZI, R AF GAROFALO, A CHIRIVI, RGS SCANZIANI, E MAYO, JG VECCHI, A GIAVAZZI, R TI COMPARATIVE-STUDY ON THE METASTATIC BEHAVIOR OF HUMAN TUMORS IN NUDE, BEIGE/NUDE/XID AND SEVERE COMBINED IMMUNODEFICIENT MICE SO INVASION & METASTASIS LA English DT Article DE NUDE MICE; SEVERE COMBINED IMMUNODEFICIENT MICE; BEIGE/NUDE/XID MICE; METASTASIS; HUMAN TUMORS ID NATURAL-KILLER ACTIVITY; SCID MICE; NK CELLS; GROWTH; MOUSE; CARCINOMA; LEUKEMIAS; MUTATION; THERAPY; TISSUE AB The growth and metastatic behavior of human tumor cell lines were studied in nude, beige/nude/xid (bg/nu/xid) and severe combined immunodeficient (SCID) mice. One melanoma, two colon carcinomas and one renal carcinoma grew subcutaneously in the three strains of mice with no significant differences in tumor take and growth rate. One ovarian carcinoma formed a subcutaneously growing tumor only in SCID mice. Spontaneous metastases were observed only in mice with advanced subcutaneous tumors or at histological examination, but more frequently in bg/nu/xid and SCID mice than in nude mice. A375M melanoma formed more lung colonies in nude and bg/nu/xid mice than in SCID mice. HT-29LM colon carcinoma injected intravenously or intrasplenically formed more lung and liver colonies and lymph node metastases in bg/nu/xid mice than in nude and SCID mice. The treatment of SCID mice with anti-asGM1 serum depleted NK activity and enhanced the number of lung colonies by A375M melanoma and HT-29LM colon carcinoma. Bg/nu/xid or SCID mice may therefore offer some advantages for studying the malignant behavior of human solid tumors and differences may depend on the experimental conditions and on the tumor type. C1 MARIO NEGRI INST PHARMACOL RES,I-24100 BERGAMO,ITALY. UNIV MILAN,IST ANAT PATOL VET & PATOL AVIARE,MILAN,ITALY. NCI,FCRDC,DTP,DCT,FREDERICK,MD. NR 37 TC 46 Z9 47 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0251-1789 J9 INVAS METAST JI Invasion Metastasis PD MAR-APR PY 1993 VL 13 IS 2 BP 82 EP 91 PG 10 WC Oncology SC Oncology GA MJ522 UT WOS:A1993MJ52200003 PM 8225855 ER PT J AU WHITCUP, SM DEBARGE, LR ROSEN, H NUSSENBLATT, RB CHAN, CC AF WHITCUP, SM DEBARGE, LR ROSEN, H NUSSENBLATT, RB CHAN, CC TI MONOCLONAL-ANTIBODY AGAINST CD11B CD18 INHIBITS ENDOTOXIN-INDUCED UVEITIS SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE CELL ADHESION MOLECULES; ENDOTOXIN; EYE; MAC-1; UVEITIS ID INTERCELLULAR-ADHESION MOLECULE-1; COMPLEMENT RECEPTOR; HUMAN-NEUTROPHILS; CELLS-INVITRO; UP-REGULATION; ICAM-1 CD54; LIPOPOLYSACCHARIDE; INFLAMMATION; ADHERENCE; MICE AB Purpose. To examine the serial expression of cell adhesion molecules in C3H/HeN mice with endotoxin-induced uveitis, and to study the effect of treatment with a monoclonal antibody against Mac-I on the development of endotoxin-induced uveitis. Methods. Immunohistochemical staining was used to document the serial expression of Mac-1, intercellular adhesion molecule-1 (ICAM-1), and lymphocyte function-associated antigen-1 (LFA-1) in eyes of C3H/HeN mice with endotoxin-induced uveitis. Then, in two separate experiments, endotoxin-induced uveitis was produced in a total of 48 mice by injecting Salmonella typhimurium endotoxin into one hind footpad. At the time of endotoxin injection, 24 mice received an intraperitoneal injection of anti-Mac-1 antibody and 24 control mice received an intraperitoneal injection of rat IgG. Histopathologic sections of eyes taken 24 hours after endotoxin injection were graded by two masked observers on a scale of 0 to 4. Results. Intercellular adhesion molecule-1 was first expressed on the ciliary body epithelium 6 hr after endotoxin injection and Mac-1 and LFA-1 were expressed on infiltrating inflammatory cells 12 hr after endotoxin injection. Treatment with anti-MAC-1 antibody significantly inhibited the development of ocular inflammation when compared with treatment with control IgG (P<0.001). Conclusion. Intercellular adhesion molecule-1 is expressed in the eye before clinical or histologic signs of inflammation. Furthermore, treatment with antibody against Mac-1 significantly inhibits the development of endotoxin-induced uveitis in mice and suggests that anti-Mac-1 antibody may be useful for treating acute ocular inflammation. C1 MERCK SHARP & DOHME LTD,RAHWAY,NJ 07065. RP WHITCUP, SM (reprint author), NEI,IMMUNOL LAB,BLDG 10,RM 10N 202,BETHESDA,MD 20892, USA. NR 52 TC 60 Z9 60 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR PY 1993 VL 34 IS 3 BP 673 EP 681 PG 9 WC Ophthalmology SC Ophthalmology GA KR641 UT WOS:A1993KR64100026 PM 8095493 ER PT J AU HUFF, JE MELNICK, R AF HUFF, JE MELNICK, R TI IDENTIFYING CARCINOGENS SO ISSUES IN SCIENCE AND TECHNOLOGY LA English DT Editorial Material RP HUFF, JE (reprint author), NIEHS,RISK EVALUAT,RES TRIANGLE PK,NC 27709, USA. NR 1 TC 1 Z9 1 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0748-5492 J9 ISSUES SCI TECHNOL JI Issues Sci. Technol. PD SPR PY 1993 VL 9 IS 3 BP 14 EP 15 PG 2 WC Engineering, Multidisciplinary; Engineering, Industrial; Multidisciplinary Sciences; Social Issues SC Engineering; Science & Technology - Other Topics; Social Issues GA KY168 UT WOS:A1993KY16800011 ER PT J AU WALSH, C WERNZ, JC LEVINE, A RARICK, M WILLSON, E MELENDEZ, D BONNEM, E THOMPSON, J SHELTON, B AF WALSH, C WERNZ, JC LEVINE, A RARICK, M WILLSON, E MELENDEZ, D BONNEM, E THOMPSON, J SHELTON, B TI PHASE-I TRIAL OF M-BACOD AND GRANULOCYTE MACROPHAGE COLONY STIMULATING FACTOR IN HIV-ASSOCIATED NON-HODGKINS-LYMPHOMA SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE NON-HODGKINS LYMPHOMA; HIV; COLONY STIMULATING FACTORS ID ACQUIRED IMMUNODEFICIENCY SYNDROME; CHEMOTHERAPY AB The use of full-dose intensive regimens of chemotherapy in patients with HIV-associated lymphoma has often resulted in severe toxicity, treatment delay, and reduced subsequent dosing. We conducted a Phase I trial to evaluate the toxicity of the combination of m-BACOD (methotrexate, Bleomycin, doxorubicin, cyclophosphamide, vincristine, dexamethasone) with granulocyte-macrophage colony stimulating factor (GMCSF) in these patients. A total of 17 patients were entered and treated at three dose levels of m-BACOD in combination with a fixed dose of GMCSF. Eight patients received standard dose m-BACOD plus GMCSF without experiencing dose-limiting hematologic toxicity, although significant nonhematologic toxicity was seen. We conclude that it is feasible to treat patients with HIV-associated lymphoma using standard dose m-BACOD plus GMCSF, but further study is needed to determine whether full-dose regimens improve survival when compared with reduced dose regimens in these individuals. C1 UNIV SO CALIF, SCH MED, LOS ANGELES, CA 90033 USA. NIAID, DIV AIDS, AIDS CLIN TRIALS UNIT, BETHESDA, MD 20892 USA. RP WALSH, C (reprint author), NYU, SCH MED, KAPLAN COMPREHENS CANC CTR, 550 1ST AVE, NEW YORK, NY 10016 USA. NR 15 TC 37 Z9 37 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. PD MAR PY 1993 VL 6 IS 3 BP 265 EP 271 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA KN542 UT WOS:A1993KN54200009 PM 7680712 ER PT J AU FISCHL, MA KROWN, SE OBOYLE, KP MITSUYASU, R MILES, S WERNZ, JC VOLBERDING, PA KAHN, J GROOPMAN, JE FEINBERG, J WOODY, M AF FISCHL, MA KROWN, SE OBOYLE, KP MITSUYASU, R MILES, S WERNZ, JC VOLBERDING, PA KAHN, J GROOPMAN, JE FEINBERG, J WOODY, M TI WEEKLY DOXORUBICIN IN THE TREATMENT OF PATIENTS WITH AIDS-RELATED KAPOSIS-SARCOMA SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Article DE KAPOSIS SARCOMA; CYTOTOXIC CHEMOTHERAPY; DOXORUBICIN ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; IMMUNE-DEFICIENCY SYNDROME; LEUKOCYTE-A INTERFERON; LYMPHOBLASTOID INTERFERON; VINCRISTINE; THERAPY AB Fifty-three patients with AIDS-related Kaposi's sarcoma and no previous treatment with cytotoxic chemotherapy enrolled in a phase II multicenter study to evaluate the safety and efficacy of weekly doxorubicin treatment. Doxorubicin was given intravenously at a dose of 15 mg/m2. Patients were stratified for purposes of analyses by tumor burden and coexistence of HIV-associated signs and symptoms; stratum I included patients with cutaneous disease alone and no symptoms, and stratum II included patients with visceral disease, tumor-associated edema, a previous opportunistic infection, or systemic symptoms. Fifty-one patients were evaluable for toxicity and 50 for tumor response. Five patients had a partial response (10%); 32, a minor response (64%); 12, no change (24%); and one, progression (2%) as the best measurable response. Partial response durations ranged from 4 to 14 weeks. Fifteen patients subsequently showed progression while on treatment. A significantly greater number of patients in stratum I (20. 1%) had a partial response compared with those in stratum II (0%, p = 0.009). The major toxicities included nausea (37%), stomatitis (9.8%), mucositis (13.7%), and moderate to severe neutropenia (71%). Neutropenia was dose limiting and resulted in discontinuation of doxorubicin in 18% of the patients. Two patients developed cardiac toxicity. In conclusion, doxorubicin treatment induced relatively few tumor responses and remission durations were short. Treatment was limited by a high rate of toxicity. C1 NIAID,DIV AIDS,ROCKVILLE,MD. UNIV CALIF SAN FRANCISCO,SAN FRANCISCO GEN HOSP,SAN FRANCISCO,CA 94110. MEM SLOAN KETTERING CANC CTR,NEW YORK,NY 10021. UNIV CALIF LOS ANGELES,LOS ANGELES,CA 90024. NYU MED CTR,NEW YORK,NY 10016. RES TRIANGLE INST,RES TRIANGLE PK,NC 27709. HARVARD UNIV,SCH MED,NEW ENGLAND DEACONESS HOSP,BOSTON,MA 02115. RP FISCHL, MA (reprint author), UNIV MIAMI,SCH MED,DEPT MED R-60A,POB 016960,MIAMI,FL 33101, USA. NR 24 TC 66 Z9 66 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD MAR PY 1993 VL 6 IS 3 BP 259 EP 264 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA KN542 UT WOS:A1993KN54200008 PM 8450401 ER PT J AU RODRIGUEZ, EM DEMOYA, EA GUERRERO, E MONTERROSO, ER QUINN, TC PUELLO, E DEQUINONES, MR THORINGTON, B GLASNER, PD ZACARIAS, F VERMUND, SH AF RODRIGUEZ, EM DEMOYA, EA GUERRERO, E MONTERROSO, ER QUINN, TC PUELLO, E DEQUINONES, MR THORINGTON, B GLASNER, PD ZACARIAS, F VERMUND, SH TI HIV-1 AND HTLV-I IN SEXUALLY-TRANSMITTED DISEASE CLINICS IN THE DOMINICAN-REPUBLIC SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Article DE HUMAN IMMUNODEFICIENCY VIRUS TYPE-1 (HIV-1); DOMINICAN-REPUBLIC; HUMAN T-LYMPHOTROPIC VIRUS TYPE-I (HTLV-I); SEX BEHAVIOR; SEXUALLY TRANSMITTED DISEASES (STDS); GENITAL ULCER DISEASE ID HUMAN-IMMUNODEFICIENCY-VIRUS; TRANSMISSION; INFECTION AB A cross-sectional seroprevalence study of human immunodeficiency virus type 1 (HIV-1) and human T-cell lymphotropic virus type I (HTLV-I) was undertaken among 494 attendees in two Santo Domingo sexually transmitted disease clinics in 1989. All participants were evaluated for Neisseria gonorrhoeae, Chlamydia trachomatis, syphilis, and genital ulcers. Of the 494 participants, 15 (3.00%) were positive for HIV-1 and 14 (2.8%) were positive for HTLV-I. Twelve of 371 (3.2%) men were HIV-1 seropositive: 0 of 68 homosexual/bisexual and 12 (4.0%) of 302 heterosexual men (one seronegative male could not be classified). Three (2.4%) of 123 women were HIV-1 seropositive. One (1.5%) homosexual/bisexual man, five (1.7%) heterosexual men, and eight (6.5%) women were HTLV-I seropositive. Among heterosexual men, HIV-1 was associated with multiple lifetime sex partners (O.R. = 5.9; 95% C.I. = 1.4,23; p = 0.007). HIV-1 was associated with genital ulcer disease among women (p = 0.004). Among women, HTLV-I was associated with professional sex work (O.R. = 18; 95% C.I. = 2.1,>100; p = 0.001). These findings suggest the need for control of sexually transmitted diseases and targeted educational programs for prevention of HIV-1 and HTLV-I among individuals with high-risk behaviors in the Dominican Republic. C1 SECRETARIA SALUD PUBL ASISTENCIA SOCIAL,PROGRAMA CONTROL ENFERMEDADES TRANSMIS SEXUAL & SIDA,SANTO DOMINGO,DOMINICAN REP. WHO,PAN AMER HLTH ORG,HLTH SITUAT & TREND ASSESSMENT PROGRAM,WASHINGTON,DC. NEW ENGLAND RES INST,WATERTOWN,MA. RP RODRIGUEZ, EM (reprint author), NIAID,DAIDS,VTEB,6003 EXECUT BLVD,ROOM 2A23,BETHESDA,MD 20892, USA. OI Vermund, Sten/0000-0001-7289-8698 FU NIAID NIH HHS [N01-AI-72649] NR 26 TC 14 Z9 15 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD MAR PY 1993 VL 6 IS 3 BP 313 EP 318 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA KN542 UT WOS:A1993KN54200017 PM 8450407 ER PT J AU JOSHI, S LAKSHMINARAYANA, MR GOWDA, GAN KHETRAPAL, CL AF JOSHI, S LAKSHMINARAYANA, MR GOWDA, GAN KHETRAPAL, CL TI C-13 NMR-STUDIES OF LIPID MOBILIZATION PATTERN IN GERMINATING GROUNDNUT (ARACHIS-HYPOGAEA L) SEEDS SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article AB The products of lipid mobilization in groundnut (Arachis hypogaea L.) seeds as a function of time immediately after imbibition are monitored by C-13 NMR. Different parts of the embryonic axis, namely, the radicle, hypocotyl, and plumule, exhibit characteristic time dependent C-13 NMR spectra observed at 24-h intervals after imbibition. The various stages in the transformation of storage lipids present in different parts of the embryonic axis are clearly demonstrated. The transformaton of storage lipids is completed first in the radicle followed by the hypocotyl and finally the plumule. A mechanism of the transformation of the storage lipids is discussed. C1 NIH,BETHESDA,MD 20892. UNIV AGR SCI BANGALORE,DEPT BOT & PHYS,BANGALORE 560065,KARNATAKA,INDIA. INDIAN INST SCI,SOPHISTICATED INSTRUMENTS FACIL,BANGALORE 560012,KARNATAKA,INDIA. NR 4 TC 2 Z9 2 U1 1 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0021-8561 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD MAR PY 1993 VL 41 IS 3 BP 481 EP 482 DI 10.1021/jf00027a025 PG 2 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA KT439 UT WOS:A1993KT43900025 ER PT J AU PARMAR, D BURKA, LT AF PARMAR, D BURKA, LT TI STUDIES ON THE INTERACTION OF FURAN WITH HEPATIC CYTOCHROME-P-450 SO JOURNAL OF BIOCHEMICAL TOXICOLOGY LA English DT Article ID RAT-LIVER CYTOCHROME-P-450; SUICIDE INACTIVATION; PROSTHETIC HEME; PULMONARY; ETHANOL; METABOLITES; 4-IPOMEANOL; ACTIVATION; INDUCTION; IMIDAZOLE AB In vitro incubation of rat liver microsomes with [C-14]-furan in the presence of NADPH resulted in the covalent incorporation of furan-derived radioactivity in microsomal protein. Compared to microsomes from untreated rats a two- to threefold increase in binding was observed with microsomes from phenobarbital-treated rats and a four- to five-fold increase was observed with microsomes from rats pretreated with imidazole or pyrazole. Covalent binding was reduced with microsomes from rats pretreated with beta-naphthoflavone. Chemicals containing an amine group (semi-carbazide), those in which the amine group is blocked but have a free thiol group (N-acetylcysteine), and those which have both an amine and a thiol group (glutathione) effectively blocked binding of [C-14]-furan to microsomal protein. A decrease in cytochrome P-450 (P-450) content and decreases in the activities of P-450-dependent aniline hydroxylase, 7-ethoxycoumarin-O-deethylase (ECD), and 7-ethoxyresorufin-O-deethylase (ERD) was observed 24 hours after a single oral administration of 8 or 25 mg/kg of furan, suggesting that the reactive intermediate formed during P-450 catalyzed metabolism could be binding with nucleophilic groups within the P-450. In vitro studies indicated a significant decrease in the activity of aniline hydroxylase in pyrazole microsomes and ECD in phenobarbital microsomes without any significant change in the CO-binding spectrum of P-450 or in the total microsomal heme content, suggesting that furan inhibits the P-450s induced by PB and pyrazole. An almost equal distribution of furan-derived radioactivity in the heme and protein fractions of the CO-binding particles after in vitro treatment of microsomes with furan suggests binding of furan metabolites with heme and apoprotein of P-450, and, probably, due to this interaction, furan is acting as a suicide inhibitor of P-450. C1 NIEHS,POB 12233,RES TRIANGLE PK,NC 27709. NR 30 TC 30 Z9 32 U1 0 U2 2 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0887-2082 J9 J BIOCHEM TOXICOL JI J. Biochem. Toxicol. PD MAR PY 1993 VL 8 IS 1 BP 1 EP 9 DI 10.1002/jbt.2570080103 PG 9 WC Toxicology SC Toxicology GA KX007 UT WOS:A1993KX00700001 PM 8492299 ER PT J AU GRZESIEK, S BAX, A AF GRZESIEK, S BAX, A TI AMINO-ACID TYPE DETERMINATION IN THE SEQUENTIAL ASSIGNMENT PROCEDURE OF UNIFORMLY C-13/N-15-ENRICHED PROTEINS SO JOURNAL OF BIOMOLECULAR NMR LA English DT Article DE C-13 CHEMICAL SHIFTS; CONSTANT-TIME; TRIPLE RESONANCE; SEQUENTIAL ASSIGNMENT; 3D NMR ID TRIPLE-RESONANCE NMR; COUPLING-CONSTANTS; LARGER PROTEINS; SPECTROSCOPY; C-13; SPECTRA; H-1; INTERLEUKIN-1-BETA; MAGNETIZATION; CALMODULIN AB Experiments and procedures are described that greatly alleviate the sequential assignment process of uniformly C-13/N-15-enriched proteins by determining the type of amino acid from experiments that correlate side chain with backbone amide resonances. A recently proposed 3D NMR experiment, CBCA(CO)NH, correlates C(alpha) and C(beta) resonances to the backbone amide H-1 and N-15 resonances of the next residue (Grzesiek, S. and Bax, A. (1992) J. Am. Chem. Soc., 114, 6291-6293). An extension of this experiment is described which correlates the proton H(beta) and H(alpha) resonances to the amide H-1 and N-15 resonances of the next amino acid, and a detailed product operator description is given. A simple 2D-edited constant-time HSQC experiment is described which rapidly identifies H(beta) and C(beta) resonances of aromatic or Asn/Asp residues. The extent to which combined knowledge of the C(alpha) and C(beta) chemical shift values determines the amino acid type is investigated, and it is demonstrated that the combined C(alpha) and C(beta) chemical shifts of three or four adjacent residues usually are sufficient for defining a unique position in the protein sequence. RP GRZESIEK, S (reprint author), NIDDKD,CHEM PHYS LAB,BETHESDA,MD 20892, USA. NR 41 TC 634 Z9 637 U1 2 U2 20 PU ESCOM SCI PUBL BV PI LEIDEN PA PO BOX 214, 2300 AE LEIDEN, NETHERLANDS SN 0925-2738 J9 J BIOMOL NMR JI J. Biomol. NMR PD MAR PY 1993 VL 3 IS 2 BP 185 EP 204 PG 20 WC Biochemistry & Molecular Biology; Spectroscopy SC Biochemistry & Molecular Biology; Spectroscopy GA KV741 UT WOS:A1993KV74100004 PM 8477186 ER PT J AU HUMPHREY, JS PETERS, PJ YUAN, LC BONIFACINO, JS AF HUMPHREY, JS PETERS, PJ YUAN, LC BONIFACINO, JS TI LOCALIZATION OF TGN38 TO THE TRANS-GOLGI NETWORK - INVOLVEMENT OF A CYTOPLASMIC TYROSINE-CONTAINING SEQUENCE SO JOURNAL OF CELL BIOLOGY LA English DT Article ID MEMBRANE-SPANNING DOMAIN; KEX1 GENE ENCODES; CLASS-I MOLECULES; HUMAN T-CELLS; MANNOSE-6-PHOSPHATE RECEPTOR; INTERLEUKIN-2 RECEPTOR; ENDOPLASMIC-RETICULUM; TRANSFERRIN RECEPTOR; COATED VESICLES; ANTI-TAC AB Protein localization to the TGN was investigated by examining the subcellular distribution of chimeric proteins in which the cytoplasmic and/or transmembrane domains of the TGN protein, TGN38, were substituted for the analogous domains of the plasma membrane protein, Tac. Using immunofluorescence and immunoelectron microscopy, the COOH-terminal cytoplasmic domain of TGN38 was found to be sufficient for localization of the chimeric proteins to the TGN. Deletion analysis identified an 11-amino acid segment containing the critical sequence, YQRL, as being sufficient for TGN localization. TGN localization was abrogated by mutation of the tyrosine or leucine residues in this sequence to alanine, or of the arginine residue to aspartate. In addition to specifying TGN localization, the 11-amino acid segment was active as an internalization signal, although the property of internalization alone was insufficient to confer TGN localization. Overexpression of chimeric proteins containing TGN localization determinants resulted in their detection at the plasma membrane and in intracellular vesicles, and abolished detection of endogenous TGN38. These results suggest that discrete cytoplasmic determinants can mediate protein localization to the TGN, and reveal a novel role for tyrosine-based motifs in this process. RP HUMPHREY, JS (reprint author), NICHHD,CELL BIOL & METAB BRANCH,BETHESDA,MD 20892, USA. OI Bonifacino, Juan S./0000-0002-5673-6370 NR 76 TC 226 Z9 226 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD MAR PY 1993 VL 120 IS 5 BP 1123 EP 1135 DI 10.1083/jcb.120.5.1123 PG 13 WC Cell Biology SC Cell Biology GA KN669 UT WOS:A1993KN66900006 PM 8436587 ER PT J AU DAAR, I YEW, N WOUDE, GFV AF DAAR, I YEW, N WOUDE, GFV TI INHIBITION OF MOS-INDUCED OOCYTE MATURATION BY PROTEIN KINASE-A SO JOURNAL OF CELL BIOLOGY LA English DT Article ID CYCLIC-AMP PHOSPHODIESTERASE; XENOPUS-LAEVIS OOCYTES; ONCOGENIC RAS PROTEIN; MEIOTIC MATURATION; ADENYLATE-CYCLASE; S6 KINASE; PROGESTERONE INHIBITION; AMPHIBIAN OOCYTES; CELL-CYCLE; PHOSPHORYLATION AB The relationship between the mos protooncogene protein and cAMP-dependent protein kinase (PKA) during the maturation of Xenopus oocytes was investigated. Microinjection of the PKA catalytic subunit (PKA(c)) into Xenopus oocytes inhibited oocyte maturation induced by the mos product but did not markedly affect the autophosphorylation activity of injected mos protein. By contrast, PKA(c) did not inhibit maturation promoting factor (MPF) activation or germinal vesicle breakdown (GVBD) that was initiated by injecting crude MPF preparations. In addition, inhibiting endogenous PKA activity by microinjecting the PKA regulatory subunit (PKA(r)) induced oocyte maturation that was dependent upon the presence of the endogenous mos product. Moreover, PKA(r) potentiated mos protein-induced MPF activation in the absence of progesterone and protein synthesis. These data are consistent with the hypothesis that progesterone-induced release from G2/M is regulated via PKA(c) and that PKA(c) negatively regulates a downstream target that is positively regulated by mos. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL,BASIC RES PROGRAM,FREDERICK,MD 21702. OI Daar, Ira/0000-0003-2657-526X FU NCI NIH HHS [N01-CO-74101] NR 49 TC 64 Z9 65 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD MAR PY 1993 VL 120 IS 5 BP 1197 EP 1202 DI 10.1083/jcb.120.5.1197 PG 6 WC Cell Biology SC Cell Biology GA KN669 UT WOS:A1993KN66900013 PM 8436591 ER PT J AU KARTASOVA, T ROOP, DR HOLBROOK, KA YUSPA, SH AF KARTASOVA, T ROOP, DR HOLBROOK, KA YUSPA, SH TI MOUSE DIFFERENTIATION-SPECIFIC KERATIN-1 AND KERATIN-10 REQUIRE A PREEXISTING KERATIN SCAFFOLD TO FORM A FILAMENT NETWORK SO JOURNAL OF CELL BIOLOGY LA English DT Article ID INTERMEDIATE-SIZED FILAMENTS; EPIDERMAL KERATIN; EPITHELIAL-CELLS; GENE-EXPRESSION; MESSENGER-RNA; TERMINAL DIFFERENTIATION; NONEPITHELIAL CELLS; SEQUENCE; DNA; MICROINJECTION AB Keratins 1 (K1) and 10 (K10) are the predominant cytoskeletal intermediate filaments of epidermal cells during transition from the proliferative to the terminal differentiation stage. In situ, formation of the K1/K10 intermediate filament network occurs in the cytoplasm of cells with a preexisting cytoskeleton composed of keratins 5 and 14. To define cytoskeletal interactions permissive for formation of the K1/K10 filamentous network, active copies of mouse K1 and K10 genes were introduced into fibroblasts (NIH 3T3) which do not normally express these proteins. Transient and stable transfectants, as well as heterokaryons produced by fusions with epithelial cells, were evaluated for expression of K1 and K10 proteins and filament formation using specific antibodies. In contrast to keratin pairs K5/K14 and K8/K18, the K1/K10 pair failed to form an extensive keratin filament network on its own, although small isolated dense K1/K10 filament bundles were observed throughout the cytoplasm by EM. K1 and K10 filaments integrated only into the preexisting K5/K14 network upon fusion of the NIH 3T3 (K1/K10) cells with epithelial cells expressing endogenous K5/K14 or with NIH 3T3 cells which were transfected with active copies of the K5 and K14 genes. When combinations of active recombinant gene constructs for keratins 1, 5, 10, and 14 were tested in transient NIH 3T3 transfections, the most intact cytokeratin network observed by immunofluorescence was formed by the K5/K14 pair. The K1/K14 pair was capable of forming a cytoskeletal network, but the network was poorly developed, and usually perinuclear. Transfection of K10 in combination with K5 or K1 resulted in cytoplasmic agglomerates, but not a cytoskeleton. These results suggest that the formation of the suprabasal cytoskeleton in epidermis is dependent on the preexisting basal cell intermediate filament network. Furthermore, restrictions on filament formation appear to be more stringent for K10 than for K1. C1 NCI,DIV CANC ETIOL,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BETHESDA,MD 20892. BAYLOR COLL MED,DEPT CELL BIOL,HOUSTON,TX 77030. UNIV WASHINGTON,DEPT BIOL STRUCT,SEATTLE,WA 98195. NR 49 TC 46 Z9 47 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD MAR PY 1993 VL 120 IS 5 BP 1251 EP 1261 DI 10.1083/jcb.120.5.1251 PG 11 WC Cell Biology SC Cell Biology GA KN669 UT WOS:A1993KN66900018 PM 7679677 ER PT J AU SUPRYNOWICZ, FA AF SUPRYNOWICZ, FA TI INACTIVATION OF CDC2 KINASE DURING MITOSIS REQUIRES REGULATED AND CONSTITUTIVE PROTEINS IN A CELL-FREE SYSTEM SO JOURNAL OF CELL SCIENCE LA English DT Article DE CDC2 KINASE; MITOSIS; CELL-FREE SYSTEM ID HISTONE H-1 KINASE; MATURATION-PROMOTING FACTOR; CHINESE-HAMSTER CELLS; M-PHASE; MITOTIC FACTORS; CYCLIN-B; TYROSINE PHOSPHORYLATION; MAMMALIAN-CELLS; NUCLEAR LAMINA; MICROCYSTIN-LR AB Inactivation of the cyclin-p34cdc2 protein kinase complex is a major requirement for anaphase onset and exit from mitosis. To facilitate identification of specific molecules that regulate this event in mammalian cells, I have developed a cell-free assay in which cdc2 kinase associated with a chromosomal fraction from metaphase tissue culture cells is inactivated by a cell-cycle-regulated cytosolic system. In vitro kinase inactivation requires ATP, Mg2+ and the dephosphorylation of one or more sites in the chromosomal fraction by protein phosphatase 1 and/or 2A. Cyclin B is destroyed during inactivation, while the level of p34cdc2 remains constant. Ammonium sulfate fractionation resolves the cytosolic inactivating system into at least two distinct protein components that are both required for inactivation and are differentially regulated during mitosis. C1 NCI,BIOCHEM LAB,BETHESDA,MD 20892. NR 61 TC 4 Z9 4 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 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD MAR PY 1993 VL 104 BP 873 EP 881 PN 3 PG 9 WC Cell Biology SC Cell Biology GA KY983 UT WOS:A1993KY98300027 PM 8314879 ER PT J AU LI, LW KRUSZEWSKI, FH PUNNONEN, K TUCKER, RW YUSPA, SH HENNINGS, H AF LI, LW KRUSZEWSKI, FH PUNNONEN, K TUCKER, RW YUSPA, SH HENNINGS, H TI STRONTIUM INDUCES MURINE KERATINOCYTE DIFFERENTIATION INVITRO IN THE PRESENCE OF SERUM AND CALCIUM SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID MOUSE EPIDERMAL-CELLS; INTRACELLULAR-FREE CALCIUM; INOSITOL PHOSPHATE-METABOLISM; CULTURED HUMAN KERATINOCYTES; PROTEIN KINASE-C; TERMINAL DIFFERENTIATION; EXTRACELLULAR CALCIUM; TUMOR PROMOTERS; EXPRESSION; TRANSGLUTAMINASE AB Primary mouse keratinocytes in culture are induced to terminally differentiate by increasing extracellular Ca2+ concentrations (Ca(o)) from 0.05 mM to greater-than-or-equal-to 0.1 mM. The addition of Sr2+ (greater-than-or-equal-to 2.5 mM) to medium containing 0.05 mM Ca2+ induces focal stratification and terminal differentiation, which are similar to that found after increasing the Ca(o) to 0.12 mM. Sr2+ in 0.05 mM Ca2+ medium induces the expression of the differentiation-specific keratins, keratin 1 (K1), keratin 10 (Kl 0), and the granular cell marker, filaggrin, as determined by both immunoblotting and immunofluorescence. Sr2+ induces the expression of those differentiation markers in a dose dependent manner, with an optimal concentration of 5 mM. In the absence of Ca2+ in the medium, the Sr2+ effects are reduced, and Sr2+ is ineffective when both Ca2+ and serum are deleted from the medium. Sr2+ treatment increases the ratio of fluorescence intensity of the intracellular Ca2+ sensitive probe, fura-2, indicating an associated rise in the level of intracellular free Ca2+ and/or Sr2+. At doses sufficient to induce differentiation, Sr2+ also increases the level of inositol phosphates in primary keratinocytes within 30 min. The uptake curves of Sr-85(2+) by primary keratinocytes are similar to those of Ca-45(2+). At low concentrations, the initial uptake of both Ca-45(2+) and Sr-85(2+) reaches a plateau within 1 hr; at higher concentrations, the uptake of both Ca-45(2+) and Sr-85(2+) increases continuously for 12 hr. In keratinocytes pre-equilibrated with Ca-45(2+) in 0.05 MM Ca2+ medium, Sr2+ causes an increase of Ca-45(2+) uptake, which is dependent on the presence of serum. These results suggest that Sr2+ utilizes the same signalling pathway as Ca2+ to induce keratinocyte terminal differentiation and that Ca2+ may be required to exert these effects. C1 NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BETHESDA,MD 20892. JOHNS HOPKINS UNIV HOSP,CTR ONCOL,BALTIMORE,MD 21205. NR 47 TC 16 Z9 17 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD MAR PY 1993 VL 154 IS 3 BP 643 EP 653 DI 10.1002/jcp.1041540324 PG 11 WC Cell Biology; Physiology SC Cell Biology; Physiology GA KP604 UT WOS:A1993KP60400023 PM 7679679 ER PT J AU STROMBERG, C NAVERI, L SAAVEDRA, JM AF STROMBERG, C NAVERI, L SAAVEDRA, JM TI NONPEPTIDE ANGIOTENSIN AT1 AND AT2 RECEPTOR LIGANDS MODULATE THE UPPER LIMIT OF CEREBRAL BLOOD-FLOW AUTOREGULATION IN RATS SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE ANGIOTENSIN RECEPTORS; CEREBROVASCULAR CIRCULATION; HYPERTENSION; LASER-DOPPLER FLOWMETRY; LOSARTAN; PD-123319 ID CONVERTING ENZYME-INHIBITION; II BINDING-SITES; AUTO-REGULATION; BRAIN; SUBTYPES; ARTERIES; SYSTEM AB We investigated the effect of angiotensin AT1 and AT2 receptor blockade on the upper limit of CBF autoregulation in pentobarbital-anesthetized rats. CBF was measured by laser-Doppler flowmetry from the parietal cortex and MABP was increased by intravenous phenylephrine infusion. Neither the AT1 antagonist losartan nor the AT2 ligand PD 123319 nor angiotensin II (ANG II) in the presence of losartan affected baseline CBF. When the blood pressure was increased in the control group, CBF remained fairly constant up to 145 mm Hg and increased steeply after 150 mm Hg. Both PD 123319 (7-10 mg/kg) and losartan (1-10 mg/kg) shifted the upper limit of CBF autoregulation toward higher pressures. Intravenous infusion of PD 123319 was more effective than bolus injection. The losartan effect was dose dependent. Selective stimulation of AT2 receptors with an intravenous ANG II infusion (0.54 mug/min) in the presence of losartan did not reverse the effect of losartan on CBF autoregulation, but, on the contrary, appeared to further shift the upper limit of autoregulation toward higher pressures. The results implicate a role for both AT1 and AT2 angiotensin receptors in the regulation of CBF. RP STROMBERG, C (reprint author), NIMH,CLIN SCI LAB,PHARMACOL SECT,BLDG 10,RM 2D-45,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 42 TC 46 Z9 46 U1 0 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 1993 VL 13 IS 2 BP 298 EP 303 PG 6 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA KM808 UT WOS:A1993KM80800016 PM 8436622 ER PT J AU DIENEL, GA CRUZ, NF SOKOLOFF, L AF DIENEL, GA CRUZ, NF SOKOLOFF, L TI METABOLITES OF 2-DEOXY-[C-14]GLUCOSE IN PLASMA AND BRAIN - INFLUENCE ON RATE OF GLUCOSE-UTILIZATION DETERMINED WITH DEOXYGLUCOSE METHOD IN RAT-BRAIN SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE GLUCOSE; METABOLISM ID STABILITY INVIVO; NMR-SPECTROSCOPY; 2-DEOXY-D-GLUCOSE; 2-DEOXYGLUCOSE; GLYCOSYLATION; OLIGOSACCHARIDES; INTERFERENCE AB The [14]deoxyglucose ([C-14]DG) method depends upon quantitative trapping of metabolites in brain at the site of phosphorylation, and in the usual procedure it is assumed that all the label in plasma is in free DG. Our previous finding of labeled nonacidic derivatives of DG in plasma raised the possibility that some metabolites of DG might not be fully retained in body tissues and therefore cause overestimation of the integrated specific activity of the precursor pool determined from assay of label in plasma and/or underestimation of the true size of the metabolite fraction in brain. In the present study, metabolism of DG in rat tissues by secondary pathways was examined and found to be more extensive than previously recognized. When C-14-labeled compounds in ethanol extracts of either plasma or brain were separated by anion exchange HPLC, eight fractions were obtained. C-14-labeled metabolites in plasma were detected after a 35-min lag and gradually increased in amount with time after an intravenous pulse. In brain, deoxyglucose-6-phosphate was further metabolized, mainly to deoxyglucose-1-phosphate and deoxyglucose-1,6-phosphate. These are acid-labile compounds and accounted for approximately 20% of the C-14 in the metabolite pool in brain. The rate constants for net loss of C-14 from the metabolite pool between 45 and 180 min after a pulse were similar (0.4-0.5%/min) in vivo and in intact postmortem brain. The rate constant for loss of deoxyglucose-6-phosphate (DG-6-P) in vivo (approximately 0.7%/min) was, however, about twice that for postmortem brain, suggesting that a significant fraction of the DG-6-P lost in vivo is due to its further metabolism by energy-dependent reactions. C-14-labeled metabolites of [C-14]DG in plasma and brain do not interfere with determination of local rates of glucose utilization in brain in normal, conscious rats by the autoradiographic method if the prescribed procedures and a 45-min experimental period are used. RP DIENEL, GA (reprint author), NIMH,CEREBRAL METAB LAB,BLDG 36,RM 1A-05,BETHESDA,MD 20892, USA. NR 45 TC 26 Z9 26 U1 0 U2 1 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 1993 VL 13 IS 2 BP 315 EP 327 PG 13 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA KM808 UT WOS:A1993KM80800019 PM 8436625 ER PT J AU MAHER, F VANNUCCI, SJ SIMPSON, IA AF MAHER, F VANNUCCI, SJ SIMPSON, IA TI GLUCOSE TRANSPORTER ISOFORMS IN BRAIN - ABSENCE OF GLUT3 FROM THE BLOOD-BRAIN-BARRIER SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Note DE BLOOD BRAIN BARRIER; GLUCOSE TRANSPORTER; GLUT3; MICROVESSELS ID RAT-BRAIN; PRIMARY CULTURES; MESSENGER-RNA; GLIAL-CELLS; LOCALIZATION; INSULIN; TISSUES; PROTEIN AB Two glucose transporter (GLUT) isoforms have been identified in brain. The GLUT1 isoform is abundant in cerebral microvessels and may be present in glia and neurons, whereas GLUT3 is probably the major neuronal glucose transporter. This study investigates whether GLUT3 is also present in microvessels from rat, human, and canine brain, by means of antisera directed against the divergent C-terminal sequences of mouse and human GLUT3. GLUT1 was detected in whole brain as two molecular mass forms: 55 kDa in microvessels and 45 kDa in cortical neuronal/glial membranes. With the aid of the appropriate antisera to the species-specific sequences, GLUT3 was detected in rat and human cortical membranes but not in isolated rat or human microvessels. These antisera failed to detect GLUT3 in either canine cortical membranes or canine microvessels, implying additional species specificity in the C-terminal sequence. C1 PENN STATE UNIV,MILTON S HERSHEY MED CTR,COLL MED,DEPT PEDIAT,HERSHEY,PA 17033. RP MAHER, F (reprint author), NIDDK,DIABET BRANCH,EXPTL DIABET METAB & NUTR SECT,BETHESDA,MD 20892, USA. NR 18 TC 72 Z9 73 U1 0 U2 3 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD MAR PY 1993 VL 13 IS 2 BP 342 EP 345 PG 4 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA KM808 UT WOS:A1993KM80800022 PM 8436627 ER PT J AU MULLER, DC ELAHI, D PRATLEY, RE TOBIN, JD ANDRES, R AF MULLER, DC ELAHI, D PRATLEY, RE TOBIN, JD ANDRES, R TI AN EPIDEMIOLOGIC TEST OF THE HYPERINSULINEMIA-HYPERTENSION HYPOTHESIS SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID BLOOD-PRESSURE; PLASMA-INSULIN; OBESITY; GLUCOSE; METABOLISM AB The association between hyperinsulinemia and hypertension was tested in a population of 421 men and 228 women from the Baltimore Longitudinal Study of Aging. Subjects are white, middle-class, generally healthy, community-dwelling volunteers who ranged in age from 17-95 yr. Those with diseases or medications known to influence any of the studied variables were excluded from the analysis. Twenty-five percent of the subjects were borderline or hypertensive [systolic blood pressure (BP) greater-than-or-equal-to 140 or diastolic BP greater-than-or-equal-to 90 mm Hg]. Standard oral glucose tolerance tests were performed; the logarithms of the fasting insulin level and insulin area were used in the analyses. In addition, body mass index and percent body fat (from age and skinfold thickness equations) and waist hip ratio were computed. In simple correlations, systolic BP and diastolic BP were statistically significantly related to insulin levels (only 1-4% of the variance was explained). Since age, body fat, fat distribution, insulin levels, and BP were highly intercorrelated, insulin and blood pressure correlations were examined after controlling for the confounding variables. Correlations of BP and insulin levels adjusted for age, body fat, and fat distribution were entirely nonsignificant. In this large noninterventive population study, the hyperinsulinemia-hypertension hypothesis is not confirmed. C1 NIA, GERONTOL RES CTR, APPL PHYSIOL LAB, BALTIMORE, MD 21224 USA. HARVARD UNIV, BETH ISRAEL HOSP, DEPT MED, DIV AGING, BOSTON, MA 02215 USA. HARVARD UNIV, BRIGHAM & WOMENS HOSP, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, BOSTON, MA 02115 USA. RP MULLER, DC (reprint author), NIA, FRANCIS SCOTT KEY MED CTR, GERONTOL RES CTR, CLIN PHYSIOL LAB, BALTIMORE, MD 21224 USA. FU NIA NIH HHS [AG-00599, AG-088121] NR 24 TC 82 Z9 83 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 1993 VL 76 IS 3 BP 544 EP 548 DI 10.1210/jc.76.3.544 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA KQ341 UT WOS:A1993KQ34100003 PM 8445009 ER PT J AU SCHMIDT, PJ GROVER, GN ROYBYRNE, PP RUBINOW, DR AF SCHMIDT, PJ GROVER, GN ROYBYRNE, PP RUBINOW, DR TI THYROID-FUNCTION IN WOMEN WITH PREMENSTRUAL-SYNDROME SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID PROLACTIN RESPONSES; LEVOTHYROXINE; HYPOTHYROIDISM; THYROTROPIN; REPLACEMENT; DISORDER; HORMONE AB We have examined the relationship between thyroid function and the presence of symptoms in women with prospectively confirmed premenstrual syndrome (PMS) in the following ways: 1) basal thyroid function tests (n = 124); 2) thyroid auto-antibody levels (n = 63); 3) TRH stimulation tests performed during the follicular phase (n = 39) or during both the follicular and luteal phase (n = 21); and 4) the efficacy Of L-T, in the treatment of PMS (n = 30). Results: Thirteen women (10.5%) had basal evidence of either grade I or II hypothyroidism or hyperthyroidism. Elevated thyroid auto-antibody titers were observed in eight women (13%). Eighteen women (30%) (all with normal basal TSH levels) had abnormal responses to TRH, either blunted (n = 6) or exaggerated (n = 12). L-T, was not superior to placebo in the treatment of PMS in a double blind placebo controlled cross-over trial. Although it is clear that PMS is not simply masked hypothyroidism, abnormalities of stimulated thyroid function appear with greater than expected frequency in women with PMS and may define a subgroup of women with this disorder. L-T4 supplementation appears to have no place in the routine management of PMS. RP SCHMIDT, PJ (reprint author), NIMH, BLDG 10, ROOM 3N238, 9000 ROCKVILLE PIKE, BETHESDA, MD 20892 USA. NR 25 TC 26 Z9 26 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 1993 VL 76 IS 3 BP 671 EP 674 DI 10.1210/jc.76.3.671 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA KQ341 UT WOS:A1993KQ34100025 PM 8445024 ER PT J AU YANOVSKI, SZ YANOVSKI, JA GWIRTSMAN, HE BERNAT, A GOLD, PW CHROUSOS, GP AF YANOVSKI, SZ YANOVSKI, JA GWIRTSMAN, HE BERNAT, A GOLD, PW CHROUSOS, GP TI NORMAL DEXAMETHASONE SUPPRESSION IN OBESE BINGE AND NONBINGE EATERS WITH RAPID WEIGHT-LOSS SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID PITUITARY-ADRENAL-AXIS; LOW-CALORIE DIET; THYROID-HORMONES; PROTEIN; BULIMIA; CORTISOL; METABOLISM AB Natural or experimental starvation is frequently associated with hypercortisolism, reflected as incomplete suppression of serum cortisol after dexamethasone. To determine whether rapid weight loss per se or some other aspect of starvation induces disruption of the hypothalamic-pituitary-adrenal (HPA) axis, we evaluated 2 categories of obese women (body mass index >30 kg/m2) undergoing rapid weight loss: binge eaters (n = 12) and nonbinge eaters (n = 8). We performed psychometric evaluation and 1 mg overnight dexamethasone suppression tests in the obese subjects, as well as in 12 race- and age-matched normal-weight women. The obese women were tested before and after 12 weeks of a 3349 kJ/day (800 kcal/day) liquid formula diet, and lost an average of 19.3 kg, which represented 17.3% of their total body weight. Binge eaters, who were initially more depressed than either nonbinge eaters or normal-weight controls, had a significant amelioration of their symptoms with weight loss. Neither group had evidence of disruption of the HPA axis before or after weight loss. Thus, the rate of failure to suppress cortisol after dexamethasone was approximately 10% in each of the obese and control groups, and did not differ between the pre-and postweight loss condition or between binge eaters and nonbinge eaters. Serum free T4 was unchanged, whereas T3 fell significantly with weight loss. We conclude that weight loss may improve affect in the obese without altering HPA axis activity, and postulate that one of the concomitants of restricted energy intake, perhaps in combination with a threshold body weight, may be of greater importance in causing abnormalities of dexamethasone suppression testing than rapid weight loss per se. C1 NICHHD, DEV ENDOCRINOL BRANCH, BETHESDA, MD 20892 USA. NIDDKDMA, DIV DIGEST DIS & NUTR, BETHESDA, MD 20892 USA. NIMH, PERSONAL DISORDERS BRANCH, BETHESDA, MD 20892 USA. RP YANOVSKI, SZ (reprint author), NIMH, CLIN NEUROENDOCRINOL BRANCH, BLDG 10 3S231, 9000 ROCKVILLE PIKE, BETHESDA, MD 20892 USA. NR 38 TC 20 Z9 20 U1 1 U2 1 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 1993 VL 76 IS 3 BP 675 EP 679 DI 10.1210/jc.76.3.675 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA KQ341 UT WOS:A1993KQ34100026 PM 8445025 ER PT J AU KARL, M LAMBERTS, SWJ DETERAWADLEIGH, SD ENCIO, IJ STRATAKIS, CA HURLEY, DM ACCILI, D CHROUSOS, GP AF KARL, M LAMBERTS, SWJ DETERAWADLEIGH, SD ENCIO, IJ STRATAKIS, CA HURLEY, DM ACCILI, D CHROUSOS, GP TI FAMILIAL GLUCOCORTICOID RESISTANCE CAUSED BY A SPLICE SITE DELETION IN THE HUMAN GLUCOCORTICOID RECEPTOR GENE SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID PRIMARY CORTISOL RESISTANCE; HORMONE-BINDING DOMAIN; THYROID-HORMONE; DNA-BINDING; MUTATION; IDENTIFICATION; LOCALIZATION; DISEASE; RNA AB The clinical syndrome of generalized, compensated glucocorticoid resistance is characterized by increased cortisol secretion without clinical evidence of hyper- or hypocortisolism, and manifestations of androgen and/or mineralocorticoid excess. This condition results from partial failure of the glucocorticoid receptor (GR) to modulate transcription of its target genes. We studied the molecular mechanisms of this syndrome in a Dutch kindred, whose affected members had hypercortisolism and approximately half of normal GRs, and whose proband was a young woman with manifestations of hyperandrogenism. Using the polymerase chain reaction to amplify and sequence each of the nine exons of the GR gene alpha, along with their 5'- and 3'-flanking regions, we identified a 4-base deletion at the 3'-boundary of exon 6 in one GR allele (DELTA4), which removed a donor splice site in all three affected members studied. In contrast, the sequence of exon 6 in the two unaffected siblings was normal. A single nucleotide substitution causing an amino acid substitution in the amino terminal domain of the GR (asparagine to serine, codon 363) was also discovered in exon 2 of the other allele (G1220) in the proband, in one of her affected brothers and in her unaffected sister. The functional importance of this mutation was tested in a cotransfection study using the recombinant expression vector pRShGR-Ser363 and the glucocorticoid responsive vector mouse mammary tumor virus-chloramphenicol transferase. This amino acid substitution did not alter the function of the glucocorticoid receptor. Using reverse transcription-polymerase chain reaction we could only identify messenger RNA transcripts of the G1220-allele but not of the DELTA4-allele in the affected members of this family who were heterozygous for the G1220 mutation. This deletion in the glucocorticoid receptor gene was, thus, associated with the expression of only one allele and a decrease of GR protein by 50% in affected members of this glucocorticoid resistant family. The mutation identified in exon 2 did not segregate with the disease and appears to be of no functional significance. The presence of the null allele was apparently compensated for by increased cortisol production at the expense of concurrent hyperandrogenism. C1 NIMH, CLIN NEUROGENET BRANCH, BETHESDA, MD 20892 USA. NIDDKD, DIABET BRANCH, BETHESDA, MD 20892 USA. ERASMUS UNIV, DEPT MED, 3000 DR ROTTERDAM, NETHERLANDS. RP KARL, M (reprint author), NICHHD, DEV ENDOCRINOL BRANCH, BLDG 10, ROOM 10N 240, BETHESDA, MD 20892 USA. OI Encio, Ignacio/0000-0003-1732-1989 NR 40 TC 189 Z9 199 U1 0 U2 1 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 1993 VL 76 IS 3 BP 683 EP 689 DI 10.1210/jc.76.3.683 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA KQ341 UT WOS:A1993KQ34100028 PM 8445027 ER PT J AU SKARLATOS, SI DICHEK, HL FOJO, SS BREWER, HB KRUTH, HS AF SKARLATOS, SI DICHEK, HL FOJO, SS BREWER, HB KRUTH, HS TI ABSENCE OF TRIGLYCERIDE ACCUMULATION IN LIPOPROTEIN LIPASE-DEFICIENT HUMAN MONOCYTE-MACROPHAGES INCUBATED WITH HUMAN VERY LOW-DENSITY-LIPOPROTEIN SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Note ID MOUSE PERITONEAL-MACROPHAGES; SECRETION; METABOLISM; CULTURE AB Lipoprotein lipase, a lipolytic enzyme essential for normal hydrolysis of triglycerides in very low.density lipoprotein (VLDL) and chylomicrons, is found in several cell types, including macrophages. The role of lipoprotein lipase in mediating the uptake of normal VLDL triglycerides into human cultured monocyte-derived macrophages was studied using macrophage cells from a functionally lipoprotein lipase-deficient patient and macrophages of cells from a normal subject. After incubation with VLDL, massive accumulation of phase refractile (lipid) inclusions were noted by phase contrast microscopy within the normal, but not within the lipoprotein lipase-deficient, macrophages. Chemical determinations of intracellular lipid confirmed massive triglyceride accumulation within normal macrophages, but not in lipoprotein lipase-deficient macrophages. VLDL-derived cholesterol did not accumulate in either cell. These results confirm an additional role of lipoprotein lipase, that of mediating triglyceride accumulation into macrophages from normal human VLDL. Human monocyte-macrophages genetically deficient in a functional lipoprotein lipase will be useful to determine the role of lipoprotein lipase in macrophage accumulation of lipid from other forms of triglyceride-carrying lipoproteins, including hypertriglyceridemic VLDL, betaVLDL, and chylomicrons. C1 NATL HEART LUNG & BLOOD INST, MOLEC DIS BRANCH,EXPTL ATHEROSCLEROSIS SECT, BLDG 10,ROOM 5N-113, BETHESDA, MD 20892 USA. NR 29 TC 25 Z9 25 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 1993 VL 76 IS 3 BP 793 EP 796 DI 10.1210/jc.76.3.793 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA KQ341 UT WOS:A1993KQ34100047 PM 8383147 ER PT J AU CLERICI, M HAKIM, FT VENZON, DJ BLATT, S HENDRIX, CW WYNN, TA SHEARER, GM AF CLERICI, M HAKIM, FT VENZON, DJ BLATT, S HENDRIX, CW WYNN, TA SHEARER, GM TI CHANGES IN INTERLEUKIN-2 AND INTERLEUKIN-4 PRODUCTION IN ASYMPTOMATIC, HUMAN IMMUNODEFICIENCY VIRUS-SEROPOSITIVE INDIVIDUALS SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE INTERLEUKIN-2; INTERLEUKIN-4; INTERLEUKIN-10; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; T-LYMPHOCYTES ID T-HELPER-CELL; ANTIGEN-PRESENTING CELL; CYTOKINE PRODUCTION; INFECTED INDIVIDUALS; SUPPRESSOR FACTORS; ENVELOPE PROTEIN; AIDS PATIENTS; INVITRO; HIV; SUBSETS AB Infection with HIV results in an incremental loss of T helper cell (TH) function, which can occur years before CD4 cell numbers are critically reduced and AIDS is diagnosed. All TH function is not affected, however, because B cell activation and hypergammaglobulinema are also characteristic of this period. Recently, in a murine model of AIDS an early loss in production of the CD4 cytokines IL-2 and IFN-gamma was correlated with an increase in the B cell stimulatory cytokines IL-4, IL-5, and IL-10. We therefore assessed the production of IL-4 generated by PBL from HIV-seropositive (HIV+) individuals who did not have AIDS, yet who exhibited different TH functional categories based on their IL-2 production profiles. We observed that the decreases in recall antigen-stimulated IL-2 production were accompanied by an increase in IL-4 production. The loss of recall antigen-stimulated responses in HIV+ individuals could be reversed in vitro by anti-IL4 antibody. Our results suggest that the TH functions assessed by IL-4 production replace the normally dominant TH function of antigen-stimulated IL-2 production in the progression toward AIDS, and raise the possibility of cytokine cross-regulation in AIDS therapy. C1 NCI,EXPTL IMMUNOL BRANCH,BLDG 10,ROOM 4B-17,BETHESDA,MD 20892. NIAID,PARASIT DIS LAB,BETHESDA,MD 20892. WILFORD HALL USAF MED CTR,HIV UNIT,LACKLAND AFB,TX 78236. NCI,BIOSTAT & DATA MANAGEMENT SECT,BETHESDA,MD 20892. RI Venzon, David/B-3078-2008; Wynn, Thomas/C-2797-2011; Hendrix, Craig/G-4182-2014 OI Hendrix, Craig/0000-0002-5696-8665 NR 52 TC 479 Z9 481 U1 0 U2 11 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAR PY 1993 VL 91 IS 3 BP 759 EP 765 DI 10.1172/JCI116294 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA KR461 UT WOS:A1993KR46100004 PM 8450057 ER PT J AU LOVE, LA RADER, JI CROFFORD, LJ RAYBOURNE, RB PRINCIPATO, MA PAGE, SW TRUCKSESS, MW SMITH, MJ DUGAN, EM TURNER, ML ZELAZOWSKI, E ZELAZOWSKI, P STERNBERG, EM AF LOVE, LA RADER, JI CROFFORD, LJ RAYBOURNE, RB PRINCIPATO, MA PAGE, SW TRUCKSESS, MW SMITH, MJ DUGAN, EM TURNER, ML ZELAZOWSKI, E ZELAZOWSKI, P STERNBERG, EM TI PATHOLOGICAL AND IMMUNOLOGICAL EFFECTS OF INGESTING L-TRYPTOPHAN AND 1,1'-ETHYLIDENEBIS(L-TRYPTOPHAN) IN LEWIS RATS SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE EOSINOPHILIA-MYALGIA SYNDROME; IMMUNE ACTIVATION; FIBROSIS; PANCREATITIS; SUPPLEMENT ID EOSINOPHILIA-MYALGIA-SYNDROME; SCLERODERMA; FASCIITIS; ILLNESS; EMS AB The eosinophilia-myalgia syndrome (EMS) has been associated with ingestion of L-tryptophan (L-TRP) produced by a single manufacturer. Epidemiological data implicated 1,1'-ethylidenebis(L-tryptophan) (EBT) (peak 97 or peak E) as a possible etiologic agent. We showed previously that Lewis rats treated with the L-TRP implicated in EMS develop fasciitis and perimyositis similar to those seen in human EMS. We now report the pathology associated with the treatment of Lewis rats with synthetic EBT and/Or L-TRP. Atl animals treated for 6 wk with case-associated L-TRP or EBT developed significant myofascial thickening, compared with animals in the vehicle control and control L-TRP groups. However, even those animals receiving the control L-TRP showed a mild but significant increase in the thickness of the myofascia, compared with vehicle-treated control animals. All animals except vehicle controls also exhibited significant pancreatic pathology, including fibrosis and acinar changes. Only animals treated with case-associated L-TRP for 6 wk showed evidence of immune activation with increased frequency of CD8, Ia, and IL-2 receptor-positive cells in the peripheral blood. Animals receiving L-TRP or EBT for < 6 wk did not show significant differences in myofascial thickness, although these animals did show pancreatic acinar changes. Although these results demonstrate for the first time the pathological effects of EBT, they do not rule out the possibility that other impurities in the EMS-case-associated L-TRP may also contribute to some of the features of EMS. C1 US FDA,CTR FOOD SAFETY & APPL NUTR,WASHINGTON,DC 20204. NCI,BETHESDA,MD 20892. NIMH,ALCOHOL DRUG ABUSE & MENTAL HLTH ADM,BETHESDA,MD 20892. NIAMSD,BETHESDA,MD 20892. RI Crofford, Leslie/J-8010-2013 NR 35 TC 53 Z9 53 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAR PY 1993 VL 91 IS 3 BP 804 EP 811 DI 10.1172/JCI116300 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA KR461 UT WOS:A1993KR46100010 PM 8450062 ER PT J AU ZHOU, J BONDY, CA AF ZHOU, J BONDY, CA TI PLACENTAL GLUCOSE TRANSPORTER GENE-EXPRESSION AND METABOLISM IN THE RAT SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE DEOXYGLUCOSE; INSITU HYBRIDIZATION; TROPHOBLAST; DECIDUA; EMBRYONIC DEVELOPMENT ID INSULIN RECEPTORS; PROTEIN; CLONING; LIVER AB In situ hybridization was used to evaluate patterns of gene expression for glucose transporters 1-4 (GT1-4) in the rat uteroplacenta from the time of implantation through term, and in vivo regional placental glucose metabolism was measured by C-14-labeled 2-deoxyglucose uptake. GT1 mRNA was highly abundant and GT3 was barely detected in the postimplantation decidual reaction. GT1 and 3 mRNAs were colocalized in the labyrinthine syncitiotrophoblast layer of the chorioallantoic placenta, which forms the membranous barrier between maternal and fetal circulations. The level of labyrinthine GT3 mRNA showed no change from midgestation through term; however, the volume of the labyrinth and hence total GT 3 gene expression increased greatly during this period. Labyrinthine GT1 mRNA levels, in contrast, showed significant diminution near term. GT1 mRNA was also localized in the placental growth plate, or junctional zone, where it was most abundant during the period of rapid placental growth and was decreased at term. Placental glucose metabolism, as reflected by steady-state 2-deoxyglucose uptake, was highest in the junctional zone during the rapid growth phase during midgestation, and decreased significantly at term, in parallel with GT1 gene expression. These findings suggest that GT1 is responsible for supplying glucose for use as a placental fuel and that GT3 is important for glucose transfer to the embryo. RP ZHOU, J (reprint author), NICHHD,DEV ENDOCRINOL BRANCH,BLDG 10,ROOM 10N262,BETHESDA,MD 20892, USA. NR 26 TC 99 Z9 100 U1 1 U2 5 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAR PY 1993 VL 91 IS 3 BP 845 EP 852 DI 10.1172/JCI116305 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA KR461 UT WOS:A1993KR46100015 PM 8450065 ER PT J AU SCHWARTZ, CC ZECH, LA VANDENBROEK, JM COOPER, PS AF SCHWARTZ, CC ZECH, LA VANDENBROEK, JM COOPER, PS TI CHOLESTEROL KINETICS IN SUBJECTS WITH BILE FISTULA - POSITIVE RELATIONSHIP BETWEEN SIZE OF THE BILE-ACID PRECURSOR POOL AND BILE-ACID SYNTHETIC RATE SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE HIGH DENSITY LIPOPROTEIN; BLOOD CELL CHOLESTEROL; ESTERIFIED CHOLESTEROL; MULTICOMPARTMENTAL ANALYSIS; HEPATIC CHOLESTEROL ID HIGH-DENSITY LIPOPROTEIN; MULTICOMPARTMENTAL ANALYSIS; ENDOPLASMIC-RETICULUM; PLASMA-MEMBRANE; METABOLISM; 7-ALPHA-HYDROXYLASE; TURNOVER; ENZYME; CELL AB Our aim was to identify and quantitate cholesterol pools and transport pathways in blood and liver. By studying bile fistula subjects, using several types of isotopic preparations, simultaneous labeling of separate cholesterol pools and sampling all components of blood and bile at frequent intervals, we developed a comprehensive multicompartmental model for cholesterol within the rapidly miscible pool. Data in six components (bile acids, esterified cholesterol in whole plasma, and free cholesterol in blood cells, bile, a lipoproteins, and beta lipoproteins) were modeled simultaneously with the SAAM program. The analysis revealed extensive exchange of free cholesterol between HDL and liver, blood cells, and other tissues. There was net free cholesterol transport from HDL to the liver in most subjects. The major organ that removed esterified cholesterol from blood was the liver. A large portion (4,211 mumol) of total hepatic cholesterol comprised a pool that turned over rapidly (t1/2 of 72 min) by exchanging mainly with plasma HDL and was the major source of bile acids and biliary cholesterol. Only 6% of hepatic newly synthesized cholesterol was used directly for bile acid synthesis: the analysis showed that 94% of newly synthesized cholesterol was partitioned into the large hepatic pool (putative plasma membrane free cholesterol) which exchanged rapidly with plasma lipoproteins. Bile acid synthetic rate correlated directly with the size of the large hepatic pool. In conclusion, hepatic and blood cholesterol pools and transports have been quantitated. HDL plays a central role in free cholesterol exchange/transport between all tissues and plasma. In humans, the metabolically active pool comprises a large portion of total hepatic cholesterol that, in part, regulates bile acid synthesis. C1 NHLBI,BETHESDA,MD 20892. RP SCHWARTZ, CC (reprint author), VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,DEPT MED,BOX 711,MCV STN,RICHMOND,VA 23298, USA. FU NCRR NIH HHS [RR00065]; NIADDK NIH HHS [AM25920]; NIDDK NIH HHS [P01-DK38030] NR 31 TC 50 Z9 50 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAR PY 1993 VL 91 IS 3 BP 923 EP 938 DI 10.1172/JCI116314 PG 16 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA KR461 UT WOS:A1993KR46100024 PM 8450070 ER PT J AU CID, MC GRANT, DS HOFFMAN, GS AUERBACH, R FAUCI, AS KLEINMAN, HK AF CID, MC GRANT, DS HOFFMAN, GS AUERBACH, R FAUCI, AS KLEINMAN, HK TI IDENTIFICATION OF HAPTOGLOBIN AS AN ANGIOGENIC FACTOR IN SERA FROM PATIENTS WITH SYSTEMIC VASCULITIS SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE VASCULITIS; INFLAMMATORY DISEASES; ANGIOGENESIS; BASEMENT MEMBRANE; ENDOTHELIAL CELL ID HUMAN-ENDOTHELIAL CELLS; CAPILLARY-LIKE STRUCTURES; PROTEIN HPR EPITOPES; ACUTE PHASE RESPONSE; BASEMENT-MEMBRANE; EXTRACELLULAR-MATRIX; MYOCARDIAL INFARCT; MESSENGER-RNA; INVITRO; CANCER AB Angiogenesis is an important process in chronic inflammatory diseases. We observed that sera from patients with systemic vasculitis stimulated angiogenesis in an in vitro model using human umbilical vein endothelial cells cultured on a basement membrane (Matrigel) substrate. After 40% ammonium sulfate precipitation, angiogenic activity remained in the low molecular weight fraction and could be inactivated by heat. SDS-page of serum FPLC fractions exhibiting maximal angiogenic activity demonstrated two prominent species of 45 and 16-20 kD in patients' sera. These bands were much less apparent in sera obtained from control subjects. Amino-terminal sequencing of the 45-kD protein demonstrated that it was haptoglobin. Purified haptoglobin stimulated angiogenesis in a dose-dependent manner. The angiogenic activity of vasculitis patients' sera was partially inhibited by an antihaptoglobin antibody. Furthermore, serum haptoglobin levels in vasculitis patients correlated both with disease and angiogenic activity. Haptoglobin angiogenic activity was confirmed in two in vivo models using an implanted disc and a subcutaneous injection of basement membrane. Stimulation of angiogenesis is a newly recognized biological function of haptoglobin. The increased levels of haptoglobin found in chronic inflammatory conditions may play an important role in tissue repair. In systemic vasculitis, haptoglobin might also compensate for ischemia by promoting development of collateral vessels. C1 NIDR,DEV BIOL LAB,BLDG 30,ROOM 407,BETHESDA,MD 20892. NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. UNIV WISCONSIN,DEV BIOL LAB,MADISON,WI 53706. OI Cid Xutgla, Maria Cinta/0000-0002-4730-0938 NR 49 TC 192 Z9 196 U1 0 U2 7 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAR PY 1993 VL 91 IS 3 BP 977 EP 985 DI 10.1172/JCI116319 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA KR461 UT WOS:A1993KR46100029 PM 7680672 ER PT J AU PADILLANORIEGA, L WERNERECKERT, R MACKOW, ER GORZIGLIA, M LARRALDE, G TANIGUCHI, K GREENBERG, HB AF PADILLANORIEGA, L WERNERECKERT, R MACKOW, ER GORZIGLIA, M LARRALDE, G TANIGUCHI, K GREENBERG, HB TI SEROLOGIC ANALYSIS OF HUMAN ROTAVIRUS SEROTYPES P1A AND P2 BY USING MONOCLONAL-ANTIBODIES SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID AMINO-ACID-SEQUENCE; RHESUS ROTAVIRUS; GENOMIC CHARACTERIZATION; REASSORTANT ROTAVIRUSES; NEUTRALIZATION EPITOPES; ANTIGENIC VARIANTS; 4TH GENE; VP3; IDENTIFICATION; PROTEIN AB Three human rotavirus (HRV) VP4 serotypes and one subtype have been described on the basis of a fourfold or an eightfold-or-greater difference in neutralization titer when tested with hyperimmune antisera to recombinant VP4 or VP8* (serotypes PIA, P1B, P2, and P3). To start to analyze the antigenic basis underlying serotype specificity, we produced a library of 13 VP4-specific neutralizing monoclonal antibodies (NMAbs) to two HRVs, the serotype PIA strain Wa and the serotype P2 strain ST3, and characterized the reactivity of these NMAbs with a panel of serotypically diverse HRV strains by neutralization assay and enzyme-linked immunosorbent assay (ELISA). We characterized the serotypic specificity of the NMAbs by using a fourfold or an eightfold-or-greater difference in titer against the homologous (i.e., immunogen) and heterologous strains as a criterion for serotype. Some ST3-derived NMAbs reacted specifically with serotype P2 HRVs by ELISA and/or neutralization assay, while some Wa-derived NMAbs reacted specifically by ELISA and/or neutralization assay with some or all serotype P1A HRVs. Other Wa- and ST3-derived NMAbs reacted with some or all serotype PIA and P2 HRV strains by neutralization assay and ELISA. Most NMAbs did not react with serotype P1B or P3 strains. In previous studies, three distinct operationally defined epitopes have been identified on VP4 by examining the reactivity patterns of selected antigenic variants of HRV strain KU. At least one of the NMAbs described here recognizes an epitope unrelated to these previously identified epitopes, since it neutralized both KU and its variants. C1 VET ADM MED CTR,PALO ALTO,CA 94304. UNIV NACL AUTONOMA MEXICO,INST BIOTECNOL,DEPT BIOL MOLEC,CUERNAVACA,MORELOS 62271,MEXICO. INST MEXICANO SEGURO SOCIAL,UNIDAD INVEST CLIN ENFERMEDADES,INFECCIOSAS & PARASITARIAS,MEXICO CITY 06765,MEXICO. NIAID,INFECT DIS LAB,BETHESDA,MD 20892. SAPPORO MED COLL,DEPT HYG & EPIDEMIOL,SAPPORO,HOKKAIDO 060,JAPAN. RP PADILLANORIEGA, L (reprint author), STANFORD UNIV,MED CTR,SCH MED,DIV GASTROENTEROL,STANFORD,CA 94305, USA. FU NIAID NIH HHS [R01AI21362]; NIDDK NIH HHS [P30DK3707] NR 32 TC 51 Z9 51 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 1993 VL 31 IS 3 BP 622 EP 628 PG 7 WC Microbiology SC Microbiology GA KM810 UT WOS:A1993KM81000028 PM 7681440 ER PT J AU HANNON, H BEHETS, F QUINN, TC AF HANNON, H BEHETS, F QUINN, TC TI STABILITY OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 ANTIBODIES IN WHOLE BLOOD-IMPREGNATED FILTER PAPERS UNDER VARIOUS TROPICAL CONDITIONS - REPLY SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Letter C1 FAMILY HLTH INT,RES TRIANGLE PK,NC. NIAID,BETHESDA,MD 20892. RP HANNON, H (reprint author), CTR DIS CONTROL,ATLANTA,GA 30333, USA. NR 2 TC 2 Z9 4 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD MAR PY 1993 VL 31 IS 3 BP 765 EP 766 PG 2 WC Microbiology SC Microbiology GA KM810 UT WOS:A1993KM81000067 ER PT J AU WEBER, J YANG, JC TOPALIAN, SL PARKINSON, DR SCHWARTZENTRUBER, DS ETTINGHAUSEN, SE GUNN, H MIXON, A KIM, H COLE, D LEVIN, R ROSENBERG, SA AF WEBER, J YANG, JC TOPALIAN, SL PARKINSON, DR SCHWARTZENTRUBER, DS ETTINGHAUSEN, SE GUNN, H MIXON, A KIM, H COLE, D LEVIN, R ROSENBERG, SA TI PHASE-I TRIAL OF SUBCUTANEOUS INTERLEUKIN-6 IN PATIENTS WITH ADVANCED MALIGNANCIES SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID PLASMACYTOMA GROWTH-FACTOR; STIMULATORY FACTOR-II; CELL GROWTH; RECOMBINANT INTERLEUKIN-6; LYMPHOCYTES-T; INVIVO; INTERFERON-BETA-2; INVITRO; DIFFERENTIATION; BSF-2 C1 SANDOZ INC,PHARMACEUT,E HANOVER,NJ 07936. RP WEBER, J (reprint author), NCI,SURG BRANCH,BLDG 10,ROOM 2B42,BETHESDA,MD 20892, USA. NR 35 TC 189 Z9 191 U1 0 U2 2 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 1993 VL 11 IS 3 BP 499 EP 506 PG 8 WC Oncology SC Oncology GA KP404 UT WOS:A1993KP40400018 PM 7680375 ER PT J AU TRAVIS, LB CURTIS, RE HANKEY, BF FRAUMENI, JF AF TRAVIS, LB CURTIS, RE HANKEY, BF FRAUMENI, JF TI ACUTE NONLYMPHOCYTIC LEUKEMIA AFTER SMALL-CELL LUNG-CANCER SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Letter ID CARCINOMA RP TRAVIS, LB (reprint author), NCI,BETHESDA,MD 20892, USA. NR 10 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 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR PY 1993 VL 11 IS 3 BP 586 EP 587 PG 2 WC Oncology SC Oncology GA KP404 UT WOS:A1993KP40400030 PM 8383192 ER PT J AU DAWSON, DA GRANT, BF AF DAWSON, DA GRANT, BF TI GENDER EFFECTS IN DIAGNOSING ALCOHOL-ABUSE AND DEPENDENCE SO JOURNAL OF CLINICAL PSYCHOLOGY LA English DT Article ID SEX-DIFFERENCES; WOMEN AB Using a national population sample of 43,809 adults, male and female responses were compared for 41 indicators of alcohol abuse and dependence. While men reported all indicators more often than did women, the male to female ratio of positive responses varied according to both the construct represented by the item and its underlying prevalence. Items that might be construed as signs of weakness - physical effects, psychological effects, and loss of control or powerlessness - had lower male/female ratios than other items. Excess male prevalence was greatest for the least prevalent indicators. The paper presents alternative interpretations of these findings and discusses their implications for diagnostic classification. RP DAWSON, DA (reprint author), NIAAA,DBE,5600 FISHERS LANE,RM 14C-26,ROCKVILLE,MD 20857, USA. NR 23 TC 13 Z9 13 U1 0 U2 0 PU CLINICAL PSYCHOLOGY PUBL CO PI BRANDON PA 4 CONANT SQUARE, BRANDON, VT 05733 SN 0021-9762 J9 J CLIN PSYCHOL JI J. Clin. Psychol. PD MAR PY 1993 VL 49 IS 2 BP 298 EP 307 DI 10.1002/1097-4679(199303)49:2<298::AID-JCLP2270490225>3.0.CO;2-Z PG 10 WC Psychology, Clinical SC Psychology GA KZ345 UT WOS:A1993KZ34500023 PM 8486813 ER PT J AU DICHIRO, G AF DICHIRO, G TI OLDENDORF,WILLIAM,H. - A REMINISCENCE FROM THE EDITOR SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Item About an Individual RP DICHIRO, G (reprint author), NIH,WARREN G MAGNUSON CLIN CTR,NEUROIMAGING BRANCH,BLDG 10,ROOM 1C453,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 0363-8715 J9 J COMPUT ASSIST TOMO JI J. Comput. Assist. Tomogr. PD MAR-APR PY 1993 VL 17 IS 2 BP 171 EP 172 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA KT176 UT WOS:A1993KT17600002 ER PT J AU ALGER, JR SYMKO, SC BIZZI, A POSSE, S DESPRES, DJ ARMSTRONG, MR AF ALGER, JR SYMKO, SC BIZZI, A POSSE, S DESPRES, DJ ARMSTRONG, MR TI ABSOLUTE QUANTITATION OF SHORT TE BRAIN H-1-MR SPECTRA AND SPECTROSCOPIC IMAGING DATA SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Article DE MAGNETIC RESONANCE SPECTROSCOPY (MRS); BRAIN; MAGNETIC RESONANCE IMAGING, TECHNIQUES ID MAGNETIC-RESONANCE SPECTROSCOPY; LOCALIZED H-1-NMR SPECTROSCOPY; PROTON NMR-SPECTROSCOPY; NONINVASIVE MEASUREMENT; MOLAR CONCENTRATIONS; INTRACRANIAL TUMORS; MR SPECTROSCOPY; CEREBRAL-TUMORS; INVIVO; METABOLITES AB A method for determining the concentrations of the materials that produce the well-resolved singlet signals in short TE brain H-1 MR spectroscopic examinations is presented. Concentration determination is achieved by a water-referencing procedure. The ratios of the areas of the choline, total creatine, and N-acetyl signals to that of the water signal from the same volume of interest (VOI) are determined using acquisitions with and without water suppression. The tissue concentrations of the molecules producing the three signals can then be determined if the water concentration in the VOI can be found. This is done with a density-weighted MR study. The MR study provides the ratio of the mean MR signal amplitude from the VOI to that from an external standard containing a known water concentration. The method's flexibility is illustrated by using it with two different single-volume localization schemes and spectroscopic imaging. Preliminary evaluations of accuracy and reproducibility are made in phantom, animal, and limited human studies. The method's advantages and limitations are discussed. C1 NIH,NATL CTR RES RESOURCES,BIOMED ENGN & INSTRUMENTAT PROGRAM,BETHESDA,MD 20892. NIH,WARREN G MAGNUSON CLIN CTR,DEPT DIAGNOST RADIOL,BETHESDA,MD 20892. RP ALGER, JR (reprint author), NINCDS,DIV INTRAMURAL RES,NEUROIMAGING BRANCH,NIH BLDG 10,RM 1C-451,BETHESDA,MD 20892, USA. RI Bizzi, Alberto/K-3141-2016 OI Bizzi, Alberto/0000-0002-0253-5274 NR 43 TC 71 Z9 71 U1 0 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0363-8715 J9 J COMPUT ASSIST TOMO JI J. Comput. Assist. Tomogr. PD MAR-APR PY 1993 VL 17 IS 2 BP 191 EP 199 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA KT176 UT WOS:A1993KT17600006 PM 8454744 ER PT J AU BISWAS, M AKOGYERAM, CO SCOTT, KR POTTI, GK GALLELLI, JF HABIB, MJ AF BISWAS, M AKOGYERAM, CO SCOTT, KR POTTI, GK GALLELLI, JF HABIB, MJ TI DEVELOPMENT OF CARBAMAZEPINE-PHOSPHOLIPID SOLID DISPERSION FORMULATIONS SO JOURNAL OF CONTROLLED RELEASE LA English DT Article DE DISSOLUTION; CARBAMAZEPINE; PHOSPHOLIPID; COPRECIPITATE ID SYSTEMS AB This study is concerned with the development of a carbamazepine (CBZ):phospholipid (PL) solid dispersion formulation with improved dissolution characteristics. CBZ powders were blended with PL to produce CBZ:PL physical mixtures or made into solid dispersions with PL by the solvent method. CBZ exhibited significantly improved dissolution rates in PL coprecipitate (coppt) as compared to the physical mixtures or CBZ alone. Dissolution studies suggested that less than 10:1 ratio of CBZ to PL (9.1% PL) was required to disperse amorphous CBZ completely in the carrier. The coppt yielded a 3.6-fold greater initial dissolution rate (computed over the 5 min of dissolution) than the pure CBZ. Also, the total amount dissolved after 60 min was 2.1-fold greater at a CBZ: dimyristoylphosphatidylglycerol (DMPG) of 10:1 ratio (9.1% DMPG) than for the corresponding pure drug. Increasing the DMPG concentration to 4:1 (20% DMPG) compositions resulted in only a further 10% increase in the initial dissolution rate and 8.5% increase in the limiting concentration. Thus, a small amount of PL improved the dissolution of CBZ to a significant level. Some effect was also observed by changing the composition of the PLs. The coppts were formulated into tablets in order to compare the dissolution profile with that of Tegretol(R), a commercially available tablet of CBZ. It was found that the total amount dissolved after 60 min was two-fold higher in our tablet formulation than the commercial product, Tegretol'. Powder X-ray diffraction spectra showed no changes in the diffraction patterns of CBZ in the coppt. It is concluded that CBZ:PL solid dispersions may have clinical advantages of quick in-vivo release to yield better bioavailability than existing commercial formulations. C1 HOWARD UNIV,COLL PHARM & PHARMACEUT SCI,WASHINGTON,DC 20059. NIH,WARREN G MAGNUSON CLIN CTR,BETHESDA,MD 20892. NR 8 TC 8 Z9 8 U1 1 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-3659 J9 J CONTROL RELEASE JI J. Control. Release PD MAR PY 1993 VL 23 IS 3 BP 239 EP 245 DI 10.1016/0168-3659(93)90005-P PG 7 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA KP597 UT WOS:A1993KP59700005 ER PT J AU BORNSTEIN, MH AF BORNSTEIN, MH TI SIBLING INTERACTION ACROSS CULTURES - THEORETICAL AND METHODOLOGICAL ISSUES - ZUKOW,PG SO JOURNAL OF CROSS-CULTURAL PSYCHOLOGY LA English DT Book Review RP BORNSTEIN, MH (reprint author), NICHHD,BETHESDA,MD 20892, USA. NR 1 TC 0 Z9 0 U1 1 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 SN 0022-0221 J9 J CROSS CULT PSYCHOL JI J. Cross-Cult. Psychol. PD MAR PY 1993 VL 24 IS 1 BP 115 EP 116 DI 10.1177/0022022193241008 PG 2 WC Psychology, Social SC Psychology GA KL331 UT WOS:A1993KL33100008 ER PT J AU FLAVIN, M NERAD, TA AF FLAVIN, M NERAD, TA TI RECLINOMONAS-AMERICANA N G, N-SP, A NEW FRESH-WATER HETEROTROPHIC FLAGELLATE SO JOURNAL OF EUKARYOTIC MICROBIOLOGY LA English DT Article DE BICOSOECA; COLPONEMA; HISTIONA; TAXONOMY; ULTRASTRUCTURE AB A new heterotrophic flagellate has been discovered from sites in Maryland, Michigan and Wyoming. The flagellate resides within a lorica constructed of a meshwork of intertwined fibrils with the outer surface invested with nail-shaped spines. The organism ''reclines'' within the lorica with its ventral aspect directed upward, and has two heterodynamic flagella, neither of which bears mastigonemes. One flagellum is directed upward and the other is arched over the ventral aspect of the body. Ingestion of bacteria takes place al the left posterior half of the cell. The organism is anchored to the lorica on the fight posterior side by a series of regularly spaced cytoplasmic bridges and at the left anterior of the cell by a cytoplasmic appendage similar to the ''languette cytoplasmique'' found in some bicosoecids. The right side of the cell is raised into a flattened lip with the outer margin reinforced by a ribbon of microtubules. The new flagellate has mitochondria with tubular cristae and lacks a Golgi. A new genus is created to accommodate both the new flagellate described herein and Histiona campanula Penard. A new family is proposed to include the new genus and Histiona. C1 NHLBI,CELL BIOL LAB,BETHESDA,MD 20892. NR 17 TC 31 Z9 32 U1 1 U2 1 PU SOC PROTOZOOLOGISTS PI LAWRENCE PA 810 E 10TH ST, LAWRENCE, KS 66044 SN 1066-5234 J9 J EUKARYOT MICROBIOL JI J. Eukaryot. Microbiol. PD MAR-APR PY 1993 VL 40 IS 2 BP 172 EP 179 DI 10.1111/j.1550-7408.1993.tb04900.x PG 8 WC Microbiology SC Microbiology GA KV474 UT WOS:A1993KV47400010 PM 8461890 ER PT J AU SLOAND, E LAUGHON, B ARMSTRONG, M BARTLETT, MS BLUMENFELD, W CUSHION, M KALICA, A KOVACS, JA MARTIN, W PITT, E PESANTI, EL RICHARDS, F ROSE, R WALZER, P AF SLOAND, E LAUGHON, B ARMSTRONG, M BARTLETT, MS BLUMENFELD, W CUSHION, M KALICA, A KOVACS, JA MARTIN, W PITT, E PESANTI, EL RICHARDS, F ROSE, R WALZER, P TI THE CHALLENGE OF PNEUMOCYSTIS-CARINII CULTURE SO JOURNAL OF EUKARYOTIC MICROBIOLOGY LA English DT Article DE CULTIVATION; LUNG ID THERAPEUTIC AGENTS; INVITRO; GROWTH; CELLS; A549; AIDS AB Published and unpublished data on the cultivation of P. carinii were reviewed by a panel of investigators convened by the National Institutes of Health. Although several cell culture systems allow propagation of P. carinii for a limited time with modest rates of replication, these have not proved adequate for isolation of P. carinii in sufficient quantity to explore important basic biological investigation. Attempts at cell-free culture have yielded only transient proliferation. Because much of the unsuccessful work on cultivation of the organism has been unpublished, the panel agreed that these data may be useful to other investigators in designing experimental strategies for cultivation. Therefore, the purpose of this report is to make available this information to researchers, lest others unknowingly repeat unsuccessful methods. It is hoped that by documenting the history and the complexities of Pneumocystis culture, renewed interest and efforts will be directed toward this fundamental scientific challenge. C1 NIAID,BETHESDA,MD 20892. YALE UNIV,SCH MED,NEW HAVEN,CT 06510. INDIANA UNIV HOSP N340,MED CTR,INDIANAPOLIS,IN 46202. UNIV CALIF SAN FRANCISCO,VET ADM MED CTR,SAN FRANCISCO,CA 94121. COLL MED,DEPT INTERNAL MED,DIV INFECT DIS,CINCINNATI,OH 45220. NHLBI,BETHESDA,MD 20892. NIH,CTR CLIN,BETHESDA,MD 20892. INDIANA UNIV,SCH MED,INDIANAPOLIS,IN 46202. UNIV CONNECTICUT,VET ADM CTR,NEWINGTON,CT 06111. YALE UNIV,SCH MED,DEPT INTERNAL MED,NEW HAVEN,CT 06510. NEW ENGLAND DEACONESS HOSP,BOSTON,MA 02115. DEPT VET AFFAIRS MED CTR,CINCINNATI,OH 45220. RP SLOAND, E (reprint author), NHLBI,BLDG 31,ROOM 5A48,BETHESDA,MD 20892, USA. NR 16 TC 81 Z9 82 U1 0 U2 0 PU SOC PROTOZOOLOGISTS PI LAWRENCE PA 810 E 10TH ST, LAWRENCE, KS 66044 SN 1066-5234 J9 J EUKARYOT MICROBIOL JI J. Eukaryot. Microbiol. PD MAR-APR PY 1993 VL 40 IS 2 BP 188 EP 195 DI 10.1111/j.1550-7408.1993.tb04902.x PG 8 WC Microbiology SC Microbiology GA KV474 UT WOS:A1993KV47400012 PM 8461892 ER PT J AU ROMAGNOLI, P LAYET, C YEWDELL, J BAKKE, O GERMAIN, RN AF ROMAGNOLI, P LAYET, C YEWDELL, J BAKKE, O GERMAIN, RN TI RELATIONSHIP BETWEEN INVARIANT CHAIN EXPRESSION AND MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-II TRANSPORT INTO EARLY AND LATE ENDOCYTIC COMPARTMENTS SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID MHC CLASS-II; ANTIGEN PROCESSING CAPACITY; EPIDERMAL LANGERHANS CELLS; INTRACELLULAR-TRANSPORT; ENDOPLASMIC-RETICULUM; MEMBRANE-GLYCOPROTEINS; SURFACE EXPRESSION; INFLUENZA-VIRUS; HLA ANTIGENS; BETA-DIMERS AB Invariant chain (Ii), which associates with major histocompatibility complex (MHC) class II molecules in the endoplasmic reticulum, contains a targeting signal for transport to intracellular vesicles in the endocytic pathway. The characteristics of the target vesicles and the relationship between Ii structure and class II localization in distinct endosomal subcompartments have not been well defined. We demonstrate here that in transiently transfected COS cells expressing high levels of the p31 or p41 forms of Ii, uncleaved Ii is transported to and accumulates in transferrin-accessible (early) endosomes. Coexpressed MHC class II is also found in this same compartment. These early endosomes show altered morphology and a slower rate of content movement to later parts of the endocytic pathway. At more moderate levels of Ii expression, or after removal of a highly conserved region in the cytoplasmic tail of Ii, coexpressed class II molecules are found primarily in vesicles with the characteristics of late endosomes/prelysosomes. The li chains in these late endocytic vesicles have undergone proteolytic cleavage in the lumenal region postulated to control MHC class II peptide binding. These data indicate that the association of class II with Ii results in initial movement to early endosomes. At high levels of Ii expression, egress to later endocytic compartments is delayed and class II-Ii complexes accumulate together with endocytosed material. At lower levels of Ii expression, class II-Ii complexes are found primarily in late endosomes/prelysosomes. These data provide evidence that the route of class II transport to the site of antigen processing and loading involves movement through early endosomes to late endosomes/prelysosomes. Our results also reveal an unexpected ability of intact Ii to modify the structure and function of the early endosomal compartment, which may play a role in regulating this processing pathway. C1 NIAID,VIRAL DIS LAB,BETHESDA,MD 20892. UNIV OSLO,DEPT BIOL,N-0316 OSLO,NORWAY. RP ROMAGNOLI, P (reprint author), NIAID,IMMUNOL LAB,LYMPHOCYTE BIOL SECT,BLDG 10,ROOM 11N311,BETHESDA,MD 20892, USA. RI yewdell, jyewdell@nih.gov/A-1702-2012; Romagnoli, Paola/K-2237-2014 NR 61 TC 140 Z9 140 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD MAR 1 PY 1993 VL 177 IS 3 BP 583 EP 596 DI 10.1084/jem.177.3.583 PG 14 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA KN886 UT WOS:A1993KN88600001 PM 8436902 ER PT J AU WANG, JM MCVICAR, DW OPPENHEIM, JJ KELVIN, DJ AF WANG, JM MCVICAR, DW OPPENHEIM, JJ KELVIN, DJ TI IDENTIFICATION OF RANTES RECEPTORS ON HUMAN MONOCYTIC CELLS - COMPETITION FOR BINDING AND DESENSITIZATION BY HOMOLOGOUS CHEMOTACTIC CYTOKINES SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID HUMAN INTERLEUKIN-8 RECEPTOR; GROWTH-STIMULATORY ACTIVITY; HUMAN-NEUTROPHILS; FAMILY; EXPRESSION; MIGRATION; CLONING; SUBUNIT AB RANTES (regulated on activation, normal T expressed and secreted) is a member of the chemotactic cytokine (chemokine) beta subfamily. High affinity receptors for RANTES have been identified on a human monocytic leukemia cell line THP-1, which responded to RANTES in chemotaxis and calcium mobilization assays. Steady-state binding data analyses revealed approximately 700 binding sites/cell on THP-1 cells with a K(d) value of 400 pM, comparable to that expressed on human peripheral blood monocytes. The RANTES binding to monocytic cells was competed for by monocyte chemotactic and activating factor (MCAF) and macrophage inflammatory protein 1 (MIP-1) alpha, two other chemokine beta cytokines. Although MCAF and MIP-1alpha competed for RANTES binding to monocytes with apparent lower affinity (with estimated K(d) of 6 and 1.6, nM respectively) both of these cytokines effectively desensitized the calcium mobilization induced by RANTES. The chemotactic response of THP-1 cells to RANTES was also markedly inhibited by preincubation with MCAF or MIP-1alpha. In contrast, RANTES did not desensitize the THP-1 calcium mobilization and chemotaxis in response to MCAF or MIP-1alpha. These results, together with our previous observations that RANTES did not compete for MCAF or MIP-1alpha binding on monocytic cells, indicate the expression of promiscuous receptors on monocytes that recognize one or more cytokines within the chemokine beta family. C1 NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,EXPTL IMMUNOL LAB,FREDERICK,MD 21702. RP WANG, JM (reprint author), NCI,FCRDC,BIOL RESPONSE MODIFIERS PROGRAM,MOLEC IMMUNOREGULAT LAB,BLDG 560,RM 31-19,FREDERICK,MD 21702, USA. RI McVicar, Daniel/G-1970-2015 NR 24 TC 122 Z9 124 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD MAR 1 PY 1993 VL 177 IS 3 BP 699 EP 705 DI 10.1084/jem.177.3.699 PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA KN886 UT WOS:A1993KN88600013 PM 7679707 ER PT J AU HAYNES, BF ARTHUR, LO FROST, P MATTHEWS, TJ LANGLOIS, AJ PALKER, TJ HART, MK SCEARCE, RM JONES, DM MCDANAL, C OTTINGER, J BOLOGNESI, DP WEINHOLD, KJ AF HAYNES, BF ARTHUR, LO FROST, P MATTHEWS, TJ LANGLOIS, AJ PALKER, TJ HART, MK SCEARCE, RM JONES, DM MCDANAL, C OTTINGER, J BOLOGNESI, DP WEINHOLD, KJ TI CONVERSION OF AN IMMUNOGENIC HUMAN-IMMUNODEFICIENCY-VIRUS (HIV) ENVELOPE SYNTHETIC PEPTIDE TO A TOLEROGEN IN CHIMPANZEES BY THE FUSOGENIC DOMAIN OF HIV GP41 ENVELOPE PROTEIN SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID TOXIC LYMPHOCYTES-T; GP120; GLYCOPROTEIN; ANTIBODIES; CELLS; NEUTRALIZATION; SEQUENCE; TYPE-1; GP160; PROTECTION AB The fusogenic (F) domain of human immunodeficiency virus (HIV) gp41 envelope (env) protein has sequence similarities to many viruses and mediates the fusion of HIV-infected cells. During a survey of the immunogenicity of HIV env peptides in chimpanzees, we have observed that HIV peptide immunogenicity was dramatically altered by the NH2-terminal synthesis of the gp41 F domain to an otherwise immunogenic peptide. We compared two hybrid peptide types comprised of T helper (Th) and B cell epitopes of HIV gp120 env protein for their immunogenicity in chimpanzees. The Th-B epitope hybrid peptides contained the HIV gp120 Th cell determinant, T1 (amino acids [aa] 428-440) -synthesized NH2 terminal to gp120 V3 loop peptides, which contain B cell epitopes that induce anti-HIV-neutralizing antibodies (SP10IIIB [aa 303-321] and SP10IIIB [A] [aa 303-327]). The F-Th-B peptide contained the HIV gp41 F domain of HIVIIIB gp41 (aa 519-530) -synthesized NH2 terminal to the Th-B peptide. Whereas Th-B peptides were potent immunogens for chimpanzee antibody and T cell-proliferative responses, the F-Th-B peptide induced lower anti-HIV gp120 T and B cell responses. Moreover, immunization of chimpanzees with F-Th-B peptide but not Th-B peptides induced a significant decrease in peripheral blood T lymphocytes (mean decrease during immunization, 52%; p <0.02). Chimpanzees previously immunized with F-Th-B peptide did not respond well to immunization with Th-B peptide with T or B cell responses to HIV peptides, demonstrating that the F-Th-B peptide induced immune hyporesponsiveness to Th and B HIV gp120 env determinants. These observations raise the hypothesis that the HIV gp41 env F domain may be a biologically active immunoregulatory peptide in vivo, and by an as yet uncharacterized mechanism, promotes primate immune system hyporesponsiveness to otherwise immunogenic peptides. C1 DUKE UNIV,MED CTR,DUKE CTR AIDS RES,DEPT SURG,DURHAM,NC 27710. DUKE UNIV,MED CTR,DUKE CTR AIDS RES,DEPT MICROBIOL & IMMUNOL,DURHAM,NC 27710. NEW MEXICO STATE UNIV,CTR PRIMATE,ALAMOGORDO,NM 88310. NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,AIDS VACCINE PROGRAM,FREDERICK,MD 21702. RP HAYNES, BF (reprint author), DUKE UNIV,MED CTR,DUKE CTR AIDS RES,DEPT MED,BOX 3258,DURHAM,NC 27710, USA. FU NCI NIH HHS [CA-43447, N01-CO-74102]; NIAID NIH HHS [AI-28662] NR 31 TC 22 Z9 22 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD MAR 1 PY 1993 VL 177 IS 3 BP 717 EP 727 DI 10.1084/jem.177.3.717 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA KN886 UT WOS:A1993KN88600015 PM 7679708 ER PT J AU LUNARDIISKANDAR, Y GESSAIN, A LAM, VH GALLO, RC AF LUNARDIISKANDAR, Y GESSAIN, A LAM, VH GALLO, RC TI ABNORMAL INVITRO PROLIFERATION AND DIFFERENTIATION OF T-CELL COLONY-FORMING CELLS IN PATIENTS WITH TROPICAL SPASTIC PARAPARESIS HUMAN LYMPHOCYTE-T VIRUS TYPE-I (HTLV-I) ASSOCIATED MYELOENCEPHALOPATHY AND HEALTHY HTLV-I CARRIERS SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID PERIPHERAL-BLOOD LYMPHOCYTES; MONONUCLEAR-CELLS; AIDS PATIENTS; BONE-MARROW; MYELOPATHY; LEUKEMIA; ANTIBODIES; EXPRESSION; INTERLEUKIN-2; INTEGRATION AB T cell colonies were generated from the peripheral blood mononuclear cells (PBMC) of 10 patients with tropical spastic paraparesis/human T lymphocyte virus type I (HTLV-I)-associated myeloencephalopathy (TSP/HAM), two healthy HTLV-I carriers, and 17 healthy HTLV-I-seronegative subjects. PBMC were cultured in methylcellulose in the absence of added growth factors (spontaneous T cell colonies), or in the presence of phorbol myristate acetate and interleukin 2 (induced T cell colonies). PBMC T cell colony-forming cells (T-CFC) from all TSP/HAM patients and HTLV-I carriers were able to grow in the absence of added growth factors and/or mitogenic stimulation. Pooled spontaneous and induced colonies were composed of cells bearing CD3+, CD4+, CD8+, and CD1+ antigens. Colonies from normal HTLV-I-seronegative subjects displayed mature cells bearing the CD3+, CD4+, CD8+, and CD1- surface phenotype. In addition, spontaneous and induced T cell colonies expressed HTLV-I antigens in 18-38% of the cells from TSP/HAM patients and HTLV-I carriers. These results demonstrate that HTLV-I infection is associated with an abnormal proliferation and differentiation of T cell progenitors in vitro and that the T-CFC from HTLV-I-seropositive individuals are infected, suggesting that T-CFC abnormalities may play a predominant role in the pathophysiology of HTLV-I. C1 NCI,TUMOR CELL BIOL LAB,BLDG 37,ROOM 6A09,BETHESDA,MD 20892. NR 38 TC 21 Z9 21 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD MAR 1 PY 1993 VL 177 IS 3 BP 741 EP 750 DI 10.1084/jem.177.3.741 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA KN886 UT WOS:A1993KN88600017 PM 8094736 ER PT J AU WONG, HL COSTA, GL LOTZE, MT WAHL, SM AF WONG, HL COSTA, GL LOTZE, MT WAHL, SM TI INTERLEUKIN (IL)-4 DIFFERENTIALLY REGULATES MONOCYTE IL-1 FAMILY GENE-EXPRESSION AND SYNTHESIS INVITRO AND INVIVO SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID RECEPTOR ANTAGONIST PROTEIN; GROWTH-FACTOR-BETA; CELL-GROWTH; SUBSETS; INHIBITION; INDUCTION; DISTINCT; CLONING; GAMMA AB Interleukin (IL) 4 is a multifunctional T cell-derived cytokine that inhibits cytokine production and certain effector functions in human monocytes, while enhancing others. We show that IL-4 may contribute to the downregulation and resolution of an inflammatory response by selectively promoting expression of the IL-1 receptor antagonist (IL-1ra) that blocks the action of IL-1. IL-1ra specifically binds to the IL-1 receptor without initiating signal transduction. Peripheral blood monocytes obtained from cancer patients, before and immediately after a regimen of IL-4 immunotherapy, were examined for IL-1ra gene expression. After IL-4 therapy, monocytes from the patients showed a marked increase in IL-1ra mRNA. This selective induction of IL-1ra mRNA in circulating monocytes was reflected by significantly enhanced serum levels of IL-1ra (p <0.01) during IL-4 therapy, which declined after IL-4 treatment. In vitro analysis of IL-4 regulation of monocytes from normal individuals revealed a dose-dependent induction of IL-1ra mRNA within 2-4 h after stimulation without a concomitant effect on the expression of IL-1 mRNA. Increased IL-1ra mRNA was not due to RNA stabilization, but occurred at the level of transcription. In the presence of LPS, IL-4 not only augmented IL-1ra levels, but markedly inhibited LPS-induced IL-1 mRNA expression. The selective upregulation of IL-1ra by resting or activated monocytes, coupled with inhibition of IL-1 production by activated monocytes, as we demonstrate both in vitro and in vivo, suggests that IL-4 may prove clinically useful as a systemic antiinflammatory agent. C1 NIDR,IMMUNOL LAB,BLDG 30,ROOM 331,BETHESDA,MD 20892. NCI,SURG BRANCH,BETHESDA,MD 20892. NR 42 TC 96 Z9 96 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD MAR 1 PY 1993 VL 177 IS 3 BP 775 EP 781 DI 10.1084/jem.177.3.775 PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA KN886 UT WOS:A1993KN88600020 PM 8436908 ER PT J AU ZELLA, D CAVICCHINI, A SALEMI, M CASOLI, C LORI, F ACHILLI, G CATTANEO, E LANDINI, V BERTAZZONI, U AF ZELLA, D CAVICCHINI, A SALEMI, M CASOLI, C LORI, F ACHILLI, G CATTANEO, E LANDINI, V BERTAZZONI, U TI MOLECULAR CHARACTERIZATION OF 2 ISOLATES OF HUMAN T-CELL LEUKEMIA-VIRUS TYPE-II FROM ITALIAN DRUG-ABUSERS AND COMPARISON OF GENOME STRUCTURE WITH OTHER ISOLATES SO JOURNAL OF GENERAL VIROLOGY LA English DT Article ID LONG-TERMINAL-REPEAT; POLYMERASE CHAIN-REACTION; LEUKEMIA-VIRUS; HTLV-II; GENE-EXPRESSION; NUCLEOTIDE-SEQUENCE; INFECTION; PREVALENCE; LYMPHOMA; AIDS AB The human T cell leukaemia virus type II (HTLV-II), whose pathogenicity is as yet unclear, was recently found to be associated with intravenous drug abuse in North America and Europe. HTLV-II was isolated from two Italian drug abusers belonging to the same cohort and coinfected with human immunodeficiency virus type 1. Two new isolates, HTLV-II Gu and Va, were established in a culture of BJAB cells, a continuous B cell line (Epstein-Barr virus-negative), and characterized by nucleotide sequence analysis of the long terminal repeat (LTR) and portions of the gag, env and X regions.These sequences were compared to those of the HTLV-II Mo isolate reported in the literature. No major variations were observed in important regulatory elements of LTR nor in the stem-bulge-loop configuration known to be essential for binding of rex protein. The results obtained from the sequence of the 1988 nucleotides examined indicated a 1.6 % variability between the Gu and Va isolates and about 6 % with respect to Mo. Notable differences were found in the structure of putative open reading frames of the X region when compared to those reported for the Mo isolate. Restriction analysis of proviral DNA of two isolates and comparison with the physical map of the Mo isolate confirmed the existence of genetic heterogeneity in the HTLV-II group and demonstrated that the new isolates Gu and Va belong to the HTLV-IIb subtype. The results of this study show that the new isolates have distinct features with respect to the Mo isolate though all important regulatory elements of the LTR appear to be well conserved. C1 CNR,IST GENET BIOCHIM & EVOLUZ,VIA ABBIATEGRASSO 207,I-27100 PAVIA,ITALY. IRCCS POLICLIN S MATTEO,MALATTIE INFETT CLIN,PAVIA,ITALY. NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. AGRIMONT,MASSA CARRARA,ITALY. UNIV PARMA,I-43100 PARMA,ITALY. NR 39 TC 41 Z9 41 U1 0 U2 0 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 1993 VL 74 BP 437 EP 444 DI 10.1099/0022-1317-74-3-437 PN 3 PG 8 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA KQ511 UT WOS:A1993KQ51100014 PM 8445366 ER PT J AU MARTINGALLARDO, A FLEISCHER, E DOYLE, SA ARUMUGHAM, R COLLINS, PL HILDRETH, SW PARADISO, PR AF MARTINGALLARDO, A FLEISCHER, E DOYLE, SA ARUMUGHAM, R COLLINS, PL HILDRETH, SW PARADISO, PR TI EXPRESSION OF THE G-GLYCOPROTEIN GENE OF HUMAN RESPIRATORY SYNCYTIAL VIRUS IN SALMONELLA-TYPHIMURIUM SO JOURNAL OF GENERAL VIROLOGY LA English DT Article ID RECOMBINANT VACCINIA VIRUS; ENVELOPE GLYCOPROTEINS; MONOCLONAL-ANTIBODIES; F-GLYCOPROTEIN; G-PROTEIN; STRAINS; IDENTIFICATION; IMMUNITY AB The attachment protein. G, of human respiratory syncytial virus (RSV) is an M(r) 84K to 90K species which has a high content of N-linked and O-linked carbohydrates. The unglycosylated form of this protein was expressed by inserting a full-length cDNA copy of the mRNA from the A2 strain of RSV into a prokaryotic expression vector under the control of the lambda P(L) promoter. Salmonella typhimurium cells transformed with the G-containing plasmid synthesized a protein of M(r) 40000 that specifically reacted with polyclonal and two neutralizing monoclonal antibodies raised against the native RSV G glycoprotein. Recombinant G protein was purified by immunoaffinity chromatography using a neutralizing monoclonal antibody. Cotton rats immunized with the recombinant G protein produced serum antibodies to the G glycoprotein that neutralized RSV in vitro. The study demonstrates that the G protein of RSV can be expressed in bacteria and that at least one neutralizing epitope is not structurally dependent on carbohydrates. C1 PRAXIS BIOLOGICS INC,DEPT VIROL,300 E RIVER RD,ROCHESTER,NY 14623. NIAID,INFECT DIS LAB,BETHESDA,MD 20892. NR 29 TC 20 Z9 21 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 1993 VL 74 BP 453 EP 458 DI 10.1099/0022-1317-74-3-453 PN 3 PG 6 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA KQ511 UT WOS:A1993KQ51100016 PM 8445368 ER PT J AU MARTINEZ, A MONTUENGA, LM SPRINGALL, DR TRESTON, A CUTTITTA, F POLAK, JM AF MARTINEZ, A MONTUENGA, LM SPRINGALL, DR TRESTON, A CUTTITTA, F POLAK, JM TI IMMUNOCYTOCHEMICAL LOCALIZATION OF PEPTIDYLGLYCINE ALPHA-AMIDATING MONOOXYGENASE ENZYMES (PAM) IN HUMAN ENDOCRINE PANCREAS SO JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY LA English DT Article DE PAM; PHM; PAL; HUMAN PANCREATIC ISLETS; GLUCAGON; PP; INSULIN; SOMATOSTATIN; IMMUNOCYTOCHEMISTRY; DOUBLE IMMUNOGOLD STAINING ID ISLET SECRETORY GRANULES; PEPTIDE AMIDATION; PITUITARY-GLAND; MESSENGER-RNA; RAT; EXPRESSION; FORMS; CELLS; CDNA; PURIFICATION AB We studied the distribution of the enzymes that are involved in the post-translational alpha-amidation of regulatory peptides in human endocrine pancreas, using immunocytochemical methods for light and electron microscopy. Immunoreactivity for the two enzymes involved, peptidylglycine alpha-hydroxylating monooxygenase (PHM) and peptidyl-alpha-hydroxyglycine alpha-amidating lyase (PAL), was located in the periphery of the islets of Langerhans and in ductal endocrine cells. Staining of reverse-face serial sections demonstrated that these immunoreactivities co-localize with glucagon but not with pancreatic polypeptide (PP), insulin, or somatostatin. Double immunogold staining for electron microscopy confirmed the previous results and revealed a different localization for each enzyme inside the secretory granule: PHM is present in the central core of the glucagon-containing granules, whereas PAL is predominantly located near the granule membrane. The existence of an amidated peptide, GLP1, in the A-cells explains the presence of peptidylglycine alpha-amidating monooxygenase enzymes (PAM) in these cells. The absence of the enzymes in the PP-cells raises the possibility that a different form of amidating enzyme may be involved in the post-translational processing of this peptide. C1 ROYAL POSTGRAD MED SCH,DEPT HISTOCHEM,LONDON W12 0HS,ENGLAND. NCI,DIV CANC PREVENT & CONTROL,BIOMARKERS & PREVENT RES BRANCH,BETHESDA,MD 20892. RP MARTINEZ, A (reprint author), UNIV NAVARRA,DEPT CYTOL & HISTOL,E-31080 PAMPLONA,SPAIN. RI Martinez, Alfredo/A-3077-2013 OI Martinez, Alfredo/0000-0003-4882-4044 NR 39 TC 25 Z9 25 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 1993 VL 41 IS 3 BP 375 EP 380 PG 6 WC Cell Biology SC Cell Biology GA KM702 UT WOS:A1993KM70200006 PM 8094086 ER PT J AU MCCOY, KL NOONE, M INMAN, JK STUTZMAN, R AF MCCOY, KL NOONE, M INMAN, JK STUTZMAN, R TI EXOGENOUS ANTIGENS INTERNALIZED THROUGH TRANSFERRIN RECEPTORS ACTIVATE CD4+ T-CELLS SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; LIPOSOME-ENCAPSULATED ANTIGENS; CLASS-II MOLECULES; MONOCLONAL-ANTIBODY; INVARIANT CHAIN; B-CELLS; MEDIATED ENDOCYTOSIS; MHC MOLECULES; ENDOSOMES; TRANSPORT AB The role of endosomes in exogenous Ag processing was investigated by targeting Ag into the endosomal transport pathway via transferrin receptors. The Ag, pigeon cytochrome c and chicken OVA, were coupled to human ferric transferrin by a heteroligation technique. The conjugates were significantly more efficient than native Ag in stimulating Ag-specific CD4+ T cells, when the APC expressed transferrin receptors. The addition of ferric transferrin eliminated the enhanced response. Paraformaldehyde-fixed APC did not present the conjugates, indicating that the conjugates still required processing to activate T cells. An augmented level of T cell activation was not observed when the APC lacked transferrin receptors or when the conjugate contained the apoenzyme form of transferrin, which does not bind the receptor. The conjugate followed an intracellular pathway similar to that for transferrin, remaining in low density vesicles. Degraded conjugate appeared rapidly in culture supernatants, within 5 min, and peaked by 20 min; under these conditions a T cell response to the conjugate was elicited that was consistent with an early processing compartment. Our results suggest that antigenic peptide fragments can be generated in the early endosomes, without delivery of these Ag to the lysosomes. Thus, various Ag may have differential processing requirements, dictated by their molecular nature, that determine the site of Ag processing. C1 NIAID,IMMUNOL LAB,BETHESDA,MD 20892. RP MCCOY, KL (reprint author), VIRGINIA COMMONWEALTH UNIV,DEPT MICROBIOL & IMMUNOL,BOX 678 MCV STN,RICHMOND,VA 23298, USA. FU NCRR NIH HHS [2S07RR5679]; NIAID NIH HHS [AI28422] NR 60 TC 41 Z9 41 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 1993 VL 150 IS 5 BP 1691 EP 1704 PG 14 WC Immunology SC Immunology GA KN532 UT WOS:A1993KN53200006 PM 8094728 ER PT J AU KING, CL LOW, CC NUTMAN, TB AF KING, CL LOW, CC NUTMAN, TB TI IGE PRODUCTION IN HUMAN HELMINTH INFECTION - RECIPROCAL INTERRELATIONSHIP BETWEEN IL-4 AND IFN-GAMMA SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN B-CELLS; INTERFERON-GAMMA; IMMUNOGLOBULIN PRODUCTION; HUMAN-LYMPHOCYTES; SOLUBLE CD23; SERUM LEVELS; T-CELLS; INTERLEUKIN-4; INVITRO; ALPHA AB To determine whether there is a reciprocal relationship between IL-4 and IFN-gamma production in persons with parasite-induced elevations in serum IgE, PBMC were obtained from helminth-infected individuals with a broad range of serum IgE levels that fell into two distinct groups-extremely elevated (HI; n = 9; range, 4,129 to 18,400 ng/ml) or elevated (EL; n = 6; range, 403 to 1,01 8 ng/ml), relative to control subjects (NL; n = 7; range, 4 to 159 ng/ml). PBMC were stimulated in vitro, with Ag or mitogens, and IL-4 and IFN-gamma were measured by ELISA in culture supernatants. Helminth Ag- (but not tetanus toxoid) stimulated IL-4 production in eight of nine HI (range, 49 to 150 pg/ml) but was undetectable in either EL or NL (p < 0.01). In contrast, PBMC from EL produced significant levels of IFN-gamma to helminth Ag (GM = 358 pg/ml) compared with HI (GM = 89 pg/ml; p = 0.02) and NL (GM = 9 pg/ml; p < 0.001). Tetanus toxoid induced comparable levels of IFN-gamma among the three groups. Mitogen-driven IL-4 production was ninefold greater in HI [geometric mean (GM) = 913 pg/ml] versus EL (GM = 111 pg/ml; p < 0.01) and NL (GM = 193 pg/ml; p < 0.001) and correlated with serum IgE levels (r = 0.8; p < 0.01). Mitogen-driven IFN-gamma synthesis was equivalent among the groups. Although -parasite Ag-driven IL-4 secreting CD4+ cells were detected (by ELISPOT) among infected subjects with both high and low serum IgE levels, the number of IL-4 exceeded that of IFN-gamma-secreting cells among individuals with elevated serum IgE levels, whereas the opposite relationship existed among subjects with normal serum IgE. In a subpopulation of infected individuals (n = 4), parasite-Ag added to PBMC cultures induced polyclonal IgE that was directly associated with the parasite-Ag-driven IL-4 production and inversely related to IFN-gamma synthesis in PBMC supernatants from parallel cultures. Furthermore, neutralizing anti-IFN-gamma antibody augmented both parasite-driven IL-4 synthesis and IgE production in vitro (n = 4). The data indicate that helminth-induced serum IgE levels are directly related to an increased capacity by PBMC to produce IL-4 and inversely associated to IFN-gamma production. It further supports the concept that IL-4 and IFN-gamma reciprocally regulate IgE in vivo. C1 NIH,PARASIT DIS LAB,BETHESDA,MD 20892. RP KING, CL (reprint author), CASE WESTERN RESERVE UNIV,DIV GEOG MED,2109 ADELBERT RD,CLEVELAND,OH 44106, USA. NR 33 TC 75 Z9 76 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 1993 VL 150 IS 5 BP 1873 EP 1880 PG 8 WC Immunology SC Immunology GA KN532 UT WOS:A1993KN53200025 PM 8094729 ER PT J AU WEI, S BLANCHARD, DK LIU, JH LEONARD, WJ DJEU, JY AF WEI, S BLANCHARD, DK LIU, JH LEONARD, WJ DJEU, JY TI ACTIVATION OF TUMOR-NECROSIS-FACTOR-ALPHA PRODUCTION FROM HUMAN NEUTROPHILS BY IL-2 VIA IL-2-R-BETA SO JOURNAL OF IMMUNOLOGY LA English DT Article ID COLONY-STIMULATING FACTOR; HUMAN POLYMORPHONUCLEAR NEUTROPHILS; AFFINITY INTERLEUKIN-2 RECEPTOR; MESSENGER-RNA; CANDIDA-ALBICANS; GENE-EXPRESSION; HUMAN-MONOCYTES; BETA-CHAIN; POSTTRANSCRIPTIONAL REGULATION; INTERFERON-GAMMA AB In addition to T cells, NK cells, B cells, and monocytes, we provide new evidence that human polymorphonuclear neutrophils (PMN) can be functionally activated by IL-2 via binding to IL-2Rbeta expressed on the cell surface. Brief exposure of normal PMN to human rIL-2 enhanced both transcriptional and translational expression of TNF-alpha. The release of TNF-alpha protein by IL-2-treated PMN was inhibitable by a specific mAb against human IL-2-Rbeta. The response to IL-2 was dose and time dependent with the increase in TNF-alpha mRNA detected maximally 3 h after IL-2 exposure, followed by a continuous maintenance of high mRNA levels up to 18 h. The TNF-alpha mRNA was significantly increased above the medium control level, with as little as 10 U/ml of IL-2. Maximal transcription was obtained with 1000 U/ml of IL-2, which achieved the level observed with known neutrophil activating factors such as granulocyte-macrophage-CSF, IL-8, and Candida albicans. Using actinomycin D, it was found that new and continuous synthesis of a labile TNF-alpha mRNA was responsible for the observed high levels of transcripts. Of significance was the observation that cycloheximide could selectively modulate TNF-alpha mRNA transcription in neutrophils, depending on the cytokine used. Cycloheximide did not affect or alter TNF-alpha mRNA induction in IL-2-treated neutrophils but abrogated it in granulocyte-macrophage-CSF-treated neutrophils and superinduced transcription in C. albicans-treated neutrophils. Thus various control elements must be involved in the transcription of the TNF-alpha genes that are responsive to different cytokines and activating factors. The induction of TNF-alpha and functional activation of neutrophils by IL-2 is therefore an important immunomodulatory property of IL-2 that has not heretofore been recognized. C1 UNIV S FLORIDA,COLL MED,H LEE MOFFITT CANC CTR,DEPT MED MICROBIOL & IMMUNOL,TAMPA,FL 33612. NHLBI,PULM & MOLEC IMMUNOL SECT,BETHESDA,MD 20892. FU NCI NIH HHS [CA 46820]; NIAID NIH HHS [AI 24699] NR 50 TC 59 Z9 60 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 1993 VL 150 IS 5 BP 1979 EP 1987 PG 9 WC Immunology SC Immunology GA KN532 UT WOS:A1993KN53200037 PM 8436829 ER PT J AU GRAHAM, BS MATTHEWS, TJ BELSHE, RB CLEMENTS, ML DOLIN, R WRIGHT, PF GORSE, GJ SCHWARTZ, DH KEEFER, MC BOLOGNESI, DP COREY, L STABLEIN, DM ESTERLITZ, JR HU, SL SMITH, GE FAST, PE KOFF, WC AF GRAHAM, BS MATTHEWS, TJ BELSHE, RB CLEMENTS, ML DOLIN, R WRIGHT, PF GORSE, GJ SCHWARTZ, DH KEEFER, MC BOLOGNESI, DP COREY, L STABLEIN, DM ESTERLITZ, JR HU, SL SMITH, GE FAST, PE KOFF, WC TI AUGMENTATION OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 NEUTRALIZING ANTIBODY BY PRIMING WITH GP160 RECOMBINANT VACCINIA AND BOOSTING WITH RGP160 IN VACCINIA-NAIVE ADULTS SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID IMMUNIZATION; CHIMPANZEES; PROTECTION; INFECTION; HIV-1; GP120 AB Twelve vaccinia-naive volunteers were inoculated with recombinant vaccinia virus expressing the human immunodeficiency virus type 1 (HIV-1) strain IIIB (HIV-1IIIB) envelope glycoprotein gp160 and subsequently immunized with 640 mug of recombinant (r) gp160 protein produced in baculovirus. After booster immunization with rgp160, the sera of all vaccinees showed strong antibody responses detected by Western blot and ELISA; 8 had neutralizing activity and 5 had fusion inhibition activity against the homologous strain; 5 blocked binding of CD4 cells to gp120. Cross-reactive neutralization of HIV-1MN was detected in 3 of 8 sera that neutralized HIV-1IIIB. The combination of live recombinant vaccinia followed by subunit booster immunization was more immunogenic than either product alone and represents a promising approach for HIV-I immunoprophylaxis. Further definition of recombinant vaccinia safety and augmentation of immune responses to geographically prevalent HIV-1 strains will be necessary before expanding clinical trials to high-risk groups. C1 DUKE UNIV,MED CTR,DURHAM,NC 27710. ST LOUIS UNIV,SCH MED,ST LOUIS,MO 63104. UNIV ROCHESTER,SCH MED & DENT,ROCHESTER,NY 14642. BRISTOL MYERS SQUIBB PHARMACEUT RES INST,SEATTLE,WA. UNIV WASHINGTON,SCH MED,SEATTLE,WA 98195. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,BALTIMORE,MD 21218. JOHNS HOPKINS UNIV,SCH MED,BALTIMORE,MD 21205. EMMES CORP,POTOMAC,MD. NIAID,BETHESDA,MD 20892. MICROGENESYS,MERIDEN,CT. RP GRAHAM, BS (reprint author), VANDERBILT UNIV,MED CTR,SCH MED,DEPT MED,DIV INFECT DIS,A-3310 MCN,NASHVILLE,TN 37232, USA. RI Hu, Shiu-Lok/A-3196-2008 OI Hu, Shiu-Lok/0000-0003-4336-7964 FU NIAID NIH HHS [AI-05061, AI-05062, AI-82500] NR 14 TC 157 Z9 158 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 1993 VL 167 IS 3 BP 533 EP 537 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA KN152 UT WOS:A1993KN15200003 PM 8095059 ER PT J AU ROBERTGUROFF, M ROILIDES, E MULDOON, R VENZON, D HUSSON, R MARSHALL, D GALLO, RC PIZZO, PA AF ROBERTGUROFF, M ROILIDES, E MULDOON, R VENZON, D HUSSON, R MARSHALL, D GALLO, RC PIZZO, PA TI HUMAN-IMMUNODEFICIENCY-VIRUS (HIV) TYPE-1 STRAIN MN NEUTRALIZING ANTIBODY IN HIV-INFECTED CHILDREN - CORRELATION WITH CLINICAL STATUS AND PROGNOSTIC VALUE SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID AIDS-RELATED COMPLEX; HTLV-III; ENVELOPE GLYCOPROTEIN; MATERNAL ANTIBODIES; SYNTHETIC PEPTIDES; GP120; TRANSMISSION; EPITOPES; CHIMPANZEES; SEQUENCE AB Protective immunity to human immunodeficiency virus (HIV) was examined in 228 serial sera from 58 HIV-infected children before and during antiretroviral therapy. Binding antibodies to putative protective V3 epitopes of HIV-1IIIV and HIV-1MN were investigated by a peptide ELISA, and neutralizing antibodies by inhibition of HIV-1MN cell-free viral infection. No difference in binding of total IgG or IgG subclasses was observed between patients with mild (group A) or advanced disease (group B). However, group A patients were more likely to possess neutralizing antibody titers greater-than-or-equal-to 225 (P = .040 after adjustment for CD4). This threshold titer also predicted clinical outcome in patients with age-adjusted CD4 count > 10% of normal median. Patients with titers < 225 more frequently encountered major clinical events during follow-up than did patients with titers greater-than-or-equal-to 225 (P = .0028). Epitopes other than the linear V3 loop contribute to this protective immune response. Identification of these epitopes should assist immune therapy of AIDS and HIV vaccine development. C1 NIH,BIOSTAT & DATA MANAGEMENT SECT,BETHESDA,MD 20892. RP ROBERTGUROFF, M (reprint author), NIH,PEDIAT BRANCH,TUMOR CELL BIOL LAB,BLDG 37,ROOM GA15,BETHESDA,MD 20892, USA. RI Venzon, David/B-3078-2008 NR 30 TC 28 Z9 28 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 1993 VL 167 IS 3 BP 538 EP 546 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA KN152 UT WOS:A1993KN15200004 PM 7680059 ER PT J AU SMITH, PD EISNER, MS MANISCHEWITZ, JF GILL, VJ MASUR, H FOX, CF AF SMITH, PD EISNER, MS MANISCHEWITZ, JF GILL, VJ MASUR, H FOX, CF TI ESOPHAGEAL DISEASE IN AIDS IS ASSOCIATED WITH PATHOLOGICAL PROCESSES RATHER THAN MUCOSAL HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID IMMUNE-DEFICIENCY SYNDROME; DIAGNOSIS; INFECTION; HIV-1; CELLS; SYMPTOMS AB Twenty-five patients with AIDS and esophageal symptoms were evaluated for the presence of esophageal disease and human immunodeficiency virus type 1 (HIV-1) in the esophageal mucosa. A single infectious process caused by Candida albicans, cytomegalovirus, herpes simplex virus, varicella-zoster virus, or Mycobacterium avium-intracellulare complex or a single noninfectious process caused by Kaposi's sarcoma or reflux esophagitis was identified in 20 patients. Two processes were identified in 5 patients. HIV-1 mRNA was detected by in situ hybridization in mononuclear cells in esophageal lamina propria in 36% of patients. The presence of HIV-1 in the esophageal mucosa was not associated with a specific esophageal symptom, mucosal inflammation or ulceration, Kaposi's sarcoma, specific opportunistic infection, or response of the infection(s) to therapy. Esophageal disease in patients with AIDS appears to be associated with specific pathologic processes rather than the presence of HIV-1 in esophageal mucosa. C1 US FDA,NIDR,IMMUNOL LAB,BETHESDA,MD 20014. US FDA,DEPT CLIN PATHOL,MICROBIOL SERV,BETHESDA,MD 20014. US FDA,CTR CLIN,DEPT CRIT CARE MED,BETHESDA,MD 20014. US FDA,NIH,NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20014. US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD 20014. NR 34 TC 47 Z9 48 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 1993 VL 167 IS 3 BP 547 EP 552 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA KN152 UT WOS:A1993KN15200005 PM 8440925 ER PT J AU GLASS, GE WATSON, AJ LEDUC, JW KELEN, GD QUINN, TC CHILDS, JE AF GLASS, GE WATSON, AJ LEDUC, JW KELEN, GD QUINN, TC CHILDS, JE TI INFECTION WITH A RATBORNE HANTAVIRUS IN UNITED-STATES RESIDENTS IS CONSISTENTLY ASSOCIATED WITH HYPERTENSIVE RENAL-DISEASE SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID HEMORRHAGIC-FEVER; NEPHROPATHIA-EPIDEMICA; SYNDROME VIRUSES; RAT-POPULATIONS; BALTIMORE; ANTIBODY; MARYLAND AB A survey of 8080 subjects was conducted in Baltimore, examining the association between infection with hantaviruses and renal disease. Two groups (N = 6060) with no known risk factors were selected to establish a baseline antibody prevalence. Overall, antibody prevalence was 0.25%. Seroprevalence increased with age, without sex- or race-related differences. Patients with proteinuria showed the same patterns of infection but were more commonly seropositive (1.46%) than the reference group (OR, 3.23; P < .05). Infection among dialysis patients with end-stage renal disease was 2.76%, significantly higher than in the reference group (OR, 5.03; P < .05). In the proteinuria and the dialysis groups, hantavirus infection was consistently associated with a diagnosis of hypertensive renal disease. The association was unrelated to other chronic renal disease diagnoses. Overall, 6.5% of patients with end-stage renal disease due to hypertension were seropositive for a hantavirus. These data suggest that hantavirus infection is associated with hypertensive renal disease. C1 JOHNS HOPKINS UNIV, SCH MED, DEPT NEPHROL, BALTIMORE, MD 21205 USA. JOHNS HOPKINS UNIV, SCH MED, DIV EMERGENCY MED, BALTIMORE, MD 21205 USA. JOHNS HOPKINS UNIV, SCH MED, DIV INFECT DIS, BALTIMORE, MD 21205 USA. USA, MED RES INST INFECT DIS, DEPT EPIDEMIOL, DIV DIS ASSESSMENT, FT DETRICK, MD USA. NIAID, IMMUNOREGULAT LAB, BETHESDA, MD 20892 USA. RP GLASS, GE (reprint author), JOHNS HOPKINS UNIV, SCH HYG & PUBL HLTH, DEPT IMMUNOL & INFECT DIS, 615 N WOLFE ST, BALTIMORE, MD 21205 USA. RI Quinn, Thomas/A-2494-2010; Childs, James/B-4002-2012; OI Kelen, Gabor/0000-0002-3236-8286 NR 47 TC 104 Z9 105 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1537-6613 J9 J INFECT DIS JI J. Infect. Dis. PD MAR PY 1993 VL 167 IS 3 BP 614 EP 620 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA KN152 UT WOS:A1993KN15200014 PM 8095060 ER PT J AU WEINBERG, WC GOODMAN, LV GEORGE, C MORGAN, DL LEDBETTER, S YUSPA, SH LICHTI, U AF WEINBERG, WC GOODMAN, LV GEORGE, C MORGAN, DL LEDBETTER, S YUSPA, SH LICHTI, U TI RECONSTITUTION OF HAIR FOLLICLE DEVELOPMENT INVIVO - DETERMINATION OF FOLLICLE FORMATION, HAIR-GROWTH, AND HAIR QUALITY BY DERMAL CELLS SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID PAPILLA CELLS; MOUSE SKIN; RASHA ONCOGENE; INDUCTION; MICE; NUDE; RAT; TRANSPLANTATION; CARCINOGENESIS; IMPLANTATION AB Combinations of cultured and uncultured epidermal and dermal cell preparations from newborn and perinatal mice were grafted onto the backs of athymic nude mouse hosts to elucidate the cellular requirements for skin appendage formation. All epidermal populations studied, including a total epidermal keratinocyte preparation from trypsin-split skin, developing hair follicle buds isolated from epidermis, and preformed hair follicles isolated from dermis, make haired skin when grafted with fresh dermal cells. Only pre-formed hair follicles produce haired skin on grafts without an additional dermal component. Hair follicle buds grafted alone or with cultured dermal cells will reconstitute skin but without appendage formation. Thus, cells or factors present in fresh, but not cultured, dermal cells are essential for supporting hair growth from budding follicles, whereas more developed (pre-formed) follicles appear to contain all the necessary components for hair formation. Dissociation of isolated hair follicles by trypsin/ethylenediaminetetraacetic acid prior to grafting is permissive for hair growth, suggesting that follicle cells can be re-induced or reassociate in vivo. Dermal papilla cells, microdissected from rat vibrissal follicles and cultured for up to 14 passages, stimulate hair growth from follicle buds and influence the quality of hair growth from pre-formed hair follicles. Thus, dermal papilla cells maintain inductive capacity in culture and contribute to the reconstituted skin. This reconstitution model should be useful for identifying cell populations within the hair follicle compartment necessary for hair growth and for examining the effects of specific gene products on hair follicle growth and development in vivo. C1 UPJOHN CO,KALAMAZOO,MI 49001. BIOCON INC,ROCKVILLE,MD. RP WEINBERG, WC (reprint author), NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT,BETHESDA,MD 20892, USA. RI Weinberg, Wendy/A-8920-2009 NR 31 TC 128 Z9 140 U1 0 U2 7 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAR PY 1993 VL 100 IS 3 BP 229 EP 236 DI 10.1111/1523-1747.ep12468971 PG 8 WC Dermatology SC Dermatology GA KR121 UT WOS:A1993KR12100002 PM 8440892 ER PT J AU TUCKER, MA FRASER, MC GOLDSTEIN, AM ELDER, DE GUERRY, D ORGANIC, SM AF TUCKER, MA FRASER, MC GOLDSTEIN, AM ELDER, DE GUERRY, D ORGANIC, SM TI RISK OF MELANOMA AND OTHER CANCERS IN MELANOMA-PRONE FAMILIES SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID DYSPLASTIC NEVUS SYNDROME; CUTANEOUS MALIGNANT-MELANOMA; PRECURSOR LESIONS; TUMOR PROGRESSION; MELANOCYTIC NEVI; ASSOCIATION; NAEVI; SURVIVAL; LINKAGE; LOCUS AB We evaluated the risk of developing melanoma over time in members of 23 melanoma-prone families. All 23 families had dysplastic nevi as well as melanoma. Forty-seven melanomas occurred prospectively, all in family members with dysplastic nevi. The prospective melanomas were markedly thinner than the melanomas diagnosed prior to or at the time of the subject's entry into the study. The cumulative risk of melanoma by age 50 years among people with dysplastic nevi was 48.9% +/- 4.2%. Overall, the relative risk of a prospective melanoma among family members with previous melanoma was 229 (95% confidence interval 110-422). The risk varied by time interval and was 362 in the first 5 years, decreasing to 120 after 5 years. The risk of developing melanoma was 85 times increased (95% confidence interval 41-156) in family members with dysplastic nevi and also declined over time in this group. There was no significant excess of cancers other than melanoma. Close surveillance of these high-risk families has led to diagnosis of melanoma at an earlier developmental stage, which should result in a decrease in mortality over time. C1 UNIV PENN,SCH MED,PIGMENTED LES STUDY GRP,PHILADELPHIA,PA 19104. UNIV PENN,SCH MED,DEPT PATHOL,PHILADELPHIA,PA 19104. UNIV PENN,SCH MED,DEPT MED,PHILADELPHIA,PA 19104. RP TUCKER, MA (reprint author), NCI,GENET EPIDEMIOL BRANCH,FAMILY STUDIES SECT,EXECUT PLAZA N,BETHESDA,MD 20892, USA. RI Tucker, Margaret/B-4297-2015 NR 30 TC 70 Z9 70 U1 0 U2 2 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAR PY 1993 VL 100 IS 3 BP S350 EP S355 DI 10.1111/1523-1747.ep12470264 PG 6 WC Dermatology SC Dermatology GA KR121 UT WOS:A1993KR12100041 PM 8440923 ER PT J AU MCNELLIS, D AF MCNELLIS, D TI A VIEW FROM BETHESDA - NICHDS 30TH BIRTHDAY SO JOURNAL OF MATERNAL-FETAL INVESTIGATION LA English DT Editorial Material RP MCNELLIS, D (reprint author), NICHHD,CTR RES MOTHERS & CHILDREN,PREGNANCY & PERINATOL BRANCH,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0939-6322 J9 J MATERN-FETAL INVES JI J. Matern.-Fetal Invest. PD SPR PY 1993 VL 3 IS 2 BP 69 EP 69 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA LH858 UT WOS:A1993LH85800001 ER PT J AU SCOTT, JE AF SCOTT, JE TI MANAGED MENTAL-HEALTH-CARE - ADMINISTRATIVE AND CLINICAL ISSUES - FELDMAN,JL, FITZPATRICK,RJ SO JOURNAL OF MENTAL HEALTH ADMINISTRATION LA English DT Book Review RP SCOTT, JE (reprint author), NIAAA,ROCKVILLE,MD 20852, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 SN 0092-8623 J9 J MENT HEALTH ADMIN JI J. Ment. Health Adm. PD SPR PY 1993 VL 20 IS 1 BP 80 EP 81 PG 2 WC Health Policy & Services SC Health Care Sciences & Services GA LL854 UT WOS:A1993LL85400010 ER PT J AU ALTSCHUL, SF AF ALTSCHUL, SF TI A PROTEIN ALIGNMENT SCORING SYSTEM SENSITIVE AT ALL EVOLUTIONARY DISTANCES SO JOURNAL OF MOLECULAR EVOLUTION LA English DT Article DE HOMOLOGY; SEQUENCE COMPARISON; STATISTICAL SIGNIFICANCE; ALIGNMENT ALGORITHMS; PATTERN RECOGNITION ID AMINO-ACID SEQUENCES; PATTERN-RECOGNITION; GENERAL-METHOD; SIMILARITIES; MATRIX; IDENTIFICATION; DATABASE; HOMOLOGY; SEARCH AB Protein sequence alignments generally are constructed with the aid of a ''substitution matrix'' that specifies a score for aligning each pair of amino acids. Assuming a simple random protein model, it can be shown that any such matrix, when used for evaluating variable-length local alignments, is implicitly a ''log-odds'' matrix, with a specific probability distribution for amino acid pairs to which it is uniquely tailored. Given a model of protein evolution from which such distributions may be derived, a substitution matrix adapted to detecting relationships at any chosen evolutionary distance can be constructed. Because in a database search it generally is not known a priori what evolutionary distances will characterize the similarities found, it is necessary to employ an appropriate range of matrices in order not to overlook potential homologies. This paper formalizes this concept by defining a scoring system that is sensitive at all detectable evolutionary distances. The statistical behavior of this scoring system is analyzed, and it is shown that for a typical protein database search, estimating the originally unknown evolutionary distance appropriate to each alignment costs slightly over two bits of information, or somewhat less than a factor of five in statistical significance. A much greater cost may be incurred, however, if only a single substitution matrix, corresponding to the wrong evolutionary distance, is employed. RP NIH, NATL LIB MED, NATL CTR BIOTECHNOL INFORMAT, BETHESDA, MD 20894 USA. NR 55 TC 87 Z9 89 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0022-2844 EI 1432-1432 J9 J MOL EVOL JI J. Mol. Evol. PD MAR PY 1993 VL 36 IS 3 BP 290 EP 300 DI 10.1007/BF00160485 PG 11 WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity GA KN940 UT WOS:A1993KN94000011 PM 8483166 ER PT J AU GOZES, I BRENNEMAN, DE AF GOZES, I BRENNEMAN, DE TI NEUROPEPTIDES AS GROWTH AND DIFFERENTIATION FACTORS IN GENERAL AND VIP IN PARTICULAR SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Article DE VASOACTIVE INTESTINAL PEPTIDE; GENE EXPRESSION; GROWTH FACTORS ID VASOACTIVE-INTESTINAL-PEPTIDE; CENTRAL-NERVOUS-SYSTEM; RAT SUPRACHIASMATIC NUCLEUS; MESSENGER-RIBONUCLEIC-ACID; SPINAL-CORD CULTURES; CELL-DEATH; ELECTRICAL-ACTIVITY; NEUROTROPHIC FACTOR; NEURONAL SURVIVAL; NEUROMUSCULAR BLOCKADE AB During the course of neurodevelopment a large population of neurons die normally (Berg, 1982; Oppenheim et al., 1989). Are neuropeptides involved in the regulation of neuronal survival, maturation, and maintenance? The peptides are an ever growing family of neuroactive agents and this review shall emphasize VIP (vasoactive intestinal peptide [Said and Mutt, 1970; Gozes and Brenneman, 19891), which has been shown to be involved in maturation, growth, and maintenance of neurons (Brenneman et al., 1985a,1987,1988,1990,1990b; Brenneman and Eiden, 1986; Brenneman and Nelson, 1986). Comparative actions of other neuropeptides will also be discussed. C1 NICHHD,DEV NEUROBIOL LAB,DEV & MOLEC PHARMACOL SECT,BETHESDA,MD 20892. RP GOZES, I (reprint author), TEL AVIV UNIV,SACKLER SCH MED,DEPT CHEM PATHOL,TEL AVIV,ISRAEL. NR 83 TC 68 Z9 68 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 SN 0895-8696 J9 J MOL NEUROSCI JI J. Mol. Neurosci. PD SPR PY 1993 VL 4 IS 1 BP 1 EP 9 DI 10.1007/BF02736685 PG 9 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA KQ343 UT WOS:A1993KQ34300001 PM 8318354 ER PT J AU STALEY, J COY, DH JENSEN, RT MOODY, TW AF STALEY, J COY, DH JENSEN, RT MOODY, TW TI SOLUBILIZATION AND PURIFICATION OF BOMBESIN GASTRIN RELEASING PEPTIDE RECEPTORS FROM HUMAN CELL-LINES SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Article DE BOMBESIN; GRP; RECEPTOR; SOLUBILIZATION; PURIFICATION ID SWISS 3T3 CELLS; HIGH-AFFINITY RECEPTORS; LUNG-CANCER; LIGAND-BINDING; CROSS-LINKING; POTENT; STIMULATION; ANTAGONISTS; IDENTIFICATION; MEMBRANES AB Bombesin/gastrin releasing peptide (BN/GRP) receptors were solubilized and purified from human glioblastoma (U-118) and lung carcinoid cell lines (NCI-H720). The U-118 cells, when extracted with CHAPS/cholesterol hemisuccinate (CHS), bound (I-125-Tyr4)BN with high affinity (Kd = 2 nM) to a single class of sites (B(max) = 150 fmol/mg protein). Specific (I-125-Tyr4)BN binding was inhibited with high affinity by BN, GRP, GRP14-27, and receptor antagonists such as (D-Phe6)BN6-13methyl ester(ME) and (D-Phe6)BN6-13 propylamide(PA) (IC50 = 2,22,3, 1 and 2 nM, respectively) but not GRP1-16 or BN1-12. The solubilized and cellular receptor bound peptides with similar affinity. The solublized receptor was purified using (Lys0, Gly1-4, D-Ala5)BN and Lys3, Gly4,5, D-Tyr6)BN3-13 PA affinity resins. When eluted from the affinity resins by NaCl, the receptor bound (I-125-D-Try6)BN6-13 ME with high affinity, The NCI-H720 BN/GRP receptor was purified 86,000-fold after extraction with CHAPS/CHS and purification using both affinity resins. SDS-PAGE analysis indicated that major 65 and 115 kDa proteins were purified. These data indicate that BN/GRP receptors can be solubilized from human cells and purified using affinity chromatography techniques with retention of ligand binding activity. C1 GEORGE WASHINGTON UNIV,MED CTR,DEPT BIOCHEM & MOLEC BIOL,WASHINGTON,DC 20037. TULANE UNIV,SCH MED,DEPT MED,NEW ORLEANS,LA 70112. NIDDKD,DIGEST DIS BRANCH,BETHESDA,MD 20892. FU NCI NIH HHS [CA-45153, CA-53477] NR 33 TC 15 Z9 15 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 SN 0895-8696 J9 J MOL NEUROSCI JI J. Mol. Neurosci. PD SPR PY 1993 VL 4 IS 1 BP 29 EP 40 DI 10.1007/BF02736688 PG 12 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA KQ343 UT WOS:A1993KQ34300004 PM 8391295 ER PT J AU CARTER, CA WOURMS, JP AF CARTER, CA WOURMS, JP TI NATURALLY-OCCURRING DIBLASTODERMIC EGGS IN THE ANNUAL FISH CYNOLEBIAS - IMPLICATIONS FOR DEVELOPMENTAL REGULATION AND DETERMINATION SO JOURNAL OF MORPHOLOGY LA English DT Article ID SALMO-GAIRDNERI RICHARDSON; FUNDULUS DEEP CELLS; MORPHOGENETIC MOVEMENTS; GASTRULA STAGES; FATE MAP; ZEBRAFISH; BIOLOGY; BLASTOMERES; LOCOMOTION; BLASTULA AB Annual fish development differs from that of other teleosts because a phase of blastomere dispersion-reaggregation spatially and temporally separates epiboly from embryogenesis. The fate of dispersed blastomeres was assessed in diblastodermic eggs of the annual fishes Cynolebias whitei and C. nigripinnis. In typical teleosts, blastomere determination and the events of primary embryonic induction occur prior to or during epiboly, so diblastodermic eggs produce partially or completely duplicated embryos. In the diblastodermic eggs of Cynolebias, the two blastoderms are completely separate from the one cell stage to the high blastula. Blastoderm fusion begins during midepiboly. By the end of epiboly, blastoderm fusion has been completed, and the deep, embryo-forming blastomeres of both blastoderms have completely dispersed and intermingled to form a single cell population. A typical annual fish dispersed blastomere phase ensues. Blastomeres reaggregate into a single mass, in which one embryo develops. When hatched, the young fish have no obvious structural or functional abnormalities. We suggest that the dispersed blastomeres of annual fish eggs are equivalent and that induction or determination takes place within the reaggregate. Alternatively, dispersed cells are partially determined but highly regulative, so that, when two populations fuse, the cells sort out according to tissue type and form a single embryo. In either instance, the formation of a single, normal embryo seems to corroborate the hypothesis that the dispersed cell phase of annual fishes is an adaptation that prevents environmentally induced developmental defects. C1 CLEMSON UNIV,DEPT BIOL SCI,CLEMSON,SC 29634. NIEHS,EXPTL TOXICOL BRANCH,RES TRIANGLE PK,NC 27709. NR 55 TC 4 Z9 5 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0362-2525 J9 J MORPHOL JI J. Morphol. PD MAR PY 1993 VL 215 IS 3 BP 301 EP 312 DI 10.1002/jmor.1052150309 PG 12 WC Anatomy & Morphology SC Anatomy & Morphology GA KT148 UT WOS:A1993KT14800008 ER PT J AU GARRAFFO, HM SPANDE, TF DALY, JW BALDESSARI, A GROS, EG AF GARRAFFO, HM SPANDE, TF DALY, JW BALDESSARI, A GROS, EG TI ALKALOIDS FROM BUFONID TOADS (MELANOPHRYNISCUS) - DECAHYDROQUINOLINES, PUMILIOTOXINS AND HOMOPUMILIOTOXINS, INDOLIZIDINES, PYRROLIZIDINES, AND QUINOLIZIDINES SO JOURNAL OF NATURAL PRODUCTS LA English DT Article ID DENDROBATID POISON FROGS; 8-METHYLINDOLIZIDINES; MYOBATRACHIDAE; ANT AB Skins of bufonid toads of the genus Melanophryniscus contain several classes of alkaloids: decahydroquinolines, pumiliotoxins, allopumiliotoxins, homopumiliotoxins, both 3,5- and 5,8-disubstituted indolizidines, 3,5-disubstituted pyrrolizidines, and a 1,4-disubstituted quinolizidine. Tricyclic alkaloids, including precoccinelline [193A] and alkaloid 236, an oxime methyl ether, are present in one population of Melanophryniscus stelzneri. C1 NIDDK,BIOORGAN CHEM LAB,BETHESDA,MD 20892. UBA,FAC CIENCIAS EXACTAS & NAT,RA-1428 BUENOS AIRES,ARGENTINA. NR 20 TC 97 Z9 99 U1 0 U2 6 PU AMER SOC PHARMACOGNOSY PI CINCINNATI PA LLOYD LIBRARY & MUSEUM 917 PLUM ST, CINCINNATI, OH 45202 SN 0163-3864 J9 J NAT PROD JI J. Nat. Prod. PD MAR PY 1993 VL 56 IS 3 BP 357 EP 373 DI 10.1021/np50093a008 PG 17 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA KR544 UT WOS:A1993KR54400008 PM 8482947 ER PT J AU HABER, R BESSETTE, D HULIHANGIBLIN, B DURCAN, MJ GOLDMAN, D AF HABER, R BESSETTE, D HULIHANGIBLIN, B DURCAN, MJ GOLDMAN, D TI IDENTIFICATION OF TRYPTOPHAN 2,3-DIOXYGENASE RNA IN RODENT BRAIN SO JOURNAL OF NEUROCHEMISTRY LA English DT Note DE TRYPTOPHAN 2,3-DIOXYGENASE; RODENT BRAIN; RNA AMPLIFICATION ID INDOLEAMINE 2,3-DIOXYGENASE; INTERFERON-GAMMA; HUMAN-FIBROBLASTS; OXYGENASE GENE; INDUCTION AB The gene for tryptophan 2,3-dioxygenase (TDO) heretofore was believed to be expressed only in liver. The data presented here demonstrate that RNA encoding TDO is present in rodent brain. Oligonucleotide primers based on the rat liver TDO cDNA sequence were synthesized and used to amplify RNA derived from mouse whole brain and liver and rat brain regions by the RNA-PCR. Reaction products were purified and subjected to DNA sequencing. Identical sequences were obtained when mouse whole brain and liver RNAs were amplified, and these sequences were shown to be 96% identical to the published rat liver tryptophan TDO cDNA sequence. In addition, TDO sequences were found in RNA derived from rat brainstem, cerebellum, cortex, hypothalamus and the remainder of the brain. RP HABER, R (reprint author), NIAAA,NEUROGENET LAB,BLDG 10,RM 3C215,BETHESDA,MD 20892, USA. RI Goldman, David/F-9772-2010 OI Goldman, David/0000-0002-1724-5405 NR 18 TC 47 Z9 48 U1 0 U2 5 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 1993 VL 60 IS 3 BP 1159 EP 1162 DI 10.1111/j.1471-4159.1993.tb03269.x PG 4 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA KN155 UT WOS:A1993KN15500047 PM 7679723 ER PT J AU ANDREWS, AM MURPHY, DL AF ANDREWS, AM MURPHY, DL TI SUSTAINED DEPLETION OF CORTICAL AND HIPPOCAMPAL SEROTONIN AND NOREPINEPHRINE BUT NOT STRIATAL DOPAMINE BY 1-METHYL-4-(2'-AMINOPHENYL)-1,2,3,6-TETRAHYDROPYRIDINE (2'-NH2-MPTP) - A COMPARATIVE-STUDY WITH 2'-CH3-MPTP AND MPTP SO JOURNAL OF NEUROCHEMISTRY LA English DT Note DE MPTP; 1-METHYL-4-(2'-METHYLPHENYL)-1,2,3,6-TETRAHYDROPYRIDINE; SEROTONIN; NOREPINEPHRINE; DOPAMINE; NEUROTOXIN ID 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE MPTP; CHRONIC PARKINSONISM; ANALOGS; NEUROTOXICITY; MOUSE; METABOLITES; TOXICITY; TOOLS AB Unlike 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), which produces consistent decreases in levels of striatal dopamine (DA) with considerably smaller and more variable effects on mouse brain levels of serotonin (5-HT) and norepinephfine (NE), a novel amine-substituted MPTP analogue, 1-methyl-4-(2'-aminophenyl)-1,2,3,6-tetrahydropyridine (2'-NH2-MPTP), administered in a standard mouse dosing paradigm for MPTP (20 mg/kg x 4) did not affect striatal DA but led to marked reductions (60-70%) in levels of 5-HT, 5-hydroxyindoleacetic acid (5-HIAA), and NE measured in frontal cortex and hippocampus 1 week after treatment. Another 2'-substituted MPTP analogue, 1-methyl-4-(2'-methylphenyl)-1,2,3,6-tetrahydropyridine, affected cortical and hippocampal 5-HT, 5-HIAA, and NE only minimally, while markedly reducing the DA content in striatum (90%), thus indicating that the substituent (-NH2 versus -CH3) at the 2' position is important for the differential effects of these MPTP analogues. In a replication study with a 3-week end point, hippocampal and cortical 5-HT, 5-HIAA, and NE levels remained depressed with no indication of recovery. These results suggest that 2'-NH2-MPTP may be a novel, regionally selective neurotoxin for serotonergic and noradrenergic nerve terminals. C1 AMERICAN UNIV,DEPT MED,WASHINGTON,DC 20016. RP ANDREWS, AM (reprint author), NIMH,CLIN SCI LAB,BLDG 10,ROOM 3D41,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Andrews, Anne/B-4442-2011 OI Andrews, Anne/0000-0002-1961-4833 NR 21 TC 31 Z9 31 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAR PY 1993 VL 60 IS 3 BP 1167 EP 1170 DI 10.1111/j.1471-4159.1993.tb03271.x PG 4 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA KN155 UT WOS:A1993KN15500049 PM 8094744 ER PT J AU ROIVAINEN, R NIKKARI, ST IADAROLA, MJ KOISTINAHO, J AF ROIVAINEN, R NIKKARI, ST IADAROLA, MJ KOISTINAHO, J TI COLOCALIZATION OF THE BETA-SUBTYPE OF PROTEIN-KINASE-C AND PHOSPHORYLATION-DEPENDENT IMMUNOREACTIVITY OF NEUROFILAMENTS IN INTACT, DECENTRALIZED AND AXOTOMIZED RAT PERIPHERAL NEURONS SO JOURNAL OF NEUROCYTOLOGY LA English DT Article ID MONOCLONAL-ANTIBODIES DISTINGUISH; SUPERIOR CERVICAL-GANGLION; MAMMALIAN NEUROFILAMENTS; NEUROFIBRILLARY TANGLES; INTERMEDIATE FILAMENTS; CYTOSKELETAL PROTEINS; SENSORY NEURONS; SPINAL-CORD; PKC-BETA; SUBUNITS AB The localizations of protein kinase C-beta-immunoreactivity and phosphorylation-dependent immunoreactivity of neurofilaments were compared in rat dorsal root, hypogastric, and superior cervical ganglia. In all the ganglia studied, protein kinase C-beta and phosphorylation-dependent immunoreactivity of neurofilaments were co-localized in nerve fibres, and no fibres with only protein kinase C-beta-immunoreactivity or phosphorylation-dependent immunoreactivity of neurofilaments were observed. Most intense perikaryal protein kinase c-beta and phosphorylation-dependent neurofilament-staining were seen in large dorsal root ganglion neurons, whereas in the superior cervical ganglion only very faint protein-kinase C-beta and no phosphorylation-dependent staining was seen in the neuronal cell bodies. Both decentralization and axotomy of the superior cervical ganglion induced an accumulation of protein-kinase C-beta-immunoreactivity and phosphorylation-dependent immunoreactivity of neurofilaments in the majority of neuronal perikarya. The accumulation was first observed at 1-2 days postoperation and it persisted up to 6-10 days postoperation. In strongly labelled decentralized neuronal perikarya, precipitation of immunoreactivity was seen near the cell and nuclear membranes, whereas in axotomized neurons, immunoreactivity was often concentrated as a unipolar clump in the cytoplasm. The results show that protein kinase C-beta-immunoreactivity and phosphorylation-dependent immunoreactivity of neurofilaments are colocalized in intact rat peripheral ganglia and that both accumulate transiently in cell bodies of the superior cervical ganglion after decentralization and axotomy. C1 UNIV TAMPERE,DEPT PUBL HLTH,SF-33101 TAMPERE,FINLAND. NIDR,NEUROBIOL & ANESTHESIOL LAB,BETHESDA,MD 20892. UNIV TAMPERE,DEPT BIOMED SCI,SF-33101 TAMPERE,FINLAND. NR 55 TC 8 Z9 8 U1 0 U2 0 PU CHAPMAN HALL LTD PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8HN SN 0300-4864 J9 J NEUROCYTOL JI J. Neurocytol. PD MAR PY 1993 VL 22 IS 3 BP 154 EP 163 DI 10.1007/BF01246354 PG 10 WC Cell Biology; Neurosciences SC Cell Biology; Neurosciences & Neurology GA KQ508 UT WOS:A1993KQ50800002 PM 8478638 ER PT J AU COLBY, CL DUHAMEL, JR GOLDBERG, ME AF COLBY, CL DUHAMEL, JR GOLDBERG, ME TI VENTRAL INTRAPARIETAL AREA OF THE MACAQUE - ANATOMIC LOCATION AND VISUAL RESPONSE PROPERTIES SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID POSTERIOR PARIETAL CORTEX; CORTICO-CORTICAL CONNECTIONS; MONKEY EXTRASTRIATE CORTEX; SUPERIOR TEMPORAL SULCUS; SACCADE-RELATED ACTIVITY; FUNCTIONAL-PROPERTIES; ASSOCIATION CORTEX; RHESUS-MONKEY; CORTICOCORTICAL CONNECTIONS; TRACKING NEURONS AB 1. The middle temporal area (MT) projects to the intraparietal sulcus in the macaque monkey. We describe here a discrete area in the depths of the intraparietal sulcus containing neurons with response properties similar to those reported for area MT. We call this area the physiologically defined ventral intraparietal area, or VIP. In the present study we recorded from single neurons in VIP of alert monkeys and studied their visual and oculomotor response properties. 2. Area VIP has a high degree of selectivity for the direction of a moving stimulus. In our sample 72/88 (80%) neurons responded at least twice as well to a stimulus moving in the preferred direction compared with a stimulus moving in the null direction. The average response to stimuli moving in the preferred direction was 9.5 times as strong as the response to stimuli moving in the opposite direction, as compared with 10.9 times as strong for neurons in area MT. 3. Many neurons were also selective for speed of stimulus motion. Quantitative data from 25 neurons indicated that the distribution of preferred speeds ranged from 10 to 320-degrees/s. The degree of speed tuning was on average twice as broad as that reported for area MT. 4. Some neurons (22/41) were selective for the distance at which a stimulus was presented, preferring a stimulus of equivalent visual angle and luminance presented near (within 20 cm) or very near (within 5 cm) the face. These neurons maintained their preference for near stimuli when tested monocularly, suggesting that visual cues other than disparity can support this response. These neurons typically could not be driven by small spots presented on the tangent screen (at 57 cm). 5. Some VIP neurons responded best to a stimulus moving toward the animal. The absolute direction of visual motion was not as important for these cells as the trajectory of the stimulus: the best stimulus was one moving toward a particular point on the face from any direction. 6. VIP neurons were not active in relation to saccadic eye movements. Some neurons (10/17) were active during smooth pursuit of a small target. 7. The predominance of direction and speed selectivity in area VIP suggests that it, like other visual areas in the dorsal stream, may be involved in the analysis of visual motion. RP COLBY, CL (reprint author), NEI,SENSORIMOTOR RES LAB,BLDG 10,RM 10C101,BETHESDA,MD 20892, USA. NR 57 TC 426 Z9 430 U1 1 U2 5 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 1993 VL 69 IS 3 BP 902 EP 914 PG 13 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA KT433 UT WOS:A1993KT43300023 PM 8385201 ER PT J AU HYDE, TM FITZCHARLES, EK WEINBERGER, DR AF HYDE, TM FITZCHARLES, EK WEINBERGER, DR TI AGE-RELATED PROGNOSTIC FACTORS IN THE SEVERITY OF ILLNESS OF TOURETTES-SYNDROME IN MONOZYGOTIC TWINS SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Article ID PARKINSONS-DISEASE; TRANSMISSION AB Tourette's syndrome (TS) was studied in 18 pairs of monozygotic twins where at least one member of the twin set had TS. Sixteen twin sets were concordant for motor tics and had different ages of onset of motor tics (as reported by the mothers and/or medical records). Among these pairs, the earlier motor ticquer was more likely to have a more severe course of illness as assayed by two different indices. In the 10 sets concordant for vocal tics, the earlier vocal ticquer had a more severe course as assayed by only one index. The authors conclude that an early age of onset of motor tics may be the strongest predictor of a more severe lifetime course of a tic disorder. RP HYDE, TM (reprint author), ST ELIZABETH HOSP,NIMH,NEUROSCI RES CTR,CLIN BRAIN DISORDERS BRANCH,WASHINGTON,DC 20032, USA. NR 23 TC 1 Z9 1 U1 0 U2 0 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0895-0172 J9 J NEUROPSYCH CLIN N JI J. Neuropsychiatr. Clin. Neurosci. PD SPR PY 1993 VL 5 IS 2 BP 178 EP 182 PG 5 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA LA294 UT WOS:A1993LA29400005 ER PT J AU METZNER, JL DENTINO, AN GODARD, SL HAY, DP HAY, L LINNOILA, M AF METZNER, JL DENTINO, AN GODARD, SL HAY, DP HAY, L LINNOILA, M TI IMPAIRMENT IN DRIVING AND PSYCHIATRIC-ILLNESS SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Article ID MOTOR-VEHICLE CRASHES; TRAFFIC ACCIDENTS; PERFORMANCE; DRIVERS; ANTIDEPRESSANTS; DEMENTIA C1 UNIV COLORADO HLTH SCI CTR,BOULDER,CO. W VIRGINIA UNIV,MED CTR,SCH MED,MORGANTOWN,WV 26506. OREGON HLTH SCI UNIV,PORTLAND,OR 97201. MED COLL WISCONSIN,MILWAUKEE,WI 53226. NIAAA,ROCKVILLE,MD 20852. OI METZNER, Jeffrey/0000-0003-3665-5239 NR 60 TC 18 Z9 18 U1 1 U2 1 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0895-0172 J9 J NEUROPSYCH CLIN N JI J. Neuropsychiatr. Clin. Neurosci. PD SPR PY 1993 VL 5 IS 2 BP 211 EP 220 PG 10 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA LA294 UT WOS:A1993LA29400012 PM 8508042 ER PT J AU DIPELLEGRINO, G WISE, SP AF DIPELLEGRINO, G WISE, SP TI VISUOSPATIAL VERSUS VISUOMOTOR ACTIVITY IN THE PREMOTOR AND PREFRONTAL CORTEX OF A PRIMATE SO JOURNAL OF NEUROSCIENCE LA English DT Article DE MOTOR SYSTEM; PREMOTOR CORTEX; VISUALLY GUIDED MOVEMENT; FRONTAL LOBE; PREFRONTAL CORTEX; MOTOR SET ID DELAYED-RESPONSE PERFORMANCE; GO/NO-GO DISCRIMINATION; SPATIAL-MOTOR PROCESSES; VISUALLY GUIDED ARM; UNIT-ACTIVITY; NEURONAL-ACTIVITY; RHESUS-MONKEYS; MACAQUE MONKEY; PRECENTRAL CORTEX; INFERIOR AREA-6 AB When visuospatial stimuli instruct a limb movement, the stimulus can be said to have both sensory and sensorimotor aspects. We studied the premotor and prefrontal areas of a rhesus monkey in order to identify neuronal activity related to the motor (or instructional) aspects of such stimuli. A rhesus monkey chose limb-movement targets according to one of two rules: (1 ) visuospatial stimuli instructed and triggered a limb movement toward their locations or (2) identical stimuli triggered a movement toward a predetermined target regardless of their location. Gaze and head fixation assured that each stimulus appeared at a constant location in both retinocentric and craniocentric coordinates, as well as in allocentric space. The task required that the spatial location cued by certain stimuli had to be either remembered or attended after stimulus presentation and before movement. Thus, the visuospatial information presented under one rule differed from that presented under the other only in its motor (instructional) significance and not in its attentional, spatial, mnemonic, or strictly sensory aspects. We could thereby test and confirm the hypothesis that the motor significance of visuospatial cues should commonly affect neuronal activity in the premotor cortex, but less commonly do so in the prefrontal cortex. C1 NIMH,NEUROPHYSIOL LAB,POB 289,POOLESVILLE,MD 20837. NR 89 TC 217 Z9 218 U1 0 U2 1 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD MAR PY 1993 VL 13 IS 3 BP 1227 EP 1243 PG 17 WC Neurosciences SC Neurosciences & Neurology GA KP711 UT WOS:A1993KP71100030 PM 8441009 ER PT J AU HAMEL, CP TSILOU, E HARRIS, E PFEFFER, BA HOOKS, JJ DETRICK, B REDMOND, TM AF HAMEL, CP TSILOU, E HARRIS, E PFEFFER, BA HOOKS, JJ DETRICK, B REDMOND, TM TI A DEVELOPMENTALLY REGULATED MICROSOMAL PROTEIN-SPECIFIC FOR THE PIGMENT-EPITHELIUM OF THE VERTEBRATE RETINA SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE RETINA; RETINAL PIGMENT EPITHELIUM; RETINAL DEVELOPMENT; MICROSOMAL PROTEIN; RETINAL PIGMENT EPITHELIUM CULTURE; PHOTORECEPTORS ID DIFFERENTIATION; INVITRO; CELLS; PHAGOCYTOSIS; MEMBRANE; ANTIBODY; REGENERATION AB In the vertebrate retina, the retinal pigment epithelium (RPE) performs specific functions critical to the normal process of vision. Although some of these functions are well documented, molecular data are still scarce. Using the RPE-specific monoclonal antibody RPE9, raised against human RPE cells, we have identified a novel 65 kD protein, conserved in mammals, birds, and frogs. This RPE-specific protein was found to be nonglycosylated. It was most effectively solubilized in the presence of detergent suggesting that it is associated with the RPE cell membranes. Its partitioning in the detergent phase of Triton X-114 and its solubilization in 0.75 M and 1.0 M KCl suggest that it interacts with the membrane either through a polypeptide anchor or charged amino acids. Cell fractionation by differential solubilization and differential centrifugation demonstrated that the protein was preferentially associated with the microsomal membrane fraction, where it is the major protein. Developmental expression of this 65 kD protein was examined in neonatal rats. Morphologically well-differentiated RPE cells did not express the 65 kD protein at birth. However, expression was detectable at postnatal day 4, that is, one to two days before the photoreceptors develop their outer segments, suggesting that the expression of the 65 kD protein may be coordinated with other developmental events in the intact retina. This is further supported by the fact that RPE cells in confluent culture lose the expression of this protein within two weeks, while they maintain their characteristic epithelial morphology. Because of its specificity, its evolutionary conservation, and its timing of expression, it is possible that this protein may be involved in one of the key roles of RPE and as such is an important molecular marker for RPE differentiation. C1 NEI,RETINAL CELL & MOLEC BIOL LAB,BLDG 6,RM 339,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. NEI,IMMUNOL & VIROL LAB,BETHESDA,MD 20892. GEORGE WASHINGTON UNIV,MED CTR,DEPT PATHOL,WASHINGTON,DC 20037. OI Redmond, T. Michael/0000-0002-1813-5291 NR 38 TC 99 Z9 99 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 1993 VL 34 IS 4 BP 414 EP 425 DI 10.1002/jnr.490340406 PG 12 WC Neurosciences SC Neurosciences & Neurology GA KR072 UT WOS:A1993KR07200005 PM 8474143 ER PT J AU LUCIGNANI, G SCHMIDT, KC MORESCO, RM STRIANO, G COLOMBO, F SOKOLOFF, L FAZIO, F AF LUCIGNANI, G SCHMIDT, KC MORESCO, RM STRIANO, G COLOMBO, F SOKOLOFF, L FAZIO, F TI MEASUREMENT OF REGIONAL CEREBRAL GLUCOSE-UTILIZATION WITH FLUORINE-18-FDG AND PET IN HETEROGENEOUS TISSUES - THEORETICAL CONSIDERATIONS AND PRACTICAL PROCEDURE SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article ID BRAIN TRANSFER CONSTANTS; TIME UPTAKE DATA; METABOLIC-RATE; GRAPHICAL EVALUATION; DEOXYGLUCOSE; HUMANS; MODEL AB Functional tissue heterogeneity, i.e., inclusion of tissues with different rates of blood flow and metabolism within a single region of interest, is an unavoidable problem with PET. Errors in determination of regional cerebral glucose utilization (rCMRglc) with [F-18]FDG have resulted from the currently used simplifying assumption that all regions examined are homogeneous. We have established an optimal, yet practical procedure to minimize errors due to tissue heterogeneity in determination of rCMRglc. Effects of applying the three-rate constant kinetic model designed for homogeneous tissues with both dynamic and single-scan procedures and the Pat-lak plot were evaluated in normal subjects in experimental periods up to 120 min following tracer injection. The procedure with a single scan carried out any time within the interval between 60 and 120 min following tracer injection, combined with population average rate constants determined over a 120-min period, was found to be optimal for quantitative rCMRglc studies. C1 NIMH,CEREBRAL METAB LAB,BETHESDA,MD 20892. RP LUCIGNANI, G (reprint author), UNIV MILAN,INST H SAN RAFFAELE,DEPT NUCL MED,CNR,INB,VIA OLGETTINGA 60,I-20132 MILAN,ITALY. RI Lucignani, Giovanni/C-6773-2008 NR 17 TC 60 Z9 62 U1 0 U2 2 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAR PY 1993 VL 34 IS 3 BP 360 EP 369 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA KQ347 UT WOS:A1993KQ34700008 PM 8441024 ER PT J AU WILSON, JM THOMPSON, JR SCHNITZER, JJ BOWER, LK LILLEHEI, CW PERLMAN, ND KOLOBOW, T AF WILSON, JM THOMPSON, JR SCHNITZER, JJ BOWER, LK LILLEHEI, CW PERLMAN, ND KOLOBOW, T TI INTRATRACHEAL PULMONARY VENTILATION AND CONGENITAL DIAPHRAGMATIC-HERNIA - A REPORT OF 2 CASES SO JOURNAL OF PEDIATRIC SURGERY LA English DT Article; Proceedings Paper CT 23RD ANNUAL MEETING OF THE AMERICAN PEDIATRIC SURGICAL ASSOC CY MAY 13-16, 1992 CL COLORADO SPRINGS, CO SP AMER PEDIAT SURG ASSOC DE CONGENITAL DIAPHRAGMATIC HERNIA; EXTRACORPOREAL MEMBRANE OXYGENATION (ECMO) ID EXTRACORPOREAL MEMBRANE-OXYGENATION; AIRWAY PRESSURE C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. NIH,BETHESDA,MD 20892. RP WILSON, JM (reprint author), CHILDRENS HOSP MED CTR,DEPT SURG,FEGAN 4,300 LONGWOOD AVE,BOSTON,MA 02115, USA. NR 12 TC 35 Z9 35 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0022-3468 J9 J PEDIATR SURG JI J. Pediatr. Surg. PD MAR PY 1993 VL 28 IS 3 BP 484 EP 487 DI 10.1016/0022-3468(93)90252-G PG 4 WC Pediatrics; Surgery SC Pediatrics; Surgery GA KR551 UT WOS:A1993KR55100034 PM 8468666 ER PT J AU MCCRAE, RR COSTA, PT PIEDMONT, RL AF MCCRAE, RR COSTA, PT PIEDMONT, RL TI FOLK CONCEPTS, NATURAL-LANGUAGE, AND PSYCHOLOGICAL CONSTRUCTS - THE CALIFORNIA PSYCHOLOGICAL INVENTORY AND THE 5-FACTOR MODEL SO JOURNAL OF PERSONALITY LA English DT Article; Proceedings Paper CT CONVENTION OF THE AMERICAN PSYCHOLOGICAL ASSOC CY AUG, 1990 CL BOSTON, MA SP AMER PSYCHOL ASSOC ID NEO PERSONALITY-INVENTORY; SCALES; TRAITS; CIRCUMPLEX; OPENNESS; WELL AB Both the California Psychological Inventory (CPI; Gough, 1987) and the five-factor model of personality have roots in folk concepts of personality. The present article offers a conceptual analysis of CPI scales in terms of the five-factor model. In the first study, judges rated the item content of CPI scales in terms of the five factors. In the second, CPI scales were correlated with the factors as measured by the NEO Personality Inventory (NEO-PI; Costa & McCrae, 1985b) in a sample of 348 men and women ages 19 to 92. Both studies showed meaningful links between CPI scales and four of the factors; Agreeableness appeared to be underrepresented in CPI scales. The utility of systematic rational item analysis in terms of the five factors and the evolving relation of folk concepts to psychological constructs are discussed. RP MCCRAE, RR (reprint author), NIA,GERONTOL RES CTR,PERSONAL STRESS & COPING SECT,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. NR 58 TC 97 Z9 97 U1 1 U2 4 PU DUKE UNIV PRESS PI DURHAM PA BOX 90660, DURHAM, NC 27708-0660 SN 0022-3506 J9 J PERS JI J. Pers. PD MAR PY 1993 VL 61 IS 1 BP 1 EP 26 DI 10.1111/j.1467-6494.1993.tb00276.x PG 26 WC Psychology, Social SC Psychology GA KR774 UT WOS:A1993KR77400001 ER PT J AU REGIER, DA AF REGIER, DA TI PAPERS FROM THE NIMH CONFERENCE ON PERSONALITY-DISORDERS, WILLIAMSBURG, VA, NOVEMBER 8-10, 1990 - INTRODUCTION SO JOURNAL OF PERSONALITY DISORDERS LA English DT Editorial Material RP REGIER, DA (reprint author), NIMH,DIV CLIN RES,BETHESDA,MD 20892, USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 SN 0885-579X J9 J PERS DISORD JI J. Pers. Disord. PD SPR PY 1993 VL 7 SU S BP 2 EP 3 PG 2 WC Psychiatry SC Psychiatry GA KZ183 UT WOS:A1993KZ18300002 ER PT J AU GRANT, KA COLOMBO, G AF GRANT, KA COLOMBO, G TI DISCRIMINATIVE STIMULUS EFFECTS OF ETHANOL - EFFECT OF TRAINING DOSE ON THE SUBSTITUTION OF N-METHYL-D-ASPARTATE ANTAGONISTS SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID ANTICONVULSANT ACTIVITY; RATS; PHENCYCLIDINE; ACID; RECEPTORS; PIGEONS; CHLORDIAZEPOXIDE; DRUG; 2-AMINO-5-PHOSPHONOVALERATE; AMPHETAMINE AB The ethanol-like discriminative stimulus effects of N-methyl-D-aspartate (NMDA) antagonists that act at the NMDA recognition site [(D)-4-(3-phosphonoprop-2-enyl)piperazine-2-carboxylic acid (CPPene) and cis-4-phosphonomethyl-2-piperidine carboxylic acid] or within the NMDA associated cation channel [phencyclidine (PCP) and dizocilpine] were evaluated in rats trained to discriminate ethanol or PCP from vehicle in a two-lever discrimination procedure. Three groups of rats were trained to discriminate 1.0, 1.5 or 2.0 g/kg of ethanol from water and one group was trained to discriminate 1.5 mg/kg of PCP from saline. In the ethanol-trained groups, both PCP (1.0-5.6 mg/kg; i.p.) and dizocilpine (0.03-0.3 mg/kg; i.p.) completely substituted for ethanol in every rat tested, although the dizocilpine resulted in only partial substitution in rats trained to discriminate 1.0 g/kg of ethanol. As the training dose of ethanol increased, the potency of PCP and dizocilpine to substitute for ethanol increased. In contrast, CPPene (1-17 mg/kg; i.p.) and cis-4-phosphonomethyl-2-piperidine carboxylic acid (5.6-17 mg/kg; i.p.) resulted in partial substitution for ethanol, with lower amounts of ethanol-appropriate responding as the training dose of ethanol increased. These data indicate that uncompetitive antagonism of NMDA neurotransmission at sites within the cation channel produce discriminative stimulus effects that are similar to those of ethanol, particularly to higher ethanol doses. Neither ethanol (0.5-1.5 g/kg; i.p.) nor CPPene (5.6 and 10 mg/kg) completely substituted for the discriminative effects of PCP. The asymmetrical generalizations between ethanol and PCP are discussed in terms of the mixed discriminative effects of ethanol. C1 NIAAA, DIV INTRAMURAL CLIN & BIOMED RES, BETHESDA, MD USA. RP GRANT, KA (reprint author), WAKE FOREST UNIV, BOWMAN GRAY SCH MED, DEPT PHYSIOL & PHARMACOL, MED CTR BLVD, WINSTON SALEM, NC 27157 USA. FU NIAAA NIH HHS [AA09346] NR 51 TC 93 Z9 96 U1 0 U2 1 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 1993 VL 264 IS 3 BP 1241 EP 1247 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA KT846 UT WOS:A1993KT84600030 PM 8450461 ER PT J AU SCANZELLO, CR HATZIDIMITRIOU, G MARTELLO, AL KATZ, JL RICAURTE, GA AF SCANZELLO, CR HATZIDIMITRIOU, G MARTELLO, AL KATZ, JL RICAURTE, GA TI SEROTONERGIC RECOVERY AFTER (+/-3,4-(METHYLENEDIOXY) METHAMPHETAMINE INJURY - OBSERVATIONS IN RATS SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID BRAIN-SEROTONIN; 3,4-METHYLENEDIOXYMETHAMPHETAMINE MDMA; METHYLENEDIOXYMETHAMPHETAMINE MDMA; NEURONS; ECSTASY; NEUROTOXICITY; TERMINALS; FIBERS; FENFLURAMINE; AMPHETAMINE AB (+/-)-3,4-Methylenedioxymethamphetamine (MDMA) is a recreational drug of abuse which damages serotonin (5-HT) neurons in animals. In monkeys, the damage appears to be permanent. By contrast, in rats there is indication that neuronal recovery takes place, although there is question as to whether the recovery is sustained. The purpose of the present study was to examine the fate of 5-HT neurons in MDMA-treated rats, and to compare findings in the rat with those in the monkey. Rats were treated with MDMA (1 0 mg/kg i.p.) every 2 hr for a total dose of 40 mg/kg. Two, 8, 1 6, 32 and 52 weeks later, groups (n = 8) of MDMA-treated rats, along with age-matched controls (n = 8), were analyzed for regional brain 5-HT, 5-hydroxyindoleacetic acid and [3]paroxetine-labeled 5-HT uptake sites. Two weeks after MDMA, 5-HT neuronal markers were reduced markedly. Reductions ranged from 42 to 82% depending on brain region. By 16 weeks, there was evidence of recovery in some brain regions (e.g., hypothalamus and striatum) and by 32 weeks, recovery was nearly complete in most brain regions examined. One year after MDMA, recovery was still evident in all brain regions evaluated, although closer inspection of the group data revealed that whereas most MDMA-treated rats recovered, some did not. These few animals had severe and enduring serotonergic deficits in multiple brain regions. Morphologic immunocytochemical studies yielded results which corroborated the neurochemical findings. Together, these observations suggest that 5-HT neurons in most (but not all) rats recover from MDMA injury, and that in those rats which recover, recovery is maintained for at least 1 year after MDMA treatment. Further studies are needed to determine if recovery is sustained for longer than 1 year, and to define the factors which govern 5-HT neuronal recovery after MDMA injury. C1 NIDA,ADDICT RES CTR,BALTIMORE,MD 21224. OI Katz, Jonathan/0000-0002-1068-1159 NR 43 TC 103 Z9 107 U1 0 U2 1 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 1993 VL 264 IS 3 BP 1484 EP 1491 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA KT846 UT WOS:A1993KT84600061 PM 7680719 ER PT J AU HILTON, ME AF HILTON, ME TI AN OVERVIEW OF RECENT FINDINGS ON ALCOHOLIC BEVERAGE WARNING LABELS SO JOURNAL OF PUBLIC POLICY & MARKETING LA English DT Article RP HILTON, ME (reprint author), NIAAA,DIV CLIN & PREVENT RES,ROCKVILLE,MD 20852, USA. NR 27 TC 37 Z9 37 U1 0 U2 0 PU AMER MARKETING ASSN PI CHICAGO PA 250 SOUTH WACKER DRIVE SUITE 200, CHICAGO, IL 60606-5819 SN 0743-9156 J9 J PUBLIC POLICY MARK JI J. Public Policy Mark. PD SPR PY 1993 VL 12 IS 1 BP 1 EP 9 PG 9 WC Business SC Business & Economics GA LD532 UT WOS:A1993LD53200001 ER PT J AU WASSER, SK THOMAS, R NAIR, PP GUIDRY, C SOUTHERS, J LUCAS, J WILDT, DE MONFORT, SL AF WASSER, SK THOMAS, R NAIR, PP GUIDRY, C SOUTHERS, J LUCAS, J WILDT, DE MONFORT, SL TI EFFECTS OF DIETARY FIBER ON FECAL STEROID MEASUREMENTS IN BABOONS (PAPIO-CYNOCEPHALUS-CYNOCEPHALUS) SO JOURNAL OF REPRODUCTION AND FERTILITY LA English DT Article ID PREGNANCY DIAGNOSIS; REPRODUCTIVE SUPPRESSION; RADIOLABELED ESTRADIOL; EXCRETED STEROIDS; FECAL STEROIDS; YELLOW BABOONS; FECES; METABOLITES; ESTROGENS; HEIFERS AB A study was conducted in captive baboons to determine (i) the impact of cereal dietary fibre on faecal progestogen excretion, and (ii) whether means of controlling dietary effects could be identified. Blood was collected on 3 days per week and faeces on 5 days per week from four unanaesthetized cyclic female baboons, consecutively fed three diets of 5, 10 and 20% fibre for 90 days per diet. A 2 day lag time was detected before progesterone in the blood appeared in the faeces, regardless of diet (mean correlation was 0.62, P = 0.002). Increased dietary fibre had a negative effect on progestogen excretion (P < 0.004). Correspondence between blood and faecal progestogens was consistently greatest and the effect of dietary fibre least when faecal progestogens were expressed g-1 dry faeces. Several means of indexing faecal steroid excretion rates were examined including dehydroepiandrosterone (DHEA) and a number of byproducts of cholesterol metabolism. The cholesterol metabolite, cholestanone, was positively correlated with dietary fibre (r = 0.27; P < 0.04). Multiplying faecal progestogen concentration by the cholestanone g-1 dry faeces concentration increased the correlation between serum and cholestanone-indexed faecal progestogens (r = 0.78, P = 0.0001) compared with nonindexed progestogens (r = 0.71, P = 0.0001). We conclude that expressing faecal progestogens g-1 dry faeces may be sufficient and the most cost-effective method for controlling for most dietary effects when the objective is monitoring longitudinal endocrine status in baboons. However, it may be appropriate to express faecal progestogens by cholestanone concentrations when increased precision is needed to overcome the effects of profound variations in dietary fibre. C1 USDA,LIPID NUTR LAB,BELTSVILLE,MD 20705. NIH,PRIMATE RES UNIT,BETHESDA,MD 20892. RP WASSER, SK (reprint author), SMITHSONIAN INST,CONSERVAT & RES CTR,NATL ZOOL PK,FRONT ROYAL,VA 22630, USA. NR 27 TC 121 Z9 126 U1 2 U2 15 PU J REPROD FERTIL INC PI CAMBRIDGE PA 22 NEWMARKET RD, CAMBRIDGE, ENGLAND CB5 8DT SN 0022-4251 J9 J REPROD FERTIL JI J. Reprod. Fertil. PD MAR PY 1993 VL 97 IS 2 BP 569 EP 574 PG 6 WC Reproductive Biology SC Reproductive Biology GA KX726 UT WOS:A1993KX72600036 PM 8388960 ER PT J AU DAVIS, RO CUTTER, GR GOLDENBERG, RL HOFFMAN, HJ CLIVER, SP BRUMFIELD, CG AF DAVIS, RO CUTTER, GR GOLDENBERG, RL HOFFMAN, HJ CLIVER, SP BRUMFIELD, CG TI FETAL BIPARIETAL DIAMETER, HEAD CIRCUMFERENCE, ABDOMINAL CIRCUMFERENCE AND FEMUR LENGTH - A COMPARISON BY RACE AND SEX SO JOURNAL OF REPRODUCTIVE MEDICINE LA English DT Article ID CROWN-RUMP LENGTH; GESTATIONAL-AGE; MENSTRUAL AGE; GROWTH; POPULATION; PARAMETERS; ULTRASOUND; PREGNANCY AB Biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC) and femur length (FL) were compared by race and sex in 5,405 ultrasound examinations done on 2,831 women. Black fetuses had significantly longer FL than white fetuses; male fetuses had larger BPD, HC and AC than females. The differences in BPD, HC and AC correlated with the different birth weights observed between male and female infants, 3,253 vs. 3,153 g. The difference in birth weight between black and white infants, 3,152 vs. 3,331 g, did not correlate with differences in their respective BPD, HC and AC. Earlier delivery accounted for some but not all of the birth weight difference between black and white infants. Our data suggest that there may be differences in body length proportions (longer legs and shorter trunks in black infants) that are important factors in understanding the birth weight difference between black and white infants. Furthermore, fetal race and sex differences could account for some degree of error in the ultrasound estimation of gestational age. C1 NICHHD,BETHESDA,MD 20892. RP DAVIS, RO (reprint author), UNIV ALABAMA,DEPT OBSTET & GYNECOL,BIRMINGHAM,AL 35294, USA. FU NICHD NIH HHS [N01-HD-4-2811] NR 21 TC 41 Z9 42 U1 0 U2 6 PU SCI PRINTERS & PUBL INC PI ST LOUIS PA P.O. DRAWER 12425 8342 OLIVE BLVD, ST LOUIS, MO 63132 SN 0024-7758 J9 J REPROD MED JI J. Reprod. Med. PD MAR PY 1993 VL 38 IS 3 BP 201 EP 206 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA KT812 UT WOS:A1993KT81200010 PM 8487238 ER PT J AU STERNBERG, EM AF STERNBERG, EM TI HYPOIMMUNE FATIGUE SYNDROMES - DISEASES OF THE STRESS RESPONSE SO JOURNAL OF RHEUMATOLOGY LA English DT Editorial Material ID CORTICOTROPIN-RELEASING HORMONE; RHEUMATOID-ARTHRITIS; LEWIS RATS; DEPRESSION; CORTISOL; SYSTEM RP STERNBERG, EM (reprint author), NIMH,CLIN NEUROENDOCRINOL BRANCH,NEUROENDOCRINE IMMUNOL & BEH,BLDG 10,BETHESDA,MD 20892, USA. NR 24 TC 50 Z9 50 U1 0 U2 2 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 1993 VL 20 IS 3 BP 418 EP 421 PG 4 WC Rheumatology SC Rheumatology GA KU058 UT WOS:A1993KU05800002 PM 8478845 ER PT J AU KORZEKWA, KR TRAGER, WF MANCEWICZ, J OSAWA, Y AF KORZEKWA, KR TRAGER, WF MANCEWICZ, J OSAWA, Y TI STUDIES ON THE MECHANISM OF AROMATASE AND OTHER CYTOCHROME-P450 MEDIATED DEFORMYLATION REACTIONS SO JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY LA English DT Article; Proceedings Paper CT 3RD INTERNATIONAL AROMATASE CONF ON BASIC AND CLINICAL ASPECTS OF AROMATASE CY JUN 14-17, 1992 CL BOLOGNA, ITALY SP PENN STATE UNIV, COLL MED, MILTON S HERSHEY MED CTR, UNIV MARYLAND BALTIMORE, UNIV BOLOGNA, AKZO ORGANON INT, CIBA GEIGY, FARMITALIA CARLO ERBA, ICI PHARM, IVAX, JANSSEN RES FDN, MERRELL DOW RES INST ID HUMAN PLACENTAL MICROSOMES; ESTROGEN BIOSYNTHESIS; OLEFIN FORMATION; MODEL; AROMATIZATION; OXYGEN; TESTOSTERONE; DERIVATIVES; METABOLISM; CONVERSION AB Aromatase is a microsomal cytochrome P450 that converts androgens to estrogens by three sequential oxidations. The isolation of the 19-hydroxy and 19-oxo androgens suggests that the first two oxidations occur at the C19 carbon. However, the mechanism of the third oxidation, which results in C-10-C19 bond cleavage, has not been determined. Two proposed mechanisms which remain viable involve either initial 1beta-hydrogen atom abstraction or addition of the ferric peroxy anion from aromatase to the C19 aldehyde. Semiempirical molecular orbital calculations (AM1) were used to study potential reaction mechanisms initiated by initial 1beta-hydrogen atom abstraction. Initially, the energetics of carbon-carbon bond cleavage of the keto and enol forms of C1-radicals were studied and were found to be energetically similar. A mechanism was proposed in which the 19-oxo intermediate is subject to initial nucleophilic attack by the protein. The geometry of the A-ring in the androgens is between that for the 1-radicals and estrogen, suggesting that some transition state stabilization for the homolytic cleavage reaction can occur. More recently, studies on liver microsomal cytochrome P450 mediated deformylation of xenobiotic aldehydes supports mechanisms involving an alkyl peroxy intermediate formed by addition of the ferric peroxy anion from aromatase to the C19 aldehyde. Although this intermediate could proceed through several different concerted or non-concerted pathways, one non-concerted pathway involves the heterolytic cleavage of the dioxygen bond resulting in an active oxygenating species (iron-oxene) and a diol. The diol could then undergo hydrogen atom abstraction followed by homolytic carbon-carbon bond cleavage as in the mechanisms modeled previously. When this cleavage was modeled for seven aldehydes, a good correlation with reported experimental aldehyde turnover numbers was obtained. However, when dialkoxy derivatives of the aldehydes are subject to microsomal metabolism, the rates of carbon-carbon cleavage products do not approach the rates of deformylation of the aldehyde analog. C1 UNIV WASHINGTON,DEPT MED CHEM,SEATTLE,WA 98195. NHLBI,CHEM PHARMACOL LAB,BETHESDA,MD 20892. RP KORZEKWA, KR (reprint author), NCI,MOLEC CARCINOGENESIS LAB,BETHESDA,MD 20892, USA. FU NIGMS NIH HHS [GM 36922] NR 23 TC 25 Z9 26 U1 0 U2 5 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 1993 VL 44 IS 4-6 BP 367 EP 373 DI 10.1016/0960-0760(93)90240-W PG 7 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA KZ357 UT WOS:A1993KZ35700007 PM 8476750 ER PT J AU KOZLOWSKI, LT HENNINGFIELD, JE KEENAN, RM LEI, H LEIGH, G JELINEK, LC POPE, MA HAERTZEN, CA AF KOZLOWSKI, LT HENNINGFIELD, JE KEENAN, RM LEI, H LEIGH, G JELINEK, LC POPE, MA HAERTZEN, CA TI PATTERNS OF ALCOHOL, CIGARETTE, AND CAFFEINE AND OTHER DRUG-USE IN 2 DRUG ABUSING POPULATIONS SO JOURNAL OF SUBSTANCE ABUSE TREATMENT LA English DT Article DE COFFEE; TEA; CAFFEINE; CIGARETTES; NICOTINE; TOBACCO; HEROIN; GLUE; AMPHETAMINE; BARBITURATES; DRUG DEPENDENCE; POLYADDICTION ID SUBJECTIVE RATINGS; TOBACCO SMOKING; COFFEE; INVOLVEMENT; DEPENDENCE; ETHANOL AB Relationships were explored among the frequencies of use of various drugs by a sample of drug-abusing clients of the Addiction Research Foundation (ARF) in Toronto and by drug abusers volunteering to participate in research at the Addiction Research Center (ARC) in Baltimore. The two groups of drug-abusing individuals differed in a number of characteristics. Those from ARF were admitted primarily for diagnosis and possible treatment for alcohol and non-opioid drug problems, whereas those from the ARC were admitted for participation in research on other drugs of abuse, primarily involving opioids. Patterns of use of certain drugs tended to covary in both groups. Of particular interest was the finding that severity of alcoholism was directly related to various measures of tobacco and caffeinated beverage use. In contrast, there was little correlation between the frequency of use among other drugs of abuse (e. g., heroin, cannabis, glue) and the use of tobacco and caffeine. These findings suggest that dependence on nicotine, caffeine, and alcohol may be governed by the same factors and possibly should be considered jointly in the treatment of alcoholic persons. Frequency of use of other drugs examined may be controlled by other factors than those which determine level of use of tobacco and caffeine. C1 NIA, ADDICT RES CTR, CLIN PHARMACOL BRANCH, POB 5180, BALTIMORE, MD 21224 USA. ADDICT RES FDN, TORONTO M5S 2S1, ONTARIO, CANADA. PENN STATE UNIV, UNIV PK, PA 16802 USA. JOHNS HOPKINS UNIV, SCH MED, BALTIMORE, MD 21205 USA. NR 59 TC 61 Z9 62 U1 0 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0740-5472 J9 J SUBST ABUSE TREAT JI J. Subst. Abus. Treat. PD MAR-APR PY 1993 VL 10 IS 2 BP 171 EP 179 DI 10.1016/0740-5472(93)90042-Z PG 9 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA LM554 UT WOS:A1993LM55400011 PM 8510191 ER PT J AU SHRAYER, D KONESS, J KOUTTAB, N BOGAARS, H HEARING, VJ GERSTEN, DM MAIZEL, A WANEBO, H AF SHRAYER, D KONESS, J KOUTTAB, N BOGAARS, H HEARING, VJ GERSTEN, DM MAIZEL, A WANEBO, H TI PREIMMUNIZATION OF MICE WITH FORMALINIZED EXTRACELLULAR ANTIGENS OF MELANOMA IN COMBINATION WITH IL-2 AND SURGICAL RESECTION INCREASED SURVIVAL AND TUMOR-CONTROL IN METASTATIC MELANOMA MODEL SO JOURNAL OF SURGICAL ONCOLOGY LA English DT Article DE MELANOMA; POLYVALENT ANTIGEN; POLYCLONAL ANTIBODY; INTERLEUKIN-2; IMMUNIZATION ID ACTIVATED KILLER-CELLS; NECROSIS-FACTOR-ALPHA; AUTOREACTIVE T-CELLS; INFILTRATING LYMPHOCYTES; ANTITUMOR EFFICACY; RECOMBINANT INTERLEUKIN-2; ADOPTIVE IMMUNOTHERAPY; PULMONARY METASTASIS; MURINE; INVIVO AB Recently we found that immunization with formalinized extracellular antigens (FECAs) could induce the production of specific antimelanoma antibodies and increase the defense mechanisms of antimelanoma cellular and humoral immunity. In experiments we used pathogen-free female mice C57BL/6 18-20 g. We injected FECA (0.02 mg of protein/per S.C.subcutaneous injection) for 1 month, once per week. Concurrently we injected S.C. human recombinant IL-2: 100 U/g of weight (2,000 U/per mouse). Interleukin-2 (IL-2) was injected for 1 month, 5 days/week. On days 7, 14, 21, and 28 we took retroorbital blood from mice for the study of anti-FECA and anti-IL-2 antibody production with ELISA. Control and experimental mice were then given a subcutaneous injection with 0.5 x 10(6) cells B16-F10 melanoma in 25 mul into the middle of the tail. By 18 days 100% developed local melanoma tumors. We resected tails of all control and experimental animals 5 mm distal the base of the tail under metaphan anesthesia. The production of antibodies to FECA and IL-2 started after the 21 st day and was higher in the group of mice immunized with FECA and with IL-2 than in control animals. Combining preimmunization with FECA and IL-2 and resection of local melanoma tumors decreased the mortality and the number of mice with local recurrence and metastatic melanoma tumors to the lungs. C1 GEORGETOWN MED CTR,WASHINGTON,DC. NCI,CELL BIOL LAB,BETHESDA,MD 20892. BROWN UNIV,ROGER WILLIAMS GEN HOSP,DEPT PATHOL,PROVIDENCE,RI 02908. RP SHRAYER, D (reprint author), BROWN UNIV,ROGER WILLIAMS GEN HOSP,DEPT SURG,825 CHALKSTONE AVE,PROVIDENCE,RI 02908, USA. FU NCI NIH HHS [CA-45148] NR 40 TC 9 Z9 9 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 1993 VL 52 IS 3 BP 142 EP 149 DI 10.1002/jso.2930520303 PG 8 WC Oncology; Surgery SC Oncology; Surgery GA KQ601 UT WOS:A1993KQ60100002 PM 8441268 ER PT J AU JENSEN, PS SALZBERG, AD RICHTERS, JE WATANABE, HK AF JENSEN, PS SALZBERG, AD RICHTERS, JE WATANABE, HK TI SCALES, DIAGNOSES, AND CHILD PSYCHOPATHOLOGY .1. CBCL AND DISK RELATIONSHIPS SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE DIAGNOSTIC INTERVIEW SCHEDULE FOR CHILDREN; CHILD BEHAVIOR CHECKLIST; VALIDITY; DIAGNOSTIC INTERVIEWS; SYMPTOM SCALES ID INTERVIEWS; DISORDERS; VALIDITY; ANXIETY AB Objective: To clarify the relationship between scales and structured diagnostic interview diagnoses, the authors used a two-stage screening method to study 201 military families with one or more children ages 5 to 17. Method: Parents and children were interviewed with the Diagnostic Interview Schedule for Children (DISC 2. 1); parents also completed the Child Behavior Checklist (CBCL) while the children completed other self-report symptom scales. Results: Results indicate only a modest ability of scales to discriminate among discrete DISC-derived DSM-III-diagnoses. Inclusion of diagnostic information from both parents and children resulted in more diagnoses than from either informant alone, and the additional diagnoses consisted mostly of internalizing disorders contributed by child-derived DISC information. In general, correlations were larger between scales and diagnoses within the same informant (regardless of diagnostic construct) than across informants (but within the same diagnostic construct). Child self-report measures tended to outperform the CBCL as screeners against the overall ''caseness'' criterion on the DISC. However, child self-report scales were relatively nonspecific and showed little ability to selectively identify internalizing disorders such as anxiety and/or depression. Compared with single informant diagnoses, combined-informant diagnoses were generally superior in demonstrating broader relationships to both parent and child symptom scales. Conclusions: Additional research is needed in order to build careful crosswalks between the various approaches to assessing childhood psychopathology, to decide on optimal rules for combining information to establish diagnoses, and to validate the currently available assessment alternatives. C1 WALTER REED ARMY INST RES,DIV NEUROPSYCHIAT,DEPT MIL PSYCHIAT,WASHINGTON,DC 20307. RP JENSEN, PS (reprint author), NIMH,DIV CLIN & TREATMENT RES,CHILD & ADOLESCENT DISORDERS,ROOM 10104,ROCKVILLE,MD 20857, USA. OI Jensen, Peter/0000-0003-2387-0650 NR 18 TC 100 Z9 100 U1 3 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 1993 VL 32 IS 2 BP 397 EP 406 DI 10.1097/00004583-199303000-00022 PG 10 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA KN981 UT WOS:A1993KN98100024 PM 8444770 ER PT J AU QUYYUMI, AA PANZA, JA DIODATI, JG CALLAHAN, TS BONOW, RO EPSTEIN, SE AF QUYYUMI, AA PANZA, JA DIODATI, JG CALLAHAN, TS BONOW, RO EPSTEIN, SE TI PROGNOSTIC IMPLICATIONS OF MYOCARDIAL-ISCHEMIA DURING DAILY LIFE IN LOW-RISK PATIENTS WITH CORONARY-ARTERY DISEASE SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID MILDLY SYMPTOMATIC PATIENTS; LONG-TERM PROGNOSIS; UNSTABLE ANGINA; SILENT ISCHEMIA; STABLE ANGINA; EXERCISE; INFARCTION; DEATH; IDENTIFICATION; MORTALITY AB Objectives. The purpose of this study was to determine the incidence and prognostic importance of myocardial ischemia detected by ambulatory monitoring in low risk, medically managed patients with coronary artery disease. Background. Previous studies have demonstrated that certain high risk subsets of patients with coronary artery disease have improved survival with revascularization. The remaining low risk medically managed patients may still have episodes of silent ischemia during daily living, but the frequency and prognostic implications of such episodes in this group are unknown. Methods. We prospectively studied the incidence and prognostic significance of ST segment changes recorded during daily activities in 116 asymptomatic or mildly symptomatic low risk patients with native coronary artery disease who were followed up for 29 +/- 13 months. Low risk patients were selected after excluding patients with 1) left main disease; 2) three-vessel coronary artery disease and left ventricular dysfunction at rest; 3) three-vessel disease and inducible ischemia during exercise; and 4) two-vessel disease, left ventricular dysfunction and inducible ischemia. Results. Forty-five patients (39%) had transient episodes of ST segment depression during 48-h electrocardiographic (ECG) monitoring (total 217 episodes, lasting 7,223 min, 82% of episodes silent). There were eight acute cardiac events (seven myocardial infarctions, one episode of unstable angina) and nine patients underwent elective revascularization. Seven of the eight acute events occurred in patients without silent ischemia during monitoring. Kaplan-Meier survival analysis revealed no significant differences in event-free survival from either acute or total events in subgroups with or without silent ischemia during ambulatory ECG monitoring. None of the clinical, treadmill exercise, radionuclide ventriculographic or cardiac catheterization variables were predictive of outcome by Cox multivariate proportional hazard function analysis. Analysis of coronary arteriograms before and after acute cardiac events revealed that in five of the six patients studied, acute occlusion occurred in a coronary artery different from the artery with the severest stenosis on initial angiography. Conclusions. In patients categorized as at low risk on the basis of the results of cardiac catheterization and stress testing, silent myocardial ischemia during daily life was not uncommon, and its presence failed to predict future coronary events. C1 NHLBI,CARDIOL BRANCH,BETHESDA,MD 20892. NR 38 TC 34 Z9 35 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 1 PY 1993 VL 21 IS 3 BP 700 EP 708 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA KP177 UT WOS:A1993KP17700020 PM 8436752 ER PT J AU KURIBAYASHI, T ROBERTS, WC AF KURIBAYASHI, T ROBERTS, WC TI TETRALOGY OF FALLOT, TRUNCUS ARTERIOSUS, ABNORMAL MYOCARDIAL ARCHITECTURE AND ANOMALIES OF THE AORTIC-ARCH SYSTEM INDUCED BY BIS-DIAMINE IN RAT FETUSES SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID OCCURRING HYPERTROPHIC CARDIOMYOPATHY; NEURAL CREST ABLATION; WKY NCRJ RATS; CHICK-EMBRYOS; CARDIAC-HYPERTROPHY; GREAT-VESSELS; HEART; PATHOGENESIS; ARTERY AB Objectives. The aim of this study was to analyze the relation between anomalies of the heart and aortic arch arteries in near-term rat fetuses exposed to the chemical bis-diamine. Background. Bis-diamine is known to induce cardiovascular anomalies. Methods. Bis-diamine was given orally to normal pregnant rats, and the 65 fetuses were examined under a dissecting microscope after formalin fixation. Results. There were 26 rat fetuses (40%) with a ventricular septal defect in the perimembranous portion, of which 14 (22%) had tetralogy of Fallot, 4 (6%) had truncus arteriosus and 8 (12%) had a relatively small defect with no other major anomalies. In 44 fetuses (68%) the middle latitudinal muscle bundle of the ventricular septum was continuous with the right ventricular free wall. There were, isolated or in association, a double- or right aortic arch in 6 fetuses (9%), aberrant subclavian arteries in 9 (14%), right ductus arteriosus in 12 (18%) and agenetic ductus in 4 (6%). The cross-sectional area of the ductus, as corrected by that of the aortic isthmus, was abnormally small in 47 rats (72%). The rat fetuses with a septal defect or abnormal myocardial architecture, or both, usually had a small ductus; it was very small or absent in those retuses with tetralogy of Fallot. Of the four fetuses with truncus arteriosus, two had a vestigial vasculature on the truncus root and three had a rudimentary infundibulum. Conclusions, The cardinal defect may be the anomalous and reduced development of the sixth arch arteries, which by imposing pressure overload on the fetal right ventricle, may have led to either or both the persistence of ventricular septal defect as a vent or the formation of myocardial architecture favorable for the generation of pressure in the right ventricle. C1 NHLBI,PATHOL BRANCH,BETHESDA,MD 20892. NR 38 TC 13 Z9 13 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 1 PY 1993 VL 21 IS 3 BP 768 EP 776 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA KP177 UT WOS:A1993KP17700028 PM 8436760 ER PT J AU ATKINSON, JC FOX, PC AF ATKINSON, JC FOX, PC TI SJOGRENS-SYNDROME - ORAL AND DENTAL CONSIDERATIONS SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article ID SALIVARY-GLAND BIOPSY; DIAGNOSIS AB Patients with Sjogren's syndrome have many oral health needs. Due to the extensive oral involvement, dentists may be the first to recognize this condition. Characteristics and treatment options for this disorder are discussed and three case histories are presented. C1 NIDR,CLIN INVEST & PATIENT CARE BRANCH,BLDG 10,ROOM IN-113,BETHESDA,MD 20892. NR 28 TC 45 Z9 47 U1 0 U2 0 PU AMER DENTAL ASSN PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 SN 0002-8177 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD MAR PY 1993 VL 124 IS 3 BP 74 EP & PG 0 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA KQ005 UT WOS:A1993KQ00500012 PM 8335784 ER PT J AU MANGELS, AR HOLDEN, JM BEECHER, GR FORMAN, MR LANZA, E AF MANGELS, AR HOLDEN, JM BEECHER, GR FORMAN, MR LANZA, E TI CAROTENOID CONTENT OF FRUITS AND VEGETABLES - AN EVALUATION OF ANALYTIC DATA SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Article ID PERFORMANCE LIQUID-CHROMATOGRAPHY; VITAMIN-A VALUE; LUNG-CANCER RISK; BETA-CAROTENE; PROVITAMIN-A; ALPHA-CAROTENE; FINNISH FOODS; INDIVIDUAL CAROTENOIDS; MAJOR CAROTENOIDS; GREEN VEGETABLES AB The test of the association between dietary intake of specific carotenoids and disease incidence requires the availability of accurate and current food composition data for individual carotenoids. To generate a carotenoid database, an artificial intelligence system was developed to evaluate data for carotenoid content of food in five general categories, namely, number of samples, analytic method, sample handling, sampling plan, and analytic quality control. Within these categories, criteria have been created to rate analytic data for beta-carotene, alpha-carotene, lutein, lycopene, and beta-cryptoxanthin in fruits and vegetables. These carotenoids are also found in human blood. Following the evaluation of data, acceptable values for each carotenoid in the foods were combined to generate a database of 120 foods. The database includes the food description; median, minimum and maximum values for the specific carotenoids in each food; the number of acceptable values and their references; and a confidence code, which is an indicator of the reliability of a specific carotenoid value for a food. The carotenoid database can be used to estimate the intake of specific carotenoids in order to examine the association between dietary carotenoids and disease incidence. C1 USDA,BELTSVILLE HUMAN NUTR RES CTR,BELTSVILLE,MD 20705. NCI,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20892. FU NCI NIH HHS [YO1-CN-30609] NR 74 TC 561 Z9 579 U1 6 U2 59 PU AMER DIETETIC ASSN PI CHICAGO PA 216 W JACKSON BLVD #800, CHICAGO, IL 60606-6995 SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD MAR PY 1993 VL 93 IS 3 BP 284 EP 296 DI 10.1016/0002-8223(93)91553-3 PG 13 WC Nutrition & Dietetics SC Nutrition & Dietetics GA KQ597 UT WOS:A1993KQ59700008 PM 8440826 ER PT J AU CHUGAHUJA, JK HOLDEN, JM FORMAN, MR MANGELS, AR BEECHER, GR LANZA, E AF CHUGAHUJA, JK HOLDEN, JM FORMAN, MR MANGELS, AR BEECHER, GR LANZA, E TI THE DEVELOPMENT AND APPLICATION OF A CAROTENOID DATABASE FOR FRUITS, VEGETABLES, AND SELECTED MULTICOMPONENT FOODS SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Article ID LUNG-CANCER RISK; DIETARY VITAMIN-A; CONSUMPTION; HAWAII AB A carotenoid database for individual and multicomponent foods has been compiled that contains values for the five most common carotenoids (alpha-carotene, beta-carotene, beta-cryptoxanthin, lycopene, lutein) in 2,458 fruits, vegetables, and multicomponent foods containing fruits and vegetables. The database was used to estimate intakes of specific carotenoids for 19- to 50-year-old women (n = 1,102), using food consumption data obtained from dietary recalls in the US Department of Agriculture Continuing Survey of Food Intake by Individuals, 1986. The major contributors of alpha-carotene were carrots consumed as a single food or as an ingredient in multicomponent foods. Carrots, cantaloupe, and broccoli were the main sources of beta-carotene. Orange juices and blends, oranges, and tangerines were important contributors of beta-cryptoxanthin. Tomatoes and tomato products consumed as single foods or as ingredients in multicomponent foods provided most of the dietary lycopene. Contributors of lutein + zeaxanthin included collard, mustard, or turnip greens; spinach; and broccoli. The per capita consumption of total carotenoids (the sum of the five specific carotenoids) among these women was approximately 6 mg/day. C1 USDA ARS,BELTSVILLE AGR RES CTR,BELTSVILLE HUMAN NUTR RES CTR,BELTSVILLE,MD 20705. NCI,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20892. NR 35 TC 195 Z9 197 U1 2 U2 12 PU AMER DIETETIC ASSN PI CHICAGO PA 216 W JACKSON BLVD #800, CHICAGO, IL 60606-6995 SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD MAR PY 1993 VL 93 IS 3 BP 318 EP 323 DI 10.1016/0002-8223(93)91559-9 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA KQ597 UT WOS:A1993KQ59700013 PM 8440830 ER PT J AU ORY, MG SCHECHTMAN, KB MILLER, JP HADLEY, EC FIATARONE, MA PROVINCE, MA ARFKEN, CL MORGAN, D WEISS, S KAPLAN, M AF ORY, MG SCHECHTMAN, KB MILLER, JP HADLEY, EC FIATARONE, MA PROVINCE, MA ARFKEN, CL MORGAN, D WEISS, S KAPLAN, M TI FRAILTY AND INJURIES IN LATER LIFE - THE FICSIT TRIALS SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article ID PUBLICATION BIAS; CLINICAL-TRIALS; META-ANALYSIS; FALLS AB Physical frailty and fall-related injuries present two of the biggest threats to older people's functioning and quality of life. The Frailty and Injuries: Cooperative Studies of Intervention Techniques (FICSIT) trials represent a set of eight different clinical trials concerning physical frailty and injuries in later life. This report documents the history and organization of the trials and provides an overview of the measures being collected at multiple sites and the analytic strategies to be used for multi-site investigations. C1 WASHINGTON UNIV,SCH MED,DIV BIOSTAT,ST LOUIS,MO 63110. TUFTS UNIV,HEBREW REHABIL CTR AGED,USDA,HUMAN NUTR RES CTR,BOSTON,MA 02111. NIH,NATL CTR NURSING RES,BETHESDA,MD 20892. NIA,GERIATR PROGRAM,BETHESDA,MD 20892. HARVARD UNIV,BETH ISRAEL HOSP,SCH MED,DEPT MED,DIV AGING,BOSTON,MA 02215. BRIGHAM & WOMENS HOSP,DIV GERONTOL,BOSTON,MA 02115. RP ORY, MG (reprint author), NIA,DIV BEHAV & SOCIAL RES,BETHESDA,MD 20892, USA. OI Miller, J Philip/0000-0003-4568-6846 FU NIA NIH HHS [U01-AG09087, U01-AG09089, U01-AG09117] NR 31 TC 126 Z9 128 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 1993 VL 41 IS 3 BP 283 EP 296 PG 14 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA KP998 UT WOS:A1993KP99800016 PM 8440853 ER PT J AU BUCHNER, DM HORNBROOK, MC KUTNER, NG TINETTI, ME ORY, MG MULROW, CD SCHECHTMAN, KB GERETY, MB FIATARONE, MA WOLF, SL ROSSITER, J ARFKEN, C KANTEN, K LIPSITZ, LA SATTIN, RW DENINO, LA AF BUCHNER, DM HORNBROOK, MC KUTNER, NG TINETTI, ME ORY, MG MULROW, CD SCHECHTMAN, KB GERETY, MB FIATARONE, MA WOLF, SL ROSSITER, J ARFKEN, C KANTEN, K LIPSITZ, LA SATTIN, RW DENINO, LA TI DEVELOPMENT OF THE COMMON DATA-BASE FOR THE FICSIT TRIALS SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article ID MINI-MENTAL STATE; SELF-EFFICACY; RISK-FACTORS; FALLS; COMMUNITY; BALANCE; SCALE; FEAR AB The eight FICSIT (Frailty and Injuries: Cooperative Studies of Intervention Techniques) sites test different intervention strategies in selected target groups of older adults. To compare the relative potential of these interventions to reduce frailty and fall-related injuries, all sites share certain descriptive (risk-adjustment) measures and outcome measures. This article describes the shared measures, which are referred to as the FICSIT Common Data Base (CDB). The description is divided into four sections according to the four FICSIT committees responsible for the CDB: (1) psychosocial health and demographic measures; (2) physical health measures; (3) fall-related measures; and (4) cost and cost-effectiveness measures. Because the structure of the FICSIT trial is unusual, the CDB should expedite secondary analyses of various research questions dealing with frailty and falls. C1 SEATTLE VA MED CTR,HLTH SERV RES & DEV FIELD PROGRAM,SEATTLE,WA. AUDIE L MURPHY VET AFFAIRS HOSP,CTR GERIATR RES EDUC & CLIN,SAN ANTONIO,TX. TUFTS UNIV,HEBREW REHABIL CTR AGED,USDA,HUMAN NUTR RES CTR AGING,BOSTON,MA 02111. EMORY UNIV,SCH MED,DEPT REHABIL MED,ATLANTA,GA 30322. UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX 78284. UNIV WASHINGTON,DEPT MED,SEATTLE,WA 98195. NIA,DIV BEHAV & SOCIAL RES,BETHESDA,MD 20892. KAISER PERMANENTE,CTR HLTH RES,NW REG,PORTLAND,OR. WASHINGTON UNIV,SCH MED,DIV BIOSTAT,ST LOUIS,MO 63110. HARVARD UNIV,BETH ISRAEL HOSP,SCH MED,DEPT MED,DIV AGING,BOSTON,MA 02215. BRIGHAM & WOMENS HOSP,DIV GERONTOL,BOSTON,MA 02115. CTR DIS CONTROL,DIV INJURY CONTROL,ATLANTA,GA 30333. OREGON HLTH SCI UNIV,DEPT COMMUNITY HLTH CARE SYST,PORTLAND,OR 97201. YALE UNIV,SCH MED,NEW HAVEN,CT 06510. RP BUCHNER, DM (reprint author), UNIV WASHINGTON,DEPT HLTH SERV SC37,SEATTLE,WA 98195, USA. RI Wolf, Steven/F-6588-2010; OI Wolf, Steven/0000-0002-9446-8995; Miller, J Philip/0000-0003-4568-6846 FU NIA NIH HHS [U01-AG09087, U01-AG09089, U01-AG09117] NR 35 TC 226 Z9 234 U1 12 U2 17 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 1993 VL 41 IS 3 BP 297 EP 308 PG 12 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA KP998 UT WOS:A1993KP99800017 PM 8440854 ER PT J AU HOOVER, DR MUNOZ, A CAREY, V TAYLOR, JMG VANRADEN, M CHMIEL, JS KINGSLEY, L BACELLAR, H JACOBSON, LP KUO, V PARK, L SAAH, A FARZADEGAN, H GRAHAM, N MARGOLICK, J MCARTHUR, J ODAKA, N PHAIR, JP COHEN, B RINALDO, CR ARMSTRONG, J GUPTA, P HO, M DETELS, R VISSCHER, BR DUDLEY, J FAHEY, JL GIORGI, JV IMAGAWA, D VERMUND, SH SCHRAGER, LK KASLOW, RA AF HOOVER, DR MUNOZ, A CAREY, V TAYLOR, JMG VANRADEN, M CHMIEL, JS KINGSLEY, L BACELLAR, H JACOBSON, LP KUO, V PARK, L SAAH, A FARZADEGAN, H GRAHAM, N MARGOLICK, J MCARTHUR, J ODAKA, N PHAIR, JP COHEN, B RINALDO, CR ARMSTRONG, J GUPTA, P HO, M DETELS, R VISSCHER, BR DUDLEY, J FAHEY, JL GIORGI, JV IMAGAWA, D VERMUND, SH SCHRAGER, LK KASLOW, RA TI USING EVENTS FROM DROPOUTS IN NONPARAMETRIC SURVIVAL FUNCTION ESTIMATION WITH APPLICATION TO INCUBATION OF AIDS SO JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION LA English DT Article DE CENSORING METHOD; DROPOUT; INTERVAL CENSORING; NONPARAMETRIC SURVIVAL ANALYSIS; POSTDROPOUT RESPONSE; TRUNCATION ID CONSISTENCY AB Often postdropout responses (PDR) in study dropouts are identified from death/disease registries or other medical records. If all dropout is random, then use of postdropout responses while censoring other subjects at date of dropout (CDO/PDR) will bias non-parametric survival probability estimates downward. Censoring all individuals at the last date of study contact, ignoring postdropout information (CDO) will produce unbiased nonparametric survival estimates. As onset of the response sometimes incapacitates the individual, preventing further study participation, dropout is often positively correlated with response. In this case CDO/PDR tends to prevent nonparametric survival overestimation but could lead to underestimation. When all of the responses in dropouts are identified, then regardless of dropout cause, use of all postdropout information, together with censoring all other subjects at time of analysis (CTA/PDR) will produce unbiased minimum variance estimates. We analyze the bias properties of nonparametric survival estimates produced using CDO/PDR, CDO, and CTA/PDR censoring mechanisms under various causes of study dropout and degrees of postdropout response recovery. The goal is to identify which of these censoring methods best incorporates postdropout information. Postdropout information may create interval-censored data. To facilitate statistical analysis of such data, the likelihood function is formulated in terms of the hazard. This results in computationally simple nonparametric estimates and covariances for interval-censored and left-truncated data. An application to estimation of acquired immune deficiency (AIDS)-free time after human immunodeficiency virus (HIV)-I seroconversion using data from a long-term cohort study with considerable dropout is presented. Upper and lower bound estimates for AIDS-free survival probabilities derived using CDO and CDO/PDR are shown to be quite close when compared to the underlying variance of these estimates. C1 JOHNS HOPKINS SCH PUBL HLTH, DEPT EPIDEMIOL, BALTIMORE, MD 21205 USA. JOHNS HOPKINS SCH PUBL HLTH, DEPT BIOSTAT, BALTIMORE, MD 21205 USA. NCI, BETHESDA, MD 20892 USA. UNIV CALIF LOS ANGELES, SCH PUBL HLTH, DEPT BIOSTAT, LOS ANGELES, CA 90024 USA. UNIV CALIF LOS ANGELES, JONSSON COMPREHENS CANC CTR, LOS ANGELES, CA 90024 USA. NIAID, EPIDEMIOL & BIOMETRY BRANCH, BETHESDA, MD 20892 USA. NORTHWESTERN UNIV, SCH MED, CTR CANC, KRISTALLOG SECT, CHICAGO, IL 60611 USA. NORTHWESTERN UNIV, SCH MED, HOWARD BROWN MEM CLIN, CHICAGO, IL 60611 USA. UNIV CALIF LOS ANGELES, SCH PUBL HLTH, LOS ANGELES, CA 90024 USA. UNIV CALIF LOS ANGELES, SCH MED, LOS ANGELES, CA 90024 USA. UNIV PITTSBURGH, GRAD SCH PUBL HLTH, DEPT INFECT DIS & IMMUNOL, PITTSBURGH, PA 15261 USA. NR 11 TC 9 Z9 9 U1 0 U2 0 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 732 N WASHINGTON ST, ALEXANDRIA, VA 22314-1943 USA SN 0162-1459 J9 J AM STAT ASSOC JI J. Am. Stat. Assoc. PD MAR PY 1993 VL 88 IS 421 BP 37 EP 43 DI 10.2307/2290689 PG 7 WC Statistics & Probability SC Mathematics GA KP993 UT WOS:A1993KP99300004 ER PT J AU WACLAWIW, MA LIANG, KY AF WACLAWIW, MA LIANG, KY TI PREDICTION OF RANDOM EFFECTS IN THE GENERALIZED LINEAR-MODEL SO JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION LA English DT Article DE EMPIRICAL BAYES ESTIMATION; ESTIMATING FUNCTION; GENERALIZED LINEAR MODEL; LONGITUDINAL STUDIES; 2-STAGE RANDOM EFFECTS MODEL ID LONGITUDINAL DATA AB This article develops an estimating function-based approach to component estimation in the two-stage generalized linear model with univariate random effects and a vector of fixed effects. The novelty and unifying feature of the method is the use of estimating functions in the estimation of both the random effects and their variance. Two separate estimating procedures based on the method are proposed that differ in the intensity of numerical computation required. The estimating function approach is especially valuable in the longitudinal setting where the response variable is discrete and the number of repeated observations on each unit is small. Other key features of this empirical Bayes technique are that it uses all available data, it yields familiar forms for the estimators as special cases, and it is less computationally intensive than other methods designed to address the same problem. An application to the estimation of trends in acquired immune deficiency syndrome (AIDS) incidence across risk groups and geographical regions is presented. C1 JOHNS HOPKINS UNIV,DEPT KINDERSPITAL,BALTIMORE,MD 21205. RP WACLAWIW, MA (reprint author), NHLBI,BIOSTAT RES BRANCH,BETHESDA,MD 20892, USA. RI Liang, Kung-Yee/F-8299-2011 NR 16 TC 36 Z9 36 U1 0 U2 1 PU AMER STATISTICAL ASSOC 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 1993 VL 88 IS 421 BP 171 EP 178 DI 10.2307/2290711 PG 8 WC Statistics & Probability SC Mathematics GA KP993 UT WOS:A1993KP99300026 ER PT J AU CARROLL, RJ GAIL, MH LUBIN, JH AF CARROLL, RJ GAIL, MH LUBIN, JH TI CASE-CONTROL STUDIES WITH ERRORS IN COVARIATES SO JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION LA English DT Article DE ASYMPTOTICS; CASE-CONTROL STUDY; DIFFERENTIAL MISCLASSIFICATION; ERRORS IN VARIABLES; LOGISTIC REGRESSION; PSEUDOLIKELIHOOD ID LIKELIHOOD ESTIMATION; CONFIDENCE-INTERVALS; BINARY REGRESSION; LINEAR-MODELS; IN-VARIABLES; PARAMETERS; STATISTICS; CANCER AB We devise methods for estimating the parameters of a prospective logistic model with dichotomous response D and arbitrary covariates X from case-control data when these covariates are measured with error. We suppose that some fraction of the cases and controls provide only the error-prone covariate measurements, W (the ''incomplete'' or ''reduced'' data), whereas some of the cases and controls provide measurements on X and W (the ''complete'' data). We assume a measurement error density with a finite set of parameters alpha, namely f(W\XD)(w\x, d, alpha), and nondifferential error is treated as a special case of this model, f(W\X)(w\x, alpha). Our algorithm estimates both the logistic parameters and alpha from a pseudolikelihood. Because empirical distribution functions are used in place of needed distributions in the pseudolikelihoods, the required asymptotic theory is more elaborate than for pseudolikelihoods based on substitution for a finite number of nuisance parameters. We also examine computationally simpler methods under the assumptions that the disease is rare and that errors are nondifferential. Estimates of m(W) = E(X\W) are substituted for X in the logistic model when X is not available. Such estimates of m(W) can be obtained from the complete data described above or from an independent validation study. If measurements on X are not available, m(W) can still be estimated from replicated W measurements in some circumstances. A final approach uses approximate logistic regression techniques and is appropriate when a more accurate approximation is required than obtained by simply substituting m(W) for X. Asymptotic theory is presented for each of these procedures, and examples are used to illustrate the calculations. C1 NCI, EPIDEMIOL METHODS SECT, BETHESDA, MD 20892 USA. RP CARROLL, RJ (reprint author), TEXAS A&M UNIV SYST, DEPT STAT, COLL STN, TX 77843 USA. NR 39 TC 55 Z9 55 U1 1 U2 5 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 732 N WASHINGTON ST, ALEXANDRIA, VA 22314-1943 USA SN 0162-1459 EI 1537-274X J9 J AM STAT ASSOC JI J. Am. Stat. Assoc. PD MAR PY 1993 VL 88 IS 421 BP 185 EP 199 DI 10.2307/2290713 PG 15 WC Statistics & Probability SC Mathematics GA KP993 UT WOS:A1993KP99300028 ER PT J AU WEISS, SJ PANLILIO, LV SCHINDLER, CW AF WEISS, SJ PANLILIO, LV SCHINDLER, CW TI SELECTIVE ASSOCIATIONS PRODUCED SOLELY WITH APPETITIVE CONTINGENCIES - THE STIMULUS REINFORCER INTERACTION REVISITED SO JOURNAL OF THE EXPERIMENTAL ANALYSIS OF BEHAVIOR LA English DT Article DE SELECTIVE ASSOCIATIONS; BIOLOGICAL CONSTRAINTS ON LEARNING; STIMULUS REINFORCER INTERACTION; APPETITIVE AVERSIVE INTERACTIONS; HEDONICS; COMPOUND STIMULUS CONDITIONING; LEVER PRESS; RATS ID BIOLOGICAL CONSTRAINTS; NEGATIVE REINFORCEMENT; ATTENTION; RAT AB In studies reporting stimulus-reinforcer interactions in traditional conditioning paradigms, when a tone-light compound was associated with food the light gained stimulus control, but when the compound was paired with shock avoidance the tone gained control. However, the physical nature of the reinforcer-related events (food vs. shock) presented in the presence of the tone-light compound was always confounded with the conditioned hedonic value of the compound's presence relative to its absence. When the compound was paired with shock, its presence was negative relative to its absence (which was shock-free). In contrast, when the compound was paired with food, its presence was positive relative to its absence (which was food-free). The present experiment dealt with this confounding effect by conditioning a tone-light compound to be positive or negative, relative to its absence, solely with food reinforcement. One group of rats received food for responding in the presence of the tone-light compound and no food in its absence. The other group also responded in the presence of the compound, but received food only in its absence. These rats were trained on a chained schedule in which responding in the presence of the tone-light compound produced a terminal link signaled by the absence of the compound; responding ceased in the terminal link because it delayed food delivery. In a test session to assess stimulus control by the elements of the compound, tone and light were presented separately under extinction conditions. Rats that had been exposed to a positive correlation between food and the compound emitted almost double the responses in the presence of the light as in the presence of the tone. In comparison, rats that had been exposed to a negative correlation emitted only two thirds as many responses in the presence of the light as in the presence of the tone. Because this selective association was produced using only food, it appears that the contingencies under which a reinforcer is presented, rather than (or as well as) its physical properties, can generate the selective associations previously attributed to ''stimulus-reinforcer interactions.'' This could mean that regardless of the class of reinforcer that ultimately maintains responding (appetitive or aversive), the contingency-generated hedonic value of the compound stimulus may influence the dominant modality of stimulus control. C1 NIDA,ADDICT RES CTR,LEXINGTON,KY 40583. RP WEISS, SJ (reprint author), AMERICAN UNIV,DEPT PSYCHOL,WASHINGTON,DC 20016, USA. FU NIMH NIH HHS [MH-45545] NR 41 TC 12 Z9 12 U1 1 U2 1 PU SOC EXP ANALYSIS BEHAVIOR INC PI BLOOMINGTON PA INDIANA UNIV DEPT PSYCHOLOGY, BLOOMINGTON, IN 47405 SN 0022-5002 J9 J EXP ANAL BEHAV JI J. Exp. Anal. Behav. PD MAR PY 1993 VL 59 IS 2 BP 309 EP 322 DI 10.1901/jeab.1993.59-309 PG 14 WC Psychology, Biological; Behavioral Sciences; Psychology, Experimental SC Psychology; Behavioral Sciences GA KQ288 UT WOS:A1993KQ28800004 PM 8454957 ER PT J AU CHEN, HS KANEKO, S GIRONES, R ANDERSON, RW HORNBUCKLE, WE TENNANT, BC COTE, PJ GERIN, JL PURCELL, RH MILLER, RH AF CHEN, HS KANEKO, S GIRONES, R ANDERSON, RW HORNBUCKLE, WE TENNANT, BC COTE, PJ GERIN, JL PURCELL, RH MILLER, RH TI THE WOODCHUCK HEPATITIS VIRUS-X GENE IS IMPORTANT FOR ESTABLISHMENT OF VIRUS-INFECTION IN WOODCHUCKS SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; LONG TERMINAL REPEAT; B VIRAL-DNA; TRANS-ACTIVATION; TRANSCRIPTIONAL ACTIVATION; SURFACE-ANTIGEN; LIVER-CANCER; PROTEIN; PRODUCT; REPLICATION AB All mammalian hepadnaviruses possess a gene, termed X, that encodes a protein capable of transactivating virus gene expression. The X gene overlaps the polymerase and precore genes as well as two newly identified open reading frames (ORFs) termed ORF5 and ORF6. In this investigation, we examined whether ORF5, ORF6, and the X gene were important for the replication of woodchuck hepatitis virus (WHV) in susceptible woodchucks. First, we investigated whether proteins were produced from ORF5 and ORF6 by in vitro translation of appropriate viral transcripts, searched for antibodies against the putative proteins in the sera of animals infected with wild-type virus, and looked for an antisense WHV transcript, necessary for expression of a protein from ORF6, in the livers of acutely or chronically infected woodchucks. All such experiments yielded negative results. Next, we used oligonucleotide-directed mutagenesis to introduce termination codons into ORF5 and ORF6 at two locations within each ORF. Adult woodchucks in groups of three were transfected with one of the four mutant genomes. All of these woodchucks developed WHV infections that were indistinguishable from those of animals transfected with the wild-type WHV recombinant. Polymerase chain reaction amplification and direct DNA sequencing confirmed that reversion of the mutants to a wild-type genotype did not occur. Taken together, these data indicate that ORF5 and ORF6 are not essential for virus replication and are unlikely to represent authentic genes. Finally, we generated five WHV X-gene mutants that either removed the initiation codon for protein synthesis or truncated the carboxyl terminus of the protein by 3, 16, 31, or 52 amino acids. Groups of three adult woodchucks were transfected with one of the five X-gene mutants. Only the mutant that possessed an X gene lacking 3 amino acids from the carboxyl terminus was capable of replication within the 6-month time frame of the experiment. In contrast, all seven woodchucks transfected with wild-type WHV DNA developed markers consistent with viral infection. Thus, it is likely (P < 0.01) that the WHV X gene is important for virus replication in the natural host. C1 NIAID,INFECT DIS LAB,HEPATITIS VIRUSES SECT,BETHESDA,MD 20892. NIAID,VIRAL DIS LAB,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT IMMUNOL & INFECT DIS,BALTIMORE,MD 21205. CORNELL UNIV,COLL VET MED,ITHACA,NY 14853. GEORGETOWN UNIV,DIV MOLEC VIROL & IMMUNOL,ROCKVILLE,MD 20852. RI Girones, Rosina/B-2975-2009 OI Girones, Rosina/0000-0002-1097-6395 FU NIAID NIH HHS [N01-AI-82698, N01-AI-72623] NR 61 TC 303 Z9 314 U1 1 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 1993 VL 67 IS 3 BP 1218 EP 1226 PG 9 WC Virology SC Virology GA KM613 UT WOS:A1993KM61300010 PM 8437213 ER PT J AU CARROLL, R DERSE, D AF CARROLL, R DERSE, D TI TRANSLATION OF EQUINE INFECTIOUS-ANEMIA VIRUS BICISTRONIC TAT-REV MESSENGER-RNA REQUIRES LEAKY RIBOSOME SCANNING OF THE TAT CTG INITIATION CODON SO JOURNAL OF VIROLOGY LA English DT Article ID FIBROBLAST GROWTH-FACTOR; NON-AUG CODONS; EUKARYOTIC RIBOSOMES; MUTATIONAL ANALYSIS; ALTERNATIVE INITIATION; NUCLEOTIDE-SEQUENCE; FUNCTIONAL-ANALYSIS; POLIOVIRUS TYPE-2; GENE-EXPRESSION; LENTIVIRUS TAT AB We have examined the translational regulation of the equine infectious anemia virus (EIAV) bicistronic tat-rev mRNA. Site-directed mutagenesis of the tat leader region followed by expression of the tat-rev cDNA both in vitro and in transiently transfected cells established that tat translation is initiated exclusively at a CTG codon. Increasing the efficiency of tat translation by altering the CTG initiator to ATG resulted in a dramatic decrease in translation of the downstream (rev) cistron, indicating that leaky scanning of the tat CTG initiation codon permitted translation of the downstream rev cistron. Since the tat leader sequences precede the major EIAV splice donor and are therefore present at the 5' termini of both spliced and unspliced viral mRNAs, the expression of all EIAV structural and regulatory proteins is dependent on leaky scanning of the tat initiator. C1 NCI,FREDERICK CANC RES CTR,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21702. NR 56 TC 46 Z9 47 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD MAR PY 1993 VL 67 IS 3 BP 1433 EP 1440 PG 8 WC Virology SC Virology GA KM613 UT WOS:A1993KM61300036 PM 8382305 ER PT J AU HIRSCH, VM DAPOLITO, GA GOLDSTEIN, S MCCLURE, H EMAU, P FULTZ, PN ISAHAKIA, M LENROOT, R MYERS, G JOHNSON, PR AF HIRSCH, VM DAPOLITO, GA GOLDSTEIN, S MCCLURE, H EMAU, P FULTZ, PN ISAHAKIA, M LENROOT, R MYERS, G JOHNSON, PR TI A DISTINCT AFRICAN LENTIVIRUS FROM SYKES MONKEYS SO JOURNAL OF VIROLOGY LA English DT Article ID SIMIAN IMMUNODEFICIENCY VIRUS; NF-KAPPA-B; GREEN MONKEYS; EXPERIMENTAL-INFECTION; HIGHLY DIVERGENT; CERCOCEBUS-ATYS; MACAQUE MONKEYS; SOOTY MANGABEY; TYPE-1; DIVERSITY AB Asymptomatic infection with simian immunodeficiency virus (SIV) has been demonstrated in African Sykes' monkeys (Cercopithecus mitis albogularis), and virus isolation confirmed infection with a novel SIV from Sykes' monkeys (SIVsyk). Macaques inoculated with SIVsyk became persistently infected but remained clinically healthy. We utilized polymerase chain reaction amplification to generate a full-length, infectious molecular clone of SIVsyk. The genome organization of SIVsyk is similar to that of the other primate lentiviruses, consisting of gag, pol, vif, vpr, tat, rev, env, and nef. A unique feature is the absence of the highly conserved NF-KB binding site in the long terminal repeat. SIVsyk is genetically equidistant from other primate lentiviruses. Thus, SIVsyk represents a new group that is distinct from the four previously recognized primate lentivirus groups: human immunodeficiency virus type 1 (HIV-1), SIV from sooty mangabeys (SIVsmm) and HIV-2, SIV from African green monkeys (SIVagm), and SIV from mandrills (SIVmnd). The genetic differences between SIVsyk and SIVagm, isolates derived from monkeys of the same genus, underscore the potential for other distinct SIVs which have yet to be isolated and characterized. C1 EMORY UNIV,YERKES REG PRIMATE RES CTR,ATLANTA,GA 30322. EMORY UNIV,DEPT PATHOBIOL,ATLANTA,GA 30322. UNIV ALABAMA,MED CTR,DEPT MICROBIOL,BIRMINGHAM,AL 35294. NATL MUSEUM KENYA,INST PRIMATE RES,NAIROBI,KENYA. LOS ALAMOS NATL LAB,DIV THEORET,LOS ALAMOS,NM 87544. OHIO STATE UNIV,DEPT PEDIAT,COLUMBUS,OH 43210. RP HIRSCH, VM (reprint author), NIAID,INFECT DIS LAB,ROCKVILLE,MD 20852, USA. RI Johnson, Philip/A-6892-2009 FU NCRR NIH HHS [RR00165]; NIAID NIH HHS [N01-AI-772623] NR 47 TC 87 Z9 87 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD MAR PY 1993 VL 67 IS 3 BP 1517 EP 1528 PG 12 WC Virology SC Virology GA KM613 UT WOS:A1993KM61300045 PM 8382307 ER PT J AU DIMITROV, DS BRODER, CC BERGER, EA BLUMENTHAL, R AF DIMITROV, DS BRODER, CC BERGER, EA BLUMENTHAL, R TI CALCIUM-IONS ARE REQUIRED FOR CELL-FUSION MEDIATED BY THE CD4-HUMAN IMMUNODEFICIENCY VIRUS TYPE-1 ENVELOPE GLYCOPROTEIN INTERACTION SO JOURNAL OF VIROLOGY LA English DT Note ID INDUCED MEMBRANE-FUSION; HTLV-III/LAV ENVELOPE; SOLUBLE CD4; SENDAI VIRUS; RECEPTOR; HIV-1; DISSOCIATION; BINDING; AIDS; INFECTION AB Calcium ions are required for fusion of a wide variety of artificial and biological membranes. To examine the role of calcium ions for cell fusion mediated by interactions between CD4 and the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (gp120-gp41), we used two experimental systems: (i) cells expressing gp120-gp41 and its receptor CD4, both encoded by recombinant vaccinia viruses, and (ii) chronically infected cells producing low levels of HIV-1. Fusion was measured by counting the number of syncytia and by monitoring the redistribution of fluorescence dyes by video microscopy. Syncytia did not form in solutions without calcium ions. Addition of calcium ions partially restored the formation of syncytia. EDTA and EGTA [ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid] blocked syncytium formation in culture media containing calcium ions. Membrane fusion as monitored by fluorescence dye redistribution also required calcium ions. Cell fusion increased with an increase in calcium ion concentration from 100 muM to 10 mM but was not affected by magnesium ions in the concentration range from 0 to 30 mM. Fibrinogen and fibronectin did not promote fusion in the absence or presence of Ca2+. Binding of soluble CD4 to gp120-gp41-expressing cells was not affected by Ca2+ and Mg2+. We conclude that Ca2+ is involved in postbinding steps in cell fusion mediated by the CD4-HIV-1 envelope glycoprotein interaction. C1 NIAID, VIRAL DIS LAB, BETHESDA, MD 20892 USA. RP DIMITROV, DS (reprint author), NCI, MEMBRANE STRUCT & FUNCT SECT, BETHESDA, MD 20892 USA. NR 41 TC 41 Z9 42 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAR PY 1993 VL 67 IS 3 BP 1647 EP 1652 PG 6 WC Virology SC Virology GA KM613 UT WOS:A1993KM61300059 PM 8437234 ER PT J AU DEGUCHI, Y YAMANAKA, Y THEODOSSIOU, C NAJFELD, V KEHRL, JH AF DEGUCHI, Y YAMANAKA, Y THEODOSSIOU, C NAJFELD, V KEHRL, JH TI HIGH EXPRESSION OF 2 DIVERGED HOMEOBOX GENES, HB24 AND HB9, IN ACUTE LEUKEMIAS - MOLECULAR MARKERS OF HEMATOPOIETIC-CELL IMMATURITY SO LEUKEMIA LA English DT Article ID TRANSCRIPTION FACTOR; MYELOID-LEUKEMIA; PROTEIN; GROWTH; DOMAIN; RNA AB Homeobox genes encode for sequence-specific DNA-binding proteins which have been implicated in the control of gene expression during development and in certain adult tissues. Two recently characterized human homeobox-containing genes, HB9 and HB24, are known to be expressed in hematopoietic progenitors and to be involved in the regulation of growth and differentiation of progenitor cells to mature hematopoietic cell types. In this study, elevated levels of HB24 and HB9 mRNA expression were detected in bone marrow and peripheral blood mononuclear cells (PBMC) isolated from patients with acute myelogenous or acute lymphocytic leukemia. While the levels of both mRNAs were elevated in all the patients with acute leukemias, the levels of HB9 mRNA were more variable than those of HB24. Immunohistochemical analysis utilizing an HB24 polyclonal antiserum demonstrated elevated levels of HB24 protein in cytopreparations of acute leukemic cells. Nuclear run-on experiments showed that the increases of HB9 and HB24 mRNA transcripts in patients' cells were, at least in part, secondary to increased transcription. The expression of HB9 and HB24 correlated with the clinical status of the patient. No significant level of expression of either HB9 or HB24 was detected in PBMC isolated from patients in remission. In contrast to the findings with cells isolated from patients with acute leukemias, no significant increase in either HB9 or HB24 transcript levels were found in cells from patients with chronic lymphocytic or chronic myelogenous leukemia when compared to normal controls. These findings demonstrate that high levels of H89 and HB24 expression are common features of acute leukemia and suggest the possibility that the dysregulated expression of these two genes may contribute to leukemogenesis. However, since these two genes are markers of immature hematopoietic cells they may not have an etiologic role in leukemogenesis. C1 NIAID,IMMUNOREGULAT LAB,BLDG 10,ROOM 11B-13,BETHESDA,MD 20892. JOHNS HOPKINS UNIV HOSP,BALTIMORE,MD 20915. CUNY MT SINAI SCH MED,DIV HEMATOL,NEW YORK,NY 10029. NR 29 TC 23 Z9 24 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0887-6924 J9 LEUKEMIA JI Leukemia PD MAR PY 1993 VL 7 IS 3 BP 446 EP 451 PG 6 WC Oncology; Hematology SC Oncology; Hematology GA KT680 UT WOS:A1993KT68000015 PM 7680402 ER PT J AU GUTIERREZ, MI BHATIA, K MAGRATH, I AF GUTIERREZ, MI BHATIA, K MAGRATH, I TI REPLICATIVE VIRAL-DNA IN EPSTEIN-BARR-VIRUS ASSOCIATED BURKITTS-LYMPHOMA BIOPSIES SO LEUKEMIA RESEARCH LA English DT Article DE EBV; BURKITTS LYMPHOMA; B-CELLS; VIRAL REPLICATION; MONOCLONALITY ID HODGKINS-DISEASE; CELLS; IMMUNODEFICIENCY; ACTIVATION; TERMINI AB Epstein-Barr virus (EBV) is linked to a spectrum of human diseases including epithelial and lymphoid malignancies in which it exists predominantly in a latent state. EBV is capable of establishing replicative infection at oropharyngeal and genital sites. Replicative EBV infection also occurs in oral hairy leukoplakia, in EBV associated lymphoproliferative disorders, and to a minor degree in nasopharyngeal carcinomas. Recent evidence also suggests that EBV replication, also, may be associated with AIDS related lymphomas and Hodgkin's disease. However it is widely believed that virus in circulating B-lymphocytes and in B-cell malignancies is stringently latent. We now show that by Southern blot analysis we can detect replicative forms of virion DNA in 14.5% (8 of 55) of EBV-positive Burkitt's lymphoma biopsies. This may be the explanation for the elevation of the titres of lytic cycle EBV antigens that is associated with presentation and relapse of EBV associated Burkitt's lymphoma. C1 NCI,PEDIAT BRANCH,LYMPHOMA BIOL SECT,BLDG 10,ROOM 13N240,BETHESDA,MD 20892. NR 25 TC 16 Z9 16 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0145-2126 J9 LEUKEMIA RES JI Leuk. Res. PD MAR PY 1993 VL 17 IS 3 BP 285 EP 289 DI 10.1016/0145-2126(93)90013-B PG 5 WC Oncology; Hematology SC Oncology; Hematology GA KQ976 UT WOS:A1993KQ97600013 PM 8383779 ER PT J AU ESTERHAY, RJ AF ESTERHAY, RJ TI THE MEDICAL RECORD - PROBLEM OR SOLUTION SO M D COMPUTING LA English DT Editorial Material RP ESTERHAY, RJ (reprint author), NCI,BETHESDA,MD 20892, USA. NR 8 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0724-6811 J9 M D COMPUT JI M D Comput. PD MAR-APR PY 1993 VL 10 IS 2 BP 78 EP & PG 0 WC Computer Science, Interdisciplinary Applications; Medical Informatics SC Computer Science; Medical Informatics GA KU556 UT WOS:A1993KU55600007 PM 8469099 ER PT J AU SCHOLZ, TD CECKLER, TL BALABAN, RS AF SCHOLZ, TD CECKLER, TL BALABAN, RS TI MAGNETIZATION TRANSFER CHARACTERIZATION OF HYPERTENSIVE CARDIOMYOPATHY - SIGNIFICANCE OF TISSUE WATER-CONTENT SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE TISSUE CHARACTERIZATION; MYOCARDIUM; NUCLEAR MAGNETIC RESONANCE; HYPERTENSION ID TRANSFER CONTRAST; RESONANCE RELAXATION; MYOCARDIAL COLLAGEN; LIPID BILAYER; HEART; HYPERTROPHY; INVIVO; RATS RP SCHOLZ, TD (reprint author), NHLBI,CARDIAC ENERGET LAB,BLDG 1,ROOM B3-07,BETHESDA,MD 20892, USA. RI Balaban, Robert/A-7459-2009 OI Balaban, Robert/0000-0003-4086-0948 NR 24 TC 34 Z9 34 U1 0 U2 0 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 1993 VL 29 IS 3 BP 352 EP 357 DI 10.1002/mrm.1910290311 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA KQ358 UT WOS:A1993KQ35800010 PM 8383789 ER PT J AU CHEN, CN HOULT, DI AF CHEN, CN HOULT, DI TI THE VISUALIZATION OF RF PROBE ELECTRIC-FIELDS SO MAGNETIC RESONANCE IN MEDICINE LA English DT Note DE RF PROBE; ELECTRIC FIELDS; NMR ID SAMPLES RP CHEN, CN (reprint author), NIH,BIOMED ENGN & INSTRUMENTAT PROGRAM,BLDG 13,ROOM 3W13,BETHESDA,MD 20892, USA. NR 8 TC 8 Z9 8 U1 0 U2 5 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 1993 VL 29 IS 3 BP 386 EP 390 DI 10.1002/mrm.1910290316 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA KQ358 UT WOS:A1993KQ35800015 PM 8450747 ER PT J AU JOHNSON, GA BENVENISTE, H BLACK, RD HEDLUND, LW MARONPOT, RR SMITH, BR AF JOHNSON, GA BENVENISTE, H BLACK, RD HEDLUND, LW MARONPOT, RR SMITH, BR TI HISTOLOGY BY MAGNETIC-RESONANCE MICROSCOPY SO MAGNETIC RESONANCE QUARTERLY LA English DT Article DE MAGNETIC RESONANCE MICROSCOPY; RADIOFREQUENCY COIL; PROTON CONTRASTS; PULSE SEQUENCES; SUPERCONDUCTING RADIOFREQUENCY PROBE ID MR MICROSCOPY; CEREBRAL-ISCHEMIA; FIELD-DEPENDENCE; LIMITED RESOLUTION; LUNG PARENCHYMA; CHICK-EMBRYO; BRAIN IRON; RAT-BRAIN; DIFFUSION; NMR AB Magnetic resonance microscopy (MRM) has advanced from a technical challenge to a practical tool in a wide range of basic sciences. This article focuses on the use of MRM as a tool for histological studies. The technical challenges of limited signal to noise have been overcome by improved radio-frequency (rf) coil design and 3DFT encoding with large arrays. Resolution limits imposed by motion in in vivo studies have been overcome by improved physiologic monitoring and control and projection encoding. Integration of technologies now permits routine studies in vivo down to 50 mum. MRM has also been applied to in vitro studies of fixed tissues where absence of motion allows studies down to 10 mum. The nondestructive nature of the technique allows repeated studies of the same sample, retrospective studies through any arbitrary plane, registered studies using different contrast mechanisms, and examination of valuable specimens. The many and unique proton contrasts provided by MRM, i.e., TI, T2, and diffusion weighting, permit direct examination of the state of water in tissues, something not possible with other microscopic techniques. Finally, the inherent three-dimensional nature of MRM allows acquisition of perfectly registered isotropic 3D arrays that, when displayed with appropriate visualization tools, provide new perspectives to histologic examination. The technology of MRM continues to develop rapidly. New pulse sequences are reducing acquisition times. New computer architectures allow larger arrays. A new class of superconducting rf probe has increased the signal to noise ratio by 10 times. These developments promise routine use of MRM in histology studies with resolution to 1 mum in the near future. C1 DUKE UNIV,MED CTR,DEPT RADIOL,CTR IN VIVO MICROSCOPY,DURHAM,NC 27710. NIEHS,DIV CHEM PATHOL & TOXICOL,RES TRIANGLE PK,NC 27709. GE CO,CTR RES & DEV,SCHENECTADY,NY 12345. OI Hedlund, Laurence/0000-0001-5275-0397; Johnson, G.Allan/0000-0002-7606-5447 FU NCRR NIH HHS [P41 RR 05959]; PHS HHS [R01 4187] NR 79 TC 183 Z9 187 U1 0 U2 9 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0899-9422 J9 MAGN RESON QUART JI Magn. Reson. Q. PD MAR PY 1993 VL 9 IS 1 BP 1 EP 30 PG 30 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA MF170 UT WOS:A1993MF17000001 PM 8512830 ER PT J AU SHEFFER, AL TAGGART, VS AF SHEFFER, AL TAGGART, VS TI THE NATIONAL ASTHMA EDUCATION-PROGRAM - EXPERT PANEL REPORT GUIDELINES FOR THE DIAGNOSIS AND MANAGEMENT OF ASTHMA SO MEDICAL CARE LA English DT Article; Proceedings Paper CT WORKSHOP ON ASTHMA CARE IN U.S. : UNDERSTANDING THE EFFECTIVENESS OF HEALTH CARE DELIVERY AND BARRIERS TO GOOD CLINICAL OUTCOMES CY MAR, 1991 CL SAN DIEGO, CA SP US DEPT HHS, AGCY HLTH CARE POLICY & RES, NIAID, NHLBI, US DEPT HHS, CTR DIS CONTROL, CTR CHRON DIS PREVENT & HLTH PROMOT, AMER THORAC SOC, AMER ACAD ALLERGY & IMMUNOL, AMER COLL ALLERGY & IMMUNOL, ASTHMA & ALLERGY FDN AMER ID HYPERRESPONSIVENESS; PATHOGENESIS; SEVERITY AB The significant worldwide increase in asthma-related severity and mortality has evoked increasing concern from the medical community. To enhance early recognition and appropriate therapeutic intervention of asthma, the National Heart, Lung, and Blood Institute's National Asthma Education Program convened an expert panel to develop guidelines for the diagnosis and treatment of asthma. The guidelines discussed in this article emphasize that airway inflammation is a central characteristic of asthma. Appropriate therapy must include four components: the use of objective measures of lung function to assess the severity of asthma and to monitor the course of therapy, comprehensive pharmacologic therapy that includes medications to reverse and prevent the underlying airway inflammation and to relieve the bronchoconstriction, environmental control measures to avoid or control factors that precipitate asthma exacerbations, and patient education to foster a partnership among the patient, the patient's family, and the clinician. C1 NHLBI,DIV LUNG DIS,BETHESDA,MD 20892. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NR 17 TC 34 Z9 34 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0025-7079 J9 MED CARE JI Med. Care PD MAR PY 1993 VL 31 IS 3 SU S BP MS20 EP MS28 PG 9 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA KU840 UT WOS:A1993KU84000005 PM 8450685 ER PT J AU LAI, CC BOGUSKI, M BROEK, D POWERS, S AF LAI, CC BOGUSKI, M BROEK, D POWERS, S TI INFLUENCE OF GUANINE-NUCLEOTIDES ON COMPLEX-FORMATION BETWEEN RAS AND CDC25 PROTEINS SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID ADENYLATE-CYCLASE PATHWAY; GDP-GTP EXCHANGE; SACCHAROMYCES-CEREVISIAE; WILD-TYPE; GENE; YEAST; ACTIVATION; PURIFICATION; SUPPRESS; MUTANTS AB The SaccharomYces cerevisiae CDC25 gene and closely homologous genes in other eukaryotes encode guanine nucleotide exchange factors for Ras proteins. We have determined the minimal region of the budding yeast CDC25 gene capable of activity in vivo. The region required for full biological activity is approximately 450 residues and contains two segments homologous to other proteins: one found in both Ras-specific exchange factors and the more distant Bud5 and Lte1 proteins, and a smaller segment of 48 amino acids found only in the Ras-specific exchange factors. When expressed in Escherichia coli as a fusion protein, this region of CDC25 was found to be a potent catalyst of GDP-GTP exchange on yeast Ras2 as well as human p21H-ras but inactive in promoting exchange on the Ras-related proteins Ypt1 and Rsr1. The CDC25 fusion protein catalyzed replacement of GDP-bound to Ras2 with GTP (activation) more efficiently than that of the reverse reaction of replacement of GTP for GDP (deactivation), consistent with prior genetic analysis of CDC25 which indicated a positive role in the activation of Ras. To more directly study the physical interaction of CDC25 and Ras proteins, we developed a protein-protein binding assay. We determined that CDC25 binds tightly to Ras2 protein only in the absence of guanine nucleotides. This higher affinity of CDC25 for the nucleotide-free form than for either the GDP- or GTP-bound form suggests that CDC25 catalyzes exchange of guanine nucleotides bound to Ras proteins by stabilization of the transitory nucleotide-free state. C1 UNIV SO CALIF,SCH MED,DEPT BIOCHEM,LOS ANGELES,CA 90033. ROBERT WOOD JOHNSON MED SCH,DEPT BIOCHEM,PISCATAWAY,NJ 08854. NIH,NATL CTR BIOTECHNOL INFORMAT NATL,BETHESDA,MD 20894. ONYX PHARMACEUT,RICHMOND,CA 94806. RUTGERS STATE UNIV,GRAD PROGRAM BIOCHEM,NEW BRUNSWICK,NJ 08903. UNIV SO CALIF,SCH MED,NORRIS CANC CTR,LOS ANGELES,CA 90033. FU NCI NIH HHS [CA50261]; NIGMS NIH HHS [GM41528] NR 35 TC 110 Z9 110 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 1993 VL 13 IS 3 BP 1345 EP 1352 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA KN579 UT WOS:A1993KN57900004 PM 8441380 ER PT J AU LIU, YH YANG, NY TENG, CT AF LIU, YH YANG, NY TENG, CT TI COUP-TF ACTS AS A COMPETITIVE REPRESSOR FOR ESTROGEN RECEPTOR-MEDIATED ACTIVATION OF THE MOUSE LACTOFERRIN GENE SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID PROMOTER TRANSCRIPTION FACTOR; RAT PROLACTIN GENE; RESPONSIVE ELEMENT; GLUCOCORTICOID RECEPTOR; DNA-BINDING; THYROID-HORMONE; OVALBUMIN GENE; BREAST-CANCER; C-JUN; SUPERFAMILY AB We previously demonstrated that the estrogen response module (mERM) of the mouse lactoferrin gene, which contains an overlapping chicken ovalbumin upstream promoter transcription factor (COUP-TF)- and estrogen receptor-binding element, is responsible for estrogen induction. In this report we show that COUP-TF represses the mERM response to estrogen stimulation. Mutation and deletion of the COUP-TF-binding element or reduction of the endogenous COUP-TF increases mERM estrogen responsiveness. Likewise, overexpression of the COUP-TF expression vector blocked the estrogen-stimulated response of mERM in transfected cells. The molecular mechanism of this repression is due to the competition between COUP-TF and the estrogen receptor for binding at identical contact sites in the overlapping region of the mERM. Our results indicate that two members of the steroid-thyroid receptor superfamily work in concert to modulate lactoferrin gene expression. C1 NIEHS,REPROD & DEV TOXICOL LAB,RES TRIANGLE PK,NC 27709. NR 65 TC 100 Z9 100 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 1993 VL 13 IS 3 BP 1836 EP 1846 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA KN579 UT WOS:A1993KN57900057 PM 8441416 ER PT J AU BUSHMAN, JL ASURU, AI MATTS, RL HINNEBUSCH, AG AF BUSHMAN, JL ASURU, AI MATTS, RL HINNEBUSCH, AG TI EVIDENCE THAT GCD6 AND GCD7, TRANSLATIONAL REGULATORS OF GCN4, ARE SUBUNITS OF THE GUANINE-NUCLEOTIDE EXCHANGE FACTOR FOR EIF-2 IN SACCHAROMYCES-CEREVISIAE SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID AMINO-ACID BIOSYNTHESIS; INITIATION FACTOR-II; PROTEIN-SYNTHESIS; GENERAL CONTROL; RABBIT RETICULOCYTES; MESSENGER-RNA; ALPHA-SUBUNIT; YEAST; PHOSPHORYLATION; MECHANISM AB Starvation of the yeast Saccharomyces cerevisiae for an amino acid signals increased translation of GCN4, a transcriptional activator of amino acid biosynthetic genes. We have isolated and characterized the GCD6 and GCD7 genes and shown that their products are required to repress GCN4 translation under nonstarvation conditions. We find that both GCD6 and GCD7 show sequence similarities to components of a high-molecular-weight complex (the GCD complex) that appears to be the yeast equivalent of translation initiation factor 2B (eIF-2B), which catalyzes GDP-GTP exchange on eIF-2. Furthermore, we show that GCD6 is 30% identical to the largest subunit of eIF-2B isolated from rabbit reticulocytes. Deletion of either GCD6 or GCD7 is lethal, and nonlethal mutations in these genes increase GCN4 translation in the same fashion described for defects in known subunits of eIF-2 or the GCD complex; derepression of GCN4 is dependent on short open reading frames in the GCN4 mRNA leader and occurs independently of eIF-2alpha phosphorylation by protein kinase GCN2, which is normally required to stimulate GCN4 translation. Together, our results provide evidence that GCD6 and GCD7 are subunits of eIF-2B in S. cerevisiae and further implicate this GDP-GTP exchange factor in gene-specific translational control. C1 NICHHD,MOLEC GENET LAB,MOLEC GENET LOWER EUKARYOTES SECT,BETHESDA,MD 20892. OKLAHOMA STATE UNIV,DEPT BIOCHEM & MOLEC BIOL,DIV AGR SCI & NAT RESOURCES,STILLWATER,OK 74078. FU NIEHS NIH HHS [ES-04299] NR 60 TC 82 Z9 85 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAR PY 1993 VL 13 IS 3 BP 1920 EP 1932 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA KN579 UT WOS:A1993KN57900067 PM 8441423 ER PT J AU MAKAROV, AA KUZNETSOVA, NV PROTASEVICH, II FEDOROV, BB KOROLEV, SV STRUMINSKAYA, NK BAZHULINA, NP BALABAN, NP LESHCHINSKAYA, IB HARTLEY, RW KIRPICHNIKOV, MP YAKOVLEV, GI ESIPOVA, NG AF MAKAROV, AA KUZNETSOVA, NV PROTASEVICH, II FEDOROV, BB KOROLEV, SV STRUMINSKAYA, NK BAZHULINA, NP BALABAN, NP LESHCHINSKAYA, IB HARTLEY, RW KIRPICHNIKOV, MP YAKOVLEV, GI ESIPOVA, NG TI COMPARISON OF THERMOSTABILITY AND STRUCTURE OF CLOSELY HOMOLOGOUS RIBONUCLEASES OF BACILLUS-AMYLOLIQUEFACIENS AND BACILLUS-INTERMEDIUS 7P SO MOLECULAR BIOLOGY LA English DT Article DE BARNASE; BINASE; HEAT DENATURATION ID TRYPTOPHAN RESIDUES; BARNASE; FLUORESCENCE; PROTEINS; BARSTAR AB Parameters of heat denaturation and intrinsic fluorescence of barnase and its close homologue, binase, in the acidic medium have been determined. Barnase is denatured at pH 2.8-5.5 according to the ''all-or-none'' principle. The denaturation temperature is lower for barnase than for binase: the difference increases from 2.5 degrees C at pH 5 to 7 degrees C at pH 3. The denaturation is accompanied by similar enthalpy changes only at pH 4.5-5.5; at lower pH values it is significantly decreased in the case of barnase but not binase. Fluorescence and circular dichroism measurements do not reveal any differences in the immediate environment of aromatic residues in the two proteins. The observed difference in intrinsic fluorescence parameters is explained by quenching of Trp-94 fluorescence in barnase by His-18, which is absent from binase. Secondary structures of both native and denatured proteins do not differ either. Some differences, manifest in the dipole moment distribution, were noted in the electrostatic properties of barnase and binase. C1 KAZAN VI LENIN STATE UNIV,KAZAN 420008,RUSSIA. NIDDKD,BETHESDA,MD 20892. RP MAKAROV, AA (reprint author), VA ENGELHARDT MOLEC BIOL INST,MOSCOW 117984,RUSSIA. RI Makarov, Alexander/P-5279-2016 NR 26 TC 0 Z9 0 U1 0 U2 1 PU PLENUM PUBL CORP PI NEW YORK PA CONSULTANTS BUREAU 233 SPRING ST, NEW YORK, NY 10013 SN 0026-8933 J9 MOL BIOL+ JI Mol. Biol. PD MAR-APR PY 1993 VL 27 IS 2 BP 255 EP 263 PN 2 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MM985 UT WOS:A1993MM98500007 ER PT J AU SAUNDERS, NA BERNACKI, SH VOLLBERG, TM JETTEN, AM AF SAUNDERS, NA BERNACKI, SH VOLLBERG, TM JETTEN, AM TI REGULATION OF TRANSGLUTAMINASE TYPE-I EXPRESSION IN SQUAMOUS DIFFERENTIATING RABBIT TRACHEAL EPITHELIAL-CELLS AND HUMAN EPIDERMAL-KERATINOCYTES - EFFECTS OF RETINOIC ACID AND PHORBOL ESTERS SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID TRANSCRIPTION FACTOR; MULTISTEP PROCESS; GENE-EXPRESSION; SEQUENCES; IDENTIFICATION; PROLIFERATION; BRYOSTATINS; INHIBITION; ENVELOPE; INVITRO AB In the present study we describe the full length cDNA sequence for rabbit transglutaminase type I as well as the sequence for a 2.9-kilobase (kb) promoter fragment of the gene. Transglutaminase type I mRNA expression was inhibited in squamous differentiating epithelia by retinoic acid (RA) in a dose-dependent (EC50 = 1-2 nM) and transcriptional manner. In human epidermal keratinocytes transglutaminase type I mRNA was induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) treatment, and this induction could be inhibited by bryostatin 1. In contrast, TPA treatment inhibited the expression of c-myc mRNA. Bryostatin 1 but not RA could prevent this decrease in c-myc mRNA expression, indicating that transglutaminase type I mRNA expression was associated with differentiation and not growth arrest. An SP1 element was found within 50 base pairs 5' of the transcription initiation site. A TATA-like element (CATAAAC) was found but was not capable of activating transcription. In addition, putative response elements for C-MYC, Ker1/AP2, 2 AP1 sites, a CK-8-mer, and an AP2 site were present in the 2.9-kb fragment. Transfection of RbTE cells with the 2.9-kb fragment ligated to a promoterless luciferase vector resulted in 2.2-fold more luciferase expression in differentiated vs. undifferentiated cells. Furthermore, luciferase activity was induced 7.4-fold in human epidermal keratinocytes induced to differentiate with TPA. TPA-induced luciferase activity was inhibited by both bryostatin 1 and RA. No known RA response elements were identified in the promoter. These data indicate that response elements mediating differentiation-specific expression, retinoid sensitivity, and phorbol ester responsiveness of transglutaminase type I gene expression are contained within the proximal 2.9 kb of the promoter. C1 NIEHS,PULM PATHOBIOL LAB,CELL BIOL SECT,POB 12233,RES TRIANGLE PK,NC 27709. RI saunders, nicholas/E-1544-2014; McTaggart, Jill/G-4696-2010; OI saunders, nicholas/0000-0002-2478-3420; McTaggart, Jill/0000-0002-9000-8529; Jetten, Anton/0000-0003-0954-4445 NR 48 TC 79 Z9 80 U1 0 U2 1 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD MAR PY 1993 VL 7 IS 3 BP 387 EP 398 DI 10.1210/me.7.3.387 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA KU730 UT WOS:A1993KU73000008 PM 8097865 ER PT J AU BATRA, JK KASTURI, S GALLO, MG VOORMAN, RL MAIO, SM CHAUDHARY, VK PASTAN, I AF BATRA, JK KASTURI, S GALLO, MG VOORMAN, RL MAIO, SM CHAUDHARY, VK PASTAN, I TI INSERTION OF CONSTANT REGION DOMAINS OF HUMAN IGG(1) INTO CD4-PE40 INCREASES ITS PLASMA HALF-LIFE SO MOLECULAR IMMUNOLOGY LA English DT Article ID PSEUDOMONAS EXOTOXIN; CD4-PSEUDOMONAS EXOTOXIN; FC FRAGMENTS; TOXIN; IMMUNOTOXINS; CATABOLISM; THERAPY; PROTEIN AB CD4-PE40 is a recombinant toxin containing the binding domain of CD4 and a mutant form of Pseudomonas exotoxin A from which the cell binding domain has been removed. To increase the serum half-life of CD4-PE40, we have inserted various portions of the constant domain of human IgG1 into CD4-PE40. The constructs made include CD4-C(H)2-PE40, CD4-C(H)3-PE40, CD4-C(H)1-C(H)2-PE40 and CD4-C(H)2-C(H)3-PE40. The fusion proteins were expressed and purified from E. coli. Insertion of various domains from the constant region of IgG1 did not alter the cytotoxic activity of CD4-PE40; all these molecules were equally cytotoxic to cells expressing gp120 on their surface. However, there was a marked increase in the serum mean residence time of CD4-C(H)2-PE40 which was 115 min as compared to 47 min for CD4-PE40. Insertion of other domains also increased the half-life of CD4-PE40, however, CD4-C(H)2-PE40 was found to have the longest mean residence time in the circulation. One possible explanation for the increase in plasma half-life is diminished susceptibility of proteins to proteolysis. It was found that CD4-C(H)2-PE40 was much more resistant to proteolysis by trypsin than CD4-PE40. We proposed that insertion of the C(H)2 domain into CD4-PE40 covers up the protease sensitive sites in the molecule, thereby making the molecule less susceptible to degradation. The increase in size and reduced sensitivity to proteases could both be responsible for the increased plasma half-life of CD4-C(H)2-PE40. C1 NCI,DIV CANC BIOL DIAG & CTR,MOLEC BIOL LAB,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. UPJOHN CO,KALAMAZOO,MI 49001. NR 21 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 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD MAR PY 1993 VL 30 IS 4 BP 379 EP 386 DI 10.1016/0161-5890(93)90067-L PG 8 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA KT203 UT WOS:A1993KT20300006 PM 8455638 ER PT J AU PEPPERBERG, DR OKAJIMA, TIL WIGGERT, B RIPPS, H CROUCH, RK CHADER, GJ AF PEPPERBERG, DR OKAJIMA, TIL WIGGERT, B RIPPS, H CROUCH, RK CHADER, GJ TI INTERPHOTORECEPTOR RETINOID-BINDING PROTEIN (IRBP) - MOLECULAR-BIOLOGY AND PHYSIOLOGICAL-ROLE IN THE VISUAL CYCLE OF RHODOPSIN SO MOLECULAR NEUROBIOLOGY LA English DT Review DE INTERPHOTORECEPTOR RETINOID-BINDING PROTEIN; IRBP; RHODOPSIN; RETINOID; VISUAL CYCLE; VISUAL PIGMENT; RETINAL PIGMENT EPITHELIUM ID ROD OUTER SEGMENTS; ALL-TRANS RETINOL; VITAMIN-A COMPOUNDS; PIGMENT-EPITHELIUM; IMMUNOCYTOCHEMICAL LOCALIZATION; BOVINE RETINA; MESSENGER-RNA; PHOTORECEPTOR NEURONS; BLEACHING ADAPTATION; DARK-ADAPTATION AB The regeneration of visual pigment in rod photoreceptors of the vertebrate retina requires an exchange of retinoids between the neural retina and the retinal pigment epithelium (RPE). It has been hypothesized that interphotoreceptor retinoid-binding protein (IRBP) functions as a two-way carrier of retinoid through the aqueous compartment (interphotoreceptor matrix) that separates the RPE and the photoreceptors. The first part of this review summarizes the cellular and molecular biology of IRBP. Work on the IRBP gene indicates that the protein contains a four-fold repeat structure that may be involved in binding multiple retinoid and fatty acid ligands. These repeats and other aspects of the gene structure indicate that the gene has had an active and complex evolutionary history. IRBP mRNA is detected only in retinal photoreceptors and in the pineal gland; expression is thus restricted to the two photosensitive tissues of vertebrate organisms. In the second part of this review, we consider the results obtained in experiments that have examined the activity of IRBP in the process of visual pigment regeneration. We also consider the results obtained on the bleaching and regeneration of rhodopsin in the acutely detached retina, as well as in experiments testing the ability of IRBP to protect its retinoid ligand from isomerization and oxidation. Taken together, the findings provide evidence that, in vivo, IRBP facilitates both the delivery of all-trans retinol to the RPE and the transfer of 11-cis retinal from the RPE to bleached rod photoreceptors, and thereby directly supports the regeneration of rhodopsin in the visual cycle. C1 UNIV ILLINOIS,DEPT ANAT & CELL BIOL,CHICAGO,IL 60612. NEI,BETHESDA,MD 20892. MED UNIV S CAROLINA,DEPT OPHTHALMOL,CHARLESTON,SC 29425. MED UNIV S CAROLINA,DEPT BIOCHEM,CHARLESTON,SC 29425. RP PEPPERBERG, DR (reprint author), UNIV ILLINOIS,COLL MED,LIONS ILLINOIS EYE RES INST,DEPT OPHTHALMOL & VISUAL SCI,CHICAGO,IL 60612, USA. FU NEI NIH HHS [EY-01792, EY-05494, EY-06516] NR 119 TC 121 Z9 122 U1 0 U2 3 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 SN 0893-7648 J9 MOL NEUROBIOL JI Mol. Neurobiol. PD SPR PY 1993 VL 7 IS 1 BP 61 EP 85 DI 10.1007/BF02780609 PG 25 WC Neurosciences SC Neurosciences & Neurology GA LC623 UT WOS:A1993LC62300004 PM 8318167 ER PT J AU AKIYOSHI, J HOUGH, C CHUANG, DM AF AKIYOSHI, J HOUGH, C CHUANG, DM TI PARADOXICAL INCREASE OF 5-HYDROXYTRYPTAMINE2 RECEPTORS AND 5-HYDROXYTRYPTAMINE2 RECEPTOR MESSENGER-RNA IN CEREBELLAR GRANULE CELLS AFTER PERSISTENT 5-HYDROXYTRYPTAMINE2 RECEPTOR STIMULATION SO MOLECULAR PHARMACOLOGY LA English DT Article ID LYSERGIC-ACID DIETHYLAMIDE; PHOSPHOINOSITIDE HYDROLYSIS; PHOSPHOLIPASE-C; DOWN-REGULATION; PHOSPHATIDYLINOSITOL TURNOVER; PROSTACYCLIN SYNTHESIS; SEROTONIN RECEPTORS; CEREBRAL-CORTEX; 5-HT2 RECEPTORS; DESENSITIZATION AB Rat cerebellar granule cells express 5-hydroxytryptamine (5-HT)2 receptors that mediate phosphoinositide turnover by a pertussis toxin-sensitive mechanism. Prestimulation of these neurons with 10 muM 5-HT or (+/-)-2,5-dimethoxy-4-iodophenyl-2-aminopropane [(+/-)-DOI], a putative 5-HT2 receptor agonist, resulted in a time-dependent desensitization of the phosphoinositide response to 5-HT. The desensitization was detected within 30 min after prestimulation and reached a maximum (about 80%) decrement at 8 hr. However, [H-3]ketanserin binding to 5-HT2 receptors in crude membranes or intact cerebellar granule cells was increased by treatment with 5-HT or DOI, in a time- and concentration-dependent manner. The increase occurred after the onset of desensitization and was fully manifest (about 160-190%) at 4 hr after stimulation. Although the B(max) and K(d) were unchanged at 1 hr after 5-HT or DOI treatment, both parameters were significantly increased at 4 and 24 hr. The amount of 5-HT2 receptor mRNA detected by Northern blot hybridization using a 5-HT2 receptor-specific riboprobe was increased in parallel with the up-regulation of 5-HT2 receptor binding sites. Thus, an increase in 5-HT2 receptor mRNA was detected within 2 hr after 5-HT or DOI prestimulation, reached a maximum around 4 hr, and remained at a plateau for at least 24 hr. The levels of total RNA, m3 muscarinic acetylcholine receptor mRNA, and beta-actin mRNA were not significantly affected by these treatments. Our results demonstrated that 5-HT2 receptor binding sites and their mRNA undergo a paradoxical induction during persistent agonist stimulation. C1 NIMH,BIOL PSYCHIAT BRANCH,MOLEC NEUROBIOL SECT,BLDG 10,ROOM 3N 212,BETHESDA,MD 20892. NR 36 TC 55 Z9 55 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 1993 VL 43 IS 3 BP 349 EP 355 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA KT629 UT WOS:A1993KT62900006 PM 8383800 ER PT J AU ROHLFF, C SAFA, B RAHMAN, A CHOCHUNG, YS KLECKER, RW GLAZER, RI AF ROHLFF, C SAFA, B RAHMAN, A CHOCHUNG, YS KLECKER, RW GLAZER, RI TI REVERSAL OF RESISTANCE TO ADRIAMYCIN BY 8-CHLORO-CYCLIC AMP IN ADRIAMYCIN-RESISTANT HL-60 LEUKEMIA-CELLS IS ASSOCIATED WITH REDUCTION OF TYPE-I CYCLIC AMP-DEPENDENT PROTEIN-KINASE AND CYCLIC-AMP RESPONSE ELEMENT-BINDING PROTEIN DNA-BINDING ACTIVITIES SO MOLECULAR PHARMACOLOGY LA English DT Article ID MULTIDRUG RESISTANCE; REGULATORY SUBUNIT; TRANSCRIPTION FACTORS; GENE-TRANSCRIPTION; CATALYTIC SUBUNIT; FACTOR CREB; CAMP; GROWTH; DIFFERENTIATION; PHOSPHORYLATION AB 8-Chloro-cyclic AMP (8-Cl-cAMP) produces growth-inhibitory and differentiating activity in the promyelocytic leukemia cell line HL-60. Adriamycin (ADR)-resistant HL-60 (HL-60/AR) cells exhibit the multidrug-resistant phenotype but do not express the mdr1 gene product P-glycoprotein. To explore potential signaling processes that may be involved in this atypical form of drug resistance, 8-Cl-cAMP was used as a modulator of the cAMP second messenger signal transduction pathway. Treatment for 48 hr with a 10% inhibitory concentration of 8-Cl-cAMP potentiated ADR cytotoxicity 14-fold in HL-60/AR cells but not in the parental cell line. 8-Cl-cAMP was stable to hydrolysis in the medium after 48 hr and was present intracellularly predominantly as phosphorylated metabolites (70%) and the parent compound (30%). No difference occurred in ADR accumulation in HL-60/AR cells after treatment with 8-Cl-cAMP. Accompanying the 8-Cl-cAMP-mediated increase in ADR cytotoxicity in HL-60/AR cells was a reduction in the cytosolic type I cAMP-dependent protein kinase (PKA) and disappearance of the nuclear PKA holoenzyme. Coincident with these changes in drug-resistant cells was a marked reduction in the DNA-binding activity of the cAMP response element-binding protein to levels equivalent to those in sensitive cells. This effect appears to result from reduced phosphorylation of the cAMP response element-binding protein. These results suggest that the potentiation by 8-Cl-cAMP of ADR cytotoxicity in HL-60/AR cells occurs through down-regulation of nuclear type I PKA and cAMP response element-binding factors whose activities are regulated by PKA. C1 GEORGETOWN UNIV,MED CTR,VINCENT T LOMBARDI CANC RES CTR,WASHINGTON,DC 20007. GEORGETOWN UNIV,MED CTR,VINCENT T LOMBARDI CANC RES CTR,DEPT PHARMACOL,WASHINGTON,DC 20007. GEORGETOWN UNIV,MED CTR,VINCENT T LOMBARDI CANC RES CTR,DEPT MED,WASHINGTON,DC 20007. NCI,TUMOR IMMUNOL & BIOL LAB,BETHESDA,MD 20892. US FDA,DIV CLIN PHARMACOL,ROCKVILLE,MD 20850. NR 37 TC 31 Z9 31 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 1993 VL 43 IS 3 BP 372 EP 379 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA KT629 UT WOS:A1993KT62900009 PM 8383802 ER PT J AU SHIELDS, PG HARRIS, CC PETRUZZELLI, S BOWMAN, ED WESTON, A AF SHIELDS, PG HARRIS, CC PETRUZZELLI, S BOWMAN, ED WESTON, A TI STANDARDIZATION OF THE P-32 POSTLABELING ASSAY FOR POLYCYCLIC AROMATIC HYDROCARBON DNA ADDUCTS SO MUTAGENESIS LA English DT Article ID P-32 POSTLABELING ANALYSIS; DIOL-EPOXIDE-DNA; LUNG-CANCER; MOLECULAR EPIDEMIOLOGY; HUMAN-PLACENTA; LYMPHOCYTES; EXPOSURE; FLUORESCENCE; SENSITIVITY; ENHANCEMENT AB A modified method for the P-32-postlabeling assay that permits standardized quantitation for specific polycyclic aromatic hydrocarbon (PAH)-DNA adducts is described. This method has been designed to test the components of the 32 P-postlabeling assay for use in the chemically specific detection of individual adducts with the ultimate goal of testing the biological significance of PAH - DNA adducts in humans. The approach relies upon high performance liquid chromatography (HPLC), concomitant labeling of 2'-deoxyguanosine (dGp) as an internal standard and thin layer chromatography (TLC), which identifies unmodified nucleotides along with PAH-DNA adducts on the same TLC plate. This method assesses labeling efficiency, detects the presence of unknown inhibitors, assesses the adequacy of digestion (when combined with HPLC) and allows for the development of calibration curves for directly determined molar ratios (adduct:internal standard). Chemically synthesized adduct standards and quantitatiVe P-32-postlabeling data have been corroborated by UV spectroscopy, fluorescence spectroscopy and liquid scintillation counting where radiolabeled materials were available. Labeling efficiencies of the PAH - DNA adducts were found to be up to 100-fold less than expected and depended upon both the adduct and adduct levels (lower levels being less efficiently detected). The presence of urimodified nucleotides resulted in a 1.5-fold lower labeling efficiency. Mixtures of selected PAH - DNA adducts did not affect the labeling efficiencies of each other. The data suggest that previous P-32-postlabeling assay studies for PAH-DNA adducts may have underestimated adduct levels due to variations in labeling efficiency. C1 NCI,HUMAN CARCINOGENESIS LAB,BETHESDA,MD 20892. RI Shields, Peter/I-1644-2012 NR 39 TC 23 Z9 23 U1 0 U2 4 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0267-8357 J9 MUTAGENESIS JI Mutagenesis PD MAR PY 1993 VL 8 IS 2 BP 121 EP 126 DI 10.1093/mutage/8.2.121 PG 6 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA KT338 UT WOS:A1993KT33800006 PM 8464380 ER PT J AU TENNANT, RW AF TENNANT, RW TI STRATIFICATION OF RODENT CARCINOGENICITY BIOASSAY RESULTS TO REFLECT RELATIVE HUMAN HAZARD SO MUTATION RESEARCH LA English DT Article DE RODENT BIOASSAY; TRANSSPECIES CARCINOGENS; GENETIC INFLUENCES; GENES AND CANCER; STRATIFICATION OF BIOASSAY RESULTS ID CHEMICAL CARCINOGENESIS; MICE; RATS; SUPERFAMILY; NEOPLASMS; TOXICITY; SCHEME; RISK AB Trans-species, multiple site (particularly common site between species), mutagenic rodent carcinogens are less affected by the influences of polymorphic genes than are chemicals inducing more limited carcinogenic effects. Trans-species carcinogens, therefore, should represent a first priority for attention for human health risk. RP TENNANT, RW (reprint author), NIEHS,EXPTL CARCINOGENESIS & MUTAGENESIS BRANCH,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 25 TC 72 Z9 72 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0921-8262 J9 MUTAT RES PD MAR PY 1993 VL 286 IS 1 BP 111 EP 118 DI 10.1016/0027-5107(93)90006-2 PG 8 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA KL502 UT WOS:A1993KL50200005 PM 7678907 ER PT J AU WALDHERR, M RAGNINI, A SCHWEYEN, RJ BOGUSKI, MS AF WALDHERR, M RAGNINI, A SCHWEYEN, RJ BOGUSKI, MS TI MRS6 - YEAST HOMOLOG OF THE CHOROIDEREMIA GENE SO NATURE GENETICS LA English DT Letter ID GTP-BINDING PROTEIN; SMG P25A; REGULATORY PROTEIN; CLONING C1 NIH,NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,BETHESDA,MD 20894. RP WALDHERR, M (reprint author), UNIV VIENNA,INST MICROBIOL & GENET,DR BOHR GASSE 9,A-1030 VIENNA,AUSTRIA. NR 18 TC 48 Z9 49 U1 0 U2 3 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 1993 VL 3 IS 3 BP 193 EP 194 DI 10.1038/ng0393-193 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA KP790 UT WOS:A1993KP79000005 PM 8387377 ER PT J AU BAJOCCHI, G FELDMAN, SH CRYSTAL, RG MASTRANGELI, A AF BAJOCCHI, G FELDMAN, SH CRYSTAL, RG MASTRANGELI, A TI DIRECT INVIVO GENE-TRANSFER TO EPENDYMAL CELLS IN THE CENTRAL-NERVOUS-SYSTEM USING RECOMBINANT ADENOVIRUS VECTORS SO NATURE GENETICS LA English DT Article ID GENETICALLY MODIFIED CELLS; BLOOD-BRAIN-BARRIER; BETA-GALACTOSIDASE; DRUG DELIVERY; RAT AB To evaluate the potential for adenovirus-mediated central nervous system (CNS) gene transfer, the replication deficient recombinant adenovirus vectors Ad.RSVbetagal (coding for beta-galactosidase) and Ad-alpha1AT (coding for human alpha1-antitrypsin) were administered to the lateral ventricle of rats. Ad.RSVbetagal transferred beta-galactosidase to ependymal cells lining the ventricles whereas Ad-alpha1AT mediated alpha1-antitrypsin secretion into the cerebral spinal fluid for 1 week. These observations, together with beta-galactosidase activity in the globus pallidus and substantia nigra following stereotactic administration of Ad.RSVbetagal to the globus pallidus, suggest that adenovirus vectors will be useful for CNS gene therapy. C1 NHLBI, PULM BRANCH, BETHESDA, MD 20892 USA. NHLBI, LAB ANIM MED & SURG SECT, BETHESDA, MD 20892 USA. NR 31 TC 324 Z9 328 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 EI 1546-1718 J9 NAT GENET JI Nature Genet. PD MAR PY 1993 VL 3 IS 3 BP 229 EP 234 DI 10.1038/ng0393-229 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA KP790 UT WOS:A1993KP79000012 PM 8485578 ER PT J AU GISH, W STATES, DJ AF GISH, W STATES, DJ TI IDENTIFICATION OF PROTEIN CODING REGIONS BY DATABASE SIMILARITY SEARCH SO NATURE GENETICS LA English DT Article ID HUMAN DNA-SEQUENCES; NUCLEOTIDE-SEQUENCE; GENE; ACCURACY; GENBANK; TOOL AB Sequence similarity between a translated nucleotide sequence and a known biological protein can provide strong evidence for the presence of a homologous coding region, even between distantly related genes. The computer program BLASTX performed conceptual translation of a nucleotide query sequence followed by a protein database search in one programmatic step. We characterized the sensitivity of BLASTX recognition to the presence of substitution, insertion and deletion errors in the query sequence and to sequence divergence. Reading frames were reliably identified in the presence of 1 % query errors, a rate that is typical for primary sequence data. BLASTX is appropriate for use in moderate and large scale sequencing projects at the earliest opportunity, when the data are most prone to containing errors. RP NATL LIB MED, NATL CTR BIOTECHNOL INFORMAT, BLDG 38A, ROOM 8N806, 8600ROCKVILLE PIKE, BETHESDA, MD 20894 USA. RI Gish, Warren/C-8123-2012 NR 37 TC 1155 Z9 1183 U1 1 U2 31 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 EI 1546-1718 J9 NAT GENET JI Nature Genet. PD MAR PY 1993 VL 3 IS 3 BP 266 EP 272 DI 10.1038/ng0393-266 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA KP790 UT WOS:A1993KP79000019 PM 8485583 ER PT J AU GAUDET, SJ HAYDEN, BJ CHADER, GJ NAMBOODIRI, MAA AF GAUDET, SJ HAYDEN, BJ CHADER, GJ NAMBOODIRI, MAA TI DIFFERENTIAL REGULATION OF ARYLAMINE AND ARYLALKYLAMINE N-ACETYLTRANSFERASES IN HUMAN RETINOBLASTOMA (Y-79) CELLS SO NEUROCHEMISTRY INTERNATIONAL LA English DT Article ID ACETYLATION PHARMACOGENETICS; CYCLIC-AMP; HUMAN LIVER; REGIONAL DISTRIBUTION; MELATONIN PRODUCTION; EXPRESSION; LOCALIZATION; BUTYRATE; CLONING; PINEAL AB For the first time, arylamine and arylalkylamine N-acetyltransferase (NAT) activities are shown to be differentially regulated. In a human retinoblastoma (Y-79) cell line, arylalkylamine NAT activity, but not arylamine NAT activity increased (3-5-fold) rapidly (1-3 h) in response to treatment with dibutyryl cAMP. In contrast, treatment with butyrate showed a delayed (3-5 days) increase (3-5-fold) in arylamine NAT activity but not in arylalkylamine NAT activity. The differential response to these agents in Y-79 cells provides a model system for future studies on the regulatory relationship between the two enzyme activities. C1 GEORGETOWN UNIV,DEPT BIOL,MOLEC NEUROBIOL LAB,WASHINGTON,DC 20057. RP GAUDET, SJ (reprint author), NEI,RETINAL CELL & MOLEC BIOL LAB,BLDG 6,ROOM 309,BETHESDA,MD 20892, USA. FU NIDDK NIH HHS [DK 37024] NR 32 TC 3 Z9 3 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0197-0186 J9 NEUROCHEM INT JI Neurochem. Int. PD MAR PY 1993 VL 22 IS 3 BP 271 EP 275 DI 10.1016/0197-0186(93)90055-A PG 5 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA KN736 UT WOS:A1993KN73600007 PM 8382984 ER PT J AU BACHMAN, DL WOLF, PA LINN, RT KNOEFEL, JE COBB, JL BELANGER, AJ WHITE, LR DAGOSTINO, RB AF BACHMAN, DL WOLF, PA LINN, RT KNOEFEL, JE COBB, JL BELANGER, AJ WHITE, LR DAGOSTINO, RB TI INCIDENCE OF DEMENTIA AND PROBABLE ALZHEIMERS-DISEASE IN A GENERAL-POPULATION - THE FRAMINGHAM-STUDY SO NEUROLOGY LA English DT Article ID CLINICAL-FEATURES; DIAGNOSIS; ILLNESSES; CRITERIA; RATES; AGE AB Objective: To determine the incidence of dementia and Alzheimer's disease (AD) in a general population sample. Background: Utilizing subjects in the Framingham Study cohort determined to be free of dementia in 1976 to 1978, or on biennial examination 17 in 1982, all new cases of dementia arising in this cohort over a maximum of 10 years of follow-up were ascertained. Methods: On biennial examination 14/15, a screening neuropsychologic examination was administered to 2,117 subjects, and cases of probable prevalent dementia were identified. Beginning on examination 17 and on all successive biennial examinations, a Mini-Mental State Examination was administered. Subjects previously free of dementia and falling below age-education levels were evaluated by a neurologist and neuropsychologist to determine if dementia was present and to ascertain the dementia type using standard criteria. Results: Five-year incidence of dementia increased with age, doubling in successive 5-year age groups. Dementia incidence rose from 7.0 per 1,000 at ages 65 to 69 to 118.0 per 1,000 at ages 85 to 89 for men and women combined. Incidence of probable AD also doubled with successive quinquennia from 3.5 at ages 65 to 69 to 72.8 per 1,000 at ages 85 to 89 years. Incidence of dementia and of probable AD did not level off with age and was not different in men and women. Conclusions: In a general population sample, we determined incidence of dementia and of probable AD and will use these incident cases for study of precursors and natural history in this elderly cohort, which has been under close surveillance for over 40 years. C1 BOSTON UNIV,SCH MED,DEPT NEUROL,80 E CONCORD ST,BOSTON,MA 02118. MED UNIV S CAROLINA,DEPT NEUROL,CHARLESTON,SC 29425. BOSTON UNIV,DEPT MATH,BOSTON,MA 02215. NIA,EPIDEMIOL DEMOG & BIOMETRY PROGRAM,BETHESDA,MD 20892. FU NHLBI NIH HHS [N01-HC-38038]; NIA NIH HHS [5-R01-AG08122-05] NR 27 TC 334 Z9 335 U1 3 U2 7 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAR PY 1993 VL 43 IS 3 BP 515 EP 519 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA KT215 UT WOS:A1993KT21500011 PM 8450993 ER PT J AU BOUZAS, EA PARRY, DM ELDRIDGE, R KAISERKUPFER, MI AF BOUZAS, EA PARRY, DM ELDRIDGE, R KAISERKUPFER, MI TI VISUAL IMPAIRMENT IN PATIENTS WITH NEUROFIBROMATOSIS-2 SO NEUROLOGY LA English DT Note ID TYPE-2 C1 NEI, NIH10, 10N226, 9000 ROCKVILLE PIKE, BETHESDA, MD 20892 USA. NINCDS, BETHESDA, MD 20892 USA. NR 7 TC 29 Z9 29 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD MAR PY 1993 VL 43 IS 3 BP 622 EP 623 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA KT215 UT WOS:A1993KT21500035 PM 8451014 ER PT J AU BOJA, JW KOPAJTIC, TA AF BOJA, JW KOPAJTIC, TA TI ION CHANNEL INHIBITORS MAY FUNCTION AS POTENTIAL MODULATORS OF COCAINE BINDING SO NEUROPHARMACOLOGY LA English DT Article DE COCAINE RECEPTORS; ION CHANNEL BLOCKERS; [H-3]WIN 35,428 BINDING, RADIOLIGAND BINDING ASSAY ID REINFORCING PROPERTIES; DOPAMINE TRANSPORTER; BRAIN SYNAPTOSOMES; CALCIUM CHANNELS; MOUSE STRIATUM; H-3 COCAINE; BAY-K-8644; RECEPTORS; SODIUM; ANTAGONISTS AB The effects of NaCl, KCl and Ca2Cl were determined in a binding assay, using the analog of cocaine [H-3]WIN 3 5,428. The addition of NaCl had no effect upon specific binding; however, Ca2Cl and to a lesser extent, KCl decreased binding. Various Na+, K+, Cl- and Ca2+ Channel antagonists were tested for their ability to inhibit specific binding of [H-3]WIN 35,428. Most of the Na+ channel blockers tested were of moderate affinity, the exceptions being benzamil and flunarizine. Both of these agents also show activity at the Ca2+ channel. The K+ channel blockers were of low and moderate affinity, while the Cl- channel blockers had no effect. Of the Ca2+ channel blockers tested, only pimozide demonstrated a high affinity. This was postulated to be due to its ability to act upon both L and T-type channels. These results suggest that the Ca2+ channel blockers deserve further study as potential useful therapeutic agents in the treatment of cocaine addiction. RP NATL INST DRUG ABUSE, MOLEC PHARMACOL LAB, NEUROSCI BRANCH, ADDICT RES CTR, POB 5180, BALTIMORE, MD 21224 USA. NR 38 TC 6 Z9 6 U1 3 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3908 EI 1873-7064 J9 NEUROPHARMACOLOGY JI Neuropharmacology PD MAR PY 1993 VL 32 IS 3 BP 229 EP 234 DI 10.1016/0028-3908(93)90105-C PG 6 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA KU366 UT WOS:A1993KU36600005 PM 7682676 ER PT J AU WEIHE, E NOHR, D SHARER, L MURRAY, E RAUSCH, D EIDEN, L AF WEIHE, E NOHR, D SHARER, L MURRAY, E RAUSCH, D EIDEN, L TI CORTICAL ASTROCYTOSIS IN JUVENILE RHESUS-MONKEYS INFECTED WITH SIMIAN IMMUNODEFICIENCY VIRUS SO NEUROREPORT LA English DT Article DE AIDS; SIV; RHESUS MONKEY; MOTOR COGNITIVE IMPAIRMENT; ASTROCYTOSIS; CEREBRAL CORTEX; GRAY MATTER; GFAP ID AIDS DEMENTIA COMPLEX; FRONTAL-CORTEX; HIV-INFECTION; ENCEPHALOPATHY; FEATURES AB THE pattern of expression of GFAP immunoreactivity in astrocytes of the juvenile rhesus monkey cortex was examined following infection with simian immunodeficiency virus (SIV). Blocks of cerebral cortex plus subjacent white matter from saline- and formalin-perfused brain were examined by peroxidase-linked immunochemical and immunofluorescence staining of deparaffinized sections. Strong GFAP immunoreactivity was found in astrocytic cells in both uninfected and SIV-infected juvenile macaque in the subpial cerebral cortex and in subcortical white matter, where GFAP-positive cells were abundant. GFAP staining of cortical layers 2-6 on the other hand was weak or absent in three uninfected controls and one infected animal without cognitive impairment, but moderate to strong in animals productively infected with SIV that demonstrated cognitive and/or motor impairment. These data demonstrate a cortical locus of astrocytic activation in rhesus monkeys infected with primate immunodeficiency virus isolate SIV(B670) which, like HIV-1 in man, causes motor/cognitive impairment as well as immunodeficiency disease. C1 NIMH,CELL BIOL LAB,MOLEC NEUROSCI SECT,BETHESDA,MD 20892. UMD NEW JERSEY,SCH MED,DEPT LAB MED & PATHOL,NEWARK,NJ. NIMH,NEUROPSYCHOL LAB,BETHESDA,MD 20892. UNIV MAINZ,DEPT ANAT,W-6500 MAINZ,GERMANY. OI Eiden, Lee/0000-0001-7524-944X; Murray, Elisabeth/0000-0003-1450-1642 NR 22 TC 31 Z9 31 U1 0 U2 1 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD MAR PY 1993 VL 4 IS 3 BP 263 EP 266 DI 10.1097/00001756-199303000-00009 PG 4 WC Neurosciences SC Neurosciences & Neurology GA KT661 UT WOS:A1993KT66100009 PM 8477048 ER PT J AU LEE, WH MICHELS, KM BONDY, CA AF LEE, WH MICHELS, KM BONDY, CA TI LOCALIZATION OF INSULIN-LIKE GROWTH-FACTOR BINDING PROTEIN-2 MESSENGER-RNA DURING POSTNATAL BRAIN-DEVELOPMENT - CORRELATION WITH INSULIN-LIKE GROWTH FACTOR-I AND FACTOR-II SO NEUROSCIENCE LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; RAT-BRAIN; IGF-II; CEREBROSPINAL-FLUID; CHOROID-PLEXUS; EXPRESSION; GENE; ASTROCYTES; RECEPTORS; CELLS AB Insulin-like growth factor binding protein-2 binds insulin-like growth factors I and II with high affinity and modulates the interaction of these ligands with the type I insulin-like growth factor receptor. Previously we have shown that insulin-like growth factor binding protein-2 and insulin-like growth factor-I gene expression are spatiotemporally co-ordinated in the developing retina and cerebellum. The present study examined other brain regions and found a similar correlation in insulin-like growth factor binding protein-2 and insulin-like growth factor-I gene expression in relay stations of developing sensory and cerebellar networks of the rat. In these sites, as in the cerebellum and retina, insulin-like growth factor-I messenger RNA is localized in the principal or projection neurons and insulin-like growth factor binding protein-2 messenger RNA is localized in surrounding astroglia. Outside these sensory relay centers, the relationship of insulin-like growth factor binding protein-2 to insulin-like growth factor-I gene expression is not so well defined. In the hippocampal formation, insulin-like growth factor-I messenger RNA is present in large interneurons and insulin-like growth factor binding protein-2 messenger RNA in regional astrocytes; their timing is co-ordinated, with peak levels seen about postnatal day 12, but their anatomical association is not apparent. The least degree of correlation between local insulin-like growth factor-I and insulin-like growth factor binding protein-2 gene expression is found in the neocortex, where insulin-like growth factor-I is abundant in scattered large neurons from postnatal days 3 to 20. In contrast, insulin-like growth factor binding protein-2 messenger RNA is widely expressed throughout the neocortex from before birth to about postnatal day 12, in a pattern consistent with expression by nascent astroglia. Insulin-like growth factor binding protein-2 gene expression is greatly reduced throughout the brain by the third week after birth; in response to optic nerve transection, however, there is a resurgence of gene expression for this factor by activated astrocytes in affected retinal target regions. Insulin-like growth factor binding protein-2 and insulin-like growth factor-II messenger RNAs are co-localized in the choroid plexus and leptomeninges from the time of birth onward without diminution. In summary, insulin-like growth factor binding protein-2 demonstrates complex patterns of gene expression during postnatal brain development-some of which appear to be closely related to local insulin-like growth factor synthesis and some of which appear independent of it. The spatiotemporal correlation between astroglial insulin-like growth factor binding protein-2 and neuronal insulin-like growth factor-I expression is restricted to maturing sensory and cerebellar projection systems, suggesting a system-specific function for insulin-like growth factor-I and insulin-like growth factor binding protein-2 interaction in the differentiation of these centers. C1 NIH,CLIN SCI LAB,BD 10,RM 10N262,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. NICHHD,DEV ENDOCRINOL BRANCH,BETHESDA,MD 20892. NR 31 TC 104 Z9 106 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 1993 VL 53 IS 1 BP 251 EP 265 DI 10.1016/0306-4522(93)90303-W PG 15 WC Neurosciences SC Neurosciences & Neurology GA KR757 UT WOS:A1993KR75700026 PM 7682300 ER PT J AU KIRCHMAIR, R HOGUEANGELETTI, R GUTIERREZ, J FISCHERCOLBRIE, R WINKLER, H AF KIRCHMAIR, R HOGUEANGELETTI, R GUTIERREZ, J FISCHERCOLBRIE, R WINKLER, H TI SECRETONEURIN - A NEUROPEPTIDE GENERATED IN BRAIN, ADRENAL-MEDULLA AND OTHER ENDOCRINE TISSUES BY PROTEOLYTIC PROCESSING OF SECRETOGRANIN-II (CHROMOGRANIN-C) SO NEUROSCIENCE LA English DT Article ID CHROMAFFIN GRANULES; IMMUNOLOGICAL CHARACTERIZATION; RAT-BRAIN; IMMUNOHISTOCHEMICAL LOCALIZATION; SECRETORY PROTEINS; COMMON ANTIGENS; CELLS; PITUITARY; COMPONENT; PEPTIDES AB Secretogranin II (chromogranin C), originally described as tyrosine sulfated protein of the anterior pituitary, is present in large dense core vesicles of several endocrine cells and neurons. We raised antisera in rabbits to conjugates of two synthetic peptides (bovine secretogranin 133-151 and rat secretogranin 154-186) flanked in the primary structure of secretogranin II by pairs of basic residues and used them to investigate the proteolytic processing of this protein by immunoblotting and a newly developed radioimmunoassay. The sensitivity of this assay was 30 fmol for secretogranin 154-186 and 60 fmol for secretogranin 133-151. The highest degree of processing of secretogranin II (> 90%) occurs in brain. One of the peptides (secretogranin 133-151) is not generated to any significant ''tent. The other peptide, secretogranin 154-186, however, is formed in vivo, and in brain the free peptide apparently represents the predominant form. The highest concentrations of secretogranin 154-186 are found in the hypothalamus, two- to six-fold lower levels are present in the hippocampus, caudate nucleus, thalamus and brainstem. These concentrations are comparable to those of established neuropeptides. In order to indicate the special relevance of secretogranin II and of this peptide for brain we have named this peptide secretoneurin. The newly developed radioimmunoassay for this peptide will be a useful tool to establish its physiologic role in brain. C1 UNIV INNSBRUCK, DEPT PHARMACOL, PETER MAYR STR 1A, A-6020 INNSBRUCK, AUSTRIA. YESHIVA UNIV ALBERT EINSTEIN COLL MED, BRONX, NY 10461 USA. NIMH, CELL BIOL LAB, BETHESDA, MD 20892 USA. NR 34 TC 231 Z9 233 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD MAR PY 1993 VL 53 IS 2 BP 359 EP 365 DI 10.1016/0306-4522(93)90200-Y PG 7 WC Neurosciences SC Neurosciences & Neurology GA KV305 UT WOS:A1993KV30500005 PM 8492910 ER PT J AU SAVORY, J HERMAN, MM HUNDLEY, JC SEWARD, RL GRIGGS, CM KATSETOS, CD WILLS, MR AF SAVORY, J HERMAN, MM HUNDLEY, JC SEWARD, RL GRIGGS, CM KATSETOS, CD WILLS, MR TI QUANTITATIVE STUDIES ON ALUMINUM DEPOSITION AND ITS EFFECTS ON NEUROFILAMENT PROTEIN EXPRESSION AND PHOSPHORYLATION, FOLLOWING THE INTRAVENTRICULAR ADMINISTRATION OF ALUMINUM MALTOLATE TO ADULT-RABBITS SO NEUROTOXICOLOGY LA English DT Article DE ALUMINUM TOXICITY; NEUROFILAMENT PROTEINS; PHOSPHORYLATION; GENE EXPRESSION ID MYELOPATHY AB The deposition of aluminum (Al) in the brain and spinal cord of adult male New Zealand white rabbits was monitored following the intraventricular administration of Al maltolate. Although decreasing concentrations of Al were observed from the injection site (approximately 10 mug/g dry tissue) to the lumbar cord (2.1 mug/g), argyrophilic tangles were present in the perikarya and proximal neurites of neurons as far distal as the lumbar and sacral cord areas. Quantitative immunoblot studies of the three neurofilament protein isoforms failed to detect changes resulting from Al maltolate treatment. Similarly no significant alterations in the total phosphate content of these cytoskeletal proteins were observed. Lastly, on Northern blots, the expression of genes encoding for the 200 kDa and 68 kDa neurofilament proteins also was unaffected by Al maltolate treatment. (C) 1993 Intox Press, Inc. C1 ST ELIZABETH HOSP,NIMH,CTR NEUROSCI,WASHINGTON,DC 20032. HAHNEMANN UNIV,DEPT NEUROL,PHILADELPHIA,PA 19102. HAHNEMANN UNIV,DEPT PATHOL & LAB MED,PHILADELPHIA,PA 19102. UNIV VIRGINIA,HLTH SCI CTR,DEPT BIOCHEM,CHARLOTTESVILLE,VA 22908. UNIV VIRGINIA,HLTH SCI CTR,DEPT INTERNAL MED,CHARLOTTESVILLE,VA 22908. RP SAVORY, J (reprint author), UNIV VIRGINIA,HLTH SCI CTR,DEPT PATHOL,BOX 168,CHARLOTTESVILLE,VA 22908, USA. NR 14 TC 22 Z9 22 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 1993 VL 14 IS 1 BP 9 EP 12 PG 4 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA LK375 UT WOS:A1993LK37500002 PM 8361684 ER PT J AU TANDON, P BARONE, S BONNER, MJ ALI, SF TILSON, HA AF TANDON, P BARONE, S BONNER, MJ ALI, SF TILSON, HA TI THE ROLE OF THE SEPTOHIPPOCAMPAL PATHWAY IN THE MEDIATION OF COLCHICINE-INDUCED COMPENSATORY CHANGES IN THE RAT HIPPOCAMPUS SO NEUROTOXICOLOGY LA English DT Article DE INOSITOL PHOSPHATE; ACETYLCHOLINESTERASE; ACHE; CHOLINE ACETYLTRANSFERASE; CHAT; QNB BINDING; REACTIVE SYNAPTOGENESIS ID STIMULATED PHOSPHOINOSITIDE HYDROLYSIS; LESION-INDUCED SYNAPTOGENESIS; DENTATE GYRUS; ADULT-RAT; SEPTAL-LESIONS; BRAIN; PROJECTIONS; METABOLISM; DEAFFERENTATION; CONNECTIONS AB To study the involvement of the septohippocampal pathway in colchicine-induced changes in the hippocampus, colchicine was used to lesion the septum and/or hippocampus of male, Fischer-344 rats. Rats were killed 12 weeks post-lesion and histochemical and biochemical measurements were performed. [H-3]-QNB binding, choline acetyltransferase (ChAT) activity and agonist-stimulated release of inositol phosphates (IPs) were measured in hippocampal slices. AChE histochemistry was also performed to visualize AChE positive fibers in the hippocampus. Increases in ChAT activity, AChE staining and carbachol-stimulated IP release observed in hippocampal-lesioned animals were attenuated in animals receiving both septal and hippocampal lesions. However, the decrease observed in [H-3]-QNB binding sites after intradentate colchicine was not affected by septal lesions. Subsequent studies also found enhanced sensitivity to excitatory amino acid (EAA)-stimulated IP release in hippocampal-lesioned animals. Similar to the changes observed in carbachol-stimulated PI hydrolysis, this increase was also long-lasting. However, the hyperstimulation of EAA-induced IP release was not attenuated by the septal lesion. Thus, it appears that the neurochemical and morphological changes observed in the hippocampus following intradentate colchicine are dependent upon more than one afferent projection to the hippocampus. (C) 1993 Intox Press, Inc. C1 MANTECH ENVIRONM TECHNOL INC, RES TRIANGLE PK, NC 27711 USA. NCTR, DIV REPROD & DEV TOXICOL, JEFFERSON, AR 72079 USA. NIEHS, MOLEC & INTEGRAT NEUROSCI LAB, RES TRIANGLE PK, NC 27709 USA. NR 54 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0161-813X EI 1872-9711 J9 NEUROTOXICOLOGY JI Neurotoxicology PD SPR PY 1993 VL 14 IS 1 BP 41 EP 50 PG 10 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA LK375 UT WOS:A1993LK37500008 PM 8361677 ER PT J AU BLOOR, JE ECKERTMAKSIC, M HODOSCEK, M MAKSIC, ZB POLJANEC, K AF BLOOR, JE ECKERTMAKSIC, M HODOSCEK, M MAKSIC, ZB POLJANEC, K TI ABINITIO CALCULATIONS OF THE MILLS-NIXON EFFECT IN INDAN, TETRALIN AND IN RELATED SYSTEMS SO NEW JOURNAL OF CHEMISTRY LA English DT Article ID RING ANNELATED AROMATICS; PI-BOND LOCALIZATION; BENZOCYCLOPROPENES; CHEMISTRY; MOLECULES; QUESTION; FIXATION; BENZENE; STRAIN AB Structural properties of indan, tetralin, indene and the indenyl radical are examined by the 3-21G ab initio procedure. It was found that distal bonds of the benzene ring in tetralin exhibit a tiny distortion which resembles an anti-Mills-Nixon (MN) effect. However, it is so small that it is more of conceptual than practical significance. The other three compounds on the other hand show the MN type of deformation but to a different extent. The effect is extremely small in indan and quite substantial in the indenyl radical. Hence the difference in electrophilic substitution reactivity at beta- and alpha-positions in the former molecule should be ascribed to features of the transition structures. Geometric variations are interpreted in terms of rehybridization at the carbon junction atoms and changes in pi-bond orders. Experimental evidence on the structural features is very limited, but available data are in accordance with theoretical findings. C1 RUDJER BOSKOVIC INST,41001 ZAGREB,CROATIA. UNIV ZAGREB,FAC SCI & MATH,41000 ZAGREB,CROATIA. JOZEF STEFAN INST,61111 LJUBLJANA,SLOVENIA. NIH,DEPT HLTH & HUMAN SERV,BETHESDA,MD 20892. RP BLOOR, JE (reprint author), UNIV TENNESSEE,DEPT CHEM,KNOXVILLE,TN 37996, USA. NR 42 TC 10 Z9 10 U1 0 U2 1 PU GAUTHIER-VILLARS PI PARIS PA S P E S-JOURNAL DEPT, 120 BD ST GERMAIN, F-75006 PARIS, FRANCE SN 1144-0546 J9 NEW J CHEM JI New J. Chem. PD MAR PY 1993 VL 17 IS 3 BP 157 EP 160 PG 4 WC Chemistry, Multidisciplinary SC Chemistry GA KZ011 UT WOS:A1993KZ01100003 ER PT J AU BATISTA, MC BRAVO, N CARTLEDGE, TP LORIAUX, DL MERRIAM, GR NIEMAN, LK AF BATISTA, MC BRAVO, N CARTLEDGE, TP LORIAUX, DL MERRIAM, GR NIEMAN, LK TI SERUM LEVELS OF PLACENTAL PROTEIN-14 DO NOT ACCURATELY REFLECT HISTOLOGIC MATURATION OF THE ENDOMETRIUM SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID LUTEAL PHASE DEFECTS; PREGNANCY; BIOPSIES; OVULATION; DIAGNOSIS; WOMEN; PP14 AB Objective: To determine whether serum levels of placental protein 14, a major product of the progesterone-induced secretory endometrium, accurately reflect histologic maturation of the endometrium. Methods: Daily serum levels of placental protein 14 were compared in 50 normally cycling women with normal or delayed endometrial maturation, as assessed by histologic dating of an endometrial biopsy in the midluteal phase of the same cycle. Ten of these subjects had placental protein 14 measurements but no biopsy in an additional cycle to examine the potential effects of the biopsy on secretion of this protein. Results: Serum placental protein 14 concentrations started to increase 8 days after the LH surge and peaked at similar levels on the first day of the next menses in biopsy and non-biopsy cycles. The biopsy cycles had a shorter luteal phase but a slightly faster increase in placental protein 14 concentrations. Both the integrated secretion of this protein and single measurements on the day of the biopsy or at the onset of the next menses overlapped substantially in women with different degrees of endometrial development, even when differentiation of the endometrium was severely delayed. Conclusion: Serum measurements of placental protein 14 do not accurately predict, and thus should not replace, histologic evaluation of the endometrium at nidation. C1 NICHHD,DEV ENDOCRINOL BRANCH,BLDG 10,ROOM 10N262,BETHESDA,MD 20892. NIH,WARREN GRANT MAGNUSON CLIN CTR,DEPT NURSING,BETHESDA,MD 20892. RI Batista, Marcelo/K-4305-2013 NR 25 TC 12 Z9 12 U1 0 U2 0 PU ELSEVIER SCIENCE 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 1993 VL 81 IS 3 BP 439 EP 443 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA KN206 UT WOS:A1993KN20600026 PM 8437802 ER PT J AU GUTMANN, DH BOGUSKI, M MARCHUK, D WIGLER, M COLLINS, FS BALLESTER, R AF GUTMANN, DH BOGUSKI, M MARCHUK, D WIGLER, M COLLINS, FS BALLESTER, R TI ANALYSIS OF THE NEUROFIBROMATOSIS TYPE-1 (NF1) GAP-RELATED DOMAIN BY SITE-DIRECTED MUTAGENESIS SO ONCOGENE LA English DT Article ID AFFINITY CAMP PHOSPHODIESTERASE; GTPASE-ACTIVATING PROTEIN; SACCHAROMYCES-CEREVISIAE; GENE-PRODUCT; RAS GTPASE; MAMMALIAN GAP; YEAST; IDENTIFICATION; SEQUENCE; ENCODES AB The gene for von Recklinghausen neurofibromatosis type 1 (NF1) was recently identified by positional cloning and found to encode a protein with sequence similarity to a family of eucaryotic GTPase-activating proteins (GAPs). Expression of the NF1-GAP-related domain (NF1GRD) has been shown to complement yeast strains deficient in the yeast GAP homologs, IRA1 and IRA2, to interact with human RAS proteins and to accelerate the conversion of ras-GTP to ras-GDP. Further analysis of this region has revealed a number of residues that are highly conserved between members of the GAP family. Mutational analysis of a representative number of these residues produced one of three effects: (1) no change in NF1GRD function. (2) complete disruption of NF1GRD function and (3) intermediate retention of NF1GRD function. One of these mutations at residue 1423 was shown to have reduced ability to negatively regulate ras in yeast, which is interesting in tight of a recent report demonstrating a similar naturally occurring mutation in human malignancies. C1 UNIV MICHIGAN,DEPT NEUROL,ANN ARBOR,MI 48109. UNIV MICHIGAN,DEPT HUMAN GENET,ANN ARBOR,MI 48109. UNIV MICHIGAN,DEPT RADIAT ONCOL,ANN ARBOR,MI 48109. UNIV MICHIGAN,DEPT INTERNAL MED,ANN ARBOR,MI 48109. NIH,NATL CTR BIOTECHNOL INFORMAT,BETHESDA,MD 20894. COLD SPRING HARBOR LAB,COLD SPRING HARBOR,NY 11724. OI Wigler, Michael/0000-0003-4396-1971 FU NINDS NIH HHS [NS23410] NR 39 TC 54 Z9 54 U1 0 U2 2 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD MAR PY 1993 VL 8 IS 3 BP 761 EP 769 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA KN008 UT WOS:A1993KN00800029 PM 8437860 ER PT J AU FLEISCHMAN, LF PILARO, AM MURAKAMI, K KONDOH, A FISHER, RJ PAPAS, TS AF FLEISCHMAN, LF PILARO, AM MURAKAMI, K KONDOH, A FISHER, RJ PAPAS, TS TI C-ETS-1-PROTEIN IS HYPERPHOSPHORYLATED DURING MITOSIS SO ONCOGENE LA English DT Article ID LONG TERMINAL REPEAT; NUCLEAR-ENVELOPE BREAKDOWN; LEUKEMIA-VIRUS HTLV-1; PROTEIN KINASE-II; V-ETS ONCOGENE; DIFFERENTIAL PHOSPHORYLATION; TRANSCRIPTIONAL ACTIVATORS; C-ETS-1 PROTOONCOGENE; MAMMALIAN-CELLS; DNA-BINDING AB The ets-1 and ets-2 proto-oncogene products can serve as transcription factors and become phosphorylated in response to Ca2+-mediated signals. We have examined expression of Ets proteins during the cell cycle in cells svnchronized by centrifugal elutriation or nocodazole-induced mitotic block. Both methods revealed the presence of a hyperphosphorylated isoform of Ets-1 during the mitotic phase. This isoform showed a characteristic mobility shift and was observed during mitosis in each of four cell lines (three human T-cell lines and a human astrocytoma) that express ets-1. In elutriated cells, only a small portion of the Ets-1 in cells from the G2/M fractions was hyperphosphorylated, while in nocodazole-arrested cells more of the Ets-1 was shifted. When cells were released from nocodazole arrest, this isoform disappeared within 1-2h as cells completed mitosis and entered G1. This suggests that hyperphosphorylated Ets-1 is present transiently during early mitosis, before or around the time of the metaphase-anaphase transition. Exposure of unsynchronized cells to okadaic acid resulted in a dramatic hyperphosphorylation of virtually all Ets-1, suggesting that changes in cellular phosphatase activity are important for cell cycle regulation of Ets-1. Hyperphosphorylated Ets-1 appears to arise from multiple phosphorylations on serine in the exon 7-encoded domain of the protein and did not appear to alter sequence-specific DNA-binding activity. Although enhanced phosphorylation of Ets-2 was detected in nocodazole-arrested cells, no Ets-2 hyperphosphorylation was seen. C1 NCI,EXPTL IMMUNOL LAB,FREDERICK,MD 21702. DYNCORP,PROGRAM RESOURCES INC,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. RP FLEISCHMAN, LF (reprint author), NCI,MOLEC ONCOL LAB,FREDERICK,MD 21702, USA. RI Fisher, Robert/B-1431-2009 NR 49 TC 31 Z9 31 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD MAR PY 1993 VL 8 IS 3 BP 771 EP 780 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA KN008 UT WOS:A1993KN00800030 PM 8437861 ER PT J AU SUN, Y HEGAMYER, G COLBURN, NH AF SUN, Y HEGAMYER, G COLBURN, NH TI NASOPHARYNGEAL CARCINOMA SHOWS NO DETECTABLE RETINOBLASTOMA SUSCEPTIBILITY GENE ALTERATIONS SO ONCOGENE LA English DT Note ID EPSTEIN-BARR VIRUS; HUMAN PROSTATE CARCINOMA; CELL LINES HNE-1; LARGE T-ANTIGEN; HUMAN BLADDER; RB GENE; INACTIVATION; EXPRESSION; PROTEIN; MUTATIONS AB Since multistage carcinogenesis is frequently associated with the loss of suppressor gene activity, and since in over 90% of cases of nasopharyngeal carcinoma (NPC) p53 alterations are not involved [Sun, Y., Hegamyer, G.H., Cheng, Y.-J., Hildesheim, A., Chen, J.-Y., Chen, I.-H., Cao, Y., Yao, K.-T. & Colburn, N.H. (1992). Proc. Natl. Acad. Sci. USA, 89, 6516-6520] we investigated the possible involvement of the inactivation of the retinoblastoma susceptibility gene (RB) in nasopharyngeal carcinogenesis. We analysed the expression, gross structure and possible point mutation of the RB gene in an NPC cell line as well as seven NPC biopsies obtained from seven patients. The NPC cell line expresses the RB gene with a normal size and abundance, as assayed by reverse transcriptase polymerase chain reaction (RT-PCR) and Northern hybridization. No point mutation was detected in two independent E1A/large T-binding regions, which are the common sites for mutations in the RB gene. NPC biopsies also showed no point mutations at four exon-intron boundaries at which point mutations have been reported in other human carcinomas. The biopsies and cell tine had no deletions in the promoter region of the gene and showed no gross deletions or rearrangements. Taken together, we conclude that, in contrast to multistage carcinogenesis leading to human retinoblastoma, osteogenic sarcomas and carcinomas of lung, breast, bladder and prostate, nasopharyngeal carcinogenesis appears unlikely to involve RB gene alterations. C1 NCI,CELL BIOL SECT,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21702. NCI,FCRDC,DYNCORP,PROGRAM RESOURCES INC,BCDP,FREDERICK,MD 21702. FU NCI NIH HHS [N01-CO-74102] NR 42 TC 61 Z9 70 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD MAR PY 1993 VL 8 IS 3 BP 791 EP 795 PG 5 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA KN008 UT WOS:A1993KN00800033 PM 8437863 ER PT J AU BOUZAS, EA KRASNEWICH, D KOUTROUMANIDIS, M PAPADIMITRIOU, A MARINI, JC KAISERKUPFER, MI AF BOUZAS, EA KRASNEWICH, D KOUTROUMANIDIS, M PAPADIMITRIOU, A MARINI, JC KAISERKUPFER, MI TI OPHTHALMOLOGIC EXAMINATION IN THE DIAGNOSIS OF PROTEUS SYNDROME SO OPHTHALMOLOGY LA English DT Article ID NEUROFIBROMATOSIS; MANIFESTATIONS; TUMORS AB Purpose: To describe the clinical features of Proteus syndrome, a rare recently recognized hamartoneoplastic malformation, with emphasis on the ocular findings. Methods: Complete physical and ocular examination of two new patients with Proteus syndrome. Results: The two reported cases illustrate the wide clinical polymorphism of Proteus syndrome and the overlap of its clinical manifestations with those of other overgrowth syndromes. Both patients had periorbital exostoses and epibulbar tumors. The ocular findings are compared with those in the literature. Conclusion: Considering the paucity of information in the ophthalmic literature, this article explores the role of the ophthalmologist in diagnosing this rare entity. C1 NEI,10-10N22L,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. RED CROSS HOSP,DEPT OPHTHALMOL,ATHENS,GREECE. NICHHD,BETHESDA,MD 20892. RED CROSS HOSP,DEPT NEUROL,ATHENS,GREECE. NR 25 TC 22 Z9 22 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD MAR PY 1993 VL 100 IS 3 BP 334 EP 338 PG 5 WC Ophthalmology SC Ophthalmology GA KT500 UT WOS:A1993KT50000016 PM 8460002 ER PT J AU ZHAO, JL SASTRY, SM SPERDUTO, RD CHEW, EY REMALEY, NA YANNUZZI, LA SORENSON, JA SEDDON, JM GRAGOUDAS, ES PULIAFITO, CA BURTON, TC FARBER, MD BLAIR, N STELMACK, T AXELROD, A HALLER, J PUSIN, S CASSEL, G SEIGEL, D SPERDUTO, RD HILLER, R CHEW, E TAMBOLI, A MILLER, DT SOWELL, AL GUNTER, EW DUNN, M AF ZHAO, JL SASTRY, SM SPERDUTO, RD CHEW, EY REMALEY, NA YANNUZZI, LA SORENSON, JA SEDDON, JM GRAGOUDAS, ES PULIAFITO, CA BURTON, TC FARBER, MD BLAIR, N STELMACK, T AXELROD, A HALLER, J PUSIN, S CASSEL, G SEIGEL, D SPERDUTO, RD HILLER, R CHEW, E TAMBOLI, A MILLER, DT SOWELL, AL GUNTER, EW DUNN, M TI ARTERIOVENOUS CROSSING PATTERNS IN BRANCH RETINAL VEIN OCCLUSION SO OPHTHALMOLOGY LA English DT Article AB Purpose: The study was designed to evaluate the relative anatomic position of the crossing vessels at the site of occlusion in eyes with branch retinal vein occlusion (BRVO). Methods: Fundus photographs of 106 eyes (104 patients) with recent BRVO from the Eye Disease Case-Control Study were used to examine the relative position of artery and vein at occluded crossings. Three separate comparison groups were formed by identifying corresponding arteriovenous crossings for each occluded crossing in: (1) the ipsilateral but opposite vessel arcade within eyes affected by BRVO; (2) the same quadrant in unaffected eyes of BRVO patients; and (3) the same quadrant in eyes of patients without BRVO, matched by age, sex, and race with the BRVO patients. Results: The site of obstruction of the branch vein was an arteriovenous crossing in all affected eyes. In 99% of eyes with BRVO, the artery was located anterior to the vein at the obstructed site. In the three comparison groups, the artery was anterior to the vein in 62%, 61%, and 54% of the crossings, respectively, yielding statistically significant differences for each group of control crossings compared with BRVO crossings (P < 0.001). Conclusion: Finding the vein to be consistently between the more rigid artery and the retina at almost all arteriovenous crossings affected by BRVO suggests a possible role for mechanical obstruction in the pathogenesis of BRVO. C1 NEI,DEPT HLTH & HUMAN SERV,BIOMETRY & EPIDEMIOL PROGRAM,BLDG 31,6A24,BETHESDA,MD 20892. MANHATTAN EYE EAR & THROAT HOSP,NEW YORK,NY 10021. HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,BOSTON,MA 02114. MED COLL WISCONSIN,MILWAUKEE,WI 53226. ORKAND CORP,CTR COORDINATING,SILVER SPRING,MD. UNIV ILLINOIS,CHICAGO,IL 60680. JOHNS HOPKINS UNIV HOSP,WILMER OPHTHALMOL INST,BALTIMORE,MD 21205. CTR DIS CONTROL,CTR ENVIRONM HLTH & HYG CONTROL,DIV ENVIRONM HLTH LAB SCI,ATLANTA,GA 30333. FU Intramural NIH HHS [Z99 EY999999] NR 11 TC 81 Z9 87 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD MAR PY 1993 VL 100 IS 3 BP 423 EP 428 PG 6 WC Ophthalmology SC Ophthalmology GA KT500 UT WOS:A1993KT50000030 PM 8460014 ER PT J AU LEBOVICS, RS MURTHY, VV KARMEN, A AF LEBOVICS, RS MURTHY, VV KARMEN, A TI LEUKOCYTE ESTERASE-ACTIVITY IN EFFUSION FLUID OF PATIENTS WITH OTITIS-MEDIA SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article AB Fluid obtained during myringotomy and tube placement in 20 patients with middle ear effusions was assayed for leukocyte esterase activity using a quantitative spectrophotometric assay. This quantitative assay used the synthetic substrate, N-tosyl indoxyl alaninate. Seven of the 20 samples showed no measurable enzyme activity (8 U/ml or less). The remaining samples demonstrated activity ranging from 20 to 1600 units. Although enzyme activity did not correlate well with the physical appearance of the fluid, it did correlate with clinical history, suggesting the presence of a purulent exudate rather than serous effusion. Leukocyte esterase activity in the fluid appears to hold promise as an indicator for the presence of chronic middle ear infection. The enzyme can be assayed by a simple and fast diagnostic strip test, with results available almost immediately. C1 YESHIVA UNIV ALBERT EINSTEIN COLL MED,DEPT LAB MED,BRONX,NY 10461. RP LEBOVICS, RS (reprint author), NIDOCD,10-5N-226,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 6 TC 8 Z9 8 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD MAR PY 1993 VL 108 IS 3 BP 248 EP 250 PG 3 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA KU224 UT WOS:A1993KU22400007 PM 8464637 ER PT J AU PETRI, WA CLARK, CG BRAGA, LL MANN, BJ AF PETRI, WA CLARK, CG BRAGA, LL MANN, BJ TI INTERNATIONAL SEMINAR ON AMEBIASIS SO PARASITOLOGY TODAY LA English DT Editorial Material C1 NIH,BETHESDA,MD 20892. UNIV FED CEARA,BR-60000 FORTALEZA,CEARA,BRAZIL. RP PETRI, WA (reprint author), UNIV VIRGINIA,HLTH SCI CTR,DEPT MED,CHARLOTTESVILLE,VA 22908, USA. OI Clark, C Graham/0000-0002-0521-0977 NR 0 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0169-4758 J9 PARASITOL TODAY JI Parasitol. Today PD MAR PY 1993 VL 9 IS 3 BP 73 EP 76 DI 10.1016/0169-4758(93)90203-R PG 4 WC Parasitology SC Parasitology GA KP069 UT WOS:A1993KP06900001 ER PT J AU VOLLMER, G LIGHTNER, VA CARTER, CA SIEGAL, GP ERICKSON, HP KNUPPEN, R KAUFMAN, DG AF VOLLMER, G LIGHTNER, VA CARTER, CA SIEGAL, GP ERICKSON, HP KNUPPEN, R KAUFMAN, DG TI LOCALIZATION OF TENASCIN IN UTERINE SARCOMAS AND PARTIALLY TRANSFORMED ENDOMETRIAL STROMAL CELLS SO PATHOBIOLOGY LA English DT Article DE UTERINE STROMA; MESENCHYMAL MALIGNANCY; EXTRACELLULAR MATRIX; TENASCIN EXPRESSION; ONCOGENE TRANSFECTION; CARCINOGENESIS; CONFOCAL LASER SCANNING MICROSCOPY ID GROWTH FACTOR-BETA; EXTRACELLULAR-MATRIX; NEURAL CREST; MONOCLONAL-ANTIBODY; MAMMARY-GLAND; FIBRONECTIN; IDENTIFICATION; HEXABRACHION; EXPRESSION; PROTEIN AB Normal mesenchymal cells within developing embryonic organs and transformed stromal cells in organs undergoing spontaneous carcinogenesis have the capacity for normal or altered expression of the extracellular matrix glycoprotein tenascin (Tn). Mesenchymal cell constituents of normal adult organs show only a very limited tendency to deposit Tn in their extracellular matrix. In the present study, we investigated whether malignant human mesenchymal cells derived from uterine sarcomas or normal human endometrial stromal cells partially transformed via transfection with selected oncogenes have the capacity to produce and deposit Tn. We reached the following conclusions: (1) compared with normal endometrial tissues, uterine sarcomas show heterogeneous, but increased, immunoreactive staining patterns exclusively within the extracellular compartment, regardless of the histologic subtype of the tumor; (2) in vitro, all normal and transfected stromal cells and cell lines examined secreted Tn into the tissue culture medium; (3) this secretory ability was not translated into morphologic uniformity, since immunoreactivity detected by confocal laser scanning microscopy was observed in only selected cell populations; (4) also, the deposition and the incorporation of Tn depended upon the density of transfected cells, and (5) double-staining experiments revealed that Tn could always be localized in close proximity to fibronectin. In summary, the production of Tn is increased in most cases of human uterine sarcoma. The capacity of stromal cells to deposit Tn in a matrix-like structure in vitro, rather than increase production of Tn, is correlated with the degree of neoplastic progression. C1 DUKE UNIV,MED CTR,DEPT CELL BIOL,DURHAM,NC 27710. NIEHS,EXPTL CARCINOGENESIS & MUTAGENESIS BRANCH,RES TRIANGLE PK,NC 27709. UNIV ALABAMA,CTR COMPREHENS CANC,DEPT PATHOL,BIRMINGHAM,AL 35294. UNIV ALABAMA,CTR COMPREHENS CANC,DEPT CELL BIOL,BIRMINGHAM,AL 35294. UNIV ALABAMA,CTR COMPREHENS CANC,DEPT SURG,BIRMINGHAM,AL 35294. UNIV N CAROLINA,DEPT PATHOL,CHAPEL HILL,NC 27514. RP VOLLMER, G (reprint author), MED UNIV LUBECK,INST BIOCHEM ENDOKRINOL,RATZEBURGER ALLEE 160,W-2400 LUBECK,GERMANY. RI Siegal, Gene/A-8653-2009 FU NCI NIH HHS [CA 31733]; NIAMS NIH HHS [AR 38479]; NIEHS NIH HHS [ES 07017] NR 40 TC 7 Z9 7 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 1993 VL 61 IS 2 BP 67 EP 76 DI 10.1159/000163763 PG 10 WC Cell Biology; Pathology SC Cell Biology; Pathology GA LH783 UT WOS:A1993LH78300002 PM 7692874 ER PT J AU WHANGPENG, J AF WHANGPENG, J TI CYTOGENETICS OF ASKINS TUMOR - CRITICAL COMMENTARY SO PATHOLOGY RESEARCH AND PRACTICE LA English DT Letter RP WHANGPENG, J (reprint author), NCI,MED BRANCH,CYTOGENET ONCOL SECT,BLDG 10,ROOM 12N226,BETHESDA,MD 20892, USA. NR 1 TC 1 Z9 1 U1 0 U2 0 PU GUSTAV FISCHER VERLAG PI JENA PA VILLENGANG 2, D-07745 JENA, GERMANY SN 0344-0338 J9 PATHOL RES PRACT JI Pathol. Res. Pract. PD MAR PY 1993 VL 189 IS 2 BP 241 EP 242 PG 2 WC Pathology SC Pathology GA KY676 UT WOS:A1993KY67600025 ER PT J AU ALLENDE, M PIZZO, PA HOROWITZ, M PASS, HI WALSH, TJ AF ALLENDE, M PIZZO, PA HOROWITZ, M PASS, HI WALSH, TJ TI PULMONARY CRYPTOCOCCOSIS PRESENTING AS METASTASES IN CHILDREN WITH SARCOMAS SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Article DE CRYPTOCOCCOSIS (PULMONARY); SARCOMAS (METASTATIC); BIOPSY (LUNG); CRYPTOCOCCUS-NEOFORMANS ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; KETOCONAZOLE; INFECTION; MYCOSES C1 NCI,PEDIAT BRANCH,INFECT DIS SECT,BLDG 10,ROOM 13N-240,BETHESDA,MD 20892. NR 24 TC 13 Z9 14 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 1993 VL 12 IS 3 BP 240 EP 243 DI 10.1097/00006454-199303000-00014 PG 4 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA KQ953 UT WOS:A1993KQ95300013 PM 8451102 ER PT J AU HALL, CB GRANOFF, DM GROMISCH, DS HALSEY, NA KOHL, S MARCUSE, EK MARKS, MI NANKERVIS, GA PICKERING, LK SCOTT, GB STEELE, RW YOGEV, R PETER, G BART, KJ BROOME, C HARDEGREE, MC JACOBS, RF MACDONALD, NE ORENSTEIN, WA RABINOVICH, G AF HALL, CB GRANOFF, DM GROMISCH, DS HALSEY, NA KOHL, S MARCUSE, EK MARKS, MI NANKERVIS, GA PICKERING, LK SCOTT, GB STEELE, RW YOGEV, R PETER, G BART, KJ BROOME, C HARDEGREE, MC JACOBS, RF MACDONALD, NE ORENSTEIN, WA RABINOVICH, G TI THE USE OF ORAL ACYCLOVIR IN OTHERWISE HEALTHY-CHILDREN WITH VARICELLA SO PEDIATRICS LA English DT Article ID HERPES-SIMPLEX VIRUS; ZOSTER VIRUS; ANTIBODY-RESPONSE; CHICKENPOX; COMPLICATIONS; INFECTION; RESISTANT; THERAPY; IMPACT C1 CTR DIS CONTROL,ATLANTA,GA 30333. US FDA,WASHINGTON,DC 20204. NIH,BETHESDA,MD 20892. RI Steele, Russell/A-6075-2011 NR 22 TC 35 Z9 39 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 1993 VL 91 IS 3 BP 674 EP 676 PG 3 WC Pediatrics SC Pediatrics GA KP638 UT WOS:A1993KP63800034 ER PT J AU PENG, CK MIETUS, J HAUSDORFF, JM HAVLIN, S STANLEY, HE GOLDBERGER, AL AF PENG, CK MIETUS, J HAUSDORFF, JM HAVLIN, S STANLEY, HE GOLDBERGER, AL TI LONG-RANGE ANTICORRELATIONS AND NON-GAUSSIAN BEHAVIOR OF THE HEARTBEAT SO PHYSICAL REVIEW LETTERS LA English DT Article ID FLUCTUATION AB We find that the successive increments in the cardiac beat-to-beat intervals of healthy subjects display scale-invariant, long-range anticorrelations (up to 10(4) heart beats). Furthermore, we find that the histogram for the heartbeat intervals increments is well described by a Levy stable distribution. For a group of subjects with severe heart disease, we find that the distribution is unchanged, but the long-range correlations vanish. Therefore, the different scaling behavior in health and disease must relate to the underlying dynamics of the heartbeat. C1 BOSTON UNIV,DEPT PHYS,BOSTON,MA 02215. HARVARD UNIV,BETH ISRAEL HOSP,SCH MED,DIV CARDIOVASC,BOSTON,MA 02215. NIH,DIV COMP RES & TECHNOL,PHYS SCI LAB,BETHESDA,MD 20892. RP PENG, CK (reprint author), BOSTON UNIV,CTR POLYMER STUDIES,BOSTON,MA 02215, USA. RI Peng, Chung-Kang/E-1489-2011 OI Peng, Chung-Kang/0000-0003-3666-9833 NR 22 TC 681 Z9 687 U1 5 U2 23 PU AMERICAN PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 0031-9007 J9 PHYS REV LETT JI Phys. Rev. Lett. PD MAR 1 PY 1993 VL 70 IS 9 BP 1343 EP 1346 DI 10.1103/PhysRevLett.70.1343 PG 4 WC Physics, Multidisciplinary SC Physics GA KN887 UT WOS:A1993KN88700040 PM 10054352 ER PT J AU BELCHER, JD ELLISON, RC SHEPARD, WE BIGELOW, C WEBBER, LS WILMORE, JH PARCEL, GS ZUCKER, DM LUEPKER, RV AF BELCHER, JD ELLISON, RC SHEPARD, WE BIGELOW, C WEBBER, LS WILMORE, JH PARCEL, GS ZUCKER, DM LUEPKER, RV TI LIPID AND LIPOPROTEIN DISTRIBUTIONS IN CHILDREN BY ETHNIC-GROUP, GENDER, AND GEOGRAPHIC LOCATION - PRELIMINARY FINDINGS OF THE CHILD AND ADOLESCENT TRIAL FOR CARDIOVASCULAR HEALTH (CATCH) SO PREVENTIVE MEDICINE LA English DT Article ID BOGALUSA-HEART; BIRACIAL COMMUNITY; SCHOOL-CHILDREN; TRIGLYCERIDE LEVELS; PLASMA-CHOLESTEROL; SERUM-LIPIDS; RISK-FACTORS; MUSCATINE; TRACKING; WHITE C1 BOSTON UNIV,SCH MED,EVANS DEPT MED,PREVENT MED & EPIDEMIOL SECT,BOSTON,MA 02118. UNIV CALIF SAN DIEGO,DEPT PEDIAT,LA JOLLA,CA 92093. UNIV MASSACHUSETTS,SCH PUBL HLTH,AMHERST,MA 01003. LOUISIANA STATE UNIV,MED CTR,DEPT MED,NEW ORLEANS,LA 70112. UNIV TEXAS,DEPT KINESIOL & HLTH EDUC,AUSTIN,TX 78712. UNIV TEXAS,HLTH SCI CTR,CTR HLTH PROMOT RES & DEV,HOUSTON,TX 77225. NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,BIOSTAT RES BRANCH,BETHESDA,MD 20892. RP BELCHER, JD (reprint author), UNIV MINNESOTA,SCH PUBL HLTH,DIV EPIDEMIOL,1300 S 2ND ST,MINNEAPOLIS,MN 55054, USA. NR 19 TC 31 Z9 31 U1 2 U2 3 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0091-7435 J9 PREV MED JI Prev. Med. PD MAR PY 1993 VL 22 IS 2 BP 143 EP 153 DI 10.1006/pmed.1993.1012 PG 11 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA KY569 UT WOS:A1993KY56900001 PM 8512601 ER PT J AU OMICHINSKI, JG TRAINOR, C EVANS, T GRONENBORN, AM CLORE, GM FELSENFELD, G AF OMICHINSKI, JG TRAINOR, C EVANS, T GRONENBORN, AM CLORE, GM FELSENFELD, G TI A SMALL SINGLE-FINGER PEPTIDE FROM THE ERYTHROID TRANSCRIPTION FACTOR GATA-1 BINDS SPECIFICALLY TO DNA AS A ZINC OR IRON COMPLEX SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE ZINC FINGER; GLOBIN GENE REGULATION ID NITROGEN REGULATORY GENE; NUCLEAR-PROTEIN FACTORS; SACCHAROMYCES-CEREVISIAE; GLUCOCORTICOID RECEPTOR; GLOBIN PROMOTER; EXPRESSION; ACTIVATION; RUBREDOXIN; RESOLUTION; SEQUENCE AB Sequence-specific DNA binding has been demonstrated for a synthetic peptide comprising only one of the two ''finger''-like domains of the erythroid transcription factor GATA-1 (also termed Eryf-1, NF-E1, or GF-1). Quantitative analysis of gel-retardation assays yields a specific association constant of 1.2 x 10(8) M, compared with values of about 10(9) M for the full-length natural GATA-1 protein. By the use of peptides of various lengths, it was possible to delineate the smallest region necessary for specific binding. A single C-terminal finger of the double-finger motif is necessary but not sufficient for sequence-specific interaction. Basic amino acids located C-terminal to the finger (some more than 20 amino acids away) are also essential for tight binding. In addition to demonstrating that zinc is important for the formation of an active binding complex, we show that other ions, notably Fe2+, can fulfill this role. Our results make it clear that the GATA-1 metal binding motif is quite distinct from that found in the steroid hormone family and that GATA-1 is a member of a separate class of DNA binding proteins. C1 NIDDKD,MOLEC BIOL LAB,BETHESDA,MD 20892. RP OMICHINSKI, JG (reprint author), NIDDKD,CHEM PHYS LAB,BETHESDA,MD 20892, USA. RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 NR 41 TC 120 Z9 121 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 1 PY 1993 VL 90 IS 5 BP 1676 EP 1680 DI 10.1073/pnas.90.5.1676 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA KP979 UT WOS:A1993KP97900011 PM 8446581 ER PT J AU GHOSH, P TAN, TH RICE, NR SICA, A YOUNG, HA AF GHOSH, P TAN, TH RICE, NR SICA, A YOUNG, HA TI THE INTERLEUKIN-2 CD28-RESPONSIVE COMPLEX CONTAINS AT LEAST 3 MEMBERS OF THE NF KAPPA-B FAMILY - C-REL, P50, AND P65 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID T-CELL PROLIFERATION; LONG TERMINAL REPEAT; GENE-EXPRESSION; RESPONSE ELEMENT; MOLECULE CD28; ACTIVATION; ANTIGEN; TRANSCRIPTION; RECEPTOR; PATHWAY AB Optimal activation of T cells requires at least two signals. One signal can be delivered by the antigen-specific T-cell receptor, and the second signal is provided by the costimulatory molecule(s) delivered by the antigen-presenting cell. CD28 is a T-cell surface molecule and stimulation through this protein plays an important role in delivering the second activation signal. In this report, we show that in human peripheral blood T cells, CD28-mediated signal transduction involves the rel family proteins-c-Rel, p50, and p65. Treatment of peripheral blood T cells with phorbol 12-myristate 13-acetate (PMA) and anti-CD28 monoclonal antibody (mAb) results in augmentation of nuclear c-Rel, p50, and p65, and this augmentation can occur in the presence of the immunosupressant cyclosporin A. It is also shown in this report that, in response to PMA/anti-CD28 mAb or anti-CD3/anti-CD28 mAb, c-Rel, p50, and p65 are associated with CD28-responsive element present in the promoter of the human interleukin 2 gene. The functional significance of c-Rel involvement in the CD28-responsive complex is demonstrated by transient transfection analysis, where cotransfection of c-Rel augments the level of expression of a chloramphenicol acetyltransferase reporter gene linked to the CD28-responsive element. C1 NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES DYNCORP INC,MOLEC VIROL & CARCINOGENESIS LAB,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES DYNCORP INC,BIOL CARCINOGENESIS DEV PROGRAM,FREDERICK,MD 21702. RP GHOSH, P (reprint author), NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES DYNCORP INC,EXPTL IMMUNOL LAB,FREDERICK,MD 21702, USA. RI Tan, Tse-Hua/E-3983-2010 OI Tan, Tse-Hua/0000-0003-4969-3170 FU NCI NIH HHS [N01-CO-74101, N01-CO-74102] NR 33 TC 196 Z9 199 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 MAR 1 PY 1993 VL 90 IS 5 BP 1696 EP 1700 DI 10.1073/pnas.90.5.1696 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA KP979 UT WOS:A1993KP97900015 PM 8383323 ER PT J AU FELDER, CC MACARTHUR, L MA, AL GUSOVSKY, F KOHN, EC AF FELDER, CC MACARTHUR, L MA, AL GUSOVSKY, F KOHN, EC TI TUMOR-SUPPRESSOR FUNCTION OF MUSCARINIC ACETYLCHOLINE-RECEPTORS IS ASSOCIATED WITH ACTIVATION OF RECEPTOR-OPERATED CALCIUM INFLUX SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE SIGNAL TRANSDUCTION; TYROSINE KINASE; CHO CELL; PHOSPHOLIPASE-A2; PHOSPHOLIPASE-D ID EPIDERMAL GROWTH-FACTOR; ARACHIDONIC-ACID; TYROSINE PHOSPHORYLATION; SIGNAL TRANSDUCTION; CA2+ INFLUX; 3T3 CELLS; PROTEIN; KINASE; EXPRESSION; ONCOGENES AB Several members of the family of guanine nucleotide-binding protein (G protein)-coupled receptors have recently been shown to induce agonist-dependent foci development in NIH 3T3 cells and tumors in nude mice. We selected the five subtypes of the muscarinic acetylcholine receptor family to investigate their role in tumor suppression. When transfected and expressed in CHO-K1 Chinese hamster ovary cells, m1, m3, and m5 muscarinic acetylcholine receptor activation resulted in a morphology change. Receptor activation did not slow or inhibit monolayer growth of CHOm5 cells in culture but markedly inhibited density-independent growth in soft agar and suppressed tumor formation in nude mice. Receptor-mediated tumor suppression was found to be agonist-dependent and reversible and was blocked with a muscarinic receptor antagonist. Of the five signaling pathways associated with the m1, m3, and m5 receptors, only receptor-operated, and inositol trisphosphate-independent, calcium influx was found to correlate with inhibition of tumorigenicity. These data suggest a pivotal role for inositol trisphosphate-independent receptor-regulated calcium homeostasis in CHO-K1 tumor suppression. C1 NCI,MED BRANCH,BETHESDA,MD 20892. NCI,PATHOL LAB,BETHESDA,MD 20892. NIDDKD,BIOORGAN CHEM LAB,BETHESDA,MD 20892. RP FELDER, CC (reprint author), NIMH,CELL BIOL LAB,BLDG 36,ROOM 3A-15,BETHESDA,MD 20892, USA. NR 30 TC 50 Z9 53 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 MAR 1 PY 1993 VL 90 IS 5 BP 1706 EP 1710 DI 10.1073/pnas.90.5.1706 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA KP979 UT WOS:A1993KP97900017 PM 7680475 ER PT J AU BUKH, J MILLER, RH KEW, MC PURCELL, RH AF BUKH, J MILLER, RH KEW, MC PURCELL, RH TI HEPATITIS-C VIRUS-RNA IN SOUTHERN AFRICAN BLACKS WITH HEPATOCELLULAR-CARCINOMA SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE NON-A; NON-B-HEPATITIS; CHRONIC HEPATITIS; POLYMERASE CHAIN REACTION ID NON-B-HEPATITIS; POLYMERASE CHAIN-REACTION; POST-TRANSFUSION HEPATITIS; NON-A-HEPATITIS; ITALIAN PATIENTS; VIRAL-HEPATITIS; UNITED-STATES; ANTIBODIES; PREVALENCE; INFECTION AB We used a sensitive and specific cDNA polymerase chain reaction assay to detect hepatitis C virus (HCV) RNA in serum samples from 128 unselected southern African Blacks with hepatocellular carcinoma (HCC) and found HCV RNA in 26 (20.3%) of these patients. Antibodies to HCV (anti-HCV) were detected in 59 patients (46.1%) with a first-generation ELISA test, and only 19 of these patients were HCV RNA-positive. Anti-HCV was detected in 25 patients (19.5%) with a second-generation ELISA test, and 17 of these patients were HCV RNA-positive. Among the second-generation ELISA- and HCV RNA-positive patients, 14 were anti-HCV positive, 2 were indeterminate, and 1 was anti-HCV negative in a second-generation recombinant immunoblot assay, whereas all patients who were second-generation ELISA positive, but HCV RNA negative, were anti-HCV negative in this immunoblot assay. A total of 5 patients were negative in both ELISA tests but were HCV RNA positive. Seventy-one patients (55.5%) had evidence of a current HBV infection, 50 (39.1%) had evidence of a previous infection, and 7 (5.5%) had no evidence of a current or previous HBV infection. The prevalence of current HBV infection was significantly lower in patients who were positive for HCV RNA than in those who were negative (P = 0.001). This difference was not dependent on sex, age, or geographical location of the patients. The mean age of HCC patients positive for HCV RNA (52.3 years) was significantly higher (P < 0.001) than that of negative patients (40.3 years), and the difference was not dependent on HBV status or geographical location, Patients positive for HCV RNA were more likely to be urban than were negative patients. Thus, a significant number of southern African Blacks with HCC had a current HCV infection but not a current HBV infection, further suggesting that infection with HCV plays a role, albeit minor. in the development of HCC in this population. C1 UNIV WITWATERSRAND,DEPT MED,JOHANNESBURG 2001,SOUTH AFRICA. RP BUKH, J (reprint author), NIAID,INFECT DIS LAB,HEPATITIS VIRUSES SECT,BETHESDA,MD 20892, USA. FU NIAID NIH HHS [N01-AI72623] NR 45 TC 71 Z9 70 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 MAR 1 PY 1993 VL 90 IS 5 BP 1848 EP 1851 DI 10.1073/pnas.90.5.1848 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA KP979 UT WOS:A1993KP97900046 PM 8383330 ER PT J AU GRANT, DS KLEINMAN, HK GOLDBERG, ID BHARGAVA, MM NICKOLOFF, BJ KINSELLA, JL POLVERINI, P ROSEN, EM AF GRANT, DS KLEINMAN, HK GOLDBERG, ID BHARGAVA, MM NICKOLOFF, BJ KINSELLA, JL POLVERINI, P ROSEN, EM TI SCATTER FACTOR INDUCES BLOOD-VESSEL FORMATION INVIVO SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE HEPATOCYTE GROWTH FACTOR; ANGIOGENESIS; ENDOTHELIUM; PSORIASIS; PLASMINOGEN ACTIVATOR ID HEPATOCYTE GROWTH-FACTOR; INTERLEUKIN-6 GENE-EXPRESSION; HUMAN-ENDOTHELIAL CELLS; TUMOR NECROSIS FACTOR; EXTRACELLULAR-MATRIX; MOLECULAR-CLONING; EPITHELIAL-CELLS; FACTOR-BETA; INVITRO; ANGIOGENESIS AB Scatter factor (also known as hepatocyte growth factor) is a glycoprotein secreted by stromal cells that stimulates cell motility and proliferation. In vitro, scatter factor stimulates vascular endothelial cell migration, proliferation, and organization into capillary-like tubes. Using two different in vivo assays, we showed that physiologic quantities of purified native mouse scatter factor and recombinant human hepatocyte growth factor induce angiogenesis (the formation of new blood vessels). The angiogenic activity was blocked by specific anti-scatter factor antibodies. Scatter factor induced cultured microvascular endothelial cells to accumulate and secrete significantly increased quantities of urokinase, an enzyme associated with development of an invasive endothelial phenotype during angiogenesis. We further showed that immunoreactive scatter factor is present surrounding sites of blood vessel formation in psoriatic skin. These findings suggest that scatter factor may act as a paracrine mediator in pathologic angiogenesis associated with human inflammatory disease. C1 YALE UNIV, SCH MED,DEPT THERAPEUT RADIOL, HUNTER RADIAT THERAPY 132,333 CEDAR ST, NEW HAVEN, CT 06510 USA. NIDR, DEV BIOL LAB, BETHESDA, MD 20892 USA. LONG ISL JEWISH MED CTR, DEPT RADIAT ONCOL, NEW HYDE PK, NY 11042 USA. UNIV MICHIGAN, SCH MED, DEPT PATHOL, ANN ARBOR, MI 48109 USA. NIA, CARDIOVASC SCI LAB, BALTIMORE, MD 21224 USA. NORTHWESTERN UNIV, DEPT PATHOL, CHICAGO, IL 60611 USA. FU NCI NIH HHS [CA50516] NR 43 TC 615 Z9 636 U1 1 U2 6 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 1 PY 1993 VL 90 IS 5 BP 1937 EP 1941 DI 10.1073/pnas.90.5.1937 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA KP979 UT WOS:A1993KP97900064 PM 7680481 ER PT J AU CARSTEA, ED POLYMEROPOULOS, MH PARKER, CC DETERAWADLEIGH, SD ONEILL, RR PATTERSON, MC GOLDIN, E XIAO, H STRAUB, RE VANIER, MT BRADY, RO PENTCHEV, PG AF CARSTEA, ED POLYMEROPOULOS, MH PARKER, CC DETERAWADLEIGH, SD ONEILL, RR PATTERSON, MC GOLDIN, E XIAO, H STRAUB, RE VANIER, MT BRADY, RO PENTCHEV, PG TI LINKAGE OF NIEMANN-PICK DISEASE TYPE-C TO HUMAN CHROMOSOME-18 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID LOW-DENSITY LIPOPROTEIN; DEFECTIVE INTRACELLULAR MOBILIZATION; CHOLESTEROL STORAGE DISORDER; LYSOSOMAL ACCUMULATION; MOUSE MODEL; ESTERIFICATION; FIBROBLASTS; MICE; MUTANT AB We analyzed the involvement of chromosome 18 in Niemann-Pick disease type C (NPC), an autosomal recessive cholesterol-processing disorder. Within affected off-spring, the chromosome 18 parental contributions were identified by using allele-specific microsatellite markers. Significant linkage of NPC to an 18p genomic marker, D18S40, was indicated by a two-point lod score of 3.84. Analysis of meiotic chromosomal breakpoint patterns among the affected individuals indicated that the NPC gene is pericentromerically localized on human chromosome 18. C1 ST ELIZABETH HOSP,CTR NEUROSCI,NIMH,BIOCHEM GENET LAB,WASHINGTON,DC 20032. COLUMBIA UNIV,DEPT PSYCHIAT & GENET & DEV,NEW YORK,NY 10032. NIMH,CLIN NEUROGENET BRANCH,BETHESDA,MD 20892. LYONS SUD SCH MED,DEPT BIOCHEM,F-69921 OULLINS,FRANCE. RP CARSTEA, ED (reprint author), NINCDS,DEV & METAB NEUROL BRANCH,BETHESDA,MD 20892, USA. OI Patterson, Marc/0000-0002-1116-126X NR 26 TC 87 Z9 89 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 1 PY 1993 VL 90 IS 5 BP 2002 EP 2004 DI 10.1073/pnas.90.5.2002 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA KP979 UT WOS:A1993KP97900077 PM 8446622 ER PT J AU PALUMBO, GJ GLASGOW, WC BULLER, RML AF PALUMBO, GJ GLASGOW, WC BULLER, RML TI POXVIRUS-INDUCED ALTERATION OF ARACHIDONATE METABOLISM SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE LIPOXYGENASE; CYCLOOXYGENASE; PROSTAGLANDIN; INFLAMMATION ID VIRUS GROWTH-FACTOR; PORCINE LEUKOCYTES; ACID METABOLISM; RELEASE; LEUKOTRIENES; INHIBITION; INFECTION; CELLS; PHOSPHOLIPASE-A2; PROSTAGLANDINS AB Recent evidence suggests that orthopoxviruses have an obligate requirement for arachidonic acid metabolites during replication in vivo and in vitro. Our report indicates that a virus family (Poxviridae) possesses multiple genes that function to regulate arachidonate metabolism. Analyses of BS-C-1 cells infected with cowpox virus or vaccinia virus detected enhanced arachidonate product formation from both the cyclooxygenase (specifically prostaglandins E2 and F2alpha) and lipoxygenase (specifically 15-hydroxyeicosatetraenoic acid and 12-hydroxyeicosatetraenoic acid) pathways. In contrast, human parainfluenza type 3 or herpes simplex virus type 1 infections did not increase arachidonate metabolism. Results were consistent with a virus early-gene product either directly mediating or inducing a host factor that mediated the upregulation of arachidonate metabolism, although vaccinia growth factor was not responsible. In addition, the cowpox virus 38-kDa protein-encoding gene, which is associated with inhibition of an inflammatory response, correlated with inhibition of formation of a product biochemically characteristic of (14R,15S)-dihydroxyeicosatetraenoic acid. We propose that orthopoxvirus-induced up-regulation of arachidonic acid metabolism during infection renders the infected cells susceptible to generation of inflammatory mediators from both the cyclooxygenase and the lipoxygenase pathways, and poxviruses, therefore, possess at least one gene (38K) that can alter the lipoxygenase-metabolite spectrum. C1 NIEHS, MOLEC BIOPHYS LAB, RES TRIANGLE PK, NC 27709 USA. RP PALUMBO, GJ (reprint author), NIAID, VIRAL DIS LAB, BETHESDA, MD 20892 USA. NR 38 TC 37 Z9 37 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 1 PY 1993 VL 90 IS 5 BP 2020 EP 2024 DI 10.1073/pnas.90.5.2020 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA KP979 UT WOS:A1993KP97900081 PM 8383332 ER PT J AU DEGRASSI, A HILBERT, DM RUDIKOFF, S ANDERSON, AO POTTER, M COON, HG AF DEGRASSI, A HILBERT, DM RUDIKOFF, S ANDERSON, AO POTTER, M COON, HG TI INVITRO CULTURE OF PRIMARY PLASMACYTOMAS REQUIRES STROMAL CELL FEEDER LAYERS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE ADHESION; NEOPLASIA; PLASMA CELLS ID HUMAN MULTIPLE-MYELOMA; MONOCLONAL ANTIBODY; TISSUE-CULTURE; GROWTH; ESTABLISHMENT; LINES; INTERLEUKIN-6; MACROPHAGE; MOUSE; PROLIFERATION AB Attempts to grow primary murine plasmacytomas in vitro have, to date, been largely unsuccessful. In this study, we demonstrate that long-term in vitro growth of primary plasmacytomas is accomplished by using feeder layers composed of stromal cells from the initial site of plasmacytomagenesis. The early neoplastic lines established in this manner are dependent on physical contact with the stromal layer, which is mediated in part by CD44, for growth and survival. The stromal cells provide at least two stimuli for the plasma cells, one being interleukin 6 and the second, of unknown nature, resulting from direct physical interaction that cannot be replaced by soluble factors. These plasma cell lines have been passaged for as long as 20 months yet still maintain characteristics associated with primary plasmacytomas as they will grow in vivo only in pristane-primed animals, indicating a continued dependence on the pristane-induced microenvironment characteristic of early-stage tumors. The ability to grow primary plasmacytomas in culture and maintain their ''primary'' properties provides a model system for detailed analysis of early events in plasma cell tumor progression involving neoplastic cells completely dependent on physical contact with a stromal feeder layer for survival and expansion. C1 NCI,GENET LAB,BLDG 37,ROOM 2B15,BETHESDA,MD 20892. USA,MED RES INST INFECT DIS,FREDERICK,MD 21701. NR 32 TC 60 Z9 61 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 MAR 1 PY 1993 VL 90 IS 5 BP 2060 EP 2064 DI 10.1073/pnas.90.5.2060 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA KP979 UT WOS:A1993KP97900089 PM 8446628 ER PT J AU PICKENS, RW BATTJES, R SVIKIS, DS GUPMAN, AE AF PICKENS, RW BATTJES, R SVIKIS, DS GUPMAN, AE TI SUBSTANCE USE RISK-FACTORS FOR HIV-INFECTION SO PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Article ID INTRAVENOUS-DRUG-USERS; HUMAN-IMMUNODEFICIENCY-VIRUS; SEXUAL-BEHAVIOR; COCAINE USE; ABUSERS; AIDS C1 NIDA,ROCKVILLE,MD. FRANCES SCOTT KEY MED CTR,BALTIMORE,MD. JOHNS HOPKINS UNIV,SCH MED,BALTIMORE,MD 21205. RP PICKENS, RW (reprint author), NIDA,ADDICT RES CTR,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. NR 30 TC 5 Z9 5 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0193-953X J9 PSYCHIAT CLIN N AM JI Psychiatr. Clin. North Amer. PD MAR PY 1993 VL 16 IS 1 BP 119 EP 125 PG 7 WC Psychiatry SC Psychiatry GA KZ893 UT WOS:A1993KZ89300012 PM 8456038 ER PT J AU GORELICK, DA AF GORELICK, DA TI OVERVIEW OF PHARMACOLOGICAL TREATMENT APPROACHES FOR ALCOHOL AND OTHER DRUG-ADDICTION - INTOXICATION, WITHDRAWAL, AND RELAPSE PREVENTION SO PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Article ID LONG-TERM USE; SMOKING-CESSATION; HEROIN-ADDICTS; COCAINE ABUSE; FOLLOW-UP; PLACEBO; CARBAMAZEPINE; DEPENDENCE; NICOTINE; THERAPY C1 UNIV MARYLAND,SCH MED,DEPT PSYCHIAT,BALTIMORE,MD 21201. RP GORELICK, DA (reprint author), NIDA,ADDICT RES CTR,TREATMENT BRANCH,4940 EASTERN AVE,BLDG C,BALTIMORE,MD 21224, USA. NR 68 TC 20 Z9 21 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0193-953X J9 PSYCHIAT CLIN N AM JI Psychiatr. Clin. North Amer. PD MAR PY 1993 VL 16 IS 1 BP 141 EP 156 PG 16 WC Psychiatry SC Psychiatry GA KZ893 UT WOS:A1993KZ89300014 PM 8456040 ER PT J AU LEIBENLUFT, E MOUL, DE SCHWARTZ, PJ MADDEN, PA WEHR, TA AF LEIBENLUFT, E MOUL, DE SCHWARTZ, PJ MADDEN, PA WEHR, TA TI A CLINICAL-TRIAL OF SLEEP-DEPRIVATION IN COMBINATION WITH ANTIDEPRESSANT MEDICATION SO PSYCHIATRY RESEARCH LA English DT Article DE AFFECTIVE DISORDER; THYROID STIMULATING HORMONE; TRIIODOTHYRONINE; PROLACTIN; CORTISOL ID THYROID-HORMONE CONCENTRATIONS; THYROTROPIN-RELEASING-HORMONE; DEPRESSED-PATIENTS; PLASMA CORTISOL; GROWTH-HORMONE; PROLACTIN; THERAPY; SECRETION; RADIOIMMUNOASSAY; PREDICTION AB The literature suggests that sleep deprivation can potentiate the effect of antidepressant medication in depressed patients. However, the clinical efficacy of sleep deprivation has not been demonstrated definitively, in part because it is difficult to design an adequate control condition. We conducted a trial of sleep deprivation in 26 depressed patients who remained symptomatic despite 3 months of treatment with antidepressant medication. Since the literature indicates that early sleep deprivation (ESD), carried out in the first half of the night, is a less effective antidepressant than late sleep deprivation (LSD), carried out in the second half of the night, we designed a study that attempted to use ESD as a control condition for LSD. Patients were randomly assigned to ESD or LSD, received a total of 4 nights of sleep deprivation over 2 weeks, and were followed in clinic for the 3 subsequent weeks. ESD proved to be as effective an antidepressant as LSD, with the overall sample showing a mild, but statistically significant, response. There was a significant correlation between patients' acute response at the time of the first course of sleep deprivation treatments and their improvement over the course of the study. There were significant changes in plasma levels of thyroid stimulating hormone, free triiodothyronine, prolactin, and cortisol measured at 8 a.m. before and after sleep deprivation, and in the followup period, but there were no significant correlations between changes in hormonal levels and either acute or chronic response to sleep deprivation. RP LEIBENLUFT, E (reprint author), NIMH,CLIN PSYCHOBIOL BRANCH,BLDG 10,RM 4S-239,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 40 TC 35 Z9 35 U1 0 U2 2 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD MAR PY 1993 VL 46 IS 3 BP 213 EP 227 DI 10.1016/0165-1781(93)90090-4 PG 15 WC Psychiatry SC Psychiatry GA LA134 UT WOS:A1993LA13400001 PM 8493292 ER PT J AU ANDERSON, DE AUSTIN, J HAYTHORNTHWAITE, JA AF ANDERSON, DE AUSTIN, J HAYTHORNTHWAITE, JA TI BLOOD-PRESSURE DURING SUSTAINED INHIBITORY BREATHING IN THE NATURAL-ENVIRONMENT SO PSYCHOPHYSIOLOGY LA English DT Article DE BLOOD PRESSURE; HEART RATE; RESPIRATION; CARDIOVASCULAR AMBULATORY MONITORING ID SALT SENSITIVITY; SLEEP-APNEA; VENTILATION; HYPERTENSION; EXERCISE; MONITOR AB Previous studies reported that breathing frequency of laboratory dogs decreased preceding the onset of an avoidance task and that this decrease was accompanied by increases in blood pressure and decreases in heart rate. Low frequency/normal tidal volume breathing has also been observed in ambulatory humans, but the cardiovascular concomitants of this inhibitory breathing pattern remain to be determined. The present study recorded blood pressure and heart rate in humans during periods of inhibitory breathing in the natural environment. Systolic and mean pressure were higher during inhibitory breathing than at other times, but no differences in diastolic pressure or heart rate were observed. Inhibitory breathing was differentially associated with the workplace and with social situations. Thus, major components of a physiological pattern that predisposes laboratory animals to sodium-sensitive experimental hypertension have now been observed to covary in ambulatory humans. Whether inhibitory breathing in the natural environment is a correlate or a cause of elevated blood pressure remains to be determined. RP ANDERSON, DE (reprint author), NIA,BIOBEHAV SCI LAB,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. NR 33 TC 10 Z9 10 U1 0 U2 0 PU SOC PSYCHOPHYSIOL RES PI WASHINGTON PA 1010 VERMONT AVE NW SUITE 1100, WASHINGTON, DC 20005 SN 0048-5772 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PD MAR PY 1993 VL 30 IS 2 BP 131 EP 137 DI 10.1111/j.1469-8986.1993.tb01726.x PG 7 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA KL222 UT WOS:A1993KL22200001 PM 8434076 ER PT J AU STEINER, H FRITZ, GK MRAZEK, D GONZALES, J JENSEN, P AF STEINER, H FRITZ, GK MRAZEK, D GONZALES, J JENSEN, P TI PEDIATRIC AND PSYCHIATRIC COMORBIDITY .1. THE FUTURE OF CONSULTATION-LIAISON PSYCHIATRY SO PSYCHOSOMATICS LA English DT Editorial Material ID DEPENDENT DIABETES-MELLITUS; CHILDREN; ILLNESS C1 NIMH,DIV APPL & SERV RES,SERV RES BRANCH,BETHESDA,MD 20892. NIMH,DIV APPL & SERV RES,ADOLESCENT DISORDERS BRANCH,BETHESDA,MD 20892. CHILDRENS HOSP,NATL MED CTR,DEPT PSYCHIAT,WASHINGTON,DC 20010. GEORGE WASHINGTON UNIV,SCH MED,DEPT PSYCHIAT,WASHINGTON,DC 20052. GEORGE WASHINGTON UNIV,SCH MED,DEPT PEDIAT,WASHINGTON,DC 20052. BROWN UNIV,DEPT PEDIAT PSYCHIAT,PROVIDENCE,RI 02912. STANFORD UNIV,PACKARD CHILDRENS HOSP,DEPT PEDIAT PSYCHIAT,PALO ALTO,CA 94304. STANFORD UNIV,PACKARD CHILDRENS HOSP,DIV CHILD PSYCHIAT,PALO ALTO,CA 94304. NR 7 TC 7 Z9 7 U1 0 U2 0 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD MAR-APR PY 1993 VL 34 IS 2 BP 107 EP 111 PG 5 WC Psychiatry; Psychology SC Psychiatry; Psychology GA KP461 UT WOS:A1993KP46100001 PM 8456151 ER PT J AU NOBLE, JA CACES, MF STEFFENS, RA STINSON, FS AF NOBLE, JA CACES, MF STEFFENS, RA STINSON, FS TI CIRRHOSIS HOSPITALIZATION AND MORTALITY TRENDS, 1970-87 SO PUBLIC HEALTH REPORTS LA English DT Article ID DRINKING AB The decline in cirrhosis mortality in recent years in light of increases in cirrhosis morbidity, as reflected in hospital discharge data, is examined. Although there does not appear to be a single explanation for the decline in mortality, it is suggested that increased identification and treatment, as measured by substantial increases in the rates of hospitalization involving cirrhosis, may be a contributing factor. If, as suggested by hospitalization data that indicate a decreasing proportion of patients with cirrhosis die during their hospital stay, a major portion of the increase in cirrhosis admissions was for patients with less severe cases, these patients would be more responsive to treatment and would have a relatively better prognosis. The identification of contributing factors that may be responsible for the decline in cirrhosis mortality can provide support for the continuation of early diagnosis and treatment in already identified populations. The same kind of support can be extended to other population subgroups that have yet to show the same decline in cirrhosis mortality. C1 CYGNUS CORP,WASHINGTON,DC. CSR INC,WASHINGTON,DC. RP NOBLE, JA (reprint author), NIAAA,DIV BIOMETRY & EPIDEMIOL,PARKLAWN BLDG ROOM 14C-26,5600 FISHERS LANE,ROCKVILLE,MD 20857, USA. NR 22 TC 19 Z9 19 U1 0 U2 1 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPT OF DOCUMENTS, WASHINGTON, DC 20402-9325 SN 0033-3549 J9 PUBLIC HEALTH REP JI Public Health Rep. PD MAR-APR PY 1993 VL 108 IS 2 BP 192 EP 197 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA KW841 UT WOS:A1993KW84100008 PM 8464975 ER PT J AU MILLER, DL AF MILLER, DL TI IN TRANSIT SO RADIOLOGY LA English DT Editorial Material DE ANGIOGRAPHY, CONTRAST MEDIA; ANIMALS; EDITORIALS; CONTRAST MEDIA, EXPERIMENTAL STUDIES; CONTRAST MEDIA, FATTY ACID; LIVER, BLOOD SUPPLY; LIVER NEOPLASMS, CHEMOTHERAPEUTIC INFUSION; LIVER NEOPLASMS, DIAGNOSIS ID HEPATIC-ARTERY INJECTION; HEPATOCELLULAR-CARCINOMA; IODIZED OIL; I-131-LABELED LIPIODOL; LIVER METASTASES; GELATIN SPONGE; PORTAL-VEIN; CANCER; DRUG; CHEMOEMBOLIZATION RP MILLER, DL (reprint author), NIH,WARREN GRANT MAGNUSON CLIN CTR,DEPT DIAGNOST RADIOL,BLDG 10,BETHESDA,MD 20892, USA. NR 19 TC 5 Z9 5 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 1993 VL 186 IS 3 BP 633 EP 634 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA KN053 UT WOS:A1993KN05300004 PM 8381549 ER PT J AU DAVIDSON, AJ HAYES, WS HARTMAN, DS MCCARTHY, WF DAVIS, CJ AF DAVIDSON, AJ HAYES, WS HARTMAN, DS MCCARTHY, WF DAVIS, CJ TI RENAL ONCOCYTOMA AND CARCINOMA - FAILURE OF DIFFERENTIATION WITH CT SO RADIOLOGY LA English DT Article DE KIDNEY NEOPLASMS; KIDNEY NEOPLASMS, DIAGNOSIS; ONCOCYTOMA ID CELL CARCINOMA; NEOPLASMS; FEATURES; DIAGNOSIS; TUMOR AB The authors studied the hypothesis that oncocytoma and adenocarcinoma of the kidney can be differentiated with computed tomographic (CT) criteria and that differences would become more apparent as tumors enlarged. On contrast material-enhanced scans, homogeneous attenuation throughout the tumor and a central, sharply marginated, stellate area of low attenuation were considered predictors of oncocytoma. Any area of decreased attenuation in the tumor except for a stellate, central area was used as a predictor of adenocarcinoma. Among oncocytomas larger than 3 cm in diameter, 67% exhibited the criteria for oncocytoma and 33% met the criterion for adenocarcinoma; among smaller oncocytomas, the respective results were 82% and 18%. Among adenocarcinomas larger than 3 cm in diameter, 84% fulfilled the criterion for malignancy and 16% were incorrectly predicted to be oncocytomas; among smaller adenocarcinomas, the respective results were 58% and 42%. The authors conclude that the CT criteria used are poor predictors of the diagnosis of oncocytoma or adenocarcinoma regardless of tumor size. C1 USAF,INST PATHOL,DEPT BIOSTAT & EPIDEMIOL,WASHINGTON,DC 20306. USAF,INST PATHOL,DEPT GENITOURINARY PATHOL,WASHINGTON,DC 20306. JOHNS HOPKINS UNIV,DEPT RADIOL,BALTIMORE,MD 21218. JOHNS HOPKINS UNIV,CTR RADIOL SCI,BALTIMORE,MD 21218. NIH,CTR CLIN,DEPT RADIOL,BETHESDA,MD 20892. PENN STATE UNIV,MILTON S HERSHEY MED CTR,DEPT RADIOL,HERSHEY,PA 17033. RP DAVIDSON, AJ (reprint author), USAF,INST PATHOL,DEPT RADIOL PATHOL,ALASKA AVE & FERN ST,WASHINGTON,DC 20306, USA. NR 20 TC 76 Z9 86 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 1993 VL 186 IS 3 BP 693 EP 696 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA KN053 UT WOS:A1993KN05300016 PM 8430176 ER PT J AU KNUTTEL, A SCHMITT, JM BARNES, R KNUTSON, JR AF KNUTTEL, A SCHMITT, JM BARNES, R KNUTSON, JR TI ACOUSTOOPTIC SCANNING AND INTERFERING PHOTON DENSITY WAVES FOR PRECISE LOCALIZATION OF AN ABSORBING (OR FLUORESCENT) BODY IN A TURBID MEDIUM SO REVIEW OF SCIENTIFIC INSTRUMENTS LA English DT Article ID TIME; MODEL AB In most optical methods proposed for imaging an absorbing object embedded in a turbid medium, data are collected using a single source and detector scanned mechanically across the surface of the medium. In our setup, we exploited destructive interference of diffusive photon density waves originating from two sources to localize an absorbing (or fluorescent) body in a scattering medium. A frequency-domain instrumentation is described that scans several laser-beam spots across the surface of a turbid medium using 1D (or 2D) acousto-optical deflectors. An additional acousto-optic deflector is used to establish arbitrary phase shifts for the interfering photon-density waves. A destructive interference pattern was created to laterally localize an absorbing (or fluorescent) body in the reflection and transmission modes. In some experiments the destructive interference pattern was altered by modulating the individual beam intensities to improve sensitivity and ameliorate surface texture problems. The experimental results were retrieved from a gated intensified CCD camera at 246 MHz modulation frequency. Results indicate that less than a 1 mm displacement of a small object embedded 10 mm in a medium with optical characteristics similar to bloodless skin tissue can be detected. C1 NIH,NATL CTR RES RESOURCES,BIOMED ENGN & INSTRUMENTAT PROGRAM,BETHESDA,MD 20892. NHLBI,CELL BIOL LAB,BETHESDA,MD 20892. RP KNUTTEL, A (reprint author), NHLBI,CARDIAC ENERGET LAB,BETHESDA,MD 20892, USA. NR 19 TC 26 Z9 26 U1 0 U2 2 PU AMER INST PHYSICS PI WOODBURY PA CIRCULATION FULFILLMENT DIV, 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2999 SN 0034-6748 J9 REV SCI INSTRUM JI Rev. Sci. Instrum. PD MAR PY 1993 VL 64 IS 3 BP 638 EP 644 PG 7 WC Instruments & Instrumentation; Physics, Applied SC Instruments & Instrumentation; Physics GA KT534 UT WOS:A1993KT53400007 ER PT J AU RHIM, JS THRAVES, P DRITSCHILO, A KUETTEL, MR LEE, MS AF RHIM, JS THRAVES, P DRITSCHILO, A KUETTEL, MR LEE, MS TI RADIATION-INDUCED NEOPLASTIC TRANSFORMATION OF HUMAN-CELLS SO SCANNING MICROSCOPY LA English DT Article DE RADIATION; TRANSFORMATION; HUMAN CELLS ID CO-60 GAMMA-RAYS; HUMAN EPIDERMAL-KERATINOCYTES; NORMAL HUMAN-FIBROBLASTS; TUMORIGENICITY ASSAY; IONIZING-RADIATION; MAMMALIAN-CELLS; SARCOMA-VIRUSES; RAS ONCOGENES; GENES; INVITRO AB Ionizing radiation can induce cancers in humans and animals and can cause in vitro neoplastic transformation of various rodent cell systems. However, numerous attempts to achieve neoplastic transformation of human cells by radiation have generally proven unsuccessful. Neoplastic transformation of immortalized human epidermal keratinocytes by X-ray irradiation has recently been reported. The carcinogenic effect of radiation on cultured human cells will be briefly reviewed. The current state-of-the-art in radiation-induced transformation of human cells in culture is presented. This will provide insight into the molecular and cellular mechanisms in the conversion of normal cells to a neoplastic state of growth. C1 GEORGETOWN UNIV, SCH MED, DEPT RADIAT MED, WASHINGTON, DC 20007 USA. RP NCI, CELLULAR & MOLEC BIOL LAB, BLDG 37, ROOM 1E24, BETHESDA, MD 20892 USA. NR 45 TC 4 Z9 6 U1 0 U2 0 PU SCANNING MICROSCOPY INT PI CHICAGO PA PO BOX 66507, AMF O'HARE, CHICAGO, IL 60666 USA SN 0891-7035 J9 SCANNING MICROSCOPY JI Scanning Microsc. PD MAR PY 1993 VL 7 IS 1 BP 209 EP 216 PG 8 WC Microscopy SC Microscopy GA LA654 UT WOS:A1993LA65400022 PM 8316792 ER PT J AU TORREY, EF RAGLAND, JD GOLD, JM GOLDBERG, TE BOWLER, AE BIGELOW, LB GOTTESMAN, II AF TORREY, EF RAGLAND, JD GOLD, JM GOLDBERG, TE BOWLER, AE BIGELOW, LB GOTTESMAN, II TI HANDEDNESS IN TWINS WITH SCHIZOPHRENIA - WAS BOKLAGE CORRECT SO SCHIZOPHRENIA RESEARCH LA English DT Note DE HANDEDNESS; LATERALITY; TWINS; (SCHIZOPHRENIA) ID LATERALITY; PREFERENCE AB Boklage's report of increased non-right handedness among monozygotic twins with schizophrenia has been cited as evidence to support an association of abnormal brain lateralization with the development of schizophrenia. The present study found no such association. Two previous attempts to replicate Boklage's findings (Luchins et al. 1980; Lewis et al. 1989) also reported little support. Studies of twin handedness do not appear to support an association of brain lateralization and schizophrenia. C1 ST ELIZABETH HOSP,NIMH,NEUROPSYCHIAT RES CTR,WASHINGTON,DC 20032. UNIV PENN,DEPT PSYCHIAT,PHILADELPHIA,PA 19104. UNIV VIRGINIA,DEPT PSYCHOL,CHARLOTTESVILLE,VA 22903. RI G, I/D-8042-2011 NR 15 TC 9 Z9 9 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAR PY 1993 VL 9 IS 1 BP 83 EP 85 PG 3 WC Psychiatry SC Psychiatry GA KR865 UT WOS:A1993KR86500013 PM 8461274 ER PT J AU KUSEK, JW AGODOA, LY JONES, CA AF KUSEK, JW AGODOA, LY JONES, CA TI MORBIDITY AND MORTALITY AMONG HEMODIALYSIS-PATIENTS - A PLAN FOR ACTION SO SEMINARS IN DIALYSIS LA English DT Editorial Material RP KUSEK, JW (reprint author), NIDDK,DIV KIDNEY DIS,ROOM 3A04,5333 WESTBARD AVE,BETHESDA,MD 20892, USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0894-0959 J9 SEMIN DIALYSIS JI Semin. Dial. PD MAR-APR PY 1993 VL 6 IS 2 BP 81 EP 83 DI 10.1111/j.1525-139X.1993.tb00263.x PG 3 WC Urology & Nephrology SC Urology & Nephrology GA KU801 UT WOS:A1993KU80100001 ER PT J AU KNEPPER, MA SANDS, JM AF KNEPPER, MA SANDS, JM TI UPDATE IN PHYSIOLOGY .3. INTRODUCTION SO SEMINARS IN NEPHROLOGY LA English DT Editorial Material C1 DUKE UNIV,DEPT MATH,DURHAM,NC 27706. ROYAL PRINCE ALFRED HOSP,DEPT RENAL MED,CAMPERDOWN,NSW 2050,AUSTRALIA. EMORY UNIV,SCH MED,DEPT MED,DIV RENAL,ATLANTA,GA 30322. RP KNEPPER, MA (reprint author), NHLBI,KIDNEY & ELECTROLYTE METAB LAB,BLDG 10,ROOM 6N307,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9295 J9 SEMIN NEPHROL JI Semin. Nephrol. PD MAR PY 1993 VL 13 IS 2 BP 145 EP 145 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA KR899 UT WOS:A1993KR89900001 ER PT J AU CHOU, CL KNEPPER, MA LAYTON, HE AF CHOU, CL KNEPPER, MA LAYTON, HE TI URINARY CONCENTRATING MECHANISM - THE ROLE OF THE INNER MEDULLA SO SEMINARS IN NEPHROLOGY LA English DT Article ID THICK ASCENDING LIMB; CENTRAL CORE MODEL; COLLECTING DUCT; WATER TRANSPORT; DESCENDING-LIMB; HENLES LOOP; SODIUM-CHLORIDE; UREA TRANSPORT; COUNTERFLOW SYSTEM; MATHEMATICAL-MODEL C1 DUKE UNIV,DEPT MATH,DURHAM,NC 27706. RP CHOU, CL (reprint author), NHLBI,KIDNEY & ELECTROLYTE METAB LAB,BLDG 10,ROOM 6N307,BETHESDA,MD 20892, USA. NR 72 TC 9 Z9 9 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9295 J9 SEMIN NEPHROL JI Semin. Nephrol. PD MAR PY 1993 VL 13 IS 2 BP 168 EP 181 PG 14 WC Urology & Nephrology SC Urology & Nephrology GA KR899 UT WOS:A1993KR89900004 PM 8465117 ER PT J AU GARCIAPEREZ, A AF GARCIAPEREZ, A TI ORGANIC OSMOLYTES IN THE KIDNEY SO SEMINARS IN NEPHROLOGY LA English DT Article ID RENAL MEDULLARY CELLS; PAPILLARY EPITHELIAL-CELLS; HIGH EXTRACELLULAR NACL; ALDOSE REDUCTASE; INNER MEDULLA; OSMOTIC REGULATION; XENOPUS-OOCYTES; MDCK CELLS; RAT; SORBITOL RP GARCIAPEREZ, A (reprint author), NHLBI,KIDNEY & ELECTROLYTE METAB LAB,BLDG 10,ROOM 6N307,BETHESDA,MD 20892, USA. NR 58 TC 6 Z9 6 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9295 J9 SEMIN NEPHROL JI Semin. Nephrol. PD MAR PY 1993 VL 13 IS 2 BP 182 EP 190 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA KR899 UT WOS:A1993KR89900005 PM 8465118 ER PT J AU WITTES, RE AF WITTES, RE TI SMALL-CELL LUNG-CANCER - AN OVERVIEW OF ISSUES IN THERAPY SO SEMINARS IN SURGICAL ONCOLOGY LA English DT Article DE MULTIDRUG CHEMOTHERAPY; MYCLOID GROWTH FACTORS; RADIOTHERAPY; CRANIAL IRRADIATION; SURGERY AB As one of the few chemo- and radiosensitive neoplasms among the common epithelial solid tumors of adults, small-cell lung cancer has long tantalized clinical investigators. Although for the last 15-20 years therapy has yielded high remission rates, including substantial complete remission rates, results have not improved very much over nearly two decades of intensive therapeutic research, and long-term disease-free survival remains an elusive goal for the large majority of patients. At this point the number of promising untested hypotheses in therapy is quite small, and major advances will probably have to await either the serendipitous discovery of much more active drugs than we now possess, or else the purposeful development of new approaches based on insights into the nature of the transformed state and the biology of SCLC itself. RP WITTES, RE (reprint author), NCI,MED BRANCH,BLDG 10,RM 12 N 228,BETHESDA,MD 20892, USA. NR 0 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 8756-0437 J9 SEMIN SURG ONCOL JI Semin. Surg. Oncol. PD MAR-APR PY 1993 VL 9 IS 2 BP 127 EP 134 DI 10.1002/ssu.2980090211 PG 8 WC Oncology; Surgery SC Oncology; Surgery GA KT070 UT WOS:A1993KT07000010 PM 8387690 ER PT J AU POGREBNIAK, HW PASS, HI AF POGREBNIAK, HW PASS, HI TI INITIAL AND REOPERATIVE PULMONARY METASTASECTOMY - INDICATIONS, TECHNIQUE, AND RESULTS SO SEMINARS IN SURGICAL ONCOLOGY LA English DT Article DE LUNG; MALIGNANCY; STERNOTOMY; RESECTION AB The ability to predict which patients will derive a survival benefit from pulmonary metastasectomy is limited. Most patients remain asymptomatic until the disease becomes advanced, and therefore computerized tomography (CT) of the chest has become the standard of care for follow-up of patients at risk for pulmonary metastases. The most important predictor of post-thoracotomy survival in patients at the National Cancer Institute with soft tissue, osteogenic, and pediatric sarcomas as well as melanoma and renal cell carcinoma has been the ability to render the patient disease-free. Tumor histology, disease-free interval, and possibly number of nodules are also determinants of survival. Median sternotomy is the preferred approach for initial and repeat metastasectomies and every effort should be made to preserve pulmonary parenchyma. Resection of pulmonary metastases has become an accepted therapeutic modality, but selection of surgical candidates, and operative planning needs to be individualized. C1 NCI,THORAC ONCOL SECT,SURG BRANCH,BLDG 10,ROOM 2B07,BETHESDA,MD 20892. NR 0 TC 24 Z9 24 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 8756-0437 J9 SEMIN SURG ONCOL JI Semin. Surg. Oncol. PD MAR-APR PY 1993 VL 9 IS 2 BP 142 EP 149 DI 10.1002/ssu.2980090213 PG 8 WC Oncology; Surgery SC Oncology; Surgery GA KT070 UT WOS:A1993KT07000012 PM 8488356 ER PT J AU DOYLE, M JOHNSTONE, PAS WATKINS, EB AF DOYLE, M JOHNSTONE, PAS WATKINS, EB TI ROLE OF RADIATION-THERAPY IN MANAGEMENT OF PULMONARY KAPOSIS-SARCOMA SO SOUTHERN MEDICAL JOURNAL LA English DT Article ID ACQUIRED IMMUNODEFICIENCY SYNDROME; VINBLASTINE; AIDS; CHEMOTHERAPY; VINCRISTINE; COMBINATION AB Although the incidence of AIDS-related Kaposi's sarcoma (KS) has been declining in recent years, the uncommon and unfortunate progression to symptomatic pulmonary KS still represents a significant therapeutic challenge. Pulmonary KS generally occurs in the late stages of the disease. Review of the literature and of the experience of the Walter Reed Army Medical Center Radiation Oncology Service suggests that early intervention with radiation therapy may provide palliation of the often distressing symptoms that herald KS-induced respiratory failure and may have a favorable impact on quality of life and survival time. C1 UNIFORMED SERV UNIV HLTH SCI, BETHESDA, MD 20814 USA. NCI, RADIAT ONCOL BRANCH, BETHESDA, MD 20892 USA. RP WALTER REED ARMY MED CTR, DEPT PSYCHIAT, RADIAT THERAPY SERV, WASHINGTON, DC 20307 USA. NR 19 TC 10 Z9 10 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0038-4348 EI 1541-8243 J9 SOUTH MED J JI South.Med.J. PD MAR PY 1993 VL 86 IS 3 BP 285 EP 288 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA KT726 UT WOS:A1993KT72600005 PM 7680826 ER PT J AU ELLENBERG, SS GELLER, N SIMON, R YUSUF, S AF ELLENBERG, SS GELLER, N SIMON, R YUSUF, S TI PROCEEDINGS OF PRACTICAL ISSUES IN DATA MONITORING OF CLINICAL-TRIALS, BETHESDA, MARYLAND, USA, 27-28 JANUARY 1992 SO STATISTICS IN MEDICINE LA English DT Editorial Material C1 NHLBI,BETHESDA,MD 20892. NCI,BETHESDA,MD 20892. RP ELLENBERG, SS (reprint author), NIAID,BETHESDA,MD 20892, USA. NR 0 TC 19 Z9 19 U1 0 U2 0 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 MAR PY 1993 VL 12 IS 5-6 BP 415 EP 415 DI 10.1002/sim.4780120502 PG 1 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 KX071 UT WOS:A1993KX07100001 ER PT J AU FRIEDMAN, L AF FRIEDMAN, L TI THE NHLBI MODEL - A 25 YEAR HISTORY SO STATISTICS IN MEDICINE LA English DT Article ID TRIAL AB Although newer techniques and procedures have been developed, many of the clinical trial design and monitoring concepts used today in the NHLBI were implemented 25 years ago. Among these are the organizational structure of multicentre trials and the use of an independent data monitoring committee. Examples of data monitoring committee discussions and decisions are provided. RP FRIEDMAN, L (reprint author), NHLBI, FED BLDG 5C01, BETHESDA, MD 20892 USA. NR 16 TC 12 Z9 12 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0277-6715 EI 1097-0258 J9 STAT MED JI Stat. Med. PD MAR PY 1993 VL 12 IS 5-6 BP 425 EP 431 DI 10.1002/sim.4780120505 PG 7 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 KX071 UT WOS:A1993KX07100004 PM 8493421 ER PT J AU HARRINGTON, D FRIEDMAN, L GENT, M MEIER, P FROMMER, P TEMPLE, R TOGNONI, G TAYLOR, W SIEBERT, C MONSEES, D AF HARRINGTON, D FRIEDMAN, L GENT, M MEIER, P FROMMER, P TEMPLE, R TOGNONI, G TAYLOR, W SIEBERT, C MONSEES, D TI BEHIND CLOSED DOORS, THE DATA MONITORING BOARD IN RANDOMIZED CLINICAL-TRIALS - THE NHLBI MODEL - A 25 YEAR HISTORY - DISCUSSION SO STATISTICS IN MEDICINE LA English DT Discussion RP FRIEDMAN, L (reprint author), NHLBI,FED BLDG 5C01,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0277-6715 J9 STAT MED JI Stat. Med. PD MAR PY 1993 VL 12 IS 5-6 BP 433 EP 434 PG 2 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 KX071 UT WOS:A1993KX07100005 ER PT J AU ELLENBERG, S CROWLEY, J MEINERT, C GEORGE, S POCOCK, S ARMITAGE, P SIMON, R YUSUF, S WITTES, J AF ELLENBERG, S CROWLEY, J MEINERT, C GEORGE, S POCOCK, S ARMITAGE, P SIMON, R YUSUF, S WITTES, J TI A SURVEY OF MONITORING PRACTICES IN CANCER CLINICAL-TRIALS - DATA MONITORING COMMITTEES FOR SOUTHWEST ONCOLOGY GROUP CLINICAL-TRIALS - DISCUSSION SO STATISTICS IN MEDICINE LA English DT Discussion C1 NIAID,DIV AIDS,BIOSTAT RES BRANCH,BETHESDA,MD 20892. FRED HUTCHINSON CANC RES CTR,SW ONCOL GRP,SEATTLE,WA 98104. DUKE UNIV,MED CTR,DIV BIOMETRY,DURHAM,NC 27710. NHLBI,BETHESDA,MD 20892. STAT COLLABORAT,WASHINGTON,DC 20036. NR 0 TC 1 Z9 1 U1 0 U2 2 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0277-6715 J9 STAT MED JI Stat. Med. PD MAR PY 1993 VL 12 IS 5-6 BP 457 EP 459 PG 3 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 KX071 UT WOS:A1993KX07100008 ER PT J AU ELLENBERG, SS MYERS, MW BLACKWELDER, WC HOTH, DF AF ELLENBERG, SS MYERS, MW BLACKWELDER, WC HOTH, DF TI THE USE OF EXTERNAL MONITORING COMMITTEES IN CLINICAL-TRIALS OF THE NATIONAL-INSTITUTE-OF-ALLERGY-AND-INFECTIOUS-DISEASES SO STATISTICS IN MEDICINE LA English DT Article ID HERPES-SIMPLEX ENCEPHALITIS; THERAPY AB Randomized clinical trials are being conducted and/or sponsored by all scientific divisions of the National Institute of Allergy and Infectious Diseases (NIAID). External committees to review the progress of ongoing trials and to make recommendations to the Institute concerning continuation or termination are an integral part of many of these trials. These committees have evolved considerably from the ad hoc committees, called together when a need arose, which were used beginning in the mid 1970s. Currently, there are many monitoring committees operating for NIAID-sponsored trials. They function in a variety of ways, based partially on historical precedent and partially on the specialized requirements of the particular trial; there is no 'standard operating procedure' for the Institute, or even for divisions within the Institute. One of the major issues faced in establishing the data and safety monitoring board for AIDS treatment trials was access to the meetings of this board and to the reports of interim data that the board reviewed. After much discussion, procedures were established that restrict such access to a very limited group of programme and statistical centre staff. These procedures, while remaining controversial, appear necessary to ensure confidentiality and the integrity of the clinical trials process. C1 NIAID,DIV AIDS,BIOSTAT RES BRANCH,BETHESDA,MD 20892. BOEHRINGER INGELHEIM PHARMACEUT INC,RIDGEFIELD,CT 06877. NIAID,DIV MICROBIOL & INFECT DIS,EPIDEMIOL & BIOMETRY BRANCH,BETHESDA,MD 20892. NR 11 TC 12 Z9 12 U1 0 U2 0 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 MAR PY 1993 VL 12 IS 5-6 BP 461 EP 467 DI 10.1002/sim.4780120510 PG 7 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 KX071 UT WOS:A1993KX07100009 PM 8493424 ER PT J AU TOGNONI ELLENBERG, S FINKELSTEIN, D MEINERT AF TOGNONI ELLENBERG, S FINKELSTEIN, D MEINERT TI THE USE OF EXTERNAL MONITORING COMMITTEES IN TRIALS OF INFECTIOUS-DISEASES - DISCUSSION SO STATISTICS IN MEDICINE LA English DT Discussion C1 NIAID,DIV AIDS,BIOSTAT RES BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAR PY 1993 VL 12 IS 5-6 BP 469 EP 469 PG 1 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 KX071 UT WOS:A1993KX07100010 ER PT J AU MEIER HARRINGTON ROCKHOLD, F WILLIAMS, G BROWN HERSON, J BUYSE, M DEYKIN, D YUSUF AF MEIER HARRINGTON ROCKHOLD, F WILLIAMS, G BROWN HERSON, J BUYSE, M DEYKIN, D YUSUF TI DATA MONITORING AND INTERIM ANALYSES IN THE PHARMACEUTICAL-INDUSTRY - ETHICAL AND LOGISTICAL CONSIDERATIONS - MONITORING OF CLINICAL-TRIALS AND INTERIM ANALYSES FROM A DRUG SPONSORS POINT-OF-VIEW - DISCUSSION SO STATISTICS IN MEDICINE LA English DT Discussion C1 SMITHKLINE BEECHAM PHARMACEUT,FOUR FALLS CORP CTR,ROUTE 23 & WOODMONT AVE,POB 1510,KING OF PRUSSIA,PA 19406. MERCK SHARP & DOHME LTD,BIOSTAT & RES DATA SYST,W POINT,PA 19486. APPL LOG ASSOCIATES INC,HOUSTON,TX 77005. INT INST DRUG DEV 1D2,B-1050 BRUSSELS,BELGIUM. NHLBI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0277-6715 J9 STAT MED JI Stat. Med. PD MAR PY 1993 VL 12 IS 5-6 BP 493 EP 495 PG 3 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 KX071 UT WOS:A1993KX07100013 ER PT J AU GREEN, S ONEILL, R DEMETS, D WITTES BUYSE MEIER BROWN POCOCK TEMPLE ARMITAGE YUSUF FRIEDEWALD, W MEINERT SIMON AF GREEN, S ONEILL, R DEMETS, D WITTES BUYSE MEIER BROWN POCOCK TEMPLE ARMITAGE YUSUF FRIEDEWALD, W MEINERT SIMON TI MONITORING CLINICAL-TRIALS - EXPERIENCE OF, AND PROPOSALS UNDER CONSIDERATION BY THE CANCER-THERAPY-COMMITTEE OF THE BRITISH-MEDICAL-RESEARCH-COUNCIL - THE USE OF DATA MONITORING COMMITTEES IN CANADIAN TRIAL GROUPS - INTERIM ANALYSES, STOPPING RULES AND DATA MONITORING IN CLINICAL-TRIALS IN EUROPE - DISCUSSION SO STATISTICS IN MEDICINE LA English DT Discussion C1 US FDA,CTR DRUG EVALUAT & RES,OFF EPIDEMIOL & BIOSTAT,PARKLAWN BLDG,ROCKVILLE,MD 20857. UNIV LONDON LONDON SCH HYG & TROP MED,MED STAT UNIT,LONDON WC1E 7HT,ENGLAND. STAT COLLABERAT,WASHINGTON,DC 20036. INT INST DRUG DEV,B-1050 BRUSSELS,BELGIUM. NCI,BIOMETR RES BRANCH,BETHESDA,MD 20892. NHLBI,BETHESDA,MD 20892. RI Friedewald, William/C-8034-2011 NR 0 TC 1 Z9 1 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0277-6715 J9 STAT MED JI Stat. Med. PD MAR PY 1993 VL 12 IS 5-6 BP 521 EP 525 PG 5 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 KX071 UT WOS:A1993KX07100017 ER PT J AU YUSUF WHITLEY, R ASSENZO, R FLEMING, T DEYKIN HAWKINS, B MEIER GENT TOGNONI ELLENBERG, J WITTES ARMITAGE MONSEES, D GREEN SIMON BOISSEL, JP BRISTOW, D MEINERT POCOCK WILLIAMS TOGNONI HARTMAN, A TEMPLE ASSENZO ELLENBERG, S GELLER, N TAYLOR, W BRISTOW PAPERMASTER, B ROCKHOLD DIXON, D AF YUSUF WHITLEY, R ASSENZO, R FLEMING, T DEYKIN HAWKINS, B MEIER GENT TOGNONI ELLENBERG, J WITTES ARMITAGE MONSEES, D GREEN SIMON BOISSEL, JP BRISTOW, D MEINERT POCOCK WILLIAMS TOGNONI HARTMAN, A TEMPLE ASSENZO ELLENBERG, S GELLER, N TAYLOR, W BRISTOW PAPERMASTER, B ROCKHOLD DIXON, D TI THE OPERATION OF DATA MONITORING COMMITTEES - DISCUSSION SO STATISTICS IN MEDICINE LA English DT Discussion C1 UNIV WASHINGTON,DEPT BIOSTAT,SEATTLE,WA 98195. STAT COLLABORAT,WASHINGTON,DC 20036. FRED HUTCHINSON CANC RES CTR,SW ONCOL GRP,SEATTLE,WA 98104. MERCK SHARP & DOHME LTD,BIOSTAT & RES DATA SYST,W POINT,PA 19486. US FDA,CBER,OELPS,DIV BIOSTAT & EPIDEMIOL,ROCKVILLE,MD 20892. NHLBI,BETHESDA,MD 20892. RP YUSUF (reprint author), NHLBI,BETHESDA,MD 20892, USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0277-6715 J9 STAT MED JI Stat. Med. PD MAR PY 1993 VL 12 IS 5-6 BP 527 EP 542 PG 16 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 KX071 UT WOS:A1993KX07100018 ER PT J AU GELLER, NL STYLIANOU, M AF GELLER, NL STYLIANOU, M TI PRACTICAL ISSUES IN DATA MONITORING OF CLINICAL-TRIALS - SUMMARY OF RESPONSES TO A QUESTIONNAIRE AT NIH SO STATISTICS IN MEDICINE LA English DT Article AB A targeted poll was undertaken to compare and contrast models of data monitoring of randomized clinical trials sponsored by the National Institutes of Health. In an attempt to represent the institutes which conduct clinical trials, twelve individuals were selected and asked to respond to a questionnaire specifically prepared for this workshop. The response rate was 100 per cent. Most of the large trials sponsored by the institutes have independent, formally constituted data monitoring committees. There was one institute which does not have any data monitoring committees. The questionnaire is described in detail and a summary of the results is given. RP GELLER, NL (reprint author), NHLBI,BIOSTAT RES BRANCH,7550 WISCONSIN AVE,BETHESDA,MD 20892, USA. NR 1 TC 9 Z9 9 U1 0 U2 0 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 MAR PY 1993 VL 12 IS 5-6 BP 543 EP 551 DI 10.1002/sim.4780120520 PG 9 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 KX071 UT WOS:A1993KX07100019 PM 8493430 ER PT J AU YUSUF, S MILTON, R GELLER MILTON AF YUSUF, S MILTON, R GELLER MILTON TI PRACTICAL ISSUES IN DATA MONITORING OF CLINICAL-TRIALS - SUMMARY OF RESPONSES TO A QUESTIONNAIRE AT NIH - DISCUSSION SO STATISTICS IN MEDICINE LA English DT Discussion RP YUSUF, S (reprint author), NHLBI,BETHESDA,MD 20892, USA. NR 0 TC 2 Z9 2 U1 0 U2 0 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 MAR PY 1993 VL 12 IS 5-6 BP 553 EP 553 PG 1 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 KX071 UT WOS:A1993KX07100020 ER PT J AU HARRINGTON, D FLEMING BUYSE, M BUYSE YUSUF LEE, YJ MEIER, P AF HARRINGTON, D FLEMING BUYSE, M BUYSE YUSUF LEE, YJ MEIER, P TI DATA MONITORING COMMITTEES AND CAPTURING RELEVANT INFORMATION OF HIGH-QUALITY - DISCUSSION SO STATISTICS IN MEDICINE LA English DT Discussion C1 UNIV WASHINGTON,DEPT BIOSTAT,SC-32,SEATTLE,WA 98195. INT INST DRUG DEV,B-1050 BRUSSELS,BELGIUM. NHLBI,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 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 MAR PY 1993 VL 12 IS 5-6 BP 571 EP 573 PG 3 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 KX071 UT WOS:A1993KX07100024 ER PT J AU MEIER WALTERS, L ARMITAGE, P GELLER AF MEIER WALTERS, L ARMITAGE, P GELLER TI DATA MONITORING COMMITTEES - THE MORAL CASE FOR MAXIMUM FEASIBLE INDEPENDENCE - DISCUSSION SO STATISTICS IN MEDICINE LA English DT Discussion C1 GEORGETOWN UNIV,KENNEDY INST ETH,WASHINGTON,DC 20057. GEORGETOWN UNIV,DEPT PHILOSOPHY,WASHINGTON,DC 20057. NHLBI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAR PY 1993 VL 12 IS 5-6 BP 581 EP 582 PG 2 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 KX071 UT WOS:A1993KX07100026 ER PT J AU SIMON, R ARMITAGE HARRINGTON BRISTOW, D WALKER, M GENT, M ARMITAGE ELLENBERG, S PROSCHAN, M FRIEDEWALD, W POCOCK, S TOGNONI FRIEDEWALD FREEDMAN, L BOISSEL, JP POCOCK PATER, J HERSON GREEN, S GAIL, M GEHAN, E BUYSE MYERS, M AF SIMON, R ARMITAGE HARRINGTON BRISTOW, D WALKER, M GENT, M ARMITAGE ELLENBERG, S PROSCHAN, M FRIEDEWALD, W POCOCK, S TOGNONI FRIEDEWALD FREEDMAN, L BOISSEL, JP POCOCK PATER, J HERSON GREEN, S GAIL, M GEHAN, E BUYSE MYERS, M TI SCIENTIFIC ISSUES IN DATA MONITORING - DISCUSSION SO STATISTICS IN MEDICINE LA English DT Discussion C1 UNIV LONDON LONDON SCH HYG & TROP MED,MED STAT UNIT,LONDON WC1E 7HT,ENGLAND. UNIV TEXAS,MD ANDERSON CANC CTR,DEPT BIOMATH,HOUSTON,TX 77030. US FDA,CBER,OELPS,DIV BIOSTAT & EPIDEMIOL,ROCKVILLE,MD 20852. NHLBI,BETHESDA,MD 20892. RP SIMON, R (reprint author), NCI,BIOMETR RES BRANCH,BETHESDA,MD 20892, USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0277-6715 J9 STAT MED JI Stat. Med. PD MAR PY 1993 VL 12 IS 5-6 BP 583 EP 600 PG 18 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 KX071 UT WOS:A1993KX07100027 ER PT J AU MEIER ONEILL POCOCK HERSON YUSUF BLACKWELDER, W ZUCKER, D FEIGAL, D AF MEIER ONEILL POCOCK HERSON YUSUF BLACKWELDER, W ZUCKER, D FEIGAL, D TI SOME FDA PERSPECTIVES ON DATA MONITORING IN CLINICAL-TRIALS IN DRUG DEVELOPMENT - DISCUSSION SO STATISTICS IN MEDICINE LA English DT Discussion C1 US FDA,CTR DRUG EVALUAT & RES,OFF EPIDEMIOL & BIOSTAT,PARKLAWN BLDG,ROCKVILLE,MD 20857. UNIV LONDON LONDON SCH HYG & TROP MED,MED STAT UNIT,LONDON WC1E 7HT,ENGLAND. NHLBI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAR PY 1993 VL 12 IS 5-6 BP 609 EP 614 PG 6 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 KX071 UT WOS:A1993KX07100029 ER PT J AU WEISMAN, Y CASSORLA, F MALOZOWSKI, S KRIEG, RJ GOLDRAY, D KAYE, AM SOMJEN, D AF WEISMAN, Y CASSORLA, F MALOZOWSKI, S KRIEG, RJ GOLDRAY, D KAYE, AM SOMJEN, D TI SEX-SPECIFIC RESPONSE OF BONE-CELLS TO GONADAL-STEROIDS - MODULATION IN PERINATALLY ANDROGENIZED FEMALES AND IN TESTICULAR FEMINIZED MALE-RATS SO STEROIDS LA English DT Article DE GONADAL STEROIDS; DIAPHYSEAL BONE; CALVARIA CELLS; ANDROGENIZED FEMALE RATS; TESTICULAR FEMINIZED MALE RATS; ESTRADIOL; DIHYDROTESTOSTERONE; SEXUAL DIFFERENTIATION ID GROWTH-HORMONE SECRETION; OSTEOBLAST-LIKE CELLS; CREATINE-KINASE; PARATHYROID-HORMONE; ESTROGEN-RECEPTORS; DNA-SYNTHESIS; PROLIFERATION; PROTEIN; 17-BETA-ESTRADIOL; IDENTIFICATION AB We have found previously that rat diaphyseal bone in vivo, as well as rat embryo calvaria cells in culture, show a sex-specific response to gonadal steroids in stimulation of creatine kinase (CK)-specific activity, and the rate of [H-3]thymidine incorporation into DNA; male-derived cells responded only to testosterone or to dihydrotestosterone (DHT), whereas female-derived cells were stimulated exclusively by estradiol (E2). In this study, we tested whether developmental hormone manipulation could alter this sex specificity. We showed that diaphyseal bone of prenatally or neonatally androgenized female rats responds to a single injection of either E2 (5 mug/rat) or DHT (50 mug/rat) at 3-4 weeks postandrogenization. This response of androgenized female diaphyseal bone to androgen gradually declines; 3 months posttreatment, diaphyseal bone no longer responds to DHT and reverts to its original sex specificity. Rat embryo calvaria cell cultures prepared from female fetuses androgenized in utero showed the same lack of hormonal specificity, that is, the cells responded to both E2 (30 nM) or DHT (300 nM). Cells derived from the male siblings of the prenatally androgenized rats were not affected and responded only to DHT. In contrast to experiments in utero, in vitro administration of testosterone (1 muM) or E2 (1 muM) to calvaria cells from female embryos failed to cause the cells to respond to DHT. Androgen receptor-deficient (Tfm) male rats, which have approximately 10% of the normal response to androgens, also showed a response to both testosterone and E2 in comparison to their normal male siblings, whose bones responded only to androgens. Estrogen injection into Tfm males resulted in as large an increase in the specific activity of CK as found after DHT injection. These results suggest that during development the receptor-mediated pathway of response to both androgens and estrogens exists in the bones of both sexes. However, the sex-specific response to sex steroid hormones by diaphyseal bone appears to depend on both prior and continuing exposure to the dominant sex steroid in each sex. C1 TEL AVIV UNIV,ICHILOV HOSP,SACKLER FAC MED,ENDOCRINE UNIT,TEL AVIV,ISRAEL. TEL AVIV UNIV,ICHILOV HOSP,SACKLER FAC MED,DEPT GERIATR B,TEL AVIV,ISRAEL. NICHHD,DEV ENDOCRINOL BRANCH,BETHESDA,MD 20892. US FDA,DIV METAB & ENDOCRINE DRUG PROD,ROCKVILLE,MD 20857. VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,DEPT ANAT,RICHMOND,VA 23298. WEIZMANN INST SCI,DEPT HORMONE RES,IL-76100 REHOVOT,ISRAEL. RP WEISMAN, Y (reprint author), TEL AVIV UNIV,ICHILOV HOSP,SACKLER FAC MED,BONE DIS UNIT,6 WEIZMANN ST,IL-64239 TEL AVIV,ISRAEL. NR 36 TC 32 Z9 32 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 1993 VL 58 IS 3 BP 126 EP 133 DI 10.1016/0039-128X(93)90049-S PG 8 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA KU168 UT WOS:A1993KU16800006 PM 8475517 ER PT J AU WEISSMAN, AD CALDECOTTHAZARD, S AF WEISSMAN, AD CALDECOTTHAZARD, S TI IN UTERO METHAMPHETAMINE EFFECTS .1. BEHAVIOR AND MONOAMINE UPTAKE SITES IN ADULT OFFSPRING SO SYNAPSE LA English DT Article DE OPEN FIELD; MORRIS WATER MAZE; [H-3]-PAROXETINE; [H-3]-GBR-12935; [H-3]MAZINDOL; DOPAMINE; SEROTONIN; NOREPINEPHRINE; AMPHETAMINE; REGENERATION; NEUROTOXICITY ID LONG-LASTING DOPAMINE; RAT-BRAIN; D-AMPHETAMINE; STRIATAL DOPAMINE; FRONTAL-CORTEX; METHYLAMPHETAMINE; BINDING; NEURONS; DAMAGE; NORADRENALINE AB Chronic in utero methamphetamine treatment, throughout gestation in rats, resulted in alterations in both behavior and brain monoamine function in the adult offspring. The higher dose of methamphetamine (10 mg/kg/b.i.d.) caused a significant decrease in square crossing and rearing in an open field, as well as a regional increase of serotonin and dopamine uptake sites. In contrast, the lower dose of in utero methamphetamine (2 mg/kg/b.i.d.) resulted in a significant decrease in regional densities of serotonin and dopamine uptake sites, and only decreased rearing behavior. Across treatment groups, there were significant correlations between open-field square crossing activity and the number of uptake sites in specific brain areas. Other measured behaviors, such as the neonate righting reflex and the adult Morris water maze performance, were unaffected by either in utero drug regimen. These results are discussed in terms of the known neurotoxicity of amphetamines and the ability of the immature nervous system to compensate for fetal exposure to methamphetamine. C1 FLORIDA HOSP,CTR PSYCHIAT,ORLANDO,FL 32803. RP WEISSMAN, AD (reprint author), NIDA,ADDICT RES CTR,NEUROSCI BRANCH,BALTIMORE,MD 21224, USA. NR 61 TC 28 Z9 28 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0887-4476 J9 SYNAPSE JI Synapse PD MAR PY 1993 VL 13 IS 3 BP 241 EP 250 DI 10.1002/syn.890130307 PG 10 WC Neurosciences SC Neurosciences & Neurology GA KR736 UT WOS:A1993KR73600006 PM 8497809 ER PT J AU UENG, TH UENG, YF CHEN, TL PARK, SS IWASAKI, M GUENGERICH, FP AF UENG, TH UENG, YF CHEN, TL PARK, SS IWASAKI, M GUENGERICH, FP TI INDUCTION OF CYTOCHROME-P450-DEPENDENT MONOOXYGENASES IN HAMSTER TISSUES BY FASTING SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article ID N-NITROSODIMETHYLAMINE DEMETHYLASE; LIVER-MICROSOMES; RAT-LIVER; CYTOCHROME-P-450 ENZYMES; MONOCLONAL-ANTIBODIES; DRUG-METABOLISM; ETHANOL; ACETONE; PURIFICATION; KIDNEY C1 NCI,FCRDC,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21702. NATL TAIWAN UNIV,COLL MED,DEPT BIOCHEM,TAIPEI,TAIWAN. VANDERBILT UNIV,MED CTR,SCH MED,DEPT BIOCHEM,NASHVILLE,TN 37232. VANDERBILT UNIV,MED CTR,SCH MED,CTR MOLEC TOXICOL,NASHVILLE,TN 37232. RP UENG, TH (reprint author), NATL TAIWAN UNIV,COLL MED,INST TOXICOL,1 JEN AI RD,SECT 1,TAIPEI,TAIWAN. FU NCI NIH HHS [CA44353]; NIEHS NIH HHS [ES00267] NR 47 TC 31 Z9 31 U1 0 U2 3 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD MAR PY 1993 VL 119 IS 1 BP 66 EP 73 DI 10.1006/taap.1993.1045 PG 8 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA KR292 UT WOS:A1993KR29200009 PM 8470125 ER PT J AU FARRIS, FF DEDRICK, RL ALLEN, PV SMITH, JC AF FARRIS, FF DEDRICK, RL ALLEN, PV SMITH, JC TI PHYSIOLOGICAL MODEL FOR THE PHARMACOKINETICS OF METHYL MERCURY IN THE GROWING RAT SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article ID INORGANIC MERCURY; BILIARY-EXCRETION; METHYLMERCURY SECRETION; GLUTATHIONE; TRANSPORT; CHLORIDE; BIOTRANSFORMATION; MOUSE; BRAIN; DEPENDENCE C1 NIH,NATL CTR RES RESOURCES,BIOMED ENGN & INSTRUMENTAT PROGRAM,BETHESDA,MD 20892. UNIV ROCHESTER,SCH MED,ENVIRONM HLTH SCI CTR,ROCHESTER,NY 14620. RP FARRIS, FF (reprint author), US FDA,CTR DRUG EVALUAT & RES,DIV CLIN PHARMACOL,4 RES COURT,ROOM 314,ROCKVILLE,MD 20850, USA. FU NIEHS NIH HHS [ES-01247, ES-01248] NR 79 TC 62 Z9 63 U1 0 U2 13 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD MAR PY 1993 VL 119 IS 1 BP 74 EP 90 DI 10.1006/taap.1993.1046 PG 17 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA KR292 UT WOS:A1993KR29200010 PM 8470126 ER PT J AU DEMBY, KB SANCHEZ, IM GHANAYEM, BI AF DEMBY, KB SANCHEZ, IM GHANAYEM, BI TI SINGLE DOSE BLOOD TOXICOKINETICS OF METHACRYLONITRILE IN THE F344 RAT SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article ID ALIPHATIC NITRILES; ACUTE TOXICITY; ACRYLONITRILE; MUTAGENICITY RP DEMBY, KB (reprint author), NIEHS,RES TRIANGLE PK,NC 27709, USA. NR 25 TC 2 Z9 2 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD MAR PY 1993 VL 119 IS 1 BP 115 EP 121 DI 10.1006/taap.1993.1050 PG 7 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA KR292 UT WOS:A1993KR29200014 PM 8470115 ER PT J AU YUAN, JH AF YUAN, JH TI MODELING BLOOD-PLASMA CONCENTRATIONS IN DOSED FEED AND DOSED DRINKING-WATER TOXICOLOGY STUDIES SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article ID RAT RP YUAN, JH (reprint author), NIEHS,NATL TOXICOL PROGRAM,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 17 TC 29 Z9 29 U1 0 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD MAR PY 1993 VL 119 IS 1 BP 131 EP 141 DI 10.1006/taap.1993.1052 PG 11 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA KR292 UT WOS:A1993KR29200016 PM 8470117 ER PT J AU POTTER, WT GARRY, VF KELLY, JT TARONE, R GRIFFITH, J NELSON, RL AF POTTER, WT GARRY, VF KELLY, JT TARONE, R GRIFFITH, J NELSON, RL TI RADIOMETRIC ASSAY OF RED-CELL AND PLASMA CHOLINESTERASE IN PESTICIDE APPLIERS FROM MINNESOTA SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Note ID ERYTHROCYTE ACETYLCHOLINESTERASE ACTIVITY; INHIBITORS; PHOSPHINE; EXPOSURE; DRUGS C1 UNIV MINNESOTA,ENVIRONM MED & PATHOL LAB,STONE LAB 1,1ST FLOOR,421 29TH AVE SE,MINNEAPOLIS,MN 55414. UNIV TULSA,DEPT CHEM,TULSA,OK 74104. UNIV MINNESOTA,FAMILY PRACTICE & COMMUNITY HLTH LAB,MINNEAPOLIS,MN 55414. NCI,BIOSTAT BRANCH,BETHESDA,MD 20892. US EPA,HLTH EFFECTS RES LAB,CHAPEL HILL,NC 27514. NR 29 TC 17 Z9 17 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD MAR PY 1993 VL 119 IS 1 BP 150 EP 155 DI 10.1006/taap.1993.1054 PG 6 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA KR292 UT WOS:A1993KR29200018 PM 8470119 ER PT J AU WILSON, RA SHER, A AF WILSON, RA SHER, A TI VACCINES AGAINST SCHISTOSOMES - AN ALTERNATIVE VIEW SO TRANSACTIONS OF THE ROYAL SOCIETY OF TROPICAL MEDICINE AND HYGIENE LA English DT Letter C1 NIAID,PARASIT DIS LAB,BETHESDA,MD 20892. RP WILSON, RA (reprint author), UNIV YORK,DEPT BIOL,YORK YO1 5DD,N YORKSHIRE,ENGLAND. NR 7 TC 6 Z9 6 U1 0 U2 0 PU ROYAL SOC TROPICAL MEDICINE PI LONDON PA MANSON HOUSE 26 PORTLAND PLACE, LONDON, ENGLAND W1N 4EY SN 0035-9203 J9 T ROY SOC TROP MED H JI Trans. Roy. Soc. Trop. Med. Hyg. PD MAR-APR PY 1993 VL 87 IS 2 BP 237 EP 237 DI 10.1016/0035-9203(93)90512-O PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA LC477 UT WOS:A1993LC47700041 PM 8337740 ER PT J AU NATANSON, C HOFFMAN, WD KOEV, LA DOLAN, DP BANKS, SM BACHER, J DANNER, RL KLEIN, HG PARRILLO, JE AF NATANSON, C HOFFMAN, WD KOEV, LA DOLAN, DP BANKS, SM BACHER, J DANNER, RL KLEIN, HG PARRILLO, JE TI PLASMA-EXCHANGE DOES NOT IMPROVE SURVIVAL IN A CANINE MODEL OF HUMAN SEPTIC SHOCK SO TRANSFUSION LA English DT Article ID PLASMAPHERESIS; COMPLICATIONS; DYSFUNCTION; CHALLENGES; ENDOTOXIN AB Whether plasma exchange would improve survival in antibiotic-treated canines with septic shock was investigated. Escherichia coli O86H8 (1.4 x 10(10)) was surgically implanted as an intraperitoneal clot in 18 two-year-old (10-12 kg) purpose-bred beagles. Beginning 4 hours after surgery, all animals received cefoxitin and gentamicin for 5 days. Three treatment groups were defined: 1) a no apheresis, or control group, (n = 6); 2) a sham apheresis group, whose whole blood plasma was removed, separated, and then transfused (n = 6); and 3) a plasma exchange group from whom blood and plasma were removed and separated, to whom the blood was returned, and in whom infected plasma was replaced with compatible fresh-frozen canine plasma (n = 6). For the sham apheresis and plasma exchange groups, a commercial blood cell processor was used to separate 1.5 blood volumes of plasma at 5 and 24 hours after surgery. Serial radionuclide left ventricular ejection fractions and femoral and pulmonary arterial catheter hemodynamics were measured simultaneously in awake animals. All six animals in the plasma exchange group died. In both the sham and control groups, only one of six animals survived. Survival times were ordered (median in hours) (control [372 h] > sham apheresis [48 h] > plasma exchange [24 h] [p<0.038]). Decreases in mean cardiac index and mean arterial pressure (from before apheresis to after) at 5 to 7 hours after surgery were ordered (plasma exchange > sham apheresis > control; p<0.03). Thus, plasma exchange in this controlled trial of septic shock was associated with decreased survival and worsened hemodynamics. When extrapolated to humans, these results suggest that plasma exchange would be unlikely to provide therapeutic benefit and might produce harmful effects in patients with septic shock. C1 NIH,VET RESOURCES PROGRAM,SURG UNIT,BETHESDA,MD 20892. NIH,DEPT TRANSFUS MED,BETHESDA,MD 20892. RP NATANSON, C (reprint author), NIH,DEPT CRIT CARE MED,CTR CLIN,BLDG 10,ROOM 10D-48,BETHESDA,MD 20892, USA. NR 26 TC 38 Z9 38 U1 0 U2 1 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 SN 0041-1132 J9 TRANSFUSION JI Transfusion PD MAR PY 1993 VL 33 IS 3 BP 243 EP 248 DI 10.1046/j.1537-2995.1993.33393174451.x PG 6 WC Hematology SC Hematology GA KQ447 UT WOS:A1993KQ44700012 PM 8438226 ER PT J AU DASSO, M AF DASSO, M TI RCC1 IN THE CELL-CYCLE - THE REGULATOR OF CHROMOSOME CONDENSATION TAKES ON NEW ROLES SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Review ID GENE RCC1; BINDING PROTEIN; MESSENGER-RNA; YEAST; DROSOPHILA; MUTATION; MITOSIS; HOMOLOG; MUTANT; ONSET AB In the eukaryotic cell cycle, nuclear DNA replication (S phase) and mitosis (M phase) are linked such that replication must be complete before mitosis can begin. In order for this coupling to work, there must be some system for detecting unreplicated DNA and transducing an inhibitory signal to prevent the activation of mitotic factors. The DNA-bound protein RCC1 is involved in this regulatory process since mitosis initiates before DNA synthesis is finished in the absence of RCC1. This has led to the proposal that RCC1 is a signalling molecule, detecting unreplicated DNA and producing the inhibitory signal. However, mutants in RCC1 show defects beyond their inability to regulate the cell cycle, suggesting other roles for the RCC1 protein in the nucleus and thus hitherto unexplored relationships between cell cycle control and other cellular processes. RP DASSO, M (reprint author), NICHHD,MOLEC EMBRYOL LAB,BETHESDA,MD 20892, USA. OI Dasso, Mary/0000-0002-5410-1371 NR 34 TC 146 Z9 146 U1 0 U2 2 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 1993 VL 18 IS 3 BP 96 EP 101 DI 10.1016/0968-0004(93)90161-F PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA KT955 UT WOS:A1993KT95500010 PM 8480369 ER PT J AU LEE, SW KAHN, ML DICHEK, DA AF LEE, SW KAHN, ML DICHEK, DA TI CONTROL OF CLOT LYSIS BY GENE-TRANSFER SO TRENDS IN CARDIOVASCULAR MEDICINE LA English DT Article ID TISSUE PLASMINOGEN-ACTIVATOR; MODIFIED ENDOTHELIAL-CELLS; EXPRESSION INVIVO; RETROVIRAL VECTORS; INHIBITOR GENE; ARTERIAL-WALL; FIBRINOLYSIS; INDUCTION; CORONARY; COMPLEX AB Intravascular clot formation is a local process that can result in serious clinical consequences, including limb loss and death. Gene transfer and expression of recombinant plasminogen activators in the endothelial cells of the vessel wall offer an attractive approach to the enhancement of local fibrinolytic activity. In vitro studies have demonstrated that endothelial cell fibrinolytic activity can be increased by gene transfer of either secreted or cell surface-anchored plasminogen activators. Future work will define the ability of gene transfer to facilitate clot lysis in vivo. RP LEE, SW (reprint author), NHLBI,MOLEC HEMATOL BRANCH,BETHESDA,MD 20892, USA. NR 43 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 1050-1738 J9 TRENDS CARDIOVAS MED JI Trends Cardiovasc. Med. PD MAR-APR PY 1993 VL 3 IS 2 BP 61 EP 66 DI 10.1016/1050-1738(93)90038-8 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA KT739 UT WOS:A1993KT73900005 PM 21244953 ER PT J AU HATFIELD, D DIAMOND, A AF HATFIELD, D DIAMOND, A TI UGA - A SPLIT PERSONALITY IN THE UNIVERSAL GENETIC-CODE SO TRENDS IN GENETICS LA English DT Letter ID TRANSFER-RNA; INSERTS SELENOCYSTEINE; TRYPTOPHAN; PROTEIN C1 UNIV CHICAGO,DEPT RADIAT & CELLULAR ONCOL,CHICAGO,IL 60639. RP HATFIELD, D (reprint author), NCI,EXPTL CARCINOGENESIS LAB,BETHESDA,MD 20892, USA. NR 29 TC 37 Z9 38 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0168-9525 J9 TRENDS GENET JI Trends Genet. PD MAR PY 1993 VL 9 IS 3 BP 69 EP 70 DI 10.1016/0168-9525(93)90215-4 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA KN895 UT WOS:A1993KN89500002 PM 8488562 ER PT J AU KENNISON, JA AF KENNISON, JA TI TRANSCRIPTIONAL ACTIVATION OF DROSOPHILA HOMEOTIC GENES FROM DISTANT REGULATORY ELEMENTS SO TRENDS IN GENETICS LA English DT Review ID BITHORAX COMPLEX; ULTRABITHORAX; TRITHORAX; MELANOGASTER; REPRESSION; EXPRESSION; POLYCOMB; REGION; SNF2 AB In Drosophila the genes responsible for specifying segment identity (the homeotic genes) are transcribed in complex patterns during development. Mutations that mimic loss of homeotic gene activity identify cis-acting DNA sequences and trans-acting proteins required for transcriptional activation. Some of the trans-acting proteins may facilitate interactions between cis-regulatory elements and the promoter by bringing together distant chromosomal elements. RP KENNISON, JA (reprint author), NICHHD,MOLEC GENET LAB,BETHESDA,MD 20892, USA. NR 35 TC 137 Z9 138 U1 1 U2 5 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0168-9525 J9 TRENDS GENET JI Trends Genet. PD MAR PY 1993 VL 9 IS 3 BP 75 EP 79 DI 10.1016/0168-9525(93)90227-9 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA KN895 UT WOS:A1993KN89500006 PM 8098166 ER PT J AU UHL, G BLUM, K NOBLE, E SMITH, S AF UHL, G BLUM, K NOBLE, E SMITH, S TI SUBSTANCE-ABUSE VULNERABILITY AND D2 RECEPTOR GENES SO TRENDS IN NEUROSCIENCES LA English DT Article ID D2-DOPAMINE RECEPTOR; ALLELIC ASSOCIATION; DRUG-ABUSE; ALCOHOLISM; DOPAMINE; DISORDERS; LOCUS AB Dopamine systems are key to the actions of several substances. Interindividual differences In genes encoding proteins involved In dopaminergic neurotransmission could plausibly explain some of the genetic bases for inter-individual differences in vulnerability to substance abuse. The restriction fragment length polymorphism (RFLP) markers TaqI A1 and B1 at the dopamine D2 receptor (DRD2) gene locus in Caucasians are associated with substance abuse behaviors, In most, but not all, studies of alcoholics and polysubstance abusers, these TaqI A1 and B1 gene markers are present more often in substance abusers than in control individuals. No study has identified substance abusers or controls by sampling randomly from the general population; allelic association findings could thus conceivably be confounded by RFLP differences based on ethnicity or other factors. However, meta-analyses of the data from controlled studies available to date are consistent with the proposal that DRD2 gene variants contribute to inter-individual differences in vulnerability to alcoholism and polysubstance abuse. C1 NIDA,ADDICT RES CTR,ETIOL LAB,BALTIMORE,MD 21224. UNIV TEXAS,HLTH SCI CTR,DEPT PHARMACOL,SAN ANTONIO,TX 78284. UNIV WISCONSIN,DEPT PSYCHOL,MADISON,WI 53706. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROL,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROSCI,BALTIMORE,MD 21205. UNIV CALIF LOS ANGELES,SCH MED,ALCOHOL RES CTR,LOS ANGELES,CA 90024. RP UHL, G (reprint author), NIDA,ADDICT RES CTR,MOLEC NEUROBIOL LAB,BOX 5180,BALTIMORE,MD 21224, USA. NR 36 TC 114 Z9 116 U1 2 U2 5 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0166-2236 J9 TRENDS NEUROSCI JI Trends Neurosci. PD MAR PY 1993 VL 16 IS 3 BP 83 EP 88 DI 10.1016/0166-2236(93)90128-9 PG 6 WC Neurosciences SC Neurosciences & Neurology GA KN179 UT WOS:A1993KN17900001 PM 7681236 ER PT J AU BOOY, FP PAWLEY, JB AF BOOY, FP PAWLEY, JB TI CRYO-CRINKLING - WHAT HAPPENS TO CARBON-FILMS ON COPPER GRIDS AT LOW-TEMPERATURE SO ULTRAMICROSCOPY LA English DT Article ID ELECTRON-MICROSCOPY; CRYSTALS AB A study of the surface flatness of carbon films on copper grids used for cryo-electron microscopy has been carried out using a Hitachi S-900 low-voltage SEM. Dramatic changes in flatness were observed after cooling from room temperature to -170-degrees-C. The changes were similar both for carbon films that had been floated from a mica surface and for those initially deposited on the surface of plastic films. Results demonstrate that films prepared on copper grids that appear flat at room temperature become extensively, but reversibly, puckered at -170-degrees-C. The linear thermal expansion coefficient (alpha) for copper is 16.2 x 10(-6)/degrees-C and the puckering can be explained by assuming that the coefficient for amorphous carbon is substantially less. Measurements on grids made of titanium, molybdenum and tungsten (coefficients 8.5, 5 and 4.5 x 10(-6)/degrees-C, respectively) showed significantly less puckering. C1 UNIV WISCONSIN,MADISON,WI 53706. RP BOOY, FP (reprint author), NIAMS,LSB,BLDG 6,ROOM 114,BETHESDA,MD 20892, USA. FU NCRR NIH HHS [DRR 570] NR 15 TC 38 Z9 38 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3991 J9 ULTRAMICROSCOPY JI Ultramicroscopy PD MAR PY 1993 VL 48 IS 3 BP 273 EP 280 DI 10.1016/0304-3991(93)90101-3 PG 8 WC Microscopy SC Microscopy GA KW650 UT WOS:A1993KW65000004 PM 8475597 ER PT J AU BATHURST, IC GIBSON, HL KANSOPON, J HAHM, BK GREEN, KM CHANG, SP HUI, GSN SIDDIQUI, WA INSELBURG, J MILLET, P QUAKYI, IA KASLOW, DC BARR, PJ AF BATHURST, IC GIBSON, HL KANSOPON, J HAHM, BK GREEN, KM CHANG, SP HUI, GSN SIDDIQUI, WA INSELBURG, J MILLET, P QUAKYI, IA KASLOW, DC BARR, PJ TI AN EXPERIMENTAL VACCINE COCKTAIL FOR PLASMODIUM-FALCIPARUM MALARIA SO VACCINE LA English DT Article DE MALARIA VACCINE CANDIDATES; HUMORAL IMMUNE RESPONSE; INHIBITION OF LIVER CELL INVASION; INHIBITION OF PARASITEMIA; TRANSMISSION-BLOCKING IMMUNITY ID SACCHAROMYCES-CEREVISIAE; PROTECTIVE IMMUNITY; SPOROZOITE VACCINE; SURFACE-ANTIGEN; AOTUS MONKEYS; SERA PROTEINS; IMMUNOGENICITY; EXPRESSION; SAFETY; YEAST AB Surface proteins from several different life-cycle stages of the malaria parasite Plasmodium falciparum were expressed at high levels in the yeast Saccharomyces cerevisiae. Purified proteins, both individually and in cocktails, were used to immunize mice and goats in conjunction with either Freund's adjuvant or a muramyl tripeptide-based adjuvant. Immune responses were measured by enzyme-linked immunosorbent assays and by the ability of antisera to inhibit (1) the invasion of hepatocytes by live sporozoites, (2) in vitro invasion of human erythrocytes by live merozoites, and (3) the development of oocytes in the mosquito vector. These results suggest that cocktails of different stage-specific antigens can provide the components necessary to block the development of the malaria parasite at multiple stages of its life cycle. C1 LEAHI HOSP,DEPT TROP MED,HONOLULU,HI. DARTMOUTH COLL,HITCHCOCK MED CTR,DARTMOUTH MED SCH,DEPT MICROBIOL,HANOVER,NH 03756. CTR DIS CONTROL,NATL CTR INFECT DIS,DIV PARASIT DIS,ATLANTA,GA 30333. NIAID,PARASIT DIS LAB,BETHESDA,MD 20892. RP BATHURST, IC (reprint author), CHIRON CORP,4560 HORTON ST,EMERYVILLE,CA, USA. FU NIAID NIH HHS [AI23562] NR 38 TC 22 Z9 22 U1 0 U2 1 PU BUTTERWORTH-HEINEMANN LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0264-410X J9 VACCINE JI Vaccine PD MAR PY 1993 VL 11 IS 4 BP 449 EP 456 DI 10.1016/0264-410X(93)90287-8 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA KR214 UT WOS:A1993KR21400011 PM 8470430 ER PT J AU CULLEN, JM SANDGREN, EP BRINSTER, RL MARONPOT, RR AF CULLEN, JM SANDGREN, EP BRINSTER, RL MARONPOT, RR TI HISTOLOGIC CHARACTERIZATION OF HEPATIC CARCINOGENESIS IN TRANSGENIC MICE EXPRESSING SV40 T-ANTIGENS SO VETERINARY PATHOLOGY LA English DT Article DE LIVER; NEOPLASIA; ONCOGENE; SIMIAN VIRUS-40; T-ANTIGENS; TRANSGENIC MICE ID HUMAN ALPHA-1-ANTITRYPSIN GENE; CHEMICAL CARCINOGENESIS; LIVER CARCINOGENESIS; REGULATORY ELEMENTS; MOUSE SYSTEM; HUMAN CANCER; ONCOGENES; TUMORS; CELLS AB The development of hepatic neoplasms was histologically characterized in transgenic mice that expressed an albumin enhancer-promotor/SV40 T-antigen fusion gene. At least five transgenic and three control mice were examined at monthly intervals over a 3-month period. At 1 month of age, five transgenic mice (two male, three female) and three controls (one male, two female) were examined. Five transgenic mice (two male, three female) and three controls (one male, two female) were examined at 2 months of age. Fourteen transgenic mice (12 male, two female) and three controls (two male, one female) were examined at 3 months of age. At 1 month of age, liver-to-body weight ratios of transgenic mice were increased nearly twofold as compared with controls. Histologically, livers from transgenic mice were characterized by dysplastic hepatocytes with marked variation in nucleus and cell size. At 2 months of age, livers from transgenic mice were 2.5 times larger than control livers and contained numerous 1-5-mm cystic spaces. Transgenic livers also contained multiple eosinophilic, basophilic, and clear foci, as well as cystic, hyperplastic bile ducts and biliary adenomas. At 3 months of age, transgenic livers were enlarged over eightfold as compared with controls and contained numerous cysts and solid masses up to 2 cm in diameter. Trabecular, glandular, and anaplastic hepatocellular carcinomas, as well as benign and malignant biliary neoplasms, were diagnosed. No metastasis was observed. Subcutaneous trabecular hepatocellular carcinomas developed in two of three syngeneic mice that had received transplants of a solid hepatic neoplasm, confirming the neoplastic behavior of these tumors. These experiments, in which viral oncogene expression is targeted to all hepatocytes, support the multistage hypothesis of tumor development and illustrate the similarities in morphologic response of liver to a variety of carcinogenic insults. C1 UNIV PENN,SCH VET MED,DEPT REPROD PHYSIOL,PHILADELPHIA,PA 19104. NIEHS,NATL TOXICOL PROGRAM,RES TRIANGLE PK,NC 27709. RP CULLEN, JM (reprint author), N CAROLINA STATE UNIV,COLL VET MED,DEPT MICROBIOL PATHOL & PARASITOL,RALEIGH,NC 27695, USA. FU NCI NIH HHS [CA38635] NR 28 TC 15 Z9 15 U1 0 U2 1 PU AMER COLL VET PATHOLOGIST PI LAWRENCE PA 810 EAST 10TH STREET, LAWRENCE, KS 66044 SN 0300-9858 J9 VET PATHOL JI Vet. Pathol. PD MAR PY 1993 VL 30 IS 2 BP 111 EP 118 PG 8 WC Pathology; Veterinary Sciences SC Pathology; Veterinary Sciences GA KV429 UT WOS:A1993KV42900003 PM 8385835 ER PT J AU ANDRESSON, OS ELSER, JE TOBIN, GJ GREENWOOD, JD GONDA, MA GEORGSSON, G ANDRESDOTTIR, V BENEDIKTSDOTTIR, E CARLSDOTTIR, HM MANTYLA, EO RAFNAR, B PALSSON, PA CASEY, JW PETURSSON, G AF ANDRESSON, OS ELSER, JE TOBIN, GJ GREENWOOD, JD GONDA, MA GEORGSSON, G ANDRESDOTTIR, V BENEDIKTSDOTTIR, E CARLSDOTTIR, HM MANTYLA, EO RAFNAR, B PALSSON, PA CASEY, JW PETURSSON, G TI NUCLEOTIDE-SEQUENCE AND BIOLOGICAL PROPERTIES OF A PATHOGENIC PROVIRAL MOLECULAR CLONE OF NEUROVIRULENT VISNA VIRUS SO VIROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; REVERSE-TRANSCRIPTASE; DNA; LENTIVIRUS; SHEEP; EXPRESSION; INFECTION; GENE; AIDS; MACROPHAGES C1 NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,CELL & MOLEC STRUCT LAB,FREDERICK,MD 21702. CORNELL UNIV,NEW YORK STATE COLL VET MED,DEPT MICROBIOL IMMUNOL & PARASITOL,ITHACA,NY 14853. RP ANDRESSON, OS (reprint author), UNIV ICELAND,INST EXPTL PATHOL,IS-112 REYKJAVIK,ICELAND. FU FIC NIH HHS [1FO5 TWO 4302-01]; NCI NIH HHS [N01-CO-74102] NR 48 TC 76 Z9 83 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD MAR PY 1993 VL 193 IS 1 BP 89 EP 105 DI 10.1006/viro.1993.1106 PG 17 WC Virology SC Virology GA KN057 UT WOS:A1993KN05700010 PM 8382414 ER PT J AU WANG, Y DETRICK, B HOOKS, JJ AF WANG, Y DETRICK, B HOOKS, JJ TI CORONAVIRUS (JHM) REPLICATION WITHIN THE RETINA - ANALYSIS OF CELL TROPISM IN MOUSE RETINAL CELL-CULTURES SO VIROLOGY LA English DT Article ID MURINE HEPATITIS-VIRUS; INVITRO MODELS; DEMYELINATING DISEASES; STRAIN JHM; INFECTION; PERSISTENCE; INVIVO; EXPRESSION; ASTROCYTE; ANTIGEN C1 NEI,IMMUNOL & VIROL SECT,IMMUNOL LAB,BETHESDA,MD 20892. GEORGE WASHINGTON UNIV,MED CTR,DEPT PATHOL,WASHINGTON,DC 20037. NR 37 TC 14 Z9 14 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD MAR PY 1993 VL 193 IS 1 BP 124 EP 137 DI 10.1006/viro.1993.1109 PG 14 WC Virology SC Virology GA KN057 UT WOS:A1993KN05700013 PM 8382393 ER PT J AU MEIER, JL HOLMAN, RP CROEN, KD SMIALEK, JE STRAUS, SE AF MEIER, JL HOLMAN, RP CROEN, KD SMIALEK, JE STRAUS, SE TI VARICELLA-ZOSTER VIRUS TRANSCRIPTION IN HUMAN TRIGEMINAL GANGLIA SO VIROLOGY LA English DT Article ID THORACIC GANGLIA; DNA-SEQUENCE; RNA; EXPRESSION; NEURONS; ACID C1 NIAID,MED VIROL SECT,CLIN INVEST LAB,BLDG 10,ROOM 11N228,BETHESDA,MD 20892. OFF MED EXAMINER,BALTIMORE,MD. NR 27 TC 108 Z9 110 U1 0 U2 4 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD MAR PY 1993 VL 193 IS 1 BP 193 EP 200 DI 10.1006/viro.1993.1115 PG 8 WC Virology SC Virology GA KN057 UT WOS:A1993KN05700019 PM 7679857 ER PT J AU SPALHOLZ, BA MCBRIDE, AA SARAFI, T QUINTERO, J AF SPALHOLZ, BA MCBRIDE, AA SARAFI, T QUINTERO, J TI BINDING OF BOVINE PAPILLOMAVIRUS-E1 TO THE ORIGIN IS NOT SUFFICIENT FOR DNA-REPLICATION SO VIROLOGY LA English DT Article ID VIRUS-40 CORE ORIGIN; OPEN READING FRAME; T-ANTIGEN; TRANSCRIPTIONAL REGULATION; SV40 ORIGIN; MOUSE CELLS; E2 PROTEIN; E1; TYPE-1; EXPRESSION RP SPALHOLZ, BA (reprint author), NCI,TUMOR VIRUS BIOL LAB,BETHESDA,MD 20892, USA. OI McBride, Alison/0000-0001-5607-5157 NR 45 TC 61 Z9 61 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD MAR PY 1993 VL 193 IS 1 BP 201 EP 212 DI 10.1006/viro.1993.1116 PG 12 WC Virology SC Virology GA KN057 UT WOS:A1993KN05700020 PM 8382395 ER PT J AU MORGAN, RA DORNSIFE, RE ANDERSON, WF HOOVER, EA AF MORGAN, RA DORNSIFE, RE ANDERSON, WF HOOVER, EA TI INVITRO INFECTION OF HUMAN BONE-MARROW BY FELINE LEUKEMIA VIRUSES SO VIROLOGY LA English DT Note ID MEDIATED GENE-TRANSFER; TRANSDUCED STEM-CELLS; APLASTIC-ANEMIA; IMMUNODEFICIENCY SYNDROME; HOST RANGE; RETROVIRUS; PATHOGENESIS; COMBINATION; RECIPIENTS; EXPRESSION C1 COLORADO STATE UNIV,DEPT PATHOL,FT COLLINS,CO 80523. RP MORGAN, RA (reprint author), NHLBI,MOLEC HEMATOL BRANCH,BETHESDA,MD 20892, USA. FU NCI NIH HHS [CA-48594] NR 21 TC 9 Z9 9 U1 2 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD MAR PY 1993 VL 193 IS 1 BP 439 EP 442 DI 10.1006/viro.1993.1141 PG 4 WC Virology SC Virology GA KN057 UT WOS:A1993KN05700045 PM 8382406 ER PT J AU MAJONE, F SEMMES, OJ JEANG, KT AF MAJONE, F SEMMES, OJ JEANG, KT TI INDUCTION OF MICRONUCLEI BY HTLV-I TAX - A CELLULAR-ASSAY FOR FUNCTION SO VIROLOGY LA English DT Note ID VIRUS TYPE-I; TRANS-ACTIVATOR PROTEIN; LEUKEMIA-VIRUS; GENE; CELLS; EXPRESSION; GROWTH; TRANSFORMATION; ANEUPLOIDY; ONCOGENE C1 NIAID,MOLEC MICROBIOL LAB,BETHESDA,MD 20892. RI Jeang, Kuan-Teh/A-2424-2008 NR 27 TC 75 Z9 76 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD MAR PY 1993 VL 193 IS 1 BP 456 EP 459 DI 10.1006/viro.1993.1145 PG 4 WC Virology SC Virology GA KN057 UT WOS:A1993KN05700049 PM 8438579 ER PT J AU BRODER, CC DIMITROV, DS BLUMENTHAL, R BERGER, EA AF BRODER, CC DIMITROV, DS BLUMENTHAL, R BERGER, EA TI THE BLOCK TO HIV-1 ENVELOPE GLYCOPROTEIN-MEDIATED MEMBRANE-FUSION IN ANIMAL-CELLS EXPRESSING HUMAN CD4 CAN BE OVERCOME BY A HUMAN CELL COMPONENT(S) SO VIROLOGY LA English DT Note ID HUMAN-IMMUNODEFICIENCY-VIRUS; RECOMBINANT VACCINIA VIRUSES; SYNCYTIUM FORMATION; HTLV-III; INFECTION; TYPE-1; RECEPTOR; LFA-1; AIDS; GENE C1 NIAID,VIRAL DIS LAB,BETHESDA,MD 20892. NCI,MEMBRANE STRUCT & FUNCT SECT,BETHESDA,MD 20892. NR 45 TC 120 Z9 121 U1 2 U2 4 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD MAR PY 1993 VL 193 IS 1 BP 483 EP 491 DI 10.1006/viro.1993.1151 PG 9 WC Virology SC Virology GA KN057 UT WOS:A1993KN05700055 PM 8438583 ER PT J AU HARDY, ME GORZIGLIA, M WOODE, GN AF HARDY, ME GORZIGLIA, M WOODE, GN TI THE OUTER CAPSID PROTEIN VP4 OF EQUINE ROTAVIRUS STRAIN H-2 REPRESENTS A UNIQUE VP4 TYPE BY AMINO-ACID-SEQUENCE ANALYSIS SO VIROLOGY LA English DT Note ID ANTIGENIC RELATIONSHIPS; RHESUS ROTAVIRUS; BOVINE ROTAVIRUS; G-SEROTYPE; GENOMIC CHARACTERIZATION; SURFACE-PROTEINS; SUBGROUP-I; NEUTRALIZATION; FOALS; GENE C1 TEXAS A&M UNIV SYST,COLL VET MED,DEPT VET PATHOBIOL,COLL STN,TX 77843. NIH,INFECT DIS LAB,BETHESDA,MD 20892. NR 47 TC 22 Z9 23 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD MAR PY 1993 VL 193 IS 1 BP 492 EP 497 DI 10.1006/viro.1993.1152 PG 6 WC Virology SC Virology GA KN057 UT WOS:A1993KN05700056 PM 8382410 ER PT J AU KEW, MC CHESTNUT, T BALDWIN, BH HORNBUCKLE, WE TENNANT, BC PURCELL, RH MILLER, RH AF KEW, MC CHESTNUT, T BALDWIN, BH HORNBUCKLE, WE TENNANT, BC PURCELL, RH MILLER, RH TI HETEROGENEITY OF THE WOODCHUCK HEPATITIS-VIRUS GENOME IN A CHRONICALLY INFECTED WOODCHUCK SO VIRUS RESEARCH LA English DT Article DE WOODCHUCK HEPATITIS VIRUS; NUCLEOTIDE SEQUENCE ID B VIRUS; NUCLEOTIDE-SEQUENCE; E-ANTIGEN; ANTIBODY; REGION AB The nucleotide sequence of an isolate of woodchuck hepatitis virus (WHV) from the serum of a woodchuck trapped in New York state (WHVNY) was compared with the sequences of previously published isolates. The nucleotide sequence of WHVNY was closest to that of an isolate originating from New Jersey: the two genomes shared a 15 nucleotide in-frame deletion in the region where the presurface and polymerase genes overlap (nucleotides 3260-3274) and differed by 54 point mutations (1.6% of genome). Amino acid differences ranged from 0.4% in the surface gene to 5.7% in the X gene. Three isolates from woodchucks that originated in Pennsylvania and Maryland did not contain the deletion and differed from WHVNY by 102 to 106 point mutations (3.0% to 3.2% of nucleotides). Amino acid changes ranged from 0.5% in the core gene to 5.7% in the X-gene. Thus, WHVNY differed little from previous isolates. Next, the genomes from 102 independent clones of WHVNY were compared to ascertain the extent of sequence variation among WHV genomes in a chronically infected animal. A total of 98 clones had genomes of unit length while 2 clones had genomes shorter than unit length and 2 clones had genomes longer than unit length. The clones not of unit length possessed deletions or inverted duplications of sequence. The rate of mutation in the viral genes was 2.65 mutations per 10,000 nucleotides in the precore domain, 1.27 per 10,000 in the X-gene, 0.98 per 10,000 in the presurface gene, and 3.77 per 10,000 at the 5' end of the core gene. Overall, mutations occurred at only 12 (0.016%) of the 74,842 nucleotide positions sequenced. C1 NIAID,HEPATITIS VIRUSES SECT,INFECT DIS LAB,BETHESDA,MD 20892. CORNELL UNIV,COLL VET MED,ITHACA,NY 14853. FU NIAID NIH HHS [N01 AI82698] NR 13 TC 8 Z9 8 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-1702 J9 VIRUS RES JI Virus Res. PD MAR PY 1993 VL 27 IS 3 BP 229 EP 237 DI 10.1016/0168-1702(93)90035-L PG 9 WC Virology SC Virology GA KV391 UT WOS:A1993KV39100002 PM 8488722 ER PT J AU KIM, ND YOO, JK WON, SM PARK, SS GELBOIN, HV AF KIM, ND YOO, JK WON, SM PARK, SS GELBOIN, HV TI PHENYTOIN INDUCTION OF CYTOCHROME P4502B IN MICE - EFFECTS ON HEXOBARBITAL HYDROXYLASE-ACTIVITY SO XENOBIOTICA LA English DT Article ID RAT-LIVER; NEOPLASTIC LESIONS; DEETHYLASE; METABOLISM AB 1. Treatment of ICR and C57BL/6 mice with phenytoin (50 mg/kg, i.p., 3 days) resulted in approximately 33 and 43% increases in hepatic cytochrome P450 levels relative to uninduced microsomes, respectively. Phenytoin treatment caused a 63% decrease in hexobarbital sleeping time in ICR mice (19 versus 52 min). 2. Both Western immunoblot analysis and solid phase radioimmunoassay using monoclonal anti-rat P4502B antibody showed that P4502B was increased significantly in phenytoin-induced mouse microsomes compared with uninduced mice. P4502B9 was the predominantly induced form whereas 2B10 was elevated marginally. Phenytoin was as efficacious as phenobarbital in increasing P4502B. 3. Phenytoin treatment resulted in an approximately 8-fold increase in hexobarbital hydroxylase activity whereas phenobarbital treatment caused an approximately 13-fold increase. Addition of anti-P4502B antibody produced complete inhibition of hexobarbital oxidation in phenytoin-induced microsomes, indicating that raised P4502B in phenytoin-induced microsomes is associated with the increased hexobarbital hydroxylase activity. 4. Phenytoin failed to increase P4501A in either C57BL/6 or ICR mice, as assessed by both immunoblot analysis and metabolic activities. Although both aryl hydrocarbon hydroxylase and 7-ethoxycoumarin deethylase activities were raised -two-fold following phenytoin treatment, the metabolic activities were not inhibited by anti-P4501A antibody. 5. These results provide evidence that phenytoin induces P4502B in mice with pronounced increase in hexobarbital hydroxylase activity, and fails to induce P4501A in either C57BL/6 or ICR mice. C1 YUHAN CO LTD,CENT RES INST,KYONG GI DO 435030,SOUTH KOREA. NCI,FREDERICK CANC RES FACIL,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21701. SEOUL NATL UNIV,COLL PHARM,SEOUL 151742,SOUTH KOREA. RP KIM, ND (reprint author), NCI,MOLEC CARCINOGENESIS LAB,BETHESDA,MD 20892, USA. NR 19 TC 8 Z9 8 U1 1 U2 1 PU TAYLOR & FRANCIS LTD PI LONDON PA ONE GUNDPOWDER SQUARE, LONDON, ENGLAND EC4A 3DE SN 0049-8254 J9 XENOBIOTICA JI Xenobiotica PD MAR PY 1993 VL 23 IS 3 BP 217 EP 225 PG 9 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA KX691 UT WOS:A1993KX69100001 PM 8498085 ER PT J AU BRADY, JP PIATIGORSKY, J AF BRADY, JP PIATIGORSKY, J TI CLONING AND CHARACTERIZATION OF A NOVEL ZINC-FINGER PROTEIN-ENCODING CDNA FROM THE MOUSE EYE LENS SO GENE LA English DT Article DE NUCLEIC ACID-BINDING DOMAIN; PCR; EVOLUTION; EXPRESSION CONSTRUCT ID 3' UNTRANSLATED REGION; A-CRYSTALLIN GENE; MESSENGER-RNA DEGRADATION; DNA-BINDING; TRANSCRIPTION FACTOR; NUCLEOTIDE-SEQUENCE; ALPHA; EVOLUTION; PROMOTER; FAMILY AB Zinc fingers (Zf) are a common structural motif found in many nucleic acid-binding proteins. In an effort to identify potential transcription factors in the mouse eye lens, we have isolated a Zf-containing clone from a newborn mouse lens cDNA library. The clone, named pMLZ-4, is 4.5 kb in length and contains an open reading frame of 1073 bp. The putative pMLZ-4 protein consists of a short, N-terminal acidic domain followed by twelve tandemly arrayed Zf of the C2H2 variety. The remaining 3.2 kb of the cDNA comprises the 3'-untranslated region. PCR analysis detected the presence of pMLZ-4 RNA in liver, heart, kidney, spleen and brain of newborn mice. Hybridization of pMLZ-4 to genomic DNA from a number of species of vertebrates revealed the presence of homologous sequences only in mouse and rat. Unexpectedly, the probe also hybridized to a single band in yeast DNA digested with EcoRI. NIH3T3 cells were stably transformed with a construct that over-expresses the pMLZ-4 mRNA. The stably transformed cells did not differ in appearance from untransformed cells, and an analysis of proteins from transformed and untransformed cells failed to detect any differences resulting from over-expression of the pMLZ-4 mRNA. C1 NEI,MOLEC & DEV BIOL LAB,BLDG 6,ROOM 205,BETHESDA,MD 20892. NR 50 TC 12 Z9 13 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD FEB 28 PY 1993 VL 124 IS 2 BP 207 EP 214 DI 10.1016/0378-1119(93)90395-J PG 8 WC Genetics & Heredity SC Genetics & Heredity GA KQ446 UT WOS:A1993KQ44600007 PM 8444344 ER PT J AU CECCHINI, S BONARDI, R MAZZOTTA, A GRAZZINI, G IOSSA, A CIATTO, S AF CECCHINI, S BONARDI, R MAZZOTTA, A GRAZZINI, G IOSSA, A CIATTO, S TI TESTING CERVICOGRAPHY AND CERVICOSCOPY AS SCREENING-TESTS FOR CERVICAL-CANCER SO TUMORI LA English DT Article DE CERVICAL CANCER SCREENING; CERVICAL CYTOLOGY; CERVICOGRAPHY ID PAPANICOLAOU SMEAR; NEGATIVE SMEARS; CYTOLOGY; RATES; SENSITIVITY; FLORENCE; PROGRAM AB Aims and Background. Suboptimal sensitivity is currently reported for Pap test in screening for cervical cancer. Colposcopy is known to be more sensitive than cytology but its use as a screening test Is not possible due to costs and complexity. Screening by cervicography has been suggested as a compromise being less costly and feasible. The present study evaluates the feasibility of screening by cervicography and cervicoscopy (naked eye examination of the cervix after acetic acid lavage) on a consecutive screening series. Methods: Cervicography and cervicoscopy were performed by the smear taker in subjects consecutively attending a screening clinic. Women with abnormal cytology (atypia or more severe lesion) and/or abnormal cervicography or cervicoscopy (acetowhite lesion) underwent colposcopic assessment. The three screening methods were compared according to positivity rate, CIN 2-3 detection rate and positive predictive value. Results: 2105 consecutive subjects were screened. Positivity rate was 3.8 %, 15.3 % or 25.4 % for cytology, cervicography or cervicoscopy, respectively, 486 of 555 women attended the assessment phase, 281 directed biopsies were performed and 8 CIN 2-3 lesions were detected. Cytology, cervicography and cervicoscopy, detected 5.5, or 7 of 8 CIN 2-3 lesions, respectively. The positive predictive value was 0 % for cytologic atypia, 25 % for cytologic SIL, 1.75 % for cervicography and 2.05 % for cervicoscopy. Detecting one CIN 2-3 lesion at cytology cost $ 5,543. The cost per each additional cytologically negative CIN 2-3 lesion detected at cervicography or cervicoscopy was $ 12,947 or $ 3,916, respectively. Conclusions: The study confirms the limited sensitivity of cytology for CIN 2-3. The association of cervicography was not cost effective. Cervicoscopy was poorly specific but increased the detection rate of CIN 2-3 at relatively low costs. Cervicoscopy is worth further evaluation as a screening test. C1 CTR STUDIO PREVENZ ONCOL,VIALE A VOLTA 171,I-50131 FLORENCE,ITALY. NATL CANC INST,GENOA,ITALY. RI Grazzini, Grazia/K-8503-2016 OI Grazzini, Grazia/0000-0002-9713-3007 NR 23 TC 41 Z9 42 U1 0 U2 2 PU PENSIERO SCIENTIFICO EDITOR PI ROME PA VIA BRADANO 3/C, 00199 ROME, ITALY SN 0300-8916 J9 TUMORI JI Tumori PD FEB 28 PY 1993 VL 79 IS 1 BP 22 EP 25 PG 4 WC Oncology SC Oncology GA LE160 UT WOS:A1993LE16000004 PM 8497916 ER PT J AU WANG, RYH SHIH, JWK HAYES, MM ALTER, HJ WEAR, DJ LO, SC AF WANG, RYH SHIH, JWK HAYES, MM ALTER, HJ WEAR, DJ LO, SC TI ANTIBODIES TO MYCOPLASMA-PENETRANS IN HIV-INFECTED PATIENTS - REPLY SO LANCET LA English DT Letter C1 NIH,CTR CLIN,DEPT TRANSFUS MED,BETHESDA,MD 20892. RP WANG, RYH (reprint author), ARMED FORCES INST PATHOL,AMER REGISTRY PATHOL,DEPT INFECT & PARASIT DIS PATHOL,WASHINGTON,DC 20306, USA. NR 6 TC 2 Z9 2 U1 0 U2 0 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD FEB 27 PY 1993 VL 341 IS 8844 BP 558 EP 558 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA KP083 UT WOS:A1993KP08300030 ER PT J AU BLACK, S AF BLACK, S TI A PROVISIONAL MECHANISM FOR REGULATING THE AMINOACYL-TRANSFER RNA-SYNTHETASES SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID PHOTOSYNTHESIS; YEAST RP BLACK, S (reprint author), NIDDKD,BIOCHEM PHARMACOL LAB,BETHESDA,MD 20892, USA. NR 19 TC 3 Z9 3 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD FEB 26 PY 1993 VL 191 IS 1 BP 95 EP 102 DI 10.1006/bbrc.1993.1189 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA KQ344 UT WOS:A1993KQ34400014 PM 8447838 ER PT J AU GALDZICKI, Z COAN, E RAPOPORT, SI AF GALDZICKI, Z COAN, E RAPOPORT, SI TI CULTURED HIPPOCAMPAL-NEURONS FROM TRISOMY 16 MOUSE, A MODEL FOR DOWNS-SYNDROME, HAVE AN ABNORMAL ACTION-POTENTIAL DUE TO A REDUCED INWARD SODIUM CURRENT SO BRAIN RESEARCH LA English DT Article DE TRISOMY 16; DOWNS SYNDROME; ACTION POTENTIAL; CURRENT; HIPPOCAMPUS; PRIMARY CULTURE; MOUSE; PATCH-CLAMP ID DORSAL-ROOT GANGLION; ELECTRICAL MEMBRANE-PROPERTIES; NERVE GROWTH-FACTOR; PYRAMIDAL NEURONS; GUINEA-PIG; ELECTROPHYSIOLOGICAL PROPERTIES; HUMAN CHROMOSOME-21; SYNDROME REGION; FETAL MOUSE; FETUS AB Mouse trisomy 16 is an animal model for Down's syndrome (human trisomy 21). The whole-cell patch-clamp technique was used to compare passive and active electrical properties of trisomy 16 and diploid mouse 16 fetal hippocampal neurons maintained in culture for 2-5 weeks. There was no significant difference in any mean passive property, including resting potential, membrane resistance, capacitance and time constant. However, in trisomic neurons, the action potential had a 20% significantly slower rising phase and a 20% significantly smaller inward sodium current and inward sodium conductance than did control neurons. The outward conductance was not altered. The ratio of maximum inward conductance to maximum outward conductance was 30% less in the trisomy 16 cells. These results indicate that trisomy 16 hippocampal neurons have abnormal active electrical properties, most likely reflecting reduced sodium channel membrane density. Such subtle differences may influence elaboration of the hippocampus during development. RP GALDZICKI, Z (reprint author), NIA,NEUROSCI LAB,BLDG 10,ROOM 6C103,BETHESDA,MD 20892, USA. NR 51 TC 47 Z9 47 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD FEB 26 PY 1993 VL 604 IS 1-2 BP 69 EP 78 DI 10.1016/0006-8993(93)90353-O PG 10 WC Neurosciences SC Neurosciences & Neurology GA KN960 UT WOS:A1993KN96000009 PM 8384514 ER PT J AU CONSTANTOULAKIS, P CAMPBELL, M FELBER, BK NASIOULAS, G AFONINA, E PAVLAKIS, GN AF CONSTANTOULAKIS, P CAMPBELL, M FELBER, BK NASIOULAS, G AFONINA, E PAVLAKIS, GN TI INHIBITION OF REV-MEDIATED HIV-1 EXPRESSION BY AN RNA-BINDING PROTEIN ENCODED BY THE INTERFERON-INDUCIBLE-9-27 GENE SO SCIENCE LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; VIRAL MESSENGER-RNA; INTERFERON-STIMULATED GENES; KAPOSIS-SARCOMA; TARGET SEQUENCE; FUNCTIONAL-ANALYSIS; TRANS-ACTIVATOR; ALPHA; REPLICATION; GAMMA AB Interferon inhibits expression of human immunodeficiency virus type-1 (HIV-1) through unknown mechanisms. A gene inducible by interferon-alpha (IFN-alpha) and interferon-gamma (IFN-gamma) was isolated by screening of a human complementary DNA library for proteins binding to the Rev-responsive element (RRE) of HIV-1. The product of this gene, RBP9-27, was shown to bind RNA in vitro and to inhibit HIV-1 expression after transfection into human cells. RBP9-27 primarily inhibited Rev-dependent posttranscriptional steps of viral gene expression. Thus, RBP9-27 is a cellular factor that antagonizes Rev function. These results suggest an interferon-induced antiviral mechanism operating through the induction of RNA binding proteins such as RBP9-27. Elucidation of RBP9-27 function may lead to a better understanding of the mechanism of interferon action during HIV-1 infection. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,HUMAN RETROVIRUS SECT,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,HUMAN RETROVIRUS PATHOGENESIS GRP,FREDERICK,MD 21702. FU NCI NIH HHS [N0-CO-74101] NR 67 TC 48 Z9 50 U1 0 U2 4 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD FEB 26 PY 1993 VL 259 IS 5099 BP 1314 EP 1318 DI 10.1126/science.7680491 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA KN883 UT WOS:A1993KN88300028 PM 7680491 ER PT J AU COLOMBO, MF RAU, DC PARSEGIAN, VA AF COLOMBO, MF RAU, DC PARSEGIAN, VA TI THE ROLE OF WATER IN HEMOGLOBIN-FUNCTION AND STABILITY - RESPONSE SO SCIENCE LA English DT Article ID DNA DOUBLE HELICES; HYDRATION FORCES; BILAYERS C1 NIDDKD,BIOCHEM & METAB LAB,BETHESDA,MD 20892. NIH,DIV COMP RES & TECHNOL,PHYS SCI LAB,BETHESDA,MD 20892. RP COLOMBO, MF (reprint author), UNIV ESTADUAL PAULISTA,INST BIOCIENCIAS LETTRAS & CIENCIAS EXATAS,DEPT FIS,BR-15055 S JOSE RIO P,SP,BRAZIL. RI Colombo, Marcio/K-5229-2013 OI Colombo, Marcio/0000-0003-3035-3926 NR 8 TC 2 Z9 2 U1 1 U2 2 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD FEB 26 PY 1993 VL 259 IS 5099 BP 1336 EP 1336 DI 10.1126/science.259.5099.1336 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA KN883 UT WOS:A1993KN88300035 PM 17732254 ER PT J AU WICKNER, RB AF WICKNER, RB TI DOUBLE-STRANDED-RNA VIRUS-REPLICATION AND PACKAGING SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Review ID SACCHAROMYCES-CEREVISIAE; READING FRAMES; L-A; PROTEIN; YEAST; ENCODES; BACTERIOPHAGE-PHI-6; POLYPEPTIDES; PARTICLES; ROTAVIRUS RP WICKNER, RB (reprint author), NIDDKD,GENET SIMPLE EUKARYOTES SECT,BLDG 8,RM 207,BETHESDA,MD 20892, USA. NR 38 TC 43 Z9 45 U1 2 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD FEB 25 PY 1993 VL 268 IS 6 BP 3797 EP 3800 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA KN533 UT WOS:A1993KN53300001 PM 8440674 ER PT J AU HALLENBECK, PL PHYILLAIER, M NIKODEM, VM AF HALLENBECK, PL PHYILLAIER, M NIKODEM, VM TI DIVERGENT EFFECTS OF 9-CIS-RETINOIC ACID RECEPTOR ON POSITIVE AND NEGATIVE THYROID-HORMONE RECEPTOR-DEPENDENT GENE-EXPRESSION SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Note ID OSTEOCALCIN GENE; RESPONSIVE ELEMENT; RETINOIC ACID; BINDING; PROMOTER AB The thyroid hormone (TH)-inducible expression of some genes has recently been shown to be enhanced by 9-cis-retinoic acid (9-cis-RA) receptor (RXR). This effect appears to be at least partially elicited by the ability of RXR to heterodimerize with TH receptor (THR) and enhance its binding to the cis-acting thyroid hormone responsive elements (TREs) found within those genes. However, whether RXRbeta enhances TH/THR-mediated transactivation of all TRE-containing genes, and if RXR has any effect on TH-dependent negative regulation are not known. In the present study, we show that the TH/THR-inducible expression of the myelin basic protein (MBP) gene is not enhanced by RXRbeta, despite high affinity binding of the RXRbeta.THRalpha heterodimer to the MBP-TRE. We also demonstrate that RXRbeta reverses the TH/THR-dependent down-regulation mediated by the negative TRE found within the promoter of the mouse thyroid stimulating hormone gene (TSH). The ligand for RXRbeta (9-cis-RA), either alone or in combination with TH, did not enhance the transcription mediated by either the MBP-TRE, TSH-TRE, or the malic enzyme (ME)-TRE. However, the ME-TRE is known to confer RXRbeta-dependent enhancement of TH-induced gene expression. Thus, the capacity of RXRbeta to modulate TH-dependent transcriptional regulation depends upon the nature of the TRE. C1 NIDDKD,GENET & BIOCHEM BRANCH,BETHESDA,MD 20892. NR 28 TC 53 Z9 53 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD FEB 25 PY 1993 VL 268 IS 6 BP 3825 EP 3828 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA KN533 UT WOS:A1993KN53300008 PM 7680034 ER PT J AU MENNITI, FS MILLER, RN PUTNEY, JW SHEARS, SB AF MENNITI, FS MILLER, RN PUTNEY, JW SHEARS, SB TI TURNOVER OF INOSITOL POLYPHOSPHATE PYROPHOSPHATES IN PANCREATOMA CELLS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MYOINOSITOL 1,3,4,5,6-PENTAKISPHOSPHATE; PENTAKISPHOSPHATE; HEXAKISPHOSPHATE; METABOLISM; PHOSPHATES; 1,3,4-TRISPHOSPHATE; TETRAKISPHOSPHATES; PHOSPHORYLATION; CALCIUM AB There is little information concerning the intracellular function of inositol 1,3,4,5,6-pentakis- and hexakisphosphate, despite their being the most abundant inositol polyphosphates. Current opinions that they play passive roles as antioxidants (Graf, E., Mahoney, J. R., Bryant, R. G., and Eaton, J. W. (1987) J. Biol. Chem. 259, 3620-3624) or ''housekeeping'' molecules (Berridge, M. J., and Irvine, R. F. (1989) Nature 341, 197-205) arises from belief in their metabolic lethargy. However, we have discovered that celt homogenates, incubated with 5 mm fluoride and 5 mM ATP, converted both inositol hexakisphosphate (K(m) = 2 +/-0.5 muM, V(max) = 9 +/- 2 pmol/mg of protein/min) and inositol 1,3,4,5,6-pentakisphosphate (K(m) = 13 +/- 4 muM, V(max) = 11 +/- 5 pmol/mg of protein/min) to more polar products. These reactions were also observed in intact cells treated with 0.5-20 mM fluoride, and the precursor/product relationships were confirmed by comparing the effects of fluoride on cells differentially labeled with [H-3]inositol in either short-term or pulse-chase protocols. The novel products were determined to be inositol pyrophosphates because of their relatively specific hydrolysis by tobacco pyrophosphatase and alkaline phosphatase. The pyrophosphates were metabolized rapidly by cell homogenates back to their pentakisphosphate and hexakisphosphate precursors. This endogenous pyrophosphatase activity was inhibited by up to 99% by 5 mM fluoride in vitro. In intact cells incubated with 10 mM fluoride, about 20% of the inositol 1,3,4,5,6-pentakisphosphate pool, and 50% of the inositol hexakisphosphate pool were each converted to pyrophosphate derivatives within 1 h. C1 NIEHS,CELLULAR & MOLEC PHARMACOL LAB,INOSITOL LIPID SECT,RES TRIANGLE PK,NC 27709. NIEHS,CALCIUM REGULAT SECT,RES TRIANGLE PK,NC 27709. OI Menniti, Frank/0000-0003-2612-9534 NR 28 TC 139 Z9 141 U1 1 U2 5 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 25 PY 1993 VL 268 IS 6 BP 3850 EP 3856 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA KN533 UT WOS:A1993KN53300013 PM 8382679 ER PT J AU YIM, MB CHOCK, PB STADTMAN, ER AF YIM, MB CHOCK, PB STADTMAN, ER TI ENZYME FUNCTION OF COPPER, ZINC SUPEROXIDE-DISMUTASE AS A FREE-RADICAL GENERATOR SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ELECTRON-SPIN-RESONANCE; HYDROGEN-PEROXIDE; HYDROXYL RADICALS; GLUTATHIONE-PEROXIDASE; PULSE-RADIOLYSIS; CATION RADICALS; INACTIVATION; KINETICS; PARAQUAT; TRAPS AB The peroxidative activity-of Cu,Zn-containing superoxide dismutase (Cu,Zn-SOD) was studied by using a chromogen, 2,2'-azinobis-(3-ethylbenzthiazoline-6-sulfonate) (ABTS) which reacts with .OH radicals to form ABTS+., and the spin traps, N-tert-butyl-alpha-phenylnitrone (PBN) and 5,5-dimethyl-1-pyrroline N-oxide (DMPO). The formation of ABTS+. in this study required both active Cu,Zn-SOD and H2O2 and followed first order kinetics with respect to SOD and H2O2. However, it showed a binding isotherm with ABTS that yielded a dissociation constant of ABTS-enzyme as K(d) = 7.1 +/- 0.5 muM. The K(d) values for DMPO and PBN were obtained as 0.63 and 11 mM, respectively, by competition reactions. A radical scavenger, formate anion, inhibits the formation of ABTS+., whereas ethanol does not. The results together indicate that DMPO and anionic scavengers have easy access inside the positively charged active channel of Cu,Zn-SOD and are thus in a position to intercept the newly formed .OH radicals. PBN and ethanol, however, stay outside of the channel and are not able to compete with ABTS for .OH radicals. We trapped free radicals, which were produced in the presence of free radical scavengers, with PBN. The formation curve of PBN-hydroxyethyl radical adduct observed in the presence of ethanol indicated that the enzyme became inactivated in a relatively short period. In contrast, in the presence of anionic scavenger formate, formyl radicals were produced catalytically, and the enzyme activity was protected by the formate against H2O2 inactivation. Thus Cu,Zn-SOD behaves as an enzyme that catalyzes the formation of free radicals using anionic scavengers and H2O2 as substrates. RP NHLBI, BIOCHEM LAB, BLDG 3, RM 202, BETHESDA, MD 20892 USA. NR 54 TC 208 Z9 211 U1 2 U2 6 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD FEB 25 PY 1993 VL 268 IS 6 BP 4099 EP 4105 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA KN533 UT WOS:A1993KN53300047 PM 8382691 ER PT J AU KIRKNESS, EF FRASER, CM AF KIRKNESS, EF FRASER, CM TI A STRONG PROMOTER ELEMENT IS LOCATED BETWEEN ALTERNATIVE EXONS OF A GENE ENCODING THE HUMAN GAMMA-AMINOBUTYRIC ACID-TYPE-A RECEPTOR BETA-3 SUBUNIT (GABRB3) SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GABAA RECEPTOR; TRANSCRIPTION INITIATION; MESSENGER-RNAS; MOLECULAR-BIOLOGY; REGION; EXPRESSION; DISTINCT; BINDING; PEPTIDE; CHROMOSOME-15 AB The gene that encodes the beta3 subunit of the gamma-aminobutyrate-Type A (GABA(A)) receptor is widely expressed in brain tissue and has been associated with imprinted genetic disorders. Here, the 5' regions of the human and rat genes were characterized and found to be highly conserved in both coding and non-coding sequences. A novel transcript of the human gene revealed the existence of an alternative exon 1 (exon 1a) that encodes a variant signal sequence. Relative levels of the alternative transcripts were found to vary between fetal and adult brain, and between different brain regions. Endogenous beta3 subunit transcripts were also detected in several immortalized cell lines, including human kidney 293 cells. Transcription of exon 1 is initiated from multiple sites within a pyrimidine-rich region of the gene. This region of the human gene also exhibits strong promoter activity and binds nuclear factors at a site which overlaps the transcriptional start sites. The promoter element was shown to bind Sp1 and at least one other unidentified nuclear factor. C1 NIAAA,NEUROGENET LAB,MOLEC NEUROBIOL SECT,ROCKVILLE,MD 20852. OI Fraser, Claire/0000-0003-1462-2428 NR 57 TC 90 Z9 94 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 25 PY 1993 VL 268 IS 6 BP 4420 EP 4428 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA KN533 UT WOS:A1993KN53300088 PM 8382702 ER PT J AU TSAIMORRIS, CH XIE, XZ WANG, W BUCZKO, E DUFAU, ML AF TSAIMORRIS, CH XIE, XZ WANG, W BUCZKO, E DUFAU, ML TI PROMOTER AND REGULATORY REGIONS OF THE RAT LUTEINIZING-HORMONE RECEPTOR GENE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TRANSCRIPTION FACTOR; ULTRABITHORAX PROMOTER; RNA-POLYMERASE; SEQUENCE; INDUCTION; INVITRO; CELL AB The region of transcriptional activity in the rat luteinizing hormone receptor gene was localized to the 5'-flanking 173-base pair (bp) sequence in transfected mouse Leydig tumor cells and non-expressing Chinese hamster ovarian (CHO) and HeLa cells. Repression of activity in all cell types was induced by at least two domains located between -174 and -990 bp. An additional inhibitory region between -1237 and -2056 bp observed only in CHO and HeLa cells may contribute to the absence of receptor expression in these cells. Analysis of the 173-bp region revealed a promoter domain between -1 and -137 bp containing no TATA or CAAT boxes, but with three SP1 sites and three initiator elements located at transcriptional start sites -14, -19, and -33. Gel retardation studies showed a protein-binding DNA domain about 30 bp upstream of the transcriptional start sites and an adjacent domain containing an SP1 element that are required for maximal activity in all cell types and may play a role in basal transcription. A second promoter domain (-120 to -173 bp) with a protein-binding SP1 element had minor activity in Leydig cells but was prominent in CHO and HeLa cells. Leydig cell-specific DNA-binding protein(s) for each of the promoter domains were detected and may be of importance in transcriptional regulation. The control of gene transcription by differential activation of these promoter domains could be involved in hormone-induced regulation of luteinizing hormone receptor expression in the gonads. RP TSAIMORRIS, CH (reprint author), NICHHD,ENDOCRINOL & REPROD RES BRANCH,MOLEC ENDOCRINOL SECT,BETHESDA,MD 20892, USA. NR 23 TC 48 Z9 48 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD FEB 25 PY 1993 VL 268 IS 6 BP 4447 EP 4452 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA KN533 UT WOS:A1993KN53300091 PM 8440726 ER PT J AU ROSENBERG, HF ACKERMAN, SJ TENEN, DG AF ROSENBERG, HF ACKERMAN, SJ TENEN, DG TI CHARACTERIZATION OF A DISTINCT BINDING-SITE FOR THE PROKARYOTIC CHAPERONE, GROEL, ON A HUMAN GRANULOCYTE RIBONUCLEASE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID EOSINOPHIL CATIONIC PROTEIN; RIBULOSE BISPHOSPHATE CARBOXYLASE; HEAT-SHOCK PROTEINS; ESCHERICHIA-COLI GROEL; RIBULOSEBISPHOSPHATE-CARBOXYLASE; MOLECULAR-CLONING; BACTERIOPHAGE MORPHOGENESIS; MITOCHONDRIAL PROTEIN; ATP HYDROLYSIS; GENE AB Although ribonucleases fold into correct tertiary conformation in vitro guided solely by information contained in the primary amino acid sequence (Sela, M., White, F. H., and Anfinsen, C. B. (1957) Science 124, 691-693), it is not clear whether folding of these proteins proceeds unassisted in a complex intracellular environment. We describe here the specific and high affinity binding of groEL, the prokaryotic homolog of the heat shock protein 60 family of molecular chaperones, to recombinant eosinophil cationic protein and eosinophil-derived neurotoxin, two members of the human ribonuclease gene family. We have determined that groEL binds to a unique peptide sequence near the amino terminus of nascent eosinophil cationic protein that includes the first of eight cysteine residues. This binding site functions independently and can confer groEL binding activity on an unrelated carrier protein. GroEL dissociates from the binding site upon addition of ATP and Mg2+; no other cations or cofactors are necessary. These findings suggest the possibility that interaction with a groEL-like molecular chaperone may be a requirement for correct folding and/or translocation of eukaryotic ribonucleases in vivo. C1 BETH ISRAEL HOSP,DEPT MED,BOSTON,MA 02215. RP ROSENBERG, HF (reprint author), NIAID,HOST DEF LAB,BLDG 10,RM 11N114,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. FU NHLBI NIH HHS [HL02288]; NIAID NIH HHS [AI25230, AI22660] NR 72 TC 25 Z9 25 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD FEB 25 PY 1993 VL 268 IS 6 BP 4499 EP 4503 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA KN533 UT WOS:A1993KN53300099 PM 8095049 ER PT J AU TOMAREV, SI ZINOVIEVA, RD GUO, K PIATIGORSKY, J AF TOMAREV, SI ZINOVIEVA, RD GUO, K PIATIGORSKY, J TI SQUID GLUTATHIONE-S-TRANSFERASE - RELATIONSHIPS WITH OTHER GLUTATHIONE S-TRANSFERASES AND S-CRYSTALLINS OF CEPHALOPODS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ARGININOSUCCINATE LYASE; DIRECTED MUTAGENESIS; NUCLEOTIDE-SEQUENCE; STRUCTURAL PROTEIN; MULTIGENE FAMILY; GENE-EXPRESSION; CDNA CLONE; P-GENE; RAT; LENS AB Glutathione S-transferase (GST, EC 2.5.1.18) was purified from the digestive gland of the squid Ommastrephes sloani pacificus. It had high enzymatic activity for the 1-chloro-2,4-dinitrobenzene substrate and was composed of a major and a minor polypeptide band, both with molecular masses near 25 kDa on SDS-polyacrylamide gels. GST cDNA clones were derived from the digestive gland mRNA. The deduced GSTs of the longest cDNAs (pGST5 and pGST11) containing the entire coding sequence have a molecular mass near 23 kDa. Sequence comparisons showed that the squid GST is 42-44% identical to both squid and octopus S-crystallins (the major proteins of the lens), 32-34% identical to class pi and 29-32% identical to class alpha GSTs of vertebrates, and 19-23% identical to other GSTs of vertebrates and insects. Northern blot hybridization revealed that GST mRNAs were much more abundant in the digestive gland than in the testis, mantle, or lens. Analysis of a squid GST gene indicated that it has an exon-intron structure similar to that of the vertebrate class pi GST gene. An apparently novel repetitive element was identified in the 5'-flanking sequence of the squid GST gene. Our results suggest that multiple duplications of an ancestral GST gene gave rise to a family of enzymatically inactive crystallins specialized for lens refraction and one (or two) active GST enzyme expressed preferentially, but not exclusively, in the digestive gland in squids. This differs from the innovation of refractive function from a metabolic enzyme by increased expression in the lens with minimal or no gene duplication, as occurred among the enzyme-crystallins of vertebrates. RP TOMAREV, SI (reprint author), NEI,MOLEC & DEV BIOL LAB,BETHESDA,MD 20892, USA. NR 56 TC 55 Z9 56 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 25 PY 1993 VL 268 IS 6 BP 4534 EP 4542 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA KN533 UT WOS:A1993KN53300105 PM 8440736 ER PT J AU DEVITA, VT HUBBARD, SM AF DEVITA, VT HUBBARD, SM TI DRUG-THERAPY - HODGKINS-DISEASE SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Review ID BONE-MARROW TRANSPLANTATION; COMBINED MODALITY TREATMENT; HIGH-DOSE CHEMOTHERAPY; PROSPECTIVE RANDOMIZED TRIAL; COMBINATION CHEMOTHERAPY; RADIATION-THERAPY; MOPP CHEMOTHERAPY; SALVAGE CHEMOTHERAPY; COMPLETE REMISSION; HYBRID PROGRAM C1 NCI,BETHESDA,MD 20892. RP DEVITA, VT (reprint author), MEM SLOAN KETTERING CANC CTR,1275 YORK AVE,NEW YORK,NY 10021, USA. NR 61 TC 96 Z9 97 U1 0 U2 1 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD FEB 25 PY 1993 VL 328 IS 8 BP 560 EP 565 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA KP053 UT WOS:A1993KP05300008 PM 8426624 ER PT J AU GOOD, PJ REBBERT, ML DAWID, IB AF GOOD, PJ REBBERT, ML DAWID, IB TI 3 NEW MEMBERS OF THE RNP PROTEIN FAMILY IN XENOPUS SO NUCLEIC ACIDS RESEARCH LA English DT Article ID NUCLEAR RIBONUCLEOPROTEIN-PARTICLES; B-HNRNP PROTEIN; BINDING PROTEINS; SEQUENCE-ANALYSIS; CORE PROTEIN-A1; NERVOUS-SYSTEM; CDNA CLONING; SEX-LETHAL; GENE; LAEVIS AB Many RNP proteins contain one or more copies of the RNA recognition motif (RRM) and are thought to be involved in cellular RNA metabolism. We have previously characterized in Xenopus a nervous system specific gene, nrp1, that is more similar to the hnRNP A/B proteins than to other known proteins (K.Richter, P.J.Good, and I.B.Dawid (1990), New Biol. 2,556 - 565). PCR amplification with degenerate primers was used to identify additional cDNAs encoding two RRMs in Xenopus. Three previously uncharacterized genes were identified. Two genes encode hnRNP A/B proteins with two RRMs and a glycine-rich domain. One of these is the Xenopus homolog of the human A2/B1 gene; the other, named hnRNP A3, is similar to both the A1 and A2 hnRNP genes. The Xenopus hnRNP A1, A2 and A3 genes are expressed throughout development and in all adult tissues. Multiple protein isoforms for the hnRNP A2 gene are predicted that differ by the insertion of short peptide sequences in the glycine-rich domain. The third newly isolated gene, named xrp1, encodes a protein that is related by sequence to the nrp1 protein but is expressed ubiquitously. Despite the similarity to nuclear RNP proteins, both the nrp1 and xrp1 proteins are localized to the cytoplasm in the Xenopus oocyte. The xrp1 gene may have a function in all cells that is similar to that executed by nrp1 specifically within the nervous system. RP NICHHD, MOLEC GENET LAB, BETHESDA, MD 20892 USA. NR 61 TC 37 Z9 41 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD FEB 25 PY 1993 VL 21 IS 4 BP 999 EP 1006 DI 10.1093/nar/21.4.999 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA KR189 UT WOS:A1993KR18900028 PM 8451200 ER PT J AU TILLY, K CAMPBELL, J AF TILLY, K CAMPBELL, J TI A BORRELIA-BURGDORFERI HOMOLOG OF THE ESCHERICHIA-COLI RHO GENE SO NUCLEIC ACIDS RESEARCH LA English DT Note ID TERMINATION; PROTEIN; SITE RP TILLY, K (reprint author), NIAID,ROCKY MT LABS,MICROBIAL STRUCT & FUNCT LAB,HAMILTON,MT 59840, USA. NR 5 TC 8 Z9 10 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD FEB 25 PY 1993 VL 21 IS 4 BP 1040 EP 1040 DI 10.1093/nar/21.4.1040 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA KR189 UT WOS:A1993KR18900039 PM 8451174 ER PT J AU CELI, FS ZENILMAN, ME SHULDINER, AR AF CELI, FS ZENILMAN, ME SHULDINER, AR TI A RAPID AND VERSATILE METHOD TO SYNTHESIZE INTERNAL STANDARDS FOR COMPETITIVE PCR SO NUCLEIC ACIDS RESEARCH LA English DT Note C1 NIA,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,SCH MED,BALTIMORE,MD 21205. NR 3 TC 309 Z9 326 U1 1 U2 5 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD FEB 25 PY 1993 VL 21 IS 4 BP 1047 EP 1047 DI 10.1093/nar/21.4.1047 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA KR189 UT WOS:A1993KR18900045 PM 8451177 ER PT J AU LILLIEBLANTON, M ANTHONY, JC SCHUSTER, CR AF LILLIEBLANTON, M ANTHONY, JC SCHUSTER, CR TI PROBING THE MEANING OF RACIAL ETHNIC-GROUP COMPARISONS IN CRACK COCAINE SMOKING SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article AB Objective.-To probe the meaning of reported racial and ethnic group differences in the prevalence of crack cocaine smoking and to estimate the degree to which crack cocaine smoking is associated with personal factors specific to race/ethnicity. Design.-Through reanalysis of data from the 1988 National Household Survey of Drug Abuse (NHSDA), we compared racial/ethnic group differences in crack cocaine smoking. To hold constant social and environmental risk factors that might potentially confound racial comparisons, we used an epidemiologic strategy that involves poststratification of respondents into neighborhood risk sets. A conditional logistic regression model was used to estimate the relative odds of crack use by race/ethnicity. Patients or Other Participants.-The 1988 NHSDA interviewed 8814 individuals residing within households in the United States. Subjects were selected using a multistage area probability sampling of all residents aged 12 years and older. Results.-Once respondents were grouped into neighborhood clusters, the relative odds (RO) of crack use did not differ significantly for African Americans (RO, 0.85; 95% confidence interval [CI], 0.37 to 1.93) or for Hispanic Americans (RO, 0.88; 95% CI, 0.47 to 1.67) compared with white Americans. Conclusion.-Findings of race-associated differences are often presented as if a person's race has intrinsic explanatory power. This analysis provides evidence that, given similar social and environmental conditions, crack use does not strongly depend on race-specific (eg, biologic) personal factors. Although the study finding does not refute the previous analysis, it provides evidence that prevalence estimates unadjusted for social environmental risk factors may lead to misunderstanding about the role of race or ethnicity in the epidemiology of crack use. Future research should seek to identify which characteristics of the neighborhood social environment are important and potentially modifiable determinants of drug use. C1 NIDA,ADDICT RES CTR,POB 5180,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT HLTH POLICY & MANAGEMENT,BALTIMORE,MD 21218. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT MENTAL HYG,BALTIMORE,MD 21218. FU NIDA NIH HHS [DA04392] NR 11 TC 125 Z9 126 U1 5 U2 11 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 24 PY 1993 VL 269 IS 8 BP 993 EP 997 DI 10.1001/jama.269.8.993 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA KM603 UT WOS:A1993KM60300026 PM 8429605 ER PT J AU HALL, WH GOLLAN, JL BULKLEY, GB DIEHL, AM ELASHOFF, JD FEDERLE, MP HENDERSON, JM HOGAN, WJ KELLY, KA MASSANARI, DL POWELL, DW RIKKERS, LF SORRELL, M THIEL, TK WILSON, JAP AF HALL, WH GOLLAN, JL BULKLEY, GB DIEHL, AM ELASHOFF, JD FEDERLE, MP HENDERSON, JM HOGAN, WJ KELLY, KA MASSANARI, DL POWELL, DW RIKKERS, LF SORRELL, M THIEL, TK WILSON, JAP TI GALLSTONES AND LAPAROSCOPIC CHOLECYSTECTOMY SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material C1 HARVARD UNIV, SCH MED, BOSTON, MA 02115 USA. BRIGHAM & WOMENS HOSP, DIV GASTROENTEROL, BOSTON, MA 02115 USA. JOHNS HOPKINS MED INST, BALTIMORE, MD 21205 USA. JOHNS HOPKINS UNIV, SCH MED, DEPT MED, DIV GASTROENTEROL, BALTIMORE, MD 21205 USA. CEDARS SINAI MED CTR, DEPT MED, DIV BIOSTAT, LOS ANGELES, CA 90048 USA. UNIV CALIF LOS ANGELES, MED CTR, LOS ANGELES, CA USA. UNIV PITTSBURGH, PITTSBURGH, PA 15260 USA. CLEVELAND CLIN EDUC FDN, DEPT GEN SURG, CLEVELAND, OH 44106 USA. MED COLL WISCONSIN, MILWAUKEE, WI 53226 USA. FROEDBERT MEM LUTHERAN HOSP, DIV GASTROENTEROL, MILWAUKEE, WI USA. MAYO CLIN & MAYO FDN, MAYO MED SCH, DEPT SURG, ROCHESTER, MN 55905 USA. SANFORD FAMILY HLTH CARE PA, SANFORD, ME USA. UNIV TEXAS, MED BRANCH, DEPT INTERNAL MED, GALVESTON, TX 77550 USA. UNIV NEBRASKA, MED CTR, DEPT SURG, OMAHA, NE 68105 USA. UNIV NEBRASKA, MED CTR, LIVER TRANSPLANT PROGRAM, OMAHA, NE 68105 USA. AMER LIVER FDN, CEDAR GROVE, NJ USA. DUKE UNIV, MED CTR, DIV GASTROENTEROL, OUTPATIENT SERV, DURHAM, NC 27710 USA. RP HALL, WH (reprint author), NIH, OFF MED APPLICAT RES, FED BLDG, ROOM 618, BETHESDA, MD 20892 USA. RI Powell, Don/K-4774-2014 NR 0 TC 152 Z9 157 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD FEB 24 PY 1993 VL 269 IS 8 BP 1018 EP 1024 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA KM603 UT WOS:A1993KM60300031 ER PT J AU YUAN, DS WANK, SA GARDNER, JD AF YUAN, DS WANK, SA GARDNER, JD TI CIBACRON BLUE-INDUCED ENHANCEMENT OF AGONIST BINDING TO CHOLECYSTOKININ (CCK) RECEPTORS IN SOLUBILIZED PANCREATIC MEMBRANES SO BIOCHIMICA ET BIOPHYSICA ACTA LA English DT Article DE CIBACRON BLUE; CHOLECYSTOKIN RECEPTOR; RECEPTOR BINDING; (PANCREAS) ID NUCLEOTIDE REGULATORY PROTEINS; VASOACTIVE INTESTINAL PEPTIDE; BETA-ADRENERGIC-RECEPTOR; BRAIN; ANTAGONIST; COMPLEX; RECONSTITUTION; PURIFICATION; ASSOCIATION; CYCLASE AB The pancreatic receptor for cholecystokinin (CCK) typifies many G protein-coupled receptors in that its ability to bind agonist can be reduced by GTP or the solubilization of membranes. We found, however, that a dye, cibacron blue, caused up to a 6-fold increase in binding of the CCK receptor agonist, I-125-CCK-8, to rat pancreatic membranes solubilized with digitonin. Binding optimally enhanced in this manner was comparable to binding of I-125-CCK-8 to native membranes with respect to time-course, maximal amount bound, reversibility, and sensitivity to inhibition by various CCK receptor ligands. Increases in affinity of the CCK receptor for CCK-8 accounted fully for the enhancement of binding of I-125-CCK-8. Cibacron blue did not enhance binding of I-125-CCK-8 to native membranes, and also failed to enhance binding of the CCK receptor antagonist, [H-3]L-364,718, to solubilized or native membranes. The ability of cibacron blue to enhance binding of agonist but not that of antagonist suggests that this dye may mimic or perhaps stimulate the effects of G protein on CCK receptors. Such a phenomenon may provide new insights into the mechanisms by which receptors distinguish agonists from antagonists. C1 ST LOUIS UNIV, MED CTR, DEPT INTERNAL MED, 1402 S GRAND, ST LOUIS, MO 63104 USA. NIDDKD, DIGEST DIS BRANCH, BETHESDA, MD USA. NR 40 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-3002 J9 BIOCHIM BIOPHYS ACTA JI Biochim. Biophys. Acta PD FEB 23 PY 1993 VL 1146 IS 1 BP 52 EP 58 DI 10.1016/0005-2736(93)90337-Y PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA KN957 UT WOS:A1993KN95700007 PM 8443227 ER PT J AU ALBORNOZ, L JONES, JM VEECH, RL AF ALBORNOZ, L JONES, JM VEECH, RL TI LIVER CYTOTOXIC LYMPHOCYTES AND THEIR MEDIATION OF HEPATIC CELL INJURY AFTER CHRONIC ETHANOL (ETOH) SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAAA,ROCKVILLE,MD 20852. UNIV ARKANSAS MED SCI HOSP,DEPT PATHOL,LITTLE ROCK,AR 72205. 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 FEB 23 PY 1993 VL 7 IS 4 BP A842 EP A842 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA KP975 UT WOS:A1993KP97501854 ER PT J AU BANKERT, L VOYLES, N MISHRA, B MEZEY, E GEARHART, J MISHRA, L AF BANKERT, L VOYLES, N MISHRA, B MEZEY, E GEARHART, J MISHRA, L TI IDENTIFICATION OF 2-NOVEL STAGE SPECIFIC GENES FROM DEVELOPING LIVER SO FASEB JOURNAL LA English DT Meeting Abstract C1 VAMC,WASHINGTON,DC 20422. NCI,BALTIMORE,MD 20814. JOHNS HOPKINS UNIV,BALTIMORE,MD 21205. 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 FEB 23 PY 1993 VL 7 IS 4 BP A821 EP A821 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA KP975 UT WOS:A1993KP97501733 ER PT J AU BARNES, DM SYKES, DB MILLER, DS AF BARNES, DM SYKES, DB MILLER, DS TI PERVANADATE (PV), AN INSULIN MIMIC, ACTS THROUGH MG++ TO STIMULATE PROTEIN-SYNTHESIS 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 FEB 23 PY 1993 VL 7 IS 4 BP A832 EP A832 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA KP975 UT WOS:A1993KP97501797 ER PT J AU BRACKETT, LE DALY, JW AF BRACKETT, LE DALY, JW TI CHARACTERIZATION OF THE A(2B) ADENOSINE (ADO) RECEPTOR IN NIH3T3 FIBROBLASTS SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIDDK,BETHESDA,MD. BROWN UNIV,PROVIDENCE,RI 02912. NR 0 TC 1 Z9 1 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB 23 PY 1993 VL 7 IS 4 BP A693 EP A693 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA KP975 UT WOS:A1993KP97501003 ER PT J AU CASTRO, GD SIMPSON, JT CASTRO, JA AF CASTRO, GD SIMPSON, JT CASTRO, JA TI INTERACTION OF CHEMICALLY-INDUCED TRICHLOROMETHYL FREE-RADICALS WITH THYMINE A MASS-SPECTROMETRIC STUDY SO FASEB JOURNAL LA English DT Meeting Abstract C1 CONSEJO NACL INVEST CIENT & TECN,CITEFA,CTR INVEST TOXICOL,RA-1603 VILLA MARTELLI,ARGENTINA. NIMH,CLIN SCI LAB,ANALYT BIOCHEM SECT,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 FEB 23 PY 1993 VL 7 IS 4 BP A657 EP A657 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA KP975 UT WOS:A1993KP97500802 ER PT J AU CHEN, ZH GUNDIMEDA, U ANDERSON, WB GOPALAKRISHNA, R AF CHEN, ZH GUNDIMEDA, U ANDERSON, WB GOPALAKRISHNA, R TI MULTIWELL FILTRATION ASSAY FOR PHORBOL ESTER BINDING - COMPARISON OF OPTIMAL CONDITIONS OF BINDING FOR PURIFIED PROTEIN-KINASE-C AND CYTOSOL SO FASEB JOURNAL LA English DT Meeting Abstract C1 USC LOS ANGELES,SCH MED,DEPT PHARMACOL & NUTR,LOS ANGELES,CA 90033. NCI,CELL ONCOL 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 FEB 23 PY 1993 VL 7 IS 4 BP A715 EP A715 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA KP975 UT WOS:A1993KP97501126 ER PT J AU CIUFFO, GM VISWANATHAN, M SELTZER, AM SAAVEDRA, JM AF CIUFFO, GM VISWANATHAN, M SELTZER, AM SAAVEDRA, JM TI GLOMERULAR ANGIOTENSIN-II RECEPTOR SUBTYPES DURING DEVELOPMENT OF RAT-KIDNEY SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIMH,CLIN SCI LAB,PHARMACOL SECT,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 FEB 23 PY 1993 VL 7 IS 4 BP A587 EP A587 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA KP975 UT WOS:A1993KP97500399 ER PT J AU CURRENS, MJ GULAKOWSKI, RJ MORAN, RA MCMAHON, JB BOYD, MR AF CURRENS, MJ GULAKOWSKI, RJ MORAN, RA MCMAHON, JB BOYD, MR TI BIOLOGICAL CHARACTERIZATION OF THE ANTI-HIV ACTIVITY OF CALANOLIDE-A SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,DRUG DISCOVERY RES & DEV LAB,FREDERICK,MD 21701. NR 1 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB 23 PY 1993 VL 7 IS 4 BP A691 EP A691 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA KP975 UT WOS:A1993KP97500992 ER PT J AU DONG, C AZNAVOORIAN, S LIOTTA, LA AF DONG, C AZNAVOORIAN, S LIOTTA, LA TI TYPE-IV COLLAGEN-INDUCED PSEUDOPOD PROTRUSION DURING TUMOR-CELL METASTASIS SO FASEB JOURNAL LA English DT Meeting Abstract C1 PENN STATE UNIV,BIOENGN PROGRAM,UNIV PK,PA 16802. NCI,PATHOL LAB,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 FEB 23 PY 1993 VL 7 IS 4 BP A883 EP A883 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA KP975 UT WOS:A1993KP97502096 ER PT J AU FONSECA, MI BUTTON, D RISTIC, HA BROWN, RD AF FONSECA, MI BUTTON, D RISTIC, HA BROWN, RD TI LOCALIZATION AND AGONIST MEDIATED REDISTRIBUTION OF ALPHA(1B)-ADRENERGIC RECEPTOR MONITORED BY ANTIPEPTIDE ANTIBODIES SO FASEB JOURNAL LA English DT Meeting Abstract C1 UNIV ILLINOIS,DEPT PHARMACOL,CHICAGO,IL 60680. NIMH,CELL BIOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB 23 PY 1993 VL 7 IS 4 BP A695 EP A695 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA KP975 UT WOS:A1993KP97501011 ER PT J AU FONTVIEILLE, AM SPRAUL, M CHOUTEAU, C RAVUSSIN, E AF FONTVIEILLE, AM SPRAUL, M CHOUTEAU, C RAVUSSIN, E TI RESTING METABOLIC-RATE OF 5-YEAR OLD PIMA INDIAN AND CAUCASIAN CHILDREN SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIDDK,CDNS,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 FEB 23 PY 1993 VL 7 IS 4 BP A648 EP A648 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA KP975 UT WOS:A1993KP97500747 ER PT J AU GARZA, HH MAYO, S DECOSTA, BR BOWEN, W CARR, DJJ AF GARZA, HH MAYO, S DECOSTA, BR BOWEN, W CARR, DJJ TI CHARACTERIZATION OF SIGMA RECEPTORS ON SPLENIC LYMPHOCYTES SO FASEB JOURNAL LA English DT Meeting Abstract C1 LSU,MED CTR,DEPT MICROBIOL IMMUNOL & PARASITOL,NEW ORLEANS,LA 70112. NIDDKD,MED CHEM LAB,BETHESDA,MD 20852. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB 23 PY 1993 VL 7 IS 4 BP A852 EP A852 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA KP975 UT WOS:A1993KP97501916 ER PT J AU GOLOMB, E TRACHEWSKY, D KEISER, HR AF GOLOMB, E TRACHEWSKY, D KEISER, HR TI ANGIOTENSIN-II PROMOTES AND MAINTAINS ISOPROTERENOL-INITIATED CARDIAC-HYPERTROPHY IN RATS SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI,HYPERTENS ENDOCRINE BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB 23 PY 1993 VL 7 IS 4 BP A751 EP A751 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA KP975 UT WOS:A1993KP97501330 ER PT J AU GOPALAKRISHNA, R GUNDIMEDA, U CHEN, ZH ANDERSON, WB AF GOPALAKRISHNA, R GUNDIMEDA, U CHEN, ZH ANDERSON, WB TI THE ANTITUMOR PROMOTER VITAMIN-E DECREASES THE RATE OF DOWN-REGULATION OF PROTEIN-KINASE-C INDUCED BY PHORBOL ESTERS AND OXIDANTS SO FASEB JOURNAL LA English DT Meeting Abstract C1 USC LOS ANGELES,SCH MED,LOS ANGELES,CA 90033. NCI,CELL ONCOL 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 FEB 23 PY 1993 VL 7 IS 4 BP A865 EP A865 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA KP975 UT WOS:A1993KP97501991 ER PT J AU HERMAN, EH ZHANG, J CHADWICK, DP FERRANS, VJ GREEN, MD AF HERMAN, EH ZHANG, J CHADWICK, DP FERRANS, VJ GREEN, MD TI THE ANTIVIRAL DRUG FIAC CAUSES MYOCARDIAL ALTERATIONS IN RATS SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA,LAUREL,MD 20708. NHLBI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB 23 PY 1993 VL 7 IS 4 BP A683 EP A683 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA KP975 UT WOS:A1993KP97500946 ER PT J AU HORVATH, I SANDOR, NT MCLAUGHLIN, AC AF HORVATH, I SANDOR, NT MCLAUGHLIN, AC TI INVOLVEMENT OF NITRIC-OXIDE PATHWAY IN THE ADJUSTMENT OF CEREBROCORTICAL BLOOD-FLOW AND OXYGEN-CONSUMPTION DURING HYPERCAPNIA SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAAA,ROCKVILLE,MD 20852. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB 23 PY 1993 VL 7 IS 4 BP A530 EP A530 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA KP975 UT WOS:A1993KP97500067 ER PT J AU KAZANIETZ, MG ARECES, LB BAHADOR, A MISCHAK, H MUSHINSKI, JF BLUMBERG, PM AF KAZANIETZ, MG ARECES, LB BAHADOR, A MISCHAK, H MUSHINSKI, JF BLUMBERG, PM TI CHARACTERIZATION OF LIGANDS AND SUBSTRATES FOR PKC ISOZYMES EXPRESSED IN THE BACULOVIRUS EXPRESSION SYSTEM SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. RI Mischak, Harald/E-8685-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB 23 PY 1993 VL 7 IS 4 BP A601 EP A601 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA KP975 UT WOS:A1993KP97500474 ER EF